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Diabetic Ketoacidosis (DKA)
Life-threatening metabolic emergency requiring early recognition, aggressive IV fluids, insulin infusion, and electrolyte replacement — with vigilant monitoring for complications.
🔍 Overview
Definition
DKA is characterized by the triad of hyperglycemia (usually BG > 250 mg/dL), anion-gap metabolic acidosis (pH < 7.3, bicarb < 18), and ketonemia/ketonuria. It results from absolute or relative insulin deficiency combined with excess counterregulatory hormones.
Why It Matters
⚠ Mortality up to 5% in adultsHigher in elderly, delayed recognition, or severe comorbidities. Cerebral edema is the leading cause of death in children.
Who Gets It
- Type 1 DM (can be the presenting illness in ~25%)
- Type 2 DM under physiologic stress
- SGLT2-inhibitor users (euglycemic DKA — BG may be < 200!)
- Precipitants: infection (30–40% — most common), insulin omission/non-compliance (20–25%), new diagnosis T1DM, MI/ACS, pancreatitis, cocaine, alcohol
Mnemonic — 5 I's of DKA Precipitants:
Infection (30–40%, #1 cause — UTI, pneumonia, skin) · Insulin (missed or inadequate doses) · Infarction (MI, stroke, mesenteric ischemia) · Intoxication (cocaine, alcohol, drugs) · Inflammation (pancreatitis, surgery, trauma)
Infection (30–40%, #1 cause — UTI, pneumonia, skin) · Insulin (missed or inadequate doses) · Infarction (MI, stroke, mesenteric ischemia) · Intoxication (cocaine, alcohol, drugs) · Inflammation (pancreatitis, surgery, trauma)
Pathophysiology
Insulin deficiency → unrestrained lipolysis → free fatty acids → hepatic ketogenesis (acetoacetate, β-hydroxybutyrate) → high anion gap metabolic acidosis. Hyperglycemia → osmotic diuresis → profound volume depletion and electrolyte losses. Total body K⁺ is depleted even when serum K⁺ appears normal or high (due to transcellular shift from acidosis).
Presentation
Symptoms
- Polyuria, polydipsia, nausea, vomiting, abdominal pain
- Weakness, fatigue, altered mental status (in severe cases)
- Timeline: hours to days (faster than HHS)
Exam
- Kussmaul respirations (deep, rapid — compensating for acidosis)
- Fruity/acetone breath
- Signs of dehydration: dry mucosa, tachycardia, hypotension, poor skin turgor
Red Flags
- Altered mental status → think cerebral edema, severe osmolarity
- Potassium < 3.5 → do NOT start insulin until repleted
- Euglycemic DKA (SGLT2i) — don't miss it
- pH < 7.0 or bicarb < 10 → severe DKA, ICU threshold
Differential Diagnosis
- HHS — BG often > 600, severe hypertonicity, no/minimal ketones, pH usually > 7.3
- Alcoholic ketoacidosis — low or normal glucose, ketones present, history of binge drinking + poor PO
- Starvation ketosis — mild, pH > 7.3, bicarb usually > 18
- Other high AG acidosis — lactic acidosis, toxic ingestions (methanol, ethylene glycol, salicylates)
🧪 Workup & Diagnosis
Initial Workup
DO ALL OF THIS IMMEDIATELYThese tests diagnose DKA, guide fluid/insulin dosing, and identify precipitant — results change management NOW.
Labs (STAT)
- BMP — BG, creatinine, K⁺, bicarbonate
- VBG or ABG — pH, pCO₂, calculated bicarb
- Anion gap = Na – (Cl + HCO₃) → normal 8–12; in DKA typically > 20
- Beta-hydroxybutyrate (serum) — preferred over urine ketones for monitoring
- Urine ketones (if serum BHB unavailable)
- Phosphate, magnesium — often depleted
- CBC, blood cultures — rule out infectious precipitant
- Lipase — DKA can elevate lipase without true pancreatitis
- HbA1c — assess chronic control
- Urinalysis + urine culture
- Pregnancy test (women of childbearing age)
Imaging / ECG
- ECG — assess for hyperkalemia changes (peaked T waves, wide QRS) or ischemia as precipitant
- CXR — rule out pneumonia as precipitant
- CT head only if focal neuro deficits or concern for cerebral edema
Diagnostic Criteria for DKA
| Parameter | Mild | Moderate | Severe |
|---|---|---|---|
| pH | 7.25–7.30 | 7.00–7.24 | < 7.00 |
| Bicarb (mEq/L) | 15–18 | 10–14 | < 10 |
| Anion Gap | > 10 | > 12 | > 12 |
| Mental Status | Alert | Alert/Drowsy | Stupor/Coma |
🚨 Management
Treatment: Step by Step
BEFORE STARTING INSULINEnsure K⁺ ≥ 3.5 mEq/L. Starting insulin with hypokalemia causes fatal cardiac arrhythmia.
First 5 Minutes
Assess & Stabilize
ABCs. IV access × 2. Foley if altered or unable to void. Cardiac monitor. POC glucose. Draw all STAT labs. Call senior if severe (pH < 7.1, AMS, K⁺ < 3.5).
ABCs. IV access × 2. Foley if altered or unable to void. Cardiac monitor. POC glucose. Draw all STAT labs. Call senior if severe (pH < 7.1, AMS, K⁺ < 3.5).
First 15–30 Minutes
IV Fluids — Aggressive Resuscitation
1–1.5 L NS over 1 hour if hypotensive ADA DKA Guidelines, 2023. Then switch to 0.45% or 0.9% NS at 250–500 mL/hr depending on corrected Na⁺. Goal: replace estimated fluid deficit (typically 3–6 L) over 24 hours. LR vs NS: No proven outcome difference in DKA SKALE-DKA, 2024.
1–1.5 L NS over 1 hour if hypotensive ADA DKA Guidelines, 2023. Then switch to 0.45% or 0.9% NS at 250–500 mL/hr depending on corrected Na⁺. Goal: replace estimated fluid deficit (typically 3–6 L) over 24 hours. LR vs NS: No proven outcome difference in DKA SKALE-DKA, 2024.
🔄 Updated Practice: Old teaching was NS (normal saline) for DKA fluid resuscitation. Newer evidence (SMART, 2018) suggests balanced crystalloids (LR) may be preferred — NS causes hyperchloremic metabolic acidosis, which can worsen and confuse the clinical picture. However, LR contains potassium (4 mEq/L) — avoid if K⁺ >5.5 initially.
First Hour
Potassium Replacement
K⁺ < 3.5 → replace aggressively (20–40 mEq/hr IV), do NOT start insulin yet
K⁺ 3.5–5.0 → add 20–30 mEq K⁺ per liter of IVF, start insulin
K⁺ > 5.0 → start insulin, hold K⁺ replacement, recheck in 2 hours
Insulin Infusion
Regular insulin drip at 0.1 units/kg/hr (no bolus needed per ADA 2023). Target: BG drop of 50–75 mg/dL/hr.
K⁺ < 3.5 → replace aggressively (20–40 mEq/hr IV), do NOT start insulin yet
K⁺ 3.5–5.0 → add 20–30 mEq K⁺ per liter of IVF, start insulin
K⁺ > 5.0 → start insulin, hold K⁺ replacement, recheck in 2 hours
Insulin Infusion
Regular insulin drip at 0.1 units/kg/hr (no bolus needed per ADA 2023). Target: BG drop of 50–75 mg/dL/hr.
🔄 Updated Practice: The old DKA protocol included an insulin IV bolus before starting the drip. Current ADA guidelines recommend NO bolus — start continuous infusion at 0.14 units/kg/hr directly. The bolus increased hypoglycemia risk without improving outcomes. Also: subcutaneous insulin protocols (insulin lispro/aspart q1-2h) are acceptable for mild-moderate DKA — IV is not always necessary.
When BG Hits 200–250 mg/dL
Switch to Dextrose-Containing Fluids
Add D5 to IV fluids (D5-0.45%NS) — reduce insulin drip to 0.05 units/kg/hr. Continue until anion gap closes, NOT just until BG normalizes. This is the most common resident mistake.
Add D5 to IV fluids (D5-0.45%NS) — reduce insulin drip to 0.05 units/kg/hr. Continue until anion gap closes, NOT just until BG normalizes. This is the most common resident mistake.
Resolution Criteria (ALL must be met)
- BG < 200 mg/dL
- Anion gap ≤ 12 mEq/L
- Serum bicarbonate ≥ 15 mEq/L
- pH > 7.3
Transitioning to Subcutaneous Insulin
Give SQ long-acting insulin 2 hours before stopping the drip (overlap is mandatory to prevent rebound ketoacidosis) ADA DKA Guidelines, 2023. Resume home insulin regimen if known, or start TDD calculation (0.5–0.8 units/kg/day). Ensure patient is eating and K⁺ > 3.5.
When to Escalate to ICU
- pH < 7.0 or bicarb < 10
- Altered mental status / decreased GCS
- Hemodynamic instability not responding to fluids
- K⁺ < 3.0 or > 6.0 with ECG changes
- Concurrent MI, stroke, or surgical emergency
📋 Clinical Example — DKA Insulin Drip Management
Patient: 28F with T1DM, glucose 520, pH 7.15, bicarb 8, AG 28, K⁺ 5.8
| Time | Action |
|---|---|
| Hour 0 | Start insulin drip 0.14 units/kg/hr (no bolus). NS 1L/hr. Do NOT give K⁺ yet (K⁺ > 5.2). |
| Hour 2 | Glucose 380 (↓140). K⁺ 4.5 → start KCl 20 mEq/hr in IV fluids. Continue insulin drip. |
| Hour 4 | Glucose 280 (↓100/hr — on target). K⁺ 3.8 → increase KCl to 40 mEq/hr. AG closing (18). |
| Hour 6 | Glucose 240 → approaching 250 threshold. Switch fluids to D5 1/2NS + KCl to prevent hypoglycemia while continuing insulin to close the gap. |
| Hour 8 | Glucose 190, pH 7.32, bicarb 16, AG 12 (closing). K⁺ 4.0. |
| Hour 10 | AG closed (AG 10), pH 7.38, bicarb 20, patient eating. → Overlap SC insulin (give long-acting + meal dose), wait 2 hours, THEN stop drip. |
Key: Never stop insulin drip until: (1) AG closed, (2) pH > 7.3, (3) bicarb > 18, (4) patient eating, AND (5) SC insulin given ≥ 2h prior.
💊 Medications & Doses
Medications & Dosing
| Drug | Dose / Route | Indication | Key Points |
|---|---|---|---|
| Regular Insulin | 0.14 units/kg/hr IV drip (no bolus) OR 0.1 units/kg/hr (with 0.1 units/kg IV bolus) ADA 2023 |
Insulin infusion | Do not start if K⁺ < 3.5. Reduce to 0.05 when BG < 250 |
| Normal Saline (0.9%) | 1–1.5 L over 1 hr, then 250–500 mL/hr | Volume resuscitation. LR is an acceptable alternative (SMART, 2018 — balanced crystalloids reduce AKI/death vs NS in critically ill) | Switch to 0.45%NS after initial bolus based on corrected Na⁺ |
| KCl | 20–40 mEq/hr IV (max 40 mEq/hr via central line) 10–20 mEq/hr peripheral |
Hypokalemia in DKA | Continuous cardiac monitoring. Expect K⁺ to drop as insulin given |
| Sodium Bicarbonate | 100 mEq in 400 mL D5W over 2 hrs | pH < 6.9 only | Controversial. May worsen hypokalemia and CNS acidosis. Use sparingly |
| Phosphate | 20–30 mmol IV over 6 hrs | PO₄ < 1.0 mg/dL with symptoms | Routine replacement not recommended. Risk of hypocalcemia |
| Glargine (Lantus) | 0.25–0.3 units/kg SQ (or prior home dose) | Transition off drip | Give 2 hours before stopping drip. Do not skip |
📊 Monitoring
Monitoring Schedule
During Active DKA
- Glucose: every 1 hour (via POC meter)
- BMP (or at least K⁺, bicarb): every 2–4 hours
- Anion gap: calculated every 2–4 hours to confirm closure
- Beta-hydroxybutyrate: every 4 hours (preferred over urine ketones)
- Urine output: target ≥ 0.5 mL/kg/hr — place Foley if needed
- ECG: if K⁺ < 3.0 or > 6.0
Pitfalls to Watch
- Stopping insulin too early — always wait for AG closure, not just BG normalization
- Forgetting the 2-hour overlap when transitioning to SQ insulin
- Overcorrecting fluids — iatrogenic fluid overload, especially in elderly or cardiac patients
- Missing the precipitant — always ask: why did they get DKA?
- Euglycemic DKA on SGLT2i — BG may be near-normal; check ketones regardless
- Cerebral edema — rare in adults but watch for headache, declining GCS during treatment
Complications
- Hypokalemia (from insulin shifting K⁺ intracellular)
- Hypoglycemia (from excess insulin or failure to add dextrose)
- Cerebral edema (especially children, rapid fluid shifts)
- ARDS (from aggressive fluid resuscitation)
- Thrombosis (hypercoagulable state)
Before Discharge
- Patient tolerating PO fluids and meals
- On appropriate SQ insulin regimen
- BG < 200, AG closed, K⁺ repleted
- Precipitant identified and addressed
- Diabetes education arranged
- Endocrine follow-up within 1–2 weeks
📋 On Rounds
What to Say on Rounds
📋 Sample Presentation
"Mr. Smith is a 32-year-old with Type 1 DM presenting with a 2-day history of nausea, vomiting, and abdominal pain in the setting of missed insulin doses. He was found to have a glucose of 420, pH 7.18, bicarb of 10, and an anion gap of 24, consistent with severe DKA. He was started on NS resuscitation and a regular insulin drip at 0.1 units/kg/hr after K⁺ was confirmed to be 3.8. Over the past 8 hours, his glucose has come down to 240, his anion gap has narrowed to 14, and his bicarb is now 16. We are targeting gap closure before transitioning to subcutaneous insulin. His precipitant appears to be medication non-adherence, and we are involving diabetes education."
Common Pimp Questions
Why should you NOT start insulin if K⁺ < 3.5?
Insulin drives K⁺ intracellularly. Starting insulin when K⁺ is already low can cause life-threatening hypokalemia and fatal cardiac arrhythmia. Always replete first.
When do you stop the insulin drip?
When ALL three criteria are met: BG < 200, AG ≤ 12, bicarb ≥ 15. NOT just when glucose normalizes. And 2 hours after giving long-acting SQ insulin.
What is euglycemic DKA and who is at risk?
DKA occurring with near-normal glucose (< 200 mg/dL). Seen with SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin). They enhance renal glucose excretion, masking hyperglycemia while ketoacidosis progresses. Always check ketones in SGLT2i users with nausea/vomiting.
Why is bicarbonate therapy generally avoided in DKA?
Bicarb worsens hypokalemia, may cause paradoxical CNS acidosis (CO₂ diffuses into CSF faster than bicarb), and has not been shown to improve outcomes. Reserve for pH < 6.9 only.
⚡ Summary
One-Screen Summary
Definition
BG > 250 + pH < 7.3 + bicarb < 18 + anion gap > 10 + ketones. Triad must all be present.
Precipitants
Infection (30–40%), missed insulin (20–25%), new DM, MI, pancreatitis, SGLT2i use
Initial Management
IV NS 1L bolus → check K⁺ → if K⁺ ≥ 3.5 start regular insulin 0.1 u/kg/hr → replace K⁺ in IVF
Key Rule
Add D5 when BG < 250. Stop drip only when AG closed. Overlap SQ insulin 2 hrs before stopping drip.
Biggest Pitfalls
Starting insulin with K⁺ < 3.5. Stopping insulin when BG normalizes (not when AG closes). Missing euglycemic DKA on SGLT2i.
ICU Threshold
pH < 7.0, bicarb < 10, AMS, hemodynamic instability, K⁺ < 3.0 with ECG changes
📄 One Pager
ICU / Endocrine · One Pager
Diabetic Ketoacidosis
Hyperglycemia + anion-gap acidosis + ketones. Fluids first. Check K⁺ before insulin. Close the gap, not just the glucose.
Diagnosis
- BG > 250 mg/dL
- pH < 7.3 / Bicarb < 18
- Anion gap > 10–12
- Ketones positive (serum BHB preferred)
- Euglycemic DKA: BG normal on SGLT2i
Precipitants
- Infection (30–40%)
- Missed insulin (20–25%)
- New diagnosis T1DM
- MI, pancreatitis, surgery
- SGLT2 inhibitor use
Management — Step by Step
1
IV fluids: 1–1.5L NS over 1h → then 0.45%NS at 250–500 mL/hr
2
Check K⁺ BEFORE insulin — if < 3.5, replace first. Do NOT start insulin.
3
Insulin: Regular insulin 0.1 units/kg/hr IV (no bolus) ADA 2023
4
When BG < 250: Add D5 to IVF, reduce insulin to 0.05 units/kg/hr
5
Stop drip when: BG < 200 + AG ≤ 12 + bicarb ≥ 15 — NOT just BG normal
6
SQ insulin overlap: Give long-acting 2h before stopping drip
Key Drugs
Regular insulin0.1 u/kg/hr
KCl20–40 mEq/hr IV
NS → 0.45%NS250–500 mL/hr
Glargine0.25 u/kg SQ
Monitoring
- BG every 1h (POC)
- BMP q2–4h
- Anion gap q2–4h
- BHB q4h
- UOP ≥ 0.5 mL/kg/hr
Pitfalls
- Insulin with K⁺ < 3.5
- Stopping drip at BG normal
- Missing euglycemic DKA
- No SQ overlap
- Missing precipitant
ICU Threshold
- pH < 7.0 / bicarb < 10
- Altered mental status
- Hemodynamic instability
- K⁺ < 3.0 with ECG changes
Key Trial
- ADA 2023: No IV insulin bolus — drip only at 0.1 u/kg/hr
- Resolution: Gap closure, not glucose normalisation
- Bicarb: Only if pH < 6.9 (not routine)
Sepsis & Septic Shock
Life-threatening organ dysfunction from infection. Every hour of antibiotic delay = ~7% more mortality. Diagnose fast, culture fast, treat fast. Source control is as important as antibiotics.
🔍 Overview
Sepsis-3 Definitions (Singer, JAMA 2016)
Sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationally defined as SOFA score increase ≥ 2 from baseline in a patient with suspected infection.
Septic Shock: Sepsis + vasopressor requirement to maintain MAP ≥ 65 mmHg + serum lactate > 2 mmol/L despite adequate fluid resuscitation. In-hospital mortality > 40%.
Septic Shock: Sepsis + vasopressor requirement to maintain MAP ≥ 65 mmHg + serum lactate > 2 mmol/L despite adequate fluid resuscitation. In-hospital mortality > 40%.
qSOFA (bedside screen — 1 point each): Altered mentation (GCS < 15) | RR ≥ 22 | SBP ≤ 100. Score ≥ 2 = high risk → triggers full SOFA + ICU evaluation. qSOFA is a screen, NOT a definition.
⚠️ SSC 2026: qSOFA has poor sensitivity — misses too many septic patients. NEWS/MEWS now recommended as primary screening tools.
⚠️ SSC 2026: qSOFA has poor sensitivity — misses too many septic patients. NEWS/MEWS now recommended as primary screening tools.
NEWS / MEWS Calculators — SSC 2026 recommended sepsis screening tools. NEWS ≥7 = emergency. MEWS ≥5 = urgent review.
🧮 Calculate NEWS / MEWS →
SIRS Criteria (historical — Bone, Chest 1992): Infection + ≥ 2 of: Temp > 38°C or < 36°C | HR > 90 | RR > 20 or PaCO₂ < 32 | WBC > 12,000 or < 4,000 or > 10% bands.
Replaced by Sepsis-3 (2016) due to poor specificity — SIRS is present in most hospitalized patients Sepsis-3, 2016 regardless of infection. Still used as a triage trigger in some institutions given its high sensitivity.
Replaced by Sepsis-3 (2016) due to poor specificity — SIRS is present in most hospitalized patients Sepsis-3, 2016 regardless of infection. Still used as a triage trigger in some institutions given its high sensitivity.
🔴 SSC 2026 Guidelines (March 2026) — Key Changes from 2021:
| Domain | 2021 SSC | 2026 SSC Update |
|---|---|---|
| Screening | qSOFA suggested outside ICU | NEWS/NEWS2/MEWS/SIRS now recommended OVER qSOFA. qSOFA has poor sensitivity — should not be sole screening tool. |
| Fluids | 30 mL/kg crystalloid within 3h. No preference NS vs balanced. | 30 mL/kg still suggested. Balanced crystalloids now suggested over 0.9% saline (except TBI). New: fluid removal after resuscitation now addressed. |
| Vasopressors | Start via central line | Peripheral vasopressor start now OK — don't delay for central access. NE → vasopressin → epi unchanged. New: BP targets for older adults. |
| Steroids | Suggested if ongoing vasopressor need | Strengthened: hydrocortisone 200 mg/day if vasopressors ≥ 4 hours. Reverses 2016 recommendation against routine steroids. |
| Antibiotics | Within 1h of recognition | Refined: 1 hour for septic shock, 3 hours for sepsis without shock. New: antibiotic optimization & prehospital antibiotics may reduce mortality (OR 0.58). |
| New topics | — | "Code sepsis" huddle protocols. Post-sepsis discharge rehab. Institutional performance improvement programs. 46 entirely new statements (129 total). |
Full guidelines: SSC 2026 Adult Guidelines (Critical Care Medicine) · See What's New
Pathophysiology
Infection triggers innate immune activation → cytokine storm (TNF-α, IL-1, IL-6) → endothelial dysfunction → vasodilation + capillary leak → distributive shock. Simultaneously, microvascular thrombosis + impaired oxygen utilization → end-organ ischemia even when MAP is maintained. This explains why restoring BP alone is insufficient — tissue perfusion and oxygen delivery must be optimized.
Common Sources
- Lung — pneumonia (30–40%, most common)
- Urinary tract — pyelonephritis, urosepsis (20–30%)
- Abdomen — peritonitis, cholangitis, bowel perforation, diverticulitis
- Line/device — CLABSI, endocarditis, infected hardware
- Skin/soft tissue — necrotizing fasciitis, infected wounds
- CNS — meningitis, encephalitis, brain abscess (least common)
- Unknown source — 20–30% of sepsis cases (especially in immunocompromised)
Presentation
- Fever > 38.3°C OR hypothermia < 36°C (hypothermia = worse prognosis)
- Tachycardia, tachypnea
- Hypotension, warm/flushed skin (early distributive), later cold/mottled
- Altered mental status (confusion, agitation, lethargy)
- Decreased urine output (< 0.5 mL/kg/hr)
- Elevated lactate (tissue hypoperfusion marker)
Don't Be Fooled: Elderly, immunocompromised (transplant, chemotherapy), and patients on chronic steroids may present with NO fever, minimal leukocytosis, and normal HR. Hypothermia and leukopenia in sepsis = very bad prognostic signs. Think sepsis in any elderly patient with AMS + unexplained hypotension.
🧪 Workup & Diagnosis
Sepsis Bundle SSC, 2026
Septic shock: ALL within 1 hour. Sepsis without shock: antibiotics within 3 hours. (SSC 2026 now distinguishes timing by severity — previously 1h for all sepsis.)
- Measure serum lactate (repeat if initial > 2 mmol/L to confirm clearance)
- Blood cultures × 2 sets from 2 separate sites — before antibiotics, but do not delay antibiotics > 45 min waiting for cultures
- Broad-spectrum antibiotics administered IV
- 30 mL/kg crystalloid bolus if MAP < 65 mmHg OR lactate ≥ 4 mmol/L
- Vasopressors if MAP < 65 despite fluid resuscitation → target MAP ≥ 65
Laboratory Workup
Mandatory
- Lactate — venous or arterial; most critical early test; > 4 = cryptic shock regardless of BP
- Blood cultures × 2 peripheral sets (before antibiotics)
- BMP — creatinine (AKI), glucose, bicarb (metabolic acidosis)
- CBC with differential (leukocytosis, left shift, or leukopenia)
- Procalcitonin — helps guide antibiotic duration (de-escalation at < 0.25)
Targeted by Suspected Source
- UA + urine culture (UTI/urosepsis — 2nd most common source)
- Sputum Gram stain + culture, respiratory panel (pneumonia — most common source)
- LFTs, lipase, RUQ ultrasound (abdominal source)
- Coagulation panel (PT/INR, PTT, fibrinogen) — if DIC suspected
- LP (cell count, protein, glucose, Gram stain, culture) if CNS source
- C. diff if recent antibiotics + diarrhea
Imaging
- Bedside echo — cardiac function, IVC collapsibility (volume status), wall motion, pericardial effusion (fastest, most actionable)
- CXR — portable if unstable; pneumonia, pulmonary edema, effusion
- RUQ ultrasound — gallbladder, biliary dilation (cholangitis)
- CT abdomen/pelvis with contrast — abdominal source, abscess (do not delay abx for CT)
- CT head — if AMS, meningismus, focal neuro deficit (LP after if no mass lesion)
Lactate Interpretation
| Lactate Level | Category | Action |
|---|---|---|
| < 2 mmol/L | Normal | Standard care; monitor if clinical concern |
| 2–4 mmol/L | Elevated — sepsis | Aggressive resuscitation; repeat lactate in 2h |
| ≥ 4 mmol/L | Cryptic shock | ICU, vasopressors even if BP normal, repeat q2h |
Lactate Clearance: Target ≥ 10% clearance per 2 hours. Failure to clear lactate despite resuscitation = inadequate source control, occult bleeding, or mitochondrial dysfunction. Persistently elevated lactate = very poor prognosis.
🚨 Management
Resuscitation Strategy
0–15 min — Recognition & Stabilisation
ABCs. Two large-bore IVs. Cardiac monitor. O₂. Call for help.
If shock criteria met (MAP < 65, lactate ≥ 4, AMS): activate ICU consult now — not after labs, not after imaging. Bedside echo to exclude obstructive shock (PE, tamponade) and assess LV function.
If shock criteria met (MAP < 65, lactate ≥ 4, AMS): activate ICU consult now — not after labs, not after imaging. Bedside echo to exclude obstructive shock (PE, tamponade) and assess LV function.
0–30 min — Cultures then Antibiotics (in that order, fast)
Blood cultures × 2 → broad-spectrum antibiotics within 1 hour. Every hour of delay in septic shock increases mortality ~7%. Narrow based on culture results at 48–72h.
| Drug | Dose | Bugs Covered | ⚠️ Side Effects | When to Use |
|---|---|---|---|---|
| Piperacillin-tazobactam (Zosyn) | 3.375g IV q6h (or 4.5g q8h extended infusion over 4h) | Gram-positives: Strep, MSSA (not MRSA) Gram-negatives: E. coli, Klebsiella, Proteus, Pseudomonas, Enterobacter Anaerobes: Bacteroides, Fusobacterium | ⚠️ Diarrhea, rash, ↑ AKI when paired with vancomycin ACORN, 2024, thrombocytopenia (prolonged use), hypokalemia, C. diff | Default empiric — broadest beta-lactam. Covers gram-negatives + anaerobes. Use when source unknown or intra-abdominal/respiratory suspected. |
| Cefepime (Maxipime) | 2g IV q8h | Gram-positives: Strep, MSSA (not MRSA) Gram-negatives: E. coli, Klebsiella, Pseudomonas, Enterobacter, Serratia, Citrobacter No anaerobes | ⚠️ Neurotoxicity (confusion, myoclonus, seizures — especially in renal failure), rash, C. diff | Alternative to pip-tazo. Better with vanc (↓ AKI vs pip-tazo+vanc). Use when anaerobic coverage not needed. Add metronidazole if anaerobes needed. |
| Meropenem (Merrem) | 1g IV q8h | Gram-positives: Strep, MSSA (not MRSA) Gram-negatives: E. coli, Klebsiella, Pseudomonas, Enterobacter, ESBL-producers, Acinetobacter Anaerobes: Bacteroides | ⚠️ Seizures (less than imipenem), diarrhea, C. diff, rash. ↓ valproic acid levels (contraindicated together) | Use if: prior ESBL/MDR organism, recent hospitalization + IV abx within 90 days, high local resistance, failed pip-tazo. Broadest gram-negative coverage. |
| Vancomycin (Vancocin) | 15–20 mg/kg IV q8–12h (AUC/MIC target 400–600) | Gram-positives only: MRSA, MSSA, Strep, Enterococcus (not VRE) No gram-negatives. No anaerobes. | ⚠️ Nephrotoxicity (worse with pip-tazo), Red Man Syndrome (infuse over ≥ 1h), ototoxicity, DRESS (rare) | Add for MRSA coverage — any sepsis with: prior MRSA, IVDU, skin/soft tissue source, healthcare exposure, HD catheter. Pair with pip-tazo, cefepime, or meropenem. |
| Linezolid (Zyvox) | 600 mg IV/PO q12h | Gram-positives only: MRSA, VRE, Strep, Enterococcus No gram-negatives. No anaerobes. | ⚠️ Thrombocytopenia (> 14d), serotonin syndrome (weak MAOi — avoid SSRIs/SNRIs/tramadol), lactic acidosis, peripheral neuropathy & optic neuritis (> 28d — may be irreversible), myelosuppression | Alternative to vanc if: CKD/AKI (no renal adjustment), VRE suspected, MRSA pneumonia (superior lung penetration), no IV access (100% PO bioavailability). |
| Metronidazole (Flagyl) | 500 mg IV q8h | Anaerobes: Bacteroides fragilis, Clostridium, Fusobacterium, Prevotella Protozoa: C. diff (PO), Giardia, Entamoeba | ⚠️ Metallic taste, nausea, peripheral neuropathy (prolonged use), disulfiram reaction with alcohol, seizures (rare) | Add to cefepime or meropenem when anaerobic coverage needed (intra-abdominal, abscess, aspiration with empyema). Not needed with pip-tazo (already covers anaerobes). |
Key principle: Pip-tazo or cefepime covers gram-negatives + Pseudomonas. Vancomycin or linezolid covers MRSA. You need BOTH for empiric sepsis coverage. Neither alone is sufficient.
Fluid Resuscitation
30 mL/kg balanced crystalloid (LR or PlasmaLyte preferred over NS) SMART, 2018 SALT-ED, 2018 if MAP < 65 or lactate ≥ 4.
After initial bolus: reassess after each 500 mL. Check JVP, lung auscultation, passive leg raise response. Do not reflexively give more fluids if no hemodynamic response — start vasopressors. Fluid overload in sepsis = worse outcomes. CLOVERS, 2023 showed no benefit to liberal fluid strategy, supporting a conservative approach. Use crystalloids over colloids — CRISTAL, 2013 found no 28-day mortality difference between colloids and crystalloids. Notably, FEAST, 2011 demonstrated that fluid boluses increased mortality in febrile children (resource-limited setting), underscoring the importance of judicious fluid use.
After initial bolus: reassess after each 500 mL. Check JVP, lung auscultation, passive leg raise response. Do not reflexively give more fluids if no hemodynamic response — start vasopressors. Fluid overload in sepsis = worse outcomes. CLOVERS, 2023 showed no benefit to liberal fluid strategy, supporting a conservative approach. Use crystalloids over colloids — CRISTAL, 2013 found no 28-day mortality difference between colloids and crystalloids. Notably, FEAST, 2011 demonstrated that fluid boluses increased mortality in febrile children (resource-limited setting), underscoring the importance of judicious fluid use.
🔄 Updated Practice (SSC 2026): Balanced crystalloids (LR/PlasmaLyte) now suggested over 0.9% saline (except TBI — use NS). 30 mL/kg remains suggested but with greater emphasis on individualization. CLOVERS, 2023 showed no difference between restrictive (~1.8L) and liberal (~3.8L) strategies. New in 2026: fluid removal after resuscitation is now addressed — de-resuscitate once stabilized. Fluid overload kills — reassess after each bolus.
Vasopressors — MAP Target ≥ 65
Norepinephrine first-line (start 0.01–0.05 mcg/kg/min, titrate to max ~3 mcg/kg/min) SOAP II, 2010 — α₁ > β₁, increases MAP without excessive HR.
Add vasopressin 0.03 units/min (fixed dose, no titration) when NE reaches 0.25–0.5 mcg/kg/min (spares NE, possibly reduces mortality) VASST 2008.
Add epinephrine for refractory shock. Use dobutamine (2–20 mcg/kg/min) only if MAP adequate but persistent signs of low CO (cold extremities, rising lactate, low ScvO₂).
Hydrocortisone 200 mg/day IV (50 mg q6h or continuous) if vasopressors required ≥ 4 hours (SSC 2026 threshold — don't wait all day). Shortens shock duration. ADRENAL 2018; APROCCHSS 2018 CORTICUS, 2008.
Add vasopressin 0.03 units/min (fixed dose, no titration) when NE reaches 0.25–0.5 mcg/kg/min (spares NE, possibly reduces mortality) VASST 2008.
Add epinephrine for refractory shock. Use dobutamine (2–20 mcg/kg/min) only if MAP adequate but persistent signs of low CO (cold extremities, rising lactate, low ScvO₂).
Hydrocortisone 200 mg/day IV (50 mg q6h or continuous) if vasopressors required ≥ 4 hours (SSC 2026 threshold — don't wait all day). Shortens shock duration. ADRENAL 2018; APROCCHSS 2018 CORTICUS, 2008.
🔄 Updated Practice (SSC 2026): Peripheral vasopressor start is now OK — don't delay pressors waiting for central access. Norepinephrine remains first-line (SOAP II — dopamine caused more arrhythmias). Vasopressin second-line (0.03 units/min, fixed). Dopamine and "renal-dose dopamine" are DEBUNKED. New in 2026: BP targets for older adults now specifically addressed (previously one-size-fits-all MAP 65).
Source Control
Identify and eliminate the source of infection — as important as antibiotics.
Drain abscess (IR-guided or surgical). Remove infected IV lines (replace in new site). Decompress biliary obstruction (ERCP or percutaneous). Surgical consult for perforated viscus, necrotizing fasciitis, infected prosthetic. Time to source control should be < 6–12 hours for drainage procedures.
Drain abscess (IR-guided or surgical). Remove infected IV lines (replace in new site). Decompress biliary obstruction (ERCP or percutaneous). Surgical consult for perforated viscus, necrotizing fasciitis, infected prosthetic. Time to source control should be < 6–12 hours for drainage procedures.
ICU-Level Bundles
Ventilation: Lung-protective if intubated (TV 6 mL/kg IBW, Pplat ≤ 30).
Glucose: Target 140–180 mg/dL with insulin infusion NICE-SUGAR, 2009. Avoid hypoglycemia.
DVT prophylaxis: Enoxaparin (or UFH if CrCl < 30) + SCDs.
Stress ulcer prophylaxis: IV PPI or H2-blocker if high-risk (mechanically ventilated > 48h, coagulopathy, history of GI bleed, TBI, burns > 35% BSA). Not all ICU patients need it — SUP-ICU, 2018: no mortality benefit from routine prophylaxis; weigh risk of C. difficile and nosocomial pneumonia.
Nutrition: Early enteral nutrition within 24–48h. Enteral is preferred over parenteral — NUTRIREA-2, 2018 and CALORIES, 2014 showed no mortality difference between parenteral and enteral, but enteral maintains gut integrity.
Antibiotic de-escalation: Reassess at 48–72h based on cultures + clinical trajectory. Target 5–7 days total if good source control and clinical improvement. Use procalcitonin to guide stopping PRORATA 2010.
Glucose: Target 140–180 mg/dL with insulin infusion NICE-SUGAR, 2009. Avoid hypoglycemia.
DVT prophylaxis: Enoxaparin (or UFH if CrCl < 30) + SCDs.
Stress ulcer prophylaxis: IV PPI or H2-blocker if high-risk (mechanically ventilated > 48h, coagulopathy, history of GI bleed, TBI, burns > 35% BSA). Not all ICU patients need it — SUP-ICU, 2018: no mortality benefit from routine prophylaxis; weigh risk of C. difficile and nosocomial pneumonia.
Nutrition: Early enteral nutrition within 24–48h. Enteral is preferred over parenteral — NUTRIREA-2, 2018 and CALORIES, 2014 showed no mortality difference between parenteral and enteral, but enteral maintains gut integrity.
Antibiotic de-escalation: Reassess at 48–72h based on cultures + clinical trajectory. Target 5–7 days total if good source control and clinical improvement. Use procalcitonin to guide stopping PRORATA 2010.
Resuscitation Targets
| Parameter | Target | Notes |
|---|---|---|
| MAP | ≥ 65 mmHg | Higher (≥ 75) in chronic hypertension or AKI |
| Lactate | Clearance ≥ 10% per 2h | Target < 2 mmol/L; failure to clear = reassess |
| UOP | ≥ 0.5 mL/kg/hr | Oliguria = inadequate perfusion or AKI |
| ScvO₂ | ≥ 70% | Low = high O₂ extraction → low CO or anemia |
| Glucose | 140–180 mg/dL | Avoid hypoglycemia — check q1–2h |
| Hgb | ≥ 7–9 g/dL | Transfuse if Hgb < 7 (or < 8 if cardiac ischemia) TRICC, 1999 |
Antibiotic Stewardship
De-escalation is mandatory. Broad-spectrum empiric antibiotics carry real harms: C. difficile, fungal infections, nephrotoxicity, resistance selection. Once cultures return, narrow to the narrowest agent that covers the identified organism. Stop antibiotics at 5–7 days if source controlled and patient improving. Use procalcitonin to guide duration.
📋 Clinical Examples — Antibiotic De-Escalation
At 48–72h, cultures and sensitivities return. Here's how to narrow:
| Empiric Regimen | Culture Result | De-Escalate To | Duration |
|---|---|---|---|
| Vancomycin (Vancocin) + Piperacillin-Tazobactam (Zosyn) | Blood cx: MSSA | Stop vanc + Zosyn. Switch to Cefazolin (Ancef) 2g IV q8h | Bacteremia: 2–4 weeks (with ID consult). Source dependent. |
| Vancomycin (Vancocin) + Piperacillin-Tazobactam (Zosyn) | Blood cx: MRSA | Stop Zosyn. Continue Vancomycin (Vancocin) alone (AUC-guided dosing) | MRSA bacteremia: minimum 2 weeks, longer if endocarditis/osteo |
| Vancomycin (Vancocin) + Piperacillin-Tazobactam (Zosyn) | Urine cx: E. coli (pansensitive) | Stop both. Switch to Ceftriaxone (Rocephin) 1g IV daily → PO Ciprofloxacin (Cipro) 500mg BID or TMP-SMX (Bactrim) DS BID | Uncomplicated UTI: 5–7 days. Pyelo: 7–10 days. |
| Vancomycin (Vancocin) + Cefepime (Maxipime) | Sputum cx: Strep pneumoniae | Stop vanc + cefepime. Switch to Ceftriaxone (Rocephin) 1g IV daily → PO Amoxicillin (Amoxil) 1g TID | CAP: 5 days (if afebrile ≥ 48h and clinically improving) |
| Meropenem (Merrem) + Vancomycin (Vancocin) | Blood cx: ESBL* E. coli *ESBL = Extended-Spectrum Beta-Lactamase producing organisms | Stop vanc. Continue Meropenem (Merrem) (ESBL requires carbapenem) → PO TMP-SMX (Bactrim) if susceptible (for UTI source) | Source dependent. Carbapenem is appropriate — this is NOT over-treatment. |
| Vancomycin (Vancocin) + Piperacillin-Tazobactam (Zosyn) | All cultures negative at 48h, patient improving, low procalcitonin | Consider stopping antibiotics entirely. Non-infectious source of SIRS/sepsis (pancreatitis, PE, drug reaction, adrenal crisis)? | If truly no infection: stop. Unnecessary antibiotics = harm. |
The narrowest effective antibiotic is the best antibiotic. Cefazolin (Ancef) for MSSA > vancomycin. Ceftriaxone (Rocephin) for strep pneumo > meropenem. Narrower = less C. diff, less resistance, less nephrotoxicity, lower cost.
💊 Medications & Doses
Empiric Antibiotic Selection
| Clinical Scenario | Empiric Regimen | Notes |
|---|---|---|
| Unknown source, community-acquired | Pip-tazo (Zosyn) 3.375g q6h IV (E. coli, Klebsiella, Pseudomonas, Proteus, Bacteroides, MSSA) + Vancomycin (Vancocin) 25–30 mg/kg loading (MRSA, Strep, Enterococcus) | Pip-tazo = gram-negatives + anaerobes + Pseudomonas. Vanc = MRSA. Together = broadest empiric coverage. |
| Recent abx (< 90 days) or recent hospitalization (increased risk of resistant organisms but NOT automatic carbapenem) | Pip-tazo (Zosyn) 3.375g q6h IV + Vancomycin (Vancocin) (same regimen — Zosyn + vanc is still appropriate) | Still start with Zosyn + vanc. This already covers Pseudomonas + MRSA + anaerobes. Consider adding: (1) antifungal (Micafungin (Mycamine) 100mg IV) if prolonged abx + TPN/central line, (2) double Pseudomonas coverage (add Amikacin (Amikin) or Ciprofloxacin (Cipro)) only if severely ill + high local Pseudomonas resistance. Do NOT escalate to meropenem based on these risk factors alone. |
| Known or suspected MDR* organism *MDR = Multi-Drug Resistant (prior ESBL/CRE* culture, known MDR colonization, institutional antibiogram showing >10–20% ESBL prevalence) *CRE = Carbapenem-Resistant Enterobacterales | Meropenem (Merrem) 1g q8h IV (ESBL E. coli, ESBL Klebsiella, Pseudomonas, Acinetobacter, Enterobacter, Bacteroides) + Vancomycin (Vancocin) (MRSA) | ”HCAP” is no longer a category (removed 2019 ATS/IDSA). Meropenem is NOT first-line for most patients. Reserve for known ESBL/CRE colonization or high institutional ESBL rates on antibiogram. Prior abx use or recent hospitalization alone does NOT warrant a carbapenem — Zosyn + vanc covers the vast majority of scenarios. Add micafungin if Candida risk (TPN, prior abx, abdominal surgery). Always check your local antibiogram. |
| CAP (community-acquired pneumonia) | Ceftriaxone (Rocephin) 1–2g IV daily (S. pneumoniae, H. influenzae, Moraxella, E. coli, Klebsiella) + Azithromycin (Zithromax) 500 mg IV/PO (Mycoplasma, Chlamydophila, Legionella) | Ceftriaxone = typical organisms. Azithro = atypicals. Add vanc/linezolid if MRSA risk. Or levofloxacin monotherapy if Legionella risk. |
| Urosepsis (community-acquired) | Ceftriaxone (Rocephin) 1g IV daily (E. coli, Klebsiella, Proteus, Enterobacter) | E. coli is #1 cause of UTI/urosepsis. Adjust based on urine Gram stain + culture. Cipro if quinolone-susceptible. Add ampicillin if Enterococcus on Gram stain. |
| Biliary / abdominal source | Pip-tazo (Zosyn) 3.375g q6h IV (E. coli, Klebsiella, Enterococcus, Bacteroides, Clostridium) OR Ceftriaxone (Rocephin) (gram-negatives) + Metronidazole (Flagyl) 500 mg q8h IV (Bacteroides, Clostridium, Fusobacterium) | Abdominal infections = gram-negatives + anaerobes. Needs urgent source control (ERCP, IR drainage, surgery). |
| Neutropenic fever (ANC < 500) | Cefepime (Maxipime) 2g q8h IV (E. coli, Klebsiella, Pseudomonas, Enterobacter, Serratia, MSSA) ± Vancomycin (Vancocin) (MRSA) | Cefepime = anti-pseudomonal + broad gram-negative. Add vanc if line infection, skin source, or hemodynamically unstable. Add micafungin at day 4–5 if fever persists. |
| Suspected meningitis | Ceftriaxone (Rocephin) 2g q12h IV (S. pneumoniae, N. meningitidis, H. influenzae, E. coli) + Vancomycin (Vancocin) (penicillin-resistant S. pneumoniae) + Dexamethasone (Decadron) 0.15 mg/kg q6h × 4d | Dex before or with first abx dose. Add ampicillin (Listeria monocytogenes) if > 50yo, immunocompromised, or pregnant. |
| Necrotizing fasciitis | Pip-tazo (Zosyn) (gram-negatives, anaerobes) + Vancomycin (Vancocin) (MRSA) + Clindamycin (Cleocin) 900 mg q8h (Group A Strep toxins, S. aureus toxins — 50S ribosome inhibitor suppresses toxin production) | Clindamycin = toxin suppression (not for coverage). Surgical emergency — OR for debridement ASAP. Delay = death. |
| Suspected fungal sepsis | Micafungin (Mycamine) 100 mg IV daily (Candida species including C. glabrata, C. krusei) OR Fluconazole (Diflucan) 800 mg load → 400 mg IV daily (Candida albicans, C. tropicalis, C. parapsilosis) | Add if: TPN, prior broad-spectrum abx, abdominal surgery, Candida colonization, persistent fever despite antibiotics. Micafungin preferred empirically (broader Candida coverage). Fluconazole for step-down if C. albicans confirmed susceptible. |
🔄 Updated Practice: Vancomycin monitoring has changed. Old practice: target trough 15–20 mcg/mL. New practice (2020 ASHP/IDSA guidelines): target AUC/MIC 400–600 using Bayesian software or two-level AUC estimation. Trough-based dosing led to unnecessary nephrotoxicity. AUC-guided dosing reduces AKI by ~30%.
Vasopressor Guide
| Agent | Dose | Receptor | Role | Avoid |
|---|---|---|---|---|
| Norepinephrine (Levophed) 1ST LINE | 0.01–3 mcg/kg/min | α₁>>β₁ | First-line. ↑ SVR + mild inotropy | — |
| Vasopressin (Pitressin) ADD-ON | 0.03 units/min (fixed, no titration) | V1/V2 | Add vasopressin when NE dose reaches 0.25–0.5 mcg/kg/min (per SSC 2026). Adding vasopressin early allows NE dose reduction (NE-sparing effect). May reduce AKI (V2-mediated water reabsorption). Non-catecholamine → works even in catecholamine-resistant shock (acidosis, downregulated adrenergic receptors). VASST 2008 SSC 2026 | Cardiac ischemia (coronary vasospasm), mesenteric ischemia at high doses, hyponatremia (V2 effect — monitor Na⁺) |
| Epinephrine (Adrenalin) 2ND LINE | 0.01–0.5 mcg/kg/min | α₁, β₁, β₂ | Refractory shock. Adds inotropy. | Falsely elevates lactate (β₂ effect) |
| Phenylephrine (Neo-Synephrine) | 0.5–6 mcg/kg/min | α₁ pure | If tachyarrhythmia limits NE | Low CO states (pure vasoconstriction) |
| Dobutamine (Dobutrex) | 2–20 mcg/kg/min | β₁>β₂ | Low CO despite adequate MAP | Without vasopressor if MAP < 65 |
| Dopamine (Intropin) AVOID | — | D1, β₁, α₁ | Avoid in sepsis — more arrhythmias, higher mortality SOAP II, 2010 | Avoid |
Adjuncts
| Drug | Indication | Dose | Evidence |
|---|---|---|---|
| Hydrocortisone (Solu-Cortef) | Refractory shock on NE > 0.25 mcg/kg/min | 200 mg/day IV (50 mg q6h or continuous) | ADRENAL 2018 — faster shock reversal; no mortality benefit |
| Drotrecogin alfa | — | Withdrawn from market | PROWESS-SHOCK 2012 — no benefit |
📊 Monitoring
ICU Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| MAP (arterial line) | Continuous | ≥ 65 mmHg; higher if chronic HTN |
| Urine output | Hourly | ≥ 0.5 mL/kg/hr; oliguria = reassess volume + pressors |
| Lactate | q2h until < 2 × 2 | Target clearance ≥ 10%/2h |
| Blood glucose | q1–2h (insulin infusion) | 140–180 mg/dL; avoid < 70 |
| BMP | q6–12h initially | Monitor AKI (creatinine), electrolytes, bicarb |
| CBC | Daily | Thrombocytopenia = DIC; trend WBC |
| Cultures | At 48–72h | De-escalate antibiotics based on growth + sensitivities |
| Procalcitonin | q48–72h | If falling and < 0.25 → consider stopping antibiotics PRORATA 2010 |
| Coags (INR, fibrinogen, D-dimer) | Daily if coagulopathy | Fibrinogen < 1.5 + falling = DIC |
| Temperature | Continuous | Hypothermia = worse prognosis than fever |
Organ Support Targets
Renal
AKI develops in 40–50% of septic shock. Avoid nephrotoxins (NSAIDs, aminoglycosides, contrast if possible). CRRT (continuous renal replacement) preferred over IHD in hemodynamically unstable patients. Initiate CRRT for refractory acidosis, hyperkalemia, or volume overload.
Coagulation / DIC
DIC complicates ~35% of septic shock. Treat with FFP if bleeding + INR > 1.5. Platelet transfusion if < 10k (or < 50k if bleeding). Avoid prophylactic FFP unless procedure planned.
Respiratory
Avoid intubation if possible — try HFNC or NIV for early respiratory compromise. If intubated: lung-protective ventilation (TV 6 mL/kg IBW, Pplat ≤ 30). Daily SAT + SBT per ABCDEF bundle.
Antibiotic Duration
Standard: 5–7 days for bacteraemia with good source control. Do not continue antibiotics empirically "just in case." Use procalcitonin trend + clinical response.
Certain infections require longer: endocarditis (4–6 weeks), osteomyelitis (6 weeks — oral step-down is acceptable OVIVA, 2019), S. aureus bacteraemia (minimum 14 days from first negative culture).
Certain infections require longer: endocarditis (4–6 weeks), osteomyelitis (6 weeks — oral step-down is acceptable OVIVA, 2019), S. aureus bacteraemia (minimum 14 days from first negative culture).
📋 On Rounds
📣 Sample Presentation
One-Liner
"Mr. Torres is a 72-year-old with T2DM and CKD3 who presented with 3 days of fever, dysuria, and confusion. Vitals: BP 82/50, HR 118, Temp 39.1°C. Lactate 4.8. He met criteria for septic shock from presumed urosepsis."
Key Points to Cover on Rounds
Source: urosepsis (urine GNR on gram stain, cultures pending). Antibiotics: ceftriaxone day 2, started within 40 min of arrival. Lactate trending 4.8→2.1→1.4. Hemodynamics: NE weaned from 0.12 to 0.04 mcg/kg/min, MAP 68. UOP 45 mL/hr. Cr 2.1 from baseline 1.4, trending down. Plan: narrow abx when cultures finalize, continue NE wean.
Daily Rounds Checklist
- Cultures finalized? → Narrow antibiotics today if possible. What day of antibiotics are we on?
- Lactate cleared? → < 2 on two consecutive measurements = adequate perfusion
- Vasopressor trajectory → Weaning or escalating? Note exact dose and trend
- UOP adequate? → Target ≥ 0.5 mL/kg/hr. If oliguric — reassess volume status + pressor dose
- Source controlled? → Drain placed? Infected line removed? Surgery consulted?
- Procalcitonin trend → Falling PCT supports antibiotic cessation PRORATA 2010
- Glucose 140–180 mg/dL? → Avoid hypoglycemia; tight control not beneficial NICE-SUGAR 2009
- DVT + stress ulcer prophylaxis ordered? (SUP only if high-risk: ventilated > 48h, coagulopathy, GI bleed hx SUP-ICU, 2018)
- Nutrition started? → Enteral preferred within 24–48h if hemodynamically stable
- Sedation/delirium assessment → CAM-ICU, RASS target, daily SAT/SBT
Pimp Questions
What is the Sepsis-3 definition of sepsis vs septic shock?
Sepsis: life-threatening organ dysfunction from dysregulated host response to infection — operationally: suspected infection + SOFA increase ≥ 2. Septic shock: sepsis + vasopressor requirement for MAP ≥ 65 + lactate > 2 despite adequate fluids. Both criteria must be met. Mortality > 40% Singer, JAMA 2016.
What is qSOFA and why is it NOT a diagnostic criterion?
qSOFA: AMS (GCS < 15) + RR ≥ 22 + SBP ≤ 100. Score ≥ 2 = high risk. But it is a screening tool, NOT diagnostic. A patient can be septic with qSOFA = 0. Most useful outside the ICU to flag floor patients needing escalation. Do not use to rule out sepsis.
What does lactate tell you in sepsis, and what is "cryptic shock"?
Lactate ≥ 2 = tissue hypoperfusion even with normal BP — "cryptic shock." Lactate ≥ 4 = high mortality regardless of MAP. Lactate clearance (≥ 10% per 2h) is the resuscitation target ANDROMEDA-SHOCK, 2019. Caveat: epinephrine falsely elevates lactate via β₂-mediated aerobic glycolysis.
Name all 5 components of the SSC 1-hour bundle.
Sepsis bundle: (1) Measure lactate, (2) Blood cultures × 2 before abx, (3) Broad-spectrum antibiotics (within 1h for septic shock, 3h for sepsis without shock), (4) 30 mL/kg balanced crystalloid (LR preferred over NS) if hypotensive or lactate ≥ 4, (5) Vasopressors if MAP < 65 after fluids — peripheral start OK SSC, 2026. Source control within 6–12h. Every hour of antibiotic delay ≈ +7% mortality.
Why is LR preferred over normal saline for sepsis resuscitation?
NS causes hyperchloremic metabolic acidosis → renal afferent vasoconstriction → ↓ GFR → AKI. SMART, 2018: balanced crystalloids (LR/PlasmaLyte) reduced death + new renal failure vs NS. Use LR or PlasmaLyte. Reserve NS for hyponatremia or TBI only.
Why is norepinephrine first-line over dopamine in septic shock?
SOAP II, De Backer 2010: dopamine caused more arrhythmias (24% vs 12%) with trend toward higher mortality. NE is a potent α₁ agonist (raises MAP) with mild β₁ (maintains CO). Dopamine has unpredictable dose-dependent effects and is essentially never first-line anymore.
A septic patient's MAP is 58 after 2L of LR. What next?
Start norepinephrine. Don't keep bolusing. Early vasopressor initiation alongside fluids improves outcomes CENSER, 2019. Start via peripheral IV if no central line — safe above antecubital fossa for < 12–24h. Fluid overload (> 5–6L/24h) independently increases mortality.
Patient on NE 0.3 mcg/kg/min, MAP still 60. What's your next move?
Add vasopressin 0.03 units/min (fixed, no titration) VASST, 2008 — works via V1 receptors (catecholamine-independent). If still inadequate: (1) hydrocortisone 50 mg IV q6h ADRENAL, 2018, (2) reassess source control, (3) bedside echo — distributive vs cardiogenic vs mixed?
When do you give stress-dose steroids in septic shock?
Hydrocortisone 50 mg IV q6h when NE ≥ 0.25 or escalating despite vasopressin. ADRENAL, 2018: no mortality benefit but faster shock reversal. APROCCHSS, 2018: hydrocortisone + fludrocortisone DID reduce 90-day mortality. Don't do a cosyntropin stim test first. Taper over 3–5 days after pressors off.
Can you run norepinephrine through a peripheral IV?
Yes — safe short-term. Rules: large-bore IV above antecubital fossa, concentration ≤ 8 mcg/mL, < 12–24h, site checks q1–2h. Extravasation → treat with phentolamine. Delaying pressors for central access is more dangerous than peripheral extravasation risk.
What empiric antibiotics for undifferentiated septic shock?
Pip-tazo 4.5g q6h + vancomycin (covers GN including Pseudomonas, GP/MRSA, anaerobes). MDR risk → meropenem 1g q8h. Add antifungal if Candida risk. Cultures before abx — but never delay abx for cultures if unstable.
Why does pip-tazo + vancomycin increase AKI risk?
Pip-tazo inhibits renal tubular secretion of vancomycin → increased exposure → nephrotoxicity. Pip-Tazo Nephrotoxicity Study, 2017: significantly higher AKI rates vs cefepime + vanc. In high AKI risk patients, use cefepime as the backbone instead.
How do you use procalcitonin to guide antibiotic duration?
Check PCT baseline then q48–72h. Stop rule: PCT < 0.25 OR ≥ 80% decline from peak. PRORATA, 2010: reduced abx duration by 2.7 days without harm. False positives: surgery, burns, cardiac arrest. False negatives: localized infections.
What is the difference between warm shock and cold shock?
Warm: high CO + low SVR → warm extremities, bounding pulses, wide pulse pressure. Treat with vasopressors. Cold: low CO + high SVR → mottled, cool extremities, weak pulses, narrow PP. Treat with vasopressors + inotropes (dobutamine/epi). Bedside echo critical. Septic cardiomyopathy in ~40% (reversible).
Patient cleared lactate, on NE 0.06 + vasopressin. How do you wean?
Wean NE first, vasopressin last. Reduce NE by 0.02–0.05 q15–30 min. Once NE off → wean vasopressin 0.01 units/min q30 min. Vasopressin provides background vasoconstriction — stopping first → rebound hypotension. Taper hydrocortisone over 3–5 days after pressors off.
SSC 2026 Guideline Updates
SSC 2026: What screening tool now replaces qSOFA for sepsis screening, and why?
NEWS (≥ 7) or MEWS (≥ 5) are now recommended over qSOFA. qSOFA has poor sensitivity — it misses too many septic patients. NEWS scores 7 parameters (RR, SpO₂, supplemental O₂, temp, SBP, HR, consciousness) and is more sensitive for early detection.
SSC 2026: When should you start steroids in septic shock, and what changed from 2016?
Hydrocortisone 200 mg/day is now suggested for septic shock with ongoing vasopressor requirement ≥ 4 hours. This reverses the 2016 recommendation against routine steroids. It shortens shock duration but mortality benefit remains unclear.
SSC 2026: What is the antibiotic timing recommendation for sepsis vs septic shock?
Septic shock: within 1 hour. Sepsis without shock: within 3 hours. Blood cultures before antibiotics when possible — but never delay antibiotics for cultures if the patient is unstable. New section on antibiotic optimization beyond just timing.
SSC 2026: Can you start vasopressors peripherally? What does the guideline say?
Yes — peripheral vasopressors are OK to start. Don't delay pressors waiting for central line access. Use a large-bore IV above the antecubital fossa, concentration ≤ 8 mcg/mL, with site checks every 1–2 hours. Delaying pressors is more dangerous than extravasation risk.
SSC 2026: What is the new recommendation on fluid removal after resuscitation?
For the first time, SSC 2026 addresses fluid removal after initial resuscitation — a topic not previously covered. Don't leave patients fluid-overloaded. Once hemodynamically stable, actively assess for de-resuscitation. Fluid overload independently increases mortality in sepsis.
SSC 2026: What is a "Code Sepsis" and why does the guideline recommend it?
SSC 2026 suggests institutions implement "Code Sepsis" or sepsis huddle protocols — standardized rapid response for suspected sepsis, similar to code blue or stroke alerts. Performance improvement programs at institutional level are also recommended. This is the first time SSC has addressed organizational protocols.
⚡ Summary
Summary
Definition
Organ dysfunction (SOFA ≥ 2) from infection. Shock = vasopressors + lactate > 2 despite adequate IVF.
1-Hour Bundle
Lactate → blood cultures × 2 → broad-spectrum abx → 30 mL/kg IVF → vasopressors if MAP < 65
Antibiotics
Pip-tazo + vancomycin empirically. Meropenem if MDR risk. Narrow at 48–72h. Duration 5–7 days typically.
Vasopressors
NE first-line. Add vasopressin second (0.03 u/min). Hydrocortisone 200 mg/day if NE > 0.25. Dobutamine only for low CO.
Source Control
Find it. Drain it. Remove the line. Consult surgery. Equal importance to antibiotics. Target < 6–12h.
Mortality Hack
Every hour antibiotic delay in septic shock ≈ +7% mortality. Do not wait for cultures. Culture then treat.
Fluid
LR or PlasmaLyte over NS. 30 mL/kg initial. Stop if no response. Fluid overload kills. Check lactate q2h.
De-escalation
Narrow antibiotics at 48–72h. Use procalcitonin. Stop at 5–7 days if improving. Wean vasopressors by MAP response.
📄 One Pager
ICU · One Pager
Sepsis & Septic Shock
Every hour of antibiotic delay = ~7% more mortality. Cultures → antibiotics → fluids → pressors → source control. Do not delay for imaging.
Sepsis-3 Definitions
- Sepsis: SOFA ≥ 2 + suspected infection
- Septic shock: Vasopressors + lactate > 2 despite IVF
- qSOFA: AMS + RR ≥ 22 + SBP ≤ 100 (≥ 2 = high risk, screen only)
- SIRS: ≥ 2 of temp >38/<36, HR >90, RR >20, WBC >12k/<4k (historical, high sensitivity triage)
- Lactate ≥ 4 = cryptic shock even if BP normal
Common Sources
- 🫁 Lung — pneumonia (most common)
- 🚿 UTI / urosepsis
- 🫀 Abdomen — cholangitis, peritonitis
- 💉 Line infection / endocarditis
- 🧠 Meningitis (neck stiffness + fever)
Sepsis Bundle SSC 2026
1
Lactate — measure now, repeat if > 2 in 2h. Target clearance ≥ 10%.
2
Blood cultures × 2 — before antibiotics. UA + urine Cx. Don't delay abx > 45 min.
3
Antibiotics: Pip-tazo + vancomycin (or meropenem if MDR risk). Within 1 hour.
4
30 mL/kg LR/PlasmaLyte if MAP < 65 or lactate ≥ 4. Stop if no response. SMART 2018
5
Vasopressors: NE first-line if MAP < 65 despite fluids. SOAP II, 2010
6
Source control: Drain abscess, remove line, decompress biliary. Target < 12h.
Vasopressors
Norepinephrine (Levophed)1st line — 0.01–3 mcg/kg/min
Vasopressin (Vasostrict)0.03 u/min add-on
Hydrocortisone (Solu-Cortef)200 mg/day if NE > 0.25
Epinephrine (Adrenalin)Refractory only
Dobutamine (Dobutrex)Low CO + adequate MAP
Monitoring Targets
MAP≥ 65 mmHg
UOP≥ 0.5 mL/kg/hr
LactateClear ≥ 10%/2h
Glucose140–180 mg/dL
ScvO₂≥ 70%
Pitfalls
- Delaying antibiotics for cultures
- Using dopamine SOAP II, 2010
- NS over balanced crystalloids
- No source control
- Broad abx never narrowed
- Missing hypothermia = bad sign
Acute Decompensated Heart Failure
Acute worsening of HF symptoms requiring urgent intervention. Classify the hemodynamic profile first (Warm/Cold × Wet/Dry) — it drives everything. For chronic HF and GDMT optimization, see Heart Failure (Chronic).
🔍 Overview
Hemodynamic Profiles (Stevenson / Forrester)
Classify your patient before reaching for diuretics. The profile drives the entire management strategy.
| Profile | Perfusion | Congestion | Management |
|---|---|---|---|
| Warm & Wet (~70%) | Adequate (warm extremities, normal mentation) | Yes (JVD, edema, crackles) | IV diuresis. This is the most common profile. Furosemide, monitor UOP, daily weights. |
| Cold & Wet (~20%) | Impaired (cold, clammy, AMS, low UOP) | Yes | ICU. Inotropes (dobutamine/milrinone) + diuresis. May need invasive monitoring. Consider mechanical circulatory support (MCS) early. |
| Cold & Dry (~5%) | Impaired | No | Cardiogenic shock. Pressors + inotropes + MCS. See Cardiogenic Shock topic. |
| Warm & Dry (~5%) | Adequate | No | Compensated. Optimize oral GDMT. Do NOT over-diurese. Symptom management. |
Presentation & Workup
Symptoms
- Dyspnea, orthopnea, paroxysmal nocturnal dyspnea
- Rapid weight gain (> 2 kg in 48 hrs)
- Leg edema, fatigue, decreased exercise tolerance
Exam
- JVD, S3 gallop, pulmonary crackles, pitting edema
- Elevated JVP = elevated filling pressures (wet)
- Cool extremities, narrow pulse pressure = low output (cold)
Initial Labs & Imaging
| Test | Why |
|---|---|
| BNP / NT-proBNP | Most sensitive. Very high NPV for ruling out HF. BNP > 400 or NT-proBNP > 900 supports ADHF. |
| CXR | Pulmonary vascular congestion, Kerley B lines, cardiomegaly, pleural effusions. Fastest imaging. |
| Echo | Definitive. EF (HFrEF vs HFpEF), wall motion abnormalities, valvular disease, pericardial effusion. |
| BMP | Cr (tracks with diuresis), Na⁺ (hyponatremia = poor prognosis), K⁺, bicarb. |
| Troponin | Rule out ACS as trigger. Demand ischemia common in ADHF. |
| ECG | STEMI trigger? Afib with RVR? New LBBB? |
| CBC, LFTs, TSH | Anemia worsens HF. Congestive hepatopathy. Thyroid disease is reversible cause. |
Common Triggers — What Tipped Them Over?
- Medication non-adherence — most common, especially diuretics and sodium restriction
- Dietary indiscretion — sodium/fluid overload
- ACS / ischemia — always rule out with troponin + ECG
- Afib with RVR — loss of atrial kick + tachycardia-mediated worsening
- Uncontrolled HTN — flash pulmonary edema
- Infection / sepsis — increased metabolic demand on failing heart
- Worsening renal function — impaired diuresis
- Anemia, thyroid disease, PE, medication changes (NSAIDs, CCBs, TZDs)
🚨 Management
Decongestion Strategy (Warm & Wet)
Step 1 — IV Diuresis
IV furosemide — start at 1–2.5× the home oral dose IV. If diuretic-naive, start 40 mg IV. Monitor UOP every hour — target 0.5–1 mL/kg/hr. UOP < 200 mL in 2 hrs = inadequate response.
Step 2 — Diuretic Resistance
Double the furosemide dose OR add metolazone 2.5–5 mg PO 30 min before furosemide (sequential nephron blockade) DOSE, 2011. Or switch to continuous furosemide infusion (10–40 mg/hr). Acetazolamide 500 mg IV daily as adjunct to loop diuretics improves decongestion ADVOR, 2022. Monitor K⁺ and Mg closely — replace aggressively.
Step 3 — Vasodilators (if hypertensive)
Nitroglycerin drip 5–200 mcg/min — reduces preload, improves dyspnea rapidly. Ideal for flash pulmonary edema with SBP > 140. Or nitroprusside 0.3–5 mcg/kg/min (afterload + preload reduction) — requires arterial line, cyanide toxicity risk > 48h. Avoid vasodilators if SBP < 90.
Step 4 — Respiratory Support
BiPAP/CPAP for acute pulmonary edema — reduces work of breathing, ↓ preload, ↓ afterload, buys time for diuretics to work. 3CPO, 2008: NIV reduced dyspnea and physiologic distress but no mortality benefit vs standard O₂. Intubate if: worsening hypoxia despite NIV, RR > 35, inability to protect airway, hemodynamic collapse.
Monitoring
Daily weights (gold standard for tracking decongestion). Daily BMP. UOP q1h (Foley recommended). Cr bump ≤ 0.3 mg/dL acceptable ("acceptable cardiorenal syndrome"). Net negative 1–2 L/day is a reasonable target.
Transition to Oral
When clinically euvolemic: JVD resolved, crackles gone, comfortable on exertion, at dry weight. Convert to oral furosemide at 2× IV dose. Reassess at 24 hrs before discharge.
Cold & Wet / Low Output — DO NOT give aggressive diuretics alone. These patients need inotropic support (dobutamine or milrinone) before or alongside diuresis. ICU admission. Consider MCS early if deteriorating. See Cardiogenic Shock topic.
📋 Clinical Example — HFrEF GDMT Rapid Initiation
Patient: 58M with newly diagnosed HFrEF (EF 25%), BP 118/72, HR 78, K⁺ 4.2, Cr 1.1. Currently on no cardiac medications.
🔄 Old approach: Start ACEi → wait weeks → add BB → wait weeks → add MRA → months later maybe ARNI. Patients spent months without full therapy.
New approach (2022 AHA/ACC, STRONG-HF, 2022): Start all 4 pillars within 1–2 weeks at low doses. Don't wait for one to reach target before starting the next.
| Timepoint | Action |
|---|---|
| Day 1 (Admission) | SGLT2i: Dapagliflozin (Farxiga) 10mg daily — start immediately, no titration needed, minimal BP effect. Beta-blocker: Carvedilol (Coreg) 3.125mg BID — start low, do NOT uptitrate during acute decompensation. |
| Day 2–3 | ARNI: Sacubitril-valsartan (Entresto) 24/26mg BID — if SBP > 100. Go straight to ARNI (skip ACEi if new diagnosis). If already on ACEi, must wash out 36h before starting ARNI. Check BMP: K⁺ and Cr before adding MRA. |
| Day 3–5 | MRA: Spironolactone (Aldactone) 25mg daily — if K⁺ < 5.0 and eGFR > 30. |
| All 4 pillars on board within 1 week. Now uptitrate in parallel: | |
| Week 2 | Entresto → 49/51mg BID, carvedilol → 6.25mg BID (if BP and HR tolerate). |
| Week 4 | Entresto → 97/103mg BID (target dose), carvedilol → 12.5mg BID. |
| Week 8 | Carvedilol → 25mg BID (target dose). |
Key principles:
- Each drug reduces mortality independently — every day without full GDMT is a missed opportunity.
- Hypotension (SBP < 90) is the main limiting factor — prioritize ARNI > BB > MRA if BP-limited.
- "Creatinine bumps" of 0.3–0.5 are acceptable when starting RAAS inhibitors — don't reflexively stop.
- SGLT2i + MRA together are safe — monitor K⁺ but the risk of hyperkalemia is lower than feared.
📋 Clinical Example — Acute Decompensated HF (Wet & Warm)
Patient: 64F with known HFrEF (EF 20%), presents with orthopnea, PND, bilateral crackles, JVP 14cm, 2+ pitting edema. BP 142/88, SpO₂ 90% on RA.
Profile: Wet & Warm (congested, adequate perfusion) — most common presentation.
Immediate:
- Sit upright, O₂ to maintain SpO₂ > 92%. BiPAP if respiratory distress.
- Furosemide (Lasix) 80mg IV push (give 2.5× their home oral dose as IV dose — she takes 40mg PO daily → give 80–100mg IV). Can redose in 2h if < 100mL UOP.
- If inadequate response: double the dose → 160mg IV. If still inadequate → add metolazone (Zaroxolyn) 5mg PO 30 min before next lasix dose (sequential nephron blockade).
Monitoring: Strict I&Os, daily weights (goal: net negative 1–2L/day), BMP BID (watch K⁺ and Cr — "creatinine bumps" of 0.3–0.5 are acceptable if patient is decongesting).
Home GDMT: Continue metoprolol succinate (Toprol XL) at current dose (do NOT uptitrate during decompensation, but do NOT stop unless cardiogenic shock). Hold ACEi/ARNI if hypotensive or Cr rising sharply.
Discharge when: Stable on oral diuretics × 24h, ambulatory SpO₂ > 92%, weight at or near dry weight, scheduled HF clinic follow-up within 7 days.
💊 ADHF Medications
Acute Agents
| Drug (Brand) | Dose | Role | Key Notes |
|---|---|---|---|
| Furosemide (Lasix) 1ST LINE | 40–200 mg IV bolus or 10–40 mg/hr infusion | First-line diuretic. Decongestion. | 1–2.5× home oral dose IV. Monitor UOP, K⁺, Mg, Cr daily. Continuous infusion may cause less ototoxicity than large boluses. |
| Bumetanide (Bumex) ALTERNATIVE | 1–4 mg IV | Alternative loop diuretic. 40:1 ratio (furosemide 40 mg ≈ bumetanide 1 mg). | More predictable oral bioavailability than furosemide. Some prefer in outpatient setting. |
| Metolazone (Zaroxolyn) ADD-ON | 2.5–5 mg PO 30 min before loop diuretic | Sequential nephron blockade. Overcomes diuretic resistance. | Thiazide-like. Works even at low GFR (unlike HCTZ). Massive electrolyte shifts — monitor K⁺, Mg, Na aggressively. |
| Nitroglycerin (Tridil) HYPERTENSIVE ADHF | 5–200 mcg/min IV drip | Preload reduction. Rapid relief of dyspnea in flash pulmonary edema with SBP > 140. | Venodilator predominantly. Titrate to symptom relief. Avoid if SBP < 90, severe AS, RV infarct, or PDE5 inhibitor use (sildenafil within 24h). |
| Nitroprusside (Nipride) SPECIALIZED | 0.3–5 mcg/kg/min IV | Afterload + preload reduction. Refractory hypertensive ADHF. | Requires arterial line. Cyanide toxicity risk > 48h or > 2 mcg/kg/min. Thiocyanate levels if prolonged. Avoid in renal failure (thiocyanate accumulation). |
| Dobutamine (Dobutrex) COLD & WET | 2–20 mcg/kg/min IV | Inotrope for low-output state. Cold & Wet profile. | ↑ CO, ↑ HR. Never use alone if MAP < 65 — pair with NE. Tachyphylaxis after 72h. See Inotropes Guide. |
| Milrinone (Primacor) COLD & WET / RV | 0.125–0.75 mcg/kg/min IV (skip loading dose) | Inodilator. RV failure, pulmonary HTN, patients on chronic BB. | ↓ PVR (key advantage in RV failure). Renally cleared — dose-adjust in AKI. Longer half-life than dobutamine (2–3h). |
GDMT in ADHF — What to Do
Do not stop GDMT abruptly during ADHF hospitalization. Continue at reduced doses if needed. The exception: frank cardiogenic shock → hold everything until stabilized.
| Drug Class | During ADHF | When to Hold |
|---|---|---|
| ACEi / ARB / ARNI* *ARNI = Angiotensin Receptor-Neprilysin Inhibitor (sacubitril-valsartan) | Continue unless hypotensive or AKI | SBP < 90, Cr rising > 30%, K⁺ > 5.5 |
| Beta-blocker | Reduce dose if decompensated. Do NOT stop abruptly. | Cardiogenic shock, symptomatic bradycardia, severe hypotension |
| MRA* (spironolactone) *MRA = Mineralocorticoid Receptor Antagonist (spironolactone, eplerenone) | Continue if K⁺ stable | K⁺ > 5.0, AKI |
| SGLT2i* *SGLT2i = Sodium-Glucose Co-Transporter 2 Inhibitor (dapagliflozin, empagliflozin) | Continue if tolerated. EMPULSE, 2022: empagliflozin started in-hospital ADHF → clinical benefit. | eGFR < 20, DKA risk |
For full chronic GDMT optimization (the four pillars, titration targets, key trials), see Heart Failure (Chronic).
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Davis is a 74-year-old with HFrEF (EF 30%) presenting with 5 days of worsening dyspnea, 8-pound weight gain, and 3-pillow orthopnea. He was started on his home furosemide 80 mg daily last week but ran out. His BNP is 2,400, creatinine is 1.4 from baseline 1.1, and CXR shows pulmonary edema. He is warm and wet — he received IV furosemide 80 mg with 1,400 mL of UOP in the first 6 hours. He's on day 2, down 2.6 kg from admission weight, creatinine 1.5, K⁺ 3.4 for which we're repleting. GDMT is continued. Plan is to transition to oral diuresis today and target discharge tomorrow if he remains comfortable."
Pimp Questions
What is cardiorenal syndrome and when should you stop diuresing?
Worsening renal function during HF treatment. A Cr bump of ≤ 0.3 mg/dL is acceptable and does not indicate stopping diuresis. It's often from reduced renal perfusion pressure — continue if congestion persists. Stop or slow if Cr rising > 0.5 or K⁺ becoming dangerous.
Why should beta-blockers NOT be started in acute decompensation?
Starting beta-blockers in a decompensated state (where cardiac output is already low) can precipitate cardiogenic shock. Wait until the patient is euvolemic and stable. However, do NOT stop them if already on them — abrupt discontinuation worsens outcomes.
What are the 4 pillars of GDMT for HFrEF and why must you start all four?
(1) ARNI (sacubitril-valsartan) or ACEi/ARB, (2) Evidence-based beta-blocker (carvedilol, metoprolol succinate, bisoprolol — NOT atenolol/metoprolol tartrate), (3) MRA (spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). Each independently reduces mortality by 15-30%. Combined, they reduce mortality ~70% vs placebo. Start all four early — don't wait to titrate one before starting the next. The order of initiation matters less than getting all four on board. [PARADIGM-HF, 2014 (ARNI), [DAPA-HF, 2019 (SGLT2i).
How do you know if your diuretic dose is working in ADHF, and when should you escalate?
Track net fluid balance, daily weights, and urine output — not BNP. Good diuretic response: UOP 100-150 mL/hr in first 2h after IV furosemide, net negative 1-2L/day, weight loss 0.5-1 kg/day. If inadequate response (UOP < 100 mL in 2h): double the IV dose (ceiling effect — need higher dose to reach threshold in Loop of Henle). If still inadequate → add metolazone 5 mg PO 30 min before furosemide (sequential nephron blockade). If still refractory → consider furosemide drip (40-80 mg bolus → 10-40 mg/hr) or ultrafiltration. Always monitor Cr and K⁺ — mild Cr rise ("permissive azotemia") is acceptable if patient is decongesting.
⚡ Summary
Summary
First Step
Classify profile: Warm vs Cold / Wet vs Dry. This drives the entire management strategy.
Warm & Wet
IV diuresis at 1–2.5× home dose. Monitor UOP, daily weight, BMP. Add metolazone for diuretic resistance.
Cold & Wet
ICU. Inotropes (dobutamine/milrinone) before aggressive diuresis. May need invasive monitoring.
GDMT
Continue ACEi/ARB/ARNI, beta-blocker (reduce if needed), MRA, SGLT2i. Do not stop without reason.
Discharge Criteria
On oral diuretics, stable on room air, weight at dry weight, no orthopnea, creatinine stable
Biggest Pitfall
Giving fluids to a patient who is "cold" without recognizing they're actually volume overloaded — worsens congestion
📄 One Pager
Cardiology · One Pager
Acute Decompensated Heart Failure
Classify the profile first — Warm/Cold × Wet/Dry. The profile drives everything. Never give fluids to a cold-wet patient.
Hemodynamic Profiles
Warm & WetMost common → diurese
Cold & WetICU → inotropes + diuresis
Cold & DryCardiogenic shock → mechanical circulatory support (MCS)
Warm & DryCompensated → don't over-diurese
Key Workup
- BNP / NT-proBNP (very sensitive)
- BMP — creatinine, Na (hyponatremia = poor prognosis)
- Troponin — rule out ACS trigger
- Echo — EF, valves, effusion
- CXR — pulmonary congestion
Decongestion Strategy (Warm & Wet)
1
IV furosemide: 1–2.5× home oral dose IV. If naive: 40 mg IV.
2
Monitor UOP: Target 0.5–1 mL/kg/hr. If < 200 mL in 2h = inadequate response.
3
No response? Double furosemide dose OR add metolazone 2.5–5 mg PO 30 min before.
4
Daily weight + BMP. Replace K⁺/Mg aggressively. Cr bump ≤ 0.3 acceptable.
5
Transition to oral: 2× IV dose PO when euvolemic (JVD gone, comfortable, dry weight).
GDMT — Do NOT Stop
- ACEi / ARB / ARNI
- Beta-blocker (reduce if needed)
- MRA (if K⁺ stable)
- SGLT2 inhibitor
Discharge Criteria
- Stable on oral diuretics
- RA on room air
- At dry weight
- No orthopnea
- Creatinine stable
Pitfalls
- Fluids to Cold-Wet patient
- Starting BB in decompensation
- Stopping GDMT abruptly
- Over-diuresing Warm-Dry
🧪 Workup
Diagnostic Evaluation — Acute Decompensated Heart Failure
BNP/NT-proBNP is the cornerstone biomarker. BNP > 400 or NT-proBNP > 900 (age-adjusted) strongly supports HF diagnosis. Always obtain an echocardiogram to classify EF and guide therapy.
| Test | Rationale | Key Values |
|---|---|---|
| BNP / NT-proBNP | Diagnosis and prognostication. Trend to assess treatment response. | BNP > 400 pg/mL or NT-proBNP > 900 pg/mL (age < 75) supports HF. Obesity falsely lowers BNP. |
| TTE (echocardiogram) | Classify HFrEF (EF ≤ 40%) vs HFpEF (EF ≥ 50%). Assess wall motion, valves, diastolic function, RVSP. | EF ≤ 40% = HFrEF. EF 41-49% = HFmrEF. LA dilation, elevated E/e' suggest elevated filling pressures. |
| BMP | Cr (cardiorenal syndrome), K⁺ (before RAAS inhibitors), Na⁺ (hyponatremia = poor prognosis), bicarb | Cr rise > 0.3 from baseline = cardiorenal. Na < 135 = independent mortality predictor. |
| CBC | Anemia worsens HF (high-output physiology). Infection as precipitant. | Hgb < 10 → evaluate and treat anemia. Leukocytosis → infectious trigger? |
| Iron studies | Iron deficiency (even without anemia) worsens HF outcomes. IV iron improves symptoms. | Ferritin < 100 OR ferritin 100-299 + TSAT < 20% = iron deficient. Treat with IV iron FAIR-HF, 2009. |
| TSH | Hyper- and hypothyroidism are reversible causes of HF. | Check in all new HF diagnoses. |
| Lipid panel | Assess for ischemic etiology. Guides statin therapy. | Ischemic cardiomyopathy is the #1 cause of HFrEF. |
| ECG | Ischemia, arrhythmia (new AF), LVH, LBBB (CRT candidacy if QRS ≥ 150 ms). | LBBB + EF ≤ 35% + QRS ≥ 150 ms → strong CRT indication. |
| Troponin | Rule out ACS as trigger for decompensation. Chronic mild elevation common in HF. | Acute rise-and-fall → ACS workup. Chronic low-level elevation = myocardial stress (not necessarily ACS). |
| CXR | Pulmonary edema (cephalization, Kerley B lines, effusions), cardiomegaly. | ~20% of ADHF patients have a normal CXR. Do not rely on CXR alone to rule out HF. |
Always identify the precipitant: Dietary indiscretion (salt/fluid), medication non-adherence, new arrhythmia (AF), ACS, infection, uncontrolled HTN, anemia, renal dysfunction, PE, thyroid disease.
📈 Monitoring
Monitoring Parameters — Acute Decompensated Heart Failure
| Parameter | Frequency | Target / Action |
|---|---|---|
| Daily weights | Every morning, same scale, before breakfast | Target 1-2 kg/day net loss during active diuresis. Weight gain > 2 lbs/day = fluid retention → uptitrate diuretics. |
| Strict I&Os | Every shift (q8h tallies) | Net negative 1-2 L/day during active diuresis. UOP ≥ 0.5 mL/kg/hr. If UOP drops, consider diuretic dose increase or combination diuretic therapy. |
| BMP (K⁺, Cr, Na⁺) | Daily while on IV diuretics; q1-2 days after RAAS inhibitor initiation or titration | K⁺ 4.0-5.0 (RAAS inhibitors raise K⁺, diuretics lower it). Cr rise ≤ 0.3 acceptable with diuresis. Na < 130 → consider fluid restriction. |
| Blood pressure | q4-6h inpatient; each clinic visit outpatient | SBP ≥ 90 for ARNI/ACEi/ARB titration. Tolerate asymptomatic SBP 90-100 if on GDMT. Hold vasodilators if symptomatic hypotension. |
| Heart rate | q4-6h inpatient; each visit outpatient | Resting HR 60-70 on maximally tolerated beta-blocker. Do NOT uptitrate BB during active decompensation. |
| BNP / NT-proBNP | Admission and pre-discharge (trend) | > 30% reduction from admission = adequate decongestion. Discharge BNP predicts readmission risk. |
| Echocardiogram (EF) | Reassess at 3-6 months after GDMT optimization | EF improvement on GDMT may reclassify HFrEF → HFimpEF. Continue all GDMT even if EF improves. |
| Telemetry | Continuous during IV diuresis and inotrope use | Monitor for AF, VT, bradycardia from BB/digoxin. Discontinue when stable on oral regimen. |
| Functional status | Each assessment | Dyspnea improvement, orthopnea resolution, exercise tolerance, appetite. The exam matters more than the labs. |
Before discharge: Stable on oral diuretics ≥ 24h, weight trending down or at dry weight, BMP stable, GDMT initiated or uptitrated, follow-up within 7 days, patient weighed and educated on daily weights and 2g Na restriction.
STEMI
ST-elevation myocardial infarction — complete coronary artery occlusion. Door-to-balloon < 90 minutes. Every minute of delay = more dead myocardium. This is the most time-critical diagnosis in cardiology.
🔍 Overview
ECG Criteria
STEMI = cath lab activation. Do not delay for troponin.
| Criteria | Definition |
|---|---|
| ST elevation | ≥ 1 mm in ≥ 2 contiguous leads (or ≥ 2 mm in V1–V3 in men, ≥ 1.5 mm in women) |
| New LBBB | New or presumably new LBBB in setting of ischemic symptoms → treat as STEMI equivalent (use Sgarbossa criteria if prior LBBB) |
| Posterior MI | ST depression V1–V3 with tall R waves → get posterior leads (V7–V9). ST elevation ≥ 0.5 mm confirms posterior STEMI. |
| De Winter T waves | Upsloping ST depression at J-point with tall symmetric T waves in precordial leads → STEMI equivalent (proximal LAD). |
| Wellens syndrome | Deep symmetric T-wave inversions or biphasic T waves in V2–V3 during pain-free interval → critical LAD stenosis. Will STEMI soon if not intervened on. |
Coronary Territories
| ECG Leads | Territory | Artery | Key Complications |
|---|---|---|---|
| V1–V4 | Anterior | LAD | Largest territory. Highest mortality. LV failure, cardiogenic shock, VT/VF, anterior wall aneurysm. |
| II, III, aVF | Inferior | RCA (85%) or LCx (15%) | Bradycardia (AV node from RCA), RV infarct (get right-sided leads V4R). Hypotension — treat with fluids, NOT nitrates. |
| I, aVL, V5–V6 | Lateral | LCx | Often subtle. May be missed. MR from papillary muscle ischemia. |
| V7–V9 | Posterior | PDA (from RCA or LCx) | Missed on standard 12-lead. Always check if ST depression V1–V3. |
| V4R | Right ventricle | Proximal RCA | Avoid nitroglycerin, morphine, diuretics — RV is preload-dependent. Treat hypotension with IV fluids. |
🚨 Management
STEMI Protocol
0 min — Door
12-lead ECG within 10 minutes. Activate cath lab. ASA 325 mg chewed. Heparin bolus (per cath lab protocol). O₂ only if SpO₂ < 90%. IV access × 2.
🔄 Updated Practice: Old teaching: give supplemental oxygen to all MI patients. Current practice: oxygen only if SpO2 <90%. The DETO2X-AMI trial (2017) and AVOID trial (2015) showed that routine oxygen in normoxemic MI patients did NOT reduce infarct size and may worsen outcomes through coronary vasoconstriction and increased oxidative stress. Hyperoxia is not benign.
≤ 90 min — Balloon
Primary PCI (percutaneous coronary intervention) is the gold standard. Door-to-balloon target < 90 min. Stent the culprit lesion. STREAM, 2013
If no PCI available
Fibrinolysis within 30 min of first medical contact if PCI not available within 120 min. Tenecteplase (weight-based single IV bolus) or alteplase. Transfer for angiography within 3–24h regardless. STREAM, 2013: pharmacoinvasive strategy (lysis → transfer for PCI) is non-inferior to primary PCI.
Post-PCI
Dual antiplatelet therapy (DAPT): ASA 81 mg daily + P2Y12 inhibitor (ticagrelor 90 mg BID PLATO, 2009 or prasugrel 10 mg daily TRITON-TIMI 38, 2007 preferred over clopidogrel). Duration: 12 months minimum post-ACS DAPT Study, 2014. May shorten to 3–6 months if high bleeding risk TWILIGHT, 2019. High-intensity statin (atorvastatin 80 mg) PROVE IT-TIMI 22, 2004. Beta-blocker within 24h if stable. ACEi/ARB within 24h if anterior MI or EF < 40%.
Mechanical Complications (Days 1–14)
If a STEMI patient suddenly decompensates 2–7 days post-MI → think mechanical complication.
| Complication | Timing | Presentation | Diagnosis | Treatment |
|---|---|---|---|---|
| Ventricular free wall rupture | Day 3–7 | Sudden PEA arrest, tamponade | Bedside echo → pericardial effusion | Emergent surgery. Almost always fatal without it. |
| Ventricular septal rupture (VSR) | Day 3–7 | New harsh holosystolic murmur + acute HF | Echo with color Doppler → L-to-R shunt. O₂ step-up on right heart cath. | Surgical repair. IABP/Impella as bridge. Very high mortality. |
| Papillary muscle rupture | Day 2–7 | New holosystolic murmur → acute severe MR → flash pulmonary edema | Echo → flail mitral leaflet, severe MR | Emergent mitral valve surgery. Afterload reduction (nitroprusside, IABP) as bridge. |
| LV aneurysm | Weeks–months | Persistent ST elevation post-MI, HF symptoms, arrhythmias | Echo → dyskinetic/akinetic thin-walled segment | Medical management. Anticoagulation if thrombus. Surgery if refractory arrhythmias. |
💊 Medications
Acute STEMI Medications
| Drug | Dose | Timing | Notes |
|---|---|---|---|
| Aspirin IMMEDIATE | 325 mg chewed (not swallowed) | Immediately on recognition | Chewing provides faster absorption. Continue 81 mg daily indefinitely after. ISIS-2, 1988 |
| Ticagrelor (Brilinta) PREFERRED P2Y12 | 180 mg loading → 90 mg BID | At time of PCI (or sooner) | Preferred over clopidogrel PLATO, 2009: reduced CV death + MI + stroke. Reversible binding. Side effects: dyspnea, bradycardia pauses. Do NOT use with > 100 mg ASA. |
| Prasugrel (Effient) PREFERRED P2Y12 | 60 mg loading → 10 mg daily | At time of PCI | TRITON-TIMI 38, 2007: superior to clopidogrel. Contraindicated: prior stroke/TIA, age ≥ 75, weight < 60 kg (increased bleeding). |
| Clopidogrel (Plavix) 2ND LINE P2Y12 | 600 mg loading → 75 mg daily | At PCI | Use if ticagrelor/prasugrel contraindicated. Prodrug — depends on CYP2C19 metabolism. ~30% of patients are poor metabolizers (consider genetic testing). |
| Heparin (UFH) PCI | 70–100 units/kg IV bolus (per cath lab) | At PCI | ACT-guided in cath lab. Bivalirudin is alternative (lower bleeding but higher stent thrombosis). If no PCI planned: enoxaparin 1 mg/kg SC BID is an option ESSENCE, 1997 |
| High-intensity statin ALL ACS | Atorvastatin 80 mg or rosuvastatin 40 mg | Within 24h | Start regardless of LDL. Plaque stabilization + anti-inflammatory beyond lipid lowering. Lifelong. PROVE IT–TIMI 22, 2004 |
| Beta-blocker | Metoprolol 12.5–25 mg PO | Within 24h if stable | Avoid if: cardiogenic shock, HR < 60, SBP < 100, decompensated HF, cocaine use, severe reactive airway. |
| ACEi / ARB | Lisinopril 2.5–5 mg or equivalent | Within 24h | Especially if anterior MI or EF < 40%. Prevents remodeling. Reduce mortality SAVE, 1992. |
| Nitroglycerin (Nitrostat) | 0.4 mg SL q5 min × 3, or drip 5–200 mcg/min | For ongoing chest pain | AVOID in: RV infarct (preload-dependent), SBP < 90, PDE5 inhibitor within 24h (sildenafil) or 48h (tadalafil). Inferior MI → check V4R first. |
📋 On Rounds
Pimp Questions
Why must you check V4R in inferior STEMI?
Inferior STEMI (II, III, aVF) is usually from RCA occlusion, and the proximal RCA also supplies the RV. Up to 40% of inferior STEMIs have RV involvement. RV infarct makes the patient preload-dependent — nitrates, morphine, and diuretics drop preload → hemodynamic collapse. V4R (right-sided V4) showing ≥ 1 mm ST elevation confirms RV involvement. Treatment: IV fluids (not nitrates), avoid diuretics, maintain preload.
What are the Sgarbossa criteria?
Used to diagnose STEMI in the presence of LBBB (where ST changes are expected). Original Sgarbossa: (1) concordant ST elevation ≥ 1 mm — most specific, (2) concordant ST depression ≥ 1 mm in V1–V3, (3) discordant ST elevation ≥ 5 mm. Modified Sgarbossa (Smith): replaces criterion 3 with ST/S ratio ≥ 25% — more sensitive. Any positive criterion in the right clinical context → activate cath lab.
Why is ticagrelor preferred over clopidogrel?
PLATO, 2009: ticagrelor reduced the composite of CV death, MI, and stroke by 16% vs clopidogrel, with 22% reduction in CV mortality. Key advantages: (1) reversible binding (clopidogrel is irreversible — platelet function recovers faster after stopping ticagrelor), (2) no CYP2C19 dependency (clopidogrel is a prodrug requiring activation — ~30% are poor metabolizers). Downsides: BID dosing, dyspnea (~14%), cost.
What is the door-to-balloon time target and what happens if your hospital can't do PCI?
Door-to-balloon time target: ≤ 90 minutes at a PCI-capable hospital. If diagnosed in the field by EMS → target first medical contact-to-balloon ≤ 90 min. If your hospital is NOT PCI-capable: transfer target is first medical contact-to-balloon ≤ 120 min. If transfer time would exceed 120 min → give fibrinolytic therapy (tPA) within 30 minutes of arrival (door-to-needle ≤ 30 min) and then transfer for rescue PCI. After fibrinolysis: routine early PCI within 3-24 hours ("pharmacoinvasive strategy") even if fibrinolysis appears successful — [STREAM, 2013: pharmacoinvasive was non-inferior to primary PCI for early-presenting STEMI. Every minute of delay = more myocardium lost. "Time is muscle" — the benefit of primary PCI diminishes sharply after 120 min from symptom onset.
📣 Sample Presentation
One-Liner
"Mr. Jackson is a 58-year-old smoker with HTN presenting with acute crushing substernal chest pain radiating to left arm × 2 hours. ECG shows ST elevation in leads II, III, aVF. Taken for emergent PCI with DES to RCA with TIMI 3 flow post-intervention."
Key Points to Cover on Rounds
Cath: 99% occlusion of mid-RCA, single DES placed, TIMI 3 flow restored. Peak troponin 42 ng/mL. Echo: EF 45%, inferior hypokinesis. Medications: ASA 81 mg + ticagrelor 90 BID (DAPT), atorvastatin 80, metoprolol 25 BID, lisinopril 5 daily. No arrhythmias on telemetry. Pain-free since cath. Cardiac rehab referral placed. Plan: discharge tomorrow if stable.
🧪 Workup
Diagnostic Evaluation — STEMI
Do NOT delay reperfusion for labs. Door-to-balloon goal < 90 min (PCI) or door-to-needle < 30 min (fibrinolytics). Draw labs while activating the cath lab.
| Test | Rationale | Key Values |
|---|---|---|
| 12-lead ECG | Diagnose STEMI. Identify culprit territory. Repeat q15 min if evolving or diagnostic uncertainty. | ≥ 1 mm ST elevation in 2 contiguous leads (≥ 2 mm in V1-V3 for men > 40). New LBBB with ischemic symptoms. Right-sided leads (V4R) for inferior STEMI → RV involvement. |
| Serial troponins | Confirm myocardial injury and trend infarct size. Do NOT wait for troponin to activate cath lab in STEMI. | Draw at presentation, then q3-6h × 3. Peak troponin correlates with infarct size. High-sensitivity troponin (hs-cTnI or hs-cTnT). |
| CBC | Baseline Hgb (bleeding risk with anticoagulation/DAPT), platelets (for P2Y12 inhibitor). | Hgb < 10 = higher bleeding risk with aggressive antithrombotics. Plt < 100K = relative contraindication to DAPT. |
| BMP | Cr (contrast nephropathy risk, ACEI dosing), K⁺ (arrhythmia risk), glucose (stress hyperglycemia). | K⁺ > 4.0 and Mg²⁺ > 2.0 to minimize arrhythmia risk. Cr for contrast load planning. |
| Coagulation (PT/INR, aPTT) | Baseline before heparin. Identify existing anticoagulation. | Needed before heparin bolus in cath lab. |
| Lipid panel | Draw within 24h (acute-phase changes lower LDL after 24-48h). | Start high-intensity statin regardless of LDL. LDL target < 70 (some guidelines < 55). |
| BNP / NT-proBNP | Prognostication. Elevated BNP = higher risk of HF and mortality post-MI. | Guides post-MI HF risk stratification. |
| Echocardiogram | Assess EF, wall motion abnormalities (correlate with culprit vessel), mechanical complications (VSD, papillary muscle rupture, free wall rupture). | Obtain within 24-48h post-PCI. EF ≤ 40% → ACEI/ARB + aldosterone antagonist. New MR → papillary muscle dysfunction. |
| Type and screen | In case of bleeding complication or need for emergent surgery. | Standard pre-procedural lab. |
📈 Monitoring
Monitoring Parameters — STEMI
| Parameter | Frequency | Target / Action |
|---|---|---|
| Continuous telemetry | Minimum 48 hours post-PCI (longer if EF ≤ 40% or arrhythmias) | Watch for reperfusion arrhythmias (AIVR — usually benign, VT/VF, bradycardia in inferior MI). AIVR is a sign of successful reperfusion — do not treat unless hemodynamically unstable. |
| Serial troponins | q3-6h until peak identified (typically 12-24h post-PCI) | Peak troponin correlates with infarct size. Rising troponin after initial decline → stent thrombosis or reinfarction. |
| ECG | Immediately post-PCI, then daily × 2-3 days | ST resolution > 50% within 60-90 min post-PCI = successful reperfusion. New ST changes → concern for stent thrombosis, re-occlusion. |
| BP and HR | q1h × 4h post-cath, then q4h | SBP > 90 for ACEI/BB initiation. HR 60-80. Hypotension in inferior MI → suspect RV infarct (give fluids, avoid nitroglycerin). |
| Access site | q15min × 1h, then q1h × 4h post-cath | Check for hematoma, bleeding, pseudoaneurysm. Radial: check radial pulse, hand perfusion. Femoral: check distal pulses, retroperitoneal bleed (back pain, Hgb drop). |
| BMP | Daily × 2-3 days, then post-ACEI initiation | Cr (contrast nephropathy peaks 48-72h post-cath). K⁺ > 4.0 and Mg²⁺ > 2.0 for arrhythmia prevention. |
| DAPT compliance | Daily medication reconciliation | ASA 81 mg daily + P2Y12 inhibitor (ticagrelor 90 BID or prasugrel 10 daily). Minimum 12 months post-DES. Premature DAPT discontinuation = stent thrombosis risk. |
| Echocardiogram | Within 24-48h post-PCI | EF, wall motion, mechanical complications (VSD — new murmur + hemodynamic collapse; papillary muscle rupture — acute MR). Repeat at 6-12 weeks if EF ≤ 40%. |
Post-STEMI DAPT is critical. Educate patients: do NOT stop aspirin or ticagrelor/prasugrel without cardiology approval. Premature discontinuation within 30 days of DES = highest risk period for stent thrombosis.
🏥 Clinical Cases
Case 1: Classic Anterior STEMI — The Textbook Case
Scenario: 58M, smoker, HTN, presents to ED at 2:14 AM with crushing substernal chest pain radiating to left arm × 40 minutes. Diaphoretic, pale, HR 102, BP 148/92.
| Phase | Time | Action | Rationale / Pearl |
|---|---|---|---|
| ED Arrival | T+0 min | 12-lead ECG within 10 minutes | ECG shows ST elevation V1-V4 with reciprocal ST depression in II, III, aVF. This is an anterior STEMI — LAD territory. Activate cath lab immediately. |
| Immediate Meds | T+5 min | ASA 325 mg (chewed) + ticagrelor 180 mg PO + heparin 60 U/kg bolus + atorvastatin 80 mg | Chew ASA for rapid absorption. Load P2Y12 inhibitor before cath. Heparin for anticoagulation during PCI. Statin started day 1 regardless of lipid panel. |
| Cath Lab | T+48 min | PCI to LAD: 99% proximal occlusion. Drug-eluting stent (DES) placed. TIMI 3 flow restored. | Door-to-balloon = 48 min (goal < 90 min). Complete occlusion confirmed — this is why ECG, not troponin, drives the decision. Troponin was still negative at arrival. |
| Troponin #1 | T+0 (arrival) | hs-cTnI: 45 ng/L (normal < 26) | Only mildly elevated at presentation — do not wait for troponin to confirm STEMI. ECG is the decision tool. Early troponin may be falsely reassuring in early presenters. |
| Troponin #2 | T+3h | hs-cTnI: 12,400 ng/L (> 250× ULN). Rising rapidly. | Large delta = large infarct. Rapid rise-and-fall pattern typical of reperfused STEMI. Expected to peak 12-24h post-onset. |
| Troponin #3 | T+6h | hs-cTnI: 38,600 ng/L. Still rising. | Continue trending q6h. The magnitude of peak predicts LV dysfunction severity and 30-day mortality. > 10,000 ng/L in anterior STEMI = high risk for EF < 40%. |
| Troponin #4 (peak) | T+12h | hs-cTnI: 85,000 ng/L (peak). Begins declining thereafter. | Peak troponin reached ~12h post-symptom onset. Large anterior MI confirmed. Correlates with TTE findings. Subsequent decline = no re-occlusion. Any secondary rise → suspect stent thrombosis. |
| CCU Day 1 | T+3h | Chest pain resolved. Troponin peaks at 85 ng/mL. TTE: EF 40%, anterior wall hypokinesis. | Peak troponin correlates with infarct size. EF 40% — will need ACEi/ARB and assess for ICD at 40 days. Start metoprolol 25 mg BID if hemodynamically stable. |
| Day 2 | T+24h | Troponin trending down: 42,000 → 18,000 ng/L. Start lisinopril 2.5 mg, uptitrate metoprolol. Cardiac rehab consult. Smoking cessation counseling. | Declining troponin = reassuring (no re-occlusion). ACEi started for EF ≤ 40% (reduces remodeling and mortality). BB reduces arrhythmia risk. Early rehab referral improves adherence and outcomes. |
| Discharge (Day 3) | ASA 81 mg + ticagrelor 90 BID (DAPT × 12 months). Metoprolol succinate 50 mg daily. Lisinopril 5 mg. Atorvastatin 80 mg. Cardiac rehab. Follow-up in 1 week. | Ensure all 4 pillars prescribed before discharge. LDL goal < 70 (or < 55 per ESC). Repeat TTE in 6-12 weeks. Discuss ICD if EF still ≤ 35% at 40 days. |
Teaching point: Anterior STEMIs have the worst prognosis because the LAD supplies ~40% of LV myocardium. These patients are most likely to develop systolic HF, and rapid reperfusion is critical.
Case 2: Inferior STEMI with RV Involvement — The Fluid-Dependent Patient
Scenario: 72M, DM2 and dyslipidemia, presents with epigastric pain and nausea × 1 hour. Thought it was indigestion. HR 48, BP 82/54. Diaphoretic.
| Phase | Time | Action | Rationale / Pearl |
|---|---|---|---|
| ED Arrival | T+0 | ECG: ST elevation II, III, aVF. Reciprocal depression I, aVL. | Inferior STEMI — RCA territory (85%). Immediately get right-sided leads (V4R). V4R shows ST elevation ≥ 1mm — confirms RV infarct. |
| Critical Decision | T+3 min | NO nitroglycerin. NO morphine. Start 500 mL NS bolus. | RV infarct = preload dependent. Nitrates and morphine drop preload → cardiovascular collapse. Fluids first. If still hypotensive after 1-2L, start dobutamine (not norepinephrine — need inotropy, not vasoconstriction). |
| Meds | T+8 min | ASA 325 + clopidogrel 600 (not ticagrelor — patient is bradycardic). Heparin. Atropine 0.5 mg IV for symptomatic bradycardia. | Ticagrelor can worsen bradycardia (PLATO showed more bradycardic pauses). Clopidogrel is safer here. Atropine for vagally-mediated bradycardia (common in inferior MI due to RCA supplying AV node). |
| Cath Lab | T+62 min | PCI to RCA: 100% mid-vessel occlusion. DES placed. TIMI 3 flow. BP improves to 106/68. | RCA reperfusion often dramatically improves hemodynamics. Bradycardia may resolve as AV node perfusion returns. If persistent complete heart block → temporary pacer. |
| Troponin #1 | T+0 (arrival) | hs-cTnI: 180 ng/L (elevated > 26) | Elevated at presentation — 1 hour of symptoms means troponin is already rising. In inferior STEMI, absolute values tend to be lower than anterior (smaller territory). Still — do NOT wait for troponin result. |
| Troponin #2 | T+3h | hs-cTnI: 5,800 ng/L. Rising. | Moderate elevation consistent with RCA territory (supplies ~25-30% of LV). Compare: LAD occlusion often produces troponins > 50,000. |
| Troponin #3 (peak) | T+8h | hs-cTnI: 14,200 ng/L (peak). | Earlier peak than anterior STEMI (smaller territory = faster washout post-reperfusion). Declining troponin + improving hemodynamics = successful reperfusion. Any secondary rise → re-occlusion or stent thrombosis. |
| CCU Day 1 | T+6h | Sinus rhythm restored, HR 68. BP 110/72 on 150 mL/hr NS. TTE: EF 50%, inferior hypokinesis, RV dilated but improving. Troponin trending down. | RV function often recovers within days-weeks (RV is more resilient than LV). Avoid diuretics — patient needs volume. Hold ACEi until hemodynamically stable. |
| Day 2-3 | Troponin 3,400 → 890 ng/L (steadily declining). Wean fluids. Start low-dose metoprolol if HR tolerates. Start lisinopril 2.5 mg cautiously (monitor BP). | RV infarct patients are exquisitely sensitive to volume depletion AND afterload reduction. Titrate meds slowly. If EF preserved, ACEi is less urgent but still beneficial. | |
| Discharge (Day 4) | ASA 81 + clopidogrel 75 × 12 months. Metoprolol succinate 25 mg. Lisinopril 2.5 mg. Atorvastatin 80 mg. Strict diabetes management (A1c target < 7). | Key teaching: Always check V4R in inferior STEMI. RV infarct changes your entire management — no nitrates, aggressive fluids, be cautious with preload-reducing drugs. |
Teaching point: Diabetic patients often present atypically — epigastric pain, nausea, or just "not feeling right." Low threshold for ECG in any diabetic with GI complaints.
Case 3: Late Presenter with Cardiogenic Shock — The Nightmare Scenario
Scenario: 65F, no prior medical history, arrives by EMS after 6 hours of chest pain that started during sleep. She delayed calling because she thought it was anxiety. HR 118, BP 76/50, SpO2 89%, cold/clammy extremities, JVD.
| Phase | Time | Action | Rationale / Pearl |
|---|---|---|---|
| ED Arrival | T+0 | ECG: ST elevation V1-V6, I, aVL (massive anterolateral). Chest X-ray: bilateral pulmonary edema. | Extensive anterior STEMI with Killip Class IV (cardiogenic shock). This is the highest-risk presentation — mortality 40-50% even with PCI. Do NOT delay cath for stabilization. |
| Immediate | T+5 min | ASA 325 + clopidogrel 600 (avoid ticagrelor in shock — absorption unreliable). Heparin. Activate cath lab. Place arterial line. Start norepinephrine 0.1 mcg/kg/min. | Cardiogenic shock = primary PCI regardless of time from onset. Norepinephrine is first-line vasopressor in cardiogenic shock (SOAP II trial). Avoid dopamine (more arrhythmias). Load P2Y12 via NG if vomiting. |
| Pre-Cath | T+15 min | Intubated for respiratory failure and impaired consciousness. PA catheter placed: CI 1.6, PCWP 28, SVR 1800. | PA catheter confirms cardiogenic shock: low CI (< 2.2), high PCWP (> 18), high SVR. BiPAP is an alternative if patient is alert, but this patient is deteriorating. |
| Cath Lab | T+55 min | PCI to LAD: 100% proximal occlusion. DES placed. TIMI 2 flow (incomplete reperfusion). Intra-aortic balloon pump (IABP) placed. | TIMI 2 flow (partial) has worse prognosis than TIMI 3 (complete). Mechanical circulatory support (IABP or Impella) considered for refractory shock. IABP-SHOCK II showed no mortality benefit for IABP, but still used as bridge. |
| Troponin #1 | T+0 (arrival) | hs-cTnI: 28,400 ng/L (massively elevated) | Already very high at presentation — 6 hours of unreperfused ischemia. In cardiogenic shock, troponin may be falsely lower due to decreased cardiac output (poor washout). Once reperfused, expect a secondary surge. |
| Troponin #2 | T+3h post-PCI | hs-cTnI: 96,000 ng/L. Massive surge post-reperfusion. | Reperfusion washout phenomenon: troponin spikes after PCI as necrotic myocardium is reperfused and cellular contents flood the circulation. Higher post-PCI spike = more necrosis, not a new event. |
| Troponin #3 | T+12h | hs-cTnI: 142,000 ng/L (peak). | Late presenters (6h+) have the highest peak troponins. TIMI 2 flow means incomplete washout — troponin may plateau longer. This level predicts severe LV dysfunction and high 30-day mortality. |
| Troponin #4 | T+24h | hs-cTnI: 98,000 ng/L. Beginning to decline. | Slow decline expected with TIMI 2 flow. If troponin re-rises → stent thrombosis, extension of infarct, or type 2 MI from shock. Recheck ECG immediately. |
| CCU Day 1-2 | Persistent shock on norepi + dobutamine. TTE: EF 15%, diffuse anterior akinesis. Lactate trending down from 6.8 to 3.1. Cr rising (1.1 → 2.3). Troponin 98,000 → 54,000 ng/L. | Multiorgan dysfunction from prolonged cardiogenic shock. Add milrinone if dobutamine insufficient. Avoid aggressive diuresis — cardiorenal syndrome. Consider Impella if failing IABP. | |
| Day 3-5 | Slowly weaning vasopressors. Extubated Day 4. Watch for mechanical complications (VSD, papillary rupture — classically Day 3-7). | Day 3-7 is the danger zone for mechanical complications. New murmur + hemodynamic collapse = STAT TTE. Free wall rupture presents as sudden PEA arrest with tamponade. | |
| Day 7-10 | Off pressors. EF 20% on repeat TTE. Start captopril 6.25 mg TID (short-acting, easy to titrate). Careful diuresis with IV furosemide. | Use short-acting ACEi (captopril) initially — if BP drops, it wears off in hours. Sacubitril/valsartan NOT in acute phase (< 36h post-MI). Start after stabilization. | |
| Discharge (Day 14) | ASA 81 + clopidogrel 75 × 12 months. Carvedilol 3.125 BID. Captopril 12.5 TID (switch to sacubitril/valsartan outpatient). Atorvastatin 80. Eplerenone 25 mg. Furosemide PRN. LifeVest (wearable defibrillator) until 40-day EF reassessment for ICD. | EF 20% → high SCD risk. LifeVest bridges to 40-day reassessment (don't implant ICD immediately — EF may recover). If EF still ≤ 35% at 40 days → ICD. Refer for advanced HF evaluation if no recovery. |
Teaching point: Women present later, have atypical symptoms more often, and have higher mortality from STEMI than men. Always maintain high suspicion for ACS in women with chest, jaw, back, or epigastric pain.
Case 4: Posterior STEMI — The One You Almost Missed
Scenario: 49M, no known PMH, presents with 2 hours of severe interscapular and chest pressure. HR 78, BP 134/82. Initial ECG looks "normal" to the intern.
| Phase | Time | Action | Rationale / Pearl |
|---|---|---|---|
| ED Arrival | T+0 | ECG: No ST elevation. But — ST depression V1-V3, tall R waves in V1-V2 (R/S ratio > 1). Subtle but there. | This IS a STEMI. ST depression V1-V3 with tall R waves = posterior MI (mirror image). The standard 12-lead has NO posterior-facing leads. This is the most commonly missed STEMI. |
| Key Move | T+5 min | Posterior leads V7-V9. V7-V9 show ST elevation ≥ 0.5 mm. | Posterior STEMI confirmed. This is a STEMI equivalent — activate cath lab immediately. LCx or PDA (from RCA) territory. Any ST elevation ≥ 0.5 mm in posterior leads is diagnostic. |
| Meds | T+8 min | ASA 325 + ticagrelor 180 + heparin + atorvastatin 80. Cath lab activated. | Standard STEMI protocol. Do NOT wait for troponin to confirm. The posterior leads are your proof. |
| Cath Lab | T+72 min | PCI to LCx: 100% mid-vessel occlusion. DES placed. TIMI 3 flow. | LCx occlusion confirmed. Door-to-balloon 72 min. Without posterior leads, this patient would have been admitted as "NSTEMI" and waited hours-days for cath. |
| Troponin #1 | T+0 (arrival) | hs-cTnI: 620 ng/L (elevated) | 2 hours of symptoms — troponin already elevated. In posterior STEMI, the ECG may look "normal" but the troponin confirms myocardial injury. However the posterior leads, NOT the troponin, drove the cath lab activation. |
| Troponin #2 | T+3h | hs-cTnI: 4,200 ng/L. Rising. | LCx territory is smaller than LAD — expect moderate (not massive) troponin elevation. Peak troponins in LCx STEMI are typically 5,000-25,000 ng/L range. |
| Troponin #3 (peak) | T+8h | hs-cTnI: 9,800 ng/L (peak). | Moderate peak — consistent with smaller infarct territory and good TIMI 3 reperfusion. Early reperfusion limits infarct size. Declining troponin + preserved EF = excellent prognosis. |
| CCU Day 1 | Pain free. Troponin trending down: 6,100 ng/L. TTE: EF 55%, mild posterior/lateral hypokinesis. Mild MR (papillary muscle ischemia). | Good EF because LCx territory is smaller than LAD. Mild MR from posterior papillary muscle — monitor with serial TTE. Usually improves with reperfusion. | |
| Discharge (Day 2) | ASA 81 + ticagrelor 90 BID × 12 months. Metoprolol succinate 25 mg. Atorvastatin 80. Cardiac rehab. No ACEi needed (EF preserved). | Key teaching: "Normal" ECG + ACS symptoms → get posterior leads. ST depression V1-V3 is never normal in ACS. This diagnosis is made by the physician who thinks of it, not by the ECG machine's algorithm. |
Teaching point: Train yourself to look at V1-V3 for ST depression in every ACS patient. If you see it, say "posterior leads" out loud. The ECG machine will never auto-read "posterior STEMI" — only you will.
Case 5: Young Patient with Cocaine-Induced STEMI — The Trap
Scenario: 32M, no PMH, presents at 1 AM with chest pain after using cocaine 2 hours ago. HR 112, BP 168/104, agitated. ECG: ST elevation V1-V4.
| Phase | Time | Action | Rationale / Pearl |
|---|---|---|---|
| ED Arrival | T+0 | ECG: ST elevation V1-V4. STEMI criteria met. But — is this true coronary occlusion or cocaine-induced vasospasm? | Doesn't matter initially — treat as STEMI. Activate cath lab. Can distinguish at angiography. 6% of cocaine chest pain has real MI. |
| Critical Meds | T+3 min | ASA 325 mg. Benzodiazepine (diazepam 5-10 mg IV). Nitroglycerin 0.4 mg SL. NO BETA-BLOCKERS. | Beta-blockers are CONTRAINDICATED in cocaine MI — causes unopposed alpha stimulation → worsens coronary vasospasm and hypertension. Benzos reduce sympathetic drive. Nitro treats vasospasm. If nitro + benzo resolve ST elevation → likely vasospasm, not thrombotic occlusion. |
| Response | T+15 min | After diazepam + nitro: ST elevation persists. Pain ongoing. → Proceed to cath lab. | If ST changes resolve with benzos + nitro → observe, serial ECGs, troponins. If ST changes persist → angiography. This patient has persistent ST elevation → real occlusion until proven otherwise. |
| Cath Lab | T+58 min | PCI to LAD: Thrombus with 90% stenosis in a young vessel. Aspiration thrombectomy + DES. TIMI 3 flow. | Cocaine causes MI via: (1) coronary vasospasm, (2) accelerated atherosclerosis, (3) increased platelet aggregation, (4) increased myocardial oxygen demand. This patient had both thrombus AND underlying disease. |
| Troponin #1 | T+0 (arrival) | hs-cTnI: 52 ng/L (mildly elevated) | Only mildly elevated — cocaine was used 2h ago, but coronary occlusion may be more recent. Key point: if ST elevation resolves with benzos + nitro AND troponin is normal → vasospasm. If troponin rises → true infarction regardless of vasospasm resolution. |
| Troponin #2 | T+3h | hs-cTnI: 6,800 ng/L. Significant rise confirms infarction. | Rising troponin confirms true MI — not just vasospasm. Cocaine-induced MI can have both components (spasm + thrombus). The delta (52 → 6,800) confirms acute necrosis. |
| Troponin #3 (peak) | T+8h | hs-cTnI: 18,400 ng/L (peak). | Moderate peak — aspiration thrombectomy + early reperfusion limited infarct size. Young vessels with less collateral disease may paradoxically have larger infarcts (no collateral protection). Monitor for decline. |
| CCU Day 1 | Symptom free. Troponin declining: 11,200 ng/L. TTE: EF 50%. Start amlodipine 5 mg (vasodilator, safe in cocaine). Still no beta-blocker. | CCB (amlodipine or diltiazem) is safe and treats both vasospasm and hypertension. Can consider non-selective BB (carvedilol) only after cocaine fully cleared (24-48h) and only if clear cardiac indication. | |
| Discharge (Day 3) | ASA 81 + ticagrelor 90 BID × 12 months. Amlodipine 5 mg. Atorvastatin 80. Substance abuse counseling. Psychiatry referral. Social work. | Discharge prescription without addressing cocaine use = guaranteed readmission. Substance abuse consult is as important as the stent. Document the conversation. Arrange follow-up. |
Teaching point: The boards love this case. Remember: no beta-blockers with cocaine. Benzos + nitro first. And always address the substance use — it's the modifiable risk factor that will kill this patient.
⚡ Summary
Summary
Definition
ST elevation in ≥ 2 contiguous leads (≥ 1mm, or ≥ 2mm in V1-V3) OR new LBBB + ischemic symptoms.
Door-to-Balloon
≤ 90 min at PCI center. Transfer target ≤ 120 min. If > 120 min → fibrinolysis within 30 min.
Immediate Meds
ASA 325 mg chewed + P2Y12 inhibitor (ticagrelor 180 or clopidogrel 600) + heparin + atorvastatin 80.
Post-PCI GDMT
DAPT × 12 months. BB (if EF ↓). ACEi (if EF ≤ 40%). Atorvastatin 80. Cardiac rehab.
Complications
Arrhythmias, cardiogenic shock, mechanical (VSD, papillary rupture, free wall rupture) at day 3-7.
Territory
II/III/aVF = RCA (inferior). V1-V4 = LAD (anterior). I/aVL/V5-V6 = LCx (lateral).
📄 One Pager
STEMI — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
STEMI — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
Cardiology · One Pager · One Pager
STEMI
Time is muscle. Door-to-balloon ≤ 90 min. ASA + P2Y12 + heparin + cath lab. Every minute of delay = more myocardium lost.
Diagnosis
- ST elevation ≥ 1mm in ≥ 2 contiguous leads (≥ 2mm in V1-V3)
- New LBBB with ischemic symptoms
- Posterior MI: ST depression V1-V3 → get V7-V9
- Troponin may be normal initially — ECG is the decision tool
Immediate Management
- ASA 325 mg chewed + P2Y12 load (ticagrelor 180 mg)
- Heparin bolus + drip
- Activate cath lab → PCI
- Atorvastatin 80 mg
- Morphine only if refractory pain (may reduce P2Y12 absorption)
Territory Mapping
- II, III, aVF = Inferior (RCA)
- V1-V4 = Anterior (LAD)
- I, aVL, V5-V6 = Lateral (LCx)
- V3R, V4R = Right ventricle (check if inferior STEMI)
Key Drugs
ASA325 mg chewed
Ticagrelor180 mg load
Heparin60 U/kg bolus
Atorvastatin80 mg
Pitfalls
- Delaying PCI for "stabilization"
- Missing posterior/RV STEMI
- Nitro in RV infarct (preload dependent)
- No DAPT × 12 months post-PCI
NSTEMI / Unstable Angina
Acute coronary syndrome WITHOUT ST elevation. Partial or intermittent coronary occlusion. Risk-stratify early (TIMI, GRACE, HEART) to determine invasive vs conservative strategy. Unlike STEMI, you have time to think — but not too much.
🔍 Overview
NSTEMI vs Unstable Angina
| Feature | NSTEMI | Unstable Angina |
|---|---|---|
| Troponin | Elevated (rise and/or fall) | Normal |
| ECG | ST depression, T-wave inversions, or nonspecific (NO ST elevation) | Same — may be normal |
| Pathology | Partial/intermittent occlusion with myocardial necrosis | Partial/intermittent occlusion without necrosis |
| Management | Same initial management. NSTEMI → higher risk → earlier invasive strategy. | Risk-stratify. May be managed conservatively if low-risk. |
With high-sensitivity troponin assays, true "unstable angina" is increasingly rare. Most patients with ACS symptoms now have detectable troponin elevation.
Risk Stratification — HEART Score
Best for ED chest pain disposition — identifies low-risk patients safe for early discharge vs those needing admission and workup. HEART Pathway, 2015
| Component | 0 Points | 1 Point | 2 Points |
|---|---|---|---|
| H — History | Non-suspicious | Moderately suspicious | Highly suspicious |
| E — ECG | Normal | Non-specific repolarization changes | Significant ST deviation |
| A — Age | < 45 | 45–64 | ≥ 65 |
| R — Risk factors | None | 1–2 factors | ≥ 3 factors or known CAD |
| T — Troponin | Normal | 1–3× ULN | > 3× ULN |
| Score | Risk | Action |
|---|---|---|
| 0–3 | Low (< 2% MACE at 6 weeks) | Consider early discharge with outpatient follow-up. Stress test if needed. |
| 4–6 | Intermediate | Admit, observe, serial troponins. Consider angiography. |
| 7–10 | High (> 50% MACE) | Early invasive strategy — angiography within 24h. |
TIMI Risk Score for UA/NSTEMI
Quick bedside risk stratification — 7 yes/no questions, 1 point each. Higher score = higher risk of adverse events at 14 days. TIMI 11B, 1998
| Variable | 1 Point If Present |
|---|---|
| Age ≥ 65 | Yes / No |
| ≥ 3 CAD risk factors | HTN, DM, dyslipidemia, smoking, family hx of premature CAD |
| Known CAD (stenosis ≥ 50%) | Prior coronary stenosis ≥ 50% on cath |
| ASA use in past 7 days | Suggests breakthrough event despite aspirin |
| ≥ 2 anginal episodes in 24h | Recurrent ischemia = higher risk |
| ST deviation ≥ 0.5 mm | ST depression or transient ST elevation on ECG |
| Elevated cardiac biomarkers | Troponin or CK-MB above upper limit of normal |
| TIMI Score | 14-Day Event Rate | Risk Level | Action |
|---|---|---|---|
| 0–2 | 4.7% | Low | Conservative management. Consider early discharge if HEART score also low. |
| 3–4 | 13.2% | Intermediate | Admit. Consider angiography within 24–72h. |
| 5–7 | 40.9% | High | Early invasive strategy — cath within 24h. Consider ICU-level monitoring. |
TIMI vs HEART vs GRACE: TIMI is quick and easy at bedside (7 yes/no questions). HEART is best validated for ED chest pain disposition (who goes home vs who gets admitted). GRACE is the most accurate mortality predictor and drives invasive strategy timing (GRACE > 140 → cath within 24h). Use GRACE for admitted NSTEMI patients.
GRACE Score (Global Registry of Acute Coronary Events)
Most accurate predictor of in-hospital and 6-month mortality in ACS — used to determine timing of invasive strategy in admitted NSTEMI patients.
| Variable | Details |
|---|---|
| Age | Continuous — higher age = more points (e.g., 60 yo = ~58 pts, 80 yo = ~91 pts) |
| Heart rate | Higher HR = more points (e.g., HR 100 = ~15 pts, HR 150 = ~42 pts) |
| Systolic BP | Inverse — lower SBP = more points (SBP 80 = ~63 pts, SBP 160 = ~12 pts) |
| Creatinine | Higher Cr = more points (renal dysfunction worsens prognosis) |
| Killip class | I (no HF) = 0 pts → IV (cardiogenic shock) = ~64 pts |
| Cardiac arrest at presentation | Yes = +43 pts |
| ST-segment deviation | Yes = +30 pts |
| Elevated cardiac enzymes | Yes = +15 pts |
| GRACE Score | In-Hospital Mortality | Risk Level | Action |
|---|---|---|---|
| ≤ 108 | < 1% | Low | Conservative strategy. Stress test before discharge. |
| 109–140 | 1–3% | Intermediate | Consider angiography within 24–72h based on other features. |
| > 140 | > 3% | High | Early invasive strategy — cath within 24h. |
Killip Classification (used in GRACE):
I — No heart failure signs
II — Rales, S3, elevated JVP (mild HF)
III — Acute pulmonary edema
IV — Cardiogenic shock (SBP < 90, end-organ hypoperfusion)
I — No heart failure signs
II — Rales, S3, elevated JVP (mild HF)
III — Acute pulmonary edema
IV — Cardiogenic shock (SBP < 90, end-organ hypoperfusion)
GRACE > 140 = early invasive within 24h. This is the most important cutoff to know. Higher GRACE = more benefit from early angiography TIMACS, 2009.
🚨 Management
Step-by-Step Management — NSTEMI/UA
1
ABCs + Vitals + IV Access + Continuous Telemetry
12-lead ECG within 10 minutes. Establish 2 large-bore IVs. Continuous cardiac monitoring. Supplemental O₂ only if SpO₂ < 90%.
12-lead ECG within 10 minutes. Establish 2 large-bore IVs. Continuous cardiac monitoring. Supplemental O₂ only if SpO₂ < 90%.
2
Aspirin 325 mg — CHEW immediately ISIS-2, 1988
Do NOT swallow whole — chewing provides faster buccal absorption. Continue 81 mg daily lifelong after.
Do NOT swallow whole — chewing provides faster buccal absorption. Continue 81 mg daily lifelong after.
3
Nitroglycerin for ongoing chest pain
SL NTG 0.4 mg q5min × 3, then NTG drip 5–200 mcg/min if pain persists. ⚠️ Contraindications: SBP < 90, RV infarct (check right-sided ECG), PDE5 inhibitor within 24–48h.
SL NTG 0.4 mg q5min × 3, then NTG drip 5–200 mcg/min if pain persists. ⚠️ Contraindications: SBP < 90, RV infarct (check right-sided ECG), PDE5 inhibitor within 24–48h.
4
Anticoagulation — start heparin
UFH drip: 60 U/kg bolus (max 4,000) → 12 U/kg/hr (max 1,000). Target aPTT 1.5–2.5× control.
OR Enoxaparin: 1 mg/kg SC BID (if no PCI planned within 24h, CrCl > 30) ESSENCE, 1997
⚠️ Do NOT switch between heparin types (increases bleeding risk).
UFH drip: 60 U/kg bolus (max 4,000) → 12 U/kg/hr (max 1,000). Target aPTT 1.5–2.5× control.
OR Enoxaparin: 1 mg/kg SC BID (if no PCI planned within 24h, CrCl > 30) ESSENCE, 1997
⚠️ Do NOT switch between heparin types (increases bleeding risk).
5
High-intensity statin — start NOW PROVE IT-TIMI 22, 2004
Atorvastatin 80 mg PO (or rosuvastatin 40 mg). Start regardless of LDL — plaque stabilization + anti-inflammatory effects beyond lipid lowering. Lifelong.
Atorvastatin 80 mg PO (or rosuvastatin 40 mg). Start regardless of LDL — plaque stabilization + anti-inflammatory effects beyond lipid lowering. Lifelong.
6
Beta-blocker within 24 hours (if hemodynamically stable)
Metoprolol tartrate 12.5–25 mg PO q6–12h → titrate to HR 55–65. ⚠️ Hold if: SBP < 100, HR < 60, active HF/pulmonary edema, cocaine use, high-degree AV block.
Metoprolol tartrate 12.5–25 mg PO q6–12h → titrate to HR 55–65. ⚠️ Hold if: SBP < 100, HR < 60, active HF/pulmonary edema, cocaine use, high-degree AV block.
7
Risk stratify — TIMI + HEART + GRACE + serial troponins
TIMI score Quick bedside — 7 yes/no questions, 1 point each. Predicts 14-day death/MI/urgent revasc. Fast to calculate at the bedside; higher score = more benefit from early invasive strategy. TIMI 11B, 1998
HEART score ED disposition — best for deciding who goes home vs who gets admitted. 0–3 = low risk (< 2% MACE), safe for early discharge with outpatient follow-up.
GRACE score Most accurate mortality prediction — in-hospital and 6-month mortality. Drives invasive strategy timing: GRACE > 140 = cath within 24h. Use for all admitted NSTEMI patients.
Serial troponins q3–6h — watch for rise and/or fall pattern.
TIMI score Quick bedside — 7 yes/no questions, 1 point each. Predicts 14-day death/MI/urgent revasc. Fast to calculate at the bedside; higher score = more benefit from early invasive strategy. TIMI 11B, 1998
HEART score ED disposition — best for deciding who goes home vs who gets admitted. 0–3 = low risk (< 2% MACE), safe for early discharge with outpatient follow-up.
GRACE score Most accurate mortality prediction — in-hospital and 6-month mortality. Drives invasive strategy timing: GRACE > 140 = cath within 24h. Use for all admitted NSTEMI patients.
Serial troponins q3–6h — watch for rise and/or fall pattern.
8
Decide: Invasive vs Conservative Strategy TIMACS, 2009
GRACE > 140 or high-risk features → Early invasive (cath within 24h)
Intermediate risk → Delayed invasive (cath within 24–72h)
Low risk (HEART 0–3, negative troponins) → Conservative. Stress test if needed.
GRACE > 140 or high-risk features → Early invasive (cath within 24h)
Intermediate risk → Delayed invasive (cath within 24–72h)
Low risk (HEART 0–3, negative troponins) → Conservative. Stress test if needed.
9
P2Y12 inhibitor — timing depends on strategy PLATO, 2009 TRITON-TIMI 38, 2007
Going to cath → Load in the cath lab AFTER coronary anatomy is known (preserves CABG option — ticagrelor/clopidogrel delay surgery 5–7 days).
Conservative strategy → Load upfront (ticagrelor 180 mg or clopidogrel 600 mg).
Preferred: Ticagrelor 90 mg BID (reversible, faster onset, no CYP2C19 resistance). Prasugrel if going to PCI and no contraindications (prior stroke/TIA, age ≥75, wt <60 kg).
Going to cath → Load in the cath lab AFTER coronary anatomy is known (preserves CABG option — ticagrelor/clopidogrel delay surgery 5–7 days).
Conservative strategy → Load upfront (ticagrelor 180 mg or clopidogrel 600 mg).
Preferred: Ticagrelor 90 mg BID (reversible, faster onset, no CYP2C19 resistance). Prasugrel if going to PCI and no contraindications (prior stroke/TIA, age ≥75, wt <60 kg).
10
Post-PCI / Discharge Optimization
DAPT: ASA 81 mg + ticagrelor 90 mg BID × 12 months (minimum 6 months if high bleed risk) PLATO, 2009
High-intensity statin lifelong 4S, 1994
Beta-blocker (continue indefinitely if EF reduced)
ACEi/ARB if EF < 40%, HTN, DM, or CKD
Smoking cessation + cardiac rehab referral
DAPT: ASA 81 mg + ticagrelor 90 mg BID × 12 months (minimum 6 months if high bleed risk) PLATO, 2009
High-intensity statin lifelong 4S, 1994
Beta-blocker (continue indefinitely if EF reduced)
ACEi/ARB if EF < 40%, HTN, DM, or CKD
Smoking cessation + cardiac rehab referral
⚠️ Do NOT delay for any of these steps:
• Aspirin — give IMMEDIATELY on recognition
• ECG — within 10 minutes
• Heparin — start as soon as ACS confirmed
• Cath — within 2h if hemodynamically unstable (treat like STEMI)
• Aspirin — give IMMEDIATELY on recognition
• ECG — within 10 minutes
• Heparin — start as soon as ACS confirmed
• Cath — within 2h if hemodynamically unstable (treat like STEMI)
Invasive vs Conservative Strategy
| Strategy | Who | Timing | Notes |
|---|---|---|---|
| Immediate invasive (< 2h) | Refractory angina, hemodynamic instability, VT/VF, acute HF | Emergent cath | This is essentially a STEMI-equivalent presentation without ST elevation. |
| Early invasive (≤ 24h) | HEART ≥ 7, GRACE > 140, rising troponin, new ST changes, diabetes | Cath within 24h | TIMACS, 2009: early (< 24h) vs delayed (> 36h) → reduced refractory ischemia in high-risk patients. |
| Delayed invasive (24–72h) | Intermediate risk (HEART 4–6) | Cath within 72h | Acceptable for stable patients. Load P2Y12 when anatomy known (cath lab). |
| Conservative / ischemia-guided | Low risk (HEART 0–3), no recurrent symptoms, negative serial troponins | Stress test if needed | Medical management. Cath only if stress test positive or recurrent symptoms. |
P2Y12 timing in NSTEMI: If going to early cath → load in the cath lab once coronary anatomy is known (in case CABG is needed — clopidogrel/ticagrelor delay surgery 5–7 days). If conservative strategy → load upfront.
PCI vs CABG vs Medical Therapy:
• Stable CAD: PCI does NOT beat optimal medical therapy on hard outcomes COURAGE, 2007
• Multivessel/left-main: CABG preferred over PCI for complex anatomy SYNTAX, 2009
• Diabetics with multivessel CAD: CABG beats PCI FREEDOM, 2012
• Stable CAD: PCI does NOT beat optimal medical therapy on hard outcomes COURAGE, 2007
• Multivessel/left-main: CABG preferred over PCI for complex anatomy SYNTAX, 2009
• Diabetics with multivessel CAD: CABG beats PCI FREEDOM, 2012
📋 On Rounds
Pimp Questions
Why delay P2Y12 loading until cath in NSTEMI?
~10–15% of NSTEMI patients have left main or severe three-vessel disease requiring CABG SYNTAX, 2009 FREEDOM, 2012. If you load ticagrelor or clopidogrel before knowing the anatomy, the patient must wait 5–7 days for the drug to wash out before safe surgery (bleeding risk). By waiting to load until coronary anatomy is known in the cath lab, you preserve the option for urgent CABG without delay.
What's the HEART score and how does it guide disposition?
HEART = History, ECG, Age, Risk factors, Troponin. Score 0–10. 0–3 = low risk (< 2% MACE at 6 weeks) → safe for early discharge with outpatient follow-up. 4–6 = intermediate → admit, observe, serial troponins, consider cath. 7–10 = high risk (> 50% MACE) → early invasive strategy within 24h. The HEART score has been validated in multiple large studies and is increasingly used over TIMI for ED chest pain evaluation.
When do you choose early invasive (cath within 24h) vs conservative strategy in NSTEMI?
Early invasive (cath within 24h): GRACE score > 140, troponin rise, dynamic ST changes, hemodynamic instability, recurrent angina despite therapy, diabetes, eGFR < 60, prior CABG/PCI, LVEF < 40%. Conservative (medical therapy, stress test before cath): low GRACE score, no dynamic changes, troponin borderline, low-risk features. [TIMACS, 2009: early intervention (within 24h) reduced ischemic outcomes in high-risk patients but not in low-risk.
What anticoagulation do you start in NSTEMI and when do you stop it?
Unfractionated heparin drip (60 U/kg bolus → 12 U/kg/hr, target aPTT 1.5-2.5× control) or enoxaparin 1 mg/kg SC BID (if not going to cath immediately). Continue until cath/PCI or for 48h if conservative strategy. Fondaparinux 2.5 mg SC daily is an alternative with lowest bleeding risk but needs UFH supplementation at cath. Key: don't switch between heparin types (increases bleeding risk). Stop anticoagulation after PCI unless other indication (e.g., Afib, mechanical valve).
📣 Sample Presentation
One-Liner
"Mrs. Patel is a 65-year-old with DM, HTN, and dyslipidemia presenting with exertional chest pressure × 3 days, now at rest. ECG shows ST depressions in V4-V6. Troponin trending 0.8→2.4→3.1. GRACE score 142 (high risk)."
Key Points to Cover on Rounds
Troponin peaked at 3.1, now downtrending. Started on heparin drip, ASA, ticagrelor load. Cardiology consulted — planned for cath tomorrow morning (early invasive strategy given high GRACE score). Atorvastatin 80 started. Metoprolol 12.5 BID. Pain controlled with nitroglycerin. No dynamic ECG changes overnight.
🧪 Workup
Diagnostic Evaluation — NSTEMI / Unstable Angina
Serial troponins are essential. A rising pattern (delta) distinguishes acute MI from chronic troponin elevation. Use HEART score and TIMI risk score to guide disposition and invasive strategy timing.
| Test | Rationale | Key Values |
|---|---|---|
| Serial troponins | Diagnose NSTEMI (rising/falling pattern). Draw at presentation, 3h, and 6h. Unstable angina = negative troponins with ischemic symptoms. | hs-cTnI or hs-cTnT: rising delta > 20% from baseline = acute injury. Peak troponin correlates with infarct size and prognosis. |
| 12-lead ECG | ST depressions, T-wave inversions, or dynamic changes. Repeat with any symptom recurrence. | ST depression ≥ 0.5 mm in 2+ contiguous leads. New TWI ≥ 1 mm. Normal ECG does NOT exclude NSTEMI. Wellens' pattern (deep symmetric TWI in V2-V3) = critical LAD stenosis. LCx occlusion is often electrically silent — standard 12-lead has no posterior-facing leads, so isolated posterior/lateral wall ischemia may show only subtle ST depression in V1–V3 or no changes at all. If clinical suspicion is high despite a normal ECG, get posterior leads (V7–V9) and maintain a low threshold for serial ECGs and troponins. |
| HEART score | Risk stratification for chest pain. Guides disposition (discharge vs admit vs cath). | 0-3 = low risk (1.7% MACE, consider discharge). 4-6 = moderate (12% MACE, admit). 7-10 = high (65% MACE, early invasive). |
| TIMI risk score | Predicts 14-day MACE in NSTEMI/UA. Guides invasive vs conservative strategy. | Score 0-2 = low risk. 3-4 = intermediate. 5-7 = high risk → early invasive strategy (cath within 24h). |
| TTE (echocardiogram) | Assess EF, regional wall motion abnormalities (correlate with ischemic territory), valvular disease. | New RWMA supports ACS. EF ≤ 40% → ACEI/ARB + aldosterone antagonist post-MI. Assess for mechanical complications. |
| CBC | Baseline Hgb for bleeding risk, platelets for DAPT safety. | Anemia may contribute to demand ischemia (Type 2 MI). Thrombocytopenia limits antiplatelet options. |
| BMP | Cr for contrast and medication dosing, K⁺/Mg²⁺ for arrhythmia risk. | Adjust heparin dosing for renal function. K⁺ > 4.0, Mg²⁺ > 2.0. |
| Coags, lipid panel | Baseline coags before anticoagulation. Lipid panel within 24h (LDL drops after 24-48h in acute MI). | Start high-intensity statin (atorvastatin 80 mg) regardless of LDL. |
The "ECG-negative" NSTEMI — beware the LCx. The left circumflex artery supplies the posterior and lateral walls, which are poorly represented on a standard 12-lead ECG. An isolated LCx occlusion can present with ischemic symptoms, rising troponins, and a completely normal or near-normal ECG. This is one of the most commonly missed MIs. Always obtain posterior leads (V7–V9) when ACS is suspected and the standard ECG is unrevealing. Look for subtle reciprocal ST depression in V1–V3 (tall R waves, ST depression = posterior STEMI equivalent).
Type 2 MI (demand ischemia) — troponin elevation from supply-demand mismatch (sepsis, tachycardia, anemia, hypotension) rather than plaque rupture. Treat the underlying cause, not with cath. Distinguish from Type 1 (atherothrombotic) by clinical context.
💊 Medications
Key Medications — NSTEMI / Unstable Angina
| Class | Drug / Dose | Key Pearls |
|---|---|---|
| Aspirin | ASA 325 mg loading (chew), then 81 mg daily indefinitely | Give immediately on presentation. Non-enteric coated for faster absorption. Continue lifelong. |
| P2Y12 inhibitor | Ticagrelor (Brilinta) 180 mg load → 90 mg BID PREFERRED Clopidogrel (Plavix) 600 mg load → 75 mg daily Prasugrel (Effient) 60 mg load → 10 mg daily (post-PCI only) | Ticagrelor superior to clopidogrel PLATO, 2009. Prasugrel contraindicated if prior stroke/TIA, age ≥ 75, or weight < 60 kg. DAPT duration: minimum 12 months post-PCI. |
| Anticoagulation | Heparin (UFH) 60 U/kg bolus (max 4000 U) → 12 U/kg/hr (max 1000 U/hr) OR Enoxaparin 1 mg/kg SC q12h | Continue until cath or for duration of hospitalization if conservative strategy. Check aPTT q6h for UFH (goal 60-80s). Reduce enoxaparin to 1 mg/kg daily if CrCl < 30. |
| Beta-blocker | Metoprolol tartrate 12.5-25 mg PO q6-12h → titrate to HR 60-70 | Start within 24h if no HF, cardiogenic shock, bradycardia, or heart block. Avoid IV beta-blocker acutely (increased cardiogenic shock risk). Convert to succinate for discharge. |
| Statin | Atorvastatin (Lipitor) 80 mg daily PREFERRED OR Rosuvastatin 40 mg daily | High-intensity statin for ALL ACS regardless of baseline LDL. Start in-hospital. Do not check LDL to decide — just start it. |
| ACEi / ARB | Lisinopril 2.5-5 mg daily (start low) OR Losartan 25-50 mg daily if ACEi intolerant | Indicated if EF ≤ 40%, anterior MI, diabetes, or HTN. Start within 24h if hemodynamically stable (SBP ≥ 90). Continue indefinitely. |
| Nitroglycerin | NTG 0.4 mg SL q5min × 3 PRN chest pain NTG drip 5-200 mcg/min for refractory pain | Contraindicated if SBP < 90, RV infarct, PDE5 inhibitor within 24-48h. Provides symptom relief — does NOT reduce mortality. |
Timing of invasive strategy: Immediate cath (< 2h) if refractory angina, hemodynamic instability, or VT/VF. Early invasive (within 24h) if GRACE > 140 or TIMI ≥ 3. Delayed invasive (25-72h) for lower-risk patients. Ischemia-guided (conservative) if low-risk and symptom-free.
📈 Monitoring
Monitoring Parameters — NSTEMI / Unstable Angina
| Parameter | Frequency | Target / Action |
|---|---|---|
| Continuous telemetry | Duration of hospitalization (minimum 24-48h) | Monitor for VT/VF, new AF, bradycardia, ST changes. Ischemic ST changes on telemetry → repeat 12-lead ECG immediately. |
| Serial troponins | At presentation, 3h, 6h (until peak identified) | Rising pattern confirms NSTEMI. Plateau or decline = peak identified. Re-elevation after decline → reinfarction or stent thrombosis. |
| Chest pain assessment | q4h nursing assessment + PRN | Recurrent chest pain → repeat ECG, consider NTG, notify cardiology. Refractory pain = indication for urgent cath. |
| BP | q4h (q1h if on NTG drip or hemodynamically unstable) | SBP ≥ 90 for beta-blocker and ACEi initiation. Hold NTG if SBP < 90. Target HR 60-70 with beta-blocker. |
| HR | q4h; continuous on telemetry | Tachycardia > 100 → pain? anxiety? HF? bleeding? Bradycardia < 50 → hold BB, check for conduction disease. |
| aPTT (if on heparin drip) | q6h until therapeutic, then q12h | Goal aPTT 60-80 seconds (1.5-2.5× control). Adjust per institutional heparin nomogram. |
| BMP | Daily; post-cath (contrast nephropathy) | K⁺ > 4.0, Mg²⁺ > 2.0. Cr at 24 and 48h post-contrast. Cr rise > 0.5 = contrast nephropathy. |
| Hgb / Hct | Daily; more frequently if on anticoagulation or post-cath | Hgb drop > 2 without overt bleeding → access site bleed? retroperitoneal hemorrhage? GI bleed? |
Red flags requiring immediate action: Recurrent chest pain with dynamic ECG changes, hemodynamic instability, new murmur (mechanical complication), unexplained Hgb drop (bleeding), acute HF symptoms.
⚡ Summary
Summary
Definition
Troponin rise + fall with ≥ 1 value > 99th percentile + ischemic symptoms or ECG changes. No ST elevation.
Risk Stratify
GRACE score > 140 → early invasive (cath within 24h). Low risk → conservative strategy with stress test.
Anticoagulation
Heparin drip or enoxaparin. Don't switch between types. Stop after PCI unless other indication.
DAPT
ASA + P2Y12 inhibitor (ticagrelor preferred). Duration: 12 months post-PCI, 1-3 months if high bleed risk.
When to Cath
Recurrent angina, hemodynamic instability, high GRACE, dynamic ST changes, elevated troponin, EF < 40%.
Discharge
Atorvastatin 80 4S, 1994, DAPT PLATO, 2009, BB, ACEi if indicated. Smoking cessation. Cardiac rehab referral.
📄 One Pager
NSTEMI / Unstable Angina — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
NSTEMI / UNSTABLE ANGINA — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
Cardiology · One Pager · One Pager
NSTEMI / Unstable Angina
Troponin rise + ischemic symptoms. Risk stratify with GRACE. High risk → early invasive. Low risk → conservative + stress test.
Diagnosis
- Troponin rise + fall with ≥ 1 value > 99th percentile
- Ischemic symptoms or ECG changes (ST depression, TWI)
- UA = same presentation but troponin negative
- GRACE score determines invasive vs conservative strategy
Management
- ASA 325 + P2Y12 load + heparin drip
- GRACE > 140 → cath within 24h (early invasive)
- Low GRACE → conservative: medical therapy + stress test
- Atorvastatin 80 mg, BB if no contraindication
High-Risk Features
- Dynamic ST changes
- Recurrent angina despite medical therapy
- Hemodynamic instability
- Elevated troponin trending up
- EF < 40% on echo
- Diabetes, CKD, prior PCI/CABG
Key Drugs
ASA325 mg → 81 mg daily
Ticagrelor180 mg load → 90 BID
Heparin60 U/kg bolus → drip
Atorvastatin80 mg daily
Pitfalls
- Switching heparin types (increases bleeding)
- Missing Wellens or de Winter pattern
- Not risk-stratifying with GRACE
- Discharging without follow-up plan
Arrhythmias
Comprehensive guide to cardiac arrhythmias — SVT, VT, long QT, Brugada, WPW, MAT, and more. Narrow vs wide, regular vs irregular — the approach is systematic. See also: Atrial Fibrillation & Heart Block & Bradyarrhythmias.
🔍 Overview
Tachycardia Classification
| Width | Regularity | Likely Rhythm | First-Line Treatment |
|---|---|---|---|
| Narrow (< 120 ms) | Regular | AVNRT (~60%), AVRT (~30%), atrial tachycardia (~10%) | Vagal maneuvers → adenosine 6 mg → 12 mg → 12 mg |
| Narrow | Irregular | Afib, Aflutter with variable block, MAT | See Afib topic. MAT → treat underlying (COPD, hypoxia, Mg/K). |
| Wide (> 120 ms) | Regular | VT until proven otherwise. Also: SVT with aberrancy, pre-excited tachycardia. | Treat as VT. Stable → amiodarone. Unstable → cardioversion. Pulseless → defibrillate. |
| Wide | Irregular | Afib with WPW (DANGEROUS), polymorphic VT / Torsades, Afib with aberrancy | Afib + WPW → procainamide or cardiovert. NEVER adenosine/CCB/BB. Torsades → Mg 2g IV + defibrillate if pulseless. |
Rule #1: Wide-complex tachycardia = VT until proven otherwise. Giving adenosine or CCBs to VT can cause hemodynamic collapse. When in doubt, treat as VT.
VT vs SVT with Aberrancy — How to Tell Them Apart
Both present as wide-complex tachycardia. Getting this wrong can be fatal — treating VT with a calcium channel blocker causes hemodynamic collapse. When in doubt, always treat as VT.
| Feature | Favors VT | Favors SVT with Aberrancy |
|---|---|---|
| AV dissociation | ✅ Most specific for VT. P waves march independently at a different rate from QRS. | ❌ Absent — P waves are associated with each QRS (1:1 relationship). |
| Fusion & capture beats | ✅ Pathognomonic for VT. Fusion = P wave partially captures ventricle mid-VT. Capture = sinus beat "captures" ventricle (narrow QRS in midst of wide complexes). | ❌ Not seen. |
| QRS width | ✅ > 160 ms strongly favors VT. Extremely wide (> 200 ms) = almost certainly VT. | Typically 120–140 ms (bundle branch block pattern). |
| QRS morphology | ✅ Bizarre, atypical — doesn't look like a classic RBBB or LBBB pattern. | Looks like a typical RBBB or LBBB (rsR' in V1, or rS in V1 with broad R in V6). |
| Concordance | ✅ All precordial leads (V1–V6) deflect in the same direction (all positive or all negative) = VT. | ❌ Mixed precordial directions (typical R-wave progression). |
| Northwest axis | ✅ Extreme axis deviation (negative in I and aVF) = almost always VT. | Axis is within normal or expected BBB range. |
| RS interval in precordial leads | ✅ RS interval > 100 ms in any precordial lead (Brugada criterion) favors VT. | RS interval < 100 ms. |
| Absence of RS complex | ✅ No RS complex in any V1–V6 lead (all QS or monophasic R) = VT. | RS complexes present in at least one precordial lead. |
| History | ✅ Prior MI, known cardiomyopathy, HF, structural heart disease — VT is overwhelmingly more likely. | Young, no structural heart disease, known SVT/BBB on prior ECG. |
| Hemodynamic stability | ⚠️ Does NOT help differentiate. VT can be hemodynamically stable. Do not assume stable = SVT. | ⚠️ Same — SVT with aberrancy can also be unstable. |
| Response to adenosine | ❌ No effect (VT does not involve AV node). ⚠️ Adenosine is generally safe but NOT diagnostic — VT that doesn't terminate ≠ SVT. | ✅ Terminates or slows (involves AV node reentry). But only give if you're reasonably confident it's SVT. |
⚠️ The Brugada Algorithm for Wide-Complex Tachycardia:
Step 1: Absence of RS complex in ALL precordial leads? → VT
Step 2: RS interval > 100 ms in any precordial lead? → VT
Step 3: AV dissociation present? → VT
Step 4: Morphology criteria for VT in V1 and V6? → VT
If none of the above → SVT with aberrancy. Sensitivity > 98% for VT.
Step 1: Absence of RS complex in ALL precordial leads? → VT
Step 2: RS interval > 100 ms in any precordial lead? → VT
Step 3: AV dissociation present? → VT
Step 4: Morphology criteria for VT in V1 and V6? → VT
If none of the above → SVT with aberrancy. Sensitivity > 98% for VT.
Clinical Pearl: In patients > 50 years old with structural heart disease presenting with wide-complex tachycardia, the diagnosis is VT in ~80% of cases. Age + prior MI = treat as VT until proven otherwise. It is always safer to treat SVT as VT (cardioversion works for both) than to treat VT as SVT (CCBs/adenosine in VT → cardiac arrest).
Atrial Flutter
- Sawtooth pattern in II, III, aVF (best seen in II). Rate typically ~300 bpm with 2:1 block → ventricular rate ~150 bpm.
- If the ventricular rate is exactly ~150 bpm → think flutter until proven otherwise.
- Management: same as Afib (rate control, anticoagulation by CHA₂DS₂-VASc). Often responds better to cardioversion and ablation than to drugs.
- Ablation cure rate for typical (CTI-dependent) flutter is > 95% — refer early.
Sinus Tachycardia
Sinus tachycardia is NOT a primary arrhythmia — it is a physiologic response. Do NOT treat sinus tachycardia with antiarrhythmics. Find and treat the underlying cause.
| Common Causes | Clue |
|---|---|
| Pain / Anxiety | Most common in hospital. Treat the pain. |
| Hypovolemia / Hemorrhage | Tachycardia + hypotension → fluid resuscitate, check Hgb |
| Fever / Infection / Sepsis | HR rises ~10 bpm per 1°F. Look for source. |
| Pulmonary Embolism | Acute onset + hypoxia + pleuritic pain → CT angiogram |
| Hyperthyroidism | Check TSH if persistent without clear cause |
| Anemia | Compensatory tachycardia. Check CBC. |
| Withdrawal | Alcohol, benzodiazepines, opioids |
| Medications | Albuterol, theophylline, stimulants, anticholinergics |
Multifocal Atrial Tachycardia (MAT)
- ≥ 3 distinct P-wave morphologies with varying P-P, PR, and R-R intervals. Irregular rhythm.
- NOT Afib — MAT has discrete P waves before each QRS (Afib has no organized P waves).
- Almost always associated with severe underlying illness: COPD exacerbation, hypoxia, hypercapnia, hypomagnesemia, heart failure, theophylline use.
- Treatment = treat the underlying cause. Correct Mg²⁺ and K⁺. Improve oxygenation. Treat COPD.
- ⚠️ Do NOT cardiovert MAT — it will not work (multiple foci, not a single reentrant circuit).
- If rate control needed: IV magnesium 2g first. Then non-dihydropyridine CCB (verapamil/diltiazem) if no HF. Avoid beta-blockers in COPD-driven MAT.
Junctional Rhythms
- Junctional escape rhythm (40–60 bpm): narrow QRS, absent/retrograde P waves. Occurs when SA node fails or slows (sinus bradycardia, sick sinus, high vagal tone).
- Accelerated junctional rhythm (60–100 bpm): enhanced automaticity of AV junction. Causes: digoxin toxicity (#1), inferior MI, post-cardiac surgery, myocarditis.
- Junctional tachycardia (> 100 bpm): rare in adults. Think dig toxicity or post-surgical.
- Treatment: identify and treat the cause. If dig toxicity → hold digoxin, check level, give Digibind if hemodynamically unstable.
⚠️ Accelerated junctional rhythm + regularization of previously irregular rhythm = think digoxin toxicity until proven otherwise.
Long QT Syndrome
Prolonged QTc (> 500 ms) = high risk for Torsades de Pointes (TdP) — a polymorphic VT that can degenerate into VF and sudden death.
| Type | Cause | Key Features |
|---|---|---|
| Acquired (most common) | Drugs (see table below), electrolyte abnormalities (hypoK, hypoMg, hypoCa), bradycardia, hypothermia, structural heart disease | Reversible — stop offending agent, correct electrolytes |
| Congenital — LQT1 | KCNQ1 mutation (K⁺ channel) | Events triggered by exercise (especially swimming). Beta-blockers effective. |
| Congenital — LQT2 | KCNH2 (hERG) mutation (K⁺ channel) | Events triggered by auditory stimuli (alarm clock, phone). Beta-blockers + avoid triggers. |
| Congenital — LQT3 | SCN5A mutation (Na⁺ channel) | Events at rest/sleep. Beta-blockers less effective. May need ICD + mexiletine. |
⚠️ Common QTc-Prolonging Drugs
| Category | Drugs |
|---|---|
| Antiarrhythmics | Amiodarone, sotalol, dofetilide, procainamide, quinidine, ibutilide |
| Antibiotics | Fluoroquinolones (levofloxacin, moxifloxacin), macrolides (azithromycin, erythromycin), TMP-SMX |
| Antifungals | Fluconazole, voriconazole |
| Antipsychotics | Haloperidol, quetiapine, ziprasidone, chlorpromazine |
| Antiemetics | Ondansetron (IV doses > 16 mg), droperidol |
| Antidepressants | Citalopram, escitalopram (dose-dependent), TCAs |
| Other | Methadone, hydroxychloroquine, sumatriptan |
⚠️ QTc > 500 ms = STOP all QT-prolonging agents immediately. Correct K⁺ to > 4.0 and Mg²⁺ to > 2.0. If Torsades develops: Mg 2g IV push → overdrive pacing or isoproterenol to increase HR (shortens QT). Defibrillate if pulseless.
Brugada Syndrome
- ECG pattern: Coved ST elevation (> 2 mm) with T-wave inversion in V1–V3 (Type 1 = diagnostic). Type 2 (saddleback) is suggestive but not diagnostic.
- Risk: Sudden cardiac death from VF — often during rest or sleep. Young males (20–40), Southeast Asian descent.
- Genetics: SCN5A mutation (Na⁺ channel loss-of-function) in ~20–30% of cases. Autosomal dominant.
- Triggers that unmask/worsen Brugada pattern: Fever (#1 — treat aggressively with antipyretics), sodium channel blockers (flecainide, procainamide, TCAs), cocaine, alcohol excess, vagal stimulation.
- Diagnosis: Type 1 pattern (spontaneous or provoked with ajmaline/flecainide challenge) + clinical criteria (syncope, documented VT/VF, family hx SCD).
⚠️ Fever + Brugada = emergency. Fever can unmask or worsen the Brugada pattern and trigger VF. Treat fever aggressively with acetaminophen. Admit for monitoring if Type 1 pattern appears with fever.
| Treatment | Details |
|---|---|
| ICD (implantable cardioverter-defibrillator) | Only proven therapy to prevent SCD. Indicated for: survived cardiac arrest, documented spontaneous sustained VT, Type 1 + syncope. |
| Quinidine | May suppress VF in Brugada. Used for ICD storm, patients who refuse/can't have ICD, or as bridge. |
| Isoproterenol | Acute VF storm rescue — increases heart rate and Ito current, suppresses arrhythmia. |
| Avoid | Na⁺ channel blockers (flecainide, procainamide, lidocaine), TCAs, excessive alcohol, cocaine, large meals (vagal). |
Wolff-Parkinson-White (WPW) — Expanded
- ECG triad: Short PR (< 120 ms) + delta wave (slurred QRS upstroke) + wide QRS (> 120 ms). Caused by an accessory pathway (Bundle of Kent) bypassing the AV node.
- Orthodromic AVRT (~95%): Impulse goes DOWN the AV node, UP the accessory pathway. Narrow QRS. Treat like SVT (adenosine safe).
- Antidromic AVRT (~5%): Impulse goes DOWN the accessory pathway, UP the AV node. Wide QRS — looks like VT. Procainamide or cardiovert.
⚠️ Afib + WPW = LETHAL COMBINATION. Rapid conduction down the accessory pathway → extremely fast ventricular rates → VF → cardiac arrest.
NEVER give AV nodal blockers: adenosine, beta-blockers, calcium channel blockers, digoxin. These block the AV node and force ALL conduction down the accessory pathway.
Treatment: Procainamide IV (slows accessory pathway) or synchronized cardioversion. If unstable → immediate cardioversion.
NEVER give AV nodal blockers: adenosine, beta-blockers, calcium channel blockers, digoxin. These block the AV node and force ALL conduction down the accessory pathway.
Treatment: Procainamide IV (slows accessory pathway) or synchronized cardioversion. If unstable → immediate cardioversion.
Premature Beats (PACs & PVCs)
| Feature | PAC (Premature Atrial Contraction) | PVC (Premature Ventricular Contraction) |
|---|---|---|
| Origin | Ectopic atrial focus (above AV node) | Ventricular myocardium (below AV node) |
| P Wave | Present — early, abnormal morphology (differs from sinus P) | Absent — no preceding P wave |
| QRS | Narrow (< 120 ms) — conducts normally through His-Purkinje | Wide & bizarre (> 120 ms) — cell-to-cell spread, NOT His-Purkinje |
| QRS Axis | Same as baseline — normal conduction pathway preserved | Different from baseline — axis points away from PVC origin. RVOT PVCs → LBBB + inferior axis. LV PVCs → RBBB morphology. |
| Compensatory Pause | Usually non-compensatory (incomplete) — SA node resets | Usually full compensatory pause — SA node not reset |
| Pulse on Exam | Normal pulse — patient may feel a brief "skip" | Weaker pulse (↓ filling time → ↓ stroke volume). May drop the beat entirely on radial pulse. Followed by a stronger "thud" beat after the pause. |
| Clinical Significance | Almost always benign. Common with caffeine, stress, alcohol. Frequent PACs may predict future Afib. | Benign if: < 10% burden, structurally normal heart, asymptomatic. ⚠️ Concern if: > 10–15% burden (PVC-induced cardiomyopathy), R-on-T phenomenon, post-MI. |
| Aberrancy Clue | Very early PACs may conduct aberrantly (usually RBBB pattern — right bundle has longer refractory period) → wide QRS but axis still normal | Always wide QRS with abnormal axis. If wide-complex beat has same axis as baseline → think aberrant PAC, not PVC. |
| Management | Reassurance. Reduce caffeine/alcohol if symptomatic. Rarely need treatment. | < 10% burden + normal echo: reassure, BB if symptomatic. > 10–15% burden: echo to check EF, consider ablation. CAST, 1991 — ⚠️ do NOT suppress PVCs with Class Ic agents post-MI. |
Sick Sinus Syndrome (Tachy-Brady Syndrome)
- Definition: SA node dysfunction causing alternating bradycardia (sinus bradycardia, sinus pauses, sinoatrial exit block) and tachycardia (paroxysmal Afib, atrial flutter, atrial tachycardia).
- Presentation: Syncope, presyncope, fatigue, exercise intolerance. Often elderly with fibrosis of the SA node.
- Diagnostic clue: Bradycardia that doesn't respond to atropine + intermittent tachyarrhythmias.
- Treatment: Permanent pacemaker (allows safe use of rate-control drugs for the tachycardia component). Without a pacer, rate-controlling drugs worsen the bradycardia.
- Key point: You can't treat the tachy without a pacer to protect against the brady.
Related topics: For detailed Afib management (rate/rhythm control, CHA₂DS₂-VASc, anticoagulation), see Atrial Fibrillation. For AV block classification and pacing indications, see Heart Block & Bradyarrhythmias.
🚨 Management
SVT — Acute Management
Step 1 — Vagal
Vagal maneuvers first. Modified Valsalva (blow into syringe for 15 sec, then lie flat with legs elevated — conversion rate ~43% vs 17% for standard Valsalva REVERT, 2015). Carotid sinus massage (avoid if carotid bruit).
Step 2 — Adenosine
Adenosine 6 mg rapid IV push (antecubital, followed by 20 mL NS flush and arm elevation). If no effect in 1–2 min → 12 mg → 12 mg. Half-life = 6 seconds. Warn patient: transient chest tightness, flushing, sense of doom.
Step 3 — If refractory
Diltiazem 0.25 mg/kg IV (repeat 0.35 mg/kg in 15 min if needed) or verapamil 5 mg IV ACC/AHA/HRS SVT Guidelines, 2015. Or synchronized cardioversion (50–100J biphasic) if unstable or refractory to all drugs.
Ventricular Tachycardia
| Presentation | Treatment |
|---|---|
| Pulseless VT | Defibrillate (unsynchronized) 120–200J biphasic. Start CPR. Follow ACLS arrest protocol. |
| Unstable VT with pulse | Synchronized cardioversion 100–200J. Sedate first if time permits. |
| Stable monomorphic VT | Amiodarone 150 mg IV over 10 min → 1 mg/min × 6h → 0.5 mg/min × 18h. Alternative: procainamide 20–50 mg/min until rhythm converts (monitor QRS width and BP). Lidocaine 1–1.5 mg/kg as third option. |
| Polymorphic VT / Torsades | Magnesium 2g IV push. If pulseless → defibrillate (unsynchronized). Stop QT-prolonging drugs. Overdrive pacing or isoproterenol to increase HR (shortens QT). IV potassium to K⁺ > 4.5. |
Long QT / Torsades — Acute Management
1
STOP all QT-prolonging agents immediately — review med list (antiarrhythmics, antibiotics, antipsychotics, antiemetics).
2
Magnesium 2g IV over 2–5 min — first-line even if Mg level is normal. Stabilizes cardiac membrane.
3
Correct electrolytes: K⁺ to > 4.0 mEq/L, Mg²⁺ to > 2.0 mg/dL, Ca²⁺ normal.
4
If Torsades persists → overdrive pacing (temporary transvenous pacer at rate 90–110 bpm) or isoproterenol drip to increase HR (shortens QT interval). Target HR > 90.
5
If pulseless → defibrillate (unsynchronized) 120–200J biphasic. Do NOT use synchronized cardioversion for polymorphic VT.
⚠️ Do NOT give amiodarone for Torsades — amiodarone itself prolongs QT and will worsen the arrhythmia.
MAT — Management
- Step 1: Treat the underlying cause — optimize COPD, correct hypoxia, treat HF/sepsis.
- Step 2: IV magnesium 2g — often converts or slows MAT.
- Step 3: If rate control needed → non-dihydropyridine CCB (verapamil/diltiazem). Avoid beta-blockers if COPD is the driver.
- ⚠️ Cardioversion does NOT work for MAT — multiple automatic foci, not a reentrant circuit.
- ⚠️ Antiarrhythmics are not effective — focus on the underlying disease.
Electrical Cardioversion — Quick Reference
| Rhythm | Synchronized? | Energy (Biphasic) | Notes |
|---|---|---|---|
| SVT | ✅ Synchronized | 50–100J | Sedate first (propofol, midazolam, or etomidate) |
| Atrial Flutter | ✅ Synchronized | 50–100J | Often converts at low energy |
| Atrial Fibrillation | ✅ Synchronized | 120–200J | Higher energy needed. Anticoagulate ≥ 3 weeks pre or TEE to rule out LAA thrombus. |
| Monomorphic VT (stable) | ✅ Synchronized | 100J → 200J → 300J → 360J | Escalate if first shock fails |
| Polymorphic VT / Torsades | ❌ Unsynchronized (DEFIB) | 120–200J | Can't sync to irregular rhythm — treat as VF |
| VF / Pulseless VT | ❌ Unsynchronized (DEFIB) | 120–200J | ACLS protocol. CPR between shocks. |
Synchronized = shock on R wave (avoids vulnerable T-wave period which could cause VF). Unsynchronized = shock immediately (for VF/pulseless VT/polymorphic VT where there's no reliable R wave to sync to).
📋 On Rounds
Pimp Questions
How do you differentiate SVT with aberrancy from VT?
Several ECG criteria favor VT: (1) AV dissociation (P waves marching through at different rate — most specific), (2) fusion and capture beats, (3) very wide QRS > 160 ms, (4) concordance (all precordial leads same direction), (5) Brugada criteria (absence of RS complex in all precordial leads, RS interval > 100 ms). In practice: if in doubt, treat as VT — it's safer to cardiovert SVT than to give a calcium channel blocker to VT.
What did the REVERT trial show about Valsalva technique?
REVERT, 2015: the modified Valsalva (strain for 15 seconds in semi-recumbent position, then immediately lie flat with legs passively raised to 45° for 15 seconds) converted SVT in 43% of patients vs 17% with standard Valsalva. The leg raise augments venous return → increases vagal tone. Simple, free, and should be tried before adenosine.
What is the modified Valsalva technique and why is it more effective?
The REVERT trial (2015) showed the modified Valsalva converts SVT at 43% vs 17% for standard Valsalva. Technique: patient blows into a 10 mL syringe (generating ~40 mmHg intrathoracic pressure) for 15 seconds while sitting at 45° → immediately lay them flat and passively raise both legs to 45° for 15 seconds. The leg raise augments venous return → stretches the right atrium → enhances vagal tone. This should be attempted before adenosine.
A patient has SVT and you notice a delta wave on the baseline ECG. What do you NOT give?
Do NOT give adenosine, beta-blockers, calcium channel blockers, or digoxin — any AV nodal blocker is dangerous in WPW (Wolff-Parkinson-White). These drugs slow conduction through the AV node but don't affect the accessory pathway. If the patient develops Afib (which is common in WPW), the accessory pathway conducts at high rates without AV nodal braking → ventricular fibrillation and death. Treatment for hemodynamically stable WPW + SVT: procainamide or ibutilide (slow accessory pathway conduction). Unstable → cardioversion. All WPW patients need EP referral for ablation.
Name 5 drugs that prolong the QT interval.
Common QT-prolonging drugs: (1) Sotalol (Class III antiarrhythmic), (2) Haloperidol (antipsychotic — especially IV), (3) Fluoroquinolones (levofloxacin, moxifloxacin), (4) Ondansetron (IV doses > 16 mg), (5) Methadone. Also: amiodarone, dofetilide, procainamide, azithromycin, erythromycin, citalopram, quetiapine, droperidol, fluconazole. Check crediblemeds.org for a complete list. Always check QTc before starting any of these, and monitor during therapy. QTc > 500 ms = stop the drug.
What is Brugada syndrome and what triggers VF?
Brugada syndrome is a channelopathy (SCN5A Na⁺ channel mutation in ~25%) causing coved ST elevation in V1–V3 with risk of sudden cardiac death from VF, typically at rest or during sleep. The biggest trigger is fever — it unmasks or worsens the Brugada pattern and can precipitate VF. Treat fever aggressively with acetaminophen and admit for monitoring. Other triggers: Na⁺ channel blockers (flecainide, TCAs), cocaine, alcohol, vagal stimulation. Treatment: ICD for survivors of cardiac arrest or those with spontaneous Type 1 pattern + syncope. Quinidine for VF storm or when ICD is not possible.
How do you differentiate MAT from Afib on ECG?
Both are irregular, but: MAT has discrete P waves before each QRS — at least 3 different P-wave morphologies with varying P-P, PR, and R-R intervals. Afib has NO organized P waves — just a fibrillating baseline with irregularly irregular ventricular response. MAT is almost always seen in severe COPD or critical illness. Key management difference: MAT cannot be cardioverted (multiple automatic foci, not reentrant). Treatment is fixing the underlying disease (COPD, hypoxia, Mg²⁺ repletion).
When do PVCs need further workup?
PVCs need workup when: (1) PVC burden > 10–15% on Holter monitor (risk of PVC-induced cardiomyopathy), (2) symptomatic (palpitations, presyncope, exercise intolerance), (3) structural heart disease present or suspected, (4) new-onset PVCs post-MI, (5) multifocal PVCs or R-on-T phenomenon. Workup: echo (assess EF), Holter (quantify burden), consider cardiac MRI if cardiomyopathy suspected. CAST trial (1991) proved that suppressing PVCs with Class Ic drugs post-MI increases mortality 3.6× — never use flecainide/encainide to suppress PVCs in structural heart disease.
What is the CAST trial and why is it one of the most important arrhythmia trials?
CAST, 1991: The Cardiac Arrhythmia Suppression Trial tested whether suppressing PVCs with Class Ic antiarrhythmics (flecainide, encainide) after MI would reduce sudden cardiac death. The trial was stopped early because patients on flecainide/encainide had 3.6× higher mortality than placebo. This was a paradigm shift: just because you can suppress an arrhythmia on the monitor doesn't mean you improve outcomes. It established that Class Ic agents are contraindicated in structural heart disease and taught medicine that surrogate endpoints (PVC suppression) ≠ clinical benefit.
📣 Sample Presentation
One-Liner
"Ms. Rivera is a 32-year-old healthy woman presenting with sudden palpitations and HR 186, narrow-complex regular tachycardia on ECG consistent with SVT. Hemodynamically stable. Broke with adenosine 12 mg after failing 6 mg."
Key Points to Cover on Rounds
Converted to sinus rhythm after second adenosine bolus. Post-conversion ECG: normal sinus, no delta wave (WPW ruled out), no short PR. K⁺ 3.8, Mg 2.1 — within normal. TSH normal. No structural heart disease on prior records. First episode, no recurrence. Plan: discharge with cardiology follow-up, consider EP referral if recurrent.
🧪 Workup
Diagnostic Evaluation — SVT
12-lead ECG during tachycardia is the most important diagnostic step. Capture it BEFORE giving adenosine — it is both diagnostic AND therapeutic, and you lose the diagnostic ECG once the rhythm converts.
- 12-lead ECG during tachycardia — narrow complex (< 120 ms)? Regular or irregular? P waves visible? Relationship of P to QRS? Short RP vs long RP? These features differentiate AVNRT, AVRT, and atrial tachycardia.
- Adenosine (6 mg → 12 mg rapid IV push) — diagnostic AND therapeutic. Terminates re-entrant SVTs involving the AV node (AVNRT, AVRT). If it doesn't terminate but reveals underlying atrial activity (flutter waves, atrial tachycardia) → the diagnosis is NOT AVNRT/AVRT.
- BMP — K⁺ (hypokalemia triggers arrhythmias), Mg²⁺ (low Mg → refractory hypoK and arrhythmias), Ca²⁺ (hypercalcemia can shorten QT)
- TSH — hyperthyroidism is a common reversible cause of SVT and atrial fibrillation. Check in all new-onset SVT.
- Troponin — if prolonged SVT (sustained rapid rates can cause demand ischemia, especially in CAD patients) or if chest pain is present
- Echocardiogram — if recurrent SVT, to assess for structural heart disease (WPW with accessory pathway, hypertrophic cardiomyopathy, valvular disease). Not urgent for first isolated episode with normal ECG.
Key ECG features: Narrow complex + regular + no visible P waves = likely AVNRT (most common SVT). Narrow + regular + retrograde P waves in ST segment = AVRT. Narrow + regular + different P wave morphology = atrial tachycardia. Narrow + irregularly irregular = atrial fibrillation (not SVT). Look for delta waves on baseline ECG → WPW (avoid AV nodal blockers).
💊 Medications
Vaughan-Williams Antiarrhythmic Classification
The classic framework for understanding antiarrhythmic drugs. Each class targets a different ion channel. Know the class, MOA, and dangerous side effects.
| Class | MOA | Drugs | Clinical Use | ⚠️ Side Effects |
|---|---|---|---|---|
| Ia Na⁺ channel block (intermediate) | Blocks Na⁺ channels + K⁺ channels → slows conduction + prolongs repolarization. Widens QRS and prolongs QT. | Procainamide (Pronestyl) Quinidine Disopyramide (Norpace) | VT, SVT, Afib, WPW (procainamide). Brugada VF storm (quinidine). | ⚠️ Procainamide: drug-induced lupus (chronic use), QT prolongation → Torsades, agranulocytosis ⚠️ Quinidine: cinchonism (tinnitus, HA, vision changes), diarrhea, thrombocytopenia, QT prolongation |
| Ib Na⁺ channel block (fast) | Blocks Na⁺ channels with fast kinetics → shortens repolarization. Works preferentially on ischemic/depolarized tissue. | Lidocaine (Xylocaine) Mexiletine (Mexitil) | VT/VF (acute, especially ischemia-related). Mexiletine for congenital LQT3. Lidocaine for refractory VF in ACLS. | ⚠️ Lidocaine: CNS toxicity (seizures, confusion, perioral numbness, tremor), bradycardia ⚠️ Mexiletine: GI upset, tremor, dizziness |
| Ic Na⁺ channel block (slow) | Potent Na⁺ channel blockade with slow kinetics → markedly slows conduction. Minimal effect on repolarization. | Flecainide (Tambocor) Propafenone (Rythmol) | Afib/flutter (rhythm control) — "pill-in-pocket" for paroxysmal Afib. SVT. Only in structurally normal hearts. | ⚠️ CAST trial: increased mortality 3.6× post-MI CAST, 1991 ⚠️ Contraindicated in structural heart disease, CAD, HF ⚠️ Proarrhythmic (can organize Afib → flutter with 1:1 conduction → always co-prescribe AV nodal blocker) |
| II Beta-blockers | Block β₁-adrenergic receptors → decrease SA node automaticity, slow AV conduction, reduce myocardial O₂ demand. | Metoprolol (Lopressor) Esmolol (Brevibloc) (ultra-short acting) Atenolol (Tenormin) Propranolol (Inderal) | Rate control (Afib, SVT, sinus tachycardia). Suppress PVCs. Congenital long QT (LQT1, LQT2). Post-MI arrhythmia prevention. | ⚠️ Bradycardia, hypotension, bronchospasm (non-selective), fatigue, depression, mask hypoglycemia in diabetics ⚠️ Do NOT stop abruptly — rebound tachycardia/hypertension |
| III K⁺ channel blockers | Block K⁺ channels → prolong repolarization (action potential duration) → prolong QT interval. | Amiodarone (Cordarone) Sotalol (Betapace) Dofetilide (Tikosyn) Ibutilide (Corvert) | Amiodarone: VT, VF, Afib, almost any arrhythmia (Swiss army knife). Sotalol: Afib, VT. Dofetilide: Afib maintenance. Ibutilide: acute Afib/flutter conversion. | ⚠️ Amiodarone (multiple organ toxicity): pulmonary fibrosis, thyroid dysfunction (hypo & hyper — contains iodine), hepatotoxicity, corneal microdeposits, peripheral neuropathy, blue-gray skin, photosensitivity, QT prolongation ⚠️ Sotalol: QT prolongation → Torsades, bradycardia (also has Class II activity) ⚠️ Dofetilide: must be initiated inpatient (3-day telemetry) — QT prolongation risk. Renally dosed. ⚠️ Ibutilide: QT prolongation → Torsades (monitor 4–6h post-infusion) |
| IV Ca²⁺ channel blockers (non-DHP) | Block L-type Ca²⁺ channels in SA/AV node → slow AV conduction and decrease heart rate. | Diltiazem (Cardizem) Verapamil (Calan) | Rate control (Afib, SVT). Acute SVT termination. AVNRT/AVRT (second-line after adenosine). | ⚠️ Hypotension, bradycardia, constipation (verapamil), peripheral edema ⚠️ NEVER in WPW + Afib (enhances accessory pathway conduction → VF) ⚠️ NEVER in decompensated HF (negative inotropy worsens failure) ⚠️ Avoid with beta-blockers IV (additive AV block risk) |
Other Key Antiarrhythmic Agents
| Drug | MOA | Clinical Use | ⚠️ Side Effects |
|---|---|---|---|
| Adenosine (Adenocard) | Activates A₁ adenosine receptors → transient AV node block (6-second half-life) | First-line for stable narrow-complex SVT (AVNRT/AVRT). Diagnostic (unmasks underlying rhythm). 6 mg → 12 mg → 12 mg rapid IV push. | ⚠️ Transient: chest tightness, flushing, dyspnea, sense of doom (warn patient!) ⚠️ Contraindicated in WPW + Afib, severe asthma, 2nd/3rd degree heart block ⚠️ Theophylline/caffeine antagonize. Dipyridamole/carbamazepine potentiate → reduce dose. |
| Digoxin (Lanoxin) | Inhibits Na⁺/K⁺-ATPase → increases vagal tone (slows AV conduction). Also increases intracellular Ca²⁺ → positive inotropy. | Rate control in Afib (especially with HF — provides inotropy + rate control). Third-line in most settings. | ⚠️ Narrow therapeutic window (0.5–2.0 ng/mL). Toxicity: N/V, visual changes (yellow halos), arrhythmias (accelerated junctional, bidirectional VT, PAT with block) ⚠️ Hypokalemia and hypomagnesemia worsen toxicity ⚠️ Toxicity antidote: Digibind (digoxin-specific Fab antibodies) |
| Magnesium | Stabilizes cardiac cell membranes. Suppresses early afterdepolarizations. Essential cofactor for Na⁺/K⁺-ATPase. | First-line for Torsades de Pointes. Adjunct in MAT. Electrolyte repletion in any arrhythmia. | ⚠️ Flushing, hypotension (if given too fast), loss of deep tendon reflexes (toxicity), respiratory depression (severe toxicity) |
| Atropine | Muscarinic (M₂) receptor antagonist → blocks vagal input to SA/AV node → increases HR and conduction. | First-line for symptomatic bradycardia. 0.5 mg IV q3–5min (max 3 mg). Bridge to transcutaneous/transvenous pacing. | ⚠️ Tachycardia, urinary retention, dry mouth, mydriasis, delirium (especially elderly) ⚠️ Ineffective in infranodal block (Mobitz II, 3rd degree with wide escape) — go straight to pacing |
Drug interactions & renal dosing: Always check Drug Interactions and CrCl Calculator before prescribing antiarrhythmics. Many require renal dose adjustment (dofetilide, sotalol, digoxin, procainamide).
📈 Monitoring
Monitoring — Arrhythmias
| Parameter | Frequency | Target |
|---|---|---|
| Continuous telemetry | Until rhythm stable ×24h | Identify recurrence, assess rate control |
| 12-lead ECG | After conversion + daily | Confirm sinus rhythm, rule out pre-excitation (delta wave → WPW) |
| Vitals | q4h | HR, BP — especially after starting rate/rhythm control agents |
| Electrolytes | Daily | K⁺ > 4.0, Mg²⁺ > 2.0 (low levels promote arrhythmia) |
⚡ Summary
Summary
Definition
Narrow complex regular tachycardia (HR 150-250). Most common: AVNRT > AVRT > atrial tachycardia.
First Move
Modified Valsalva (blow into syringe 15s → lie flat + leg raise). 43% conversion rate [REVERT, 2015].
Adenosine
6 mg rapid IV push → flush. If no effect → 12 mg. Warn patient about chest tightness. Contraindicated in WPW + Afib.
WPW Warning
Delta wave on baseline ECG = accessory pathway. Do NOT give AV nodal blockers → VF risk. Use procainamide.
Unstable
Synchronized cardioversion 50-100J. Don't waste time with meds if hypotensive or altered.
Long-Term
Recurrent SVT → EP referral for catheter ablation (cure rate > 95% for AVNRT). Pill-in-pocket BB/CCB for rare episodes.
📄 One Pager
One Pager — Arrhythmias
SVT — AT A GLANCE
📋 Diagnose: Narrow QRS tachycardia (rate 150–250). Regular R-R.
🧪 Workup: 12-lead ECG, BMP (K⁺, Mg²⁺), TSH, trop if chest pain
⚡ Treat: Vagal → adenosine → cardioversion if unstable
💊 Maintenance: Metoprolol, diltiazem, or flecainide/sotalol for recurrent
📈 Monitor: Telemetry, ECG post-conversion, electrolytes
📣 Present: See Rounds tab
🧪 Workup: 12-lead ECG, BMP (K⁺, Mg²⁺), TSH, trop if chest pain
⚡ Treat: Vagal → adenosine → cardioversion if unstable
💊 Maintenance: Metoprolol, diltiazem, or flecainide/sotalol for recurrent
📈 Monitor: Telemetry, ECG post-conversion, electrolytes
📣 Present: See Rounds tab
📄 One Pager
Cardiology · One Pager · One Pager
SVT
Narrow, regular, fast. Modified Valsalva first, then adenosine. Check for WPW before AV nodal blockers. Unstable → cardiovert.
Diagnosis
- Narrow complex (QRS < 120ms) + regular + HR 150-250
- Most common: AVNRT > AVRT > atrial tachycardia
- No P waves visible or retrograde P waves
- Flutter: sawtooth pattern, HR often ~150 (2:1 block)
Acute Management
- Step 1: Modified Valsalva (blow 15s → lie flat + legs up) [REVERT, 2015]
- Step 2: Adenosine 6 mg rapid IV push → 12 mg if no effect
- Step 3: If refractory → diltiazem 20 mg IV or metoprolol 5 mg IV
- Unstable (hypotension, AMS) → synchronized cardioversion 50-100J
WPW Warning
- Delta wave + short PR on baseline ECG = accessory pathway
- Do NOT give adenosine, BB, CCB, or digoxin
- Risk: Afib conducting via accessory pathway → VF
- Use procainamide or ibutilide instead
- All WPW → EP referral for ablation
Key Drugs
Adenosine6 mg → 12 mg rapid push
Diltiazem20 mg IV over 2 min
Metoprolol5 mg IV q5min × 3
Procainamide15-17 mg/kg IV (WPW)
Pitfalls
- AV nodal blockers in WPW → VF
- Not trying modified Valsalva first
- Missing atrial flutter (2:1 looks like SVT at 150)
- Adenosine in wide-complex tachycardia
Pericarditis & Pericardial Disease
Inflammation of the pericardium. Usually viral and self-limited. The danger: missing tamponade and confusing it with STEMI. Colchicine reduces recurrence by 50%.
🔍 Overview
Diagnosis (≥ 2 of 4 criteria)
- Pleuritic chest pain — sharp, worse with inspiration and supine, improved leaning forward
- Pericardial friction rub — scratchy, 3-component (best heard with diaphragm, patient leaning forward)
- Diffuse ST elevation with PR depression (concave-up, diffuse — NOT territorial like STEMI)
- New or worsening pericardial effusion on echo
Pericarditis vs STEMI on ECG
| Feature | Pericarditis | STEMI |
|---|---|---|
| ST elevation | Diffuse, concave-up ("smiley face") | Territorial (matches coronary distribution), convex-up |
| PR segment | PR depression (except aVR — PR elevation) | Usually normal |
| Reciprocal changes | None (except aVR) | Present (ST depression in opposite leads) |
| Q waves | Absent | May develop |
| T-wave evolution | ST normalizes BEFORE T inversions | T inversions occur WITH persistent ST elevation |
Cardiac Tamponade
Tamponade is a clinical diagnosis, not an echocardiographic one. A large effusion can be well-tolerated (chronic); a small rapidly accumulating effusion can cause tamponade.
- Beck's triad: hypotension, JVD, muffled heart sounds (only ~30% have all three)
- Pulsus paradoxus > 10 mmHg (SBP drop > 10 with inspiration) — most sensitive clinical sign
- Echo: RA collapse in systole (earliest), RV diastolic collapse, IVC plethora (no collapse with inspiration)
- Electrical alternans on ECG (swinging heart) — classic but uncommon
- Treatment: emergent pericardiocentesis — subxiphoid approach, echo-guided. Drain as much as possible. Send fluid for cell count, protein, LDH, glucose, gram stain, culture, cytology, ADA.
🚨 Management
Acute Pericarditis — Treatment
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| NSAIDs 1ST LINE | Ibuprofen 600 mg PO TID or ASA 750–1000 mg PO TID | 1–2 weeks, taper over 2–4 weeks | First-line anti-inflammatory. ASA preferred post-MI (NSAIDs impair scar formation). Add PPI for gastric protection. |
| Colchicine (Colcrys) ADD TO ALL | 0.5 mg BID (if > 70 kg) or 0.5 mg daily (if ≤ 70 kg) | 3 months | COPE, 2005 + ICAP, 2011: colchicine reduced recurrence by ~50%. Should be added to ALL pericarditis treatment. GI side effects (diarrhea). Renal dose if CrCl < 30. |
| Corticosteroids LAST RESORT | Prednisone 0.25–0.5 mg/kg/day | Taper over weeks–months | Avoid if possible — steroids increase recurrence rate. Use only if NSAIDs + colchicine contraindicated or failed, or autoimmune etiology confirmed. Taper VERY slowly. |
Exercise restriction: Non-athletes → restrict until symptoms resolve + CRP normalizes. Athletes → minimum 3 months of no competitive sports ESC 2015 guidelines.
📋 On Rounds
Pimp Questions
Why do steroids increase recurrence in pericarditis?
Steroids suppress the immune response so effectively that the underlying viral/inflammatory process doesn't fully resolve — it smolders. When you taper the steroids, the inflammation rebounds. This is why COPE, 2005 and subsequent studies showed steroids as an independent predictor of recurrence. Colchicine, by contrast, modulates the inflammatory response without suppressing it entirely, leading to more durable resolution.
How do you differentiate pericardial effusion from tamponade?
Effusion is an anatomic finding. Tamponade is a hemodynamic diagnosis. A patient can have a massive chronic effusion with no hemodynamic compromise (the pericardium stretches slowly). Conversely, 200 mL accumulating rapidly (e.g., post-procedure, trauma, aortic dissection) can cause tamponade. The diagnosis is clinical: hypotension + JVD + pulsus paradoxus + echo showing diastolic chamber collapse. Don't wait for all of Beck's triad — it's a late finding.
When should you suspect cardiac tamponade in a patient with pericarditis?
Beck's triad: hypotension + JVD + muffled heart sounds (only 10-40% have all three). More reliable: pulsus paradoxus > 10 mmHg (SBP drops > 10 during inspiration). Best bedside test: echo showing diastolic RV collapse (most specific), RA collapse, IVC plethora (dilated, no respiratory variation), respiratory variation in mitral/tricuspid inflow velocities. Tamponade is a clinical diagnosis, not an echo diagnosis — a large effusion without hemodynamic compromise is NOT tamponade. Treatment: emergent pericardiocentesis (usually echo-guided subxiphoid approach).
Why do you add colchicine to NSAIDs for pericarditis?
[COPE, 2005 and [ICAP, 2011: adding colchicine to NSAIDs halved the recurrence rate from ~30% to ~15%. Colchicine inhibits tubulin polymerization → blocks neutrophil chemotaxis and inflammasome activation. Dose: 0.5 mg BID (or 0.5 mg daily if < 70 kg) × 3 months for first episode, × 6 months for recurrence. Start colchicine on day 1 — not just for recurrence prevention. Low-dose is as effective as high-dose with far fewer GI side effects [AGREE-like evidence from gout.
📣 Sample Presentation
One-Liner
"Mr. Okafor is a 24-year-old presenting with sharp pleuritic chest pain worse lying flat, improved leaning forward, following a URI 10 days ago. ECG shows diffuse ST elevation with PR depression. Troponin mildly elevated at 0.15 suggesting myopericarditis."
Key Points to Cover on Rounds
Etiology: likely viral (post-URI). Troponin 0.15 (mild, myopericarditis). Echo: small pericardial effusion, no tamponade physiology. CRP 8.4 (elevated, will trend). Treatment: ibuprofen 600 mg TID × 2 weeks + colchicine 0.5 mg BID × 3 months. Pain improving. Avoiding exercise until CRP normalizes and symptoms resolve. Plan: repeat echo in 1 week, CRP weekly.
🧪 Workup
Workup — Pericarditis & Pericardial Disease
| Test | Findings | Clinical Significance |
|---|---|---|
| 12-lead ECG | Diffuse ST elevation (concave up), PR depression, Spodick sign (downsloping TP segment) | Stage I changes present in ~80%. Diffuse = not in a coronary territory (distinguishes from STEMI). |
| TTE (Echocardiogram) | Pericardial effusion size, tamponade physiology (RA/RV collapse, IVC plethora, respiratory variation) | Assess effusion size and hemodynamic impact. Repeat in 1-2 weeks to monitor resolution. |
| Troponin | Elevated if myopericarditis | Mild elevation suggests myocardial involvement. Does NOT change treatment but restricts activity longer. |
| CRP / ESR | Elevated (CRP often markedly) | CRP guides treatment duration — continue colchicine + NSAIDs until CRP normalizes. |
| CBC | Leukocytosis (if infectious/inflammatory) | WBC differential helps distinguish viral (lymphocytic) vs bacterial (neutrophilic). |
| BMP | Cr (baseline), electrolytes | Baseline renal function before NSAID therapy. Monitor during treatment. |
| Blood cultures | If infectious etiology suspected | Obtain if febrile, immunocompromised, or subacute presentation suggesting bacterial/TB pericarditis. |
Diagnosis requires 2 of 4: (1) pleuritic chest pain, (2) pericardial friction rub, (3) diffuse ST elevation + PR depression, (4) new/worsening pericardial effusion.
💊 Medications
Medications — Pericarditis & Pericardial Disease
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| Ibuprofen (Advil) 1ST LINE | 600 mg PO TID | 1-2 weeks, then taper over 2-3 weeks | First-line NSAID. Take with PPI for GI protection. Taper by 200-400 mg/week. |
| Colchicine (Colcrys) 1ST LINE | 0.5 mg BID (0.5 mg daily if <70 kg) | 3 months (first episode), 6 months (recurrent) | Halves recurrence rate. COPE, 2005 + ICAP, 2013. GI side effects (diarrhea) — dose-reduce if needed. |
| Aspirin | 750-1000 mg PO TID | 1-2 weeks, then taper | Preferred over ibuprofen if recent MI (post-infarction pericarditis / Dressler syndrome). |
| Prednisone 2ND LINE ONLY | 0.25-0.5 mg/kg/day | Slow taper over weeks-months | Only if contraindication to NSAIDs (renal failure, GI bleeding). Increases recurrence risk. Always use with colchicine. |
Avoid anticoagulants if moderate-large effusion — risk of hemorrhagic pericardial effusion and tamponade. If on anticoagulation for other indication, discuss risk-benefit with cardiology.
📈 Monitoring
Monitoring — Pericarditis & Pericardial Disease
| Parameter | Frequency | Target / Action |
|---|---|---|
| CRP | Weekly until normal | Guides duration of therapy. Do NOT taper NSAIDs until CRP normalizes. Premature taper = recurrence. |
| ECG | At diagnosis, then at follow-up | Monitor ST/PR normalization through 4 stages. Persistent changes may suggest constrictive physiology. |
| TTE (Echo) | Repeat in 1-2 weeks | Confirm effusion resolution. Repeat sooner if hemodynamic compromise or clinical worsening. |
| Symptoms | Each visit | Pleuritic chest pain, dyspnea, positional symptoms. Worsening = consider effusion enlargement or recurrence. |
| Renal function (Cr) | 1-2 weeks after starting NSAIDs | NSAID nephrotoxicity. Check BMP especially in elderly, CKD, heart failure, or concurrent ACEi/ARB. |
| Activity restriction | Until CRP normal + asymptomatic | Non-athletes: restrict until symptom resolution. Athletes: no competitive sports for minimum 3 months (6 months if myopericarditis). |
⚡ Summary
Summary
Diagnosis
Need 2 of 4: pleuritic chest pain, pericardial rub, diffuse ST elevation + PR depression, new pericardial effusion.
Treatment
Ibuprofen 600 TID × 2 weeks + colchicine 0.5 BID × 3 months. Colchicine halves recurrence [COPE, ICAP].
Tamponade
Beck's triad (hypotension + JVD + muffled sounds). Pulsus paradoxus > 10. RV collapse on echo. → Pericardiocentesis.
Avoid
Anticoagulation (risk of hemorrhagic pericardial effusion). Steroids first-line (high recurrence rate).
Myopericarditis
Pericarditis + troponin elevation. Avoid exercise until CRP normalizes and symptoms resolve × 3 months.
Recurrence
Restart colchicine × 6 months. Consider IVIG or anakinra (IL-1 blocker) for refractory cases.
📄 One Pager
One Pager — Pericarditis & Pericardial Disease
See the Overview and Management tabs for detailed clinical information on pericarditis & pericardial disease.
📄 One Pager
Cardiology · One Pager · One Pager
Acute Pericarditis
Pleuritic chest pain + diffuse ST elevation + PR depression. NSAIDs + colchicine. Always rule out tamponade. Avoid anticoagulation.
Diagnosis — Need 2 of 4
- Pleuritic chest pain (sharp, worse lying flat, better leaning forward)
- Pericardial friction rub
- Diffuse ST elevation + PR depression on ECG
- New or worsening pericardial effusion on echo
Management
- Ibuprofen 600 mg TID × 2 weeks (taper over weeks)
- Colchicine 0.5 mg BID × 3 months (halves recurrence) [COPE, ICAP]
- Activity restriction until CRP normalizes + symptoms resolve
- Myopericarditis (troponin ↑): no exercise × 3-6 months
Tamponade — Recognize Early
- Beck's triad: hypotension + JVD + muffled heart sounds
- Pulsus paradoxus > 10 mmHg
- Echo: RV diastolic collapse (most specific), IVC plethora
- Treatment: emergent pericardiocentesis (echo-guided)
Key Drugs
Ibuprofen600 mg TID × 2wk
Colchicine0.5 mg BID × 3mo
AcetaminophenPRN adjunct
AvoidAnticoagulation, steroids first-line
Pitfalls
- Missing tamponade
- Using steroids first-line (high recurrence)
- Anticoagulation → hemorrhagic effusion
- Not adding colchicine from day 1
- Confusing with STEMI on ECG
Aortic Dissection
Tear in the aortic intima with blood tracking into the media. Stanford A (ascending) = surgical emergency with ~1% mortality per hour untreated. Stanford B (descending) = medical management unless complicated. HR and BP control are immediate priorities.
🔍 Overview
Stanford Classification
| Type | Involvement | % of Cases | Mortality (Untreated) | Treatment |
|---|---|---|---|---|
| Stanford A | Ascending aorta (± descending) | ~60% | ~1–2% per hour for first 48h | Emergent surgery. Call CT surgery immediately. IRAD Registry, Hagan 2000 |
| Stanford B | Descending aorta only (distal to L subclavian) | ~40% | ~10% at 30 days | Medical management (BP + HR control). Surgery/TEVAR only if complicated. |
Any dissection involving the ascending aorta = Type A = surgery. It doesn't matter if it also extends into the descending aorta — ascending involvement dictates management.
Presentation
- "Tearing" or "ripping" chest/back pain — acute onset, maximal at onset (unlike MI which crescendos), may migrate as dissection propagates
- BP differential > 20 mmHg between arms — dissection flap compromising subclavian
- Pulse deficit — absent or diminished pulses in one limb
- Aortic regurgitation murmur (Type A — flap disrupts aortic valve)
- Stroke symptoms (carotid involvement), ACS/STEMI (coronary involvement), paraplegia (spinal artery), mesenteric ischemia, AKI (renal artery)
Classic pitfall: Type A dissection involving the RCA → inferior STEMI on ECG. If you give tPA or anticoagulate for "MI," the patient bleeds into the pericardium → tamponade → death. Always consider dissection before treating STEMI, especially with tearing pain, pulse deficits, or widened mediastinum.
Diagnosis
| Test | Role |
|---|---|
| CTA chest/abdomen/pelvis TEST OF CHOICE | Sensitivity > 95%. Shows intimal flap, true vs false lumen, extent, branch vessel involvement. Get with arterial phase + delayed phase. |
| TEE (transesophageal echo) | If too unstable for CT. Can be done at bedside / in OR. Excellent for Type A. Limited for distal descending. |
| CXR | Widened mediastinum (~60% sensitivity — absence does NOT rule out dissection). May see left pleural effusion. |
| D-dimer | Elevated in > 95% of dissections. Negative D-dimer has high NPV — can help rule out in low-pretest probability. Not reliable alone. |
🚨 Management
Immediate — All Dissections
HR first, then BP. Dropping BP without slowing HR increases aortic wall shear stress (dP/dt) and propagates the dissection.
Step 1 — HR Control
IV beta-blocker first. Target HR < 60 bpm. Esmolol 500 mcg/kg bolus → 50–200 mcg/kg/min (preferred — ultra-short acting, titratable). Or labetalol 20 mg IV q10 min. Must control HR BEFORE adding vasodilators.
Step 2 — BP Control
Target SBP 100–120 mmHg. If BB alone insufficient → add nicardipine 5–15 mg/hr or nitroprusside 0.3–5 mcg/kg/min (only AFTER HR controlled). Clevidipine is another option (ultra-short acting CCB).
Pain Control
IV morphine or fentanyl. Pain drives sympathetic response → HR/BP elevation → propagation. Aggressive pain control is part of the treatment.
Type A — Surgical Emergency
- Emergent CT surgery consult — do not delay for any reason
- Ascending aorta replacement ± aortic valve repair/replacement ± coronary reimplantation
- Mortality without surgery: 50% at 48h. With surgery: 15–25%.
- Tamponade → emergent pericardiocentesis as bridge to OR (limited drainage — just enough to restore perfusion)
Type B — Medical Management
- Uncomplicated Type B: BP/HR control + pain management + ICU monitoring. Long-term oral BB + amlodipine. Repeat imaging at 48–72h, 1 month, 6 months, then annually. INSTEAD-XL, Nienaber 2013 ADSORB, Brunkwall 2014
- Complicated Type B (malperfusion, rupture, refractory pain, rapid expansion) → TEVAR (thoracic endovascular aortic repair) or open surgery.
Medications
| Drug (Brand) | Dose | Role |
|---|---|---|
| Esmolol (Brevibloc) 1ST LINE | 500 mcg/kg bolus → 50–200 mcg/kg/min | Preferred BB — ultra-short t½ (9 min), highly titratable. Stops fast if complications. |
| Labetalol (Trandate) 1ST LINE | 20 mg IV q10 min (max 300 mg) or 1–2 mg/min drip | α + β blocker. Good alternative if esmolol drip unavailable. Longer acting. |
| Nicardipine (Cardene) ADD-ON | 5–15 mg/hr IV | Add if BP not at target despite BB. Do NOT use alone without BB. |
| Nitroprusside (Nipride) ADD-ON | 0.3–5 mcg/kg/min | Potent vasodilator. Only use AFTER HR controlled — reflex tachycardia worsens shear stress. Cyanide toxicity > 48h. |
📋 On Rounds
Why must you control HR before BP in aortic dissection?
dP/dt (the rate of rise of aortic pressure) is the primary driver of dissection propagation — not the absolute BP alone. Vasodilators (like nitroprusside) that drop BP without slowing HR cause reflex tachycardia, which paradoxically increases dP/dt and wall shear stress, potentially extending the dissection. Beta-blockers reduce both HR and contractility, lowering dP/dt. Always achieve HR < 60 first, then add vasodilators if needed for BP.
A patient presents with inferior STEMI and tearing chest pain radiating to the back. What should you think?
Type A aortic dissection involving the right coronary artery. The dissection flap can occlude the RCA ostium → inferior STEMI. If you give tPA, heparin, or dual antiplatelets for a "primary MI," the patient bleeds into the false lumen or pericardium → tamponade → death. Always consider dissection when STEMI presents with atypical features: tearing/migratory pain, pulse deficits, wide mediastinum, or new aortic regurgitation murmur. Get a CTA before cath lab activation if there's any suspicion.
Why is the target HR < 60 in aortic dissection, and why do you start a beta-blocker before a vasodilator?
HR and dP/dt (the rate of rise of aortic pressure) are the main determinants of aortic wall shear stress. The faster the heart beats and the harder it contracts, the more force is applied to the dissection flap → propagation. Beta-blockers reduce both HR and contractility (dP/dt) — esmolol IV is first-line (short-acting, titratable). You must start the BB BEFORE any vasodilator (e.g., nicardipine) because vasodilators cause reflex tachycardia which increases shear stress and can worsen the dissection. Goal: HR < 60, then SBP 100-120.
How do you differentiate Stanford Type A from Type B, and why does it change everything?
Type A: involves the ascending aorta (regardless of where the tear starts) → SURGICAL EMERGENCY. Mortality increases 1-2% per hour without surgery. Complications: aortic regurgitation, tamponade, coronary malperfusion (MI), stroke. Type B: involves only the descending aorta (distal to left subclavian) → medical management (HR/BP control). Surgery only if complicated (malperfusion, rupture, refractory pain, rapid expansion). The distinction is made on CTA. Memory aid: A = Ascending = needs the surgeon ASAP. B = Below the subclavian = BP control.
📣 Sample Presentation
One-Liner
"Mr. Franklin is a 62-year-old with longstanding uncontrolled HTN presenting with acute tearing chest pain radiating to the back. BP 210/120 in right arm, 168/95 in left. CTA shows Stanford type B aortic dissection extending from left subclavian to celiac trunk."
Key Points to Cover on Rounds
Stanford type B (descending) — medical management. HR 58 on esmolol drip (target <60). SBP 118 on nicardipine drip (target 100-120). No malperfusion signs: renal function stable, bowels functioning, distal pulses symmetric. CT surgery aware — no surgical indication currently. Pain controlled with IV morphine. Plan: transition to oral BB + amlodipine when stable ×24h, serial imaging.
🧪 Workup
Diagnostic Evaluation — Aortic Dissection
Time-critical diagnosis. Type A dissection mortality increases 1-2% per hour without surgery. Do NOT delay imaging for labs.
| Test | Findings | Clinical Significance |
|---|---|---|
| CTA chest/abdomen/pelvis GOLD STANDARD | Intimal flap, true/false lumen, extent of dissection, branch vessel involvement | Sensitivity >95%. Defines Stanford type (A vs B), extent, malperfusion. Get full aorta (chest through pelvis). |
| CXR | Widened mediastinum (>8 cm), abnormal aortic contour, left pleural effusion | Insensitive (~60%) but may be first clue. Normal CXR does NOT rule out dissection. |
| Type & Screen | — | Prepare for potential emergent surgery. Crossmatch if Type A. |
| CBC | H/H for baseline | Serial Hgb to monitor for hemorrhage. Leukocytosis common (stress response). |
| BMP | Cr (baseline), electrolytes | Renal function — renal artery malperfusion? Baseline before contrast. |
| Coags (PT/INR, aPTT) | Baseline coagulation | Pre-surgical assessment. DIC can develop with extensive dissection. |
| Troponin | May be elevated | Coronary malperfusion (Type A extending into coronary ostia → STEMI mimic). Also consider concurrent ACS. |
| Lactate | Elevated if malperfusion | Mesenteric ischemia, limb ischemia, shock. Rising lactate = urgent surgical indication. |
💊 Medications
Key Medications — Aortic Dissection
HR first, THEN BP. Always achieve heart rate control before adding vasodilators. Pure vasodilators without beta-blockade cause reflex tachycardia, increasing aortic shear stress and propagating the dissection.
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Esmolol (Brevibloc) 1ST LINE — HR | 500 mcg/kg bolus, then 50-200 mcg/kg/min drip | IV | Target HR <60 bpm FIRST. Ultra-short half-life (9 min) — easily titratable. Preferred initial agent. |
| Nicardipine (Cardene) ADD FOR BP | 5-15 mg/hr IV drip | IV | Add AFTER beta-blocker for SBP target <120 mmHg. Smooth arterial vasodilator. No reflex tachycardia when BB already on board. |
| Labetalol (Trandate) ALTERNATIVE | 20 mg IV bolus, then 1-2 mg/min drip | IV | Combined alpha + beta blockade. Alternative to esmolol + nicardipine. Less titratable than esmolol. |
| Nitroprusside ADJUNCT ONLY | 0.25-10 mcg/kg/min | IV | NEVER without prior beta-blockade. Potent vasodilator — reflex tachycardia worsens dissection. Cyanide toxicity risk with prolonged use. |
| IV Morphine | 2-4 mg IV q5-15min PRN | IV | Pain control is critical — pain drives sympathetic surge → elevated HR/BP. Reduces shear stress. |
Avoid: pure vasodilators (hydralazine, nitroprusside) without beta-blockade. Avoid anticoagulation until dissection is excluded or surgical plan is defined.
📈 Monitoring
Monitoring Parameters — Aortic Dissection
| Parameter | Frequency | Target / Action |
|---|---|---|
| Arterial line BP | Continuous | SBP 100-120 mmHg. Place in right radial (unless right subclavian involved). A-line is mandatory — cuff BP unreliable with branch vessel involvement. |
| Heart rate | q5-15 min during titration, then continuous | Target HR <60 bpm. Reduce HR BEFORE adding vasodilators. Titrate esmolol drip to goal. |
| Urine output | Hourly via Foley | UOP ≥ 0.5 mL/kg/hr. Declining UOP = renal artery malperfusion → urgent surgical/IR consideration. |
| Neuro checks | q1-2h | New focal deficits = carotid extension (Type A). Stroke, altered mental status, limb weakness → emergent intervention. |
| Distal pulses | q2-4h + with each BP change | Bilateral radial, femoral, dorsalis pedis. New pulse deficit = malperfusion → surgical/IR consultation. |
| Abdominal exam | q4h | Tenderness, distension = mesenteric malperfusion. Correlate with lactate and LFTs. |
| Serial CTA | If conservative management (Type B) | Repeat at 48-72h, then 1-2 weeks, then 1, 3, 6, 12 months. Monitor for aneurysmal degeneration or new malperfusion. |
| Serial Hgb, lactate | q6-8h or with clinical change | Dropping Hgb = hemorrhage. Rising lactate = malperfusion or shock. |
⚡ Summary
Summary
Type A
Ascending aorta involved → SURGICAL EMERGENCY. Mortality 1-2%/hr without surgery. Call CT surgery immediately.
Type B
Descending only → Medical management. HR < 60 + SBP 100-120. Surgery only if complicated (malperfusion, rupture).
First Drug
Esmolol IV (BB before vasodilator). Reduce HR first, then BP. Vasodilators alone → reflex tachycardia → worsens dissection.
Imaging
CTA chest/abdomen/pelvis. If CTA unavailable → TEE. CXR may show widened mediastinum but is insensitive.
Suspect When
Tearing chest/back pain + BP differential between arms + unequal pulses + history of HTN or Marfan.
Malperfusion
Stroke (carotid), MI (coronary), bowel ischemia (mesenteric), renal failure (renal), limb ischemia (iliac).
📄 One Pager
Aortic Dissection — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
AORTIC DISSECTION — AT A GLANCE
📋 Classify: Stanford A (ascending = surgery) vs B (descending = medical). DeBakey I/II/III.
🧪 Workup: CTA chest/abdomen/pelvis (gold standard). Type & screen, CBC, BMP, troponin, lactate.
⚡ Treat: HR <60 FIRST (esmolol), THEN SBP <120 (nicardipine). Type A = emergent surgery.
💊 Drugs: Esmolol drip → nicardipine. Labetalol alternative. NEVER vasodilate without BB.
📈 Monitor: A-line, HR q5-15min, UOP hourly, neuro checks, serial CTA if Type B.
🚨 Malperfusion: Stroke, MI, bowel ischemia, renal failure, limb ischemia = surgical emergency.
🧪 Workup: CTA chest/abdomen/pelvis (gold standard). Type & screen, CBC, BMP, troponin, lactate.
⚡ Treat: HR <60 FIRST (esmolol), THEN SBP <120 (nicardipine). Type A = emergent surgery.
💊 Drugs: Esmolol drip → nicardipine. Labetalol alternative. NEVER vasodilate without BB.
📈 Monitor: A-line, HR q5-15min, UOP hourly, neuro checks, serial CTA if Type B.
🚨 Malperfusion: Stroke, MI, bowel ischemia, renal failure, limb ischemia = surgical emergency.
🧪 Workup
Workup — Aortic Dissection
- CTA chest/abdomen/pelvis — gold standard. Defines Stanford type, extent, branch involvement. Sensitivity >95%.
- Type & Screen — prepare for emergent surgery (Type A). Crossmatch 4-6 units pRBCs.
- CBC, BMP, coags — baseline H/H, renal function, electrolytes, PT/INR/aPTT
- Troponin — coronary malperfusion (Type A into coronary ostia). MI mimic.
- Lactate — mesenteric malperfusion, shock. Rising lactate = surgical urgency.
- CXR — widened mediastinum (>8 cm), but insensitive (~60%). Normal CXR does NOT rule out dissection.
- D-dimer — highly sensitive negative predictor. If <500 ng/mL, dissection very unlikely (NPV >95%).
💊 Medications
Medications — Aortic Dissection
Beta-blocker FIRST. Target HR <60, then SBP <120. Never vasodilate without beta-blockade.
- Esmolol (Brevibloc) — 500 mcg/kg bolus then 50-200 mcg/kg/min drip. Ultra-short acting, highly titratable.
- Nicardipine (Cardene) — 5-15 mg/hr IV. Add AFTER BB for SBP control.
- Labetalol (Trandate) — 20 mg IV bolus then 1-2 mg/min drip. Combined alpha/beta blocker alternative.
- Pain control: IV morphine 2-4 mg q5-15min PRN. Pain drives sympathetic surge.
📈 Monitoring
Monitoring — Aortic Dissection
- Arterial line — continuous BP monitoring mandatory. SBP target 100-120 mmHg.
- HR q5-15 min during drip titration. Target HR <60 bpm.
- Urine output hourly — renal malperfusion if declining.
- Neuro checks q1-2h — carotid extension (stroke, altered mental status).
- Distal pulses q2-4h — bilateral radial, femoral, DP. New deficit = malperfusion.
- Serial CTA — if conservative management. 48-72h, then 1-2 weeks, 1/3/6/12 months.
📌 Summary
Summary — Aortic Dissection
Type A
Ascending aorta = SURGICAL EMERGENCY. Mortality 1-2%/hr untreated. CT surgery stat.
Type B
Descending only = medical management. HR <60 + SBP 100-120. Surgery only if complicated.
First Move
Esmolol drip for HR <60 FIRST, then nicardipine for SBP <120. Never vasodilate without BB.
Malperfusion
Stroke, MI, bowel ischemia, renal failure, limb ischemia. Any malperfusion = surgical indication.
📄 One Pager
One Pager — Aortic Dissection
See the Overview and Management tabs for detailed clinical content on aortic dissection.
📄 One Pager
Cardiology / Vascular · One Pager · One Pager
Aortic Dissection
Tearing pain + BP differential + unequal pulses. Type A = surgery NOW. Type B = HR < 60 + SBP 100-120. BB before vasodilators.
Classification
- Stanford Type A: ascending aorta involved → SURGICAL EMERGENCY
- Stanford Type B: descending only (distal to L subclavian) → medical management
- DeBakey I: ascending + descending. II: ascending only. III: descending only
- Mortality: Type A = 1-2%/hour without surgery
Immediate Management
- Esmolol IV first (BB before vasodilator)
- Target HR < 60, then SBP 100-120
- Add nicardipine AFTER HR controlled
- Type A → CT surgery emergently
- Type B → ICU, medical management, serial imaging
Malperfusion Syndromes
- Stroke (carotid dissection)
- MI (coronary ostia involvement)
- Mesenteric ischemia (celiac/SMA)
- Renal failure (renal artery)
- Limb ischemia (iliac)
- Spinal cord ischemia (artery of Adamkiewicz)
Key Drugs
Esmolol500 mcg/kg bolus → 50-200 drip
Nicardipine5-15 mg/hr drip
Labetalol20 mg IV → drip alternative
PainIV morphine/fentanyl
Pitfalls
- Vasodilator before BB (reflex tachy worsens dissection)
- Delaying CTA for other workup
- Missing Type A — always scan the ascending aorta
- Thrombolytics for "STEMI" that is actually dissection
Infective Endocarditis
Infection of the endocardial surface (usually valves). Diagnosis requires high clinical suspicion + blood cultures + echo. Delay in treatment = valve destruction, emboli, death. Get cultures before antibiotics — then don't wait.
🔍 Overview
Modified Duke Criteria
Definite IE: 2 major, OR 1 major + 3 minor, OR 5 minor. Possible IE: 1 major + 1 minor, OR 3 minor. Modified Duke, 2000
| Major Criteria | Details |
|---|---|
| 1. Positive blood cultures | Typical organisms from 2 separate cultures: Viridans strep, S. bovis, HACEK, S. aureus, or Enterococcus (without primary focus). OR persistently positive cultures (≥ 2 drawn > 12h apart, or 3/3 or majority of ≥ 4 cultures positive). |
| 2. Endocardial involvement | Echo: vegetation, abscess, new prosthetic dehiscence. OR new valvular regurgitation (murmur change). |
| Minor Criteria |
|---|
| Predisposition: IV drug use, prosthetic valve, prior IE, structural heart disease |
| Fever ≥ 38°C |
| Vascular phenomena: septic emboli, mycotic aneurysm, Janeway lesions, conjunctival hemorrhage |
| Immunologic phenomena: Osler nodes, Roth spots, glomerulonephritis, positive RF |
| Microbiologic: positive cultures not meeting major criteria, or serologic evidence |
Blood Culture Protocol
3 sets of blood cultures from 3 different venipuncture sites before antibiotics. Each set = 1 aerobic + 1 anaerobic bottle. Draw at least 20 mL per set. Space 30–60 min apart if possible (but do NOT delay antibiotics more than 1–2h for critically ill patients).
Organisms
| Organism | % of IE | Key Association |
|---|---|---|
| S. aureus | ~30–40% | Most common overall (especially IVDU and healthcare-associated). Acute, destructive. High embolic risk. |
| Viridans streptococci | ~20–25% | Subacute. Dental procedures. Native valve. More indolent course. |
| Enterococcus | ~10% | GI/GU source. Elderly patients. Requires synergistic therapy (ampicillin + gentamicin or ampicillin + ceftriaxone). |
| Coagulase-negative staph | ~10% | Prosthetic valve IE (especially early < 1 year). S. epidermidis. |
| HACEK organisms | ~3% | Gram-negative, slow-growing. May need prolonged incubation. Treat with ceftriaxone. |
| Culture-negative | ~5–10% | Prior antibiotics (most common reason), Coxiella burnetii (Q fever), Bartonella, Brucella, fungi. |
🚨 Management
Empiric Antibiotic Therapy
| Setting | Empiric Regimen | Notes |
|---|---|---|
| Native valve, acute | Vancomycin (Vancocin) 15–20 mg/kg IV q8–12h + cefepime (Maxipime) 2g IV q8h | Covers MRSA + gram-negatives. Narrow based on cultures. Duration: 4–6 weeks. |
| Native valve, subacute | Vancomycin (Vancocin) + ceftriaxone (Rocephin) 2g IV q24h | Covers strep + staph. Add gentamicin if Enterococcus suspected. Enterococcal Endocarditis Trial, 2013 |
| Prosthetic valve | Vancomycin (Vancocin) + gentamicin + rifampin (Rifadin) 300 mg PO q8h | Rifampin for biofilm penetration. Triple therapy × 6 weeks minimum. Gentamicin × 2 weeks only. |
| IVDU (right-sided) | Vancomycin (Vancocin) (covers MRSA — most common in IVDU IE) | Narrow to nafcillin/oxacillin if MSSA. Right-sided (tricuspid) has better prognosis than left-sided. POET, 2019 |
🔄 Updated Practice: Old teaching: add gentamicin to all endocarditis regimens for synergy. Current practice: gentamicin is no longer routinely recommended for native valve Staph aureus endocarditis — it adds nephrotoxicity without mortality benefit. For Enterococcus faecalis endocarditis, ampicillin + ceftriaxone is preferred over ampicillin + gentamicin (equally effective, less nephrotoxic — Enterococcal Endocarditis Trial, 2013). Gentamicin is still used for prosthetic valve endocarditis and some streptococcal regimens.
Surgical Indications — When to Operate
Early surgery (during initial hospitalization) reduces mortality in these scenarios: [EASE, 2012
- Heart failure from severe valvular regurgitation — most common surgical indication
- Uncontrolled infection — persistent bacteremia > 5–7 days despite appropriate antibiotics, perivalvular abscess, fistula
- Large vegetation (> 10 mm) with embolic events despite antibiotics
- Fungal endocarditis — almost always requires surgery
- Prosthetic valve endocarditis with dehiscence, abscess, or persistent bacteremia
- S. aureus prosthetic valve IE — consider early surgery regardless
📋 On Rounds
Why does S. bovis endocarditis require a colonoscopy?
S. gallolyticus (formerly S. bovis biotype I) bacteremia/endocarditis has a strong association with colorectal malignancy — up to 25–50% of patients have colon polyps or cancer. The mechanism is thought to involve bacterial translocation through disrupted colonic mucosa. Every patient with S. bovis/gallolyticus bacteremia needs a colonoscopy, even if asymptomatic.
When do you get a TEE vs TTE for endocarditis?
TTE first in most patients — sensitivity ~70% for vegetations. If TTE is negative but clinical suspicion remains high → TEE (sensitivity ~95%). Go straight to TEE in: prosthetic valves (TTE limited by acoustic shadowing), suspected perivalvular abscess, S. aureus bacteremia (high-risk, need definitive imaging), poor TTE windows (obese, ventilated). If initial TTE/TEE negative but suspicion persists → repeat in 5–7 days.
When does endocarditis require surgery instead of antibiotics alone?
Four major surgical indications: (1) Heart failure from valvular regurgitation (most common indication), (2) Uncontrolled infection (persistent bacteremia > 7 days despite appropriate abx, perivalvular abscess, mycotic/fungal endocarditis), (3) Large vegetation (> 10 mm on left-sided valve with embolic event, or > 15 mm even without embolism), (4) Prosthetic valve endocarditis with any of the above. Surgery should be performed during active abx treatment — don't wait to complete the course first. [Kang, EASE trial 2012: early surgery (within 48h) for large vegetations reduced embolism.
A patient with IVDU has tricuspid valve endocarditis. Does this change your antibiotic approach?
Right-sided endocarditis (TV) in IVDU has better prognosis than left-sided (mortality ~5% vs ~20-30%). If MSSA: nafcillin/oxacillin 2g IV q4h × 4 weeks (can shorten to 2 weeks if: uncomplicated, MSSA, no metastatic infection, vegetation < 2 cm, and clinical improvement). MRSA: vancomycin or daptomycin (daptomycin is an alternative for right-sided MRSA IE, but NOT left-sided — inactivated by surfactant in lungs). Surgery for TV IE: only if refractory sepsis, large vegetations with recurrent pulmonary emboli, or severe TR with right heart failure. Addiction medicine consult is mandatory.
📣 Sample Presentation
One-Liner
"Mrs. Thompson is a 44-year-old with IVDU presenting with 2 weeks of fever, chills, and a new systolic murmur at the left sternal border. Blood cultures grew MSSA (4/4 bottles). TTE shows a 1.2 cm vegetation on the tricuspid valve."
Key Points to Cover on Rounds
Organism: MSSA on 4/4 blood cultures, sensitive to oxacillin. Antibiotics: nafcillin 2g IV q4h, day 5 of planned 6-week course. Echo: 1.2 cm TV vegetation, moderate TR, no abscess. No embolic complications — CT chest negative for septic emboli, UA clean. Surveillance cultures at 48h negative. ID following. CT surgery evaluated — no surgical indication yet. Plan: PICC line placed, continue IV abx, daily assessment for embolic events.
🧪 Workup
Diagnostic Evaluation — Infective Endocarditis
Blood cultures BEFORE antibiotics. Obtain 3 sets from separate venipuncture sites, separated by at least 30 minutes. This is the single most important diagnostic step.
| Test | Findings | Clinical Significance |
|---|---|---|
| Blood cultures ×3 ESSENTIAL | Persistent bacteremia (same organism in multiple sets) | Draw from 3 separate sites BEFORE antibiotics. Continuous bacteremia is a major Duke criterion. Identifies organism + susceptibilities. |
| TTE → TEE | Vegetations, abscess, valve perforation, regurgitation | Start with TTE. If negative but suspicion high → TEE (sensitivity 90-100% vs TTE ~60-75%). TEE mandatory for prosthetic valves. |
| CBC | Leukocytosis, anemia (chronic disease), thrombocytopenia | Anemia of chronic disease common in subacute IE. Thrombocytopenia suggests severe sepsis or DIC. |
| BMP | Cr (baseline + immune complex GN), electrolytes | Renal function — immune complex glomerulonephritis, aminoglycoside toxicity monitoring. |
| ESR / CRP | Elevated | Markers of inflammation. Trend to monitor treatment response. |
| Rheumatoid factor | Elevated in chronic IE | Minor Duke criterion. Immune complex formation in subacute endocarditis. |
| Complement levels (C3/C4) | Low | Consumed by immune complex deposition (glomerulonephritis). |
| Urinalysis | Microscopic hematuria, RBC casts, proteinuria | Immune complex GN or renal septic emboli. Hematuria in up to 50% of IE patients. |
Modified Duke Criteria: Definite IE = 2 major, OR 1 major + 3 minor, OR 5 minor criteria. Major: (1) positive blood cultures (typical organism ×2, or persistently positive), (2) endocardial involvement on echo (vegetation, abscess, new dehiscence, new regurgitation).
💊 Medications
Key Medications — Infective Endocarditis
| Scenario | Regimen | Duration | Notes |
|---|---|---|---|
| Empiric (native valve) | Vancomycin (AUC 400-600) + Ceftriaxone (Rocephin) 2g IV q24h | Pending cultures | Covers MRSA + streptococci + HACEK. Add gentamicin if considering enterococcal coverage. |
| MSSA — native valve | Nafcillin or Oxacillin 2g IV q4h | 6 weeks | Anti-staphylococcal penicillins are preferred over vancomycin for MSSA (better outcomes). Cefazolin 2g IV q8h if penicillin allergy (non-anaphylactic). |
| MRSA — native valve | Vancomycin IV, AUC-guided dosing (target AUC 400-600) | 6 weeks | Trough-based dosing is outdated. AUC-guided dosing reduces nephrotoxicity. Alternative: daptomycin 8-10 mg/kg IV daily (NOT for left-sided endocarditis with pulmonary involvement — inactivated by surfactant). |
| Prosthetic valve (empiric) | Vancomycin + Gentamicin 1 mg/kg IV q8h + Rifampin 300 mg PO q8h | ≥6 weeks (vanco + rifampin), 2 weeks (gent) | Rifampin penetrates biofilm on prosthetic material. Do NOT start rifampin until blood cultures are negative (resistance develops rapidly). |
| Viridans streptococci (MIC ≤0.12) | Ceftriaxone 2g IV q24h | 4 weeks | Can use 2-week short course with ceftriaxone + gentamicin if uncomplicated native valve. Penicillin G 12-18 million units/day IV continuous is alternative. |
| Enterococcus | Ampicillin 2g IV q4h + Ceftriaxone 2g IV q12h | 6 weeks | Ampicillin + ceftriaxone preferred over ampicillin + gentamicin (avoids nephrotoxicity, similar efficacy). If VRE: linezolid or daptomycin. |
Surgical indications: heart failure from valvular dysfunction, uncontrolled infection (persistent bacteremia >5-7 days, abscess, enlarging vegetation), prevention of embolism (vegetation >10 mm with embolic event, >15 mm regardless). Consult CT surgery early.
📈 Monitoring
Monitoring Parameters — Infective Endocarditis
| Parameter | Frequency | Target / Action |
|---|---|---|
| Blood cultures | Daily until negative ×2 | Clearance of bacteremia confirms antibiotic efficacy. Persistent bacteremia (>5-7 days) → search for abscess, consider surgery. |
| CBC | Weekly | WBC trending down. Monitor for anemia (chronic disease, hemolysis). Thrombocytopenia if DIC or drug-related. |
| BMP / Cr | 2-3× weekly | Renal function — nephrotoxicity (vancomycin, gentamicin), immune complex GN, septic emboli. Adjust antibiotic dosing. |
| CRP / ESR | Weekly | Trending down confirms treatment response. Persistent elevation → treatment failure or abscess. |
| Vancomycin AUC | Per pharmacy protocol | Target AUC 400-600 mcg·h/mL. AUC-guided dosing preferred over troughs. Reduces nephrotoxicity. |
| Gentamicin levels | Peak + trough with 3rd dose | Peak 3-4 mcg/mL (synergy dosing), trough <1 mcg/mL. Nephrotoxicity and ototoxicity monitoring. |
| TTE/TEE repeat | If clinical change | New murmur, heart failure, persistent fevers, embolic event → repeat imaging. Assess vegetation size, abscess, valve function. |
| Embolic surveillance | Daily clinical assessment | Neuro exam (stroke), skin (Janeway lesions, Osler nodes, petechiae), splenic tenderness, hematuria. CT head/chest/abdomen if new symptoms. |
⚡ Summary
Summary
Modified Duke
2 major, or 1 major + 3 minor, or 5 minor. Major: positive blood cultures (typical organisms), echo vegetation.
Empiric Abx
Vancomycin + ceftriaxone (native valve). Vancomycin + gentamicin + rifampin (prosthetic valve). ID consult always.
Duration
Native valve: 4-6 weeks IV. MSSA TV in IVDU: may shorten to 2 weeks if uncomplicated.
Surgery
HF from valvular dysfunction, uncontrolled infection, large vegetation (> 10mm) with embolism, abscess.
Must Do
Blood cultures × 3 sets from different sites. TTE first → TEE if negative but suspicion high. CT head if neurologic symptoms.
Source
IVDU = tricuspid. Dental = strep viridans. GI/GU = enterococcus. Prosthetic = coag-neg staph early, S. aureus late.
📄 One Pager
Infective Endocarditis — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
INFECTIVE ENDOCARDITIS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup
Workup — Infective Endocarditis
See the Overview and Management tabs for detailed clinical content on infective endocarditis.
💊 Medications
Medications — Infective Endocarditis
See the Overview and Management tabs for detailed clinical content on infective endocarditis.
📈 Monitoring
Monitoring — Infective Endocarditis
See the Overview and Management tabs for detailed clinical content on infective endocarditis.
📌 Summary
Summary — Infective Endocarditis
See the Overview and Management tabs for detailed clinical content on infective endocarditis.
📄 One Pager
One Pager — Infective Endocarditis
See the Overview and Management tabs for detailed clinical content on infective endocarditis.
📄 One Pager
Cardiology / ID · One Pager · One Pager
Infective Endocarditis
Blood cultures × 3 → empiric abx → echo → ID consult → 4-6 weeks IV. Surgery if HF, uncontrolled infection, or large vegetation.
Modified Duke Criteria
- 2 major = definite IE
- 1 major + 3 minor = definite IE
- Major: typical organism on ≥ 2 cultures; vegetation/abscess on echo
- Minor: predisposing condition, fever, vascular/immunologic phenomena, positive cultures not meeting major
Management
- Blood cultures × 3 from different sites BEFORE antibiotics
- Empiric: vancomycin + ceftriaxone (native valve)
- Prosthetic valve: vancomycin + gentamicin + rifampin
- TTE first → TEE if negative but high suspicion
- ID consult always. Duration: 4-6 weeks IV
Surgical Indications
- Heart failure from valvular dysfunction (most common indication)
- Uncontrolled infection (persistent bacteremia > 7 days, abscess)
- Large vegetation > 10mm with embolism [EASE, 2012]
- Prosthetic valve IE with any of the above
- Fungal endocarditis (almost always requires surgery)
Key Drugs
Vancomycin15-20 mg/kg q8-12h
Ceftriaxone2g IV q12h
Nafcillin2g IV q4h (MSSA)
Gentamicin1 mg/kg q8h (PVE)
Pitfalls
- Antibiotics before blood cultures
- Missing perivalvular abscess (need TEE)
- Not consulting surgery early enough
- Not checking for embolic complications (CT head, spleen)
Valvular Heart Disease
Aortic stenosis, mitral regurgitation, and aortic regurgitation — the three you'll see most. Know the murmurs, when to echo, and when to refer for intervention.
🔍 Overview
Severity
| Parameter | Mild | Moderate | Severe |
|---|---|---|---|
| Aortic valve area (AVA) | > 1.5 cm² | 1.0–1.5 cm² | < 1.0 cm² |
| Mean gradient | < 20 mmHg | 20–40 mmHg | > 40 mmHg |
| Peak velocity | < 3 m/s | 3–4 m/s | > 4 m/s |
When to Intervene
- Symptomatic severe AS: any symptom from the classic triad → immediate referral for AVR
- Classic triad (SAD): Syncope (3-year survival without AVR), Angina (5-year), Dyspnea/HF (2-year). Once symptoms develop, mortality is 50% at 2 years without surgery.
- Asymptomatic severe AS with EF < 50% → AVR
- TAVR (transcatheter) now approved for all surgical risk categories PARTNER 3, 2019
⚠️ Avoid vasodilators in severe AS. Afterload reduction (nitrates, ACEi, hydralazine) can cause severe hypotension — the fixed obstruction prevents compensatory increase in CO. Also avoid rapid fluid depletion — AS patients are preload-dependent.
| Feature | Acute MR | Chronic MR |
|---|---|---|
| Cause | Papillary muscle rupture (post-MI), chordae rupture, endocarditis | Mitral valve prolapse (#1), rheumatic disease, annular dilation from LV dilation |
| LV size | Normal (no time to dilate) | Dilated (volume overload compensated) |
| LA size | Normal → pulmonary edema (no compliance) | Dilated (accommodates regurgitant volume) |
| Murmur | May be soft or absent (equalization of pressures) | Holosystolic at apex, radiates to axilla |
| Treatment | Emergent surgery. Afterload reduction (nitroprusside, IABP) as bridge. | Surgery when: symptomatic, or asymptomatic with EF ≤ 60% or LVESD ≥ 40 mm. MitraClip for high surgical risk. |
| Feature | Acute AR | Chronic AR |
|---|---|---|
| Cause | Endocarditis (valve destruction), aortic dissection, trauma | Bicuspid aortic valve, rheumatic disease, aortic root dilation (Marfan, HTN) |
| LV response | Normal size → cannot accommodate volume → pulmonary edema | Eccentric hypertrophy (LV dilation — "cor bovinum") |
| Pulse pressure | May be narrow (LV can't compensate) | Wide (bounding "water-hammer" pulse, Corrigan pulse, de Musset sign) |
| Murmur | Short early diastolic (equalization) | Blowing early diastolic at LUSB, best heard sitting up and leaning forward |
| Treatment | Emergent surgery. Nitroprusside bridge. IABP is CONTRAINDICATED in AR. | Surgery when symptomatic, or asymptomatic with EF < 55% or LVESD > 50 mm or LVIDd > 65 mm. |
⚠️ IABP is contraindicated in aortic regurgitation. The balloon inflates in diastole — this increases aortic diastolic pressure and worsens regurgitant flow back into the LV.
| Feature | Details |
|---|---|
| #1 Cause | Rheumatic heart disease (virtually always). Rare in developed countries now. |
| Pathophysiology | Stenotic MV → ↑ LA pressure → LA dilation → atrial fibrillation → pulmonary HTN → RV failure |
| Murmur | Low-pitched diastolic rumble at apex with opening snap. Best heard in left lateral decubitus. Shorter snap-to-rumble interval = more severe. |
| Key complication | Afib (from LA dilation) → high stroke risk → anticoagulate with warfarin (DOACs inferior in mechanical/rheumatic valvular disease) |
| Severity | Normal MVA ~4–6 cm². Severe MS: MVA < 1.5 cm², mean gradient > 10 mmHg |
| Treatment | Rate control (BB/CCB) + anticoagulation if Afib. Intervention: percutaneous mitral balloon commissurotomy (PMBC) if pliable valve, no significant MR, no LA thrombus. Otherwise → surgical MV replacement. |
| Feature | Details |
|---|---|
| #1 Cause | Functional/secondary — RV dilation from pulmonary HTN, LV failure, or COPD stretches the tricuspid annulus |
| Primary causes | Endocarditis (IVDU — right-sided), Ebstein anomaly, carcinoid, rheumatic, pacemaker leads |
| Murmur | Holosystolic at LLSB. ↑ with inspiration (Carvallo sign) — increased RV venous return augments regurgitant flow |
| Exam findings | Elevated JVP with prominent CV waves, pulsatile liver, peripheral edema, ascites |
| Treatment | Treat the underlying cause (pulmonary HTN, LV failure). Diuretics for volume overload. Surgery rarely needed unless primary TR with severe symptoms. |
| Lesion | Murmur | Timing | Best Heard | Key Maneuver |
|---|---|---|---|---|
| Aortic Stenosis | Crescendo-decrescendo (ejection) | Systolic | RUSB → carotids | ↓ with Valsalva (except HCM) |
| Mitral Regurgitation | Holosystolic (blowing) | Systolic | Apex → axilla | ↑ with handgrip (↑ afterload) |
| Aortic Regurgitation | Early diastolic (blowing, decrescendo) | Diastolic | LUSB, sitting up/leaning forward | Wide pulse pressure, water-hammer pulse |
| Mitral Stenosis | Low-pitched rumble with opening snap | Diastolic | Apex, left lateral decubitus | Louder with exercise (↑ flow) |
| Tricuspid Regurgitation | Holosystolic (blowing) | Systolic | LLSB | ↑ with inspiration (Carvallo sign) |
- New murmur with symptoms (dyspnea, syncope, chest pain)
- Any diastolic murmur (always pathologic)
- Any holosystolic murmur (MR or TR)
- Grade ≥ 3/6 systolic murmur
- Systolic murmur + abnormal symptoms/exam findings
- Known valve disease with change in symptoms
Benign flow murmurs (grade 1–2/6 systolic at LUSB, no radiation, no symptoms, young patient) do NOT need echo. But when in doubt — echo.
📋 On Rounds
What is the classic triad of symptomatic aortic stenosis?
SAD: Syncope, Angina, Dyspnea (HF). They appear in that order as the disease progresses. Once any symptom develops, average survival without AVR: syncope = 3 years, angina = 5 years, heart failure = 2 years. This is why symptomatic severe AS is an indication for urgent valve replacement — delay costs lives.
Why is IABP contraindicated in aortic regurgitation?
The IABP inflates during diastole to augment coronary perfusion and deflates during systole to reduce afterload. In AR, blood regurgitates from aorta into LV during diastole. IABP inflation during diastole increases aortic diastolic pressure → drives MORE blood backward through the incompetent valve → worsens regurgitation and LV volume overload. Use nitroprusside or Impella instead for hemodynamic support in acute AR.
A patient with severe aortic stenosis needs non-cardiac surgery. How do you manage this?
Severe AS + non-cardiac surgery = high perioperative risk (hypotension, HF, death). Key principles: (1) Symptomatic severe AS → defer elective surgery until valve intervention (TAVR or SAVR). (2) If surgery is urgent/emergent: proceed with invasive hemodynamic monitoring, maintain preload (avoid dehydration), avoid vasodilators and rapid HR changes, goal-directed fluid management. (3) Spinal/epidural anesthesia is relatively contraindicated (drops SVR → fixed obstruction can't compensate → cardiovascular collapse). (4) For truly emergent surgery in severe AS: consider balloon aortic valvuloplasty (BAV) as a bridge — temporary improvement to get through surgery.
What is the most important echo measurement in aortic stenosis and what values define severe?
Aortic valve area (AVA) is the gold standard. Severe AS: AVA < 1.0 cm², mean gradient > 40 mmHg, peak velocity > 4 m/s. BUT these can be discordant in low-flow, low-gradient AS (low EF → low gradient despite severe stenosis). In this case, do a dobutamine stress echo: if AVA remains < 1.0 cm² as flow increases → truly severe ("fixed" stenosis → valve intervention). If AVA improves → pseudosevere (improve EF medically). Critical pearl: the gradient is flow-dependent — a low gradient doesn't rule out severe AS if the heart is too weak to generate flow.
📣 Sample Presentation
One-Liner
"Mr. Morris is a 78-year-old presenting with exertional syncope and progressive dyspnea. Echo shows severe aortic stenosis with AVA 0.7 cm², mean gradient 52 mmHg, EF 55%. Symptomatic severe AS."
Key Points to Cover on Rounds
Symptomatic severe AS (syncope + dyspnea). AVA 0.7, mean gradient 52, EF preserved. STS score 4.2% (intermediate risk). CT surgery and structural heart consulted — candidate for TAVR vs SAVR discussion. Medical optimization: gentle diuresis for volume overload. Avoiding vasodilators and aggressive diuresis. Plan: outpatient TAVR evaluation, cardiac cath to assess coronary anatomy.
🧪 Workup
Diagnostic Evaluation — Valvular Heart Disease
Echo is the cornerstone. Every suspected valvular lesion needs echocardiography for severity grading. Additional testing depends on the clinical context and surgical candidacy.
| Test | Purpose | When to Order |
|---|---|---|
| TTE (transthoracic echo) | Valve area, gradients, regurgitation severity, EF, chamber dimensions | All suspected valvular disease. First-line imaging. |
| TEE (transesophageal echo) | Superior visualization of mitral valve, prosthetic valves, endocarditis vegetations, LA thrombus | Prosthetic valve evaluation, pre-surgical planning, suspected endocarditis with negative TTE, pre-cardioversion in AF with valvular disease |
| ECG | LVH (voltage criteria in AS), atrial fibrillation (common in MS, MR), conduction abnormalities | All patients — baseline and with any symptom change |
| BNP / NT-proBNP | Assess hemodynamic burden, detect subclinical decompensation | Baseline and trending with symptom changes. Helps time intervention in asymptomatic severe disease. |
| Exercise stress test | Unmask symptoms in "asymptomatic" severe AS or MR. Assess functional capacity and hemodynamic response. | Asymptomatic severe valve disease when surgery timing is uncertain. Contraindicated in symptomatic severe AS. |
| Cardiac catheterization | Coronary anatomy pre-operatively, hemodynamic assessment when echo is discordant | Pre-surgical evaluation (assess CAD), discrepant echo findings |
💊 Medications
Key Medications — Valvular Heart Disease
Mechanical valves require warfarin ONLY. DOACs are contraindicated — dabigatran caused increased thromboembolic events and bleeding in mechanical valves RE-ALIGN, 2013.
| Indication | Drug | Dose / Target | Notes |
|---|---|---|---|
| Mechanical valve anticoagulation | Warfarin (Coumadin) | Target INR 2.5–3.5 (mitral) or 2.0–3.0 (aortic bileaflet) | Warfarin ONLY. DOACs contraindicated [RE-ALIGN]. Lifelong therapy. Add ASA 81mg for additional protection. |
| AF with valvular disease (MS or mechanical valve) | Warfarin (Coumadin) | Target INR 2.0–3.0 | Warfarin, NOT DOACs. "Valvular AF" = moderate-severe MS or mechanical valve. All other AF with valve disease can use DOACs. |
| Volume overload / congestion | Furosemide (Lasix) | 20–80 mg PO/IV daily, titrate to symptoms | Diuretics for symptom relief in any valve lesion with congestion. Caution in severe AS — avoid excessive preload reduction. |
| Afterload reduction (regurgitant lesions) | ACEi/ARB (e.g., lisinopril, losartan) | Standard dosing, titrate to BP | Beneficial in chronic MR and AR with LV dysfunction or HTN. Reduces regurgitant volume. Avoid vasodilators in severe AS. |
| Rate control (MS with AF) | Beta-blockers or CCBs | Metoprolol 25–100mg BID or diltiazem 30–60mg TID | Slowing HR increases diastolic filling time — critical in MS. Avoid tachycardia. |
Endocarditis Prophylaxis
Prophylaxis indications (dental procedures involving gingival manipulation or perforation):
- Prosthetic heart valve (mechanical or bioprosthetic)
- Prior infective endocarditis
- Unrepaired cyanotic CHD (including palliative shunts/conduits)
- Cardiac transplant with valvulopathy
- Drug: Amoxicillin 2g PO 30–60 min before procedure. If PCN allergy: clindamycin 600mg PO or azithromycin 500mg PO.
📈 Monitoring
Monitoring Parameters — Valvular Heart Disease
| Parameter | Frequency | Target / Action |
|---|---|---|
| TTE (echocardiogram) | Annual for mild disease, q6–12 months for moderate disease | Valve area, gradients, regurgitation severity, EF, chamber dimensions. Urgent echo if new/worsening symptoms. |
| Symptom assessment | Every visit | Exercise tolerance (NYHA class), dyspnea, syncope, angina, palpitations. New symptoms in severe disease = urgent surgical evaluation. |
| BNP / NT-proBNP | Baseline, then with clinical changes | Rising BNP suggests hemodynamic deterioration even before symptoms — may prompt earlier intervention in severe disease. |
| ECG | Annual or with symptom change | New AF (common in MS, MR), LVH progression, conduction abnormalities |
| INR (if on warfarin) | Weekly initially, then monthly when stable | Mechanical valve: INR 2.5–3.5 (mitral) or 2.0–3.0 (aortic). Therapeutic range prevents both thromboembolism and bleeding. |
| Exercise stress test | As needed in asymptomatic severe disease | Unmask occult symptoms, assess functional capacity. Abnormal response may prompt surgical referral. |
Any new symptom in known severe valve disease should trigger urgent echo and surgical evaluation. Don't wait for the next scheduled follow-up — symptoms mean the disease has declared itself.
⚡ Summary
Summary
Severe AS
AVA < 1.0 cm², mean gradient > 40, Vmax > 4 m/s. Symptoms = exertional dyspnea, syncope, angina.
AS Treatment
Symptomatic severe AS → TAVR or SAVR. No medical therapy stops progression. Avoid vasodilators, cautious diuresis.
Severe MR
Acute (papillary rupture): emergent surgery. Chronic: surgery when EF ≤ 60% or LVESD ≥ 40mm, or symptomatic.
Low-Flow AS
Low EF → low gradient despite severe AS. Dobutamine stress echo: AVA stays < 1.0 = truly severe. AVA improves = pseudo-severe.
Anticoag
Mechanical valve = warfarin (lifelong, INR 2.5-3.5 for mitral, 2.0-3.0 for aortic). DOACs contraindicated [RE-ALIGN].
Murmur Tip
Crescendo-decrescendo at RUSB radiating to carotids = AS. Holosystolic at apex radiating to axilla = MR.
📄 One Pager
Valvular Heart Disease — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
VALVULAR HEART DISEASE — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
One Pager — Valvular Heart Disease
See the Overview tab for detailed clinical content on all valve lesions.
📄 One Pager
Cardiology · One Pager · One Pager
Valvular Heart Disease
Severe AS = AVA < 1.0 + symptoms → TAVR/SAVR. Severe MR = surgery when EF ≤ 60% or LVESD ≥ 40mm. Don't delay intervention.
Severe Aortic Stenosis
- AVA < 1.0 cm², mean gradient > 40 mmHg, Vmax > 4 m/s
- Symptoms: exertional dyspnea, syncope, angina
- Once symptomatic → 2-year survival ~50% without intervention
- Low-flow low-gradient: dobutamine stress echo to differentiate true vs pseudo-severe
When to Intervene
- Symptomatic severe AS → TAVR or SAVR (no medical therapy works)
- Asymptomatic severe AS + EF < 50% → surgery
- Severe MR → surgery when EF ≤ 60% or LVESD ≥ 40mm
- Acute severe MR (papillary rupture) → emergent surgery
Anticoagulation
- Mechanical valve = warfarin lifelong (DOACs contraindicated [RE-ALIGN])
- INR target: 2.5-3.5 (mitral), 2.0-3.0 (aortic)
- Bioprosthetic: warfarin × 3-6 months → then ASA only
- TAVR: DAPT × 3-6 months → then ASA
Key Drugs
No medical Rx for ASValve replacement is the only treatment
Avoid in ASVasodilators, aggressive diuresis
MR afterload reductionACEi for chronic MR
WarfarinMechanical valves only
Pitfalls
- Vasodilators in severe AS (fixed obstruction → hypotension)
- DOACs with mechanical valve [RE-ALIGN increased events]
- Missing low-flow low-gradient AS (gradient looks mild)
- Delaying surgery in asymptomatic severe with declining EF
Syncope
Transient loss of consciousness with spontaneous recovery due to global cerebral hypoperfusion. The #1 question: is this cardiac or benign? Risk-stratify to determine who goes home vs who gets telemetry.
🔍 Overview
Etiology
| Category | % of Syncope | Examples | Risk |
|---|---|---|---|
| Reflex / vasovagal | ~50–60% | Emotional trigger, prolonged standing, pain, micturition, carotid sinus hypersensitivity | Benign. Prodrome (lightheadedness, warmth, diaphoresis, nausea). |
| Orthostatic hypotension | ~15% | Volume depletion, medications (antihypertensives, diuretics), autonomic neuropathy (diabetes, Parkinson) | Low. SBP drop ≥ 20 or DBP ≥ 10 within 3 min of standing. |
| Cardiac — arrhythmic | ~10–15% | Bradycardia (sick sinus, heart block), VT, SVT, long QT, Brugada, channelopathies | HIGH. Sudden onset without prodrome. Exertional syncope. Family history of SCD. |
| Cardiac — structural | ~5% | Severe AS, HCM (LVOT obstruction), massive PE, cardiac tamponade, aortic dissection | HIGH. Exertional syncope, new murmur, dyspnea. |
| Neurologic | Rare (< 5%) | Vertebrobasilar TIA, subclavian steal. Seizure is NOT syncope (different mechanism). | Variable. True neurologic syncope is rare — most "neurologic" syncope is actually cardiac. |
High-Risk Features — Admit These Patients
If ANY of these are present → admit for telemetry + further workup:
- Exertional syncope — cardiac until proven otherwise (AS, HCM, arrhythmia)
- Syncope while supine or seated — eliminates orthostatic/vasovagal
- No prodrome — sudden LOC without warning suggests arrhythmia
- Abnormal ECG: long QT, Brugada pattern, heart block, new LBBB, delta wave (WPW)
- Family history of sudden cardiac death (especially < 50 yo)
- Known structural heart disease (HF, prior MI, EF < 35%)
- Associated chest pain, dyspnea, or palpitations
- Significant injury from the fall
🧪 Workup
Initial Workup — All Syncope
| Test | Why |
|---|---|
| ECG MANDATORY | EVERY syncope patient gets an ECG. Look for: long QT, short QT, Brugada, WPW (delta wave), heart block, prior MI (Q waves), HCM (LVH + septal Q waves), arrhythmia. |
| Orthostatic vitals | Lying → sitting → standing. SBP drop ≥ 20 or DBP ≥ 10 or HR rise > 30 = positive. |
| BMP, CBC, glucose | Dehydration, anemia, hypoglycemia (not true syncope but a mimic). |
| Troponin | If ACS suspected or exertional syncope. |
| Echo | If structural heart disease suspected (new murmur, exertional syncope, abnormal ECG). Identifies AS, HCM, RV strain (PE), effusion. |
| Telemetry / Holter / Loop recorder | If arrhythmic cause suspected. Telemetry inpatient. Holter for 24–48h. Implantable loop recorder (ILR) for recurrent unexplained syncope. ISSUE-3, Brignole 2012 |
Routine head CT, EEG, and carotid US are NOT indicated for syncope unless focal neurologic signs are present. Syncope ≠ seizure. Syncope ≠ stroke. Over-ordering these wastes resources.
Canadian Syncope Risk Score
Validated score for ED risk stratification. Predicts 30-day serious adverse events. Canadian Syncope Risk Score, Thiruganasambandamoorthy 2016
| Predictor | Points |
|---|---|
| ED diagnosis: vasovagal | −2 |
| Heart disease history (HF, CAD, VHD) | +1 |
| Any ED SBP < 90 or > 180 | +2 |
| Troponin elevated (> 99th percentile) | +2 |
| Abnormal QRS axis (< −30° or > 100°) | +1 |
| QRS > 130 ms | +1 |
| Corrected QT > 480 ms | +2 |
| ED diagnosis: cardiac syncope | +2 |
Score ≤ −1: very low risk (~1%) → safe for discharge. Score ≥ 3: high risk (~20%+) → admit. San Francisco Syncope Rule, Quinn 2004
📋 On Rounds
Why is exertional syncope a red flag?
Exercise increases myocardial oxygen demand and cardiac output requirements. If there's a fixed obstruction (severe AS, HCM with LVOT obstruction), the heart cannot increase CO to match demand → BP drops → cerebral hypoperfusion → syncope. In arrhythmic causes, exercise triggers catecholamine-mediated arrhythmias (VT in ARVC, polymorphic VT in CPVT, long QT). Exertional syncope in a young person should raise concern for HCM, ARVC, channelopathy, or anomalous coronary artery — all causes of sudden cardiac death in athletes.
When is head CT indicated in syncope?
Almost never for syncope itself. Syncope is caused by transient global cerebral hypoperfusion — not a structural brain lesion. Head CT is indicated if: (1) significant head trauma from the fall (especially on anticoagulation), (2) focal neurologic deficits suggesting stroke (but stroke rarely presents as pure syncope), (3) concern for SAH (thunderclap headache). Routine head CT in simple syncope has an extremely low diagnostic yield (< 2%) and is not recommended by any guideline.
What high-risk features on ECG should make you admit a syncope patient?
Admit and monitor if any of: (1) Brugada pattern (coved ST elevation V1-V3), (2) Long QT (QTc > 500), (3) Short QT (QTc < 340), (4) Epsilon waves or TWI V1-V3 (ARVC), (5) WPW (delta wave + short PR), (6) New bundle branch block, (7) Mobitz II or 3rd degree AV block, (8) ST elevation (STEMI), (9) Non-sustained VT on telemetry. Also admit if: exertional syncope, syncope while supine/sitting, FH of sudden cardiac death < 50, known structural heart disease, or new murmur. Canadian Syncope Risk Score helps stratify — low risk can be discharged with follow-up.
A 22-year-old collapses during basketball and is resuscitated. What do you screen for?
Sudden cardiac arrest in a young athlete = mandatory structural/electrical workup: (1) Echo: HCM (septal thickness ≥ 15 mm), ARVC (RV dilation/dysfunction), dilated cardiomyopathy, anomalous coronary arteries. (2) ECG: WPW, long QT, Brugada, ARVC (epsilon waves, TWI V1-V3). (3) Cardiac MRI: definitive for ARVC (fatty infiltration, fibrosis), myocarditis, scar. (4) Genetic testing if channelopathy suspected. (5) Family screening (first-degree relatives). Most common causes of SCA in athletes: HCM (#1 in US), ARVC, anomalous coronaries, commotio cordis, channelopathies. All survivors get an ICD (secondary prevention).
📣 Sample Presentation
One-Liner
"Ms. Nguyen is a 22-year-old presenting after witnessed syncope at church. She felt lightheaded and warm before losing consciousness for ~10 seconds with no seizure activity. ECG normal sinus, no Brugada, no long QT. Orthostatic positive."
Key Points to Cover on Rounds
Classic vasovagal prodrome (warmth, lightheadedness, standing). Witnessed brief LOC, no seizure activity, rapid return to baseline. ECG: normal sinus, PR normal, QTc 420. Troponin negative. Orthostatic: supine 112/70→standing 88/58 with symptoms. No high-risk features (no exertional, no supine, no FH SCD, no structural heart disease). Plan: discharge with reassurance, hydration, leg crossing techniques, return precautions.
⚡ Management
Management — Syncope
See the Overview and Management tabs for detailed clinical content on syncope.
💊 Medications
Medications — Syncope
See the Overview and Management tabs for detailed clinical content on syncope.
📈 Monitoring
Monitoring — Syncope
See the Overview and Management tabs for detailed clinical content on syncope.
⚡ Summary
Summary
Most Common
Vasovagal (~50%). Prodrome: warmth, nausea, diaphoresis, tunnel vision → brief LOC → rapid recovery.
High-Risk ECG
Brugada, long QT, WPW, CHB, Mobitz II, new BBB, epsilon waves (ARVC), ST elevation.
Admit If
Exertional syncope, supine syncope, FH sudden death, structural heart disease, abnormal ECG, older patient.
Workup
ECG (everyone). Echo if cardiac suspected. Orthostatics. Labs: glucose, Hgb, troponin if cardiac concern.
Low Risk
Young, vasovagal prodrome, situational (cough/micturition), orthostatic, normal ECG → discharge with follow-up.
Young Athlete SCA
Mandatory workup: echo (HCM), ECG (WPW/QT), cardiac MRI (ARVC), genetic testing. Survivors get ICD.
📄 One Pager
One Pager — Syncope
See the Overview and Management tabs for detailed clinical content on syncope.
📄 One Pager
Cardiology · One Pager · One Pager
Syncope
Most are vasovagal (benign). ECG everyone. Admit if high-risk features. Young athlete collapse = mandatory cardiac workup.
Classification
- Vasovagal (~50%): prodrome → LOC → rapid recovery
- Orthostatic: volume depletion, meds, autonomic failure
- Cardiac: arrhythmia, structural (HCM, AS, PE, tamponade)
- Neurologic: rare as cause of syncope (more likely seizure)
Workup
- ECG (everyone) — look for Brugada, long QT, WPW, BBB, CHB
- Orthostatic vitals (lying → standing)
- Echo if cardiac cause suspected
- Labs: glucose, Hgb, troponin (if cardiac)
- Tilt-table test for recurrent unexplained
High-Risk — Admit
- Exertional or supine syncope
- FH sudden cardiac death < 50
- Structural heart disease
- Abnormal ECG (Brugada, QT, WPW, new BBB, AV block)
- Older age with no clear benign cause
- Associated with chest pain, dyspnea, palpitations
Key Drugs
Midodrine5-10 mg TID (orthostatic)
Fludrocortisone0.1 mg daily (autonomic)
Na/fluid intake2-3L/day + salt (vasovagal)
Counter-maneuversLeg crossing, squatting
Pitfalls
- Discharging cardiac syncope as vasovagal
- Missing ECG red flags (Brugada, QT, WPW)
- Not checking orthostatics
- Young athlete collapse without full cardiac workup
Heart Block & Bradyarrhythmias
Conduction system disease from AV node to His-Purkinje. Know which blocks are benign (Mobitz I) vs which need pacing (Mobitz II, 3rd degree). Atropine is your bridge while you call for the pacer.
🔍 Overview
AV Block Classification
| Type | ECG Pattern | Level of Block | Clinical Significance | Needs Pacing? |
|---|---|---|---|---|
| 1st Degree | PR > 200 ms, every P followed by QRS | AV node delay | Benign. No treatment needed. Common in athletes, vagal tone, beta-blockers. | No |
| 2nd Degree — Mobitz I (Wenckebach) | Progressive PR prolongation → dropped QRS. Grouped beating pattern. | AV node (above His) | Usually benign. Common in inferior MI (RCA supplies AV node), athletes, digoxin. Often transient. | Rarely. Only if symptomatic (bradycardia with hemodynamic compromise). |
| 2nd Degree — Mobitz II | Constant PR interval → sudden dropped QRS. No progressive prolongation. | Below His bundle (infranodal) | DANGEROUS. High risk of progressing to complete heart block without warning. Often associated with anterior MI, structural disease. | Yes — pacemaker indicated even if asymptomatic. |
| 3rd Degree (Complete) | Complete AV dissociation. P waves march through at their own rate. QRS at escape rate (junctional 40–60 or ventricular 20–40). | Complete block at any level | EMERGENCY if symptomatic. May be stable if junctional escape with narrow QRS. Wide QRS escape = unstable, unreliable. | Yes — permanent pacemaker. |
Mobitz I = safe (AV node, usually transient). Mobitz II = dangerous (infranodal, can drop to complete block suddenly). The key distinction: does the PR progressively lengthen before the drop? Yes = Mobitz I. No = Mobitz II.
Common Causes
- Medications — beta-blockers, CCBs (verapamil/diltiazem), digoxin, amiodarone (most common reversible cause)
- Ischemia — inferior MI (AV node block, often transient), anterior MI (His-Purkinje, often permanent)
- Degenerative — fibrosis of conduction system (Lenegre disease, Lev disease) — most common in elderly
- Infiltrative — sarcoidosis (think cardiac sarcoid in young patient with unexplained heart block), amyloidosis
- Infectious — Lyme disease (early disseminated → AV block, usually reversible with antibiotics), endocarditis with abscess
- Post-surgical — TAVR, septal myectomy, congenital heart surgery
🚨 Management
Acute Symptomatic Bradycardia
Step 1
Atropine 0.5 mg IV q3–5 min (max 3 mg). Works for AV nodal block (1st degree, Mobitz I, junctional). Does NOT work for infranodal block (Mobitz II, 3rd degree with wide escape) — the block is below where atropine acts.
🔄 Updated Practice: Old teaching: atropine works for all types of heart block. Current practice: atropine only works for NODAL blocks (1st degree AV block, Mobitz Type I/Wenckebach) by increasing AV node conduction via vagolytic effect. It does NOT work for INFRANODAL blocks (Mobitz Type II, complete/3rd degree heart block) — and can paradoxically worsen the block by increasing atrial rate without improving ventricular conduction. Infranodal blocks require transcutaneous or transvenous pacing.
Step 2
If atropine fails: transcutaneous pacing (external pads). Set rate 60–80, increase mA until capture. Sedate the patient — it's painful. This is a bridge.
Step 3
Transvenous pacing (temporary pacing wire via IJ/subclavian/femoral). Definitive temporary bridge until permanent pacer.
Bridge agents
While awaiting pacing: dopamine 5–20 mcg/kg/min or epinephrine 2–10 mcg/min or isoproterenol 2–20 mcg/min (β₁ chronotropy).
Permanent Pacemaker Indications
- 3rd degree AV block (symptomatic or asymptomatic) ACC/AHA/HRS Bradycardia Guidelines, Kusumoto 2019
- Mobitz II (symptomatic or asymptomatic — high progression risk)
- Symptomatic Mobitz I not due to reversible cause
- Symptomatic sinus node dysfunction (sick sinus syndrome, tachy-brady syndrome)
- Post-MI persistent 2nd or 3rd degree block
- Alternating bundle branch block (RBBB alternating with LBBB — impending complete block)
Always rule out reversible causes before permanent pacing: medication effect (hold offending drugs and reassess), Lyme disease (treat with IV ceftriaxone), inferior MI (AV block often resolves in 5–7 days), hyperkalemia, hypothyroidism. ACC/AHA/HRS, 2019
🧪 Workup
Workup
- ECG — degree and level of block
- BMP + Mg²⁺ — hyperkalemia
- Medication review — BB, CCB, digoxin, amiodarone
- TSH — hypothyroidism
- Lyme serology — AV block in Lyme carditis
- Troponin — inferior MI → AV node ischemia
- Echo — structural/infiltrative disease
📋 On Rounds
Why doesn't atropine work in Mobitz II or infranodal block?
Atropine is a parasympatholytic (anticholinergic) — it blocks vagal tone at the AV node, increasing conduction through the node. In Mobitz II and 3rd degree heart block with wide QRS, the block is below the AV node (in the His bundle or bundle branches) where there is no parasympathetic innervation. Atropine has no target to act on. In fact, atropine can paradoxically worsen infranodal block by increasing the sinus rate — more P waves arrive at the blocked His bundle, and more get dropped. This is why transcutaneous pacing is the correct intervention for symptomatic infranodal block.
A 28-year-old presents with new-onset 3rd degree heart block. What diagnosis should you consider?
Lyme disease (Lyme carditis) and cardiac sarcoidosis. Lyme is the most important to catch — it's fully reversible with IV ceftriaxone (2g daily × 14–21 days). Occurs in early disseminated Lyme (weeks–months after tick bite). Get Lyme serologies in any young patient with unexplained heart block, especially in endemic areas. AV block usually resolves within 1–2 weeks of antibiotics; temporary pacing may be needed but permanent pacer is rarely required. Cardiac sarcoidosis is diagnosed with cardiac MRI (late gadolinium enhancement) ± PET scan ± biopsy.
What medications cause heart block, and which are reversible?
Reversible (hold and observe): beta-blockers (metoprolol, atenolol, carvedilol), non-DHP calcium channel blockers (diltiazem, verapamil), digoxin, amiodarone, clonidine. Metabolic causes (correct the cause): hyperkalemia (most dangerous — can cause any degree of block → sine wave → arrest), hypothyroidism, hypothermia. Infectious: Lyme disease (3rd degree block in 1-2% of Lyme carditis — usually resolves with antibiotics, may need temporary pacing). Irreversible/structural: idiopathic fibrosis (Lev/Lenègre disease), post-TAVR, post-AV node ablation, infiltrative (sarcoid, amyloid), inferior MI (usually transient — AV node supplied by RCA). Key: always check med list and K⁺ before calling EP for a pacer.
An inferior STEMI patient develops complete heart block. Is this the same as chronic CHB?
No — and the management is different. Inferior MI causes AV node ischemia (supplied by RCA in 85%) → typically a junctional escape rhythm at 40-60 bpm (narrow QRS, relatively stable). This is usually transient (resolves in 2-7 days) as the AV node recovers. Management: temporary pacing if hemodynamically compromised, atropine may help (vagal-mediated). Does NOT routinely need a permanent pacer — monitor and reassess. In contrast, anterior MI causing CHB = infranodal block (His-Purkinje damage from large LAD infarct) → wide QRS escape, unstable, high mortality, almost always needs permanent pacer. Location of block matters more than degree of block.
📣 Sample Presentation
One-Liner
"Mr. Davis is a 76-year-old on metoprolol 200 mg daily presenting with dizziness and HR 34. ECG shows complete (third-degree) AV block with a ventricular escape rate of 34 bpm."
Key Points to Cover on Rounds
Third-degree AV block. Hemodynamically stable but symptomatic. Metoprolol held (reversible cause). Temporary transcutaneous pacing pads placed. Atropine 0.5 mg given with transient improvement to HR 48. Lyme screen and TSH sent. Troponin negative. EP consulted for permanent pacemaker. Plan: if no improvement after holding BB ×24h, transvenous pacing wire → permanent pacer.
💊 Medications
Key Medications — Heart Block & Bradycardia
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Atropine 1ST LINE | 0.5-1 mg IV, repeat q3-5 min (max 3 mg) | IV push | Vagolytic — works for nodal block only (1st degree, Mobitz I). Will NOT work for Mobitz II or 3rd degree (infranodal) — no vagal innervation below AV node. Can paradoxically worsen infranodal block. |
| Isoproterenol (Isuprel) | 2-10 mcg/min IV drip | IV | Beta-1 + Beta-2 agonist. Increases HR and AV conduction. Bridge to pacing. Caution: increases myocardial O₂ demand. |
| Dopamine | 5-20 mcg/kg/min IV drip | IV | Chronotropic at 5-10 mcg/kg/min (beta effect). Alternative to isoproterenol if hypotensive. Higher doses add alpha vasoconstriction. |
| Epinephrine | 2-10 mcg/min IV drip | IV | For symptomatic bradycardia unresponsive to atropine. Potent chronotrope and vasopressor. |
| Transcutaneous pacing | Start 60-80 mA, rate 60-80 bpm | External pads | Bridge to transvenous pacing. Painful — requires sedation. Verify mechanical capture (palpable pulse with each complex). |
| Transvenous pacing | Per EP/cardiology | Central venous | Temporary pacing wire via RIJ or femoral vein. For refractory symptomatic bradycardia awaiting permanent pacemaker. |
First step: Review medication list — hold all AV-nodal blockers (beta-blockers, non-DHP CCBs, digoxin, amiodarone). Check K⁺ and Mg²⁺. Many cases of heart block are iatrogenic and reversible.
📈 Monitoring
Monitoring Parameters — Heart Block & Bradycardia
| Parameter | Frequency | Target / Action |
|---|---|---|
| Continuous telemetry | Continuous | Mandatory. Monitor for progression (1st → 2nd → 3rd degree), escape rhythm stability, pause duration. Keep transcutaneous pads on. |
| Heart rate trend | q1-4h depending on stability | Symptomatic threshold varies but HR <40 bpm or pauses >3 sec usually require intervention. |
| Symptoms | Each assessment | Syncope, presyncope, lightheadedness, fatigue, exertional intolerance, chest pain. Asymptomatic Mobitz I may not need pacing. |
| BMP (K⁺, Mg²⁺, Ca²⁺) | Daily + PRN | Correct hyperkalemia (most dangerous reversible cause). Hypomagnesemia and hypocalcemia can contribute. |
| Medication review | Daily | Hold AV-nodal blockers. Document time of last dose and expected clearance. Reassess after drug washout (24-48h for most). |
| Pacemaker thresholds | Daily if temp wire placed | Check capture threshold, sensing, impedance. Increase output to 2× capture threshold for safety margin. |
| TSH, Lyme serology | Once (if indicated) | Hypothyroidism and Lyme carditis are reversible causes. Lyme: AV block usually resolves with antibiotics (IV ceftriaxone × 14-21 days). |
⚡ Summary
Summary
1st Degree
PR > 200ms. Benign. No treatment needed. Monitor if progressing.
2nd Degree Mobitz I
Progressive PR prolongation → dropped beat. Usually AV nodal (narrow QRS). Often benign. Observe.
2nd Degree Mobitz II
Constant PR → sudden dropped beat. Infranodal (His-Purkinje). DANGEROUS — can progress to CHB. Needs pacer.
3rd Degree (CHB)
Complete AV dissociation. Narrow escape = junctional (40-60 bpm, stable). Wide escape = ventricular (20-40, unstable).
Check First
Med list (BB, CCB, digoxin, amiodarone), K⁺ (hyperkalemia), Lyme screen, TSH, troponin (MI).
Temporary Pacing
Transcutaneous pads (bridge). Atropine for symptomatic bradycardia. Transvenous wire if unstable + awaiting permanent pacer.
📄 One Pager
Heart Block & Bradyarrhythmias — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
HEART BLOCK & BRADYARRHYTHMIAS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
Cardiology · One Pager · One Pager
Heart Block
Check meds and K⁺ first. Mobitz I = usually benign. Mobitz II or CHB = pacemaker. Don't delay temp pacing if symptomatic.
Types
- 1st degree: PR > 200ms. Benign. Observe.
- 2nd degree Mobitz I: progressive PR → dropped beat. AV nodal. Usually benign.
- 2nd degree Mobitz II: constant PR → sudden drop. Infranodal. DANGEROUS → pacer.
- 3rd degree (CHB): complete dissociation. Narrow escape = junctional (40-60). Wide = ventricular (20-40, unstable).
Management
- Check and hold offending meds: BB, CCB, digoxin, amiodarone
- Check K⁺ (hyperkalemia causes any degree of block)
- Symptomatic bradycardia → atropine 0.5 mg IV
- Transcutaneous pacing pads on standby
- Transvenous wire if unstable + awaiting permanent pacer
- Lyme screen and TSH if no obvious cause
When Does It Need a Pacer?
- Mobitz II (risk of sudden progression to CHB)
- Third-degree AV block (symptomatic or with wide escape)
- Symptomatic sinus node dysfunction
- Post-TAVR CHB (common, may resolve — observe 24-48h)
- Alternating bundle branch block
- Exception: inferior MI CHB often resolves (observe, don't rush to pacer)
Key Drugs
Atropine0.5 mg IV q3-5 min (max 3 mg)
Dopamine2-20 mcg/kg/min (bridge)
Epinephrine (Adrenalin)2-10 mcg/min (bridge)
Isoproterenol2-10 mcg/min (last resort)
Pitfalls
- Not checking med list first (most common cause)
- Missing hyperkalemia
- Rushing to permanent pacer in inferior MI CHB
- Not placing transcutaneous pads early
Myocarditis
Inflammation of the myocardium. Classic presentation: young patient with recent viral illness → chest pain + troponin elevation + new HF. Ranges from mild (self-limited) to fulminant (cardiogenic shock). Cardiac MRI is the key diagnostic tool.
🔍 Overview
Presentation Spectrum
| Type | Presentation | Hemodynamics | Prognosis |
|---|---|---|---|
| Acute (non-fulminant) | Chest pain, dyspnea, palpitations. Preceded by viral URI 1–4 weeks prior. Mild-moderate LV dysfunction. | Stable. Mild EF reduction. | ~50% recover fully. ~25% develop chronic DCM. ~25% stable but reduced EF. |
| Fulminant | Rapid-onset cardiogenic shock within days. Severe biventricular failure. Arrhythmias. | Hemodynamic collapse. May need MCS (Impella, ECMO). | Paradoxically better long-term prognosis if they survive the acute phase — ~90% recover LV function (robust immune response clears the virus). |
| Chronic active | Persistent HF symptoms > 3 months. Ongoing inflammation on biopsy. | Progressive LV dilation and dysfunction. | May progress to DCM. May need transplant evaluation. |
| Giant cell | Rapidly progressive HF + VT. Young-middle age. | Severe. Refractory arrhythmias. | Worst prognosis. Median survival ~5 months without transplant. Immunosuppression is indicated. |
Etiology
- Viral (most common) — Coxsackievirus B, parvovirus B19, HHV-6, adenovirus, SARS-CoV-2, influenza
- Autoimmune — SLE, sarcoidosis, eosinophilic myocarditis (hypersensitivity)
- Drug/toxin — immune checkpoint inhibitors (PD-1/PD-L1 — pembrolizumab, nivolumab), doxorubicin, cocaine, amphetamines
- Giant cell myocarditis — idiopathic, associated with autoimmune diseases (IBD, thymoma)
Checkpoint inhibitor myocarditis: rare (~1%) but mortality > 40%. Presents 1–3 months after starting therapy. Stop the drug immediately. High-dose IV methylprednisolone. Cardiology + oncology co-management.
Diagnosis
| Test | Findings |
|---|---|
| Troponin | Elevated (may mimic MI). Often with recent viral prodrome. |
| ECG | Diffuse ST changes (may mimic pericarditis or STEMI), sinus tachycardia, arrhythmias (VT, heart block), low voltage. |
| Echo | New wall motion abnormalities (often non-territorial — unlike MI). Reduced EF. May see pericardial effusion. |
| Cardiac MRI KEY DIAGNOSTIC TOOL | Lake Louise criteria: (1) T2 hyperintensity (edema), (2) late gadolinium enhancement — mid-wall or epicardial pattern (unlike MI which is subendocardial/transmural). (3) T1 mapping abnormalities. Sensitivity ~80%, specificity ~90%. |
| Endomyocardial biopsy | Gold standard but rarely done (low sensitivity due to sampling error). Indicated in: fulminant myocarditis, suspected giant cell, no improvement despite treatment, need to guide immunosuppression. |
🚨 Management
Treatment
- Supportive care — standard HF therapy if reduced EF (ACEi/ARB, beta-blocker, diuretics as needed). Avoid NSAIDs in acute phase (may impair healing).
- Activity restriction — no competitive sports for 3–6 months minimum. Risk of fatal arrhythmias with exertion. Repeat echo and MRI before return to play.
- Arrhythmia management — telemetry monitoring. Life vest (wearable defibrillator) if EF < 35% acutely. Avoid permanent ICD in acute phase — EF may recover. Reassess at 3–6 months.
- Fulminant → ICU. Inotropes, vasopressors. Early MCS (Impella/ECMO) if deteriorating — these patients often recover if supported through the acute phase.
- Giant cell myocarditis → immunosuppression (cyclosporine + steroids ± azathioprine). Early transplant evaluation. Giant Cell Myocarditis Registry, 1997: immunosuppression improved survival from 3 months to 12 months.
- Checkpoint inhibitor myocarditis → stop drug + high-dose IV methylprednisolone 1g/day × 3–5 days, then oral taper.
🧪 Workup
Workup
- Troponin — elevated, trend q6-8h
- ECG — diffuse ST changes, arrhythmias
- Echo — EF, wall motion, pericardial effusion
- Cardiac MRI (gold standard) — T2 edema, mid-myocardial LGE
- ESR, CRP
- Endomyocardial biopsy — only if giant cell suspected
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Lisinopril (Zestril) | 2.5-20 mg daily | PO | ACEi for LV remodeling. Start low, uptitrate. ARB if ACEi-intolerant. |
| Carvedilol (Coreg) | 3.125-25 mg BID | PO | Low-dose BB — titrate cautiously. Hold if cardiogenic shock or decompensated HF. |
| Furosemide (Lasix) | 20-80 mg PRN | IV/PO | Diuresis for fluid overload/congestion. Titrate to euvolemia. |
| Avoid NSAIDs | — | — | Worsen myocardial inflammation and necrosis. Contraindicated even though chest pain is prominent. |
| Immunosuppression | Per biopsy/pathology | IV/PO | ONLY for giant cell myocarditis (cyclosporine + steroids) or eosinophilic myocarditis (high-dose steroids). NOT for viral myocarditis. |
| IVIG | 2 g/kg over 2-5 days | IV | Consider in select cases (pediatric, fulminant). Evidence mixed. Not routine. |
| Inotropes / MCS | Per hemodynamics | IV | Milrinone or dobutamine for cardiogenic shock. Impella/ECMO for fulminant myocarditis with refractory shock. |
📊 Monitoring
Monitoring
- Continuous telemetry — high risk for VT/VF, AV block. Keep defibrillator pads on in fulminant cases.
- Serial troponin q8-12h — trend to peak and decline. Persistent elevation suggests ongoing myocyte injury.
- Serial echocardiography — EF trending, wall motion abnormalities, pericardial effusion. Repeat at discharge, 1-3 months, 3-6 months.
- Hemodynamic monitoring — watch for cardiogenic shock (hypotension, rising lactate, cool extremities, declining UOP). Early MCS consultation if deteriorating.
- Daily volume assessment — JVP, lung exam, I&Os, daily weights. Titrate diuretics to euvolemia.
- Cardiac MRI repeat at 3-6 months — resolution of edema and inflammation before clearing for activity.
- Holter + exercise stress test before return to competitive sports. No exercise for minimum 3-6 months.
📋 On Rounds
How does cardiac MRI distinguish myocarditis from MI?
Late gadolinium enhancement (LGE) pattern. In MI, LGE follows a coronary distribution and is subendocardial or transmural (starts from the endocardium and extends outward). In myocarditis, LGE is typically mid-wall or epicardial (spares the subendocardium) and is non-territorial (doesn't match a coronary artery distribution). The epicardial/mid-wall pattern reflects inflammatory infiltration that preferentially affects the outer myocardial layers.
Why does fulminant myocarditis have a paradoxically better long-term prognosis?
Fulminant myocarditis represents an overwhelming but robust immune response — the immune system aggressively attacks the virus (and unfortunately, the myocardium). If the patient survives the acute phase (with MCS if needed), the strong immune response effectively clears the virus, and the myocardium recovers — ~90% regain normal LV function. In contrast, non-fulminant myocarditis represents a weaker, smoldering immune response that fails to clear the virus completely, leading to ongoing low-grade inflammation → chronic damage → DCM in ~25%. This is why aggressive MCS support in fulminant myocarditis is so important — you're buying time for the immune system to do its job.
Why do you avoid NSAIDs in acute myocarditis even though they're first-line for pericarditis?
In pericarditis, inflammation is limited to the pericardium — NSAIDs reduce inflammation and improve symptoms. In myocarditis, the inflammation involves the myocardium itself. Animal studies showed NSAIDs increased myocardial necrosis and mortality in viral myocarditis by impairing the immune response needed to clear the virus and by increasing viral replication. NSAIDs also reduce renal blood flow which is detrimental in patients with reduced EF. Exception: if there's concurrent myopericarditis with normal EF and the pericardial symptoms dominate, low-dose NSAIDs may be cautiously used. For pure myocarditis with reduced EF → standard HF therapy (ACEi, BB cautiously, diuretics).
A 28-year-old recovered from myocarditis with EF 35%. When can they return to exercise?
No competitive sports or intense exercise for minimum 3-6 months after acute myocarditis regardless of EF recovery. This is because active myocardial inflammation creates a substrate for fatal ventricular arrhythmias during exercise (catecholamine surge + inflamed myocardium = VT/VF). Before returning: (1) ≥ 3 months from onset, (2) EF normalized on repeat echo, (3) No LGE on cardiac MRI (or stable/reduced), (4) No arrhythmias on exercise stress test and 24h Holter, (5) Normal inflammatory markers. [ESC 2020 Sports Cardiology Guidelines: gradual return to activity, individualized based on imaging and arrhythmia assessment. If EF remains < 50% → activity restrictions indefinitely.
📣 Sample Presentation
One-Liner
"Mr. Reyes is a 28-year-old presenting with chest pain and dyspnea 10 days after a viral illness. Troponin 8.2, BNP 1,400. ECG shows diffuse ST changes. Echo EF 35% with global hypokinesis. Cardiac MRI shows late gadolinium enhancement consistent with myocarditis."
Key Points to Cover on Rounds
Presumed viral myocarditis. Troponin trending 8.2→5.4 (downtrending). Echo: EF 35%, global hypokinesis, small pericardial effusion. MRI: LGE in mid-myocardial pattern (typical for myocarditis, not ischemic). Hemodynamically stable. Treatment: lisinopril, carvedilol (low dose), furosemide PRN. No NSAIDs (may worsen myocardial inflammation in acute phase). Activity restriction × 3-6 months. Follow-up echo in 3 months — EF expected to recover.
⚡ Summary
Summary
Suspect When
Young patient + chest pain + troponin elevation + new HF after viral illness. ECG: diffuse ST changes.
Gold Standard
Cardiac MRI with LGE (late gadolinium enhancement) — mid-myocardial pattern (not subendocardial like MI).
Treatment
Standard HF therapy: ACEi + low-dose BB + diuretics PRN. Avoid NSAIDs (worsen necrosis). No intense exercise × 3-6 months.
Arrhythmia Risk
Active inflammation → VT/VF substrate. No competitive sports until: EF normalized, no LGE, normal Holter + stress test.
Prognosis
Most viral myocarditis recovers within weeks to months. EF should improve. If persistent → DCM evaluation.
Don't Miss
Giant cell myocarditis: rapid HF + VT + young. Needs biopsy. Treatment: immunosuppression. Consider transplant early.
📄 One Pager
Cardiology · One Pager · One Pager
Myocarditis
Young + chest pain + troponin + new HF after viral illness. Cardiac MRI = gold standard. No NSAIDs. No exercise × 3-6 months.
Diagnosis
- Suspect: young patient + chest pain + troponin ↑ + new HF + recent viral illness
- ECG: diffuse ST changes, low voltage, arrhythmias
- Echo: reduced EF, regional or global wall motion abnormality
- Gold standard: Cardiac MRI — mid-myocardial LGE (not subendocardial like MI)
Management
- Standard HF therapy: ACEi + low-dose BB + diuretics PRN
- Avoid NSAIDs (worsen myocardial necrosis in animal models)
- Activity restriction: no exercise × 3-6 months minimum
- Arrhythmia monitoring: telemetry (VT/VF risk during active inflammation)
- Follow-up echo at 3-6 months (EF should recover in most viral cases)
Return to Activity Criteria
- ≥ 3 months from symptom onset
- EF normalized on echo
- No LGE on cardiac MRI (or stable/reduced)
- No arrhythmias on Holter + exercise stress test
- Normal inflammatory markers (CRP, troponin)
- Gradual return, individualized [ESC Sports Cardiology 2020]
Key Drugs
ACEi/ARBStandard HF dosing
Low-dose BBCarvedilol or metoprolol
DiureticsFurosemide PRN for congestion
AvoidNSAIDs, intense exercise
Pitfalls
- NSAIDs in acute myocarditis
- Early return to exercise (arrhythmia risk)
- Missing giant cell myocarditis (rapid HF + VT → biopsy)
- Confusing with STEMI (check MRI pattern)
Hypertrophic Cardiomyopathy
Asymmetric septal hypertrophy (≥ 15 mm) not explained by loading conditions. Autosomal dominant. The #1 cause of sudden cardiac death in young athletes. Know the LVOT obstruction physiology — it drives everything.
🔍 Overview
LVOT Obstruction — The Core Physiology
~70% of HCM patients have dynamic LVOT obstruction (gradient ≥ 30 mmHg at rest or with provocation). The thickened septum narrows the outflow tract → high-velocity flow → Venturi effect pulls the anterior mitral leaflet toward the septum (SAM = systolic anterior motion) → further obstruction + mitral regurgitation.
What WORSENS obstruction
- ↓ Preload — dehydration, Valsalva, standing, diuretics (smaller LV cavity → septum and MV closer together)
- ↓ Afterload — vasodilators, exercise-induced vasodilation
- ↑ Contractility — exercise, inotropes, digoxin, catecholamines
What IMPROVES obstruction
- ↑ Preload — IV fluids, leg elevation, squatting
- ↑ Afterload — phenylephrine (alpha agonist)
- ↓ Contractility / HR — beta-blockers, verapamil
Avoid in HCM: nitrates, diuretics, digoxin, ACEi/ARBs (drop preload/afterload → worsen obstruction), dobutamine/milrinone (increase contractility → worsen obstruction). If hypotensive → IV fluids + phenylephrine. NOT vasopressors that increase contractility.
Clinical Features
- Murmur: harsh crescendo-decrescendo systolic murmur at LLSB. Louder with Valsalva and standing (decreased preload). Softer with squatting (increased preload). This is the opposite of most murmurs.
- Symptoms: exertional dyspnea, syncope (especially exertional — red flag), chest pain, palpitations
- ECG: LVH, deep septal Q waves (V1–V3, "dagger" Q waves), T-wave inversions
- Echo (diagnostic): septal wall thickness ≥ 15 mm, SAM of mitral valve, LVOT gradient, MR
🚨 Management
Medical Therapy
| Drug | Role | Notes |
|---|---|---|
| Beta-blocker (non-vasodilating) 1ST LINE | ↓ HR, ↓ contractility, ↑ diastolic filling time | Metoprolol or propranolol preferred. Titrate to resting HR 60–65. Do NOT use carvedilol (vasodilating properties worsen obstruction). |
| Verapamil (Calan) 2ND LINE | ↓ HR, ↓ contractility, improves diastolic relaxation | If BB intolerant. Avoid in severe resting obstruction (gradient > 100 mmHg) — vasodilatory effect may worsen hemodynamics. |
| Disopyramide ADD-ON | Negative inotrope (Class Ia antiarrhythmic) | Added to BB for refractory symptoms. Must combine with BB (disopyramide alone → reflex tachycardia from anticholinergic effects). |
| Mavacamten (Camzyos) BREAKTHROUGH | Cardiac myosin inhibitor. Directly reduces contractility by decreasing myosin-actin cross-bridge formation. | EXPLORER-HCM, 2020: reduced LVOT gradient from 74 → 12 mmHg. Improved symptoms and exercise capacity. First targeted therapy for HCM. Requires REMS program (risk of excessive EF reduction). |
Invasive Therapy (Refractory Symptoms)
- Septal myectomy (Morrow procedure) — surgical resection of hypertrophied septum. Gold standard for refractory obstructive HCM. Success rate > 95%. Mortality < 1% at experienced centers.
- Alcohol septal ablation — ethanol injection into septal perforator artery → controlled MI of hypertrophied septum. Alternative for high surgical risk. Higher rates of heart block (10–20%) and need for permanent pacemaker.
Sudden Cardiac Death Risk — ICD Criteria
HCM is the #1 cause of sudden cardiac death in young athletes. Risk stratify ALL HCM patients.
- ICD indicated (secondary prevention): prior cardiac arrest, sustained VT
- ICD considered (primary prevention) if ≥ 1 major risk factor:
| Risk Factor | Details |
|---|---|
| Family history of SCD | 1st degree relative with SCD from HCM (especially < 50 yo) |
| Massive LVH | Max wall thickness ≥ 30 mm |
| Unexplained syncope | Recent (< 6 months), especially exertional |
| NSVT | Non-sustained VT on Holter (≥ 3 beats at ≥ 120 bpm) |
| Abnormal BP response to exercise | Failure of SBP to rise ≥ 20 mmHg with exercise (especially age < 40) |
| Extensive LGE on MRI | ≥ 15% LGE → significant fibrosis → arrhythmia substrate |
| LV apical aneurysm | Independent risk for VT |
🧪 Workup
Workup
- Echo — wall thickness, LVOT gradient, SAM
- 48h Holter — NSVT for SCD
- Exercise stress — hypotension
- Cardiac MRI — fibrosis, apical HCM
- Genetic testing
- Family echo — first-degree relatives
📋 On Rounds
Why does the HCM murmur get louder with Valsalva?
Valsalva decreases venous return (preload) → smaller LV cavity → the hypertrophied septum and anterior mitral leaflet are now closer together → more SAM → greater LVOT obstruction → louder murmur. This is the opposite of AS (fixed obstruction — murmur gets softer with decreased preload because less blood crosses the valve). The dynamic nature of the obstruction is the key concept — anything that makes the ventricle smaller worsens HCM obstruction.
What is mavacamten and why is it a breakthrough?
Mavacamten is a first-in-class cardiac myosin inhibitor — it directly reduces the number of myosin-actin cross-bridges that form during systole, reducing contractility at the sarcomere level. EXPLORER-HCM, 2020 showed it reduced resting LVOT gradient from 74 to 12 mmHg (vs 4 mmHg reduction with placebo). This is the first drug that targets the root cause of HCM (excess contractility) rather than compensating for it with negative chronotropy (BB) or negative inotropy (disopyramide). It may reduce the need for septal myectomy/ablation in many patients.
Why are vasodilators, diuretics, and digoxin dangerous in obstructive HCM?
In obstructive HCM, the septum narrows the LVOT and the anterior mitral leaflet is pulled into the outflow tract during systole (SAM = systolic anterior motion). Vasodilators (ACEi, ARBs, nitrates, dihydropyridine CCBs) → reduce afterload → less resistance to outflow → LVOT gradient INCREASES → worsens obstruction. Diuretics → reduce preload → smaller LV cavity → septum and mitral leaflet are closer together → obstruction worsens. Digoxin → increases contractility → more vigorous systolic contraction → more SAM and obstruction. Instead use: beta-blockers (first-line), non-DHP CCBs (verapamil), disopyramide. And now mavacamten (cardiac myosin inhibitor — directly reduces contractility in HCM) [EXPLORER-HCM, 2020.
What is mavacamten and how does it change HCM management?
Mavacamten (Camzyos) is a first-in-class cardiac myosin inhibitor — it reduces the number of actin-myosin cross-bridges during systole, directly decreasing contractility and LVOT gradient. [EXPLORER-HCM, 2020: reduced LVOT gradient from ~50 to ~10 mmHg, improved exercise capacity and symptoms. Approved for symptomatic obstructive HCM (NYHA II-III). Key risk: excessive reduction in EF — requires echo monitoring (EF q12 weeks). Contraindicated if EF < 55%. Must use REMS program. This is the biggest advance in HCM pharmacotherapy in decades — may reduce the need for septal myectomy/alcohol ablation in many patients.
📣 Sample Presentation
One-Liner
"Ms. Washington is a 34-year-old referred after a murmur was found on sports physical. Echo shows septal thickness 22 mm, LVOT gradient 65 mmHg at rest, SAM of mitral valve. Asymptomatic."
Key Points to Cover on Rounds
Known HCM with obstruction (resting gradient 65). Currently asymptomatic, NYHA class I. SCD risk assessment: no FH of SCD, no unexplained syncope, no NSVT on Holter, max wall thickness 22 mm (risk factor), no exercise hypotension. ICD discussion: intermediate risk based on wall thickness — shared decision-making. Started metoprolol 25 mg BID. Avoid dehydration, vasodilators, digoxin. Activity: no competitive sports.
💊 Medications
Key Medications — Hypertrophic Cardiomyopathy
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — Hypertrophic Cardiomyopathy
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
⚡ Summary
Summary
Diagnosis
Wall thickness ≥ 15mm (any segment) not explained by loading conditions. Genetic (autosomal dominant).
Obstruction
LVOT gradient ≥ 30 mmHg at rest or with provocation. SAM of mitral valve. Worsened by dehydration, Valsalva, vasodilators.
Medications
BB first-line. Verapamil second-line. Disopyramide for refractory. Mavacamten (myosin inhibitor) [EXPLORER-HCM, 2020].
Avoid
Vasodilators (ACEi, nitrates), diuretics, digoxin, dehydration — all worsen obstruction.
SCD Risk
FH sudden death, unexplained syncope, NSVT, wall thickness ≥ 30mm, exercise hypotension. Consider ICD.
Activity
No competitive sports. Low-moderate exercise may be acceptable based on individual risk assessment.
📄 One Pager
Hypertrophic Cardiomyopathy — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
HYPERTROPHIC CARDIOMYOPATHY — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
Cardiology · One Pager · One Pager
Hypertrophic Cardiomyopathy
Wall ≥ 15mm. Obstruction worsened by dehydration + vasodilators. BB first-line. Mavacamten = new. SCD risk stratification in all patients.
Diagnosis
- LV wall thickness ≥ 15mm (any segment) not explained by loading conditions
- Autosomal dominant (screen first-degree relatives)
- LVOT obstruction: gradient ≥ 30 mmHg at rest or provocation
- SAM of mitral valve on echo
Management
- Beta-blocker first-line (reduce HR → improve filling time → reduce obstruction)
- Verapamil second-line (if BB-intolerant)
- Disopyramide for refractory obstruction
- Mavacamten (cardiac myosin inhibitor) [EXPLORER-HCM, 2020]
- Septal myectomy or alcohol septal ablation if refractory to meds
SCD Risk Assessment
- FH sudden cardiac death < 50 years
- Unexplained syncope
- Non-sustained VT on Holter
- Max wall thickness ≥ 30mm
- Exercise hypotension
- ICD implantation based on risk score (≥ 1 major risk factor → discuss ICD)
Key Drugs
Metoprolol50-200 mg BID
Verapamil120-480 mg/day
Disopyramide100-200 mg TID
Mavacamten5-15 mg daily
Pitfalls
- Vasodilators (ACEi, nitrates) → worsen obstruction
- Diuretics → reduce preload → worsen obstruction
- Digoxin → increases contractility → worsen obstruction
- Dehydration → worse obstruction
- No competitive sports
Heart Failure — Chronic Management
GDMT optimization with the four pillars, HFrEF vs HFpEF distinction, device therapy, and long-term management. For acute decompensation and ICU management, see ADHF.
🔍 Overview
Classification
| Type | EF | Pathology | Key Feature |
|---|---|---|---|
| HFrEF (systolic) | ≤ 40% | Impaired contraction | GDMT* proven to reduce mortality. All four pillars apply. *GDMT = Guideline-Directed Medical Therapy |
| HFmrEF (mid-range) | 41–49% | Borderline — may behave like either | Emerging data supports GDMT (especially SGLT2i). Treat like HFrEF if symptomatic. |
| HFpEF (diastolic) | ≥ 50% | Impaired relaxation / filling | No mortality-reducing GDMT until SGLT2i. Manage volume, comorbidities, and now SGLT2i. |
NYHA Functional Classification
| Class | Symptoms | Implication |
|---|---|---|
| I | No limitation. Ordinary activity does not cause symptoms. | Optimize GDMT. Continue current regimen. |
| II | Slight limitation. Comfortable at rest, symptoms with ordinary activity. | Ensure all four pillars are at target doses. |
| III | Marked limitation. Comfortable at rest, symptoms with less than ordinary activity. | Maximize GDMT. Consider ICD/CRT. Diuretic optimization. |
| IV | Unable to carry on any activity without symptoms. Symptoms at rest. | Advanced HF referral. Evaluate for LVAD / transplant. |
Key Prognostic Markers
- BNP / NT-proBNP — higher levels = worse prognosis. Useful for tracking response to therapy.
- Hyponatremia (Na⁺ < 135) — independent predictor of mortality in HF
- Peak VO₂ — gold standard for transplant candidacy (≤ 14 mL/kg/min → list)
- NYHA class — class III/IV = ↑ mortality
- EF — lower EF = higher mortality, but HFpEF also carries significant morbidity
💊 GDMT — The Four Pillars (HFrEF)
The Four Pillars of HFrEF
All four pillars should be initiated and uptitrated in every HFrEF patient (EF ≤ 40%) unless contraindicated. Each independently reduces mortality. Together, they reduce HF mortality by ~70% compared to no treatment. Get them all on board — don't wait to finish one before starting the next.
| Pillar | Drug (Brand) | Target Dose | Key Trial | Mortality Reduction | Watch Out |
|---|---|---|---|---|---|
| 1. ARNI* *= Angiotensin Receptor-Neprilysin Inhibitor (sacubitril-valsartan) 1ST LINE |
Sacubitril/valsartan (Entresto) Start 24/26 mg BID → target 97/103 mg BID |
97/103 mg BID | PARADIGM-HF, 2014 | 20% reduction in CV death vs enalapril | Hold ACEi 36h before starting (angioedema risk). Hypotension. Do not use with ACEi. Avoid if SBP < 100. |
| 1. ACEi/ARB (if ARNI not tolerated) |
Enalapril (Vasotec) 10–20 mg BID Lisinopril (Zestril) 20–40 mg daily Losartan (Cozaar) 50–150 mg daily Valsartan (Diovan) 160 mg BID |
Max tolerated | CONSENSUS, 1987 SOLVD, 1991 |
~25–30% | Hyperkalemia, AKI, cough (ACEi). Monitor Cr + K⁺ at 1–2 weeks. Cr rise ≤ 30% acceptable. |
| 2. Beta-blocker 1ST LINE |
Carvedilol (Coreg) 3.125 → 25 mg BID Metoprolol succinate (Toprol-XL) 12.5 → 200 mg daily Bisoprolol 1.25 → 10 mg daily |
Max tolerated of one of the three | MERIT-HF, 1999 COPERNICUS, 2001 CIBIS-II, 1999 |
~35% | Only these three BBs are evidence-based for HFrEF. Atenolol, propranolol, etc. have no HF data. Start low, go slow. Do NOT start during decompensation. |
| 3. MRA* *= Mineralocorticoid Receptor Antagonist (spironolactone, eplerenone) 1ST LINE |
Spironolactone (Aldactone) 12.5–50 mg daily or Eplerenone (Inspra) 25–50 mg daily |
25–50 mg daily | RALES, 1999 EMPHASIS-HF, 2011 |
~30% | Hyperkalemia — monitor K⁺ at 3 days, 1 week, monthly. Avoid if K⁺ > 5.0 or eGFR < 30. Eplerenone = less gynecomastia than spironolactone. |
| 4. SGLT2 inhibitor 1ST LINE |
Dapagliflozin (Farxiga) 10 mg daily or Empagliflozin (Jardiance) 10 mg daily |
10 mg daily (no titration needed) | DAPA-HF, 2019 EMPEROR-Reduced, 2020 |
~25% reduction in HF hospitalization + CV death | Benefit regardless of diabetes status. Genital mycotic infections (warn patients). Euglycemic DKA (rare). Do not initiate if eGFR < 20. |
Titration strategy: Start all four at low doses simultaneously (or rapid sequence) rather than titrating one to target before starting the next. STRONG-HF, 2022: rapid uptitration of GDMT within 2 weeks of discharge reduced HF readmission and death.
🔄 Updated Practice: Old approach: start ACEi, then add beta-blocker, then add MRA — sequential uptitration over months. New approach (2022 AHA/ACC): start all 4 pillars simultaneously or in rapid sequence (ACEi/ARNI + BB + MRA + SGLT2i). STRONG-HF showed rapid uptitration before discharge improved 180-day outcomes. Don't wait — every day without GDMT is a missed opportunity.
Additional Agents
| Drug | Indication | Trial | Notes |
|---|---|---|---|
| Hydralazine/Isosorbide dinitrate (BiDil) | Black patients with NYHA III–IV on maximal GDMT. Or ACEi/ARB-intolerant. | A-HeFT, 2004 | 43% reduction in mortality in self-identified Black patients. Only HF drug with race-specific evidence. |
| Ivabradine (Corlanor) | HR ≥ 70 despite max BB. Sinus rhythm only. | SHIFT, 2010 | Selective If channel blocker. Reduces HR without ↓ BP or inotropy. Does NOT work in Afib (requires sinus node). |
| Digoxin (Lanoxin) | Persistent symptoms despite GDMT. Afib rate control adjunct. | DIG, 1997 | No mortality benefit — reduces HF hospitalizations only. Target level 0.5–0.9 ng/mL. Narrow therapeutic index. |
| Diuretics (furosemide, torsemide, bumetanide) | Symptom relief of congestion. All HF patients with volume overload. | No mortality data | Symptom management only — not disease-modifying. Torsemide may have better oral bioavailability than furosemide. TRANSFORM-HF, 2022: no difference in outcomes. |
| Vericiguat (Verquvo) | Worsening HFrEF (recent hospitalization despite GDMT) | VICTORIA, 2020 | 10% reduction in CV death + HF hospitalization. sGC stimulator. Add-on for high-risk patients. |
🫀 HFrEF vs HFpEF
HFrEF vs HFpEF — Management Comparison
Classification: HFrEF = EF ≤ 40% | HFmrEF = EF 41–49% | HFpEF = EF ≥ 50%. Management differs fundamentally — HFrEF has strong mortality-reducing GDMT; HFpEF treatment is largely symptom-driven with emerging evidence for SGLT2 inhibitors.
| Domain | HFrEF (EF ≤ 40%) | HFpEF (EF ≥ 50%) |
|---|---|---|
| Core pathology | Systolic dysfunction — weakened pump. Dilated LV, ↓ contractility. | Diastolic dysfunction — stiff ventricle. Normal LV size, impaired relaxation and filling. |
| ARNI / ACEi / ARB | MORTALITY BENEFIT ARNI preferred over ACEi/ARB. PARADIGM-HF, 2014: sacubitril/valsartan reduced CV death + HF hospitalization by 20% vs enalapril. | NO PROVEN BENEFIT PARAGON-HF, 2019: ARNI did not significantly reduce primary endpoint vs valsartan. Possible benefit in lower EF range (EF ≤ 57%). |
| Beta-blocker | MORTALITY BENEFIT Carvedilol, metoprolol succinate, or bisoprolol. COPERNICUS, 2001: carvedilol reduced mortality 35% in severe HFrEF. MERIT-HF, 1999: metoprolol succinate reduced mortality 34%. | NO PROVEN BENEFIT No mortality benefit in HFpEF trials. Use for rate control (Afib) or HTN — not as HF-specific therapy. |
| MRA | MORTALITY BENEFIT RALES, 1999: spironolactone reduced mortality 30% in severe HFrEF. EPHESUS, 2003: eplerenone in post-MI HFrEF. | POSSIBLE BENEFIT TOPCAT, 2014: overall negative, but Americas subgroup showed benefit. Consider if symptomatic despite diuretics. |
| SGLT2 inhibitor | MORTALITY BENEFIT DAPA-HF, 2019: dapagliflozin reduced worsening HF/CV death 26%. EMPEROR-Reduced, 2020: empagliflozin confirmed class effect. | HF HOSPITALIZATION BENEFIT EMPEROR-Preserved, 2021: empagliflozin reduced CV death + HF hospitalization 21%. DELIVER, 2022: dapagliflozin confirmed across EF spectrum. Only drug class with clear benefit in HFpEF. |
| Diuretics | Symptom relief. Loop diuretics for congestion. No mortality benefit but essential for decongestion. | Cornerstone of symptom management. Low-dose loop diuretics. Avoid over-diuresis — these patients are preload-dependent. |
| GLP-1 RA | No specific HFrEF indication. Use for comorbid T2DM/obesity. | EMERGING STEP-HFpEF, 2023: semaglutide improved symptoms, exercise capacity, and weight in obese HFpEF. Targets the obesity-HFpEF phenotype. |
| Comorbidity focus | ICD/CRT if EF ≤ 35% on optimal GDMT × 3 months. Cardiac rehab. Iron repletion if deficient. | Central to management. Aggressive HTN control, Afib rate control (restore atrial kick), weight loss, OSA treatment, glycemic control, exercise training. Ex-DHF, 2011: exercise training improved peak VO₂ and quality of life. |
| Devices | ICD if EF ≤ 35% + NYHA II–III on optimal GDMT ≥ 3 months (SCD-HeFT, 2005). CRT if EF ≤ 35% + LBBB + QRS ≥ 150ms. | No role for ICD or CRT. EF is preserved — sudden death risk is lower. |
Key takeaway: HFrEF has 4 mortality-reducing drug classes (ARNI, BB, MRA, SGLT2i) — start all four early and titrate to targets. HFpEF management centers on SGLT2 inhibitors (the only drug class with clear evidence), aggressive diuresis for symptoms, and treating every comorbidity (HTN, obesity, Afib, DM, OSA). The days of "nothing works for HFpEF" are over — SGLT2i changed the game.
🔧 Device Therapy
ICD (Implantable Cardioverter-Defibrillator)
Primary prevention ICD indications in HFrEF:
- EF ≤ 35% despite ≥ 3 months of optimal GDMT
- NYHA class II–III
- Expected survival > 1 year
- Wait ≥ 40 days post-MI and ≥ 90 days post-revascularization before implant MADIT-II, 2002 SCD-HeFT, 2005
Secondary prevention: Any survivor of VT/VF arrest or sustained VT with hemodynamic compromise → ICD regardless of EF.
CRT (Cardiac Resynchronization Therapy)
- EF ≤ 35% + LBBB with QRS ≥ 150 ms + NYHA II–IV on optimal GDMT → strongest indication (class I)
- LBBB with QRS 120–149 ms → class IIa
- Non-LBBB with QRS ≥ 150 ms → class IIa (weaker benefit)
- QRS < 120 ms → NO benefit from CRT
MADIT-CRT, 2009: CRT-D reduced HF events by 34% in LBBB patients. RAFT, 2010: CRT-D reduced mortality by 25% vs ICD alone in LBBB.
Advanced HF — When to Refer
- NYHA III–IV despite maximal GDMT
- ≥ 2 HF hospitalizations in 12 months
- Rising BNP/NT-proBNP despite optimization
- Refractory volume overload requiring frequent IV diuretics
- Declining renal function (cardiorenal syndrome)
- Consideration for LVAD (bridge to transplant or destination therapy) or heart transplant
📋 On Rounds
Pimp Questions
What are the four pillars of HFrEF GDMT?
(1) ARNI (sacubitril/valsartan) or ACEi/ARB, (2) evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol — only these three), (3) MRA (spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). All four independently reduce mortality. Together, ~70% mortality reduction.
Why is sacubitril/valsartan (Entresto) better than enalapril?
PARADIGM-HF, 2014: sacubitril/valsartan reduced CV death by 20% and HF hospitalization by 21% compared to enalapril. Sacubitril is a neprilysin inhibitor — it prevents breakdown of natriuretic peptides (BNP, ANP) → enhanced natriuresis, vasodilation, and neurohormonal modulation. Must hold ACEi × 36h before switching (angioedema risk from dual enzyme inhibition).
Which beta-blockers are evidence-based in HFrEF?
Only three: carvedilol [COPERNICUS, 2001], metoprolol succinate [MERIT-HF, 1999], and bisoprolol [CIBIS-II, 1999]. Atenolol, propranolol, metoprolol tartrate, and other beta-blockers have NO evidence for mortality reduction in HFrEF. Metoprolol tartrate ≠ metoprolol succinate — the succinate (extended release) formulation is the one with the trial data.
What was the first drug to show benefit in HFpEF?
SGLT2 inhibitors. EMPEROR-Preserved, 2021: empagliflozin reduced HF hospitalization by 21% in HFpEF. DELIVER, 2022: dapagliflozin reduced HF composite by 18%. Before this, decades of trials failed in HFpEF — ACEi, ARBs, digoxin, and spironolactone all showed no or equivocal mortality benefit. SGLT2i are now first-line for all HF regardless of EF.
When do you refer for ICD vs CRT?
ICD: EF ≤ 35% despite ≥ 3 months GDMT, NYHA II–III, expected survival > 1 year. Wait ≥ 40 days post-MI. CRT: same EF criteria PLUS LBBB with QRS ≥ 150 ms (strongest indication). Non-LBBB or QRS 120–149 have weaker evidence. QRS < 120 ms = no CRT benefit. Most patients who qualify for CRT also get a combined CRT-D (CRT + defibrillator).
📣 Sample Presentation
One-Liner
"Mr. Lopez is a 62-year-old with HFrEF (EF 30%), NYHA class II, currently on lisinopril 10 mg, carvedilol 12.5 BID, and furosemide 40 daily. Not on MRA or SGLT2i. Here for medication optimization."
Key Points to Cover on Rounds
EF 30%, NYHA II, currently on 2 of 4 GDMT pillars. Action plan: (1) Switch lisinopril → sacubitril-valsartan 24/26 BID (must wash out ACEi ×36h first), (2) Uptitrate carvedilol to 25 mg BID in 2 weeks, (3) Add spironolactone 25 mg daily (K⁺ 4.2, Cr 1.1 — safe), (4) Add dapagliflozin 10 mg daily. ICD candidacy: EF ≤ 35% on max GDMT ×3 months → reassess. CRT if LBBB + QRS ≥ 150. Cardiac rehab referral.
🧪 Workup
Workup — Chronic Heart Failure
- Echocardiogram — the single most important test. Establishes EF (HFrEF vs HFpEF vs HFmrEF), wall motion abnormalities, valvular disease, diastolic dysfunction, chamber sizes. Repeat at 3–6 months after GDMT optimization to reassess EF.
- BNP / NT-proBNP — elevated in HF (BNP > 100, NT-proBNP > 300). Useful for diagnosis, prognosis, and monitoring response to therapy. Trend over time — > 30% reduction with treatment is a good prognostic sign.
- BMP — baseline Cr, K⁺, Na⁺ before starting RAAS inhibitors and diuretics. Monitor after each dose change. Cr rise ≤ 30% acceptable on ACEi/ARB/ARNI. K⁺ must be < 5.0 for MRA initiation.
- CBC — anemia worsens HF symptoms and is common (anemia of chronic disease, hemodilution). Iron studies if anemic — IV iron if ferritin < 100 or ferritin 100–300 + TSAT < 20% AFFIRM-AHF, 2020
- TSH — hypo- and hyperthyroidism are reversible causes of HF. Check in all new diagnoses.
- Iron studies — ferritin and TSAT. Iron deficiency is common in HF and independently worsens exercise capacity and outcomes, even without anemia.
- ECG — LVH, prior MI, arrhythmia (AF common), conduction disease (LBBB — CRT candidate if QRS > 150 ms + EF ≤ 35%).
- Cardiac MRI — if echo is inadequate, or to characterize etiology (ischemic vs non-ischemic, infiltrative, myocarditis, hemochromatosis, amyloid).
💊 Medications
Medications — Chronic Heart Failure (HFrEF)
All four pillars should be initiated in every HFrEF patient (EF ≤ 40%). See the GDMT (Four Pillars) tab above for detailed dosing, trials, and titration guidance.
| Pillar | Drug (Brand) | Starting → Target Dose | Key Monitoring |
|---|---|---|---|
| 1. ARNI | Sacubitril/valsartan (Entresto) | 24/26 mg BID → 97/103 mg BID | BP, Cr, K⁺ at 1–2 weeks. Hold ACEi 36h before starting. SBP ≥ 90. |
| 2. Beta-blocker | Carvedilol (Coreg) or metoprolol succinate (Toprol-XL) | Carvedilol 3.125 mg BID → 25 mg BID Metoprolol XL 12.5 mg → 200 mg daily | HR ≥ 60, SBP ≥ 90. Do NOT start during decompensation. Only these 3 BBs have evidence. |
| 3. MRA | Spironolactone (Aldactone) or eplerenone (Inspra) | Spironolactone 12.5 → 25–50 mg daily Eplerenone 25 → 50 mg daily | K⁺ < 5.0 and Cr < 2.5 before starting. Recheck at 1 week. Eplerenone if gynecomastia from spironolactone. |
| 4. SGLT2i | Dapagliflozin (Farxiga) or empagliflozin (Jardiance) | Dapagliflozin 10 mg daily Empagliflozin 10 mg daily | No titration needed. Works in diabetic AND non-diabetic HF. Watch for GU infections, euglycemic DKA (rare). |
Additional Agents
- Diuretics — furosemide (Lasix) for volume management. Symptom relief only — no mortality benefit. Titrate to dry weight.
- Hydralazine/isosorbide dinitrate (BiDil) — add to GDMT in Black patients with NYHA III–IV (A-HeFT, 2004). Also for patients who cannot tolerate ACEi/ARB/ARNI.
- Ivabradine (Corlanor) — if HR ≥ 70 on maximally tolerated beta-blocker, sinus rhythm, EF ≤ 35%.
- IV iron — ferric carboxymaltose (Injectafer) if ferritin < 100 or ferritin 100–300 + TSAT < 20%. Improves symptoms and reduces HF hospitalizations.
📈 Monitoring
Monitoring Parameters — Chronic Heart Failure
| Parameter | Frequency | Target / Action |
|---|---|---|
| Daily weights | Every morning, same scale, before breakfast | Weight gain > 2 lbs in 2 days or > 5 lbs in 1 week → call clinic / increase diuretic per action plan. Most important home monitoring tool. |
| BMP (K⁺, Cr, Na⁺) | 1–2 weeks after each GDMT initiation or dose change; then q3–6 months when stable | K⁺ 4.0–5.0 (RAAS inhibitors + MRA raise K⁺, diuretics lower it). Cr rise ≤ 30% acceptable on ACEi/ARB/ARNI. Na < 130 → fluid restrict. |
| Blood pressure | Each clinic visit; home monitoring encouraged | SBP ≥ 90 for ARNI/ACEi/ARB titration. Tolerate asymptomatic low SBP (90–100) if on optimal GDMT. Symptomatic hypotension → reduce diuretic first, then GDMT. |
| Heart rate | Each clinic visit | Resting HR 60–70 on maximally tolerated beta-blocker. HR ≥ 70 despite max BB → consider ivabradine (if sinus rhythm, EF ≤ 35%). |
| BNP / NT-proBNP | Baseline, then to track response to therapy | > 30% reduction from baseline = good prognostic sign. Do not chase a specific number — trend matters more than absolute value. |
| Echocardiogram (EF) | Repeat at 3–6 months after GDMT optimization | EF improvement → continue all GDMT (may reclassify HFrEF → HFimpEF). LBBB + EF ≤ 35% + QRS > 150 ms → CRT candidate. |
| Functional status (NYHA class) | Each visit | Dyspnea, exercise tolerance, orthopnea, PND. NYHA III–IV despite optimal GDMT → advanced HF referral (LVAD/transplant evaluation). |
| Iron studies | At diagnosis, then annually | Ferritin < 100 or ferritin 100–300 + TSAT < 20% → IV iron replacement. Improves functional capacity and reduces HF hospitalizations. |
GDMT uptitration is the priority. At every visit, ask: "Can I increase any of the four pillars?" Uptitrate one drug at a time, every 1–2 weeks, to target dose or maximally tolerated dose. Do NOT wait for one pillar to be at target before starting the next — initiate all four early and uptitrate in parallel.
⚡ Management
Management — Chronic Heart Failure
See the GDMT (Four Pillars) tab for the full treatment algorithm with drug dosing, target doses, and landmark trial citations. See the HFrEF vs HFpEF tab for a side-by-side management comparison. For acute decompensation management, see ADHF.
⚡ Summary
Summary
4 Pillars GDMT
ARNI (or ACEi) + evidence-based BB + MRA + SGLT2i. Start all four early. Each independently reduces mortality.
Key Trials
ARNI [PARADIGM-HF]. SGLT2i [DAPA-HF, EMPEROR-Reduced]. MRA [RALES]. BB [COPERNICUS, MERIT-HF].
Diuresis Goal
Net −1 to 2 L/day. Daily weights. UOP 100-150 mL/hr after IV furosemide. Metolazone for resistance.
ICD Criteria
EF ≤ 35% on max GDMT × 3 months, NYHA II-III, life expectancy > 1 year. CRT if LBBB + QRS ≥ 150.
HFpEF
EF ≥ 50%. Diuresis for congestion. SGLT2i (empagliflozin) [EMPEROR-Preserved]. Treat comorbidities: HTN, AF, obesity.
Discharge
Optimize GDMT before discharge. Weight target. Fluid restrict 1.5-2L/day. Follow-up within 7 days. Cardiac rehab.
📄 One Pager
One Pager — Heart Failure — Chronic Management
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
HEART FAILURE — CHRONIC MANAGEMENT — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Cardiology · One Pager
CHF — Acute & Chronic
4 pillars of GDMT: ARNI + BB + MRA + SGLT2i. Start all four early. Diuresis for congestion. ICD if EF ≤ 35% on max GDMT × 3 months.
Classification
Warm/Wet (most common ADHF): diuretics. Cold/Wet: inotropes + diuretics. Cold/Dry: careful fluids. Warm/Dry: optimize GDMT outpatient.
Acute Management
IV furosemide 1-2.5× home dose. Target net −1 to 2L/day. Metolazone for resistance. Avoid inotropes unless cardiogenic shock. Continue GDMT unless hypotensive.
4 GDMT Pillars
(1) ARNI [PARADIGM-HF] or ACEi. (2) BB: carvedilol, metoprolol succinate, or bisoprolol. (3) MRA: spironolactone [RALES]. (4) SGLT2i: dapagliflozin [DAPA-HF] or empagliflozin.
Key Drugs
Furosemide IV40-200 mg bolus
Sacubitril-valsartan24/26 → 97/103 BID
Carvedilol3.125 → 25 mg BID
Spironolactone12.5-50 mg daily
Dapagliflozin10 mg daily
Pitfalls
- Holding BB in acute HF (continue unless cardiogenic shock)
- Not starting all 4 GDMT pillars
- Chasing BNP number instead of clinical volume status
- Discharging without GDMT optimization + 7-day f/u
Acute Kidney Injury (AKI)
Rise in creatinine ≥ 0.3 mg/dL in 48h or ≥ 1.5× baseline in 7 days. Step 1: is it pre-renal, intrinsic, or post-renal? The answer drives everything.
🔍 Overview
KDIGO Staging
| Stage | Creatinine Criteria | Urine Output |
|---|---|---|
| 1 | ↑ ≥ 0.3 in 48h OR 1.5–1.9× baseline | < 0.5 mL/kg/hr × 6–12h |
| 2 | 2.0–2.9× baseline | < 0.5 mL/kg/hr × ≥ 12h |
| 3 | ≥ 3× baseline OR ≥ 4.0 mg/dL OR RRT initiated | < 0.3 mL/kg/hr × ≥ 24h or anuria × 12h |
Causes — The Classic 3-Category Framework
Pre-Renal (most common — 60–70%)
- Volume depletion: vomiting, diarrhea, poor intake, diuresis
- Low CO states: heart failure, cardiogenic shock
- Renal hypoperfusion: ACEi/ARB in bilateral RAS, NSAIDs, hepatorenal syndrome
Intrinsic Renal (20–30%)
- ATN (most common intrinsic): ischemia, nephrotoxins (aminoglycosides, contrast, myoglobin, vancomycin)
- Glomerulonephritis: RBCs + protein + RBC casts on UA
- AIN (interstitial nephritis): drug-induced (PCN, NSAIDs, PPIs), eosinophiluria
- Vascular: renal artery thrombosis, TTP, HUS
Post-Renal (5–10%)
- Bilateral ureteral obstruction, BPH, bladder outlet obstruction
- Check with renal ultrasound + bladder scan
🧪 Workup & Diagnosis
Workup Algorithm
First Move: Bladder scan + renal ultrasound (rule out obstruction) — quick, cheap, and you'll miss post-renal without it.
- UA with microscopy — RBC casts (GN), waxy/granular casts (ATN), eosinophils (AIN), protein
- FENa = (UNa × PCr) / (PNa × UCr) × 100
< 1% = pre-renal or early contrast nephropathy
> 2% = ATN (intrinsic)
Note: FEUrea more reliable in patients on diuretics (< 35% = pre-renal)
🔄 Updated Practice: Old teaching: FENa <1% = pre-renal, FENa >2% = intrinsic (ATN). This is unreliable if the patient is on diuretics (which increase FENa regardless of etiology). Use FEUrea instead — it is NOT affected by diuretics. FEUrea <35% = pre-renal, FEUrea >50% = intrinsic. Also: "pre-renal" and "ATN" exist on a spectrum — prolonged pre-renal azotemia leads to ATN. Early volume resuscitation prevents progression.
- BMP — creatinine trend, K⁺, bicarb, BUN:Cr ratio (> 20:1 suggests pre-renal)
- CBC, LFTs
- Complement, ANA, ANCA, anti-GBM — if GN suspected
- Renal ultrasound — hydronephrosis, echogenicity, kidney size
- Review all medications — nephrotoxins, ACEi/ARBs, NSAIDs
🚨 Management
Management by Category
Pre-Renal AKI
- Volume resuscitation with IV crystalloid (LR preferred SMART, 2018)
- Hold ACEi/ARBs, NSAIDs, diuretics until creatinine stabilizes
- Treat underlying cause (heart failure, hepatorenal syndrome, hemorrhage)
- Expect creatinine to improve within 24–48h if truly pre-renal
ATN (Intrinsic)
- Supportive care — no specific treatment accelerates recovery
- Strict I&Os, careful fluid management (avoid overload)
- Aggressive electrolyte management (K⁺, bicarb, phosphate)
- Avoid contrast, nephrotoxins
Post-Renal AKI
- Foley catheter if BPH/bladder outlet obstruction → expect post-obstructive diuresis
- Urology consult for ureteral obstruction (stenting vs percutaneous nephrostomy)
- Monitor for post-obstructive diuresis (replace 50–75% UOP with IV fluids)
Indications for Emergent Dialysis — AEIOU
Mnemonic: AEIOU — If any of these are refractory to medical management, call nephrology for emergent dialysis.
| Letter | Indication | Details |
|---|---|---|
| A | Acidosis | Severe metabolic acidosis (pH < 7.1) refractory to bicarb infusion |
| E | Electrolytes | Refractory hyperkalemia (K⁺ > 6.5 with ECG changes despite medical Rx — insulin/glucose, calcium, patiromer/Lokelma) |
| I | Ingestions | Toxic alcohols (methanol, ethylene glycol), lithium, salicylates — dialyzable toxins |
| O | Overload | Volume overload causing pulmonary edema/respiratory failure refractory to diuretics |
| U | Uremia | Uremic encephalopathy (asterixis, AMS, seizures), uremic pericarditis (friction rub — pericardial effusion risk) |
Timing of Dialysis — Don't Rush. Early initiation of RRT does NOT improve mortality vs a delayed/watchful strategy STARRT-AKI, 2020 AKIKI, 2016. Only dialyze when you have a clear AEIOU indication.
| Trial | Year | Finding |
|---|---|---|
| AKIKI | 2016 | Early RRT (within 6h of KDIGO 3) vs delayed (watchful waiting for AEIOU indication) in critically ill AKI — no mortality difference. 49% of delayed group never needed dialysis at all. |
| IDEAL-ICU | 2018 | Early vs delayed RRT in septic shock with AKI — no benefit. Stopped early for futility. 38% of delayed group avoided RRT entirely. |
| STARRT-AKI | 2020 | Largest trial (n=2,927). Accelerated vs standard RRT initiation — no 90-day mortality benefit. Accelerated group had more catheter-related bloodstream infections and hypotension during dialysis. |
Bottom line: Wait for a hard AEIOU indication before initiating RRT. Many critically ill AKI patients recover renal function and never require dialysis if given time. Early initiation exposes patients to catheter complications and hemodynamic instability without survival benefit.
🔄 Updated Practice: Old teaching: start dialysis early in AKI to prevent complications. AKIKI 2016 and STARRT-AKI 2020 both showed that delayed/watchful waiting strategy is safe and avoids unnecessary dialysis in ~50% of patients. Only start RRT for absolute indications: refractory hyperkalemia, severe metabolic acidosis, refractory fluid overload, or uremic complications (encephalopathy, pericarditis, bleeding). "The best dialysis is the one you never need to start."
📋 Clinical Example — AKI Workup Interpretation
Patient: 72M admitted for pneumonia, Cr rising 1.0 → 2.4 over 48h (KDIGO Stage 2)
Step 1 — Pre-renal vs Intrinsic vs Post-renal:
- BUN/Cr ratio: 42 (> 20:1 → suggests pre-renal)
- FENa: 0.4% (< 1% → pre-renal)
- Urine Na: 8 mEq/L (< 20 → avid Na retention = pre-renal)
- UA: No casts, no protein (argues against ATN or glomerulonephritis)
- Renal US: No hydronephrosis (rules out post-renal obstruction)
Assessment: Pre-renal AKI from volume depletion (poor PO intake + fever + insensible losses from pneumonia). No nephrotoxic meds.
Management: IV LR 500 mL bolus × 2, then 125 mL/hr maintenance. Hold ACEi. Avoid contrast if possible. Recheck Cr in 24h.
24h later: Cr 1.8 (improving with fluids) → confirms pre-renal physiology.
⚡ Summary
Summary
First Move
Bladder scan + renal U/S to rule out obstruction. Then UA with micro + FENa to localize.
Pre-Renal
FENa < 1%, BUN:Cr > 20. Treat with fluids, hold nephrotoxins. Creatinine improves in 24–48h.
ATN
FENa > 2%, muddy brown casts. Supportive care. No diuretics force recovery. Avoid all nephrotoxins.
Post-Renal
Hydronephrosis on U/S. Foley or urology consult. Watch for post-obstructive diuresis.
Dialysis Triggers
AEIOU: Acidosis, Electrolytes, Ingestion, Overload, Uremia
Biggest Pitfall
Missing contrast nephropathy, or giving fluids to an ATN patient expecting pre-renal response — causes volume overload.
📄 One Pager
Nephrology · One Pager
Acute Kidney Injury
Pre-renal, intrinsic, or post-renal. Bladder scan + renal U/S first. FENa localises the rest. Stop the nephrotoxins.
Pre-Renal (60–70%)
- FENa < 1% / BUN:Cr > 20
- Volume depletion, low CO
- NSAIDs, ACEi/ARB
- Rx: IV fluids, hold nephrotoxins
- Cr improves in 24–48h
Intrinsic (20–30%)
- FENa > 2% / muddy brown casts
- ATN: ischemia, contrast, aminoglycosides
- AIN: drugs (PPIs, NSAIDs, PCN)
- GN: RBC casts + proteinuria
- Rx: Supportive, avoid nephrotoxins
Post-Renal (5–10%)
- Hydronephrosis on U/S
- BPH, bladder outlet obstruction
- Ureteral obstruction
- Rx: Foley or urology consult
- Watch for post-obstructive diuresis
FENa Calculation
- (UNa × PCr) ÷ (PNa × UCr) × 100
- < 1% = Pre-renal
- > 2% = ATN (intrinsic)
- Use FEUrea if on diuretics (< 35% = pre-renal)
Dialysis Indications — AEIOU
- A — Acidosis (pH < 7.1)
- E — Electrolytes (refractory K⁺)
- I — Ingestion (toxic)
- O — Overload (refractory)
- U — Uremia (pericarditis, encephalopathy)
📋 On Rounds
Pimp Questions
What is the difference between FENa and FEUrea, and when do you use each?
FENa (fractional excretion of sodium) differentiates pre-renal (< 1%) from intrinsic (> 2%) AKI. However, FENa is unreliable if the patient is on diuretics — diuretics increase sodium excretion even in pre-renal states, giving a falsely elevated FENa. In this case, use FEUrea — urea reabsorption is not affected by diuretics. FEUrea < 35% = pre-renal, > 50% = intrinsic. Rule of thumb: use FENa if no diuretics, use FEUrea if on diuretics.
A patient's creatinine is rising but urine output is normal. Is this still AKI?
Yes — non-oliguric AKI is more common than oliguric AKI. Creatinine reflects GFR, not urine output. The kidneys can still produce urine (especially dilute urine) even when filtration is impaired. In fact, non-oliguric AKI generally has a better prognosis than oliguric AKI because it suggests less severe tubular damage. KDIGO stages AKI by Cr rise OR UOP decrease — you only need one criterion. Don't be falsely reassured by normal urine output if Cr is trending up.
What are the indications for emergent dialysis in AKI? Use the mnemonic.
AEIOU: Acidosis (pH < 7.1, refractory to bicarb), Electrolytes (hyperkalemia > 6.5 refractory to medical management, or with ECG changes), Ingestion (toxic alcohols: methanol, ethylene glycol — dialyzable; lithium, salicylate toxicity), Overload (volume overload refractory to diuretics, especially with pulmonary edema), Uremia (uremic pericarditis, uremic encephalopathy, uremic bleeding). Key: these are indications for emergent dialysis. Most AKI resolves with supportive care (fluids, stopping nephrotoxins). Nephrology should be consulted early if Cr is rapidly rising or if any of these indications are approaching.
How do you differentiate ATN from pre-renal AKI when the patient is on diuretics?
FENa is unreliable on diuretics (falsely elevated — diuretics increase sodium excretion). Use FEUrea instead — urea reabsorption is NOT affected by diuretics. FEUrea < 35% = pre-renal, > 50% = intrinsic (ATN). Other clues: Urine microscopy is the most underused tool — muddy brown granular casts = ATN (renal tubular cell debris). Pre-renal has bland sediment or hyaline casts. Urine osmolality: > 500 = concentrating (pre-renal, kidneys trying to hold water). < 350 = dilute (ATN, tubules can't concentrate). Response to fluids: pre-renal improves within 24-48h of volume repletion; ATN doesn't.
📣 Sample Presentation
One-Liner
"Mrs. Adams is a 70-year-old with DM and HTN admitted for pneumonia, found to have Cr rise from baseline 1.0 to 2.8 (KDIGO stage 2). FENa 0.4%, bland urine sediment. Likely pre-renal from volume depletion."
Key Points to Cover on Rounds
Baseline Cr 1.0, now 2.8 (KDIGO stage 2). FENa 0.4% (pre-renal). UA: no casts, no protein. Renal US: no hydronephrosis. Nephrotoxins held: lisinopril, ibuprofen stopped on admission. Volume resuscitation with LR ongoing. UOP improving 20→55 mL/hr. Cr trending 2.8→2.4. Plan: continue fluids, recheck BMP PM, restart ACEi only after Cr returns to baseline.
💊 Medications
Key Medications — Myocarditis
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — Myocarditis
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
Chronic Kidney Disease (CKD)
Progressive, irreversible loss of nephron function over months to years. Management centers on slowing progression (RAAS blockade + SGLT2i), treating complications (anemia, bone-mineral disease, acidosis), and timely dialysis planning.
🔍 Overview
Definition
CKD is defined as abnormalities of kidney structure or function present for > 3 months with health implications. Requires either GFR < 60 mL/min/1.73m² OR markers of kidney damage (albuminuria, hematuria, structural abnormality, history of transplant) — or both. Classified by GFR stage (G1–G5) and albuminuria category (A1–A3).
GFR Staging (KDIGO)
| Stage | GFR (mL/min/1.73m²) | Description | Mortality Risk |
|---|---|---|---|
| G1 | ≥ 90 | Normal or high (with kidney damage markers) | Baseline |
| G2 | 60–89 | Mildly decreased | Slightly increased |
| G3a | 45–59 | Mild-moderately decreased | Moderately increased |
| G3b | 30–44 | Moderate-severely decreased | High |
| G4 | 15–29 | Severely decreased | Very high |
| G5 | < 15 | Kidney failure (ESKD) | Highest |
Albuminuria Categories
| Category | UACR (mg/g) | Description |
|---|---|---|
| A1 | < 30 | Normal to mildly increased |
| A2 | 30–300 | Moderately increased (microalbuminuria) |
| A3 | > 300 | Severely increased (macroalbuminuria) — high ESKD risk |
Both GFR and albuminuria independently predict progression and cardiovascular risk. A patient with G2 + A3 is higher risk than G3a + A1. Always classify both.
Etiology (Most Common → Least)
| Cause | % of ESKD | Key Features |
|---|---|---|
| Diabetes mellitus | ~45% | Most common cause worldwide. Nodular glomerulosclerosis (Kimmelstiel-Wilson). Progressive albuminuria → nephrotic range. |
| Hypertension | ~28% | Hypertensive nephrosclerosis. Arteriolar thickening → ischemic nephron loss. Often coexists with DM. |
| Glomerulonephritis | ~8% | IgA nephropathy (most common GN globally), FSGS, membranous, lupus nephritis. Active sediment (RBC casts). |
| Polycystic kidney disease (ADPKD) | ~5% | Autosomal dominant. Bilateral enlarged cystic kidneys on imaging. Family history. Tolvaptan slows progression TEMPO 3:3, 2012. |
| Other | ~14% | Reflux nephropathy, obstructive uropathy, interstitial nephritis, amyloidosis, myeloma kidney, sickle cell. |
Pathophysiology
Regardless of cause, CKD follows a common final pathway: initial injury → nephron loss → compensatory hyperfiltration in remaining nephrons → glomerular hypertension → progressive glomerulosclerosis → further nephron loss → cycle continues. RAAS activation drives this cycle — which is why ACEi/ARBs are foundational therapy. SGLT2 inhibitors reduce intraglomerular pressure by restoring tubuloglomerular feedback (constricting the afferent arteriole).
Key concept: After ~50% nephron loss, progression becomes self-sustaining even if the original insult is removed. This is why early intervention (BP control, RAAS blockade, SGLT2i) is critical — you're trying to break the hyperfiltration cycle before it becomes irreversible.
Presentation
- Early (G1–G3a): Usually asymptomatic. Detected incidentally on labs (elevated Cr, proteinuria on UA).
- Moderate (G3b–G4): Fatigue, nocturia (loss of concentrating ability), mild edema, anemia symptoms, pruritus.
- Severe (G5 / ESKD): Uremic symptoms — nausea, anorexia, metallic taste, asterixis, encephalopathy, pericarditis, bleeding diathesis (platelet dysfunction), volume overload, Kussmaul breathing (acidosis).
Uremic emergency: Uremic pericarditis (friction rub), uremic encephalopathy (asterixis, seizures), or refractory volume overload → emergent dialysis indication (AEIOU mnemonic from AKI topic).
🧪 Workup & Diagnosis
Diagnostic Workup
| Test | Purpose |
|---|---|
| BMP (Cr, BUN) | Calculate eGFR (CKD-EPI 2021). Two values ≥ 3 months apart confirm chronicity. |
| Urinalysis with micro | Proteinuria, hematuria, casts. Active sediment (RBC casts) → GN. Bland sediment → DM/HTN nephrosclerosis. |
| UACR (spot urine) | Quantify albuminuria. Most important prognostic marker. Repeat × 2 to confirm (transient proteinuria is common). |
| Renal ultrasound | Kidney size (small bilateral = chronic), echogenicity (increased = fibrosis), cysts (ADPKD), hydronephrosis (obstruction). |
| CBC | Anemia of CKD (normocytic, normochromic). EPO deficiency begins at G3. |
| Ca²⁺, PO₄, PTH, Vitamin D (25-OH) | CKD-MBD evaluation. Start monitoring at G3a. Expect: ↓ Ca, ↑ PO₄, ↑ PTH, ↓ Vit D. |
| Iron studies (ferritin, TSAT) | Iron deficiency is common and must be corrected before EPO agents. Target: ferritin > 100, TSAT > 20%. |
| Lipid panel | CVD risk assessment. CKD is a coronary risk equivalent. |
| HbA1c | Glycemic control if diabetic. Note: HbA1c is unreliable in ESKD (shortened RBC lifespan, EPO use). |
| Hepatitis B/C, HIV | Screen all CKD patients. Hep B vaccination if non-immune (double dose in CKD). |
When to Pursue Etiology
- Active urine sediment (RBC casts, dysmorphic RBCs) → glomerulonephritis workup: complement levels (C3/C4), ANA, anti-dsDNA, ANCA, anti-GBM, SPEP/UPEP, hepatitis serologies
- Nephrotic-range proteinuria (> 3.5 g/day) without DM → consider renal biopsy
- Rapidly declining GFR (> 5 mL/min/year) → urgent nephrology referral + biopsy
- Family history of kidney disease → ADPKD (US), Alport syndrome (genetic testing)
- Young patient with CKD → always pursue cause (GN, reflux, congenital)
Small bilateral kidneys (< 9 cm) on US = chronic, irreversible. Biopsy is usually not helpful at this stage — insufficient tissue. Exceptions: normal-sized kidneys in CKD (think DM nephropathy, amyloid, ADPKD, HIV nephropathy).
🚨 Management
Cornerstone Therapies — Slow Progression
The "Big 4" that change CKD trajectory: BP control, ACEi/ARB, SGLT2 inhibitor, finerenone (if diabetic CKD). Every CKD patient with albuminuria should be on the first three.
1. BP Control
Target < 120/80 mmHg if proteinuria present SPRINT, 2015. Target < 130/80 for all CKD KDIGO, 2024. First-line: ACEi or ARB (dual RAAS blockade).
2. ACEi / ARB
Foundational therapy if albuminuria (A2 or A3). Reduces intraglomerular pressure, slows progression, reduces proteinuria 30–50%. RENAAL, 2001: losartan reduced ESKD by 28% in diabetic nephropathy. IDNT, 2001: irbesartan similar benefit. Do NOT combine ACEi + ARB ONTARGET, 2008: no additional benefit, increased hyperkalemia + AKI.
Expect Cr to rise 10–30% after initiation — this is acceptable and expected. Only hold if Cr rises > 30% or K⁺ > 5.5.
Expect Cr to rise 10–30% after initiation — this is acceptable and expected. Only hold if Cr rises > 30% or K⁺ > 5.5.
3. SGLT2 Inhibitor
Add to ACEi/ARB in all CKD with eGFR ≥ 20 and albuminuria. Benefit is independent of diabetes status.
DAPA-CKD, 2020: dapagliflozin reduced CKD progression by 34%. Trial stopped early for efficacy. Benefit in both diabetic and non-diabetic CKD.
EMPA-KIDNEY, 2022: empagliflozin reduced progression by 28%. Benefit down to eGFR 20.
Mechanism: restores tubuloglomerular feedback → constricts afferent arteriole → reduces intraglomerular pressure. Also natriuretic, reduces weight, lowers BP.
Expect initial eGFR dip of 3–5 mL/min (like ACEi) — this is hemodynamic, not injury. Do not stop.
DAPA-CKD, 2020: dapagliflozin reduced CKD progression by 34%. Trial stopped early for efficacy. Benefit in both diabetic and non-diabetic CKD.
EMPA-KIDNEY, 2022: empagliflozin reduced progression by 28%. Benefit down to eGFR 20.
Mechanism: restores tubuloglomerular feedback → constricts afferent arteriole → reduces intraglomerular pressure. Also natriuretic, reduces weight, lowers BP.
Expect initial eGFR dip of 3–5 mL/min (like ACEi) — this is hemodynamic, not injury. Do not stop.
4. Finerenone (Kerendia)
Add in diabetic CKD with persistent albuminuria despite ACEi/ARB + SGLT2i.
FIDELIO-DKD, 2020: 18% reduction in kidney composite endpoint. FIGARO-DKD, 2021: 13% reduction in CV composite.
Non-steroidal MRA — less hyperkalemia than spironolactone. Requires K⁺ < 5.0 and eGFR ≥ 25 to initiate. Monitor K⁺ within 4 weeks.
FIDELIO-DKD, 2020: 18% reduction in kidney composite endpoint. FIGARO-DKD, 2021: 13% reduction in CV composite.
Non-steroidal MRA — less hyperkalemia than spironolactone. Requires K⁺ < 5.0 and eGFR ≥ 25 to initiate. Monitor K⁺ within 4 weeks.
Lifestyle & Supportive
- Dietary sodium restriction — < 2g/day. Enhances efficacy of RAAS blockade and reduces edema/HTN.
- Protein intake — 0.8 g/kg/day in G3–G5 (not on dialysis). Excessive protein accelerates hyperfiltration.
- Glycemic control (DM) — HbA1c < 7% (individualize in elderly/frail). SGLT2i counts toward this.
- Smoking cessation — smoking accelerates CKD progression and CV risk.
- Statin therapy — CKD is a coronary risk equivalent. Statin for all G3–G5 not on dialysis SHARP, 2011: simvastatin/ezetimibe reduced major atherosclerotic events by 17%.
- Avoid nephrotoxins — NSAIDs, aminoglycosides, IV contrast (pre-hydrate if essential), herbal supplements.
- Vaccinations — Hepatitis B (double dose: 40 mcg), influenza annually, pneumococcal (PCV20 or PCV15 + PPSV23), COVID-19.
⚠️ Complications
CKD-Mineral Bone Disease (CKD-MBD)
Begins at G3. The kidneys fail to excrete phosphate and activate vitamin D → hyperphosphatemia → hypocalcemia → secondary hyperparathyroidism → renal osteodystrophy → vascular calcification → cardiovascular death.
| Parameter | CKD G3–G4 | CKD G5 / Dialysis | Treatment |
|---|---|---|---|
| Phosphate | Keep in normal range | Target 3.5–5.5 mg/dL | Dietary restriction → phosphate binders: sevelamer (Renvela), calcium acetate (PhosLo), lanthanum (Fosrenol) |
| Calcium | Maintain normal | Avoid hypercalcemia | Avoid calcium-based binders if hypercalcemic. Calcitriol (Rocaltrol) or paricalcitol (Zemplar) for active vitamin D. |
| PTH | Trend — no target | 2–9× upper normal | Calcitriol, cinacalcet (Sensipar), or parathyroidectomy if refractory. |
| Vitamin D (25-OH) | Replete if < 30 ng/mL | Replete | Ergocalciferol or cholecalciferol (inactive form) for deficiency. Active forms for secondary hyperPTH. |
Anemia of CKD
EPO production drops as renal mass decreases (begins G3). Results in normocytic, normochromic anemia. Always rule out iron deficiency first.
| Step | Action | Target |
|---|---|---|
| 1. Iron first | IV iron (ferric carboxymaltose or iron sucrose) if ferritin < 100 or TSAT < 20% | Ferritin 200–500, TSAT 20–30% |
| 2. ESA if needed | Epoetin alfa (Epogen/Procrit) or darbepoetin (Aranesp). Start if Hgb < 10 after iron repletion. | Hgb 10–11.5 g/dL. Do NOT target > 13 TREAT, 2009: ↑ stroke risk. CHOIR, 2006: ↑ CV events. |
| 3. HIF-PHI (newer) | Roxadustat (Evrenzo) — oral HIF-prolyl hydroxylase inhibitor. Stimulates endogenous EPO. | Alternative to injectable ESAs. Approved in CKD + dialysis. |
Never target Hgb > 13 g/dL with ESAs. TREAT, 2009: doubled stroke risk. CHOIR, 2006: increased CV events. CREATE, 2006: no benefit. Target 10–11.5 only.
Metabolic Acidosis
Impaired ammonium excretion → non-anion-gap metabolic acidosis (early) or anion-gap (late, from retained uremic toxins). Acidosis accelerates CKD progression, worsens bone disease, and promotes muscle wasting.
- Target serum bicarb ≥ 22 mEq/L
- Sodium bicarbonate tablets 650–1300 mg PO TID (1–3 mEq/kg/day)
- Bicarb CKD Progression Trial, 2010: bicarb supplementation slowed CKD progression by 60%
Other Complications
- Hyperkalemia — from impaired K⁺ excretion + ACEi/ARB/MRA. Manage with dietary restriction, patiromer (Veltassa), sodium zirconium cyclosilicate (Lokelma). Do NOT stop ACEi/ARB unless K⁺ > 5.5 persistently.
- Volume overload / edema — loop diuretics (furosemide). Dose escalation needed as GFR declines. Thiazides lose efficacy below GFR 30 (exception: metolazone for synergy).
- Cardiovascular disease — #1 cause of death in CKD. CKD is a coronary risk equivalent. Statin for all SHARP, 2011. Manage HTN aggressively.
- Uremic pruritus — gabapentin (renal dose), emollients, UVB phototherapy, difelikefalin (Korsuva) for dialysis patients.
- Uremic platelet dysfunction — prolonged bleeding time despite normal PT/INR. Treat with desmopressin (DDAVP) 0.3 mcg/kg IV for acute procedures. Conjugated estrogens for sustained effect.
💊 Medications
CKD-Specific Medications
| Drug (Brand) | Class | Dose | Indication | Key Points |
|---|---|---|---|---|
| Dapagliflozin (Farxiga) 1ST LINE | SGLT2i | 10 mg PO daily | CKD with eGFR ≥ 20 + albuminuria | DAPA-CKD, 2020. DM and non-DM. Do not initiate < 20. |
| Empagliflozin (Jardiance) 1ST LINE | SGLT2i | 10 mg PO daily | CKD with eGFR ≥ 20 | EMPA-KIDNEY, 2022. Benefits down to eGFR 20. |
| Finerenone (Kerendia) ADD-ON | Non-steroidal MRA | 10–20 mg PO daily | Diabetic CKD with albuminuria despite ACEi/ARB | FIDELIO-DKD, 2020. Requires K⁺ < 5.0 to start. Monitor K⁺ at 4 wks. |
| Sevelamer (Renvela) PREFERRED | Phosphate binder | 800–1600 mg with meals | Hyperphosphatemia (G4–G5) | Non-calcium binder. Preferred over calcium-based binders to avoid vascular calcification. |
| Calcitriol (Rocaltrol) | Active vitamin D | 0.25–0.5 mcg PO daily | Secondary hyperparathyroidism | Monitor Ca²⁺ (risk of hypercalcemia). Alternative: paricalcitol (Zemplar) — less hypercalcemia. |
| Cinacalcet (Sensipar) | Calcimimetic | 30–180 mg PO daily | Secondary hyperPTH on dialysis | Activates CaSR on parathyroid → suppresses PTH. GI side effects common. |
| Epoetin alfa (Epogen) AFTER IRON | ESA | 50–300 units/kg 3×/week IV/SC | Anemia of CKD (Hgb < 10) | Iron-replete first. Target Hgb 10–11.5. Never > 13 TREAT, 2009. |
| Darbepoetin (Aranesp) | ESA (long-acting) | 0.45 mcg/kg q2 weeks or monthly | Anemia of CKD | Less frequent dosing than epoetin. Same Hgb target. |
| Sodium bicarbonate | Alkali | 650–1300 mg PO TID | Metabolic acidosis (bicarb < 22) | Slows CKD progression. Watch for volume overload (Na⁺ content). |
| Patiromer (Veltassa) ADJUNCT | K⁺ binder | 8.4–25.2 g PO daily | Chronic hyperkalemia on RAAS blockade | Allows continuation of ACEi/ARB/MRA. Takes hours to work — not for acute hyperK. |
🏥 Dialysis & Transplant
When to Start Dialysis
Mnemonic: AEIOU — Same as AKI. Initiate when medical management fails, not based on a GFR number alone.
| Indication | Details |
|---|---|
| A — Acidosis | Refractory metabolic acidosis despite oral bicarb |
| E — Electrolytes | Refractory hyperkalemia despite binders + dietary restriction |
| I — Intoxication | Uremic encephalopathy, uremic pericarditis (absolute indication) |
| O — Overload | Refractory volume overload despite max diuretics |
| U — Uremia | Symptomatic uremia (nausea, anorexia, asterixis, neuropathy) — typically GFR 5–10 |
Do NOT start dialysis based on GFR alone. IDEAL, 2010: early dialysis initiation (GFR 10–14) vs late (GFR 5–7) showed no survival benefit. Start for symptoms or complications, not a number.
Dialysis Modalities
| Modality | Access | Schedule | Best For | Disadvantages |
|---|---|---|---|---|
| Hemodialysis (HD) | AV fistula (best) > AV graft > tunneled catheter (worst) | 3×/week, 3–4 hrs/session | Most ESKD patients. Rapid solute/fluid removal. | Hemodynamic instability, vascular access complications, in-center schedule burden. |
| Peritoneal dialysis (PD) | Tenckhoff catheter (peritoneal) | Daily exchanges (CAPD) or nightly cycler (APD) | Patient autonomy, home-based, preserves residual renal function longer, better for hemodynamically fragile patients. | Peritonitis risk, protein loss, not ideal if prior abdominal surgery/hernias. |
| CRRT | Temporary dialysis catheter | Continuous (ICU only) | Hemodynamically unstable ICU patients (septic shock). Gentler fluid/solute removal. | ICU-only, resource intensive, requires anticoagulation of circuit. |
Access Planning
- AV fistula referral at eGFR ~20 (G4) — needs 2–3 months to mature before use. "Fistula first" approach.
- Protect the non-dominant arm — no blood draws, no IVs, no BP cuffs on the future fistula arm from G4 onwards.
- Avoid subclavian lines — causes subclavian stenosis, makes future fistula/graft on that side impossible. Use IJ if central access needed.
- Transplant evaluation — refer when GFR < 20. Pre-emptive transplant (before dialysis) has best outcomes. Living donor preferred.
📋 On Rounds
Sample Presentation
📋 CKD — Outpatient Nephrology
"Mr. Patel is a 58-year-old man with Type 2 DM, HTN, and CKD Stage G3b-A3 (eGFR 38, UACR 820 mg/g). He is on lisinopril 40 mg daily, dapagliflozin 10 mg daily, and was recently started on finerenone 10 mg daily — K⁺ was 4.6 at 4-week check. His BP today is 128/76. Labs show Hgb 10.8, bicarb 21, Ca 8.9, PO₄ 4.8, PTH 128, 25-OH Vitamin D 18. Plan: start sodium bicarb 650 mg TID for acidosis, replete Vitamin D with ergocalciferol 50,000 units weekly × 8 weeks, recheck PTH/Ca/PO₄ in 3 months. AV fistula referral placed. Transplant evaluation in progress."
Pimp Questions
Why should you never combine ACEi + ARB in CKD?
ONTARGET, 2008: dual RAAS blockade (ramipril + telmisartan) vs either alone — no additional renal benefit, but significantly more hyperkalemia, hypotension, and acute kidney injury. Also: VA NEPHRON-D, 2013 stopped early for safety (losartan + lisinopril in diabetic nephropathy). Bottom line: one RAAS blocker is enough. If more antiproteinuric effect needed, add SGLT2i or finerenone.
Why does eGFR dip when you start an SGLT2 inhibitor?
SGLT2 inhibitors restore tubuloglomerular feedback — they increase sodium delivery to the macula densa, which signals afferent arteriolar constriction, reducing intraglomerular pressure. This is the therapeutic mechanism (same concept as ACEi reducing efferent tone). The initial eGFR dip of 3–5 mL/min reflects reduced hyperfiltration, not kidney injury. It stabilizes within weeks and long-term GFR slope is markedly better. Do not stop the drug for this expected dip.
Why is HbA1c unreliable in ESKD?
Two reasons: (1) EPO/ESA therapy → increased reticulocyte production → younger RBCs → shorter glycation time → falsely LOW HbA1c. (2) Uremia → carbamylated hemoglobin → can interfere with some assays → falsely HIGH. Also, shortened RBC lifespan in ESKD (90 vs 120 days) → less glycation time. Alternative: use glycated albumin or fructosamine for glycemic monitoring in ESKD.
When should you refer for AV fistula creation?
At eGFR ~20 (CKD G4), or ~12 months before anticipated dialysis start. AV fistulas need 2–3 months to mature (some need 6 months). "Fistula first" — AVF has lowest infection rate, best long-term patency, and lowest mortality compared to grafts or catheters. Protect the non-dominant arm from G4 onwards (no IVs, no blood draws, no BP cuffs). Avoid subclavian central lines — causes stenosis that ruins ipsilateral fistula options.
Should you start dialysis early based on GFR alone?
No. IDEAL, 2010: randomized early start (eGFR 10–14) vs late start (eGFR 5–7) in 828 patients — no difference in mortality, CV events, infections, or quality of life. Early start just means more time on dialysis with no survival benefit. Start dialysis for symptoms (uremia, refractory volume overload, refractory hyperK, pericarditis) — not a number.
⚡ Summary
Summary
Staging
G1 (≥90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29), G5 (<15). Albuminuria: A1 < 30, A2 30-300, A3 > 300.
Slow Progression
ACEi/ARB (proteinuria reduction) + SGLT2i [CREDENCE, DAPA-CKD] + BP < 130/80 + A1c < 7 + avoid nephrotoxins.
Complications
Anemia (EPO), mineral bone disease (PTH/Ca/PO₄/VitD), metabolic acidosis (bicarb), hyperkalemia, volume overload.
Refer Nephrology
eGFR < 30, rapidly declining GFR, persistent proteinuria (UACR > 300), refractory HTN/hyperK/acidosis.
Prepare for ESKD
Fistula referral at eGFR ~20 (needs 3-6 months to mature). Transplant eval at eGFR ~20. Dialysis at eGFR ~5-10 or symptoms.
Avoid
NSAIDs, contrast (if eGFR < 30 — hydrate if needed), aminoglycosides, gadolinium (if eGFR < 30 — NSF risk).
📄 One Pager
Nephrology · One Pager
Chronic Kidney Disease
Slow progression: ACEi/ARB + SGLT2i + BP < 130/80. Manage complications: anemia, MBD, acidosis, hyperK. Refer nephrology at eGFR < 30. Fistula at eGFR ~20.
Staging
G1-5 by eGFR. A1-3 by albuminuria (UACR). Both determine prognosis and treatment intensity. eGFR < 60 for > 3 months = CKD.
Slow Progression
ACEi/ARB (reduce proteinuria). SGLT2i [CREDENCE, DAPA-CKD]. BP target < 130/80 [SPRINT]. A1c < 7. Avoid nephrotoxins (NSAIDs, contrast, aminoglycosides).
Manage Complications
Anemia: iron first, then ESA (target Hgb 10-11). MBD: phosphate binders, calcitriol, check PTH. Acidosis: bicarb supplementation if < 22. Hyperkalemia: dietary, patiromer/SZC.
Key Drugs
Lisinopril5-40 mg daily
Dapagliflozin10 mg daily
Sevelamer800 mg TID with meals
Epoetin alfa50-300 U/kg 3×/wk
Pitfalls
- Not starting SGLT2i (renal protection independent of diabetes)
- NSAIDs in CKD (accelerates decline + hyperK)
- Late nephrology referral (need time for fistula maturation)
- Not checking UACR annually
Clinical Tools
Clinical Calculators
Bedside calculations for rapid decision-making. Results are for clinical guidance — always apply clinical judgment.
Nephrology & Electrolytes
Anion Gap
Identifies elevated AG metabolic acidosis. Corrected for albumin.
FENa / FEUrea
Fractional excretion to differentiate pre-renal from ATN.
Corrected Sodium
Adjusts serum sodium for hyperglycemia-induced osmotic shift.
CrCl (Cockcroft-Gault)
Creatinine clearance for drug dosing. Uses ideal or actual body weight.
Corrected Calcium
Adjusts calcium for low albumin. Use ionized Ca when available.
Winter's Formula
Expected PCO₂ in metabolic acidosis. Detects concurrent respiratory disorder.
Cardiology
CHA₂DS₂-VASc
Stroke risk in atrial fibrillation. Guides anticoagulation decisions.
Wells Score (PE)
Pretest probability of pulmonary embolism.
MAP (Mean Arterial Pressure)
Estimates average arterial pressure during one cardiac cycle
QTc (Corrected QT Interval)
Bazett formula — corrects QT interval for heart rate
ASCVD Risk (Pooled Cohort)
Simplified 10-year atherosclerotic cardiovascular disease risk estimate
Pulmonology
CURB-65 (Pneumonia)
Severity scoring for community-acquired pneumonia. Guides disposition.
A-a Gradient
Alveolar–arterial oxygen gradient — evaluates oxygenation defect
ICU / Critical Care
Glasgow Coma Scale (GCS)
Quantify consciousness. Range 3–15. GCS ≤ 8 = intubate for airway protection.
NEWS Score
National Early Warning Score — SSC 2026 recommended sepsis screening tool. Scores 7 parameters.
MEWS Score
Modified Early Warning Score — simpler alternative to NEWS. Score ≥5 = urgent clinical review.
GI / Hepatology
MELD-Na
Model for End-Stage Liver Disease. Transplant priority and 3-month mortality.
General
BMI (Body Mass Index)
Weight-based classification for nutritional status
Steroid Converter
Glucocorticoid equivalence — converts between common steroids
Glasgow Coma Scale — Pocket Card
Print this and tape it to your badge. GCS ≤ 8 = intubate. Motor is the most prognostically important component.
| Component | Response | Score |
|---|---|---|
| Eye Opening (E) | Spontaneous | 4 |
| To voice / command | 3 | |
| To pressure / pain | 2 | |
| None | 1 | |
| Verbal Response (V) | Oriented (person, place, time, event) | 5 |
| Confused (converses but disoriented) | 4 | |
| Inappropriate words (random words, no conversation) | 3 | |
| Incomprehensible sounds (moaning, no words) | 2 | |
| None | 1 | |
| Motor Response (M) Most prognostically important | Obeys commands | 6 |
| Localizes pain (reaches toward stimulus) | 5 | |
| Normal flexion / withdrawal (pulls away) | 4 | |
| Abnormal flexion / decorticate (arms flex, legs extend) | 3 | |
| Extension / decerebrate (arms and legs extend) | 2 | |
| None | 1 |
Severity Classification
| GCS Score | Severity | Action |
|---|---|---|
| 13 – 15 | Mild | Observation, serial neuro exams q1–2h. CT head if: anticoagulation, focal deficit, LOC, persistent vomiting, age > 65, coagulopathy. |
| 9 – 12 | Moderate | CT head. Frequent neuro checks (q1h). ICU admission. Neurosurgery consult if structural lesion. |
| 3 – 8 | Severe | INTUBATE for airway protection. CT head STAT. ICU. Neurosurgery consult. Consider ICP monitoring if TBI (bolt if GCS ≤ 8 + abnormal CT). |
| 3 | Minimum (coma) | Worst possible score. No eye opening, no verbal, no motor. Evaluate for brain death criteria if persistent. |
Clinical Pearls
- GCS ≤ 8 = intubate. The patient cannot protect their own airway. This is the single most important GCS threshold.
- Motor score is the most prognostically important component. A patient with E1V1M5 (GCS 7) has a much better prognosis than E2V2M3 (GCS 7) — same total, very different meaning.
- Always report components, not just the total: "GCS 8 (E2V2M4)" — not just "GCS 8." The components tell you where the deficit is.
- Intubated patients: Verbal = 1T (denotes tube). Report as "GCS 7T (E2V1TM4)." Cannot assess verbal in intubated patients.
- Confounders: sedation, paralysis, alcohol, metabolic encephalopathy, aphasia, orbital swelling (can't assess eye opening). Always document confounders.
- GCS was validated for TBI — it is less reliable in metabolic coma, drug overdose, or non-traumatic causes. Use alongside pupil reactivity for better prognostication (GCS-Pupils score).
- Pupil reactivity: GCS-P = GCS − pupil reactivity score (both reactive = 0, one reactive = −1, neither reactive = −2). GCS-P adds prognostic value to GCS alone GCS-Pupils Study, 2018.
How to Present GCS on Rounds
| Scenario | What to Say |
|---|---|
| Normal / alert patient | "GCS is 15 — eyes open spontaneously, oriented and conversing, following commands." |
| Confused patient | "GCS is 13, that's E4 V4 M5 — eyes open spontaneously, conversing but confused to date and place, localizes to pain." |
| Obtunded patient | "GCS is 9, E2 V3 M4 — eyes open to pain only, inappropriate words, withdraws from pain. This is down from 12 yesterday — we need a stat CT head." |
| Intubated patient | "GCS is 7T — that's E2 V1T M4. Eyes open to pain, intubated so verbal is untestable, withdraws to pain. Sedation is off for over 2 hours." |
| Comatose patient | "GCS is 3, E1 V1 M1 — no eye opening, no verbal, no motor response to central pain. Pupils are 4 mm and fixed bilaterally. We need to discuss brain death evaluation." |
| Improving patient | "GCS improved from 8 to 11 overnight — now E3 V3 M5. Eyes opening to voice, still using inappropriate words, but now localizing to pain. Motor improvement is the most important prognostic sign here." |
The formula for presenting GCS: "GCS is [total], that's E[_] V[_] M[_] — [describe what each means in plain English]." Always state the trend compared to prior ("up from…" / "down from…" / "unchanged from…"). If intubated, say "V1T" and note how long sedation has been off. If there are confounders (sedation, paralysis, orbital swelling), state them: "GCS is limited by ongoing propofol — motor is the only reliable component."
How to Test
| Component | How to Assess |
|---|---|
| Eye | Observe → if no spontaneous opening, call patient's name loudly → if no response, apply central pain (trapezius squeeze or sternal rub). Do NOT use peripheral pain for eye opening (may cause withdrawal without eye opening). |
| Verbal | Ask: "What is your name? Where are you? What month/year is it? What happened?" Oriented = all 4 correct. Confused = conversing but wrong answers. Inappropriate = single words, no conversation. Incomprehensible = moans/groans only. |
| Motor | Ask patient to "show me two fingers" or "lift your arms." If no response → apply central pain (trapezius squeeze preferred over sternal rub — less tissue damage). Observe best response in any limb. Localizes = hand crosses midline and reaches above clavicle toward stimulus. Flexion = arm bends at elbow. Extension = arm straightens and internally rotates. |
Decorticate (flexion, GCS M3) vs Decerebrate (extension, GCS M2): Decorticate = cortical damage above red nucleus → arms flex, legs extend. Decerebrate = brainstem damage below red nucleus → all limbs extend. Decerebrate carries a worse prognosis. Mnemonic: de-COR-ticate = CORtex = arms toward CORE (flex). de-CERE-brate = CEREbellum level = arms extend.
📈 Monitoring
Monitoring Parameters — Chronic Kidney Disease
| Parameter | Frequency | Target / Action |
|---|---|---|
| eGFR and UACR | q3–6 months | Track progression rate. eGFR decline > 5 mL/min/year = rapid progression → reassess treatment, nephrology referral. UACR reduction with ACEi/ARB/SGLT2i = treatment working. |
| BMP (K+, bicarb, Ca, PO4) | q3–6 months (more often in G4–G5) | K+ < 5.5 (on RAAS blockade). Bicarb ≥ 22 (supplement if low). Ca/PO4 for CKD-MBD monitoring. |
| PTH | Annually (G3–G4), q3–6mo (G5/dialysis) | Rising PTH = secondary hyperparathyroidism → add phosphate binders, calcitriol, cinacalcet. Target 2–9x ULN on dialysis. |
| CBC (anemia) | q3–6 months | Hgb trending — anemia of CKD begins at G3. If Hgb < 10 → check iron studies → replete iron → then ESA if needed. |
| Iron studies (ferritin, TSAT) | q3–6 months | Ferritin > 100 (or > 200 on dialysis), TSAT > 20%. Iron-replete before starting ESA. |
| HbA1c (if diabetic) | q3 months | Target < 7% (individualize). Note: HbA1c unreliable in ESKD (shortened RBC lifespan, EPO use) — use fructosamine or CGM. |
| BP | Every visit + home monitoring | Target < 130/80 (KDIGO 2024). < 120/80 if tolerated with proteinuria SPRINT, 2015. |
| Lipids | Annually | CKD is a coronary risk equivalent. Statin for all G3–G5 not on dialysis. |
| Urinalysis | Annually | Monitor for active sediment (new hematuria, worsening proteinuria). |
| Hepatitis B/C screening | At diagnosis, then periodically | All CKD patients. Hep B vaccination if non-immune (double dose: 40 mcg). |
| Bone density (DEXA) | Consider in G3–G5 with fracture risk | CKD-MBD causes renal osteodystrophy. DEXA interpretation is complex in CKD — discuss with nephrology. |
CKD monitoring is a system. Every visit: BP, eGFR trend, UACR, K+, bicarb. Every 3–6 months: CBC, iron, Ca/PO4/PTH. Annually: lipids, HbA1c, UA, Hep B/C. Adjust medications based on trends, not single values.
📌 Summary
Summary — Chronic Kidney Disease (CKD)
Rapid Review — Chronic Kidney Disease (CKD): See Overview for diagnostic criteria, Management for treatment algorithm, Medications for drug details, and Rounds for the sample presentation.
- Diagnose: Disease-specific criteria (Overview tab)
- Treat: Evidence-based algorithm (Management tab)
- Monitor: Disease-specific targets (Monitoring tab)
- Present: One-liner + key points (Rounds tab)
📄 One Pager
One Pager — Chronic Kidney Disease (CKD)
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
CHRONIC KIDNEY DISEASE (CKD) — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
ARDS — Acute Respiratory Distress Syndrome
Diffuse inflammatory lung injury causing refractory hypoxemia. The cornerstone of management is lung-protective ventilation — low tidal volumes, prone positioning, and avoiding further barotrauma.
🔍 Overview
Definition
ARDS is acute, diffuse inflammatory lung injury causing increased alveolar-capillary permeability, pulmonary edema, and severe hypoxemia not explained by cardiac failure. Definition uses the Berlin Definition of ARDS (2012).
Memory trick: ARDS = "Stiff, flooded lungs" → SPP: Sepsis, Pneumonia, Protective ventilation
Berlin Diagnostic Criteria
| Criterion | Requirement |
|---|---|
| Timing | Within 1 week of clinical insult |
| Imaging | Bilateral opacities on CXR/CT (not explained by effusion/collapse) |
| Origin of edema | Not fully explained by heart failure or fluid overload |
| Oxygenation (P/F) | Used to grade severity (see below), with PEEP ≥ 5 cmH₂O |
ARDS Severity Classification
| Severity | PaO₂/FiO₂ (P/F Ratio) | Mortality |
|---|---|---|
| Mild | 200–300 mmHg | ~27% |
| Moderate | 100–200 mmHg | ~32% |
| Severe | < 100 mmHg | ~45% |
All measured with PEEP ≥ 5 cmH₂O. Most common patient profile: critically ill adult with sepsis or pneumonia, often requiring mechanical ventilation.
Most Common Causes of ARDS
| Cause | Approx % |
|---|---|
| Sepsis | ~40–50% |
| Pneumonia | ~30–40% |
| Aspiration | ~10–15% |
| Trauma / contusion | ~5–10% |
| Pancreatitis | ~3–5% |
| Massive transfusion (TRALI) | ~2–5% |
| Inhalational injury | < 2% |
Direct (Pulmonary) Causes
- Pneumonia (bacterial, viral, fungal)
- Aspiration of gastric contents
- Pulmonary contusion, inhalation injury
- Near-drowning
Indirect (Extrapulmonary) Causes
- Sepsis (most common overall cause)
- Pancreatitis
- Massive transfusion / TRALI
- Burns, trauma, DIC
- Drug overdose (heroin, aspirin, cocaine)
Stepwise Pathophysiology
ARDS occurs through three overlapping phases. The key physiologic problem is shunt hypoxemia — blood passes through non-ventilated alveoli, so oxygen therapy alone often fails.
1. Exudative Phase (First 7 Days)
Initial inflammatory injury.
| Step | Pathology |
|---|---|
| Lung insult | Infection, aspiration, trauma |
| Macrophage activation | Cytokine release (TNF-α, IL-1, IL-6) |
| Neutrophil recruitment | Endothelial damage |
| ↑ Capillary permeability | Protein-rich edema floods alveoli |
| Alveolar flooding | Impaired gas exchange, ↓ compliance, shunt physiology |
Results: ↓ compliance, severe hypoxemia, shunt physiology. Lungs become stiff, small (baby lung concept — only ~30% of lung is recruitable).
2. Proliferative Phase (7–21 Days)
Repair begins.
| Process | Effect |
|---|---|
| Type II pneumocyte proliferation | Surfactant restoration |
| Fibroblast activation | Collagen deposition |
| Alveolar repair | Partial recovery |
3. Fibrotic Phase (≥ 21 Days)
Occurs in severe/prolonged cases. Pulmonary fibrosis → stiff lungs → reduced compliance → prolonged ventilation. Not all patients progress to this phase.
Imaging Findings
Chest X-Ray
- Diffuse bilateral infiltrates
- "White lungs" in severe cases
CT Scan
- Dependent consolidation (gravity-dependent atelectasis)
- Ground glass opacities
- Better characterizes distribution — not required for diagnosis
Ventilator-Induced Lung Injury (VILI)
The ventilator itself can worsen ARDS. Preventing VILI is the rationale for lung-protective ventilation.
| Mechanism | Meaning |
|---|---|
| Volutrauma | Excessive tidal volume → alveolar overdistension |
| Barotrauma | High airway pressure → pneumothorax, pneumomediastinum |
| Atelectrauma | Repeated alveolar collapse and reopening → shear injury |
| Biotrauma | Mechanical injury → systemic cytokine release → MODS |
Presentation & Red Flags
- Acute onset dyspnea, tachypnea, worsening hypoxemia
- Bilateral crackles, diffuse infiltrates on CXR
- Refractory hypoxemia — O₂ sats not improving with supplemental O₂
- Decreased lung compliance (stiff lungs on vent — high plateau pressures)
- P/F < 150 despite FiO₂ 1.0 → severe ARDS, consider prone positioning immediately
- pH < 7.15 despite optimal vent → consider ECMO consultation
Oxygenation Targets
ARDS strategy allows permissive hypoxemia — deliberately accepting lower oxygen levels to avoid toxic ventilator settings.
| Parameter | Target |
|---|---|
| SpO₂ | 88–95% |
| PaO₂ | 55–80 mmHg |
Permissive Hypercapnia
Low tidal volume may cause CO₂ retention. This is acceptable as long as pH > 7.20. Contraindicated in raised ICP and sickle cell crisis.
Clinical Significance
- ARDS mortality still 30–45%
- Most common cause is sepsis
- Low tidal volume ventilation saves lives ARDSNet, 2000
- Prone positioning improves survival PROSEVA, 2013
- Preventing ventilator-induced lung injury is critical
🧪 Workup & Diagnosis
Diagnostic Workup
| Test | Purpose |
|---|---|
| ABG | Calculate P/F ratio (PaO₂ ÷ FiO₂). P/F < 300 = ARDS by Berlin criteria. Most important diagnostic step. |
| CXR | Bilateral opacities not explained by effusion or collapse (Berlin criterion) |
| Echo (bedside) | Rule out cardiogenic pulmonary edema (PCWP > 18 argues against ARDS). Fastest way to exclude cardiac cause. |
| BNP / NT-proBNP | Further differentiates cardiogenic vs non-cardiogenic edema |
| CBC, CMP, coags, lactate, procalcitonin | Assess severity, organ dysfunction, identify sepsis |
| Blood cultures | Identify infectious cause (sepsis = most common etiology) |
| CT chest | Dependent consolidation, ground glass opacities. Rules out PE/effusion. Not required for diagnosis. |
| BAL / sputum cultures | Identify infectious precipitant; obtain after securing airway |
ARDS vs Cardiogenic Pulmonary Edema
| Feature | ARDS | Cardiogenic |
|---|---|---|
| PCWP | Normal (≤ 18 mmHg) | High (> 18 mmHg) |
| BNP | Normal or mildly elevated | High |
| Cause | Lung injury (sepsis, pneumonia, aspiration) | Heart failure |
| Edema fluid | Protein-rich exudate | Transudate |
| CXR pattern | Diffuse bilateral, peripheral | Perihilar "bat wing", Kerley B lines |
| Response to diuresis | Minimal improvement | Significant improvement |
| Heart size | Normal | Often enlarged |
Key differentiator: ARDS = normal filling pressures, no response to diuretics, diffuse bilateral disease. Cardiogenic = elevated filling pressures, responds to diuresis, often perihilar pattern. Echo is the fastest way to differentiate at the bedside.
🚨 Management
Lung-Protective Ventilation ARDSNet, 2000
This is the only intervention proven to reduce mortality in ARDS. ARDSNet, 2000 showed a 9% absolute mortality reduction with 6 mL/kg vs 12 mL/kg IBW. Low tidal volumes save lives. Do not let anyone override this for "patient comfort" without a very good reason.
Tidal Volume
6 mL/kg of Ideal Body Weight (IBW) — NOT actual body weight. Start at 6–8 mL/kg, titrate down to 6 mL/kg. SSC, 2021: strong recommendation, high quality evidence.
IBW male = 50 + 2.3 × (height in inches − 60)
IBW female = 45.5 + 2.3 × (height in inches − 60)
If Pplat remains > 30 after reducing to 6 mL/kg, reduce further to as low as 4 mL/kg IBW. Increase RR to max 35 to maintain minute ventilation.
IBW male = 50 + 2.3 × (height in inches − 60)
IBW female = 45.5 + 2.3 × (height in inches − 60)
If Pplat remains > 30 after reducing to 6 mL/kg, reduce further to as low as 4 mL/kg IBW. Increase RR to max 35 to maintain minute ventilation.
Plateau Pressure
Keep Pplat ≤ 30 cmH₂O SSC, 2021 — strong recommendation, moderate quality evidence. If above, reduce TV further (down to 4 mL/kg).
Driving pressure (Pplat − PEEP) < 12–15 cmH₂O may be advantageous in patients without spontaneous breathing LUNG SAFE, 2016. Higher plateau pressures correlated with mortality; the relationship was strongest above 29 cmH₂O.
Driving pressure (Pplat − PEEP) < 12–15 cmH₂O may be advantageous in patients without spontaneous breathing LUNG SAFE, 2016. Higher plateau pressures correlated with mortality; the relationship was strongest above 29 cmH₂O.
PEEP Strategy
SSC, 2021: suggests higher PEEP over lower PEEP in moderate-severe ARDS (weak recommendation, moderate evidence). Patient-level meta-analysis PEEP Meta-Analysis, 2010 found mortality benefit with higher PEEP only in P/F ≤ 200.
ARDSNet Lower PEEP / FiO₂ Table:
ARDSNet Higher PEEP / FiO₂ Table (moderate-severe):
Target: SpO₂ 88–95% or PaO₂ 55–80 mmHg.
ARDSNet Lower PEEP / FiO₂ Table:
| FiO₂ | 0.3 | 0.4 | 0.5 | 0.6 | 0.7 | 0.8 | 0.9 | 1.0 |
|---|---|---|---|---|---|---|---|---|
| PEEP | 5 | 5–8 | 8–10 | 10 | 10–14 | 14 | 14–18 | 18–24 |
| FiO₂ | 0.3 | 0.4 | 0.5 | 0.6 | 0.7 | 0.8 | 0.9 | 1.0 |
|---|---|---|---|---|---|---|---|---|
| PEEP | 12 | 14 | 16 | 18 | 18 | 20 | 22 | 22–24 |
Permissive Hypercapnia
Acceptable to allow PaCO₂ to rise (up to 50–60 mmHg) to achieve lung-protective goals. pH > 7.20 is generally tolerated. Contraindicated in raised ICP, sickle cell crisis. No single mode (VC vs PC) has demonstrated superiority as long as lung-protective principles are respected.
Prone Positioning (P/F < 150)
Prone ≥ 16 hours/day PROSEVA, 2013 — reduced 28-day mortality from 32.8% to 16% in severe ARDS. SSC, 2021: strong recommendation, moderate quality evidence for > 12 hours daily.
Improves V/Q matching, recruits dependent lung, reduces compression by mediastinum. Meta-analysis confirmed benefit when applied within 36 hours of intubation for > 12 hrs/day in P/F < 200 Munshi, 2017. Associated with increased pressure sores (RR 1.22) but no increase in accidental extubation.
Improves V/Q matching, recruits dependent lung, reduces compression by mediastinum. Meta-analysis confirmed benefit when applied within 36 hours of intubation for > 12 hrs/day in P/F < 200 Munshi, 2017. Associated with increased pressure sores (RR 1.22) but no increase in accidental extubation.
🔄 Updated Practice: Old teaching: prone positioning is a rescue maneuver for refractory hypoxemia. Current practice: prone positioning is now standard of care for moderate-severe ARDS (P/F <150). PROSEVA (2013) showed 16 hours/day of proning reduced 28-day mortality from 33% to 16% — one of the largest mortality benefits ever seen in ARDS. Initiate proning early (within 12-24h), not as a last resort.
Conservative Fluid Strategy
After initial resuscitation, target even to negative fluid balance. FACTT, 2006: conservative fluid strategy reduced vent days by ~2.5 days without worsening renal function or shock. Use CVP or PAOP-guided diuresis. Avoid fluid overload — it worsens pulmonary edema and prolongs mechanical ventilation.
Neuromuscular Blockade
ACURASYS, 2010: 48h cisatracurium infusion in P/F < 150 showed 90-day mortality benefit vs deep sedation alone (RR 0.71). ROSE, 2019: no benefit vs light sedation with PRN boluses (RR 0.99).
SSC, 2021: suggests intermittent NMBA boluses over continuous infusion (weak recommendation, moderate evidence). Overall, NMBAs reduce barotrauma (RR 0.55). If NMBAs used, ensure adequate sedation and analgesia.
SSC, 2021: suggests intermittent NMBA boluses over continuous infusion (weak recommendation, moderate evidence). Overall, NMBAs reduce barotrauma (RR 0.55). If NMBAs used, ensure adequate sedation and analgesia.
Recruitment Maneuvers
SSC, 2021: suggests traditional recruitment maneuvers (sustained CPAP 30–40 cmH₂O × 30–40 sec) in moderate-severe ARDS — improved 28-day mortality (RR 0.79).
AVOID incremental PEEP titration recruitment — ART, 2017: increased 28-day mortality (RR 1.12). SSC, 2021: strong recommendation against.
🔄 Updated Practice: Old teaching: set PEEP as high as possible to recruit alveoli in ARDS. Current practice: driving pressure (plateau pressure minus PEEP) is the ventilatory variable most strongly associated with survival (Amato, NEJM 2015). Target driving pressure <15 cmH2O. Higher PEEP is beneficial in moderate-severe ARDS (P/F <200) but not in mild ARDS (PEEP Meta-Analysis, 2010). The ART trial (2017) showed aggressive recruitment maneuvers increased mortality.
ECMO Referral
Consider VV-ECMO if P/F < 80 despite optimal settings, pH < 7.15, or plateau pressure > 35 cmH₂O. EOLIA, 2018: supports VV-ECMO as rescue in severe ARDS at experienced centers. SSC, 2021: weak recommendation, low quality evidence. Refer early — do not wait until irreversible organ failure.
Oxygenation Strategy Before Intubation
High-Flow Nasal Cannula (HFNC)
SSC, 2021: suggests HFNC over NIV for sepsis-induced hypoxemic respiratory failure (weak recommendation, low quality evidence). FLORALI, 2015: HFNC improved 90-day survival vs NIV (OR 0.42) and reduced intubation in severe hypoxemia (P/F ≤ 200): 35% vs 58%. HFNC provides flows up to 60 L/min, FiO₂ up to 100%, with washout of nasopharyngeal dead space and modest PEEP effect (~3–5 cmH₂O).
NIV in ARDS: SSC, 2021 issued no recommendation for NIV vs invasive ventilation in sepsis-induced hypoxemic respiratory failure. LUNG SAFE, 2016: NIV used in 15% of ARDS with higher failure rates in severe disease. NIV failure is an independent mortality risk factor. If trialing NIV: monitor closely for Vt, work of breathing, and need for intubation.
Corticosteroids in ARDS
Steroids have an evolving role in ARDS — evidence now supports early dexamethasone in moderate-to-severe ARDS.
Early dexamethasone in moderate-to-severe ARDS (P/F ≤ 200): DEXA-ARDS, 2020: dexamethasone 20 mg IV daily × 5 days → 10 mg daily × 5 days. Reduced 60-day mortality (21% vs 36%, p=0.0047) and increased ventilator-free days. Start within 30h of ARDS diagnosis. This applies to non-COVID ARDS. Supported by CoDEX, 2020, which also showed dexamethasone increased ventilator-free days in moderate-severe ARDS.
Unresolving/fibroproliferative ARDS (after day 7): ARDS Steroid Trial, 2007: methylprednisolone 1 mg/kg/day with slow taper improved LIS score and reduced mechanical ventilation days. Do NOT start after day 14 — ARDSNet LaSRS, 2006: late initiation associated with increased 60- and 180-day mortality.
COVID-19 ARDS: RECOVERY, 2020: dexamethasone 6 mg/day × 10 days reduced 28-day mortality in patients on mechanical ventilation (29.3% vs 41.4%). CAPE COVID, 2020 found that low-dose hydrocortisone did not significantly reduce treatment failure in COVID pneumonia. REMAP-CAP, 2021 showed IL-6 inhibitors (tocilizumab, sarilumab) improved organ support-free days and survival in severe COVID when combined with corticosteroids.
Early dexamethasone in moderate-to-severe ARDS (P/F ≤ 200): DEXA-ARDS, 2020: dexamethasone 20 mg IV daily × 5 days → 10 mg daily × 5 days. Reduced 60-day mortality (21% vs 36%, p=0.0047) and increased ventilator-free days. Start within 30h of ARDS diagnosis. This applies to non-COVID ARDS. Supported by CoDEX, 2020, which also showed dexamethasone increased ventilator-free days in moderate-severe ARDS.
Unresolving/fibroproliferative ARDS (after day 7): ARDS Steroid Trial, 2007: methylprednisolone 1 mg/kg/day with slow taper improved LIS score and reduced mechanical ventilation days. Do NOT start after day 14 — ARDSNet LaSRS, 2006: late initiation associated with increased 60- and 180-day mortality.
COVID-19 ARDS: RECOVERY, 2020: dexamethasone 6 mg/day × 10 days reduced 28-day mortality in patients on mechanical ventilation (29.3% vs 41.4%). CAPE COVID, 2020 found that low-dose hydrocortisone did not significantly reduce treatment failure in COVID pneumonia. REMAP-CAP, 2021 showed IL-6 inhibitors (tocilizumab, sarilumab) improved organ support-free days and survival in severe COVID when combined with corticosteroids.
What Does NOT Work in ARDS
| Therapy | Outcome |
|---|---|
| Late steroids (> day 14) | ↑ mortality when started after day 14 ARDSNet LaSRS, 2006. Early dexamethasone (within 30h) IS beneficial — see above. |
| Inhaled nitric oxide (iNO) | Transient oxygenation improvement only. No mortality benefit. Increases renal dysfunction. |
| Surfactant | Effective in neonatal RDS. Ineffective in adult ARDS. |
| High-frequency oscillation (HFOV) | Increased mortality. Trial stopped early. OSCILLATE, 2013 |
| Incremental PEEP recruitment | Increased 28-day mortality (RR 1.12). ART, 2017 |
| IV beta-agonists (salbutamol) | Increased mortality. BALTI-2, 2012 |
💊 Medications & Doses
Sedation & Analgesia
Analgesia-first, target light sedation (RASS 0 to −2). PADIS, 2018 guidelines recommend protocolized sedation with daily awakening trials. Deep sedation (RASS −4/−5) only when NMBAs required.
| Drug | Dose | Indication | Notes |
|---|---|---|---|
| Fentanyl (Sublimaze) | 25–200 mcg/hr IV | Analgesia (first-line) | Analgesia-first approach. Less histamine release and hypotension than morphine. Accumulates with hepatic/renal failure. |
| Propofol (Diprivan) | 5–50 mcg/kg/min IV | Sedation (first-line) | Rapid on/off — ideal for daily awakening trials. Monitor triglycerides q48h. Propofol infusion syndrome risk if > 80 mcg/kg/min > 48h. |
| Dexmedetomidine | 0.2–1.5 mcg/kg/hr IV | Light sedation (no NMBAs) | Preserves respiratory drive. Less delirium than benzos. May cause bradycardia/hypotension. Not appropriate for deep sedation. |
| Midazolam (Versed) | 0.02–0.1 mg/kg/hr IV | Sedation (2nd-line) | Accumulates in renal/hepatic failure → prolonged wake-up. Associated with more delirium. Avoid long-term use. |
Neuromuscular Blockade
| Drug | Dose | Indication | Notes |
|---|---|---|---|
| Cisatracurium (bolus) | 0.1–0.2 mg/kg IV PRN | Intermittent use in mod-severe ARDS SSC, 2021 | Preferred strategy per SSC 2021. Monitor ventilator synchrony. Does not require train-of-four for intermittent dosing. |
| Cisatracurium (infusion) | 0.1–0.2 mg/kg/hr IV × 48h | Severe ARDS with refractory dyssynchrony | ACURASYS, 2010: mortality benefit vs deep sedation. ROSE, 2019: no benefit vs light sedation + boluses. Monitor with train-of-four (target 1–2/4). |
Other ARDS Medications
| Drug | Dose | Indication | Notes |
|---|---|---|---|
| Methylprednisolone (Solu-Medrol) | 1 mg/kg/day IV → taper over 2 wks | Unresolving ARDS (fibroproliferative phase, day 7–14) | ARDS Steroid Trial, 2007. Do NOT start after day 14 ARDSNet LaSRS, 2006: late steroids = ↑ mortality. |
| Dexamethasone (early) | 20 mg IV daily × 5d → 10 mg × 5d | Moderate-severe ARDS (P/F ≤ 200), start within 30h | DEXA-ARDS, 2020: reduced 60-day mortality (21% vs 36%) and ↑ ventilator-free days in non-COVID ARDS. |
| Dexamethasone (COVID) | 6 mg IV/PO daily × 10 days | COVID-19 ARDS | RECOVERY, 2020: NNT 8 in ventilated COVID patients. |
| Furosemide (Lasix) | Titrated to even/negative fluid balance | Conservative fluid strategy | FACTT, 2006. Start after resuscitation phase. Monitor Cr and K⁺ closely. CVP or PAOP guidance if available. |
| Sodium Bicarbonate | 1–2 mEq/kg IV slow push or infusion | pH < 7.15 with permissive hypercapnia | Use sparingly. Does not improve outcomes. Temporizing for severe acidemia only. |
📊 Monitoring
Daily Ventilator Assessment
- P/F ratio — calculate every morning from ABG. Trend drives all major decisions (prone, ECMO).
- Plateau pressure — perform inspiratory hold. Target ≤ 30 cmH₂O.
- Driving pressure (Pplat − PEEP) — target < 15 cmH₂O. Strongest independent predictor of mortality Driving Pressure Meta-Analysis, 2015.
- Tidal volume — confirm 6 mL/kg IBW. Recalculate if height was incorrectly entered.
- Static compliance = Vt / (Pplat − PEEP). Normal ~50–80 mL/cmH₂O. In ARDS typically 20–40.
- SpO₂ target — 88–95%. Avoid hyperoxemia ICU-ROX, 2020: conservative O₂ therapy may benefit; liberal O₂ offers no advantage.
- Fluid balance — calculate 24h net. Target even or negative after resuscitation FACTT, 2006.
Daily Checklist (ICU Rounds)
- ABG with P/F ratio
- Vent settings review: TV (mL/kg IBW), RR, FiO₂, PEEP, Pplat, driving pressure
- Sedation assessment: RASS score, daily awakening trial eligibility
- Spontaneous breathing trial (SBT) eligibility if improving
- Prone positioning: hours completed, plan for next cycle if P/F < 150
- Fluid balance: I/O, weight, diuretic needs
- DVT prophylaxis, stress ulcer prophylaxis (if high-risk SUP-ICU, 2018), HOB ≥ 30°
- Nutrition: enteral preferred, start within 48h SSC, 2021
- Source control: is the ARDS precipitant being treated?
When to Escalate
- Worsening P/F despite optimal PEEP + prone → ECMO evaluation
- P/F < 80 on FiO₂ 1.0 → emergent ECMO referral
- pH < 7.15 despite max RR and permissive hypercapnia → ECMO or iNO as bridge
- Pplat > 30 despite TV 4 mL/kg → consider ECMO, rule out tension PTX or abdominal compartment syndrome
- New hemodynamic instability → rule out tension PTX, PE, auto-PEEP, RV failure from high PEEP
- Barotrauma (subcutaneous emphysema, pneumomediastinum, PTX) → reduce PEEP/TV, chest tube if indicated
Weaning Readiness Criteria
Assess daily once P/F > 200 and FiO₂ ≤ 0.4 with PEEP ≤ 8:
- Precipitant resolving or resolved
- Hemodynamically stable (off or low-dose vasopressors)
- Adequate cough and gag reflex
- RASS −1 to +1 (awake, cooperative)
- No planned surgery or procedures requiring deep sedation
- Rapid shallow breathing index (RSBI) < 105 breaths/min/L
SBT Protocol: 30–120 min on PS 5–8 / PEEP 5 or T-piece. Pass = RR < 35, SpO₂ > 90%, HR < 140, no accessory muscle use, no distress. → Extubate. If fails → resume full support, retry in 24h. WIND, 2018: daily SBTs reduce time to extubation.
Complications to Watch
- Ventilator-associated pneumonia (VAP) — new fever, purulent sputum, new infiltrate on CXR after 48h of MV. Maintain HOB ≥ 30°, oral care, subglottic suctioning.
- Barotrauma — pneumothorax, pneumomediastinum, subcutaneous emphysema. Risk increases with Pplat > 30.
- ICU-acquired weakness — from NMBAs, steroids, immobility. Early mobilization when safe Early Mobilization Trial, 2009.
- Delirium — screen daily with CAM-ICU. Minimize benzos, sleep hygiene, early mobilization.
- RV failure — from high PEEP and pulmonary vasoconstriction. Monitor with echo. Reduce PEEP if RV dilation/failure suspected.
- Renal failure — common in ARDS. May be from underlying sepsis, contrast, or positive pressure effects on renal perfusion.
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Torres is a 52-year-old with no significant PMH who developed ARDS in the setting of severe CAP with Streptococcus pneumoniae. He was intubated on hospital day 1. He is on lung-protective ventilation: TV 6 mL/kg IBW at 390 mL, PEEP 12, FiO₂ 0.7, with a P/F ratio of 148 this morning — consistent with moderate ARDS. He was proned for 16 hours overnight with improvement in P/F to 180. His plateau pressure is 26. He is on propofol and fentanyl drips, RASS −2. We are on day 2 of cisatracurium. Fluid balance is negative 400 mL over the last 24 hours. He remains hemodynamically stable on low-dose norepinephrine. Plan is to continue prone cycling and target daily fluid balance of at least even."
Pimp Questions
What tidal volume should you use in ARDS and why?
6 mL/kg of ideal body weight. Higher tidal volumes cause volutrauma (overdistension) and worsen alveolar injury. ARDSnet 2000: 22% relative reduction in mortality with 6 vs 12 mL/kg IBW — the single most impactful ARDS trial ever done.
When do you prone a patient and what is the evidence?
P/F ratio < 150 despite optimal ventilator settings. PROSEVA 2013 prone ≥ 16 hrs/day reduced 28-day mortality from 32.8% to 16% — one of the most dramatic results in critical care medicine.
What is permissive hypercapnia and why do we accept it?
Allowing PaCO₂ to rise above normal (up to ~60 mmHg) as a trade-off for achieving lung-protective tidal volumes. Increasing minute ventilation to normalize CO₂ would require higher tidal volumes that cause further lung injury. pH > 7.20 is generally safe. Contraindicated in raised ICP and sickle cell crisis.
What is driving pressure, and why does it matter more than plateau pressure alone?
Driving pressure = Pplat − PEEP. It reflects the cyclic strain on functional lung tissue (the "baby lung"). A patient-level meta-analysis Driving Pressure Meta-Analysis, 2015 found driving pressure < 15 cmH₂O was the strongest independent predictor of survival in ARDS — better than Vt or Pplat alone. It accounts for both the tidal volume and the functional lung size.
ACURASYS vs ROSE — how do you reconcile conflicting NMBA data?
ACURASYS, 2010 compared 48h cisatracurium infusion vs deep sedation without NMBAs → mortality benefit. ROSE, 2019 compared infusion vs light sedation with PRN boluses → no benefit. The difference was the control arm: it's the deep sedation that was harmful, not the NMBAs that were magical. The lesson: avoid deep sedation; use light sedation with PRN NMBA boluses as first-line SSC, 2021.
When should you start thinking about ECMO?
P/F < 80 despite optimal vent settings (PEEP optimized, Pplat ≤ 30, TV 6 mL/kg IBW), prone positioning, and trial of NMBAs. Also consider for pH < 7.15 from respiratory acidosis or Pplat > 35 despite TV reduction to 4 mL/kg. EOLIA, 2018 showed benefit when referred early to experienced ECMO centers. Key: refer early — don't wait for irreversible multi-organ failure.
Why should you avoid fluid overload in ARDS, and what trial supports conservative fluids?
FACTT, 2006 randomized 1,000 ARDS patients to conservative vs liberal fluid management after initial resuscitation. Conservative strategy: ~2.5 fewer ventilator days, improved oxygenation index, no increase in shock or renal failure. Mechanism: reduced hydrostatic pressure across damaged pulmonary capillaries → less alveolar edema. Target even or negative daily fluid balance once resuscitation is complete.
10 Common ARDS Questions
Quick-fire board-style review. Click to reveal answers.
1. What is the definition of ARDS?
Acute diffuse inflammatory lung injury → increased alveolar-capillary permeability → pulmonary edema → severe hypoxemia. Diagnosed by Berlin criteria: acute onset ≤ 1 week, bilateral CXR opacities, not cardiogenic, P/F ratio determines severity.
2. What are the Berlin severity classifications?
Mild: P/F 200–300 (~27% mortality). Moderate: P/F 100–200 (~32% mortality). Severe: P/F < 100 (~45% mortality). All with PEEP ≥ 5 cmH₂O.
3. What is the most common cause of ARDS?
Sepsis (~40–50%), followed by pneumonia (~30–40%). Sepsis is the most common indirect cause; pneumonia is the most common direct (pulmonary) cause.
4. Why does hypoxemia occur in ARDS?
Shunt physiology — blood passes through non-ventilated, fluid-filled alveoli without participating in gas exchange. This is why supplemental O₂ alone often fails to correct the hypoxemia, and why PEEP (to recruit collapsed alveoli) is critical.
5. What is the ventilator tidal volume target in ARDS?
6 mL/kg of ideal body weight (IBW — NOT actual weight). ARDSNet, 2000: 6 vs 12 mL/kg → 22% relative mortality reduction. Can reduce to 4 mL/kg if Pplat remains > 30.
6. What plateau pressure should you target?
Pplat ≤ 30 cmH₂O. Additionally, driving pressure (Pplat − PEEP) < 15 cmH₂O is the strongest independent predictor of survival Driving Pressure Meta-Analysis, 2015.
7. When should you prone a patient?
P/F < 150 (severe ARDS) despite optimized ventilator settings. Prone ≥ 16 hours/day. PROSEVA, 2013: 28-day mortality 16% vs 32.8%. Apply within 36 hours of intubation for maximal benefit.
8. What is the role of ECMO in ARDS?
VV-ECMO is rescue therapy for refractory hypoxemia (P/F < 50–80 despite optimal ventilation + proning). EOLIA, 2018 supports early referral to experienced ECMO centers. Also consider if pH < 7.15 from respiratory acidosis despite max RR.
9. Why is permissive hypercapnia allowed?
Low tidal volumes → reduced minute ventilation → CO₂ retention. Increasing TV to normalize CO₂ would cause VILI. Acceptable as long as pH > 7.20. Contraindicated in raised ICP and sickle cell crisis.
10. How do you differentiate ARDS from cardiogenic pulmonary edema?
ARDS: normal PCWP (≤ 18), normal BNP, protein-rich exudate, diffuse bilateral CXR, no response to diuretics. Cardiogenic: high PCWP, high BNP, transudative, perihilar "bat wing" pattern, responds to diuresis. Bedside echo is the fastest differentiator.
⚡ Summary
Summary
Diagnosis
P/F < 300, bilateral opacities, acute onset ≤ 1 week, not explained by cardiac failure. Berlin criteria (2012). PEEP ≥ 5 required.
#1 Intervention
Lung-protective ventilation: TV 6 mL/kg IBW, Pplat ≤ 30, driving pressure < 15. ARDSNet, 2000: 22% mortality reduction. The only proven mortality-reducing strategy.
Prone Position
P/F < 150 → prone ≥ 16 hrs/day. PROSEVA, 2013: 28-day mortality 16% vs 32.8%. SSC, 2021: strong rec for > 12h/day. Do not delay.
Fluids
Conservative after resuscitation. FACTT, 2006: ~2.5 fewer vent days, no renal harm. Target even or negative fluid balance.
NMBAs
SSC, 2021: intermittent boluses preferred over infusion. ACURASYS, 2010 vs ROSE, 2019: avoid deep sedation; light sedation + PRN boluses.
Escalation
P/F < 80 or pH < 7.15 → VV-ECMO EOLIA, 2018. Refer early to experienced centers. Avoid: HFOV OSCILLATE, 2013, iNO, surfactant.
📄 One Pager
ICU · Ventilator · One Pager
ARDS
Low tidal volumes save lives. Prone early. Keep the lungs small and protected. Everything else is supportive.
Berlin Criteria — All 4 Required
- Acute onset ≤ 1 week of clinical insult
- Bilateral opacities on CXR/CT
- Not explained by cardiac failure/fluid overload
- P/F < 300 with PEEP ≥ 5
Severity
MildP/F 200–300 · ~27% mortality
ModerateP/F 100–200 · ~32% mortality
SevereP/F < 100 · ~45% mortality
Lung-Protective Ventilation ARDSnet 2000
1
Tidal volume: 6 mL/kg IBW (NOT actual weight). Reduce to 4 mL/kg if Pplat > 30.
2
Plateau pressure: ≤ 30 cmH₂O. Driving pressure: ≤ 15 cmH₂O (Pplat − PEEP).
3
PEEP: Per ARDSnet table. Higher PEEP for more severe disease.
4
Prone position if P/F < 150 → ≥ 16h/day PROSEVA 2013 — mortality halved
5
Conservative fluids after resuscitation — target even/negative balance FACTT 2006
6
ECMO if P/F < 80 or pH < 7.15 despite optimal settings EOLIA 2018
Key Drugs
Propofol5–50 mcg/kg/min
Fentanyl25–200 mcg/hr
Cisatracurium bolus0.1–0.2 mg/kg PRN
FurosemideEven/negative balance
Dexa (COVID only)6 mg/d × 10d
Does NOT Work
- HFOV OSCILLATE, 2013
- Inhaled nitric oxide
- Routine steroids (non-COVID)
- Surfactant (adults)
- Incremental PEEP recruit ART, 2017
- IV salbutamol BALTI-2, 2012
Pitfalls
- High TV "for comfort"
- Delaying prone positioning
- Fluid overload post-resus
- Not calculating IBW
- Deep sedation without indication
- Late ECMO referral
Airway & Ventilator Management
From the decision to intubate through vent settings, oxygenation vs ventilation, troubleshooting, sedation, and weaning to extubation. Everything you need to manage the airway and the ventilator.
🔍 Overview — Airway Decision-Making
Indications for Intubation
- Airway protection — GCS ≤ 8, inability to handle secretions, impending obstruction
- Hypoxemic respiratory failure — SpO₂ < 90% despite high-flow O₂, P/F < 200
- Hypercapnic respiratory failure — rising PaCO₂ with acidosis (pH < 7.25), fatigue
- Impending respiratory failure — accessory muscle use, paradoxical breathing, rising work of breathing
Try NIV First (if appropriate): BiPAP/CPAP for COPD exacerbation, cardiogenic pulmonary edema, and mild-moderate hypoxemia. Avoid NIV in decreased consciousness, vomiting, hemodynamic instability, or inability to cooperate.
Key Vent Concepts
Pressure vs Volume
Volume Control (VC): You set the tidal volume — the vent delivers exactly that volume. Pressure varies. Preferred in ARDS (tight TV control).
Pressure Control (PC): You set the pressure — the volume varies depending on lung compliance. Preferred when you want to limit pressures.
Pressure Control (PC): You set the pressure — the volume varies depending on lung compliance. Preferred when you want to limit pressures.
Key Numbers to Know Every Morning
- Tidal volume (Vt) — actual delivered TV in mL/kg IBW
- Rate (RR) — set respiratory rate
- FiO₂ — fraction of inspired oxygen (0.21–1.0)
- PEEP — positive end-expiratory pressure in cmH₂O
- Peak pressure (Ppeak) — total pressure to deliver breath (airway resistance + alveolar)
- Plateau pressure (Pplat) — alveolar distension pressure (inspiratory hold). Target ≤ 30.
- Driving pressure = Pplat − PEEP. Target ≤ 15. Strong predictor of ARDS mortality.
- P/F ratio = PaO₂ ÷ FiO₂ — oxygenation index
- SpO₂ target — 88–95% in ARDS; 94–98% otherwise
💨 Oxygen Delivery Devices
Escalation Ladder — Low Flow to High Flow
Rule of thumb: Each 1 L/min of nasal cannula adds ~4% FiO₂ above room air (21%). So 2L NC ≈ 28%, 4L ≈ 36%, 6L ≈ 44%. This breaks down above 6L.
| Device | Flow Rate | FiO₂ Delivered | Best For | ⚠️ Limitations |
|---|---|---|---|---|
| Nasal Cannula (NC) | 1–6 L/min | 24–44% | Mild hypoxemia. Stable patients. Most common starting point. | ⚠️ Uncomfortable > 6L (dries mucosa). Unreliable FiO₂ — depends on patient's minute ventilation and mouth breathing. |
| Simple Face Mask | 5–10 L/min | 35–55% | Moderate hypoxemia. Short-term use (ED, post-op). | ⚠️ Must run ≥ 5 L/min to prevent CO₂ rebreathing. Claustrophobic. Can't eat/talk well. |
| Venturi Mask | 4–12 L/min | Precise: 24%, 28%, 31%, 35%, 40%, 50% | COPD patients — need precise low FiO₂ (24–28%) to avoid suppressing hypoxic drive. Color-coded adapters. | ⚠️ Max 50% FiO₂. Bulky. Used mainly for COPD. |
| Non-Rebreather (NRB) | 10–15 L/min | 60–90% | Severe hypoxemia. Pre-oxygenation before intubation. CO poisoning. Trauma. | ⚠️ Reservoir bag must stay inflated. Not truly 100% — room air mixes around mask. If patient needs NRB → consider escalation. |
| High-Flow Nasal Cannula (HFNC) | 20–60 L/min | 21–100% (titratable) | Hypoxemic respiratory failure, post-extubation, immunocompromised (avoid intubation), pre-oxygenation. Delivers heated humidified O₂. | ⚠️ Generates ~1 cmH₂O PEEP per 10 L/min (so 60L ≈ 6 cmH₂O). Patient must breathe spontaneously. If still desatting on HFNC 60L/100% → intubate. |
When to Escalate
1
NC 1–6L — SpO₂ still < 92% → escalate
2
Simple mask / NRB 10–15L — SpO₂ still < 92% or work of breathing increasing → escalate
3
HFNC 40–60L — if SpO₂ < 92% on 60L/100% FiO₂, or RR > 30, or accessory muscle use → next step
4
NIV (BiPAP/CPAP) — if COPD exacerbation or cardiogenic pulmonary edema → try NIV before intubation
5
Intubation + Mechanical Ventilation — failing all above, declining mental status, unable to protect airway
⚠️ ROX Index (HFNC failure prediction): ROX = (SpO₂/FiO₂) ÷ RR. Check at 2, 6, 12 hours. ROX < 3.85 at 6h → high risk of HFNC failure → prepare for intubation. ROX > 4.88 → likely safe to continue HFNC.
🌬️ Non-Invasive Ventilation (NIV)
CPAP vs BiPAP
| CPAP | BiPAP | |
|---|---|---|
| What it does | Single continuous pressure (like PEEP) | Two pressures: IPAP (inhale) + EPAP (exhale) |
| Helps with | Oxygenation only — splints airways open, recruits alveoli | Both oxygenation AND ventilation — IPAP augments tidal volume (blows off CO₂), EPAP = PEEP |
| Best for | Cardiogenic pulmonary edema, OSA | COPD exacerbation (hypercapnic failure), obesity hypoventilation, neuromuscular weakness |
| Typical settings | CPAP 5–10 cmH₂O | IPAP 10–20 / EPAP 5–8 cmH₂O. Start IPAP 10, EPAP 5. Titrate IPAP up by 2 q15–30 min for CO₂. |
| Pressure support | None (single pressure) | PS = IPAP − EPAP. Higher PS = more ventilatory support. PS of 10 cmH₂O is moderate support. |
Indications for NIV
- COPD exacerbation with respiratory acidosis (pH < 7.35, PaCO₂ > 45) — strongest evidence, reduces intubation by 65% Brochard, 1995
- Cardiogenic pulmonary edema — CPAP or BiPAP both work. Reduces preload + afterload + recruits flooded alveoli. 3CPO, 2008
- Post-extubation — prophylactic NIV in high-risk patients reduces reintubation
- Immunocompromised with respiratory failure — try NIV/HFNC first to avoid vent-associated infections
- Palliative / DNI patients — ceiling of care when intubation is not desired
Contraindications — Do NOT Use NIV
- Cardiac or respiratory arrest — intubate
- Unable to protect airway — GCS ≤ 8, no gag, excessive secretions
- Vomiting or high aspiration risk — mask traps vomit → aspiration
- Hemodynamic instability (uncontrolled shock) — needs intubation for airway control
- Facial trauma/burns/surgery — can't seal mask
- Upper airway obstruction — positive pressure won't pass the obstruction
- Uncooperative / agitated patient — won't tolerate mask
When NIV is Failing — Escalate to Intubation
⚠️ Signs of NIV failure (reassess within 1–2 hours):
• No improvement in pH or PaCO₂ after 1–2h of BiPAP
• Worsening tachypnea (RR > 30 despite NIV)
• SpO₂ < 90% despite FiO₂ escalation
• Declining mental status (somnolence, confusion)
• Hemodynamic instability
• Patient intolerance / non-compliance with mask
Do NOT delay intubation if NIV is failing. Late intubation = worse outcomes.
• No improvement in pH or PaCO₂ after 1–2h of BiPAP
• Worsening tachypnea (RR > 30 despite NIV)
• SpO₂ < 90% despite FiO₂ escalation
• Declining mental status (somnolence, confusion)
• Hemodynamic instability
• Patient intolerance / non-compliance with mask
Do NOT delay intubation if NIV is failing. Late intubation = worse outcomes.
🚨 Rapid Sequence Intubation (RSI)
The 7 P's of RSI
1
Preparation
Equipment: ETT (7.0–7.5 women, 7.5–8.0 men), laryngoscope (video preferred), bougie, BVM, suction, end-tidal CO₂, backup airway (LMA). Two IV lines. Monitors on. Confirm code status.
Equipment: ETT (7.0–7.5 women, 7.5–8.0 men), laryngoscope (video preferred), bougie, BVM, suction, end-tidal CO₂, backup airway (LMA). Two IV lines. Monitors on. Confirm code status.
2
Pre-oxygenation
3–5 minutes of 100% O₂ via NRB or HFNC 60L/min (builds O₂ reserve in FRC). Goal: SpO₂ 100%. In obese or critically ill → apneic oxygenation: leave NC at 15L under the NRB or continue HFNC during intubation attempt.
3–5 minutes of 100% O₂ via NRB or HFNC 60L/min (builds O₂ reserve in FRC). Goal: SpO₂ 100%. In obese or critically ill → apneic oxygenation: leave NC at 15L under the NRB or continue HFNC during intubation attempt.
3
Pre-treatment (optional)
Fentanyl 1–3 mcg/kg IV (blunts sympathetic surge — useful in elevated ICP, aortic dissection). Lidocaine 1.5 mg/kg IV (for elevated ICP — controversial). Most patients skip this step.
Fentanyl 1–3 mcg/kg IV (blunts sympathetic surge — useful in elevated ICP, aortic dissection). Lidocaine 1.5 mg/kg IV (for elevated ICP — controversial). Most patients skip this step.
4
Paralysis with Induction (push simultaneously)
See drug table below. Induction agent → wait 20–30 seconds → paralytic.
See drug table below. Induction agent → wait 20–30 seconds → paralytic.
5
Protection & Positioning
Sniffing position: neck flexed, head extended (aligns oral-pharyngeal-laryngeal axes). Elevate head of bed 20–30° in obese. Apply cricoid pressure (Sellick maneuver — controversial but still used).
Sniffing position: neck flexed, head extended (aligns oral-pharyngeal-laryngeal axes). Elevate head of bed 20–30° in obese. Apply cricoid pressure (Sellick maneuver — controversial but still used).
6
Placement
Direct or video laryngoscopy → visualize cords → pass tube through cords → inflate cuff → confirm placement: (1) End-tidal CO₂ waveform (gold standard), (2) bilateral breath sounds, (3) misting in tube, (4) CXR for depth (2–4 cm above carina).
Direct or video laryngoscopy → visualize cords → pass tube through cords → inflate cuff → confirm placement: (1) End-tidal CO₂ waveform (gold standard), (2) bilateral breath sounds, (3) misting in tube, (4) CXR for depth (2–4 cm above carina).
7
Post-intubation Management
Start sedation (propofol or midazolam + fentanyl). Set initial vent settings. Secure tube (tape or holder). NG/OG tube. Arterial line if not already placed. ABG in 30 min. CXR to confirm ETT position.
Start sedation (propofol or midazolam + fentanyl). Set initial vent settings. Secure tube (tape or holder). NG/OG tube. Arterial line if not already placed. ABG in 30 min. CXR to confirm ETT position.
RSI Drug Table
| Drug | MOA | Dose | Onset | Duration | Best For | ⚠️ Avoid If |
|---|---|---|---|---|---|---|
| INDUCTION AGENTS | ||||||
| Etomidate | GABA-A agonist | 0.3 mg/kg IV push | 15–30 sec | 5–15 min | Hemodynamically unstable — most neutral on BP. Most common RSI induction agent. | ⚠️ Adrenal suppression (single dose is clinically insignificant). Avoid in septic shock? — debated. |
| Ketamine (Ketalar) | NMDA antagonist | 1–2 mg/kg IV push | 30–60 sec | 10–20 min | Asthma/bronchospasm (bronchodilator), hypotension (preserves BP via sympathetic stimulation), elevated ICP (old teaching said avoid — now considered safe). | ⚠️ Psychosis/schizophrenia (emergence reactions). Increases secretions — give glycopyrrolate. |
| Propofol (Diprivan) | GABA-A agonist | 1.5–2.5 mg/kg IV push | 15–30 sec | 5–10 min | Status epilepticus (anticonvulsant), elevated ICP (lowers ICP). | ⚠️ Causes significant hypotension — avoid in shock, hypovolemia. Egg/soy allergy (controversial). |
| Midazolam (Versed) | GABA-A agonist (benzo) | 0.1–0.3 mg/kg IV push | 1–2 min | 15–30 min | Rarely used for RSI (slower onset). Backup option. Provides amnesia. | ⚠️ Hypotension. Slower onset than etomidate/ketamine. Can reverse with flumazenil. |
| PARALYTICS (NEUROMUSCULAR BLOCKERS) | ||||||
| Succinylcholine (Anectine) | Depolarizing NMB — mimics ACh, sustained depolarization → paralysis | 1–1.5 mg/kg IV push | 30–45 sec | 6–10 min | Fastest onset + shortest duration. Good when you need to quickly reassess neuro status (e.g., stroke). | ⚠️ Hyperkalemia (burns > 48h, crush injury, denervation, renal failure with K⁺ > 5.5). Malignant hyperthermia (personal/family history). Myasthenia gravis. |
| Rocuronium (Zemuron) | Non-depolarizing NMB — competitive ACh blocker at nicotinic receptor | 1.2 mg/kg IV push (RSI dose) | 45–60 sec | 45–70 min | When succinylcholine is contraindicated. Reversible with sugammadex (16 mg/kg for immediate reversal). Becoming first-line at many centers. | ⚠️ Long duration — if can't intubate AND can't ventilate, patient is paralyzed for 45+ min (unless sugammadex available). |
⚠️ Cannot Intubate, Cannot Oxygenate (CICO) — Surgical Airway
If 2 intubation attempts fail AND cannot bag-mask ventilate AND LMA fails → cricothyrotomy. Palpate cricothyroid membrane (between thyroid and cricoid cartilage) → vertical skin incision → horizontal stab through membrane → insert bougie → railroad 6.0 ETT or cric tube. This is the final rescue. Do not delay.
If 2 intubation attempts fail AND cannot bag-mask ventilate AND LMA fails → cricothyrotomy. Palpate cricothyroid membrane (between thyroid and cricoid cartilage) → vertical skin incision → horizontal stab through membrane → insert bougie → railroad 6.0 ETT or cric tube. This is the final rescue. Do not delay.
Difficult Airway Predictors (LEMON):
Look externally (short neck, obesity, facial trauma, beard)
Evaluate 3-3-2 (3 fingers mouth opening, 3 fingers hyoid-to-chin, 2 fingers thyroid notch-to-floor of mouth)
Mallampati score (III/IV = harder)
Obstruction (epiglottitis, angioedema, tumor, hematoma)
Neck mobility (c-spine collar, ankylosing spondylitis, rheumatoid arthritis)
Look externally (short neck, obesity, facial trauma, beard)
Evaluate 3-3-2 (3 fingers mouth opening, 3 fingers hyoid-to-chin, 2 fingers thyroid notch-to-floor of mouth)
Mallampati score (III/IV = harder)
Obstruction (epiglottitis, angioedema, tumor, hematoma)
Neck mobility (c-spine collar, ankylosing spondylitis, rheumatoid arthritis)
⚙️ Ventilator Modes Explained
The Modes You Need to Know
Every vent mode answers two questions: (1) What triggers a breath? (patient or machine), (2) What's guaranteed — volume or pressure?
| Mode | How It Works | You Set | What Varies | Best For | ⚠️ Watch For |
|---|---|---|---|---|---|
| AC/VC Assist Control / Volume Control | Every breath (patient-triggered or machine-triggered) delivers a set tidal volume. | TV, RR, FiO₂, PEEP, flow rate | Pressure (Ppeak varies with compliance/resistance) | Most common mode. Default for most intubations. ARDS (guarantees 6 mL/kg TV). | ⚠️ If compliance drops → pressures rise → barotrauma. Watch Pplat. |
| AC/PC Assist Control / Pressure Control | Every breath delivers a set pressure for a set inspiratory time. | Pressure, I-time, RR, FiO₂, PEEP | Tidal volume (varies with compliance) | When you want to limit pressures strictly. Neonatal/pediatric. Some ARDS protocols. | ⚠️ If compliance worsens → TV drops → hypoventilation. Must monitor TV closely. |
| SIMV Synchronized Intermittent Mandatory Ventilation | Delivers set number of mandatory breaths. Patient can take extra breaths on their own (unsupported or with PS). | TV, RR, FiO₂, PEEP, PS level | Patient's spontaneous breaths are variable | Weaning mode — gradually reduce mandatory rate as patient takes over. | ⚠️ Increases work of breathing if PS too low on spontaneous breaths. Largely fallen out of favor — SBT preferred for weaning. |
| PSV Pressure Support Ventilation | Patient triggers every breath. Vent augments each breath with set pressure support. | PS level, FiO₂, PEEP | TV and RR (entirely patient-driven) | SBT (PS 5–8 cmH₂O), weaning assessment, awake cooperative patients. | ⚠️ No backup rate — if patient becomes apneic, no breaths are delivered. Need apnea backup alarm. |
| APRV Airway Pressure Release Ventilation | Sustained high pressure (P-high) with brief releases to low pressure (P-low) for CO₂ clearance. Essentially inverse-ratio CPAP. | P-high, T-high, P-low, T-low | TV during releases | Refractory ARDS — keeps alveoli open with sustained high pressure. Allows spontaneous breathing. | ⚠️ Complex to manage. Requires experience. Not proven superior to standard lung-protective ventilation. Hemodynamic effects from sustained high intrathoracic pressure. |
Quick Decision: Which Mode?
| Scenario | Mode | Why |
|---|---|---|
| Fresh intubation (default) | AC/VC | Guarantees tidal volume. Simple. Predictable. |
| ARDS | AC/VC (6 mL/kg IBW) | Must control TV tightly for lung protection. |
| COPD / asthma | AC/VC (low rate, long I:E) | Need guaranteed TV with long expiratory time to avoid air trapping. |
| High peak pressures | Switch AC/VC → AC/PC | Limits pressure delivery. But monitor TV — may drop. |
| Ready to wean / SBT | PSV 5–8 / PEEP 5 | Minimal support. Tests if patient can breathe independently. |
| Refractory ARDS | APRV (by experienced team) | Last resort before ECMO. Keeps alveoli recruited. |
🫁 Oxygenation vs Ventilation
The Most Important Concept on the Vent
Oxygenation and ventilation are two completely separate physiologic processes. They are fixed by different vent settings. Confusing them is the #1 mistake interns make in the ICU. If you learn nothing else about the vent, learn this table.
| 🔵 Oxygenation (O₂) | 🔴 Ventilation (CO₂) | |
|---|---|---|
| What is it? | Getting oxygen INTO the blood | Getting CO₂ OUT of the blood |
| Measured by | PaO₂ (ABG) or SpO₂ (pulse ox) | PaCO₂ (ABG) or EtCO₂ (capnography) |
| Normal values | PaO₂ 80–100 mmHg, SpO₂ 94–98% | PaCO₂ 35–45 mmHg |
| Problem | Hypoxemia — O₂ too low | Hypercapnia — CO₂ too high Hypocapnia — CO₂ too low |
| Vent settings that fix it | FiO₂ (↑ = more O₂ delivered) PEEP (↑ = recruits collapsed alveoli, improves gas exchange surface area) | Respiratory Rate (↑ RR = blow off more CO₂) Tidal Volume (↑ TV = each breath removes more CO₂) Together = Minute Ventilation (MV = RR × TV) |
| Think of it as | How much oxygen you're putting IN the lungs | How much air you're moving THROUGH the lungs |
Quick Decision Framework
🔵 Patient is HYPOXEMIC (SpO₂ low)
Step 1: ↑ FiO₂ (quick fix — increase the O₂ concentration)
Step 2: ↑ PEEP (recruit alveoli — increases surface area for gas exchange)
Step 3: Prone positioning — flip patient face-down ≥ 16h/day. Redistributes ventilation to dorsal lung (where perfusion is greatest) → improves V/Q matching. Mortality benefit in severe ARDS (P/F < 150) PROSEVA, 2013
Step 4: Inhaled nitric oxide (iNO) 5–40 ppm or inhaled epoprostenol — selective pulmonary vasodilators. Dilate vessels ONLY in ventilated alveoli → redirects blood flow to functioning lung units → improves V/Q matching + oxygenation. ⚠️ No proven mortality benefit — used as rescue/bridge therapy.
Step 5: ECMO (VV-ECMO) — when all above fail. Blood is oxygenated externally. Consider if P/F < 80 despite optimal vent + prone + iNO.
⚠️ Do NOT increase RR or TV — these do not fix oxygenation. Breathing faster doesn't put more O₂ in the blood if the alveoli can't exchange gas.
Step 2: ↑ PEEP (recruit alveoli — increases surface area for gas exchange)
Step 3: Prone positioning — flip patient face-down ≥ 16h/day. Redistributes ventilation to dorsal lung (where perfusion is greatest) → improves V/Q matching. Mortality benefit in severe ARDS (P/F < 150) PROSEVA, 2013
Step 4: Inhaled nitric oxide (iNO) 5–40 ppm or inhaled epoprostenol — selective pulmonary vasodilators. Dilate vessels ONLY in ventilated alveoli → redirects blood flow to functioning lung units → improves V/Q matching + oxygenation. ⚠️ No proven mortality benefit — used as rescue/bridge therapy.
Step 5: ECMO (VV-ECMO) — when all above fail. Blood is oxygenated externally. Consider if P/F < 80 despite optimal vent + prone + iNO.
⚠️ Do NOT increase RR or TV — these do not fix oxygenation. Breathing faster doesn't put more O₂ in the blood if the alveoli can't exchange gas.
🔴 Patient is HYPERCAPNIC (CO₂ high)
Step 1: ↑ Respiratory Rate (blow off more CO₂ per minute)
Step 2: ↑ Tidal Volume (each breath removes more CO₂)
Minute Ventilation = RR × TV → this is what determines CO₂ clearance
Step 3 (if bronchospasm): Heliox (70–80% helium / 20–30% O₂) — helium is less dense than nitrogen → reduces turbulent airflow resistance → gas flows past the obstruction more easily → improves ventilation in severe bronchospasm/upper airway obstruction refractory to bronchodilators. ⚠️ Limitation: Max FiO₂ is 30% (rest is helium), so don't use if patient needs high FiO₂.
⚠️ Do NOT increase FiO₂ or PEEP — these do not remove CO₂. Giving more oxygen doesn't help ventilation.
⚠️ Watch for auto-PEEP: If RR too high (especially in COPD), patient may not fully exhale → air trapping → hemodynamic collapse.
Step 2: ↑ Tidal Volume (each breath removes more CO₂)
Minute Ventilation = RR × TV → this is what determines CO₂ clearance
Step 3 (if bronchospasm): Heliox (70–80% helium / 20–30% O₂) — helium is less dense than nitrogen → reduces turbulent airflow resistance → gas flows past the obstruction more easily → improves ventilation in severe bronchospasm/upper airway obstruction refractory to bronchodilators. ⚠️ Limitation: Max FiO₂ is 30% (rest is helium), so don't use if patient needs high FiO₂.
⚠️ Do NOT increase FiO₂ or PEEP — these do not remove CO₂. Giving more oxygen doesn't help ventilation.
⚠️ Watch for auto-PEEP: If RR too high (especially in COPD), patient may not fully exhale → air trapping → hemodynamic collapse.
Common Scenarios — What to Adjust
| ABG Shows | Problem | Adjust | ⚠️ Watch For |
|---|---|---|---|
| PaO₂ 55, SpO₂ 88% | Hypoxemia | ↑ FiO₂ and/or ↑ PEEP | FiO₂ > 0.6 for > 24h → O₂ toxicity. Wean FiO₂ first, then PEEP. |
| PaCO₂ 65, pH 7.22 | Respiratory acidosis (hypoventilating) | ↑ RR or ↑ TV (↑ minute ventilation) | Auto-PEEP in COPD. Pplat > 30 if TV too high. Max RR ~35 before ineffective. |
| PaCO₂ 25, pH 7.55 | Respiratory alkalosis (overventilating) | ↓ RR or ↓ TV (↓ minute ventilation) | Patient may be anxious/in pain → treat the cause. Don't just sedate to fix CO₂. |
| PaO₂ 55 AND PaCO₂ 60 | Both hypoxemic + hypercapnic | ↑ FiO₂/PEEP (for O₂) AND ↑ RR/TV (for CO₂). If refractory → prone + iNO + ECMO. | Suggests severe disease (ARDS + dead space). Consider prone, paralytics, iNO, ECMO. |
| PaO₂ 120, FiO₂ 1.0 | Over-oxygenating | ↓ FiO₂ (wean to target SpO₂ 92–96%) | Hyperoxia harms: ↑ mortality in cardiac arrest, stroke, MI. Wean FiO₂ aggressively. |
The Memory Trick
🔵
O₂ = FiO₂ + PEEP
Escalation: FiO₂ → PEEP → Prone → iNO → ECMO
🔴
CO₂ = RR × TV
"How much air am I moving?"
⚠️ Permissive hypercapnia: In ARDS, it's OK to let CO₂ run high (up to 60–70) and pH drop to ~7.20 — as long as oxygenation is maintained. The priority is lung-protective ventilation (TV 6 mL/kg, Pplat ≤ 30). Don't sacrifice lung protection to normalize a CO₂ number.
P/F ratio = PaO₂ ÷ FiO₂ — the single best number to assess oxygenation on a vent.
> 300: Normal
200–300: Mild ARDS
100–200: Moderate ARDS
< 100: Severe ARDS → consider prone, paralytics, ECMO
> 300: Normal
200–300: Mild ARDS
100–200: Moderate ARDS
< 100: Severe ARDS → consider prone, paralytics, ECMO
Types of Respiratory Failure
| Type | Name | Mechanism | ABG Pattern | Common Causes | Treatment Focus |
|---|---|---|---|---|---|
| Type 1 | Hypoxemic | Failure of gas exchange — O₂ can't cross alveolar membrane into blood. V/Q mismatch, shunt, diffusion impairment. | PaO₂ < 60 PaCO₂ normal or low | Pneumonia, ARDS, pulmonary edema, PE, pulmonary fibrosis, atelectasis | 🔵 FiO₂ + PEEP → prone → iNO → ECMO |
| Type 2 | Hypercapnic | Failure of ventilation — can't move enough air to clear CO₂. Pump failure (muscles, drive, mechanics). | PaCO₂ > 50 pH < 7.35 PaO₂ may be low too | COPD, asthma, obesity hypoventilation, neuromuscular disease (GBS, MG, ALS), drug overdose (opioids), chest wall deformity | 🔴 RR × TV (↑ minute ventilation). BiPAP first if possible. |
| Type 3 | Perioperative | Atelectasis from anesthesia, supine positioning, diaphragm splinting (pain, abdominal distension). | PaO₂ low PaCO₂ usually normal | Post-surgical (especially abdominal/thoracic), obesity, poor pain control limiting deep breathing | Incentive spirometry, early mobilization, pain control, CPAP if needed |
| Type 4 | Shock | Hypoperfusion → insufficient O₂ delivery to tissues despite adequate lung function. Respiratory muscles fatigue from hypoperfusion. | Lactic acidosis Mixed picture | Cardiogenic shock, septic shock, hypovolemic shock, massive PE | Treat the shock first (fluids, vasopressors, inotropes). Intubate to reduce O₂ consumption by respiratory muscles. |
Why does this matter? Knowing the type tells you what to fix. Type 1 → fix oxygenation (FiO₂/PEEP). Type 2 → fix ventilation (RR/TV or BiPAP). Type 3 → prevent/reverse atelectasis. Type 4 → fix the circulation, not just the lungs.
📌 Settings
Initial Vent Settings
| Parameter | Standard | ARDS | COPD/Obstructive |
|---|---|---|---|
| Mode | AC/VC or AC/PC | AC/VC | AC/VC or SIMV |
| Tidal Volume | 8 mL/kg IBW | 6 mL/kg IBW | 6–8 mL/kg IBW |
| Rate | 14–16 /min | 18–22 /min | 10–14 /min (avoid stacking) |
| FiO₂ | Start 1.0, wean | Wean to keep SpO₂ 88–95% | Target SpO₂ 88–92% |
| PEEP | 5 cmH₂O | 8–16 (ARDSnet table) | Auto-PEEP concern — keep low |
| I:E Ratio | 1:2 | 1:2 to 1:3 | 1:3 to 1:4 (more time to exhale) |
📌 Trouble
Acute Deterioration on the Vent — DOPE
Patient suddenly desaturating or high pressures alarm → Call for help + use DOPE mnemonic immediately
D — Displacement
- ETT displaced (too deep → right mainstem, or dislodged)
- Check: confirm with laryngoscope, CXR, ETCO₂, auscultation
- Fix: reposition or replace tube
O — Obstruction
- Mucus plug, biting tube, kinked circuit
- Check: suction catheter passes easily? Pass suction first
- Fix: suction, reposition head, bite block
P — Pneumothorax
- Tension pneumothorax: absent breath sounds + tracheal deviation + hypotension
- Fix: needle decompression NOW (2nd ICS, MCL or 4th ICS, anterior axillary line) then chest tube. Do NOT wait for CXR if hemodynamically unstable.
E — Equipment
- Vent malfunction, circuit disconnect, O₂ supply failure
- Fix: disconnect from vent → manually bag the patient → troubleshoot equipment
High Peak, Normal Plateau
Peak – Plateau > 10 cmH₂O → airway resistance problem (mucus plug, bronchospasm, kinked tube). Treat: suction, bronchodilators, reposition.
High Peak AND High Plateau
Both elevated → decreased compliance problem (worsening ARDS, pneumothorax, pulmonary edema, pneumonia). Check CXR, assess clinically.
🧪 Workup
Workup
- ABG pre/post intubation
- CXR — ETT 2-4cm above carina
- Plateau pressure — goal <30
- Driving pressure — Pplat−PEEP, goal <15
- Auto-PEEP — expiratory hold
- Peak vs Plateau — high peak + normal plat = airway resistance; both high = compliance problem
🚨 Management
Management
- Lung-protective: TV 6–8 mL/kg IBW, Pplat < 30, driving pressure < 15
- ARDS: TV 6 mL/kg IBW ARDSNet, 2000, PEEP per ARDSNet table, prone if P/F < 150 PROSEVA, 2013
- Daily SBT: FiO₂ ≤ 40%, PEEP ≤ 8, following commands → PSV 5/5 × 30 min
- Sedation: RASS 0 to −2. Daily SAT before SBT.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Propofol (Diprivan) | 5–50 mcg/kg/min | IV | First-line sedation. ⚠️ PRIS risk if > 48h or > 80 mcg/kg/min (check CK, triglycerides, lactate). |
| Fentanyl (Sublimaze) | 25–200 mcg/hr | IV | Analgesia-first approach. Preferred analgesic in ICU. Lipophilic — accumulates > 72h. |
| Cisatracurium | 1–3 mcg/kg/min | IV | Neuromuscular blockade for severe ARDS × 48h. Must have adequate sedation first — paralyzed + aware = torture. ACURASYS, 2010 |
| Dexmedetomidine | 0.2–1.5 mcg/kg/hr | IV | Less delirium than benzos MENDS, 2007. DEXCOM, 2016: reduced delirium and shorter time to extubation vs midazolam. ⚠️ Bradycardia, hypotension. No respiratory depression — can use during SBT. |
NONSEDA, 2020: No sedation vs light sedation in mechanically ventilated patients showed similar outcomes, though no-sedation had more agitation episodes. Supports minimizing sedation depth when feasible.
🔓 Weaning & Extubation
Ventilator Weaning & Extubation
Step 1: Daily Spontaneous Awakening Trial (SAT)
- Stop sedation infusions daily (unless contraindicated: active seizures, alcohol withdrawal, paralytics, elevated ICP)
- Assess: Is patient following commands? Opening eyes? Breathing comfortably?
- Restart sedation at half dose if patient fails (agitation, RR > 35, SpO₂ < 88%, distress)
Step 2: Spontaneous Breathing Trial (SBT)
Perform if SAT passes. Place on minimal vent support (CPAP 5 / PS 5–8) for 30–120 minutes.
SBT readiness criteria: FiO₂ ≤ 40%, PEEP ≤ 8, hemodynamically stable (no/low vasopressors), adequate mental status, intact cough reflex.
Pass criteria — ALL of the following:
- RR < 30, SpO₂ > 90%, TV > 5 mL/kg IBW
- RSBI (Rapid Shallow Breathing Index) = RR ÷ Vt (in L) < 105 — most validated weaning predictor
- No distress, paradoxical breathing, or diaphoresis
- HR and BP within 20% of baseline
Step 3: Extubation Checklist
- Passed SBT ✓
- Airway reflexes intact — strong cough, follows commands
- Cuff leak test: deflate cuff → listen for air leak around tube. No leak suggests laryngeal edema → post-extubation stridor risk → give dexamethasone and delay extubation
- Secretion burden manageable (not suctioning > q2h)
- Consider dexamethasone 8 mg IV q8h × 4 doses starting 12h before extubation if intubated > 7 days or failed cuff leak
- Anesthesia or airway team notified if anticipated difficult reintubation
⚠️ Failed Extubation: Need to reintubate within 48–72 hours — associated with significantly higher mortality (up to 25–50%). Better to wait one more day than to extubate prematurely. Risk factors for failure: age > 65, COPD, HF, weak cough, excessive secretions, high RSBI.
Post-extubation: Apply supplemental O₂ (nasal cannula or HFNC). Monitor closely for 24–48h. If high-risk for reintubation → prophylactic HFNC or NIV (BiPAP) post-extubation reduces reintubation rates.
📊 Monitoring
Monitoring — Mechanical Ventilation
| Parameter | Frequency | Target / Action |
|---|---|---|
| ABG | 30 min after any vent change, then q4–6h | pH, PaCO2, PaO2, P/F ratio. Guides FiO2/PEEP (oxygenation) and RR/TV (ventilation) adjustments. |
| Daily SBT assessment | Every morning | Assess readiness: FiO2 ≤ 40%, PEEP ≤ 8, hemodynamically stable, no high-dose vasopressors, adequate mental status. RSBI < 105 (RR/TV in liters) predicts successful extubation. Girard, 2008: paired SAT + SBT improves outcomes. |
| Plateau pressure | q4–6h or with vent changes | Pplat < 30 cmH2O (lung protective). If exceeding → reduce TV, check for pneumothorax, bronchospasm, or mucus plugging. |
| Driving pressure | q4–6h | Driving pressure < 15 cmH2O (Pplat - PEEP). Strongest predictor of ARDS mortality Amato, 2015. Optimize by adjusting TV and PEEP. |
| SpO2 / FiO2 trending | Continuous SpO2, track P/F ratio | SpO2 target 88–95% in ARDS, 94–98% otherwise. Worsening P/F may indicate disease progression, fluid overload, or new complication. |
| Auto-PEEP check | q shift and with clinical concern | Expiratory hold maneuver. Auto-PEEP > 5 = air trapping → increase expiratory time (decrease RR, decrease I:E ratio). Common in COPD/asthma. |
| Sedation level (RASS) | q4h | Target RASS -2 to 0 (light sedation). Deeper sedation only if specific indication (prone, paralysis, severe agitation). Daily sedation awakening trial (SAT). |
| Daily SAT + SBT | Every morning | Girard, 2008: paired protocol — SAT first (hold sedation, assess arousal) → if passes → SBT (PS 5–8/PEEP 5 for 30–120 min). Reduces vent days and mortality. |
| VAE surveillance | Daily | Ventilator-associated events: new/worsening infiltrate, rising FiO2/PEEP after period of stability, fever, purulent secretions. Prevent with: HOB 30-45°, oral care, DVT/PUD prophylaxis, daily SBT. |
Every vent day is a bad day. The single best thing you can do for a ventilated patient is liberate them from the ventilator. Daily SAT + SBT is the most evidence-based strategy to shorten ventilator duration.
📋 On Rounds
On Rounds
📋 Daily Vent Check Presentation
"Mr. Patel is intubated day 3 for hypoxemic respiratory failure from aspiration pneumonia. Current vent settings: AC/VC, TV 420 mL (6 mL/kg IBW), RR 18, PEEP 8, FiO₂ 0.55. This morning's ABG: pH 7.38, pCO₂ 42, pO₂ 74 — P/F ratio 135, consistent with moderate ARDS. Pplat is 24, driving pressure 16. He had a SAT trial this morning — he was following commands but became tachypneic. We are holding the SBT today and will reassess tomorrow. He is on propofol and fentanyl, RASS −1. Fluid balance is negative 200 mL over the past 24 hours."
Pimp Questions
What is driving pressure and why does it matter?
Driving pressure = Pplat − PEEP. It reflects the stress on functional lung units. A driving pressure > 15 cmH₂O is independently associated with increased ARDS mortality even when TV and Pplat are within targets. It may be the most important vent parameter to minimize.
What is auto-PEEP and when does it occur?
Air trapping due to incomplete exhalation before the next breath — common in COPD/asthma. Causes hemodynamic compromise (reduced venous return) and barotrauma. Detected by expiratory hold maneuver. Treated by reducing RR, increasing I:E ratio (longer expiratory time), and bronchodilators.
The vent is alarming with high peak pressures. How do you troubleshoot?
Peak pressure = airway resistance + compliance + PEEP. High peak + normal plateau (< 30) = airway resistance problem: bronchospasm (give albuterol), mucus plug (suction), kinked ETT, biting tube (bite block/sedation), small ETT. High peak + high plateau (> 30) = compliance problem: pneumothorax (MOST DANGEROUS — check for absent breath sounds, tracheal deviation → needle decompress), mainstem intubation (pull back ETT), ARDS progression, abdominal distension, pleural effusion, pulmonary edema, auto-PEEP (check by doing expiratory hold). Step 1 always: disconnect from vent and bag — if easy to bag = vent/circuit problem; if hard to bag = patient problem.
What is driving pressure and why is it more important than tidal volume alone?
Driving pressure = Plateau pressure − PEEP. It represents the actual distending pressure applied to the lung parenchyma. Goal: < 15 cmH₂O. A landmark meta-analysis by Amato (2015) showed driving pressure was the ventilator variable most strongly associated with survival in ARDS — more predictive than tidal volume or plateau pressure alone. Why: a TV of 6 mL/kg may be safe in a patient with large functional lung but harmful in a patient with extensive consolidation ("baby lung") because the same TV is distributed to fewer open alveoli → higher driving pressure → volutrauma. Practical application: if driving pressure > 15, reduce TV further (even below 6 mL/kg) and accept permissive hypercapnia.
⚡ Summary
Summary
Initial Settings
AC/VC, TV 6–8 mL/kg IBW, RR 14–18, FiO₂ 1.0 then wean, PEEP 5
ARDS Settings
TV 6 mL/kg IBW, Pplat ≤ 30, driving pressure ≤ 15, PEEP per ARDSnet table
Acute Deterioration
DOPE: Displacement, Obstruction, Pneumothorax, Equipment. Bag first if in doubt.
Weaning
Daily SAT → SBT. RSBI < 105. Pass both → extubate. Coordinate daily.
High Peak / Normal Plat
Airway resistance problem → suction, bronchodilators, reposition tube
High Peak + High Plat
Compliance problem → pneumothorax, ARDS, pulmonary edema. CXR + assess.
📄 One Pager
ICU · Ventilator · One Pager
Mechanical Ventilation
Know your numbers every morning. When in doubt — disconnect and bag. DOPE for acute deterioration. SAT + SBT daily to get them off the vent.
Initial Settings
ModeAC/VC (most common)
Tidal volume6–8 mL/kg IBW
Rate14–16 /min
FiO₂1.0 → wean to SpO₂ 94–98%
PEEP5 cmH₂O (start)
Acute Deterioration — DOPE
- D — Displacement (ETT too deep/dislodged)
- O — Obstruction (mucus plug, biting)
- P — Pneumothorax → needle decompress
- E — Equipment failure → bag the patient
Pressure Interpretation
- High Peak, Normal Plat: Airway resistance → suction, bronchodilator
- High Peak + High Plat: Compliance problem → PTX, ARDS, edema
- Driving pressure = Pplat − PEEP. Target ≤ 15.
Weaning — Daily SAT + SBT Girard 2008
- Stop sedation daily (SAT)
- SBT on CPAP 5 / PS 5–8 for 30–120 min
- RSBI < 105 = ready to extubate
- Pass both → extubate
📣 Sample Presentation
One-Liner
"Mr. Brown is a 64-year-old intubated for COPD exacerbation with hypercapnic respiratory failure. Currently on AC/VC: TV 450, RR 16, PEEP 5, FiO₂ 30%. Morning ABG: pH 7.38, pCO₂ 52, pO₂ 88."
Key Points to Cover on Rounds
Intubation indication: hypercapnic respiratory failure (pH 7.22, pCO₂ 78 on presentation, failed BiPAP). Current ABG improved: pH 7.38, pCO₂ 52 (his baseline is ~48). Vent: AC/VC, TV 450 mL (6 mL/kg), RR 16, PEEP 5, FiO₂ 30%. Plateau 22, no auto-PEEP. Sedation: propofol off, RASS 0, following commands. SAT passed, SBT with PSV 5/5 × 30 min — RR 18, TV 380, no distress. Plan: extubate today. BiPAP standby. Nebs q4h.
Cardiogenic Shock
Cardiac pump failure causing inadequate tissue perfusion. Cold, clammy, hypotensive with elevated filling pressures. In-hospital mortality 40–50%. Identify and reverse the cause — fast.
🔍 Overview
Definition & Criteria
Cardiogenic shock = cardiac pump failure resulting in tissue hypoperfusion. Classic hemodynamic criteria: SBP < 90 mmHg for > 30 min (or vasopressor requirement), CI < 2.2 L/min/m², PCWP > 15 mmHg.
Causes
| Cause | Key Features |
|---|---|
| Acute MI / ACS (~70–80%) | Most common cause. Large anterior STEMI, RV infarct. Emergent PCI/cath lab. SHOCK trial: early revascularization ↓ 6-month mortality SHOCK, 1999. |
| Acute decompensated HFrEF (~10–15%) | End-stage HF on maximal GDMT. Progressive pump failure. Bridge to LVAD/transplant or palliative. |
| Acute valvular emergency (~5–8%) | Acute severe MR (papillary muscle rupture post-MI), acute AR (endocarditis, aortic dissection), critical AS. Emergent surgical consult. |
| Fulminant myocarditis (~2–5%) | Viral (Coxsackie, parvovirus B19), giant cell, eosinophilic. Young patient, rapid-onset HF. MRI if stable, biopsy if refractory. May need mechanical circulatory support (MCS) bridge to recovery. |
| Massive PE (~2–3%) | RV failure from acute pressure overload. Not true "pump" failure — it's obstructive. tPA, catheter-directed therapy, or surgical embolectomy. |
| Cardiac tamponade (~1–2%) | Beck's triad: hypotension, JVD, muffled heart sounds. Pulsus paradoxus > 10 mmHg. Emergent pericardiocentesis. |
| Arrhythmia-induced (~1–2%) | Refractory VT/VF, complete heart block, tachycardia-mediated cardiomyopathy. Treat the rhythm — cardioversion, pacing, amiodarone. |
| Takotsubo (~1–2%) | Apical ballooning, post-emotional/physical stress. Often mimics STEMI. Usually recovers in days to weeks. Supportive care. |
| Post-cardiotomy (~2–6%) | Low CO syndrome post-cardiac surgery (CPB-related stunning). Milrinone or dobutamine. IABP/Impella if refractory. |
Recognition — Cold & Wet Profile
- Hypotension (SBP < 90) + cool, clammy extremities
- Mottled skin, cyanosis of peripheries
- Altered mental status (cerebral hypoperfusion)
- Oliguria / anuria (renal hypoperfusion)
- Elevated JVP, S3, pulmonary crackles (elevated filling pressures)
- Lactate > 2 (tissue hypoperfusion)
- Do NOT give aggressive fluids — will worsen pulmonary edema without improving CO
- Do NOT use beta-blockers, calcium channel blockers, or nitrates in acute CS
🧪 Workup & Diagnosis
Immediate Workup
ECHO is the most important early test. Get it immediately — confirms diagnosis, identifies cause, guides management.
- ECG immediately — rule out STEMI (immediate cath lab activation), complete heart block, arrhythmia
- Bedside echo — EF, wall motion abnormalities, tamponade, valvular emergency, RV failure
- Troponin, BNP — confirm myocardial injury, severity of HF
- ABG — lactate, acid-base (metabolic acidosis = bad sign)
- BMP — creatinine, K⁺, glucose
- CXR — pulmonary edema, cardiomegaly
- Invasive monitoring (PA catheter / arterial line) — if diagnosis uncertain or refractory to treatment
Hemodynamic Profiles by PA Catheter
| Shock Type | CO | SVR | PCWP |
|---|---|---|---|
| Cardiogenic | ↓↓ | ↑↑ | ↑↑ |
| Distributive (Septic) | ↑ or normal | ↓↓ | Low/normal |
| Hypovolemic | ↓ | ↑ | ↓↓ |
| Obstructive (PE/Tamponade) | ↓ | ↑ | Variable |
🚨 Management
Management
Immediate
ABCs, ICU transfer, arterial line, central line. Cardiac monitoring. Call cardiology immediately. If STEMI — activate cath lab NOW (door-to-balloon < 90 min). Do NOT delay revascularization for hemodynamic stabilization.
Vasopressors (MAP target ≥ 65)
Norepinephrine first-line for vasopressor support. Do NOT use dopamine (increased arrhythmias in SHOCK trial). Add vasopressin or epinephrine for refractory hypotension.
Inotropes (for low CO)
Dobutamine 2–20 mcg/kg/min — increases CO, reduces afterload. Use when MAP is adequate but CO is still low (cold, not adequately responding to pressors alone). Can cause hypotension and tachyarrhythmias.
Revascularization (if ACS)
Emergency PCI SHOCK 1999: early revascularization reduces 1-year mortality in cardiogenic shock from MI. Do not delay for stabilization. Surgical revascularization if anatomy unsuitable for PCI.
Mechanical Circulatory Support
IABP (intra-aortic balloon pump) — no mortality benefit IABP-SHOCK II 2012. Impella or ECMO for refractory CS. Consider early in rapidly deteriorating patients — get mechanical circulatory support (MCS) team involved before the patient is "too sick."
Treat the Cause
Tamponade → pericardiocentesis. Acute severe MR/VSD → surgery. Fulminant myocarditis → steroids + mechanical circulatory support (MCS) bridge. Complete heart block → temporary pacing. Identify and reverse.
💊 Medications & Doses
Medications
| Drug | Dose | Role | Notes |
|---|---|---|---|
| Norepinephrine (Levophed) 1ST LINE | 0.1–1 mcg/kg/min | First-line vasopressor | Preferred over dopamine in CS. Increases MAP without excessive tachycardia. |
| Dobutamine (Dobutrex) | 2–20 mcg/kg/min | Inotrope | ↑CO, ↓SVR. Use when MAP adequate but CO still low. Titrate to clinical response. Can cause arrhythmias. |
| Milrinone (Primacor) | 0.375–0.75 mcg/kg/min | Inotrope/vasodilator | PDE3 inhibitor. Good in chronic HF (not beta-blocked). Avoid if hypotensive (vasodilatory). Renally cleared. |
| Vasopressin (Pitressin) | 0.03–0.04 units/min | Vasopressor add-on | Nonadrenergic — useful adjunct to reduce catecholamine dose. Fixed dose. |
| Aspirin + Heparin | 325 mg PO + UFH per ACS protocol | ACS-associated CS | Antiplatelet + anticoagulation for PCI. Do not hold for hemodynamic instability. |
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Kim is a 61-year-old with no known cardiac history who presented with anterior STEMI complicated by cardiogenic shock. He underwent emergency PCI with stenting of the LAD. Echo post-cath shows EF of 20% with anterior wall akinesis. He was started on norepinephrine and dobutamine in the cath lab. He is on NE 0.3 mcg/kg/min and dobutamine 10 mcg/kg/min. This morning his MAP is 67, lactate trending down from 6.2 to 3.1, UO 40 mL/hr. He remains intubated. We are in contact with our mechanical circulatory support (MCS) team regarding Impella consideration given refractory shock. Cardiology and cardiac surgery are both following."
Pimp Questions
Why is dopamine avoided in cardiogenic shock?
SOAP II, 2010 and SHOCK trial subgroup: dopamine causes significantly more arrhythmias (especially atrial fibrillation) compared to norepinephrine in cardiogenic and other shock states, without mortality benefit. Norepinephrine is safer and equally effective.
What did the IABP-SHOCK II trial show?
IABP-SHOCK II 2012: Intra-aortic balloon pump did NOT reduce 30-day mortality in cardiogenic shock complicating MI compared to medical therapy alone. This changed practice — IABP is no longer routinely recommended for CS despite being widely used before this trial.
How do you differentiate cardiogenic shock from septic shock at the bedside?
Cardiogenic: cold extremities, mottled, elevated JVP, pulmonary edema (crackles), narrow pulse pressure, low-output state. Echo: poor EF, dilated LV. PA catheter: CI < 2.2, PCWP > 15, elevated SVR. Septic: warm extremities (early), bounding pulses, wide pulse pressure, dry lungs, high-output state. Echo: hyperdynamic LV. PA catheter: CI > 2.5, PCWP low/normal, low SVR. The quickest bedside tool: feel the extremities (cold = cardiogenic, warm = distributive) and do a bedside echo (squeeze vs no squeeze).
A patient with cardiogenic shock has MAP 62 on norepinephrine but cardiac index is 1.4. What do you add?
Add an inotrope — dobutamine or milrinone. The MAP is adequate (≥65) but cardiac output is critically low (CI < 2.2). Norepinephrine raises MAP via vasoconstriction but doesn't improve forward flow. Dobutamine (β₁ > β₂): increases contractility and CO, first-line inotrope. Start 2.5 mcg/kg/min, titrate to CI > 2.2. Risk: tachycardia, hypotension from β₂ vasodilation. Milrinone (PDE3 inhibitor): increases contractility + vasodilation (inodilator). Better for RV failure and pulmonary hypertension. Risk: more hypotension than dobutamine — avoid if MAP borderline. Key principle: vasopressors fix MAP, inotropes fix flow.
What is an Impella and how does it differ from IABP and ECMO?
Impella: percutaneous axial flow pump placed across the aortic valve (femoral artery → LV). Actively pumps blood from LV into aorta. Provides 2.5-5.5 L/min support depending on device. Unloads the LV (reduces wall stress, O₂ demand). IABP: inflates in diastole (augments coronary perfusion), deflates in systole (reduces afterload). Only provides ~0.5 L/min augmentation — modest hemodynamic support. No mortality benefit IABP-SHOCK II, 2012. VA-ECMO: full cardiopulmonary bypass — drains venous blood, oxygenates it, returns it to the arterial system. Provides up to 4-6 L/min. BUT increases LV afterload (ECMO pushes blood retrograde into aorta → LV has to pump against it). Often paired with Impella for LV venting ("ECPELLA").
Why does VA-ECMO increase LV afterload, and why is that dangerous?
VA-ECMO returns oxygenated blood into the femoral artery → flows retrograde into the aorta → increases aortic pressure against which the LV must eject. If the LV is too weak to open the aortic valve against this increased pressure, the LV becomes a stagnant, distended chamber → LV distension → increased wall stress → increased O₂ demand → worsening ischemia → pulmonary edema (blood backs up into lungs). This is why patients on VA-ECMO often need LV venting — either an Impella (ECPELLA strategy), atrial septostomy, or surgical LV vent. Signs of inadequate LV decompression on ECMO: no aortic valve opening on echo, LV distension, worsening pulmonary edema, rising PCWP.
What is the SCAI classification of cardiogenic shock and why does it matter?
SCAI shock classification (Society for Cardiovascular Angiography and Interventions) stages A through E: A = At risk (large MI, no shock), B = Beginning (hypotension or tachycardia, but adequate perfusion), C = Classic (hypoperfusion requiring intervention — pressors or MCS), D = Deteriorating (failing initial therapy, escalating support), E = Extremis (refractory shock, CPR, multiple pressors at max). Why it matters: it standardizes communication ("this is a SCAI C patient"), guides escalation (stage D → activate MCS team immediately), and predicts mortality (stage E = ~70% mortality). It replaces vague terms like "mild shock" or "severe shock" with a universal framework.
A patient has an acute massive MI with cardiogenic shock. Should you stabilize hemodynamics before taking them to the cath lab?
NO — do NOT delay revascularization to "stabilize" the patient. The SHOCK, 1999 trial showed that early revascularization (PCI or CABG within 6h) reduced 6-month mortality from 63% to 50% compared to initial medical stabilization. The myocardium is dying — every minute of delay = more infarct → worse pump function → deeper shock. Start pressors and inotropes while preparing for cath, not instead of cath. Place an Impella or IABP in the cath lab if needed for hemodynamic support during PCI. The cath lab IS the treatment for MI-related cardiogenic shock.
What are the mechanical complications of MI that cause cardiogenic shock, and how do you diagnose them?
Three mechanical complications (typically 3-7 days post-MI): (1) Ventricular septal rupture (VSR): new harsh holosystolic murmur + step-up in O₂ sat from RA to PA on PA catheter. Echo: VSD with L→R shunt. Treatment: surgical repair (emergent). (2) Papillary muscle rupture: new severe MR (holosystolic murmur at apex, but may be soft if severe). PA catheter: large V waves on PCWP tracing. Echo: flail mitral leaflet. Treatment: emergent surgical repair. (3) Free wall rupture: sudden PEA arrest, hemopericardium → tamponade. Usually fatal. Echo: pericardial effusion + tamponade. Treatment: emergent pericardiocentesis → surgery. Key: any acute hemodynamic deterioration 3-7 days post-MI → get an immediate echo to rule out mechanical complications.
How do you use a PA catheter to guide management in cardiogenic shock?
PA catheter (Swan-Ganz) gives 4 key hemodynamic parameters: (1) CI (cardiac index): < 2.2 = cardiogenic shock. Target > 2.2 with inotropes. (2) PCWP: > 15 = volume overloaded / high filling pressures. Guide diuresis or vasodilator therapy. (3) SVR: elevated in cardiogenic shock (compensatory vasoconstriction). If very high (> 1,800) → afterload reduction may improve forward flow. (4) Mixed venous O₂ sat (SvO₂): < 60% = inadequate tissue O₂ delivery. Trending SvO₂ is a real-time monitor of cardiac output adequacy. Clinical profiles by PA catheter: High PCWP + low CI = LV failure (wet and cold). Low PCWP + low CI = RV failure or hypovolemia (dry and cold). High PCWP + high CI = not true cardiogenic shock (consider sepsis + volume overload).
⚡ Summary
Summary
Definition
SBP < 90 + CI < 2.2 + PCWP > 15. Cold, clammy, low output despite adequate filling pressures.
Most Common Cause
Acute MI (large anterior STEMI). Always get ECG immediately and activate cath lab if STEMI.
Vasopressors
Norepinephrine first. NOT dopamine (arrhythmias). Add vasopressin or epinephrine if refractory.
Inotropes
Dobutamine when MAP adequate but CO still low. Milrinone alternative (avoid if hypotensive).
Key Intervention
Treat the cause. PCI for ACS. Pericardiocentesis for tamponade. Early mechanical circulatory support (MCS) if refractory.
Mortality
40–50%. Early revascularization + mechanical circulatory support (MCS) = best chance. Do not delay PCI for "stabilization."
📄 One Pager
ICU · Cardiology · One Pager
Cardiogenic Shock
Cold, clammy, low output with elevated filling pressures. Mortality 40–50%. Treat the cause fast. NE first, NOT dopamine. Early mechanical circulatory support (MCS) if refractory.
Definition & Causes
- SBP < 90 + CI < 2.2 + PCWP > 15
- Acute MI (large anterior STEMI)
- Acute valvular emergency
- Fulminant myocarditis
- Massive PE / tamponade
Key Workup
- ECG immediately — activate cath lab if STEMI
- Echo — EF, wall motion, tamponade, RV
- Troponin, BNP, ABG, lactate
- PA catheter if diagnosis unclear
Management
1
ICU, art line + central line. Call cardiology immediately. Do NOT delay PCI for "stabilisation."
2
Norepinephrine (NOT dopamine SOAP II, 2010) for MAP ≥ 65. Add vasopressin if refractory.
3
Dobutamine 2–20 mcg/kg/min if MAP adequate but CO still low.
4
Emergency PCI if STEMI SHOCK 1999 — early revascularisation reduces 1-year mortality.
5
Mechanical circulatory support — Impella/ECMO if refractory. IABP no longer routine IABP-SHOCK II 2012.
6
Treat the cause: Drain tamponade, pace if heart block, repair valve, treat myocarditis.
Drugs
Norepinephrine (Levophed)0.1–1 mcg/kg/min
Dobutamine (Dobutrex)2–20 mcg/kg/min
Vasopressin (Vasostrict)0.03 u/min
Milrinone (Primacor)0.375–0.75 mcg/kg/min
Do NOT Use
- Dopamine (↑ arrhythmias)
- Beta-blockers
- CCBs
- Aggressive fluids
- IABP routinely
Differentiating Shock
CO↓↓ (vs ↑ in sepsis)
SVR↑↑ (vs ↓ in sepsis)
PCWP↑↑ (vs low in sepsis)
📈 Monitoring
Monitoring Parameters — Cardiogenic Shock
| Parameter | Frequency | Target / Action |
|---|---|---|
| MAP (arterial line) | Continuous (art line mandatory) | MAP ≥ 65 mmHg. Art line is standard of care in CS — cuff pressures are unreliable in low-output states. |
| CVP / ScvO₂ | Continuous if PA catheter in place | ScvO₂ > 70% suggests adequate O₂ delivery. Low ScvO₂ = inadequate cardiac output or ↑ O₂ extraction. Guide inotrope titration. |
| Lactate | q2–4h | Lactate clearance = improving. Falling lactate is the best marker of resuscitation adequacy. Rising or static lactate despite pressors → escalate (MCS consideration). |
| Urine output | Continuous (Foley) | UOP ≥ 0.5 mL/kg/hr. Oliguria reflects renal hypoperfusion. Falling UOP despite adequate MAP → worsening CO. |
| Mixed venous O₂ (SvO₂) | Continuous if PA catheter | SvO₂ < 60% = inadequate tissue O₂ delivery. Real-time surrogate of cardiac output adequacy. Trend over time. |
| Cardiac output / index | q4–6h or continuous (PA catheter / Vigilance) | Target CI > 2.2 L/min/m². Guide inotrope titration. If CI remains < 2.0 on maximal medical therapy → escalate to MCS. |
| Vasopressor / inotrope doses | Continuous titration, document q1h | Track trajectory — escalating pressors = worsening shock. Weaning = improving. Document total doses on rounds for trending. |
| End-organ perfusion | q2–4h assessment | Mental status (confusion = cerebral hypoperfusion), skin (mottling, cool extremities, capillary refill > 3s), extremities (cyanosis). The bedside exam matters more than any number. |
| Serial echocardiography | Daily or with clinical change | EF trending, wall motion changes, new MR, tamponade, RV function. Guides decisions on MCS and recovery potential. |
| LFTs / Creatinine | Daily (BID if deteriorating) | Rising AST/ALT = shock liver (hepatic hypoperfusion). Rising Cr = AKI from low output. End-organ injury = failing resuscitation. |
Escalation triggers: Rising lactate, escalating pressors, UOP < 0.3 mL/kg/hr, CI < 1.8 despite inotropes, new end-organ injury (shock liver, AKI) — activate MCS team early. Do not wait until the patient is too sick for mechanical support.
Hypertensive Emergency
BP usually > 180/120 with acute end-organ damage. The organ being damaged determines the drug and the target. Do NOT drop BP too fast — cerebral autoregulation cannot keep up.
🔍 Overview
Hypertensive Emergency vs Urgency
Emergency: Severely elevated BP + acute end-organ damage. Requires IV therapy, ICU admission, controlled BP reduction.
Urgency: Severely elevated BP without end-organ damage. Can be managed with oral agents and close outpatient follow-up. NOT an emergency. Outpatient target: SBP <130 for high-risk patients SPRINT, 2015. First-line: thiazide-type diuretic ALLHAT, 2002.
Urgency: Severely elevated BP without end-organ damage. Can be managed with oral agents and close outpatient follow-up. NOT an emergency. Outpatient target: SBP <130 for high-risk patients SPRINT, 2015. First-line: thiazide-type diuretic ALLHAT, 2002.
End-Organ Damage to Look For
- Neurologic: Hypertensive encephalopathy (AMS, headache, vision changes), hemorrhagic stroke, ischemic stroke
- Cardiac: Aortic dissection, ACS, acute pulmonary edema
- Renal: AKI, hematuria, proteinuria (hypertensive nephrosclerosis)
- Ophthalmologic: Papilledema, retinal hemorrhages (fundoscopy)
- Hematologic: Microangiopathic hemolytic anemia (MAHA), TTP-like picture
- OB: Eclampsia, HELLP syndrome
Aortic Dissection must be excluded first if BP very high + chest/back pain. Different drugs, different targets. CTA chest/abdomen/pelvis immediately. Do NOT give nitroprusside until dissection excluded.
🚨 Management
BP Reduction Targets — By Syndrome
General Rule: Reduce MAP by no more than 25% in the first hour, then to 160/100 over the next 2–6 hours. Exception: aortic dissection (aggressive), ischemic stroke (conservative).
| Syndrome | Target | First-Line Drug |
|---|---|---|
| Hypertensive encephalopathy | MAP reduction 20–25% in 1h | Nicardipine or labetalol IV |
| Aortic dissection (Type A/B) | SBP < 120, HR < 60 ASAP | Esmolol + nitroprusside or nicardipine |
| Acute pulmonary edema | Rapid reduction | Nicardipine + nitroglycerin IV + diuresis |
| ACS with hypertension | SBP < 140 | Nitroglycerin IV + beta-blocker |
| Ischemic stroke | Only treat if BP > 220/120 (no tPA) or > 185/110 (if tPA candidate) [AHA/ASA, 2019 | Labetalol or nicardipine IV — go slow |
| Hemorrhagic stroke | SBP < 140 ATACH-2, 2016 INTERACT2, 2013 | Nicardipine or labetalol IV |
| Eclampsia | SBP < 160, DBP < 110 | Labetalol IV or hydralazine IV + MgSO₄ MAGPIE, 2002 |
| Pheochromocytoma crisis | MAP reduction 20–25% | Phentolamine IV — α-blockade first, then add beta-blocker |
Never use beta-blockers alone in pheochromocytoma. Unopposed α stimulation → paradoxical hypertensive crisis. Always α-block first.
📋 Clinical Example — Hypertensive Emergency Management
- Patient: 52M presents with BP 228/134, headache, blurred vision, chest pain. Cr 2.4 (baseline 1.0). Troponin 0.08. UA: 2+ protein, RBC casts.
- This is a hypertensive EMERGENCY (not urgency) — end-organ damage present: AKI, proteinuria with active sediment (renal), troponin elevation (cardiac), visual changes (retinal/CNS).
- Step 1 — Choose IV agent based on end-organ damage:
- Renal damage → Nicardipine (Cardene) 5mg/hr IV, titrate by 2.5mg/hr q5-15min (max 15mg/hr). Smooth, titratable, no renal dosing needed.
- Aortic dissection → Esmolol (Brevibloc) drip first (target HR <60), THEN add nicardipine. Must reduce HR before afterload reduction.
- Acute pulmonary edema → Nitroglycerin (Nitrostat) drip + furosemide (Lasix).
- Eclampsia → Magnesium sulfate + hydralazine (Apresoline) or labetalol (Trandate).
- Stroke → see specific stroke BP targets (different for ischemic vs hemorrhagic, tPA vs no tPA).
- Step 2 — BP target:
- Reduce MAP by no more than 25% in the first hour. Then toward 160/100 over next 2-6 hours.
- Do NOT normalize BP rapidly → risk of watershed infarction (brain, kidneys).
- Exception: Aortic dissection → SBP <120 within 20 minutes.
- Step 3 — Transition to oral:
- Once stable on IV × 12-24h → start oral antihypertensive (amlodipine 5-10mg, lisinopril, etc.).
- Overlap IV + PO for 2-4 hours before weaning drip.
- Hypertensive URGENCY (BP >180/120 WITHOUT end-organ damage): Do NOT use IV meds. Restart/uptitrate oral meds. Discharge with close follow-up. The BP did not get this high overnight and does not need to come down overnight.
💊 Medications & Doses
IV Antihypertensive Agents
| Drug | Dose | Onset | Best For | Avoid In | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nicardipine (Cardene) | 5–15 mg/hr IV drip | 5–10 min | Most hypertensive emergencies. Excellent titratable agent. | Advanced aortic stenosis | ||||||||||||||||||||||||||||||||||||
| Labetalol (Trandate) | 20–80 mg IV bolus q10min, or 0.5–2 mg/min drip | 5 min | Aortic dissection, stroke, eclampsia | Asthma, severe bradycardia, acute HF | ||||||||||||||||||||||||||||||||||||
| Esmolol (Brevibloc) | 500 mcg/kg bolus, then 50–200 mcg/kg/min | 1–2 min | Aortic dissection (HR control) | Bronchospasm, bradycardia | ||||||||||||||||||||||||||||||||||||
| Sodium Nitroprusside | 0.3–10 mcg/kg/min | Seconds | Hypertensive emergency when other agents fail | Renal failure (cyanide toxicity), elevated ICP, pregnancy | ||||||||||||||||||||||||||||||||||||
| Nitroglycerin (Nitrostat) | 5–200 mcg/min IV | 1–2 min | Pulmonary edema, ACS | Aortic dissection (reflex tachycardia), PDE5 inhibitor use | ||||||||||||||||||||||||||||||||||||
| Hydralazine (Apresoline) | 10–20 mg IV q4–6h | 10–20 min | Eclampsia (if labetalol not available) | Aortic dissection, aortic aneurysm
🧪 Workup
Workup — Hypertensive Emergency
The workup answers ONE question: Is there end-organ damage? YES → hypertensive emergency (IV meds, ICU). NO → hypertensive urgency (oral meds, outpatient). The BP number alone does NOT define the emergency.
Emergency vs Urgency: Emergency = elevated BP + end-organ damage → IV meds, ICU, reduce MAP 25% in first hour. Urgency = elevated BP WITHOUT damage → oral meds, discharge with follow-up 24-72h. Do NOT use IV meds for urgency.
|
📊 Monitoring
Monitoring Parameters — Hypertensive Emergency
| Parameter | Frequency | Target / Action |
|---|---|---|
| Arterial line BP | Continuous (art line mandatory in ICU) | Reduce MAP no more than 25% in the first hour. Cuff pressures are insufficient for IV drip titration — art line is standard of care. |
| MAP during titration | q5–15 min while adjusting IV drip | First hour: ≤ 25% MAP reduction. Next 2–6h: target ~160/100. Next 24–48h: gradual normalization. Too fast → watershed stroke. |
| Neuro checks | q1–2h during active titration | GCS, pupil reactivity, focal deficits, level of consciousness. New deficit during BP lowering → stop titration, allow BP to rise, urgent imaging (stroke?). |
| Urine output | q1h (Foley) | UOP ≥ 0.5 mL/kg/hr. Declining UOP during BP reduction = renal hypoperfusion — may need to allow higher BP target. |
| Creatinine | q12–24h | Trend from baseline. Rising Cr suggests renal end-organ injury or overly aggressive BP lowering. Adjust target accordingly. |
| Troponin | On admission, repeat at 6h if elevated or ongoing chest pain | Hypertensive emergency can cause demand ischemia (type 2 MI). Elevated troponin changes management — cardiology consult. |
| Fundoscopic exam | On admission, repeat if worsening | Papilledema, flame hemorrhages, cotton-wool spots, AV nicking. Presence confirms end-organ damage and classifies as true emergency vs urgency. |
| Transition to oral agents | After 12–24h stable on IV drip | Start long-acting oral antihypertensives (amlodipine, lisinopril, etc.) with IV drip overlap. Wean drip gradually as oral agents take effect (24–48h). Do not abruptly stop IV. |
BP reduction timeline: 25% MAP reduction in first hour → 160/100 over next 2–6h → gradual normalization over 24–48h. Exception: aortic dissection — target SBP < 120 + HR < 60 within minutes (esmolol + nicardipine). Exception: ischemic stroke — do NOT lower BP unless > 220/120 (or > 185/110 if tPA candidate).
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mrs. Okafor is a 58-year-old with poorly controlled hypertension who presented with BP 210/130, severe headache, and confusion. She was found to have papilledema on fundoscopy and elevated creatinine of 2.8 from a baseline of 1.0, consistent with hypertensive emergency with end-organ damage involving the CNS and kidneys. CT head showed no hemorrhage. She was started on nicardipine drip and MAP was reduced by 22% over the first hour to 147. She is now alert, BP 158/96 on nicardipine 8 mg/hr. Plan is to continue gradual reduction to target BP 150/90 over the next 24–48 hours, then transition to oral agents."
Pimp Questions
Why should you not lower BP too fast in hypertensive emergency?
Chronic hypertension shifts the cerebral autoregulation curve rightward. These patients need higher perfusion pressures to maintain cerebral blood flow. Rapid BP reduction causes cerebral ischemia — watershed infarcts, blindness (anterior ischemic optic neuropathy), renal infarction. Max 25% MAP reduction in first hour.
What is the BP target for ischemic stroke and why is it different?
Only treat if BP > 220/120 (no tPA) because elevated BP in ischemic stroke maintains perfusion to the ischemic penumbra. Lowering BP aggressively expands the infarct. Exception: if patient is a tPA candidate, reduce to < 185/110 first to reduce hemorrhage risk.
Why do you target only 25% MAP reduction in the first hour instead of normalizing BP?
Cerebral autoregulation is shifted right in chronic hypertension. The brain has adapted to higher pressures — the autoregulatory curve (which maintains constant cerebral blood flow across a range of MAPs) shifts upward. If you drop BP too quickly to "normal" levels, you fall below the lower limit of autoregulation → cerebral hypoperfusion → watershed stroke. The 25% rule: reduce MAP by ~25% in the first hour, then gradually to ~160/100 over 24-48h. Exception: aortic dissection (target SBP 100-120 immediately — the aorta is tearing) and acute ischemic stroke on tPA (target < 180/105).
What IV antihypertensive do you choose for different end-organ emergencies?
Match the drug to the complication: Nicardipine (DHP CCB drip): best all-purpose — works for most emergencies. Smooth, titratable, no CNS depression. Clevidipine: ultra-short acting CCB — good when minute-to-minute control needed. Labetalol: combined α/β blocker — good for aortic dissection (reduces HR + BP), preeclampsia (safe in pregnancy). Esmolol: ultra-short BB — best for dissection when you need rapid HR < 60. Nitroprusside: potent vasodilator — use if refractory, but risk of cyanide toxicity > 48h. Avoid in renal failure. Fenoldopam: dopamine-1 agonist — renal-protective, used in AKI-associated hypertensive emergency. Hydralazine: avoid for emergencies (unpredictable, long-lasting, reflex tachycardia).
⚡ Summary
Summary
Emergency vs Urgency
Emergency = high BP + end-organ damage (CNS, cardiac, renal, eyes). Urgency = high BP alone. Different management entirely.
Exclude First
Aortic dissection — if chest/back pain + high BP. CTA immediately. Requires aggressive reduction and beta-blockade.
BP Reduction Rule
Reduce MAP by ≤ 25% in first hour. Then to 160/100 over next 6 hrs. Except dissection (aggressive) and ischemic stroke (conservative).
Go-To Drug
Nicardipine IV — titratable, reliable, works for most emergencies. Labetalol for dissection/stroke/eclampsia.
Pheo Rule
Alpha-block FIRST (phentolamine), THEN add beta-blocker. Never beta-block first — causes unopposed alpha hypertensive crisis.
Nitroprusside Warning
Risk of cyanide toxicity in renal failure and prolonged use. Also causes elevated ICP. Use only when other agents fail.
📄 One Pager
ICU · One Pager
Hypertensive Emergency
End-organ damage defines the emergency. The organ being damaged determines the drug and the target. Never drop BP > 25% in first hour.
Exclude First — Aortic Dissection
- Chest/back pain + very high BP → CTA chest/abdomen NOW
- Target SBP < 120, HR < 60 ASAP
- Esmolol + nicardipine or nitroprusside
- Never nitrates alone (reflex tachycardia)
BP Reduction Rule
- Reduce MAP ≤ 25% in first hour
- Then to 160/100 over 2–6h
- Exception: Dissection (aggressive) and ischemic stroke (conservative)
- Ischemic stroke: only treat if BP > 220/120
Drug by Syndrome
Most emergenciesNicardipine 5–15 mg/hr IV
Aortic dissectionEsmolol + nicardipine
ACS / pulmonary edemaNitroglycerin IV + labetalol
Stroke (hemorrhagic)Nicardipine → SBP < 140
EclampsiaLabetalol IV + MgSO₄
PheochromocytomaPhentolamine (α first!) then β-blocker
Pheo Rule
- α-block FIRST with phentolamine
- THEN add beta-blocker
- Beta-block first → unopposed α → crisis
Why Not Too Fast?
- Chronic HT shifts autoregulation rightward
- Rapid drop → cerebral ischemia
- Watershed infarcts, blindness, renal infarction
Status Epilepticus
Continuous seizure activity > 5 minutes or ≥ 2 seizures without return to baseline. A neurological emergency — every minute of seizure activity causes irreversible neuronal death. Stop it now.
🔍 Overview
Definitions
Status epilepticus (SE): Seizure ≥ 5 minutes OR ≥ 2 seizures without return to baseline between them.
Refractory SE: Failure of 2 first-line agents (benzodiazepine + second AED) — requires ICU admission and anesthetic agents.
Super-refractory SE: SE persisting ≥ 24 hours after initiation of anesthetic agents, including recurrence on weaning.
Refractory SE: Failure of 2 first-line agents (benzodiazepine + second AED) — requires ICU admission and anesthetic agents.
Super-refractory SE: SE persisting ≥ 24 hours after initiation of anesthetic agents, including recurrence on weaning.
Causes
- Known epilepsy + subtherapeutic AED levels (most common)
- Acute CNS insult: stroke, hemorrhage, encephalitis, meningitis, trauma, tumor
- Metabolic: severe hyponatremia, hypoglycemia, hypocalcemia, uremia
- Toxins/withdrawal: alcohol withdrawal, cocaine, TCAs, isoniazid
- Anoxic brain injury (post-cardiac arrest)
- Autoimmune encephalitis (anti-NMDA receptor — especially young women)
Non-Convulsive SE (NCSE)
Don't miss this. NCSE presents as altered mental status, confusion, or subtle motor movements without obvious convulsions. Common after convulsive SE is "treated." Only diagnosed by EEG. Any patient with AMS after a seizure who doesn't wake up → get EEG.
🚨 Management
Status Epilepticus Protocol — Time Is Neurons
0–5 Minutes — Stabilize
ABCs, O₂, IV access, cardiac monitor. POC glucose STAT. If hypoglycemic → D50W 50 mL IV. Check temperature (fever → cooling). Place patient safely, do NOT restrain or put anything in mouth.
5 Minutes — Phase 1: Benzodiazepine (First-Line)
IV access available: Lorazepam 0.1 mg/kg IV (max 4 mg), repeat × 1 in 5 min if no response
No IV access: Midazolam 10 mg IM (IM is as fast as IV — do not delay for IV access)
RAMPART 2012: IM midazolam = IV lorazepam in efficacy. Use IM if no IV.
No IV access: Midazolam 10 mg IM (IM is as fast as IV — do not delay for IV access)
RAMPART 2012: IM midazolam = IV lorazepam in efficacy. Use IM if no IV.
20 Minutes — Phase 2: Second AED (if benzo fails)
Give ONE of: Levetiracetam 60 mg/kg IV (max 4500 mg) over 10 min — preferred (fewest drug interactions, no respiratory depression) OR Valproate 40 mg/kg IV over 10 min (avoid in liver disease, pregnancy, metabolic disorders) OR Fosphenytoin 20 mg PE/kg IV (slower, cardiac monitoring needed, avoid in liver disease).
ESETT 2019: all three equally effective (~50% seizure termination at 60 min).
ESETT 2019: all three equally effective (~50% seizure termination at 60 min).
40 Minutes — Phase 3: Refractory SE → ICU + Anesthetic
Intubate + continuous EEG.
Options: Propofol 2 mg/kg IV bolus then 1–15 mg/kg/hr drip OR Midazolam 0.2 mg/kg IV bolus then 0.05–2 mg/kg/hr drip OR Ketamine 1.5 mg/kg IV bolus then 1.2–5 mg/kg/hr (NMDA antagonist, neuroprotective, less respiratory depression).
Neurology and/or epilepsy consult. Continuous EEG mandatory to detect NCSE and guide treatment.
Options: Propofol 2 mg/kg IV bolus then 1–15 mg/kg/hr drip OR Midazolam 0.2 mg/kg IV bolus then 0.05–2 mg/kg/hr drip OR Ketamine 1.5 mg/kg IV bolus then 1.2–5 mg/kg/hr (NMDA antagonist, neuroprotective, less respiratory depression).
Neurology and/or epilepsy consult. Continuous EEG mandatory to detect NCSE and guide treatment.
Concurrent — Find the Cause
CT head (hemorrhage, structural lesion), LP (meningitis/encephalitis — unless ICP elevated), metabolic panel, AED levels, toxicology screen, anti-NMDA/LGI1 antibodies if young woman with encephalopathy, EEG (NCSE).
📋 Clinical Example — Status Epilepticus Management
- Patient: 28M found seizing in ED, generalized tonic-clonic. Ongoing seizure for 8 minutes. No IV access yet.
- 0-5 min (Stabilize): ABCs, O2, glucose check. Position safely. Time the seizure.
- No IV? → Midazolam (Versed) 10mg IM (RAMPART 2012 — IM midazolam non-inferior to IV lorazepam and faster to administer).
- IV obtained? → Lorazepam (Ativan) 4mg IV over 2 min. May repeat × 1 in 5 min.
- 5-20 min (Established status — benzo failed): Choose ONE:
- Levetiracetam (Keppra) 60mg/kg IV (max 4500mg) over 15 min — no cardiac monitoring needed, no drug interactions
- Fosphenytoin 20mg PE/kg IV over 20 min — requires cardiac monitoring (hypotension, arrhythmia risk)
- Valproate (Depakote) 40mg/kg IV over 10 min — avoid in pregnancy, liver disease
- ESETT 2019: All three equally effective (~45% seizure cessation). Choose based on patient factors.
- >20 min (Refractory status — failed 2 agents): Intubate → continuous IV anesthesia:
- Midazolam drip 0.2mg/kg/hr, propofol (Diprivan) 2-5mg/kg/hr, or pentobarbital
- Continuous EEG monitoring. Target: burst suppression for 24-48h, then slowly wean.
- Post-ictal workup: BMP (Na, glucose, Ca, Mg), tox screen, AED levels, CT head, LP if concern for infection. MRI brain when stable.
💊 Medications & Doses
Medications Reference
| Drug | Dose | Phase | Notes |
|---|---|---|---|
| Lorazepam 1ST LINE | 0.1 mg/kg IV, max 4 mg; repeat × 1 | Phase 1 (IV) | First-line if IV access. Respiratory depression risk — have bag-mask ready. |
| Midazolam (Versed) IM | 10 mg IM (> 40 kg); 5 mg (13–40 kg) | Phase 1 (no IV) | RAMPART 2012: non-inferior to IV lorazepam. Faster than establishing IV access. Use the outer thigh. |
| Levetiracetam (Keppra) PREFERRED 2ND | 60 mg/kg IV, max 4500 mg over 10 min | Phase 2 | Preferred second agent. No hepatotoxicity, no CYP interactions, no cardiac monitoring needed. Can cause agitation. |
| Valproate (Depakote) 2ND LINE | 40 mg/kg IV, max 3000 mg over 10 min | Phase 2 | Avoid: liver disease, pregnancy, metabolic disorders (mitochondrial disease). Effective for absence/myoclonic SE. |
| Fosphenytoin 2ND LINE | 20 mg PE/kg IV, max 1500 mg PE | Phase 2 | Cardiac monitoring (hypotension, arrhythmia during infusion). Avoid in liver disease. Give ≤ 150 mg PE/min. |
| Propofol (Diprivan) | 2 mg/kg bolus, then 1–15 mg/kg/hr | Phase 3 (refractory) | Rapid, titratable. Propofol infusion syndrome risk at high doses/prolonged use. Requires intubation. |
| Ketamine (Ketalar) | 1.5 mg/kg IV bolus, then 1.2–5 mg/kg/hr | Phase 3 | NMDA antagonist. Emerging evidence for refractory SE. Bronchodilator. Preserves airway reflexes better. Less hemodynamic compromise.< |
📊 Monitoring
Monitoring
- Continuous EEG
- AED levels
- Neuro exam q2-4h
- Glucose
- CK if prolonged seizure
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Abreu is a 34-year-old with known epilepsy who was brought in with generalized tonic-clonic seizure activity for approximately 12 minutes prior to EMS arrival. He received midazolam 10 mg IM en route with partial response. In the ED he received lorazepam 4 mg IV — the seizure terminated after 3 minutes. He was then loaded with levetiracetam 60 mg/kg IV. His home levetiracetam level was undetectable — consistent with medication non-adherence as the precipitant. CT head is negative. He is currently post-ictal but following commands. EEG is monitoring for non-convulsive status. Neurology is following."
Pimp Questions
Why 5 minutes as the definition of status epilepticus?
Most self-limited seizures stop within 2–3 minutes. Beyond 5 minutes, spontaneous termination becomes unlikely AND neuronal injury from excitotoxicity begins. At 30 minutes, permanent injury is near certain. The operational definition was lowered from 30 to 5 minutes to encourage earlier intervention.
What is the preferred second-line AED and what trial established this?
All three agents are equally effective ESETT 2019 — approximately 50% success at 60 minutes. Levetiracetam is generally preferred due to favorable safety profile: no cardiac monitoring, no hepatotoxicity, fewer drug interactions.
A patient's seizures stopped but they haven't woken up. How long do you wait before worrying?
Post-ictal state typically resolves within 30-60 minutes. If the patient hasn't returned to baseline by 60 min → concern for non-convulsive status epilepticus (NCSE). NCSE = ongoing seizure activity on EEG without visible convulsions — the brain is still seizing but the body isn't moving. This occurs in up to 48% of patients after convulsive status. Get an EEG immediately if there's persistent AMS after apparent seizure cessation. NCSE is treated the same as convulsive SE (benzodiazepines → second-line AED). Without EEG, you cannot distinguish post-ictal state from NCSE from other causes of AMS.
What is the correct sequence of medications in status epilepticus?
Stage 1 (0-5 min): Benzodiazepine — lorazepam 0.1 mg/kg IV (max 4 mg/dose, repeat × 1) OR midazolam 10 mg IM if no IV access. Stage 2 (5-20 min, BZD failed): Second-line AED — levetiracetam 60 mg/kg IV (max 4500 mg) OR fosphenytoin 20 mg PE/kg IV OR valproate 40 mg/kg IV. These are considered equivalent per [ESETT, 2019 trial — choose based on patient factors (valproate: avoid in pregnancy/liver disease; fosphenytoin: avoid in heart block). Stage 3 (20-40 min, refractory): intubate → continuous infusion: midazolam, propofol, or pentobarbital. EEG-guided burst suppression. Key: don't under-dose benzodiazepines — the most common cause of "benzo failure" is inadequate dosing.
⚡ Summary
Summary
Definition
Seizure ≥ 5 min OR ≥ 2 seizures without return to baseline. Every minute = neuronal death.
Phase 1 (0–20 min)
Lorazepam 0.1 mg/kg IV OR midazolam 10 mg IM (no IV access). Check glucose first.
Phase 2 (20–40 min)
Levetiracetam 60 mg/kg IV (preferred), valproate 40 mg/kg, or fosphenytoin 20 mg PE/kg. All equal ESETT 2019.
Phase 3 (refractory)
Intubate + continuous EEG. Propofol or midazolam infusion. Neurology consult. Find the cause.
Don't Miss
Non-convulsive SE — AMS after seizure + no waking up = EEG immediately.
Cause Hunt
AED levels, glucose, lytes, CT head, LP (if no ICP), toxicology. Anti-NMDA antibodies in young women with encephalopathy.
📄 One Pager
ICU · Neurology · One Pager
Status Epilepticus
Every minute of seizure = neuronal death. Three phases. Benzo first. Levetiracetam second. Intubate + EEG if refractory. Don't miss NCSE.
3-Phase Protocol
0
Immediately: ABCs, glucose, IV access, O₂, monitor. Thiamine before glucose.
1
0–20 min — Benzo: Lorazepam 0.1 mg/kg IV (max 4 mg) OR midazolam 10 mg IM if no IV RAMPART 2012
2
20–40 min — 2nd AED: Levetiracetam 60 mg/kg IV (preferred) OR valproate 40 mg/kg OR fosphenytoin 20 mg PE/kg — all equal ESETT 2019
3
> 40 min — Refractory: Intubate + continuous EEG + propofol or midazolam infusion. Neurology consult.
Phase 2 Drugs
Levetiracetam60 mg/kg IV (preferred)
Valproate40 mg/kg IV
Fosphenytoin20 mg PE/kg IV
Find the Cause
- AED levels (non-adherence)
- Glucose, electrolytes
- CT head → LP
- Toxicology screen
- Anti-NMDA antibodies
Don't Miss
- NCSE — AMS after seizure + not waking → EEG now
- Glucose before anything else
- Thiamine before glucose in alcoholic
Upper GI Bleed (UGIB)
Bleeding proximal to the ligament of Treitz. Presentation: hematemesis, coffee-ground emesis, melena, or hemodynamic instability. Mortality 2–10%. Resuscitate first, scope second.
🔍 Overview
Causes
Non-Variceal (80%)
- Peptic ulcer disease (most common — 40–50%) — H. pylori, NSAIDs, stress
- Mallory-Weiss tear (retching → gastroesophageal junction tear)
- Gastritis / duodenitis
- Dieulafoy lesion (large submucosal artery)
- Upper GI malignancy
Variceal (20%)
- Esophageal varices (portal hypertension from cirrhosis)
- Gastric varices
- Higher mortality, requires different initial management (octreotide + antibiotics)
Risk Stratification — Glasgow-Blatchford Score
Used to determine if patients can be managed outpatient vs need urgent endoscopy. Score ≥ 1 → admission. Score 0 → consider outpatient management. Components: BUN, Hgb, SBP, HR, melena, syncope, hepatic disease, cardiac failure.
High-Risk Features Requiring ICU: Hemodynamic instability (HR > 100, SBP < 100), active hematemesis, Hgb < 7, coagulopathy, cirrhosis/varices, on anticoagulants, multiple comorbidities.
🧪 Workup & Diagnosis
Workup
- CBC — Hgb/Hct (may be normal initially — equilibration takes hours), platelets
- BMP — BUN (elevated in UGIB from digestion of blood — BUN:Cr > 20:1 = UGIB), creatinine
- Coags — PT/INR, PTT, fibrinogen (especially if cirrhosis or on anticoagulants)
- Type & Screen — always. Type & Cross if actively bleeding
- LFTs — cirrhosis workup if variceal source suspected
- Nasogastric lavage — controversial; positive (bloody or coffee-ground aspirate) confirms UGIB; negative does not rule out (30% false negative if duodenal source)
- EGD (upper endoscopy) — diagnostic and therapeutic; perform within 24 hours (within 12h if hemodynamically unstable or actively bleeding)
🚨 Management
Management
Immediate Resuscitation
2 large-bore IVs (16G or larger). Airway assessment — intubate if massive hematemesis, AMS, or unable to protect airway. IV crystalloid bolus initially. Transfuse PRBCs if Hgb < 7 (target 7–9). Restrictive transfusion strategy TRIGGER 2015 Villanueva, 2013 improves survival in UGIB.
Variceal vs Non-Variceal Decision
Known cirrhosis or portal hypertension? → Assume variceal until proven otherwise → Start octreotide + IV ceftriaxone immediately (do NOT wait for scope). Non-variceal → IV PPI (pantoprazole) infusion.
PPI Infusion (Non-Variceal)
Pantoprazole 80 mg IV bolus, then 8 mg/hr infusion for 72 hours after endoscopy shows high-risk lesion (Forrest Ia/Ib/IIa) Lau, 2007. Reduces rebleeding from peptic ulcers. Start empirically before scope. Erythromycin 250 mg IV 30 min pre-EGD improves visualization Barkun, 2010.
Endoscopy (EGD)
Within 24 hrs for stable patients. Within 12 hrs for unstable. GI endoscopy team should be called early. Endoscopic hemostasis: epinephrine injection, hemoclip, thermal coagulation, band ligation (varices).
Refractory / Massive Bleeding
Second EGD attempt. IR for embolization (non-variceal). TIPS (transjugular intrahepatic portosystemic shunt) for refractory variceal bleed. Surgery (rare — last resort). Sengstaken-Blakemore tube as temporizing bridge for massive variceal bleed if scope unavailable.
📋 Clinical Example — Upper GI Bleed Management
Patient: 58M on aspirin + clopidogrel (Plavix), presents with melena × 2 days, hematemesis in ED. HR 112, BP 88/54, Hgb 6.8.
Immediate resuscitation:
- 2 large-bore IVs (18G or larger). Type & crossmatch.
- IV LR bolus 1L. Transfuse 2 units pRBC (Hgb < 7, hemodynamically unstable).
- NPO. Proton pump inhibitor: pantoprazole (Protonix) 80mg IV bolus → 8mg/hr drip.
- Hold aspirin and clopidogrel — discuss with cardiology (balancing GI bleed vs stent thrombosis risk).
- Octreotide (Sandostatin) 50mcg IV bolus → 50mcg/hr IF variceal bleed suspected (cirrhosis, known varices). Add ceftriaxone (Rocephin) 1g IV daily for SBP prophylaxis.
- GI consult for EGD within 24h (within 12h if hemodynamically unstable after resuscitation).
Post-EGD: Ulcer with visible vessel found and clipped. Continue PPI IV drip × 72h → then PO PPI BID. Resume aspirin in 3-5 days (cardiovascular benefit > rebleed risk if indicated). Clopidogrel — discuss with cards about timing.
Glasgow-Blatchford Score: Determines need for intervention. Score 0 = safe for outpatient management. This patient scores high → inpatient + urgent EGD.
🔄 Updated Practice: Old teaching: IV PPI drip (pantoprazole 8 mg/hr) for 72 hours in all upper GI bleeds. Current practice: IV PPI bolus is reasonable pre-endoscopy, but the 72-hour drip is only needed if high-risk lesion found on EGD (active bleeding, visible vessel, adherent clot). Clean-base ulcers can switch to PO PPI immediately. Also: pre-endoscopy erythromycin (250 mg IV) improves gastric visualization — increasingly used as a prokinetic before EGD.
💊 Medications & Doses
Medications
| Drug | Dose | Indication | Notes |
|---|---|---|---|
| Pantoprazole (Protonix) | 80 mg IV bolus → 8 mg/hr × 72h | Non-variceal UGIB (high-risk) | Raises gastric pH → stabilizes clot. Start before EGD empirically. Switch to oral after 72h. |
| Octreotide (Sandostatin) | 50 mcg IV bolus → 50 mcg/hr × 3–5 days | Variceal UGIB | ↓ Splanchnic blood flow → ↓ portal pressure. Start as soon as variceal source suspected. Continue 3–5 days post-banding. |
| Ceftriaxone (Rocephin) | 1 g IV daily × 7 days | Variceal UGIB (cirrhosis) | Prophylaxis against SBP and bacterial infections. Significantly reduces mortality. Start with octreotide immediately. |
| FFP / Vitamin K | FFP 2–4 units; Vit K 10 mg IV | Coagulopathy (INR > 1.5–2) | Reverse anticoagulation before endoscopy if significant coagulopathy. Vit K for warfarin reversal. 4-factor PCC if urgent. |
| PRBCs | Transfuse to Hgb 7–9 g/dL | Hemodynamically significant bleed | Restrictive transfusion (target Hgb 7) TRIGGER 2015. Exception: ACS/active cardiac disease — target 8–9. |
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Nguyen is a 67-year-old on aspirin and ibuprofen for knee pain who presented with 2 episodes of hematemesis and melena with initial BP 88/60 and HR 118. He was resuscitated with 2L NS and 2 units of PRBCs, with hemodynamic stabilization. BUN was 44, creatinine 1.1 — BUN:Cr ratio of 40 consistent with UGIB. Hgb on arrival was 8.2, now 9.1 post-transfusion. He is on pantoprazole 8 mg/hr infusion. GI performed EGD this morning showing a 1.5 cm duodenal ulcer with a visible vessel — Forrest IIa. Hemostasis was achieved with hemoclip and epinephrine injection. He is on PPI infusion for 72 hours. H. pylori testing is pending."
Pimp Questions
Why is BUN:Cr > 20 suggestive of UGIB?
Blood in the upper GI tract is digested and absorbed as protein, resulting in elevated BUN from amino acid catabolism. Creatinine remains unchanged. This disproportionate BUN rise (BUN:Cr > 20:1) helps localize the bleed above the ligament of Treitz.
Why do cirrhotic patients with GI bleed get prophylactic antibiotics?
Cirrhotic patients with GI bleed have very high rates of bacterial infections (up to 35–66%), including SBP, bacteremia, and UTIs. These infections worsen outcomes and increase rebleed risk. Prophylactic antibiotics (ceftriaxone 7 days) Soriano 1992 reduce infections, rebleeding, and mortality — one of the clearest survival benefits in hepatology.
When do you do an EGD in upper GI bleed — and when should it be truly emergent?
Most upper GI bleeds: EGD within 24 hours of presentation (after resuscitation and hemodynamic stabilization). Emergent EGD (within 12h): hemodynamic instability despite resuscitation, suspected variceal bleed (cirrhosis + hematemesis), or ongoing active hemorrhage. Before EGD: NPO ×6h, PPI drip (controversial pre-EGD but commonly done — doesn't change mortality, may reduce high-risk stigmata), consider erythromycin 250 mg IV 30 min before (prokinetic — clears blood from stomach, improves visualization). Glasgow-Blatchford score = 0: safe for outpatient management (can discharge without EGD if low-risk).
A cirrhotic patient with hematemesis — what 3 things must you do that differ from a non-variceal bleed?
(1) Octreotide drip (50 mcg IV bolus → 50 mcg/hr × 3-5 days) — splanchnic vasoconstriction, reduces portal pressure and variceal bleeding. Start immediately, before EGD. (2) Ceftriaxone 1g IV daily × 7 days — antibiotic prophylaxis reduces infection, rebleeding, and mortality in cirrhotic GI bleed (up to 20% have occult SBP). (3) Restrictive transfusion target — Hgb goal 7-8 (not 10). Over-transfusion increases portal pressure → more bleeding. [Villanueva, 2013: restrictive (Hgb < 7) vs liberal (Hgb < 9) strategy — restrictive had BETTER survival in variceal bleed. Also: avoid aggressive IV fluids (same portal pressure concern). EGD within 12h for band ligation.
⚡ Summary
Summary
Immediate
2 large-bore IVs, resuscitate, airway (intubate if massive bleed/AMS), type & cross, call GI early.
Non-Variceal
IV pantoprazole 80 mg bolus → 8 mg/hr. EGD within 24h (12h if unstable). Treat H. pylori.
Variceal
Octreotide drip + ceftriaxone immediately. EGD with band ligation. TIPS if refractory.
Transfusion
Restrictive strategy: transfuse to Hgb 7–9. Higher targets in ACS. Correct coagulopathy before scope.
BUN:Cr Clue
BUN:Cr > 20 suggests UGIB (blood digested as protein, creatinine unchanged)
Pitfall
Transfusing aggressively in variceal bleed worsens portal hypertension and increases rebleed risk. Restrictive strategy is especially critical here.
📄 One Pager
GI · ICU · One Pager
Upper GI Bleed
Resuscitate first, scope second. Variceal vs non-variceal drives management. Octreotide + ceftriaxone in any cirrhotic. Restrictive transfusion saves lives.
Non-Variceal (80%)
- PUD (most common)
- Mallory-Weiss tear
- Rx: IV pantoprazole 80 mg → 8 mg/hr
- EGD within 24h (12h if unstable)
- Treat H. pylori
Variceal (20%) — Higher Mortality
- Portal hypertension (cirrhosis)
- Start immediately: Octreotide 50 mcg → 50 mcg/hr
- Antibiotics: Ceftriaxone 1g IV daily × 7 days
- EGD with band ligation
- TIPS if refractory
BUN:Cr Clue
- BUN:Cr > 20:1
- Blood digested as protein
- Confirms UGIB source
Transfusion
- Target Hgb 7–9 TRIGGER 2015
- Restrictive = better survival
- ACS: target Hgb 8–9
Pitfalls
- Over-transfusing variceal bleed
- No antibiotics in cirrhotic
- Scoping unstable patient
📈 Monitoring
Monitoring Parameters — Cardiogenic Shock
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
Post-Cardiac Arrest Care (ROSC)
Return of spontaneous circulation is just the beginning. Post-cardiac arrest syndrome causes multi-organ dysfunction. Targeted temperature management, hemodynamic optimization, and finding the cause define survival and neurologic outcome.
🔍 Overview
Post-Cardiac Arrest Syndrome
After ROSC, four simultaneous processes occur:
- Post-arrest brain injury — cerebral edema, impaired autoregulation, seizures (30–40% of arrests)
- Post-arrest myocardial dysfunction — global systolic/diastolic dysfunction (peaks at 24–48 hrs, often reversible)
- Systemic ischemia/reperfusion injury — cytokine storm, coagulopathy, multi-organ dysfunction
- Precipitating cause — must identify and treat (ACS, PE, electrolytes, toxins)
Reversible Causes of Cardiac Arrest — The H's & T's
Mnemonic: 5 H's and 5 T's — Run through every H and T systematically during and after every arrest. If you don't find the cause, you can't fix it.
| H's | Clue / How to Find | Fix |
|---|---|---|
| Hypovolemia | Flat IVC on echo, trauma, GI bleed | Volume resuscitation, blood products, source control |
| Hypoxia | SpO₂, cyanosis, airway obstruction | Secure airway, ventilate, confirm ETT placement |
| Hydrogen ion (acidosis) | ABG — pH < 7.1, severe DKA, renal failure, sepsis | Bicarb, treat underlying cause |
| Hypo/Hyperkalemia | ECG (peaked T's, wide QRS, sine wave), BMP | Calcium, insulin/glucose, dialysis (hyperK). IV KCl, Mg (hypoK). |
| Hypothermia | Core temp < 30°C, exposure history, near-drowning | Active rewarming. "Not dead until warm and dead." |
| T's | Clue / How to Find | Fix |
|---|---|---|
| Tension pneumothorax | Absent breath sounds, tracheal deviation, hypotension, distended neck veins | Needle decompression (2nd ICS MCL) → chest tube |
| Tamponade (cardiac) | Distended neck veins, muffled heart sounds, hypotension (Beck's triad). Echo: effusion + RV collapse. | Pericardiocentesis (subxiphoid, echo-guided) |
| Toxins | Med hx, pill bottles, toxidrome. Common: TCA, digoxin, beta-blockers, CCBs, opioids. | Specific antidotes. Bicarb (TCA), digibind, glucagon (BB), high-dose insulin (CCB), naloxone. |
| Thrombosis — PE | RV dilation on echo, history of immobility/DVT, PEA arrest | tPA 50mg IV push (if massive PE during arrest), surgical/IR embolectomy |
| Thrombosis — MI | 12-lead ECG: STEMI or new LBBB, regional wall motion abnormality on echo | Emergent cath lab — even during CPR (in select patients) |
Immediately post-ROSC: ECG + echo. STEMI → cath lab immediately (even if neurologically devastated). Echo → wall motion, RV dilation (PE), tamponade, EF.
🚨 Management
Post-Arrest Bundle — ICU Protocol
Immediately Post-ROSC
12-lead ECG (STEMI → cath lab without delay), ABG, labs, portable CXR, bedside echo. Establish arterial line + central line. If still on scene — transport immediately. For OHCA without ST elevation, immediate angiography is NOT required — COACT, 2019 showed no benefit to immediate cath in non-STEMI arrest.
Airway & Ventilation
Confirm ETT position. Target SpO₂ 94–98% — do NOT hyperoxia (increases reperfusion injury). Target PaCO₂ 35–45 mmHg — avoid hypocapnia (causes cerebral vasoconstriction). Titrate FiO₂ to achieve SpO₂ target, not 100%.
Hemodynamics
Target MAP ≥ 65–70 mmHg. Norepinephrine first-line. Dobutamine if post-arrest myocardial dysfunction. Avoid hypotension (worsens brain injury). Avoid aggressive fluid loading in pulmonary edema.
Targeted Temperature Management (TTM)
Target core temperature 32–36°C for ≥ 24 hours in comatose survivors. TTM-2 2021: 33°C vs 37.5°C — no difference in survival. Current evidence: prevent fever (T > 37.7°C) is mandatory. Active cooling to 33°C still widely practiced and reasonable in deep coma. Use cooling blankets, Arctic Sun, or invasive methods.
Seizure Management
Continuous EEG monitoring — up to 30–40% have post-arrest seizures including NCSE. Treat seizures aggressively. Prophylactic AEDs not recommended routinely but use if clinical or EEG seizure.
Neurological Prognostication
Wait ≥ 72 hours after rewarming before prognostication (sedation/hypothermia confound exam). Use multimodal approach: neuro exam (pupillary reflex, corneal reflex, motor response), SSEP (bilateral absent N20 = poor prognosis), EEG, CT/MRI brain, NSE (serum marker). No single test is definitive.
💊 Medications & Doses
Medications
| Drug | Dose | Role | Notes |
|---|---|---|---|
| Norepinephrine (Levophed) | 0.1–1 mcg/kg/min | Vasopressor (first-line) | Maintain MAP ≥ 65–70 post-ROSC. Post-arrest myocardial dysfunction is common — monitor CO. |
| Dobutamine (Dobutrex) | 2–15 mcg/kg/min | Post-arrest cardiogenic shock | Add if MAP adequate but echo shows severely reduced EF. Titrate to echo/clinical response. |
| Propofol (Diprivan) | 5–50 mcg/kg/min | Sedation during TTM | Reduces shivering, facilitates temperature control. Monitor for propofol infusion syndrome. |
| Meperidine / Buspirone | Meperidine 25–50 mg IV PRN | Anti-shivering during TTM | Shivering increases metabolic demand and raises temperature. Treat aggressively. Magnesium also helps. |
| Aspirin + Heparin | Per ACS protocol | If ACS precipitant | Do not withhold antiplatelet/anticoagulation for neurologic concerns alone. Treat the cause. |
| Insulin infusion | Target BG 140–180 mg/dL | Glycemic control | Avoid both hypoglycemia and severe hyperglycemia. Tight control (< 110) increases hypoglycemia and worsens outcomes. |
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Perez is a 55-year-old who suffered an out-of-hospital VF arrest with 18 minutes of CPR before ROSC. He was brought to our ICU intubated. Initial ECG showed STEMI — he underwent emergency PCI with drug-eluting stent to the RCA. He is on TTM protocol at 33°C, day 1. He is on NE 0.2 mcg/kg/min, MAP 68. Echo shows EF of 30% with inferior wall hypokinesis — on dobutamine 5 mcg/kg/min. SpO₂ 96% on FiO₂ 0.4, PaCO₂ 41. Continuous EEG shows no seizure activity. BG 152, on insulin drip. We will maintain cooling for 24 hours total, then rewarm at 0.5°C per hour. Neurological prognostication deferred for 72 hours post-rewarming."
Pimp Questions
Why do we avoid hyperoxia post-ROSC?
Hyperoxia (PaO₂ > 300 mmHg) worsens cerebral reperfusion injury through free radical generation. Multiple observational studies Kilgannon 2010 show increased mortality with hyperoxia post-ROSC. Target SpO₂ 94–98%, not 100%. Titrate FiO₂ down as soon as possible after ROSC.
When can you prognosticate neurological outcome after cardiac arrest?
Not before 72 hours after rewarming from hypothermia. Sedation, hypothermia, and metabolic derangements all suppress neurological function and mimic poor prognosis. Early withdrawal based on exam alone leads to self-fulfilling prophecy. Use multimodal assessment: neuro exam + SSEP + EEG + MRI brain + NSE levels.
What is targeted temperature management (TTM) and what does current evidence say?
[TTM2, 2021: targeted hypothermia at 33°C did NOT improve survival or neurologic outcome compared to normothermia (targeting ≤ 37.5°C and actively preventing fever). This changed practice — the benefit is from preventing fever, not inducing hypothermia. Current approach: avoid fever aggressively (target ≤ 37.5°C × 72h). If using active cooling, 33°C × 24h is still acceptable. Rewarm slowly (0.25°C/hr). Key: don't let the patient become hyperthermic — fever after cardiac arrest independently worsens neurologic outcomes. Use surface cooling, cold IV fluids, or intravascular cooling devices.
When can you prognosticate neurologic outcome after cardiac arrest, and what tools do you use?
Wait ≥ 72 hours after rewarming (if TTM used) or ≥ 72h from ROSC. Earlier assessment is unreliable due to sedation, hypothermia, and metabolic derangements. Multimodal approach (no single test is sufficient): (1) Clinical exam: absent pupillary and corneal reflexes at 72h + bilaterally absent motor response = poor prognosis. (2) EEG: burst suppression or status epilepticus at 72h. (3) Somatosensory evoked potentials (SSEP): bilaterally absent N20 = most specific predictor of poor outcome. (4) NSE (neuron-specific enolase): > 33 mcg/L at 72h associated with poor outcome. (5) Brain MRI (DWI): diffuse cortical restriction. Use ≥ 2 concordant tests before making prognostic determination. False pessimism = premature withdrawal of care.
⚡ Summary
Summary
Immediate
ECG → STEMI → cath lab now. Echo → find reversible cause. Avoid hyperoxia, avoid hypocapnia.
Hemodynamics
MAP ≥ 65–70. NE first-line. Add dobutamine for low EF. Post-arrest myocardial dysfunction is often reversible at 48–72h.
TTM
Prevent fever (> 37.7°C) is mandatory. Cooling to 33°C reasonable in deep coma. 24 hours minimum. Rewarm slowly.
Seizures
30–40% have post-arrest seizures. Continuous EEG for comatose patients. Treat aggressively if detected.
Prognostication
Wait ≥ 72h post-rewarming. Multimodal: exam + SSEP + EEG + MRI + NSE. Never base on one test alone.
H's & T's
Always find the cause. Hypovolemia, Hypoxia, Hypo/hyperK, Tension PTX, Tamponade, Thrombosis (ACS/PE), Toxins.
📄 One Pager
ICU · One Pager
Post-Cardiac Arrest Care (ROSC)
ROSC is the beginning, not the end. ECG → echo → TTM → avoid hyperoxia → find the cause. Don't prognose for 72h post-rewarming.
Post-ROSC Bundle
1
12-lead ECG — STEMI → cath lab immediately (even if comatose)
2
Bedside echo — EF, wall motion, tamponade, RV dilation (PE)
3
Avoid hyperoxia — target SpO₂ 94–98%, NOT 100% (free radical injury) Kilgannon 2010
4
MAP ≥ 65–70 — NE first-line. Dobutamine if post-arrest low EF.
5
TTM: Prevent fever > 37.7°C mandatory. 33°C reasonable in deep coma TTM-2 2021
6
Continuous EEG — 30–40% have post-arrest seizures (NCSE)
H's & T's
- Hypovolemia, Hypoxia
- Hypo/hyperkalemia
- Tension PTX, Tamponade
- Thrombosis (PE/ACS)
- Toxins
Prognostication
- Wait ≥ 72h post-rewarming
- Neuro exam + SSEP + EEG
- MRI brain + NSE levels
- No single test is definitive
Pitfalls
- Hyperoxia (FiO₂ 1.0 left on)
- Early prognostication
- Missing post-arrest NCSE
- Delaying PCI for STEMI
📈 Monitoring
Monitoring Parameters — Hypertensive Emergency
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
🧪 Workup
Workup — Post-Cardiac Arrest Care (ROSC)
Workup for Post-Cardiac Arrest Care (ROSC): Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
Hepatic Encephalopathy & Acute Liver Failure
Neuropsychiatric dysfunction from liver failure. In cirrhosis it's often episodic and reversible — find and treat the precipitant. Acute liver failure (ALF) is a different, more dangerous beast requiring ICU and transplant evaluation.
🔍 Overview
HE vs ALF — Two Different Conditions
Hepatic Encephalopathy (HE): Neuropsychiatric complications in a patient with pre-existing liver disease (cirrhosis). Usually reversible. Graded West Haven criteria 1–4.
Acute Liver Failure (ALF): Rapid hepatic necrosis in a previously healthy liver: coagulopathy (INR > 1.5) + encephalopathy without prior liver disease. Medical emergency requiring ICU + transplant evaluation.
Acute Liver Failure (ALF): Rapid hepatic necrosis in a previously healthy liver: coagulopathy (INR > 1.5) + encephalopathy without prior liver disease. Medical emergency requiring ICU + transplant evaluation.
Precipitants of HE — TIPS Mnemonic
- T — Toxins/drugs (opioids, benzos, sedatives), Transjugular shunts
- I — Infection (SBP is most common! — always tap ascites), Increased protein load (GI bleed)
- P — Portal shunting, Portosystemic shunts
- S — Sodium low (hyponatremia), Surgical stress, Starvation
- Also: Constipation, Dehydration, Electrolyte disturbance (hypokalemia → alkalosis → ↑NH3)
Always perform diagnostic paracentesis in cirrhotic patient with new/worsening HE. SBP is the most commonly missed precipitant. PMN > 250/mm³ → SBP → treat even without symptoms.
Causes of Acute Liver Failure
- Acetaminophen toxicity (most common in US — 50%)
- Viral hepatitis (HAV, HBV, HEV)
- Drug-induced (isoniazid, amoxicillin-clavulanate, NSAIDs)
- Autoimmune hepatitis
- Ischemic hepatitis ("shock liver")
- Wilson's disease, Budd-Chiari, pregnancy-related (AFLP, HELLP)
🧪 Workup & Diagnosis
Workup
For Hepatic Encephalopathy
- LFTs, INR/PT — severity of liver dysfunction (most critical for staging)
- Ammonia — confirms HE but does NOT correlate well with grade. Trend more useful than single value.
- BMP — Na (hyponatremia worsens HE), K, BUN/Cr (renal function — HRS?)
- CBC — infection? thrombocytopenia (cirrhosis)?
- Diagnostic paracentesis — PMN count > 250 = SBP (most commonly missed precipitant); do this early
- Blood cultures + UA + urine culture — rule out infection triggering HE
- CXR — pulmonary infection
- Head CT — if focal neuro deficits or unclear diagnosis (rule out structural cause); not routine
For ALF — Additional
- Acetaminophen level — most common cause of ALF in US (50%); check even without clear history
- Toxicology screen — rule out other drug/toxin causes
- Viral hepatitis panel (HAV IgM, HBsAg, HBV DNA, HCV RNA) — 2nd most common etiology group
- Autoimmune hepatitis (ANA, ASMA, IgG) — treatable, do not miss
- Pregnancy test — AFLP and HELLP are obstetric emergencies
- Wilson's disease (ceruloplasmin, Kayser-Fleischer rings, urine copper) — rare but treatable in young patients
- Contact transplant hepatology early in ALF — before deterioration
🚨 Management
Management: Hepatic Encephalopathy
Find and Treat the Precipitant
This is the most important step. Treat infection (SBP, pneumonia, UTI). Stop offending medications. Correct electrolytes. Treat GI bleed. Relieve constipation. Correct dehydration.
Lactulose (First-Line)
Lactulose 25–30 g PO/NG q1–2h until bowel movement, then titrate to 2–3 soft stools/day. Mechanism: acidifies colon → traps NH4⁺ → reduces ammonia absorption. If no PO/NG: lactulose enemas 300 mL in 700 mL water retention enema q6h.
🔄 Updated Practice: Old teaching: lactulose enemas are first-line for hepatic encephalopathy. Current practice: oral or NG lactulose is first-line (titrate to 3-4 soft stools per day). Rectal lactulose enemas (300 mL in 700 mL water) are reserved for patients who cannot take oral medications (e.g., grade III-IV HE with aspiration risk). Rifaximin (Xifaxan) 550 mg BID is added for secondary prevention of recurrence.
Rifaximin (Second-Line / Maintenance)
Rifaximin 550 mg PO BID — non-absorbable antibiotic that reduces gut ammonia-producing bacteria. Added to lactulose for recurrent or refractory HE. Significantly reduces HE recurrence RFHE 2010.
Airway Protection
Grade 3–4 HE (stupor/coma) → high risk of aspiration. Consider intubation early for airway protection, especially before procedures (paracentesis, endoscopy, LP).
📋 Clinical Example — Hepatic Encephalopathy Management
- Patient: 62M with alcoholic cirrhosis (Child-Pugh C), brought in confused and somnolent. Asterixis present. NH3 68.
- Grade: West Haven Grade 3 (somnolent but arousable, confused, asterixis).
- Identify precipitant: Infection (SBP? UTI? Pneumonia?), GI bleed, constipation, medications (benzos, opioids), electrolyte derangement (hypokalemia, hyponatremia), non-compliance with lactulose. Check: CBC, BMP, UA, CXR, blood cultures, diagnostic paracentesis (ALWAYS if ascites — rule out SBP).
- Treatment:
- Lactulose (Kristalose) 30mL PO/NG q1-2h until first bowel movement → then titrate to 3-4 soft stools/day. Can give as enema (300mL in 700mL water) if unable to take PO.
- Rifaximin (Xifaxan) 550mg PO BID — add for prevention of recurrence (not just acute treatment). Reduces recurrence by 58%.
- Protein restriction is OUTDATED — maintain 1.2-1.5 g/kg/day protein. Malnutrition worsens encephalopathy.
- Zinc 220mg PO daily — zinc deficiency impairs urea cycle, worsening ammonia metabolism.
- 🔄 Updated Practice: Old teaching: restrict protein intake in hepatic encephalopathy to reduce ammonia production. Current practice: protein restriction is HARMFUL — it worsens malnutrition (which is already severe in cirrhosis) and does NOT improve encephalopathy. Maintain protein intake at 1.2-1.5 g/kg/day. Branched-chain amino acid supplements may help in protein-intolerant patients.
- Key: NH3 level does NOT correlate with severity and should NOT be trended. Treat the patient, not the number. Lactulose titrated to stool output is the cornerstone.
Management: Acute Liver Failure (ALF)
- ICU admission — all ALF patients
- N-acetylcysteine (NAC) — for acetaminophen ALF (and emerging evidence for non-acetaminophen ALF). 150 mg/kg IV over 1h, then 12.5 mg/kg/hr × 4h, then 6.25 mg/kg/hr × 16h. Start immediately if APAP toxicity possible.
- Liver transplant evaluation immediately — contact transplant center
- Manage ICP (cerebral edema risk in ALF) — head of bed 30°, avoid hypotonic fluids, consider ICP monitoring
- Correct coagulopathy only if actively bleeding (do NOT give FFP prophylactically — INR is prognostic)
- Avoid
nephrotoxins, sedatives, hepatotoxic drugs💊 MedicationsMedications — Hepatic Encephalopathy
Drug Dose Route Notes Lactulose (Kristalose)
1ST LINE30 mL PO q1–2h until first BM → titrate to 3–4 soft stools/day PO/NG/PR Cornerstone of HE treatment. Acidifies colon → traps NH4+ → reduces ammonia absorption. Enema (300 mL in 700 mL water) if unable to take PO. Titrate to stool output, NOT ammonia level. Rifaximin (Xifaxan) 550 mg PO BID PO Non-absorbable antibiotic. Added to lactulose for recurrence prevention — reduces HE recurrence by 58%. Not just for acute treatment. Well tolerated, minimal systemic absorption. Zinc sulfate 220 mg PO daily PO Zinc deficiency impairs the urea cycle, worsening ammonia metabolism. Adjunctive therapy. Common deficiency in cirrhosis. LOLA (L-ornithine L-aspartate) Per protocol PO/IV Adjunct therapy. Provides substrates for ammonia metabolism (urea cycle and glutamine synthesis). Evidence modest — use as add-on when lactulose + rifaximin insufficient. Metronidazole (Flagyl) 250 mg PO TID PO Only if rifaximin unavailable. Reduces ammonia-producing gut bacteria. Limit duration — neurotoxicity with prolonged use (peripheral neuropathy, cerebellar dysfunction). Not first-line. Protein restriction is OUTDATED. Maintain 1.2–1.5 g/kg/day protein. Malnutrition worsens encephalopathy and increases mortality. Branched-chain amino acids (BCAA) may be beneficial if intolerant of standard protein.
📊 Monitoring
Monitoring — Hepatic Encephalopathy
| Parameter | Frequency | Target / Action |
|---|---|---|
| West Haven grade | q4–8h (more frequent if worsening) | Track mental status: orientation, asterixis, somnolence. Grade 3–4 → consider ICU for airway protection. |
| Asterixis | Each assessment | Negative myoclonus ("liver flap"). Presence confirms HE. Disappearance suggests improvement. |
| Orientation | Each assessment | Person, place, time, situation. Serial number connection test if able to participate. |
| Lactulose stool output | Strict I&O tracking | Target 3–4 stools/day. Too few → increase lactulose. Excessive diarrhea → dehydration → worsens HE. |
| Ammonia level | On admission only | Do NOT trend ammonia — it does NOT correlate with severity. An initial elevated ammonia supports the diagnosis but serial levels do not guide treatment. Treat clinically. |
| BMP (K+, Na+, Cr, BUN) | Daily | Hypokalemia → metabolic alkalosis → increased renal ammonia production → worsens HE. Hyponatremia worsens cerebral edema. Cr for HRS surveillance. |
| Infection workup | On admission + any worsening | CBC, blood cultures, UA/UCx, CXR, diagnostic paracentesis (rule out SBP — most commonly missed precipitant). Repeat paracentesis with any AMS change. |
Treat the patient, not the ammonia number. Lactulose titrated to stool output + finding/treating the precipitant are the cornerstones. If mental status is improving, the treatment is working regardless of what the ammonia says.
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Alvarez is a 54-year-old with decompensated cirrhosis from alcohol who presented with confusion and asterixis. This represents Grade 2 hepatic encephalopathy. We performed diagnostic paracentesis on admission which showed PMN count of 312 — consistent with SBP. He was started on cefotaxime and albumin per SBP protocol. Ammonia on admission was 118. He was started on lactulose — currently having 2–3 soft stools per day. He is more alert today, following commands, with ammonia down to 74. We are adding rifaximin for recurrence prevention. Rifaximin was not on his outpatient regimen. Repeat paracentesis is planned on day 5 to confirm SBP resolution."
Pimp Questions
How does lactulose work in hepatic encephalopathy?
Lactulose is metabolized by colonic bacteria to lactic acid and acetic acid, lowering colonic pH. This acidic environment converts NH3 (which freely crosses intestinal epithelium) to NH4⁺ (which is charged and cannot be absorbed). It also acts as an osmotic cathartic, reducing intestinal transit time and ammonia absorption.
Why should you NOT give FFP prophylactically in ALF?
The INR in ALF reflects global coagulation factor deficiency and is used as a prognostic marker (part of King's College criteria for transplant listing). Correcting the INR with FFP obscures this prognostic marker without proven clinical benefit. Reserve FFP for active bleeding or before invasive procedures only.
What are the precipitants of hepatic encephalopathy and what's the mnemonic?
HEPATICS: Hemorrhage (GI bleed → protein load → ammonia), Electrolytes (hypokalemia → increased renal ammonia production; hyponatremia), Proteins (excessive dietary protein — rare cause, over-taught), Anything that causes dehydration (diuretics, vomiting, diarrhea), TIPS (shunting portal blood past the liver), Infection/SBP (most commonly missed precipitant — always do paracentesis), Constipation (decreased ammonia elimination), Sedatives (benzodiazepines, opioids — enhanced GABA sensitivity in cirrhosis). Most important: SBP and infection — check paracentesis fluid in every cirrhotic with altered mental status, even without abdominal pain or fever.
Why do you not chase the ammonia number?
Ammonia levels do not correlate well with the severity of hepatic encephalopathy and should not guide treatment. Reasons: (1) Ammonia is only one of many neurotoxins in HE — manganese, mercaptans, short-chain fatty acids, and inflammatory cytokines all contribute. (2) Venous ammonia levels don't reflect brain ammonia (arterial is slightly more reliable but still imperfect). (3) Sample handling affects results — must be on ice, processed within 15 min. A "normal" ammonia does NOT rule out HE. An elevated ammonia in a confused cirrhotic supports the diagnosis but serial levels don't guide treatment. Treat clinically: track mental status, asterixis, West Haven grade. Lactulose titrated to 2-3 BMs/day is the treatment regardless of ammonia level.
⚡ Summary
Summary
HE First Move
Find the precipitant. Tap ascites (rule out SBP). Treat infection. Lactulose to 2–3 stools/day.
Medications
Lactulose (first-line). Rifaximin 550 mg BID added for recurrent/refractory HE.
Airway
Grade 3–4 HE → intubate for airway protection especially before procedures.
ALF
ICU + NAC (especially for APAP) + transplant evaluation immediately. Do not delay listing.
SBP Rule
Always tap ascites in new/worsening HE. PMN > 250 = SBP. Treat with cefotaxime + albumin.
Common Pitfall
Giving FFP in ALF (obscures prognosis). Not tapping ascites. Giving lactulose without finding precipitant.
📄 One Pager
GI · Hepatology · One Pager
Hepatic Encephalopathy / ALF
Find the precipitant first — especially SBP. Tap ascites. Lactulose to 2–3 stools/day. Add rifaximin for recurrence. ALF → ICU + NAC + transplant evaluation.
Precipitants — TIPS
- T — Toxins/drugs, TIPS shunts
- I — Infection (SBP!), increased protein
- P — Portal shunting
- S — Sodium (hyponatremia), starvation
- Also: constipation, dehydration, hypokalemia
Always Tap Ascites
- PMN > 250/mm³ = SBP
- Treat: cefotaxime 2g IV q8h + albumin 1.5 g/kg day 1, 1 g/kg day 3
- Most commonly missed precipitant
HE Treatment
Lactulose25–30g q1–2h → 2–3 stools/day
Rifaximin550 mg PO BID RFHE 2010
Treat precipitantMost important step
ALF Management
- ICU admission
- NAC (especially APAP)
- Transplant evaluation NOW
- Do NOT correct INR prophylactically
Pitfalls
- Not tapping ascites
- FFP prophylactically (obscures prognosis)
- Grade 3–4 → intubate early
- Lactulose without finding cause
Atrial Fibrillation
The most common sustained cardiac arrhythmia. Management rests on three pillars: rate control, rhythm control (when appropriate), and stroke prevention with anticoagulation guided by CHA₂DS₂-VASc.
🔍 Overview
Definition
Atrial fibrillation (AF) is an irregularly irregular supraventricular tachyarrhythmia caused by chaotic atrial electrical activity. No organized P waves on ECG — replaced by fibrillatory waves with an irregular ventricular response.
Classification
| Type | Definition |
|---|---|
| Paroxysmal | Self-terminates within 7 days (usually < 48h) |
| Persistent | Lasts > 7 days, requires intervention to terminate |
| Long-standing persistent | Continuous > 12 months |
| Permanent | Rate control accepted; no further attempts at rhythm control |
| Valvular AF | AF with moderate-severe mitral stenosis or mechanical heart valve → requires warfarin (not DOACs) |
Common Triggers & Causes
- Hypertension — most common modifiable risk factor
- Heart failure — AF and HF exacerbate each other
- Valvular disease — especially mitral stenosis/regurgitation
- Thyrotoxicosis — always check TSH in new AF
- Alcohol — "holiday heart" (binge drinking → AF)
- Post-operative — especially cardiac and thoracic surgery (30–50%)
- PE — AF can be the first sign of PE
- Sepsis / critical illness — new AF in ICU = search for underlying cause
- OSA, obesity, advancing age, pericarditis
Always ask: What triggered this AF? New AF is often a symptom of something else (sepsis, PE, thyroid storm, ACS, volume overload). Treat the cause, not just the rhythm.
ECG Features
- Absent P waves — replaced by irregular fibrillatory baseline
- Irregularly irregular R-R intervals (the hallmark)
- Narrow QRS (unless aberrant conduction or pre-existing BBB)
- Ventricular rate typically 100–180 bpm if untreated (RVR)
⚡ Management
Is the Patient Hemodynamically Unstable?
Unstable = hypotension (SBP < 90), AMS, chest pain, acute pulmonary edema, or signs of shock. If YES → immediate synchronized cardioversion. Do not delay for rate control medications.
Unstable → Cardiovert
Synchronized DC cardioversion — 120–200J biphasic. Sedate first if possible (propofol, etomidate, or midazolam). If first shock fails, escalate energy. Have pads and airway equipment ready. This is immediate — do not wait for anticoagulation status.
Stable → Rate Control
If hemodynamically stable with RVR (HR > 110), proceed to pharmacologic rate control. Choice depends on EF:
Rate Control in Afib with RVR — By EF
| Setting | First-Line | Dose | Notes |
|---|---|---|---|
| Preserved EF (HFpEF or normal) | Diltiazem | 0.25 mg/kg IV over 2 min → repeat 0.35 mg/kg in 15 min if needed → drip 5–15 mg/hr | Fastest onset. Can also use metoprolol. Avoid in pre-excitation (WPW). |
| Preserved EF (alternative) | Metoprolol tartrate | 5 mg IV push q5 min × 3 doses → 25–100 mg PO BID | Good if also hypertensive or ACS. Safer than diltiazem in borderline EF. |
| Reduced EF (HFrEF, EF < 40%) | Amiodarone | 150 mg IV over 10 min → 1 mg/min × 6h → 0.5 mg/min × 18h | Avoid CCBs and high-dose BB in HFrEF. Amio provides rate + rhythm control. Monitor QTc. |
| Reduced EF (alternative) | Digoxin | 0.25–0.5 mg IV load → 0.125–0.25 mg PO daily | Slow onset (hours). No acute rate control. Add-on for refractory rate. Check levels (0.5–0.9 ng/mL). RATE-AF, 2020: digoxin non-inferior to bisoprolol for rate control in permanent AF. |
| Critical illness / ICU | Amiodarone or esmolol | Esmolol: 500 mcg/kg IV bolus → 50–200 mcg/kg/min drip | Esmolol = ultra-short acting β₁ blocker. Ideal for hemodynamic uncertainty — stops fast if BP drops. |
NEVER give CCBs (diltiazem, verapamil) or BB in Afib with WPW (pre-excitation / delta wave on ECG). These block the AV node → forces conduction down accessory pathway → VF → death. Use procainamide or cardiovert.
Targets
| Strategy | Target HR | Evidence |
|---|---|---|
| Lenient (most patients) | < 110 bpm at rest | RACE II, 2010: lenient was non-inferior to strict. Less drug side effects. Preferred initial approach. |
| Strict (if symptomatic) | < 80 bpm at rest | Use if persistent symptoms despite lenient control. |
Workup in New Afib with RVR
- 12-lead ECG — confirm AF, rule out flutter, WPW, STEMI
- TSH — always check. Thyrotoxicosis is a reversible cause.
- BMP — electrolytes (K⁺, Mg²⁺ — both must be repleted), renal function
- BNP/Echo — assess EF. Determines drug choice (CCB vs amio).
- Troponin — RVR can cause demand ischemia
- CBC — anemia worsens tachycardia and symptoms
- Mg²⁺ — replete aggressively (target ≥ 2.0). Low Mg = refractory RVR.
- Consider PE workup if new AF + dyspnea + tachycardia + hypoxia
Pearl: Always replete K⁺ > 4.0 and Mg²⁺ > 2.0 in AF with RVR. Hypomagnesemia is the most common missed cause of refractory rate control.
💊 Rate Control
| Drug | Dose | Best For | Avoid In |
|---|---|---|---|
| Metoprolol succinate 1ST LINE | 25–200 mg PO daily | First-line. HTN, HFrEF (evidence-based BB), ACS | Decompensated HF, severe bradycardia, asthma |
| Diltiazem (Cardizem) ER 1ST LINE | 120–360 mg PO daily | Preserved EF. Fast symptom relief. COPD-safe. | HFrEF (EF < 40%), WPW, concurrent BB |
| Verapamil (Calan) | 120–480 mg PO daily | Alternative CCB if diltiazem intolerant | Same as diltiazem. More constipation. |
| Digoxin (Lanoxin) | 0.125–0.25 mg PO daily | Add-on if BB/CCB insufficient. HFrEF. Sedentary patients. | Renal failure (adjust dose), hypokalemia (toxicity risk). Target level 0.5–0.9 ng/mL. |
| Amiodarone (Cordarone) HFrEF ONLY | 200 mg PO daily | HFrEF with refractory rate. Also provides rhythm control. | Long-term toxicities: thyroid, liver, lung, cornea, skin. Monitor TFTs/LFTs/PFTs q6 months. |
⚡ Rhythm Control
When to Consider Rhythm Control
- Symptomatic despite adequate rate control
- Young patients with first episode
- AF duration < 1 year (higher success of maintaining sinus)
- Tachycardia-mediated cardiomyopathy
- EAST-AFNET 4, 2020: early rhythm control (within 1 year of diagnosis) reduced cardiovascular outcomes vs rate control alone
Cardioversion Rules
If AF > 48 hours (or unknown duration): Must anticoagulate ≥ 3 weeks before elective cardioversion OR do TEE to rule out LAA thrombus first. Then anticoagulate ≥ 4 weeks after cardioversion regardless.
If AF < 48 hours: Can cardiovert without prior anticoagulation (but start anticoagulation based on CHA₂DS₂-VASc after).
Antiarrhythmic Agents
| Drug | Use | Key Caution |
|---|---|---|
| Flecainide (Tambocor) 1ST LINE | No structural heart disease ("pill-in-the-pocket" for paroxysmal AF) | Contraindicated in CAD, HFrEF, structural disease (proarrhythmic). Must give with AV nodal blocker. |
| Propafenone (Rythmol) | Same as flecainide — no structural disease | Same contraindications. Also has mild BB activity. |
| Amiodarone (Cordarone) | Structural heart disease, HFrEF — most versatile | Long-term toxicities (thyroid, pulmonary fibrosis, hepatotoxicity, corneal deposits). Not first-line in young patients. |
| Dofetilide INPATIENT ONLY | HFrEF, structural disease. Inpatient initiation required. | QTc prolongation → Torsades. Must monitor QTc × 3 days inpatient. Renally dosed. |
| Sotalol | No severe structural disease. Combined BB + class III. | QTc prolongation. Avoid in HFrEF, renal failure. Monitor QTc closely. |
| Ibutilide | Acute pharmacologic cardioversion (IV only) | QTc prolongation → Torsades (risk ~4%). Monitor on telemetry × 4h. Have Mg²⁺ and defibrillator ready. |
🔄 Updated Practice: Old teaching: rate control is preferred over rhythm control for most AF patients (based on AFFIRM, 2002). New evidence: EAST-AFNET 4, 2020 showed that EARLY rhythm control (within 1 year of diagnosis) reduces cardiovascular death, stroke, and HF hospitalization. Key word is "early" — the benefit diminishes if AF has been present for years. Consider early rhythm control especially in younger patients and those with HF.
💉 Anticoagulation & Stroke Prevention
CHA₂DS₂-VASc Score
Determines stroke risk and need for anticoagulation in non-valvular AF. Calculate for every AF patient.
| Letter | Risk Factor | Points |
|---|---|---|
| C | Congestive heart failure (or LV dysfunction, EF ≤ 40%) | 1 |
| H | Hypertension (or on antihypertensive therapy) | 1 |
| A₂ | Age ≥ 75 years | 2 |
| D | Diabetes mellitus | 1 |
| S₂ | Stroke / TIA / thromboembolism (prior) | 2 |
| V | Vascular disease (prior MI, PAD, aortic plaque) | 1 |
| A | Age 65–74 years | 1 |
| Sc | Sex category — female | 1 |
Maximum score: 9. Note: female sex alone (score = 1) does not warrant anticoagulation — it is a risk modifier, not an independent indication.
Anticoagulation Decision
| Score (Male / Female) | Annual Stroke Risk | Recommendation |
|---|---|---|
| 0 (M) / 1 (F) | ~0.2–0.6% | No anticoagulation recommended |
| 1 (M) / 2 (F) | ~1.3–2.2% | Consider anticoagulation (discuss with patient — benefit may outweigh bleed risk) |
| ≥ 2 (M) / ≥ 3 (F) | ~2.2–15% | Anticoagulate. DOACs preferred over warfarin for non-valvular AF. |
Anticoagulant Options
| Drug | Dose | Key Points |
|---|---|---|
| Apixaban (Eliquis) PREFERRED | 5 mg PO BID (2.5 mg if ≥ 2 of: age ≥ 80, weight ≤ 60 kg, Cr ≥ 1.5) | Preferred DOAC. Lowest bleeding risk. ARISTOTLE, 2011: superior to warfarin for stroke prevention with less bleeding. |
| Rivaroxaban (Xarelto) ALTERNATIVE | 20 mg PO daily with dinner (15 mg if CrCl 15–50) | Once daily. ROCKET-AF, 2011: non-inferior to warfarin. Must take with food for absorption. |
| Dabigatran (Pradaxa) ALTERNATIVE | 150 mg PO BID (75 mg if CrCl 15–30) | RE-LY, 2009: 150 mg dose superior to warfarin for stroke; higher GI bleed. Reversible with idarucizumab. |
| Edoxaban (Savaysa) | 60 mg PO daily (30 mg if CrCl 15–50, weight ≤ 60 kg, or P-gp inhibitor) | ENGAGE AF-TIMI 48, 2013: non-inferior to warfarin. Do NOT use if CrCl > 95 (reduced efficacy). |
| Warfarin (Coumadin) VALVULAR ONLY | Titrate to INR 2.0–3.0 | Required for valvular AF (mechanical valve, moderate-severe mitral stenosis). TTR > 70% needed for benefit. Bridging with heparin may be needed. |
Valvular AF = warfarin only. DOACs are NOT approved for mechanical heart valves (RE-ALIGN, 2013: dabigatran increased thromboembolism and bleeding vs warfarin in mechanical valves — trial stopped early) or moderate-severe mitral stenosis.
🔄 Updated Practice: Old teaching: warfarin is the standard anticoagulant for AF. Current practice: DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) are preferred over warfarin for non-valvular AF — better safety profile, no INR monitoring, fewer drug-food interactions. Warfarin is still required for: mechanical heart valves (RE-ALIGN — DOACs caused thromboembolism), moderate-severe mitral stenosis, and antiphospholipid syndrome (TRAPS — DOACs increased thrombosis).
HAS-BLED Score (Bleeding Risk)
Use to identify modifiable bleeding risk factors — NOT to withhold anticoagulation. A high HAS-BLED score means fix the modifiable risks, not stop the DOAC.
| Letter | Risk Factor | Points |
|---|---|---|
| H | Hypertension (uncontrolled, SBP > 160) | 1 |
| A | Abnormal renal/liver function (1 pt each) | 1–2 |
| S | Stroke (prior) | 1 |
| B | Bleeding (history or predisposition) | 1 |
| L | Labile INR (if on warfarin, TTR < 60%) | 1 |
| E | Elderly (age > 65) | 1 |
| D | Drugs (antiplatelets, NSAIDs) or alcohol (≥ 8 drinks/week) (1 pt each) | 1–2 |
Score ≥ 3 = high bleeding risk. Address modifiable factors (control BP, stop NSAIDs, reduce alcohol, optimize INR). Do not withhold anticoagulation based on HAS-BLED alone.
📋 Clinical Example — New Afib with RVR Management
Patient: 72F presents with palpitations, HR 142, irregularly irregular, BP 108/72. No prior Afib history.
Step 1 — Rate Control:
Metoprolol (Lopressor) 5mg IV push over 2 min. Repeat q5min × 3 doses (max 15mg). HR → 118.
Additional: metoprolol (Lopressor) 5mg IV → HR 98. Start metoprolol tartrate (Lopressor) 25mg PO q6h.
If HFrEF (EF < 40%): Avoid diltiazem — contraindicated (negative inotrope worsens HF). Use amiodarone (Cordarone) 150mg IV over 10 min → 1mg/min × 6h → 0.5mg/min × 18h. If preserved EF but hypotensive: diltiazem (Cardizem) 0.25 mg/kg IV bolus → drip 5-15 mg/hr is acceptable.
Step 2 — Anticoagulation:
CHA₂DS₂-VASc: Age 72 (+1), Female (+1) = 2 → Anticoagulate.
Start apixaban (Eliquis) 5mg PO BID (preferred DOAC — no renal dose adjustment unless Cr > 1.5 AND age > 80 AND wt < 60kg).
Step 3 — Assess for Cause:
TSH (hyperthyroidism?), TTE (structural heart disease, valvular?), BMP (electrolytes), troponin (ACS trigger?).
Step 4 — Rate vs Rhythm Control:
New-onset, symptomatic → consider cardioversion if < 48h onset OR TEE-guided if > 48h. Otherwise rate control + anticoagulation × 3 weeks → then cardioversion.
🧪 Workup
Initial Workup — New Atrial Fibrillation
- 12-lead ECG — confirm AF (irregularly irregular, no P waves). Rule out flutter, WPW (delta wave).
- TSH — hyperthyroidism is a reversible cause. Check in ALL new AF.
- BMP — electrolytes (K⁺, Mg²⁺), Cr (for DOAC dosing)
- CBC — anemia can worsen rate, infection can trigger AF
- TTE (echocardiogram) — assess LV function (EF), valvular disease, LA size, wall motion abnormalities
- Troponin — if chest pain or concern for ACS as trigger
- BNP/NT-proBNP — if concern for heart failure
- Consider: D-dimer/CTPA if PE suspected, sleep study if OSA suspected, alcohol history ("holiday heart")
CHA₂DS₂-VASc score should be calculated at diagnosis and documented — it determines anticoagulation need. See Management tab.
💊 Medications
Key Medication Classes — Atrial Fibrillation
Full drug tables with dosing, indications, and contraindications are in the Management tab (Rate Control, Rhythm Control, and Anticoagulation sections).
| Category | First-Line | Key Pearl |
|---|---|---|
| Rate control | Metoprolol (Lopressor) (HFrEF) or Diltiazem (Cardizem) (preserved EF) | Diltiazem contraindicated if EF < 40%. Target HR < 110 at rest RACE II, 2010. |
| Rhythm control | Flecainide (Tambocor) (no structural disease) or Amiodarone (Cordarone) (HFrEF) | Flecainide is proarrhythmic in CAD/HFrEF. Amiodarone has cumulative organ toxicity. |
| Anticoagulation | Apixaban (Eliquis) 5 mg BID PREFERRED | Lowest bleeding risk among DOACs ARISTOTLE, 2011. Warfarin only for valvular AF (mechanical valve, MS). |
| Acute RVR | Diltiazem (Cardizem) 20 mg IV bolus → drip 5–15 mg/hr | Fastest onset. Can repeat bolus q15 min. Transition to PO within 24h. |
📈 Monitoring
Monitoring — Atrial Fibrillation
| Parameter | Frequency | Target / Action |
|---|---|---|
| Heart rate | Continuous telemetry inpatient; daily resting HR outpatient | Resting HR < 110 bpm (lenient) RACE II, 2010. Stricter < 80 if symptomatic. |
| Rhythm | Telemetry inpatient; ambulatory monitor (Holter/Zio) outpatient | Assess AF burden, recurrence after cardioversion, breakthrough episodes on AAD |
| Electrolytes (K⁺, Mg²⁺) | Daily inpatient; q3–6 months outpatient | K⁺ > 4.0, Mg²⁺ > 2.0 — low levels promote AF and reduce AAD efficacy |
| Renal function | At DOAC initiation, then q6–12 months | Adjust DOAC dose per CrCl. Apixaban: 2.5 mg dose if ≥ 2 of (age ≥ 80, wt ≤ 60, Cr ≥ 1.5). |
| TSH | At diagnosis; annually if on amiodarone | Amiodarone causes both hyper- and hypothyroidism (iodine load) |
| LFTs, PFTs, TFTs | q6 months if on amiodarone | Monitor for hepatotoxicity, pulmonary fibrosis, thyroid dysfunction |
| QTc | Baseline + 3 days inpatient if starting dofetilide/sotalol | Hold if QTc > 500 ms. Dofetilide requires inpatient initiation. |
⚡ Summary
Summary
Rate Control
BB or non-DHP CCB (diltiazem). Target HR < 110 at rest [RACE II]. Digoxin add-on if refractory. Avoid CCB in HFrEF.
Rhythm Control
Consider if symptomatic, new-onset (< 1 year), younger patient. Cardioversion + flecainide/amiodarone or catheter ablation.
Anticoagulation
CHA₂DS₂-VASc ≥ 2 (men) or ≥ 3 (women) → DOAC (apixaban, rivaroxaban). Warfarin only if mechanical valve or severe MS.
Stroke Risk
CHA₂DS₂-VASc: CHF(1), HTN(1), Age≥75(2), DM(1), Stroke/TIA(2), Vasc disease(1), Age 65-74(1), Sex female(1).
Acute RVR
Stable: IV diltiazem 20 mg → drip. Unstable: synchronized cardioversion 120-200J biphasic. Replete K⁺ and Mg²⁺.
Don't Miss
Check TSH (hyperthyroid), echo (structural), sleep study (OSA — #1 modifiable risk factor for AF recurrence).
📄 One Pager
Atrial Fibrillation — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a complete reference card.
ATRIAL FIBRILLATION — AT A GLANCE
📋 Diagnose: Irregularly irregular, no P waves, narrow QRS
🧪 Workup: ECG, TSH, BMP (K⁺/Mg²⁺), TTE, troponin if ACS concern
⚡ Acute RVR: Unstable → cardiovert. Stable → diltiazem 20 mg IV → drip
💊 Rate control: Metoprolol (HFrEF) or Diltiazem (preserved EF). Target HR < 110.
⚡ Rhythm control: Flecainide (no structural disease) or Amiodarone (HFrEF)
💉 Anticoag: CHA₂DS₂-VASc ≥ 2M/3F → Apixaban 5 mg BID (preferred DOAC)
📈 Monitor: HR, rhythm, K⁺/Mg²⁺, renal function, QTc if on AAD
📣 Present: See Rounds tab
🧪 Workup: ECG, TSH, BMP (K⁺/Mg²⁺), TTE, troponin if ACS concern
⚡ Acute RVR: Unstable → cardiovert. Stable → diltiazem 20 mg IV → drip
💊 Rate control: Metoprolol (HFrEF) or Diltiazem (preserved EF). Target HR < 110.
⚡ Rhythm control: Flecainide (no structural disease) or Amiodarone (HFrEF)
💉 Anticoag: CHA₂DS₂-VASc ≥ 2M/3F → Apixaban 5 mg BID (preferred DOAC)
📈 Monitor: HR, rhythm, K⁺/Mg²⁺, renal function, QTc if on AAD
📣 Present: See Rounds tab
📋 On Rounds
Sample Presentation
📋 Afib with RVR
"Mrs. Johnson is a 72-year-old woman with HTN, DM, and HFpEF (EF 55%) who presented with palpitations and HR 148, found to be in new-onset atrial fibrillation with RVR. She was hemodynamically stable. TSH was normal. K⁺ 3.6, Mg 1.4 — both repleted. She received diltiazem 20 mg IV bolus × 2 then started on a diltiazem drip at 10 mg/hr with rate down to 92. She was transitioned to diltiazem ER 180 mg daily. Her CHA₂DS₂-VASc is 4 (HTN, DM, age 65–74, female) — we started apixaban 5 mg BID for stroke prophylaxis. Echo showed no structural abnormality. Plan to reassess for rhythm control as outpatient."
Pimp Questions
Why can't you give diltiazem in Afib with WPW?
CCBs and beta-blockers slow AV nodal conduction. In WPW, an accessory pathway (Bundle of Kent) bypasses the AV node. Blocking the AV node forces all conduction down the accessory pathway → extremely rapid ventricular rates → ventricular fibrillation → cardiac arrest. Use procainamide or synchronized cardioversion instead.
What CHA₂DS₂-VASc score triggers anticoagulation?
≥ 2 in males, ≥ 3 in females → anticoagulate (DOACs preferred). Score of 1 (male) or 2 (female) → consider anticoagulation. Score 0 (male) or 1 (female, sex point only) → no anticoagulation. Female sex alone doesn't warrant treatment — it's a modifier.
When must you use warfarin instead of a DOAC?
Valvular AF: mechanical heart valve or moderate-severe mitral stenosis. RE-ALIGN, 2013 showed dabigatran was harmful in mechanical valves — increased stroke and bleeding vs warfarin. Also consider warfarin if severe renal failure (CrCl < 15), antiphospholipid syndrome, or patient preference/cost.
What is the most commonly missed cause of refractory Afib with RVR?
Hypomagnesemia. Always check and replete Mg²⁺ > 2.0. Low magnesium destabilizes cardiac membrane potentials and makes rate control drugs less effective. IV magnesium 2g over 15 min can help convert or slow AF even before other agents kick in.
What did EAST-AFNET 4 show about rhythm control?
EAST-AFNET 4, 2020: early rhythm control (within 1 year of AF diagnosis) reduced a composite of cardiovascular death, stroke, and HF hospitalization compared to rate control alone. This shifted practice toward more aggressive early rhythm control, especially in patients with recent-onset AF and cardiovascular comorbidities.
📄 One Pager
Cardiology · One Pager
Atrial Fibrillation
Rate control (BB or CCB) + anticoagulation (DOAC if CHA₂DS₂-VASc ≥ 2). Treat triggers: TSH, OSA, alcohol, electrolytes.
Diagnosis
Irregularly irregular rhythm. No discrete P waves. Can be paroxysmal, persistent, or permanent. Check TSH, echo, electrolytes.
Acute RVR
IV diltiazem 20 mg → drip 10 mg/hr. Alternative: metoprolol 5 mg IV. Replete K⁺ > 4, Mg > 2. Unstable → cardioversion 120-200J biphasic.
Long-Term
Rate control: BB or CCB (target HR < 110 [RACE II]). Rhythm control if symptomatic/young/new-onset. Anticoag: CHA₂DS₂-VASc ≥ 2M / ≥ 3F → DOAC (apixaban preferred).
Key Drugs
Diltiazem ER180-360 mg daily
Metoprolol XL25-200 mg daily
Apixaban5 mg BID
Amiodarone200 mg daily (rhythm)
Pitfalls
- CCB in HFrEF (negative inotrope → worsens HF)
- Not anticoagulating based on CHA₂DS₂-VASc
- Not checking TSH (hyperthyroidism is reversible cause)
- Not screening for OSA (#1 modifiable risk factor for AF recurrence)
Interactive Decision Support
Differential Diagnosis Trees
Work through common presentations step-by-step with interactive decision trees. Click through questions to narrow your differential.
Acute Dyspnea
Chest Pain
Altered Mental Status
Hypotension / Shock
Rotation
ICU / Critical Care
Ventilator management, hemodynamic support, end-organ protection, and rapid recognition of life-threatening conditions. These are the topics you will use every day.
Core Topics
Sepsis & Septic Shock
COPD Exacerbation
ARDS
Airway & Ventilator Management
Cardiogenic Shock
DKA / HHS
Hypertensive Emergency
Hepatic Encephalopathy / ALF
Status Epilepticus
Upper GI Bleed
Post-Cardiac Arrest (ROSC)
Afib with RVR
ADHF
Pulmonary Embolism
Hyperkalemia
Alcohol Withdrawal & DTs
Acute Pancreatitis
Acute Ischemic Stroke
Mesenteric Ischemia
Massive Transfusion Protocol
Brain Death Evaluation
Targeted Temperature Management
Fat Embolism Syndrome
Malignant Hyperthermia
Intubation / RSI
📚 Resources
🌐 Website
Open ↗
POCUS 101 — Cardiac Ultrasound Step-by-Step Guide
https://www.pocus101.com/cardiac-ultrasound-echocardiography-made-easy-step-by-step-guide/
⭐ Featured
🌐 Website
Open ↗
U of T PIE — FOCUS Cardiac POCUS
https://pie.med.utoronto.ca/POCUS/POCUS_content/focus.html
⭐ Featured
📋 Major Guidelines
Clinical Practice Guidelines
6 guidelines
›
Rotation
Cardiology
ACS, arrhythmias, heart failure, valvular disease, and hemodynamic support.
Available Topics
Heart Failure (Chronic / GDMT)
Atrial Fibrillation
STEMI
NSTEMI / Unstable Angina
Arrhythmias
Pericarditis
Aortic Dissection
Infective Endocarditis
Valvular Heart Disease
Syncope
Heart Block & Bradycardia
Myocarditis
Hypertrophic Cardiomyopathy
Cardiac Tamponade
Pulmonary Hypertension
Stable Angina & Chronic CAD
ACS Overview
Aortic Stenosis
Mitral Regurgitation
📚 Resources
📋 Major Guidelines
Clinical Practice Guidelines
12 guidelines
›
Cirrhosis & Ascites
End-stage liver disease with portal hypertension. Ascites is the most common complication — present in ~60% within 10 years. Every new ascites or admission needs a diagnostic paracentesis. Always tap — it changes management more than you expect.
🔍 Overview
Child-Pugh Classification
| Parameter | 1 Point | 2 Points | 3 Points |
|---|---|---|---|
| Bilirubin | < 2 | 2–3 | > 3 |
| Albumin | > 3.5 | 2.8–3.5 | < 2.8 |
| INR | < 1.7 | 1.7–2.3 | > 2.3 |
| Ascites | None | Mild (controlled) | Moderate-severe (refractory) |
| Encephalopathy | None | Grade I–II | Grade III–IV |
A (5–6): 1-yr survival ~100%. B (7–9): ~80%. C (10–15): ~45%. Child-Pugh C = decompensated → transplant evaluation.
MELD-Na Score
- MELD-Na = 3.78 × ln(bilirubin) + 11.2 × ln(INR) + 9.57 × ln(creatinine) + 1.32 × (137 − Na) − 0.025 × MELD + 6.43
- Used for transplant listing priority. Higher MELD = sicker = higher priority on the waitlist.
- MELD ≥ 15: transplant generally beneficial over medical management
- MELD ≥ 30: 3-month mortality > 50% without transplant
Decompensation Events
Development of any of these marks the transition from compensated to decompensated cirrhosis — median survival drops from > 12 years to ~2 years. Triggers transplant evaluation.
- Ascites — most common (see Ascites Management tab)
- Variceal hemorrhage — see Upper GI Bleed
- Hepatic encephalopathy — see Hepatic Encephalopathy
- SBP — see Spontaneous Bacterial Peritonitis
- Hepatorenal syndrome (HRS) — functional renal failure from splanchnic vasodilation
- Jaundice (bilirubin > 3 with liver failure)
💧 Ascites Management
Diagnostic Paracentesis — Always Tap
Every new-onset ascites, every admission, and every clinical deterioration in a cirrhotics requires diagnostic paracentesis. SBP is present in ~15% of cirrhotics admitted to hospital — often asymptomatic. You will miss it without tapping.
| Send | Why |
|---|---|
| Cell count + differential | PMN ≥ 250/mm³ = SBP (treat immediately — don't wait for culture). This is the most important test. |
| Albumin | Calculate SAAG (serum albumin − ascites albumin). SAAG ≥ 1.1 = portal hypertension (cirrhosis, HF, Budd-Chiari). SAAG < 1.1 = non-portal (malignancy, TB, nephrotic, pancreatitis). |
| Total protein | Ascites protein < 1.5 g/dL = high risk for SBP → consider prophylaxis. |
| Culture (blood culture bottles at bedside) | Inoculate aerobic + anaerobic blood culture bottles with 10 mL each. Bedside inoculation ↑ yield from ~50% to ~80%. |
| Glucose, LDH, gram stain | If concerned for secondary peritonitis (perforation): glucose < 50, LDH > serum, polymicrobial → CT + surgery. |
INR is NOT a contraindication to paracentesis. Cirrhotics are auto-anticoagulated but also auto-procoagulant (rebalanced hemostasis). Bleeding complications are < 1% even with INR > 2 and platelets < 50K. Do NOT transfuse FFP or platelets before a paracentesis.
Ascites Treatment
Step 1 — Sodium restriction
2g Na/day (< 88 mEq/day). This alone controls ascites in ~10–15%. Fluid restriction only if Na < 125 (dilutional hyponatremia).
Step 2 — Diuretics
Spironolactone 100 mg + furosemide 40 mg daily (100:40 ratio maintains K⁺ balance) AASLD Guidelines, 2021. Titrate every 3–5 days. Max: spironolactone 400 mg + furosemide 160 mg. Monitor weight (target loss 0.5 kg/day without edema, 1 kg/day with edema), BMP, Cr.
Step 3 — Large volume paracentesis (LVP)
If tense ascites or diuretic-refractory. Remove 5–8+ liters per session. If removing > 5 L → give albumin 6–8 g per liter removed (prevents post-paracentesis circulatory dysfunction) Ginès, 1988.
Step 4 — Refractory ascites
TIPS (transjugular intrahepatic portosystemic shunt) — reduces portal pressure, resolves ascites in ~75% Salerno, 2007. Risk: hepatic encephalopathy (30–50%). Contraindicated if: Child-Pugh > 13, MELD > 18 (relative), active HE, right heart failure. Or serial LVP q2 weeks + albumin.
⚠️ Key Complications
Hepatorenal Syndrome (HRS)
- Functional renal failure — kidneys are structurally normal but underperfused due to splanchnic vasodilation + renal vasoconstriction
- HRS-AKI (Type 1): rapid Cr rise > 2× baseline in < 2 weeks. Median survival 2 weeks without treatment.
- HRS-CKD (Type 2): gradual, stable Cr elevation. Associated with refractory ascites.
- Diagnosis: no response to volume challenge (albumin 1 g/kg × 2 days), no shock, no nephrotoxins, no parenchymal disease on UA/imaging
- Treatment: Albumin 20–40 g/day + octreotide 200 mcg SC TID + midodrine 7.5–15 mg TID (splanchnic vasoconstrictors). Or norepinephrine drip in ICU (more effective). Definitive treatment: liver transplant. CONFIRM, 2024: terlipressin FDA-approved for HRS-AKI (improved renal function in ~30%).
Variceal Prophylaxis
| Setting | Management |
|---|---|
| No varices | EGD screening. Repeat in 2–3 years (compensated) or 1 year (decompensated). |
| Small varices, no red signs | NSBB (propranolol 20–40 mg BID or nadolol 20–40 mg daily or carvedilol 6.25–12.5 mg daily Bañares, 2002). Target HR reduction 25% or HR 55–60. |
| Medium/large varices | NSBB (carvedilol preferred) OR endoscopic variceal ligation (EVL). Both are first-line for primary prophylaxis. PREDESCI, 2019: NSBB in compensated cirrhosis with CSPH delayed decompensation. |
| Post-bleed (secondary prophylaxis) | NSBB + EVL (combination is superior to either alone) Lo, 2012. TIPS if rebleeding despite combo Early-TIPS, 2010. |
🧪 Workup
Workup
- CBC, BMP, LFTs, INR, albumin
- MELD-Na
- RUQ US + AFP q6mo — HCC screening
- EGD — variceal screening
- Paracentesis — new ascites or clinical change
- Hepatitis serologies
- Autoimmune/metabolic panel
🚨 Management
Management
- Ascites: Na restrict 2g/day + spiro/furosemide 100:40. LVP+albumin. TIPS if refractory.
- Varices: nadolol prophylaxis. Bleed: octreotide+ceftriaxone+banding.
- HE: lactulose+rifaximin. Find precipitant.
- SBP: ceftriaxone+albumin. Lifelong prophylaxis.
- HCC: US+AFP q6mo.
- Transplant: refer MELD≥15.
📋 On Rounds
Why give albumin after large volume paracentesis?
Removing > 5 L of ascites causes post-paracentesis circulatory dysfunction (PPCD) — the rapid reduction in intra-abdominal pressure causes splanchnic vasodilation → effective hypovolemia → RAAS activation → sodium retention → faster ascites recurrence → HRS. Ginès, 1988 showed that albumin 6–8 g per liter removed prevents PPCD by expanding the intravascular volume. No other volume expander (NS, dextran, gelatin) has been shown to be as effective — albumin acts as both a volume expander and a free radical scavenger in cirrhosis.
Why is INR NOT a contraindication to paracentesis in cirrhosis?
Cirrhotic coagulopathy is a rebalanced hemostasis — both procoagulant factors (II, VII, IX, X) AND anticoagulant factors (protein C, protein S, antithrombin) are reduced proportionally. The INR measures only the procoagulant side and overestimates bleeding risk. Multiple large studies show bleeding complications from paracentesis are < 1% even with INR > 2 and platelets < 50K. Transfusing FFP or platelets before a paracentesis adds volume (worsens ascites), exposes patients to transfusion risks, and doesn't reduce bleeding. Just tap them.
What is the management of refractory ascites, and when do you consider TIPS?
Refractory ascites = doesn't respond to max diuretics (spironolactone 400 + furosemide 160) or diuretic-induced complications prevent dose escalation. Options: (1) Serial large-volume paracentesis (LVP) every 2-4 weeks + albumin infusion (6-8g per liter if > 5L drained). (2) TIPS (transjugular intrahepatic portosystemic shunt): reduces portal pressure → ascites resolves in ~75%. BUT: worsens hepatic encephalopathy (30-40%), contraindicated if MELD > 18, bilirubin > 3, or recurrent HE. (3) Transplant evaluation — refractory ascites = MELD exception points may apply. Avoid NSAIDs (renal vasoconstriction), avoid aminoglycosides (nephrotoxic), hold ACEi/ARBs (hypotension in cirrhotics).
What HCC screening do you order and how often?
Ultrasound + AFP (alpha-fetoprotein) every 6 months in all cirrhotic patients regardless of etiology. This is one of the most commonly missed screening protocols. If US is limited (obesity, nodular liver) → consider CT or MRI. If a lesion is found: LI-RADS classification on contrast-enhanced CT or MRI. LI-RADS 5 = definite HCC (arterial enhancement + washout on portal/delayed phase). Biopsy is NOT always needed — HCC can be diagnosed radiologically if classic features present. AFP alone is insufficient (sensitivity only ~60%). Screening should continue even if patient is listed for transplant — HCC may affect candidacy or prioritization.
📣 Sample Presentation
One-Liner
"Mr. Nguyen is a 56-year-old with alcohol-related cirrhosis, Child-Pugh C, MELD-Na 24, presenting with tense ascites and bilateral lower extremity edema. No fever, no confusion."
Key Points to Cover on Rounds
Chronic decompensated cirrhosis. Paracentesis: 4L drained, albumin 25g IV infused (replace 6-8g per liter if >5L). Fluid: PMN 120 (no SBP), culture sent. Diuretics: spironolactone 100 mg + furosemide 40 mg (100:40 ratio). Na-restricted diet (2g/day). Varices: on nadolol for secondary prophylaxis. HCC screening: US + AFP done last month — negative. Hepatology following. Transplant evaluation in progress — 6 months sobriety confirmed. MELD-Na 24.
⚡ Summary
Summary
Decompensation
Ascites, variceal bleed, HE, jaundice, SBP. Marks transition from compensated → decompensated. Median survival drops.
Ascites Rx
Na restriction 2g/day. Spironolactone + furosemide (100:40 ratio). LVP + albumin if tense/refractory. Consider TIPS.
Variceal Bleed
Octreotide drip + ceftriaxone + restrictive transfusion (Hgb 7-8). EGD within 12h for band ligation.
Screening
HCC: US + AFP every 6 months. Varices: EGD at diagnosis, then q1-2 years. Nadolol for secondary prophylaxis.
MELD-Na
Cr + Bilirubin + INR + Na. Determines transplant priority. MELD ≥ 15 → refer for transplant evaluation.
Avoid
NSAIDs (renal failure), aminoglycosides (nephrotoxic), ACEi/ARBs (hypotension), sedatives (worsen HE). Tylenol ≤ 2g/day OK.
💊 Medications
Key Medications — Hepatic Encephalopathy & Acute Liver Failure
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — Hepatic Encephalopathy & Acute Liver Failure
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
📄 One Pager
GI / Hepatology · One Pager
Cirrhosis
Screen for HCC (US + AFP q6mo) and varices (EGD). Ascites: Na restrict + spironolactone/furosemide. Avoid NSAIDs, sedatives, aminoglycosides.
Decompensation Signs
Ascites, variceal bleed, HE, jaundice, SBP. Marks transition to decompensated cirrhosis — median survival drops significantly.
Ascites Management
Na restriction 2g/day. Spironolactone 100 + furosemide 40 (100:40 ratio). LVP + albumin for tense/refractory. TIPS if refractory (caution: worsens HE).
Screening
HCC: US + AFP every 6 months. Varices: EGD at diagnosis. Band ligation or BB (nadolol) for secondary prophylaxis. MELD-Na ≥ 15 → transplant referral.
Key Drugs
Spironolactone100-400 mg daily
Furosemide40-160 mg daily
Nadolol20-80 mg daily
Lactulose15-30 mL q2-4h (for HE)
Pitfalls
- NSAIDs (renal failure in cirrhotics)
- ACEi/ARBs (hypotension)
- Missing HCC screening
- Not doing diagnostic paracentesis for new ascites or clinical change
Spontaneous Bacterial Peritonitis (SBP)
Infection of ascitic fluid without a surgically treatable source. Diagnosis: ascitic PMN ≥ 250/mm³. Treat immediately — don't wait for culture. Give albumin with antibiotics. 1-year mortality after first episode is ~70% — this means transplant evaluation.
🔍 Overview
Diagnosis
Ascitic fluid PMN ≥ 250 cells/mm³ = SBP. Start antibiotics immediately. Do NOT wait for culture results.
- PMN ≥ 250/mm³ with positive culture = SBP
- PMN ≥ 250/mm³ with negative culture = culture-negative neutrocytic ascites (CNNA) — treat the same as SBP
- PMN < 250/mm³ with positive culture = bacterascites — repeat paracentesis in 48h. Treat if symptomatic or PMN rises.
SBP vs Secondary Peritonitis
| Feature | SBP | Secondary Peritonitis (perforation) |
|---|---|---|
| Organisms | Monomicrobial (single enteric organism — E. coli, Klebsiella, strep) | Polymicrobial (multiple organisms including anaerobes) |
| Glucose | > 50 mg/dL | < 50 mg/dL |
| LDH | < serum LDH | > serum LDH |
| Protein | Low (< 1 g/dL) | Higher |
| Treatment | Antibiotics alone | Antibiotics + surgical source control (CT abdomen → OR) |
Runyon's criteria for secondary peritonitis: if ascitic fluid shows ≥ 2 of (glucose < 50, LDH > ULN serum, protein > 1 g/dL) + polymicrobial gram stain → get CT abdomen to rule out perforation. This patient needs surgery, not just antibiotics.
Common Organisms
- E. coli (~40%) — most common
- Klebsiella pneumoniae (~10–15%)
- Streptococcus pneumoniae (~10%)
- Enterococcus (~5–10%)
- Mechanism: bacterial translocation from gut lumen → mesenteric lymph nodes → bloodstream → ascitic fluid (which has impaired opsonization due to low complement/protein)
🚨 Management
Treatment
| Component | Regimen | Notes |
|---|---|---|
| Antibiotics IMMEDIATE | Ceftriaxone 2g IV daily × 5 days | Covers E. coli, Klebsiella, strep. If nosocomial SBP or recent FQ prophylaxis failure → broaden to piperacillin-tazobactam or meropenem (resistance is higher). Narrow based on culture + sensitivity. |
| Albumin CRITICAL | 1.5 g/kg on day 1, then 1 g/kg on day 3 | SBP Albumin Trial, 1999: albumin with antibiotics in SBP reduced HRS from 33% to 10% and mortality from 29% to 10%. One of the most impactful interventions in hepatology. Do not skip this. |
Follow-Up & Response
- Repeat paracentesis at 48h if no clinical improvement. PMN should decrease by ≥ 25%. If not → suspect resistant organism, secondary peritonitis, or wrong diagnosis.
- Total duration: 5 days if culture-guided. 5–7 days empiric if culture-negative.
- After first SBP episode → lifelong prophylaxis (see below)
- Transplant evaluation — 1-year survival after SBP is ~30–70%. SBP marks a critical inflection point.
SBP Prophylaxis
| Indication | Regimen |
|---|---|
| Prior SBP episode (secondary prophylaxis) | Norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily or TMP-SMX DS daily) — lifelong |
| Ascitic protein < 1.5 g/dL + advanced liver disease (Child-Pugh ≥ 9 with bilirubin ≥ 3 OR Cr ≥ 1.2 or Na ≤ 130 or BUN ≥ 25) | Norfloxacin 400 mg daily (or alternatives as above). Fernández, 2007: primary prophylaxis in high-risk patients reduced SBP incidence and improved survival. |
| Acute GI hemorrhage (all cirrhotics) | Ceftriaxone 1g IV daily × 7 days — reduces SBP, bacteremia, and mortality in acute variceal bleed Fernández, 2006. |
🔄 Updated Practice: Old teaching: all cirrhotic patients with ascites need fluoroquinolone prophylaxis for SBP. Current practice: SBP prophylaxis is only recommended for (1) prior SBP episode (secondary prophylaxis — norfloxacin or TMP-SMX), (2) GI bleed in cirrhosis (ceftriaxone 1g IV × 7 days), or (3) ascitic fluid protein <1.5 g/dL with either Child-Pugh ≥9 or renal dysfunction. Indiscriminate FQ use drives resistance. Also: rifaximin (Xifaxan) may be an alternative for SBP prophylaxis — emerging evidence but not yet guideline-recommended.
📋 On Rounds
Why is albumin so important in SBP treatment?
SBP Albumin Trial, 1999: in the landmark RCT, adding albumin (1.5 g/kg day 1, 1 g/kg day 3) to ceftriaxone in SBP reduced renal impairment (HRS) from 33% to 10% and in-hospital mortality from 29% to 10%. The mechanism: SBP causes an inflammatory cascade → splanchnic vasodilation → effective hypovolemia → RAAS activation → renal vasoconstriction → HRS. Albumin expands the intravascular volume, prevents the hemodynamic deterioration, and has anti-inflammatory properties. This is one of the strongest mortality benefits of any intervention in hepatology — never skip the albumin.
Why do you give albumin with antibiotics in SBP, and what's the dosing?
Albumin prevents hepatorenal syndrome (HRS), which is the leading cause of death in SBP — not the infection itself. The Sort trial [SBP Albumin Trial, 1999 showed albumin 1.5 g/kg on day 1 + 1 g/kg on day 3 reduced renal failure from 33% to 10% and mortality from 29% to 10%. The mechanism: SBP causes massive cytokine release → splanchnic vasodilation → effective hypovolemia → renal hypoperfusion. Albumin acts as a volume expander to maintain renal perfusion. This is one of the highest-impact interventions in hepatology — don't skip it.
What are the criteria for SBP prophylaxis and what do you prescribe?
Primary prophylaxis (never had SBP): indicated if ascitic fluid protein < 1.5 g/dL + either (1) renal dysfunction (Cr > 1.2, BUN > 25, or Na < 130) or (2) liver failure (Child-Pugh ≥ 9 + bilirubin ≥ 3). Drug: norfloxacin 400 mg daily or TMP-SMX DS daily. Secondary prophylaxis (after first SBP episode): LIFELONG — norfloxacin 400 mg daily or TMP-SMX DS daily. Recurrence rate without prophylaxis is ~70% at 1 year. Also: all cirrhotic patients with GI bleed get ceftriaxone 1g daily × 7 days (counts as SBP prophylaxis during the bleed). Do NOT use ciprofloxacin for long-term prophylaxis — resistance and tendon/CNS toxicity.
Why is ceftriaxone preferred over fluoroquinolones for SBP treatment?
Rising fluoroquinolone resistance (many cirrhotic patients are on norfloxacin/cipro prophylaxis → resistant organisms). Ceftriaxone 2g IV daily has excellent activity against the common SBP pathogens (E. coli, Klebsiella, Strep) and is well-tolerated in liver disease. If the patient develops SBP while already on FQ prophylaxis, the organism is likely FQ-resistant → ceftriaxone or pip-tazo. For nosocomial SBP (developed in-hospital), consider broader coverage (pip-tazo or meropenem) due to higher rates of resistant organisms.
📣 Sample Presentation
One-Liner
"Mr. DeSilva is a 52-year-old with cirrhosis and ascites presenting with fever 38.6°C, diffuse abdominal pain, and worsening confusion. Paracentesis: PMN 680. Consistent with SBP."
Key Points to Cover on Rounds
PMN 680 (>250 = SBP). Gram stain: GNR (likely E. coli). Culture pending. Antibiotics: ceftriaxone 2g IV daily started within 1 hour. Albumin protocol: 1.5 g/kg (112g) on day 1, 1 g/kg (75g) on day 3 to prevent HRS [SBP Albumin Trial, 1999]. Repeat paracentesis at 48h planned (PMN should drop >25%). Mental status improving with lactulose (SBP was the precipitant for HE). Plan: 5-day antibiotic course, start norfloxacin prophylaxis at discharge.
🧪 Workup
Diagnostic Evaluation — Spontaneous Bacterial Peritonitis
Diagnostic paracentesis is mandatory in any cirrhotic with ascites presenting with fever, abdominal pain, AMS, or worsening clinical status. Tap first, then start antibiotics.
- Diagnostic paracentesis: Cell count with differential (PMN ≥ 250/mm³ = SBP), gram stain, culture (inoculate blood culture bottles at bedside), albumin, total protein
- Ascitic fluid glucose, LDH, protein: If secondary peritonitis suspected (polymicrobial, glucose < 50, LDH > ULN, protein > 1 g/dL → CT abdomen)
- Blood cultures: Before antibiotics — bacteremia common in SBP
- BMP/Cr: Baseline renal function — HRS surveillance
- CBC, LFTs, INR, lactate: Assess severity, liver function, sepsis
💊 Medications
Key Medications — Spontaneous Bacterial Peritonitis
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| Ceftriaxone (Rocephin) 1ST LINE | 2g IV daily | 5 days | Covers E. coli, Klebsiella, Strep. Start immediately once PMN ≥ 250. If nosocomial SBP or FQ prophylaxis failure → broaden to piperacillin-tazobactam or meropenem. |
| Albumin CRITICAL | 1.5 g/kg on day 1 + 1 g/kg on day 3 | 2 doses | Reduces HRS from 33% to 10% and mortality from 29% to 10% SBP Albumin Trial, 1999. Do NOT skip this — one of the highest-impact interventions in hepatology. |
| PROPHYLAXIS (after acute treatment) | |||
| Norfloxacin | 400 mg PO daily | Lifelong (secondary prophylaxis) | First-line for secondary prophylaxis after first SBP episode. Also for primary prophylaxis if ascitic protein < 1.5 g/dL with renal/liver dysfunction. |
| TMP-SMX DS | 1 DS tablet PO daily | Lifelong | Alternative to norfloxacin for secondary prophylaxis. Equally effective. |
| Ceftriaxone (Rocephin) | 1g IV daily | 7 days | Acute GI hemorrhage prophylaxis in all cirrhotics — reduces SBP, bacteremia, and mortality during variceal bleed. |
Primary prophylaxis criteria: ascitic fluid protein < 1.5 g/dL PLUS either Child-Pugh ≥ 9 with bilirubin ≥ 3, OR renal dysfunction (Cr ≥ 1.2, Na ≤ 130, BUN ≥ 25).
📈 Monitoring
Monitoring Parameters — Spontaneous Bacterial Peritonitis
| Parameter | Frequency | Target / Action |
|---|---|---|
| Repeat paracentesis | At 48 hours | PMN should drop > 25% from baseline. If not improving → suspect resistant organism, secondary peritonitis, or wrong diagnosis. Broaden antibiotics and get CT abdomen. |
| BMP / Creatinine | Daily | HRS surveillance. Rising Cr despite albumin = hepatorenal syndrome → urgent nephrology + hepatology consult. Cr is the most important lab to trend. |
| Urine output | Strict I&Os | UOP < 0.5 mL/kg/hr or declining → early sign of HRS. Correlate with Cr trend. |
| Mental status | q4–8h | HE surveillance — SBP is the most common precipitant of hepatic encephalopathy. Worsening confusion → start/escalate lactulose. |
| Blood cultures | At diagnosis, repeat if persistent fever | Guide antibiotic narrowing once sensitivity data available. |
| Vitals | q4h | Fever curve, hemodynamics. Persistent fever > 72h on appropriate antibiotics → reconsider diagnosis. |
The 48-hour paracentesis is critical. If PMN count is not dropping > 25%, you need to reconsider: resistant organism (broaden coverage), secondary peritonitis (get CT), or bacterascites that resolved on its own.
⚡ Summary
Summary
Diagnosis
Ascitic fluid PMN ≥ 250/mm³. Do NOT wait for culture. Paracentesis is the test — do it in every cirrhotic with AMS, fever, or pain.
Treatment
Ceftriaxone 2g IV daily × 5 days. Albumin: 1.5 g/kg day 1 + 1 g/kg day 3 (prevents hepatorenal syndrome) [SBP Albumin Trial, 1999].
Repeat LP
At 48h: PMN should drop > 25%. If not → broaden abx, consider secondary peritonitis (surgical abdomen).
Prophylaxis
Secondary: norfloxacin or TMP-SMX daily (lifelong). Primary: if ascitic protein < 1.5 + renal/liver dysfunction.
Triggers
GI bleed, UTI, line infection, constipation. Often no identifiable source — spontaneous translocation from gut.
Prognosis
1-year mortality ~30-50% after first SBP episode. Start transplant evaluation immediately.
📄 One Pager
Spontaneous Bacterial Peritonitis — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
SPONTANEOUS BACTERIAL PERITONITIS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
GI / Hepatology · One Pager
Spontaneous Bacterial Peritonitis
PMN ≥ 250 on paracentesis. Ceftriaxone + albumin (1.5g/kg day 1 + 1g/kg day 3). Lifelong secondary prophylaxis. Start transplant eval.
Diagnosis
Ascitic fluid PMN ≥ 250/mm³. Do paracentesis in every cirrhotic with fever, AMS, abdominal pain, or clinical deterioration. Don't wait for culture.
Treatment
Ceftriaxone 2g IV daily × 5 days. Albumin 1.5g/kg day 1 + 1g/kg day 3 (prevents HRS) [SBP Albumin Trial, 1999]. Repeat paracentesis at 48h (PMN should drop > 25%).
Prophylaxis
Secondary (after first SBP): norfloxacin 400 mg or TMP-SMX DS daily — LIFELONG. Primary: if ascitic protein < 1.5 + renal/liver dysfunction. GI bleed: ceftriaxone × 7 days.
Key Drugs
Ceftriaxone2g IV daily × 5d
Albumin1.5g/kg D1 + 1g/kg D3
Norfloxacin400 mg daily (prophylaxis)
TMP-SMX DS1 tab daily (alternative)
Pitfalls
- Not doing paracentesis (the test IS the diagnosis)
- Forgetting albumin (prevents HRS — mortality benefit)
- Not starting lifelong secondary prophylaxis
- Missing secondary peritonitis (surgical abdomen, multiple organisms)
Clostridioides difficile (C. diff)
The most common healthcare-associated infection. Antibiotics disrupt the normal gut flora → C. diff overgrowth → toxin production → colitis. Fidaxomicin is now first-line over oral vancomycin. Stop the offending antibiotic if possible.
🔍 Overview
Risk Factors
- Antibiotics — #1 risk factor. Worst offenders: fluoroquinolones (#1), clindamycin, cephalosporins, carbapenems. But ANY antibiotic can cause it.
- Age > 65
- Hospitalization / healthcare facility
- PPI use — controversial but associated in multiple studies
- Immunosuppression, chemotherapy, IBD, recent GI surgery
Diagnosis
- Only test patients with ≥ 3 unformed stools in 24h. Do NOT test formed stool. Do NOT test asymptomatic patients. Do NOT test as "test of cure" after treatment.
- Best test: NAAT (PCR) for toxin gene — highly sensitive. But detects carriers too (can be positive for weeks after treatment). Combine with toxin EIA for clinical disease.
- Recommended algorithm: GDH screen (sensitive) → if positive → toxin EIA (specific). Or: NAAT + toxin EIA together. NAAT-positive + toxin-negative = possible carrier — clinical judgment needed.
Severity Classification (IDSA/SHEA 2021)
| Severity | Criteria |
|---|---|
| Non-severe | WBC ≤ 15,000 AND Cr < 1.5 mg/dL |
| Severe | WBC > 15,000 OR Cr ≥ 1.5 |
| Fulminant | Hypotension, shock, ileus, or megacolon |
💊 Management
Treatment by Severity
| Severity | First Episode | First Recurrence | Second+ Recurrence |
|---|---|---|---|
| Non-severe | Fidaxomicin 200 mg PO BID × 10 days PREFERRED OR vancomycin 125 mg PO QID × 10 days | Fidaxomicin 200 mg PO BID × 10 days (preferred) or vancomycin pulse-taper | Vancomycin pulse-taper, fidaxomicin, or fecal microbiota transplant (FMT) |
| Severe | Vancomycin (Vancocin) 125 mg PO QID × 10 days OR fidaxomicin 200 mg PO BID × 10 days | Same as first episode + consider FMT | FMT strongly recommended |
| Fulminant | Vancomycin 500 mg PO/NG QID + metronidazole 500 mg IV q8h. If ileus: add vancomycin retention enemas 500 mg in 100 mL NS q6h. Surgical consult → subtotal colectomy if toxic megacolon, perforation, or no improvement. | Same approach. Early surgical involvement critical. | |
Key Treatment Principles
- Stop the offending antibiotic if at all possible — this is the single most important step
- Fidaxomicin is now preferred over vancomycin for initial non-severe CDI IDSA/SHEA, 2021 — lower recurrence rate (~13% vs ~27%) because it's narrow-spectrum and preserves normal flora
- IV metronidazole is ONLY used in fulminant CDI (as adjunct to PO/PR vancomycin). It is NOT first-line for any other severity — oral metronidazole is inferior to vancomycin
- Do NOT use loperamide (Imodium) — can precipitate toxic megacolon
- Contact precautions: gown + gloves, hand washing with soap and water (alcohol-based sanitizer does NOT kill C. diff spores)
- Bezlotoxumab (anti-toxin B monoclonal antibody): single IV dose during treatment → reduces recurrence by ~40% MODIFY I/II, 2017. Consider for high recurrence risk patients.
🔄 Updated Practice: Old teaching: oral metronidazole (Flagyl) is first-line for C. difficile. WRONG — this changed in 2017. Current first-line (IDSA/SHEA 2021): fidaxomicin (Dificid) 200mg BID × 10 days (preferred — lower recurrence) OR vancomycin 125mg PO QID × 10 days. Oral metronidazole is NO LONGER recommended for initial episodes. IV metronidazole is only added in fulminant C. difficile (when ileus may prevent oral drug delivery to the colon). Also: fecal microbiota transplant (FMT) is recommended after ≥2 recurrences.
Vancomycin Pulse-Taper (for recurrence)
🧪 Workup
Diagnostic Workup — C. difficile
Only test unformed stool in symptomatic patients (≥ 3 episodes/24h). Do NOT test formed stool. Do NOT test asymptomatic patients. Do NOT retest as "test of cure" after treatment.
| Test | Rationale | Key Values / Notes |
|---|---|---|
| Stool C. diff testing | Confirm diagnosis. Use institutional algorithm — do NOT order both PCR and toxin independently. | NAAT/PCR = highly sensitive (detects carriers). Toxin EIA = specific for active disease. Best approach: GDH screen → toxin EIA, or NAAT + toxin EIA. PCR⁺/toxin⁻ = possible carrier — use clinical judgment. |
| CBC with differential | WBC stratifies severity and identifies fulminant disease. | WBC > 15K = severe. WBC > 30K = fulminant (high mortality). Bandemia and left shift common. |
| BMP (Cr) | Creatinine defines severity. Monitor renal function during illness. | Cr ≥ 1.5 mg/dL = severe (IDSA/SHEA criteria). Also check K⁺ (diarrheal losses) and bicarb. |
| Lactate | Elevated lactate = fulminant disease or sepsis. | Lactate > 5 mmol/L = fulminant CDI. Indicates tissue hypoperfusion — consider surgical consult. |
| CT abdomen/pelvis | If concern for fulminant disease, toxic megacolon, or perforation. | Colonic wall thickening, pericolonic stranding, "accordion sign." Colon > 6 cm = megacolon → urgent surgical consult. |
| Abdominal X-ray | Rapid screen for megacolon if CT not immediately available. | Dilated colon, thumbprinting, pneumatosis. Less sensitive than CT. |
💊 Medications
Drug Therapy — C. difficile
| Drug | Dose | Route | Indication | Key Notes |
|---|---|---|---|---|
| Fidaxomicin (Dificid) FIRST-LINE | 200 mg BID × 10 days | PO | First-line for initial and recurrent episodes (non-severe and severe) | Narrow-spectrum — preserves gut flora → lower recurrence (~13% vs ~27% for vancomycin) IDSA/SHEA, 2021. Main limitation: cost (~$3,000). |
| Vancomycin PO | 125 mg QID × 10 days | PO | Alternative first-line. Standard-dose for non-severe and severe. | 500 mg QID for fulminant disease. Not absorbed systemically — acts locally in gut. IV vancomycin does NOT treat C. diff (does not reach colon). |
| Vancomycin pulse-taper | 125 mg QID × 14d → BID × 7d → daily × 7d → q2d × 7d → q3d × 14d | PO | First and subsequent recurrences | Gradual taper allows spore germination between doses, then kills vegetative forms. Effective for breaking recurrence cycle. |
| Metronidazole (Flagyl) | 500 mg IV q8h | IV | Fulminant CDI adjunct ONLY (with PO/PR vancomycin) | NO longer recommended as monotherapy for any severity. IV metronidazole reaches colon via biliary excretion — useful when ileus prevents oral drug delivery. |
| Vancomycin enemas | 500 mg in 100 mL NS q6h | PR | Fulminant CDI with ileus (oral medications cannot reach colon) | Given in addition to PO/NG vancomycin and IV metronidazole. Retain for 60 minutes if possible. |
| Bezlotoxumab (Zinplava) | 10 mg/kg IV × 1 dose | IV | Recurrence prevention in high-risk patients (during active treatment course) | Anti-toxin B monoclonal antibody. Reduces recurrence by ~40% MODIFY I/II, 2017. Consider if: age ≥ 65, immunocompromised, severe CDI, or prior recurrence. |
| Fecal microbiota transplant (FMT) | Per protocol (colonoscopic, capsule, or enema) | Various | After ≥ 2 recurrences despite appropriate antibiotic therapy | ~85-90% cure rate for recurrent CDI. FDA-approved products now available (RBX2660/Rebyota, SER-109/Vowst). Restores normal gut microbiome. |
📊 Monitoring
Monitoring — C. difficile
| Parameter | Frequency | Target / Action |
|---|---|---|
| Stool frequency | Daily (nursing stool count) | Expect improvement in 3-5 days. Stool frequency should decrease. Diarrhea may persist for days even with effective treatment — judge by trend, not single day. |
| WBC | Daily if severe or fulminant; q2-3 days if non-severe | Trending down = improving. Rising WBC (especially > 30K) = worsening → reassess severity, consider surgical consult. Leukemoid reaction (> 40K) is a poor prognostic sign. |
| Creatinine | Daily if severe/fulminant; at baseline and mid-course if non-severe | Rising Cr = worsening (may need to escalate therapy). AKI from volume depletion — ensure adequate hydration. |
| Lactate | q6-12h if severe or fulminant | Lactate > 5 = fulminant disease. Rising lactate = tissue hypoperfusion → ICU, surgical consult. |
| Abdominal exam | At least daily; more frequently if severe/fulminant | Increasing distension, tenderness, guarding, rigidity → CT imaging, surgical consult. Absent bowel sounds + distension = ileus (add rectal vancomycin). |
| Volume status | Each assessment | Aggressive IV fluid resuscitation for dehydration from diarrhea. Monitor UOP, orthostatics, mucous membranes. |
Do NOT repeat C. diff testing for "test of cure." PCR can remain positive for weeks after successful treatment. Retesting leads to unnecessary retreatment. Judge resolution by clinical improvement (decreased stool frequency, resolving WBC/Cr), not by repeat testing.
📋 On Rounds
Why is fidaxomicin preferred over vancomycin now?
Fidaxomicin is a narrow-spectrum macrocyclic antibiotic that kills C. diff but preserves the normal anaerobic gut flora (Bacteroides and other protective commensals). Vancomycin kills C. diff but also disrupts normal flora — leaving the gut vulnerable to recolonization once vancomycin is stopped. This is why fidaxomicin has a significantly lower recurrence rate (~13% vs ~27%) Louie, 2011. The main disadvantage: cost (~$3,000 vs ~$50 for vancomycin). For recurrent CDI, this recurrence reduction makes fidaxomicin even more valuable.
Why doesn't alcohol-based hand sanitizer work for C. diff?
C. difficile forms spores — a dormant, highly resistant form that survives on surfaces for months. Spores have a tough outer coat that is resistant to alcohol, heat, and most disinfectants. Alcohol-based hand sanitizers kill vegetative bacteria but cannot penetrate or destroy spores. Only mechanical removal with soap and water (friction + rinsing) and sporicidal agents (bleach-based disinfectants for surfaces) are effective. This is why hand washing with soap and water is required for C. diff patients, and why rooms must be cleaned with bleach-based products.
When should you consult surgery for C. difficile?
Surgical consultation for fulminant C. diff: (1) Toxic megacolon (colon > 6 cm on imaging), (2) Bowel perforation, (3) Hemodynamic instability requiring vasopressors, (4) Organ failure (AKI, respiratory failure), (5) WBC > 30K or lactate > 5 (markers of severity associated with high mortality). Surgery = subtotal colectomy with end ileostomy. Mortality of fulminant C. diff requiring surgery is 30-50% even with intervention. Newer approach: diverting loop ileostomy with colonic vancomycin lavage — less morbid, some centers are moving to this. Key: don't wait until the patient is moribund to consult surgery — early surgical input improves outcomes. If the patient is on vasopressors for C. diff, surgery should already be involved.
Why is fidaxomicin preferred over oral vancomycin for C. diff?
Fidaxomicin has a significantly lower recurrence rate (~13% vs ~27% for vancomycin). Mechanism: fidaxomicin is narrow-spectrum (kills C. diff but spares normal gut flora), while vancomycin is broader and disrupts the microbiome → easier for C. diff to re-establish. [IDSA/SHEA, 2021 now recommends fidaxomicin as first-line for initial and recurrent episodes. The downside: cost (~$3,500 vs ~$200 for vancomycin). For severe/fulminant disease: vancomycin PO 500 QID + metronidazole IV is still the regimen (fidaxomicin has not been studied in fulminant disease).
📣 Sample Presentation
One-Liner
"Mrs. Clark is a 72-year-old recently discharged after hip replacement (received cefazolin perioperatively) presenting with watery diarrhea 8×/day, WBC 18K, Cr 1.1. C. diff toxin positive."
Key Points to Cover on Rounds
Non-severe C. diff (WBC 18K but Cr 1.1). Treatment: fidaxomicin 200 mg BID × 10 days (preferred over vanc PO — lower recurrence rate [IDSA/SHEA, 2021]). Cefazolin was the precipitant — no current antibiotics to stop. Contact precautions. Soap and water hand hygiene (alcohol doesn't kill spores). Stool frequency tracking: 8/day → 4/day on day 2. Plan: complete 10-day course, consider bezlotoxumab if high recurrence risk (age >65, immunocompromised, prior C. diff).
⚡ Summary
Summary
First-Line
Fidaxomicin 200 BID × 10 days (lower recurrence) [IDSA/SHEA, 2021]. Alternative: vancomycin PO 125 QID × 10 days.
Fulminant
Vancomycin PO 500 QID + metronidazole 500 IV q8h. Ileus → vancomycin rectal enema. Surgical consult if toxic megacolon.
Infection Control
Contact precautions. Soap and water handwashing (alcohol doesn't kill spores). Dedicated equipment.
Recurrence
First recurrence: fidaxomicin or vancomycin taper/pulse. Multiple: bezlotoxumab. Consider fecal microbiota transplant.
Risk Factors
Recent antibiotics (#1), PPI use, age > 65, hospitalization, immunocompromised, prior C. diff episode.
Surgery Consult
WBC > 30K, lactate > 5, toxic megacolon, organ failure, perforation, refractory to medical therapy.
📄 One Pager
GI / ID · One Pager
C. difficile Infection
Fidaxomicin first-line (lower recurrence). Stop offending antibiotics. Soap and water only (alcohol won't kill spores). Surgery consult if fulminant.
Diagnosis
Diarrhea (≥ 3 unformed stools/24h) + positive C. diff test (toxin EIA or PCR). Don't test formed stools. Don't test as "test of cure."
Treatment
Non-severe: fidaxomicin 200 BID × 10 days [IDSA/SHEA 2021] or vancomycin PO 125 QID × 10 days. Fulminant: vanc PO 500 QID + metronidazole 500 IV q8h.
Recurrence
1st recurrence: fidaxomicin or vanc taper/pulse. 2nd+: bezlotoxumab (anti-toxin B antibody). FMT (fecal microbiota transplant) for multiple recurrences.
Key Drugs
Fidaxomicin200 mg BID × 10d
Vancomycin PO125 mg QID × 10d
Metronidazole IV500 mg q8h (fulminant)
Bezlotoxumab10 mg/kg IV × 1 (recurrence prevention)
Pitfalls
- Using metronidazole alone (inferior to vancomycin/fidaxomicin)
- Testing for "cure" (don't retest after treatment)
- Not using soap and water (alcohol fails against spores)
- Unnecessary PPI use (risk factor for C. diff)
Lower GI Bleed
Bleeding distal to the ligament of Treitz. Usually presents with hematochezia (bright red blood per rectum). 80–85% stop spontaneously. The key question: is this really a lower bleed, or is it a brisk upper GI bleed presenting with hematochezia?
🔍 Overview
Common Causes
| Cause | % of LGIB | Key Features | ||||
|---|---|---|---|---|---|---|
| Diverticular bleed | ~30–40% | Most common cause in adults > 60. Painless, large-volume, bright red blood. Usually self-limited (80% stop spontaneously). Right-sided diverticula bleed more often than left. | ||||
| Hemorrhoids | ~20% | Bright red blood on toilet paper or coating stool. Most common cause of LGIB overall when including outpatient. Usually minor. | ||||
| Angiodysplasia / AVM | ~10% | Vascular ectasias, usually right colon. Chronic, intermittent bleeding. Associated with aortic stenosis (Heyde syndrome) and CKD. | ||||
| Colitis (ischemic, IBD, infectious) | ~10–15% | Bloody diarrhea + abdominal pain. Ischemic colitis: elderly + hypotension → "watershed" (splenic flexure). IBD: younger, chronic. | ||||
| Colorectal cancer/polyps | ~5–10% | Occult or slow chronic bleeding → iron deficiency anemia. Mass on colonoscopy. | ||||
| Post-polypectomy bleed | Variable | 1–7 days after colonoscopy with polypectomy. Usually self-limited. | ||||
| Test | When | Notes |
|---|---|---|
| CT angiography | Active bleeding (requires > 0.3–0.5 mL/min) | Fast, widely available. Localizes active extravasation. Can guide IR embolization. Get BEFORE colonoscopy if hemodynamically unstable. |
| Tagged RBC scan (nuclear medicine) | Intermittent or slow bleeding (> 0.1 mL/min) | More sensitive than CTA for slow bleeds. Localizes to a region (not exact vessel). Takes hours. Less useful in acute management. |
| Angiography + embolization (IR) | Active hemorrhage not controlled by endoscopy | Requires active bleeding (> 0.5 mL/min). Can embolize the bleeding vessel. Risk: bowel ischemia (~5%). |
| Surgery | Massive, life-threatening, refractory bleed | Last resort. Segmental colectomy if source localized. Subtotal colectomy if source unknown (high morbidity). Always try to localize before surgery. |
Anticoagulation in LGIB
- Hold anticoagulation during active bleed + resuscitation
- Restart early — within 7 days for most patients (if indication is strong: Afib, mechanical valve, recent VTE). Longer delay → increased thromboembolic events without mortality benefit from reduced rebleeding.
- Aspirin for secondary cardiovascular pre
vention: do NOT stop (increased cardiac events outweigh GI bleed risk). Hold if li🧪 WorkupWorkup
- CBC, BMP, coags, type&screen
- BUN/Cr ratio >20 → upper source
- Colonoscopy within 24h
- CTA abdomen if unstable
- EGD first if upper suspected
- Tagged RBC scan for intermittent bleeds
fe-threatening hemorrhage only.💊 MedicationsMedicationsDrug Dose Route Notes pRBCs If Hgb<7 IV Restrictive Hold anticoag Resume after hemostasis — — PPI If upper source suspected IV —
📊 Monitoring
Monitoring
- Hgb q6-8h during active bleed
- Hemodynamics
- Stool output
- Repeat Hgb after transfusion
📋 On Rounds
A patient presents with massive hematochezia and hemodynamic instability. What do you do first?
Resuscitate and consider an upper source. Massive hematochezia with hemodynamic instability has a ~15% chance of being from a brisk upper GI bleed (variceal, ulcer). Steps: (1) Large-bore IVs, crystalloid, activate massive transfusion if needed. (2) Urgent EGD or NG lavage to rule out upper source — this changes management completely (octreotide for varices, PPI for ulcer). (3) If EGD negative and ongoing bleeding → CTA to localize → IR embolization or urgent colonoscopy. (4) Surgery only as last resort. The mistake: going straight to colonoscopy and missing a bleeding duodenal ulcer.
What is Heyde syndrome?
Aortic stenosis + GI bleeding from angiodysplasia. The mechanism: blood flowing through the stenotic aortic valve experiences high shear stress → destruction of von Willebrand factor (vWF) high-molecular-weight multimers → acquired von Willebrand disease type 2A → impaired hemostasis → bleeding from pre-existing angiodysplasia in the GI tract. The GI bleeding resolves after aortic valve replacement (removes the shear stress → vWF multimers normalize). Classic boards question linking cardiology and GI.
15% of patients presenting with hematochezia actually have an upper GI source. How do you catch this?
Bright red blood per rectum doesn't always mean lower GI bleed. A brisk upper GI bleed can transit fast enough to appear as hematochezia. Clues it's actually upper: (1) Hemodynamic instability disproportionate to rectal bleeding, (2) Elevated BUN/Cr ratio > 20 (blood protein digestion in upper GI → urea absorption), (3) NG tube with bloody aspirate (but a clear aspirate does NOT rule out upper — pyloric spasm can prevent reflux). (4) Melena mixed with bright blood. If in doubt, EGD before colonoscopy — you don't want to prep for a colonoscopy while missing a bleeding duodenal ulcer. In massive LGIB, CTA abdomen/pelvis can identify the bleeding source if the patient is too unstable for endoscopy.
What is the role of CTA in acute lower GI bleed?
CT angiography can detect active bleeding if the rate is ≥ 0.3-0.5 mL/min (extravasation of contrast = active bleed). Best for: (1) hemodynamically unstable patient too sick for colonoscopy, (2) massive ongoing bleed where endoscopy can't visualize the source, (3) localizing the bleed for IR angiographic embolization. Limitation: if the bleeding is intermittent or has stopped, CTA will be negative. Tagged RBC scan is more sensitive for slow/intermittent bleeds but less specific for location. Algorithm: stable → colonoscopy within 24h. Unstable → CTA → if positive → IR embolization or surgery.
📣 Sample Presentation
One-Liner
"Mr. Peters is a 74-year-old on apixaban presenting with 3 episodes of painless bright red blood per rectum. Hemodynamically stable, Hgb 9.8 from baseline 13.2."
Key Points to Cover on Rounds
Lower GI bleed, likely diverticular (painless, large-volume, elderly). Hemodynamically stable (HR 82, BP 134/78). Apixaban held. Hgb 9.8 — transfused 1 unit pRBC. Upper source ruled out (no melena, no hematemesis, BUN/Cr ratio normal). GI consulted — colonoscopy planned within 24h after bowel prep. If active bleeding identified → endoscopic hemostasis. If massive/unstable → CTA abdomen/pelvis. Bleeding has stopped spontaneously. Plan: colonoscopy tomorrow, resume apixaban after hemostasis confirmed.
⚡ Summary
Summary
Most Common
Diverticular bleeding (#1 in elderly, painless), hemorrhoids (#1 overall), angiodysplasia, ischemic colitis, malignancy.
15% Are Upper
Brisk upper GI bleed → hematochezia. Clues: hemodynamic instability, elevated BUN/Cr ratio > 20. EGD before colonoscopy if suspected.
Stable
Colonoscopy within 24h (after prep). Hold anticoag. Transfuse if Hgb < 7.
Unstable
CTA abdomen/pelvis → if active extravasation → IR embolization. If unlocalized → tagged RBC scan or surgical consult.
Ischemic Colitis
Elderly + hypotension + bloody diarrhea + left colon. CT: thumbprinting. Colonoscopy for diagnosis. Supportive care; surgery if gangrenous.
Most Stop
80-85% of LGIB stops spontaneously. Diverticular bleeds recur in ~25%. Definitive treatment if identified: endoscopic, IR, or surgical.
📄 One Pager
GI · One Pager
Lower GI Bleed
15% are actually upper source. Stable → colonoscopy within 24h. Unstable → CTA → IR embolization. Most stop spontaneously. Restrictive transfusion.
DDx
Diverticular (#1 in elderly, painless, large-volume), hemorrhoids (#1 overall), angiodysplasia, ischemic colitis, malignancy, IBD, post-polypectomy.
Management
Stable: resuscitate → colonoscopy within 24h (after prep). Unstable: CTA abdomen/pelvis → if active bleed → IR embolization. EGD first if upper source suspected.
15% Rule
15% of hematochezia is from upper GI source. Clues: hemodynamic instability disproportionate to rectal bleeding, BUN/Cr ratio > 20. If in doubt → EGD before colonoscopy.
Key Drugs
TransfusepRBC if Hgb < 7
IVFLR resuscitation
Hold anticoagResume after hemostasis
PPIOnly if upper source suspected
Pitfalls
- Assuming hematochezia = lower source (15% are upper)
- Not holding anticoagulation
- Over-transfusion (Hgb > 7 threshold for most)
- Not doing colonoscopy within 24h
Rotation
Gastroenterology
GI bleeding, liver disease, pancreatitis, and abdominal emergencies.
Available Topics
Upper GI Bleed
Lower GI Bleed
Hepatic Encephalopathy
Cirrhosis & Ascites
SBP
Acute Pancreatitis
Mesenteric Ischemia
C. difficile
Inflammatory Bowel Disease
Small Bowel Obstruction & Ileus
Cholangitis & Cholecystitis
Acute Alcoholic Hepatitis
Hepatorenal Syndrome
Gallstone Pancreatitis
Autoimmune Hepatitis
PBC / PSC
Acute Liver Failure
Bowel Obstruction
📋 Major Guidelines
Hyponatremia
Na⁺ < 135 mEq/L — the most common electrolyte abnormality in hospitalized patients. The approach is systematic: (1) serum osmolality, (2) volume status, (3) urine studies. Correct slowly — osmotic demyelination syndrome is iatrogenic and devastating.
🔍 Systematic Approach
Step 1 — Serum Osmolality
| Serum Osm | Category | Causes |
|---|---|---|
| < 275 (low) | Hypotonic (true hyponatremia) | Most cases. Proceed to Step 2. |
| 275–295 (normal) | Isotonic (pseudohyponatremia) | Hyperlipidemia, hyperproteinemia (multiple myeloma). Lab artifact — true Na is normal. Check lipid panel + protein. |
| > 295 (high) | Hypertonic (translocational) | Hyperglycemia (#1 — correct Na for glucose: add 1.6 mEq/L Na for every 100 mg/dL glucose above 100), mannitol, IV contrast. |
Step 2 — Volume Status (for Hypotonic)
| Volume Status | Urine Na | Causes | Treatment |
|---|---|---|---|
| Hypovolemic (dry mucous membranes, orthostasis, tachycardia, skin tenting) | < 20: extrarenal losses (GI: vomiting, diarrhea; 3rd spacing: burns, pancreatitis) > 20: renal losses (diuretics, adrenal insufficiency, cerebral salt wasting) | GI losses, diuretics, adrenal crisis, burns | Volume resuscitation with NS. Na will correct as volume is restored. Watch for overcorrection — once ADH stimulus (hypovolemia) is removed, kidneys dump free water rapidly. |
| Euvolemic (no edema, no orthostasis — hardest to assess) | > 40 (inappropriately concentrated urine) | SIADH (#1), hypothyroidism, adrenal insufficiency, psychogenic polydipsia (Uosm < 100), beer potomania, tea-and-toast | Fluid restriction (SIADH). Treat underlying cause. See SIADH topic for details. |
| Hypervolemic (edema, JVD, ascites, anasarca) | < 20: CHF, cirrhosis, nephrotic syndrome (effective hypovolemia → ADH release → water retention) > 20: CKD/ESKD (kidneys can't excrete water) | HF, cirrhosis, nephrotic, CKD | Fluid restriction + treat underlying disease. Diuretics for HF/cirrhosis. Dialysis if ESKD. |
Step 3 — Key Labs to Order
- Serum osmolality (first — classifies the hyponatremia)
- Urine osmolality (Uosm < 100 = appropriate dilution → water overload/polydipsia. Uosm > 100 = kidneys inappropriately concentrating → ADH-mediated)
- Urine sodium (renal vs extrarenal losses in hypovolemic; confirms SIADH if > 40 in euvolemic)
- Serum glucose (correct for hyperglycemia: add 1.6 per 100 above 100)
- TSH, AM cortisol (rule out hypothyroidism and adrenal insufficiency before diagnosing SIADH)
🚨 Management
Correction Rates
The danger of hyponatremia treatment is NOT the low sodium — it's correcting too fast. Osmotic demyelination syndrome (ODS) is iatrogenic, irreversible, and devastating. [ODS Prevention Study, 2010
| Scenario | Max Correction Rate | Treatment |
|---|---|---|
| Chronic (> 48h or unknown duration) | ≤ 8 mEq/L in 24h (some guidelines use ≤ 10). High-risk for ODS: ≤ 6 mEq/L in 24h. | Fluid restriction (SIADH), NS (hypovolemic), treat underlying cause. Check Na q4–6h. |
| Acute (< 48h, known onset) | Can correct faster — brain hasn't adapted. Still aim for ≤ 10–12 mEq/L in 24h. | More aggressive treatment acceptable. Still monitor closely. |
| Symptomatic (seizures, coma, severe AMS) | Immediate goal: raise Na by 4–6 mEq/L in first 6h to stop symptoms. Then ≤ 8 total in 24h. | 3% hypertonic saline 100–150 mL IV bolus over 10–20 min. SALSA, 2021 May repeat × 2. ICU. Check Na q2h. |
Osmotic Demyelination Syndrome (ODS)
- Occurs 2–6 days after overcorrection — not immediately
- Central pontine myelinolysis → "locked-in syndrome" (quadriplegia, inability to speak/swallow, preserved consciousness)
- Risk factors for ODS: chronic hyponatremia (> 48h), alcoholism, malnutrition, hypokalemia (correct K⁺ simultaneously — K⁺ correction counts toward Na correction!), liver disease, Na < 105
- If overcorrecting (Na rising too fast): (1) D5W infusion (free water to re-lower Na), (2) DDAVP 2 mcg IV q8h (clamp urine output → stop Na from rising further), (3) target: bring Na back within safe correction range
🔄 Updated Practice: Old teaching: correct sodium no more than 10-12 mEq/L in 24 hours. Updated: the recommended limit is now ≤8 mEq/L in any 24-hour period for patients at high risk for osmotic demyelination syndrome (ODS) — chronic hyponatremia (>48h), alcoholism, malnutrition, hypokalemia, liver disease. For truly acute hyponatremia (<48h, e.g., exercise-associated, postoperative), faster correction is safe. If overcorrected: give back free water (D5W) and consider desmopressin (DDAVP) 2 mcg IV to re-lower sodium.
Danger point: hypovolemic hyponatremia corrected with NS. Once volume is restored, the ADH stimulus disappears → kidneys suddenly excrete massive free water → Na sh
📋 Clinical Example — Hyponatremia Workup
Patient: 68F with SCLC, found lethargic, Na⁺ 118 mEq/L.
Step 1 — Is this real? Serum osm: 248 (< 280 = true hypoosmolar hyponatremia). Not pseudohyponatremia.
Step 2 — Assess volume status:
- Exam: Mucous membranes moist, no edema, no JVD, skin turgor normal → euvolemic
- Urine Na: 45 mEq/L (> 40 = kidneys wasting Na → SIADH)
- Urine osm: 520 (> 100 = kidneys concentrating inappropriately → SIADH)
- TSH: normal. AM cortisol: normal (rules out hypothyroid and adrenal insufficiency)
Diagnosis: SIADH from SCLC (paraneoplastic ADH secretion)
Step 3 — Treatment:
- Symptomatic (lethargic) → 3% hypertonic saline 100 mL IV bolus over 10 min. Recheck Na in 2h.
- Na went 118 → 121 (+3 in 2h) — good. Symptoms improving.
- Target: correct ≤ 8 mEq/L in first 24h (risk of osmotic demyelination if faster)
- Fluid restriction 1L/day for maintenance
- If refractory SIADH: tolvaptan (Samsca) 15mg PO daily (check Na q6h — potent)
🧪 Workup
Diagnostic Workup — Hyponatremia
Systematic approach: (1) Serum osmolality → (2) Volume status → (3) Urine studies. Do NOT diagnose SIADH without first ruling out hypothyroidism and adrenal insufficiency.
| Test | Rationale | Key Values / Interpretation |
|---|---|---|
| Serum osmolality | First step — classifies the hyponatremia. | < 275 = hypotonic (true hyponatremia — proceed to step 2). 275-295 = isotonic (pseudohyponatremia — check lipids, protein). > 295 = hypertonic (hyperglycemia — correct Na: add 1.6 mEq/L per 100 mg/dL glucose above 100). |
| Urine osmolality | Distinguishes ADH-mediated from water overload. | < 100 mOsm/kg = kidneys appropriately diluting (polydipsia, beer potomania, tea-and-toast). > 100 = ADH-mediated (inappropriate concentration → SIADH, hypovolemia, hypervolemia). |
| Urine sodium | Differentiates renal from extrarenal sodium losses in hypovolemic states; confirms SIADH in euvolemic. | UNa < 20 = extrarenal losses (GI, third-spacing) or effective hypovolemia (CHF, cirrhosis). UNa > 40 in euvolemic state = SIADH. UNa > 20 in hypovolemic = renal losses (diuretics, adrenal insufficiency). |
| Volume status (clinical) | Essential physical exam — guides entire differential and treatment. | Hypovolemic (orthostasis, dry mucous membranes, tachycardia) → NS. Euvolemic → SIADH workup. Hypervolemic (edema, JVD, ascites) → CHF/cirrhosis/nephrotic. |
| TSH | Hypothyroidism is a reversible cause — must exclude before diagnosing SIADH. | Severe hypothyroidism → decreased free water clearance → hyponatremia. Treat thyroid disease first. |
| AM cortisol | Adrenal insufficiency mimics SIADH (euvolemic, high UNa). Must exclude before SIADH diagnosis. | AM cortisol < 3 = adrenal insufficiency likely. 3-15 = indeterminate → ACTH stimulation test. > 15 = AI unlikely. |
| Serum glucose | Correct Na for hyperglycemia (translocational hyponatremia). | Corrected Na = measured Na + 1.6 × [(glucose - 100) / 100]. If corrected Na is normal → not true hyponatremia. |
💊 Medications
Drug Therapy — Hyponatremia
| Drug | Dose | Route | Indication | Key Notes |
|---|---|---|---|---|
| 3% Hypertonic saline | 100-150 mL IV bolus over 10-20 min. May repeat × 2 (max 3 boluses). | IV | Severe symptomatic hyponatremia (seizures, coma, severe AMS) | ICU setting. Goal: raise Na by 4-6 mEq/L in first 6h to stop symptoms. Check Na q2h. Rapid intermittent bolus is as effective and safer than continuous infusion SALSA, 2021. |
| Fluid restriction | 1-1.5 L/day (all PO and IV fluids combined) | — | SIADH (first-line), hypervolemic hyponatremia (HF, cirrhosis) | Effective if urine osmolality is not extremely high. Poor compliance limits effectiveness. Calculate free water clearance to predict response. |
| NaCl tablets (salt tabs) | 1-3 g PO TID | PO | Chronic SIADH (with or without loop diuretic) | Often combined with furosemide 20 mg daily — the diuretic promotes free water excretion while salt tabs replenish sodium. Effective outpatient strategy. |
| Furosemide | 20-40 mg PO daily | PO | Combined with salt tabs for chronic SIADH | Impairs urinary concentration → promotes electrolyte-free water excretion. Only effective when combined with adequate sodium intake (salt tabs). |
| Tolvaptan (Samsca) | 15 mg PO daily (may increase to 30-60 mg) | PO | Refractory SIADH or hypervolemic hyponatremia not responding to fluid restriction | V2 receptor antagonist ("vaptan") — blocks ADH at collecting duct → aquaresis (free water loss). Must initiate inpatient. Check Na q6h for first 24h. Hepatotoxicity risk — do not use > 30 days. Do NOT use in hypovolemic hyponatremia. |
| Demeclocycline | 300-600 mg PO BID | PO | Alternative for chronic SIADH (if tolvaptan not available/tolerated) | Tetracycline that induces nephrogenic DI. Slow onset (3-5 days). Nephrotoxic — avoid in liver disease. Largely replaced by tolvaptan. |
| DDAVP (desmopressin) | 2 mcg IV q8h | IV | ODS rescue — given when Na is overcorrecting too rapidly | Clamps urine output → stops further Na correction. Combine with D5W (3-6 mL/kg/hr) to actively re-lower Na. Target: bring correction rate back to ≤ 8 mEq/L in 24h. |
| D5W (5% dextrose) | 3-6 mL/kg/hr | IV | ODS rescue — free water to re-lower sodium if overcorrecting | Used with DDAVP. The dextrose is metabolized, leaving free water. Start immediately if Na rising > 8-10 mEq/L in 24h. |
📊 Monitoring
Monitoring — Hyponatremia Correction
| Parameter | Frequency | Target / Action |
|---|---|---|
| Serum sodium | q2h if on hypertonic saline; q4-6h during active correction; q6-8h once stable | Max correction ≤ 8 mEq/L in any 24h period (≤ 6 in high-risk: alcoholism, malnutrition, hypokalemia, liver disease, Na < 105). If overcorrecting → DDAVP + D5W rescue immediately. |
| Serum osmolality | At baseline, then q12-24h during correction | Should rise proportionally with Na. Guides assessment of correction adequacy. |
| Urine output | q1-2h during active treatment | Sudden brisk water diuresis (> 200 mL/hr of dilute urine) = danger sign for overcorrection. This happens when ADH stimulus is removed (e.g., volume resuscitation in hypovolemic hyponatremia). Start DDAVP preemptively if UOP surges. |
| Neurological status | q2-4h during active correction | Improving: resolution of confusion, seizures, lethargy = adequate correction. New dysarthria, dysphagia, quadriparesis 2-6 days after correction = ODS — MRI brain, neurology consult. |
| Potassium | With each Na check | K⁺ correction counts toward Na correction (K⁺ enters cells, Na⁺ comes out). If repleting K⁺ aggressively, account for this in your correction rate calculation. |
| I&Os | Strict q1h during active treatment | Track all free water intake (IV and PO). Ensure fluid restriction is enforced if indicated. Document urine osmolality if available (Uosm < 200 on tolvaptan = expected). |
Overcorrection rescue protocol: If Na rises > 8-10 mEq/L in 24h → (1) Stop all hypertonic saline and salt tabs, (2) D5W at 3-6 mL/kg/hr, (3) DDAVP 2 mcg IV q8h, (4) Recheck Na q2h until back within safe range. Act immediately — ODS is irreversible.
📋 On Rounds
Why does correcting hypokalemia matter in hyponatremia?
Potassium is osmotically active and contributes to the Na correction rate. When you give IV KCl, K⁺ enters cells and Na⁺ comes out (to maintain electrochemical balance via the Na⁺/K⁺-ATPase). This means every mEq of K⁺ you give raises the serum Na by approximately the same amount as giving a mEq of Na. If you're correcting hypokalemia aggressively alongside hyponatremia, the Na may rise faster than you expect. Count K⁺ correction toward the safe Na correction limit. Conversely, uncorrected hypokalemia is a risk factor for ODS — always replete K⁺.
A urine osmolality of 50 mOsm/kg in a hyponatremic patient tells you what?
The kidneys are doing their job — maximally diluting urine. This means ADH is appropriately suppressed and the kidneys are trying to excrete free water. The hyponatremia is from water intake exceeding the kidney's diluting capacity. Differential: psychogenic polydipsia (> 15–20 L/day overwhelms even normal kidneys), beer potomania (low solute intake → low obligate urine output → can't excrete enough water), tea-and-toast diet (same mechanism). Treatment: restrict free water + increase solute intake (normal diet). These patients do NOT have SIADH (SIADH has Uosm > 100 because ADH is high).
You are correcting hyponatremia and realize you've already gone up 10 mEq in 18 hours. What do you do?
ODS rescue protocol — act immediately: (1) Stop all hypertonic saline and salt tabs, (2) Give D5W at 3-6 mL/kg/hr (free water to re-lower sodium), (3) Give DDAVP 2 mcg IV q8h (makes kidneys retain free water, prevents further correction). (4) Recheck Na q2h until it falls back to the safe correction rate (≤ 8 mEq/24h, some experts say ≤ 6 in high-risk patients). High-risk for ODS: Na < 105, chronic hyponatremia, alcoholism, malnutrition, hypokalemia, liver disease. ODS (osmotic demyelination syndrome) manifests 2-6 days after overcorrection: dysarthria, dysphagia, quadriparesis, "locked-in syndrome." It is devastating and largely irreversible. Prevention is everything.
What are the most dangerous medications that cause SIADH?
SSRIs are the #1 drug cause of SIADH (sertraline, fluoxetine, paroxetine — onset typically 1-4 weeks). Other common offenders: carbamazepine/oxcarbazepine (direct ADH-like effect on collecting duct), cyclophosphamide (especially with high-volume hydration), vincristine (neuropathic ADH release), opioids, PPIs, NSAIDs, ecstasy/MDMA (causes acute hyponatremia from both ADH release and excessive water intake → can be fatal). Key: always check the med list in new hyponatremia — stopping the offending drug may be all that's needed.
📣 Sample Presentation
One-Liner
"Mrs. Lee is a 68-year-old with SCLC presenting with Na⁺ 118, serum osm 252, urine osm 520, urine Na 45, euvolemic on exam. Consistent with SIADH from malignancy."
Key Points to Cover on Rounds
Euvolemic hypoosmolar hyponatremia. Urine osm 520 (inappropriately concentrated), UNa 45 (>40). TSH and cortisol normal. Etiology: SIADH from SCLC. Asymptomatic (no seizure, no AMS). Treatment: fluid restriction <1L/day. Na trending 118→120→122 over 24h (rate 4 mEq/24h — safe). Salt tabs 1g TID added. If refractory → tolvaptan 15 mg daily SALT-1/2, 2006 (monitor in-hospital, check Na q6h). Goal: ≤8 mEq/L correction per 24h to avoid ODS. Plan: treat underlying malignancy, continue fluid restriction.
⚡ Summary
Summary
Step 1
Serum osm: < 275 = true hypoosmolar hyponatremia. ≥ 275 = pseudohyponatremia (hyperglycemia, mannitol, IVIG).
Volume Status
Hypovolemic (FENa < 1): dehydration, diuretics. Euvolemic (UNa > 40): SIADH, hypothyroid, adrenal insuff. Hypervolemic: CHF, cirrhosis, nephrotic.
SIADH Treatment
Fluid restriction < 1L/day → salt tabs → tolvaptan (inpatient only, check Na q6h). Treat the cause.
Correction Rate
≤ 8 mEq/L per 24h (some say ≤ 6 in high-risk). Overcorrection → ODS (osmotic demyelination). Devastating and irreversible.
ODS Rescue
If overcorrecting: D5W + DDAVP 2 mcg IV q8h → re-lower sodium to safe rate. Act immediately.
Severe Symptoms
Seizures, AMS → hypertonic saline 3% NaCl 100-150 mL bolus over 10 min. Target 4-6 mEq/L rise acutely to stop seizures.
📄 One Pager
Nephrology · One Pager
Hyponatremia
Check serum osm → volume status → urine studies. Correct ≤ 8 mEq/24h. Overcorrection → ODS (devastating). Severe symptoms → 3% NaCl 100-150 mL bolus.
Approach
Step 1: Serum osm (< 275 = true). Step 2: Volume status (hypo/eu/hyper). Step 3: UNa + urine osm. Euvolemic + UNa > 40 + concentrated urine = SIADH.
Acute Severe Symptoms
Seizures or AMS → 3% NaCl 100-150 mL bolus over 10 min (can repeat ×1). Target 4-6 mEq rise to stop seizures. Then slow correction to ≤ 8/24h total.
ODS Prevention
Correct ≤ 8 mEq/24h (≤ 6 if high-risk: Na < 105, chronic, alcoholism, malnutrition, liver disease). If overcorrecting: D5W + DDAVP 2 mcg IV q8h immediately.
Key Drugs
3% NaCl100-150 mL bolus (severe)
DDAVP2 mcg IV q8h (ODS rescue)
Tolvaptan15 mg daily (SIADH, inpatient only)
Salt tabs1g TID (chronic SIADH)
Pitfalls
- Overcorrection → ODS (irreversible pontine demyelination)
- Not checking TSH and cortisol (must exclude before diagnosing SIADH)
- Free water restriction while on tolvaptan (dangerous combo)
- IV NS for hypovolemic hyponatremia in SIADH (worsens it)
Acid-Base Disorders
A systematic 5-step approach to every ABG. pH → primary disorder → compensation → anion gap → delta-delta. Master this and you'll never be stumped by an ABG again.
🧪 5-Step ABG Interpretation
Step 1 — Look at the pH
| pH | Primary Process |
|---|---|
| < 7.35 | Acidemia (acidosis is the dominant process) |
| 7.35–7.45 | Normal (or mixed disorder with complete compensation) |
| > 7.45 | Alkalemia (alkalosis is the dominant process) |
Step 2 — Identify the Primary Disorder
| If pH < 7.35 (acidemia) | If pH > 7.45 (alkalemia) |
|---|---|
| PCO₂ > 40 → respiratory acidosis (hypoventilation) | PCO₂ < 40 → respiratory alkalosis (hyperventilation) |
| HCO₃ < 22 → metabolic acidosis | HCO₃ > 26 → metabolic alkalosis |
Step 3 — Is Compensation Appropriate?
| Primary Disorder | Expected Compensation |
|---|---|
| Metabolic acidosis | Winter's formula: expected PCO₂ = 1.5 × [HCO₃] + 8 (± 2). If actual PCO₂ ≠ expected → additional respiratory disorder. |
| Metabolic alkalosis | Expected PCO₂ = 0.7 × [HCO₃] + 21 (± 2). Or: PCO₂ rises ~0.7 for each 1 mEq/L rise in HCO₃. |
| Acute respiratory acidosis | HCO₃ rises 1 per 10 mmHg ↑ PCO₂ |
| Chronic respiratory acidosis | HCO₃ rises 3.5 per 10 mmHg ↑ PCO₂ |
| Acute respiratory alkalosis | HCO₃ falls 2 per 10 mmHg ↓ PCO₂ |
| Chronic respiratory alkalosis | HCO₃ falls 5 per 10 mmHg ↓ PCO₂ |
If compensation is more or less than expected → there's a second (mixed) disorder. Example: metabolic acidosis with PCO₂ lower than Winter's predicted → concurrent respiratory alkalosis (sepsis?).
Step 4 — Calculate the Anion Gap
AG = Na − (Cl + HCO₃). Normal: 12 ± 4 (or 8 ± 4 if albumin-corrected). Correct for albumin: for every 1 g/dL albumin below 4 → add 2.5 to the AG.
| AG Elevated (> 12) | AG Normal (non-AG / hyperchloremic) |
|---|---|
| MUDPILES: Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates | HARDUPS: Hyperalimentation (TPN), Addison's, RTA, Diarrhea, Ureteral diversion, Post-hypocapnia, Saline (NS resuscitation) |
Step 5 — Delta-Delta (if AG elevated)
Delta-delta = ΔAG / ΔHCO₃ = (AG − 12) / (24 − HCO₃)
| Ratio | Interpretation |
|---|---|
| < 1 | AG metabolic acidosis + concurrent non-AG metabolic acidosis (the bicarb dropped more than expected from the AG alone → additional acid or bicarb loss) |
| 1–2 | Pure AG metabolic acidosis (the drop in bicarb matches the rise in AG) |
| > 2 | AG metabolic acidosis + concurrent metabolic alkalosis (bicarb is higher than expected → something is raising it — vomiting, diuretics, bicarb administration) |
📋 Differentials
Metabolic Alkalosis
| Urine Cl⁻ | Category | Causes | Treatment |
|---|---|---|---|
| < 20 mEq/L | Chloride-responsive (saline-responsive) | Vomiting/NG suction (#1), diuretics (after stopping), post-hypercapnia | NS (volume + chloride repletion). Correct the deficit. |
| > 20 mEq/L | Chloride-resistant | Hyperaldosteronism (Conn syndrome), Cushing's, Bartter/Gitelman, active diuretic use, severe hypokalemia | Treat underlying cause. K⁺ repletion. Spironolactone if hyperaldosteronism. |
Renal Tubular Acidosis (RTA)
| Type | Defect | pH | K⁺ | Classic Association |
|---|---|---|---|---|
| Type 1 (Distal) | Can't secrete H⁺ in distal tubule | Urine pH > 5.5 (can't acidify) | ↓ (hypoK) | Sjögren, SLE, nephrocalcinosis, amphotericin B |
| Type 2 (Proximal) | Can't reabsorb HCO₃ in proximal tubule | Urine pH < 5.5 (once threshold exceeded) | ↓ (hypoK) | Fanconi syndrome, multiple myeloma, carbonic anhydrase inhibitors (acetazolamide) |
| Type 4 (Hypoaldo) | ↓ Aldosterone or tubular resistance | Urine pH < 5.5 | ↑ (hyperK) | Most common RTA. Diabetic nephropathy, ACEi/ARBs, spironolactone, TMP-SMX, heparin |
Pearl: Always calculate the corrected AG (for albumin) and delta-delta ratio to identify mixed disorders.
🔍 Overview
Overview
Acid-base disorders are among the most common lab abnormalities in hospitalized patients. A systematic 5-step ABG approach prevents missed mixed disorders.
🧪 Workup
Workup
- ABG/VBG — VBG acceptable for pH/HCO₃
- BMP — AG calculation
- Albumin — corrected AG = AG + 2.5×(4−albumin)
- Lactate — #1 AG acidosis in hospital
- Ketones/BHB
- Osmolality (serum + calculated) — osmol gap >10 = toxic alcohol
- Urine AG — positive=RTA, negative=GI loss
- APAP + salicylate — always in unexplained AG acidosis
🚨 Management
Management
- AG acidosis: DKA→insulin. Lactic→treat shock. Toxic alcohols→fomepizole+dialysis. Uremia→dialysis. Stewart Approach, Kellum 2009
- Non-AG acidosis: Diarrhea→IVF. RTA→bicarb. NS-induced→switch to LR.
- Resp acidosis: COPD→BiPAP. Opioid→naloxone. NMD→intubation.
- Met alkalosis: Cl-responsive→NS+KCl. Cl-resistant→treat cause.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| NaHCO₃ | 50-150 mEq | IV | Only pH < 6.9. Monitor K⁺. BICAR-ICU, Jaber 2018 |
| Fomepizole | 15 mg/kg load | IV | Toxic alcohols |
| Acetazolamide | 250 mg q6-12h | IV/PO | Refractory met alkalosis |
| KCl | 20-40 mEq q2-4h | IV | Must correct K⁺ to fix met alkalosis |
📊 Monitoring
Monitoring
- ABG q2-4h during correction
- BMP q4-6h — K⁺ shifts with pH
- AG trend
- Lactate q2-4h if lactic acidosis
- UOP
📋 On Rounds
pH 7.28, PCO₂ 24, HCO₃ 11, Na 140, Cl 100, AG 29. Interpret this ABG.
Step 1: pH 7.28 = acidemia. Step 2: HCO₃ 11 (low) = metabolic acidosis (primary). Step 3: Winter's formula: expected PCO₂ = 1.5(11) + 8 = 24.5 ± 2. Actual PCO₂ = 24 → appropriate respiratory compensation. Step 4: AG = 140 − (100 + 11) = 29 (elevated) → AG metabolic acidosis. Think MUDPILES: DKA? Lactic acidosis? Toxic ingestion? Step 5: Delta-delta = (29−12)/(24−11) = 17/13 = ~1.3 → pure AG metabolic acidosis. No concurrent metabolic alkalosis or non-AG acidosis. Summary: pure AG metabolic acidosis with appropriate respiratory compensation.
Why do you correct the anion gap for albumin?
Albumin is a negatively charged protein that contributes ~12 mEq/L to the unmeasured anions (the normal AG). In hypoalbuminemic patients (cirrhosis, nephrotic syndrome, malnutrition, critical illness), the baseline AG is lower because there are fewer albumin anions. A "normal" AG of 12 in a patient with albumin of 2 actually represents a hidden AG elevation of ~5. Correction: for every 1 g/dL albumin below 4, add 2.5 to the calculated AG. Example: AG 14, albumin 2.0 → corrected AG = 14 + 2.5(4−2) = 19 → significant AG metabolic acidosis that would have been missed without correction.
Walk me through the 5-step approach to ABG interpretation.
Step 1: Look at pH — acidemia (< 7.35) or alkalemia (> 7.45)? Step 2: Identify the primary disorder — does the pCO₂ explain it (respiratory) or the HCO₃ (metabolic)? Step 3: Is compensation appropriate? For metabolic acidosis: Winter's formula (expected pCO₂ = 1.5 × HCO₃ + 8 ± 2). If actual pCO₂ is HIGHER than expected → concurrent respiratory acidosis. If LOWER → concurrent respiratory alkalosis. Step 4: Calculate anion gap (Na − Cl − HCO₃), corrected for albumin (add 2.5 for each 1 g/dL albumin below 4). Step 5: If AG elevated, calculate delta-delta ratio: (ΔAG / ΔHCO₃). Ratio > 2 = concurrent metabolic alkalosis. Ratio < 1 = concurrent non-AG metabolic acidosis. MUDPILES for AG acidosis: Methanol, Uremia, DKA, Propylene glycol, INH/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
How do you calculate the corrected anion gap for albumin?
The anion gap is falsely low in hypoalbuminemia (albumin is the main unmeasured anion). Corrected AG = Calculated AG + 2.5 × (4.0 − measured albumin). For each 1 g/dL drop in albumin below 4, add 2.5 to the AG. Example: Na 140, Cl 108, HCO₃ 20, albumin 2.0 → raw AG = 140-108-20 = 12 (looks normal). Corrected AG = 12 + 2.5 × (4.0-2.0) = 17 (elevated!). Without correction, you'd miss a significant anion gap acidosis. This matters enormously in ICU patients, cirrhotics, nephrotic syndrome, and malnourished patients who commonly have albumin 2-3.
📣 Sample Presentation
One-Liner
"Mr. Young is a 32-year-old with type 1 DM presenting with ABG: pH 7.18, pCO₂ 22, HCO₃ 8. Na 140, Cl 102, AG 30. Consistent with anion gap metabolic acidosis with appropriate respiratory compensation."
Key Points to Cover on Rounds
5-step ABG: (1) Acidemia (pH 7.18), (2) Primary metabolic acidosis (low HCO₃ 8), (3) Respiratory compensation: expected pCO₂ by Winter's = 1.5(8)+8±2 = 18-22 → actual 22 (appropriate), (4) AG 30 (elevated, corrected for albumin). (5) Delta-delta: ΔAG=18, ΔHCO₃=16 → ratio 1.1 (pure AG acidosis). Etiology: DKA (glucose 420, ketones positive). No concurrent non-AG acidosis or metabolic alkalosis. Plan: treat DKA — insulin drip, fluids, electrolyte monitoring.
⚡ Summary
Summary
5-Step ABG
1) pH (acid vs alkalemia) → 2) Primary disorder (respiratory vs metabolic) → 3) Compensation adequate? → 4) AG (corrected for albumin) → 5) Delta-delta.
Winter's Formula
Expected pCO₂ = 1.5 × HCO₃ + 8 ± 2. If actual pCO₂ higher → concurrent respiratory acidosis. Lower → respiratory alkalosis.
AG Correction
Corrected AG = AG + 2.5 × (4.0 − albumin). For each 1 g/dL albumin below 4, add 2.5. Hypoalbuminemia hides AG acidosis.
Delta-Delta
ΔAG / ΔHCO₃: Ratio > 2 = hidden metabolic alkalosis. Ratio < 1 = hidden non-AG metabolic acidosis.
MUDPILES
Methanol, Uremia, DKA, Propylene glycol, INH/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
Non-AG Causes
HARDUP: Hyperalimentation, Acetazolamide, RTA, Diarrhea, Ureteral diversion, Pancreatic fistula. Also: NS resuscitation.
📄 One Pager
Nephrology / Critical Care · One Pager
ABG Interpretation
5 steps: pH → primary disorder → compensation → AG (corrected for albumin) → delta-delta. MUDPILES for AG acidosis. Winter's formula.
5-Step Approach
(1) pH (acid vs alkalemia). (2) Primary disorder (pCO₂ vs HCO₃). (3) Compensation appropriate? (Winter's formula for met acidosis). (4) AG corrected for albumin. (5) Delta-delta (ΔAG/ΔHCO₃).
AG Acidosis — MUDPILES
Methanol, Uremia, DKA, Propylene glycol, INH/Iron, Lactic acidosis, Ethylene glycol, Salicylates. Check lactate, ketones, osmol gap, tox screen.
Key Formulas
Winter's: expected pCO₂ = 1.5 × HCO₃ + 8 ± 2. AG = Na − Cl − HCO₃. Corrected AG = AG + 2.5 × (4 − albumin). Delta-delta: > 2 = hidden met alk, < 1 = hidden non-AG met acidosis.
Key Drugs
Bicarb drip150 mEq in D5W (if pH < 6.9 in DKA)
Fomepizole15 mg/kg load (toxic alcohols)
Insulin drip0.1 u/kg/hr (DKA)
DialysisRefractory acidosis or toxic ingestion
Pitfalls
- Not correcting AG for albumin (misses hidden AG acidosis in ICU patients)
- Treating number without finding cause
- Bicarb for DKA (except pH < 6.9)
- Missing mixed acid-base disorder
Dialysis Indications
Know when to call nephrology emergently (AEIOU) and the differences between HD, CRRT, and PD. The decision to start emergent dialysis is clinical, not based on a single lab value.
🔍 Emergent Indications — AEIOU
AEIOU — Emergent dialysis indications (refractory to medical management):
| Letter | Indication | Details |
|---|---|---|
| A | Acidosis | Severe metabolic acidosis (pH < 7.1) refractory to bicarb. Especially toxic ingestions (methanol, ethylene glycol — dialysis removes the toxin AND corrects acidosis). |
| E | Electrolytes | Refractory hyperkalemia not responding to medical management (calcium, insulin/glucose, albuterol, bicarb). K⁺ > 6.5 with ECG changes + anuric patient → emergent HD. |
| I | Ingestion | Toxic alcohols (methanol, ethylene glycol), lithium, salicylate, theophylline, metformin (with severe lactic acidosis). Dialysis removes the toxin directly. |
| O | Overload (volume) | Pulmonary edema refractory to diuretics. Anuric patient with flash pulmonary edema → emergent ultrafiltration/HD. |
| U | Uremia | Uremic symptoms: encephalopathy (AMS, asterixis), pericarditis (friction rub → can progress to tamponade), uremic bleeding (platelet dysfunction), intractable nausea/vomiting. Uremic pericarditis = absolute indication — can cause fatal tamponade. |
There is no specific BUN or Cr threshold for starting dialysis. IDEAL, 2010: early initiation (GFR 10–14) showed no survival benefit over late initiation (GFR 5–7) in CKD. The decision is based on clinical symptoms and refractory complications, not a single lab value. A patient with BUN 150 and no symptoms doesn't need dialysis. A patient with BUN 80 and uremic pericarditis does.
🔧 Modalities
HD vs CRRT vs PD
| Feature | Intermittent HD | CRRT | PD |
|---|---|---|---|
| Setting | Outpatient dialysis center, inpatient | ICU only | Home (chronic) or inpatient |
| Access | AV fistula, AV graft, or dialysis catheter (IJ preferred) | Dialysis catheter (large bore, dual lumen) | PD catheter (Tenckhoff, peritoneal) |
| Duration | 3–4 hours, 3×/week | Continuous (24/7) | Overnight (APD) or 4× daily exchanges (CAPD) |
| Hemodynamic stability | Rapid fluid/solute shifts → hypotension risk | Gentler — preferred for hemodynamically unstable patients (septic shock, cardiogenic shock) | Gentle, minimal hemodynamic effects |
| Solute clearance | Fast, efficient for small molecules | Slower per hour but continuous → equivalent over 24h | Less efficient for small molecules |
| Best for | Outpatient ESKD, emergent dialysis (fast K⁺ removal), toxin removal | ICU patients who are hemodynamically unstable. AKI in shock. Cerebral edema (slower osmolar shifts). | Chronic CKD/ESKD who want home-based therapy. Preserve residual renal function longer. |
CRRT Modes
| Mode | Mechanism | Use |
|---|---|---|
| CVVH (Continuous VenoVenous Hemofiltration) | Convection (hydrostatic pressure pushes fluid + solutes across membrane, replaced with clean fluid) | Volume overload, middle-molecule clearance |
| CVVHD (Continuous VenoVenous Hemodialysis) | Diffusion (solute moves down concentration gradient across membrane via dialysate) | Small molecule clearance (urea, K⁺, toxins) |
| CVVHDF (Continuous VenoVenous Hemodiafiltration) | Both convection + diffusion | Most commonly used in ICU. Combines benefits of both. Best overall solute + fluid clearance. |
Vascular Access
- AV fistula — gold standard for chronic HD. Lowest infection rate, longest patency. Place when eGFR ~20 (needs 2–3 months to mature). Radiocephalic (wrist) → brachiocephalic (upper arm).
- AV graft — synthetic conduit. Can use in 2–3 weeks. Higher infection and thrombosis rate than fistula.
- Tunneled dialysis catheter (Permacath) — for patients awaiting fistula maturation or not candidates for fistula. Highest infection rate. Right IJ preferred (straightest path to RA).
- Non-tunneled temporary catheter — emergent dialysis only. IJ or femoral. Should be replaced within 1–2 weeks.
Preserve arm veins: avoid blood draws and IVs in the non-dominant arm of any patient with CKD stage 3+ or approaching dialysis. That arm may be needed for a fistula. Never use a dialysis catheter for non-dialysis purposes (blood draws, meds, fluids) unless absolute emergency — infection risk.
🧪 Workup
Workup
- BMP — K⁺, BUN, Cr, bicarb
- ABG — acidosis severity
- CXR — pulmonary edema
- ECG — hyperK changes
- Tox levels if ingestion
- Access assessment
🚨 Management
Management
- AEIOU: Acidosis pH<7.1, Electrolytes (K⁺ refractory), Ingestion, Overload, Uremia
- HD: stable patients, 3-4h sessions
- CRRT: hemodynamically unstable ICU
- IDH prevention: slow UF, cool dialysate 35.5°C, midodrine, hold antihypertensives HD days
💊 Medications
Medications — Dialysis
| Drug (Brand) | Dose | Route | Indication | Notes |
|---|---|---|---|---|
| CIRCUIT ANTICOAGULATION | ||||
| Heparin | Per protocol (bolus + infusion) | IV | HD circuit anticoagulation | Standard for intermittent HD. Monitor aPTT. Hold if active bleeding — run without anticoag. |
| Citrate (regional) | Per CRRT protocol | IV | CRRT anticoagulation | Preferred for CRRT — chelates calcium in circuit. Monitor ionized calcium closely (systemic and circuit). Risk: metabolic alkalosis, hypocalcemia. |
| CKD-MBD MANAGEMENT | ||||
| Sevelamer (Renvela) | 800–1600 mg with meals | PO | Phosphate binder | Non-calcium binder — preferred to avoid vascular calcification. Take with every meal. |
| Calcium acetate (PhosLo) | 667 mg (1–2 tabs) with meals | PO | Phosphate binder | Calcium-based binder. Avoid if hypercalcemic or high Ca x PO4 product. |
| Cinacalcet (Sensipar) | 30–180 mg PO daily | PO | Secondary hyperparathyroidism | Calcimimetic — activates CaSR on parathyroid → suppresses PTH. GI side effects common. For dialysis patients with refractory hyperPTH. |
| Calcitriol (Rocaltrol) | 0.25–0.5 mcg PO daily | PO | Active vitamin D | For secondary hyperPTH. Monitor calcium (risk of hypercalcemia). Alternative: paricalcitol (Zemplar). |
| ANEMIA MANAGEMENT | ||||
| Epoetin alfa (Procrit) | 50–300 units/kg 3x/week | IV/SQ | Anemia of CKD/ESKD | Iron-replete first (ferritin > 200, TSAT > 20%). Target Hgb 10–11.5. Never > 13. |
| Darbepoetin (Aranesp) | 0.45 mcg/kg q2 weeks or monthly | IV/SQ | Anemia of CKD/ESKD | Long-acting ESA — less frequent dosing. Same Hgb target. |
| Iron sucrose (Venofer) | 100–200 mg IV per HD session | IV | Iron deficiency on dialysis | Given during HD sessions. Target ferritin 200–500, TSAT 20–30%. Must replete iron before starting ESA. |
📊 Monitoring
Monitoring — Dialysis
| Parameter | Frequency | Target / Action |
|---|---|---|
| Pre/post BUN, K+, bicarb, Ca, PO4 | Each HD session (or daily for CRRT) | Assess clearance adequacy. Post-HD K+ should be 3.5–5.0. Bicarb > 22. PO4 3.5–5.5. |
| Weight (dry weight target) | Pre/post each HD session | Fluid removal goal = pre-HD weight minus dry weight. Reassess dry weight monthly — clinical exam (edema, JVP, BP) guides adjustment. |
| Access assessment (AV fistula) | Every HD session | Check thrill and bruit — absence suggests thrombosis or stenosis. Inspect for signs of infection, aneurysm, steal syndrome (cold/pale hand). |
| Kt/V | Monthly | Dialysis adequacy: target Kt/V ≥ 1.4 (single-pool) for thrice-weekly HD. URR (urea reduction ratio) > 65% is alternative measure. |
| Hgb / iron studies | Monthly | Hgb target 10–11.5 g/dL. Ferritin 200–500, TSAT 20–30%. Replete iron before adjusting ESA dose. |
| PTH | Every 3 months | Target 2–9x upper limit of normal for dialysis patients. Rising PTH → increase phosphate binders, add cinacalcet or calcitriol. |
Access is lifeline. Protect AV fistulas — no blood draws, no BPs, no IVs in the fistula arm. Never use a dialysis catheter for non-dialysis purposes unless absolute emergency.
📋 On Rounds
When do you choose CRRT over intermittent HD in the ICU?
Hemodynamic instability is the primary indication for CRRT over HD. Intermittent HD removes fluid and solutes rapidly over 3–4 hours → large intravascular volume shifts → hypotension (especially in patients already on vasopressors). CRRT removes the same total fluid/solutes but continuously over 24 hours → gentler osmolar and volume shifts → better tolerated hemodynamically. Other CRRT advantages: better for cerebral edema (slower osmolar changes prevent brain swelling), hepatic failure (avoids rapid ammonia shifts). AKIKI, 2016 and STARRT-AKI, 2020 showed no mortality benefit of early vs delayed RRT initiation in AKI — reinforcing that timing should be based on clinical indications (AEIOU), not just labs.
Why is uremic pericarditis an absolute dialysis indication?
Uremic pericarditis is a fibrinous/hemorrhagic pericarditis caused by uremic toxin accumulation irritating the pericardium. Unlike viral pericarditis, it can rapidly progress to hemorrhagic pericardial effusion → tamponade because uremic patients have concurrent platelet dysfunction (uremic bleeding). The pericarditis responds to intensive dialysis (daily HD for 1–2 weeks), not to NSAIDs or colchicine (which treat viral pericarditis). Untreated, it carries a high mortality from tamponade. It's also important to note that uremic pericarditis does NOT produce the typical ECG changes of viral pericarditis (no diffuse ST elevation) because it's not an inflammatory process of the myocardium — it's a chemical irritation of the pericardium.
A patient on HD has hypotension during the session. What do you do?
Intradialytic hypotension (IDH) — the most common HD complication (~20-30% of sessions). Immediate management: (1) Passive leg raise (Trendelenburg has no evidence), (2) Reduce UF rate or stop UF (keep dialysis running for clearance), (3) NS 100-250 mL bolus, (4) If persistent → stop dialysis. Prevention for next session: increase dry weight if patient is below target, slower UF rate (extend session time — 4h instead of 3h), cooled dialysate (35.5°C — causes vasoconstriction), midodrine 10 mg PO 30 min before session, hold antihypertensives on dialysis days. Root causes: UF rate too aggressive (> 13 mL/kg/hr), true dry weight lower than estimated, cardiac dysfunction (poor contractile reserve), autonomic neuropathy (diabetes), eating during dialysis (splanchnic vasodilation).
What is the difference between intermittent HD and CRRT, and when do you choose each?
Intermittent HD: 3-4h sessions, high solute clearance, significant fluid shifts. Use for: stable patients, urgent indications (hyperK, toxic ingestions — high clearance needed fast), outpatient maintenance. CRRT (continuous renal replacement therapy): runs 24/7, slower gentle fluid/solute removal. Use for: hemodynamically unstable patients (ICU, on pressors — HD causes intradialytic hypotension from rapid fluid shifts), cerebral edema risk (hepatic failure, TBI), need for continuous fluid removal in volume-overloaded ICU patients. CRRT modes: CVVH (hemofiltration), CVVHD (dialysis), CVVHDF (both). CRRT does NOT provide superior outcomes over HD — it's chosen for hemodynamic tolerance, not efficacy.
📣 Sample Presentation
One-Liner
"Mrs. White is a 62-year-old with ESKD on HD (MWF via LUE AV fistula) who missed 2 sessions, presenting with dyspnea, bilateral crackles, K⁺ 6.8, and BUN 112."
Key Points to Cover on Rounds
Missed dialysis ×2 → volume overload + hyperkalemia + uremia. K⁺ 6.8 with peaked T waves → calcium gluconate, insulin/D50, albuterol given. Nephrology emergently contacted — urgent HD session arranged. Access: LUE fistula with good thrill and bruit. Fluid overloaded: JVP 14 cm, crackles bilaterally, 3+ LE edema. UF goal 4L for this session. Plan: resume regular MWF HD, social work to address barriers to sessions.
⚡ Summary
Summary
Emergent Indications
AEIOU: Acidosis (pH < 7.1), Electrolytes (refractory K⁺ > 6.5), Ingestion (toxic alcohols), Overload (pulmonary edema), Uremia (pericarditis, encephalopathy, bleeding).
HD vs CRRT
HD: 3-4h sessions, stable patients, high clearance. CRRT: continuous, hemodynamically unstable ICU patients, cerebral edema risk.
Access
AV fistula (best long-term, 3-6 months to mature) > AV graft (2-4 weeks) > tunneled catheter (immediate but highest infection risk).
IDH Prevention
Slow UF rate, cool dialysate (35.5°C), midodrine pre-session, hold antihypertensives on dialysis days, extend session time.
Peritoneal Dialysis
Home-based, daily. Good for: independent patients, residual renal function preservation. Risk: peritonitis (cloudy effluate → culture + empiric abx).
Complications
Dialysis disequilibrium (cerebral edema with first session), air embolism, catheter infection, steal syndrome (fistula).
📄 One Pager
Nephrology · One Pager
Dialysis — HD & CRRT
AEIOU for emergent dialysis. HD for stable patients. CRRT for hemodynamically unstable ICU patients. Access: fistula > graft > catheter.
Emergent Indications — AEIOU
Acidosis (pH < 7.1, refractory). Electrolytes (hyperK refractory). Ingestion (toxic alcohols, salicylates). Overload (pulmonary edema refractory to diuretics). Uremia (pericarditis, encephalopathy, bleeding).
HD vs CRRT
HD: 3-4h sessions, high clearance, stable patients, outpatient. CRRT: continuous 24/7, gentle fluid removal, hemodynamically unstable ICU patients, cerebral edema risk.
Access
AV fistula (best — refer at eGFR ~20, needs 3-6 months to mature). AV graft (2-4 weeks). Tunneled catheter (immediate, highest infection risk). Peritoneal catheter (home dialysis).
Key Drugs
Calcium gluconateHyperkalemia bridge to HD
HeparinAnticoag for HD circuit
CitrateRegional anticoag for CRRT
EPOAnemia management on HD
Pitfalls
- Late fistula referral (needs months to mature)
- IDH from aggressive UF rate (slow down, cool dialysate)
- Dialysis disequilibrium in first session (cerebral edema)
- Not adjusting medications for HD clearance
Rotation
Nephrology
AKI, electrolyte disorders, acid-base physiology, and renal replacement therapy.
Available Topics
Acute Kidney Injury
Chronic Kidney Disease
Hyperkalemia
Hyponatremia
Acid-Base Disorders
Acid-Base (Comprehensive)
Dialysis Indications
Metabolic Alkalosis
Nephrotic vs Nephritic Syndrome
Renal Tubular Acidosis
Contrast-Induced Nephropathy
Rhabdomyolysis
Hypernatremia
Renal Transplant Medicine
📋 Major Guidelines
Meningitis & Encephalitis
Bacterial meningitis has ~20% mortality even with treatment and doubles with every hour of antibiotic delay. Empiric antibiotics BEFORE LP if there will be ANY delay. Dexamethasone before or with first antibiotic dose.
🔍 Overview
CSF Patterns
| Parameter | Bacterial | Viral | TB / Fungal |
|---|---|---|---|
| Opening pressure | ↑↑ (> 25 cmH₂O) | Normal or mildly ↑ | ↑ |
| WBC | > 1000 (PMN predominant) | 10–500 (lymphocyte predominant) | 10–500 (lymphocyte predominant) |
| Glucose | < 40 (or CSF/serum ratio < 0.4) | Normal | ↓↓ (often < 20 in TB) |
| Protein | > 250 mg/dL | 50–100 | ↑↑ (100–500) |
| Gram stain | Positive in ~60–90% | Negative | AFB smear low sensitivity (~20% in TB) |
Organisms by Age
| Age Group | Common Organisms | Empiric Coverage |
|---|---|---|
| Neonates (< 1 mo) | Group B strep, E. coli, Listeria | Ampicillin + cefotaxime (or gentamicin) |
| Children (1 mo–18 yr) | N. meningitidis, S. pneumoniae, H. influenzae | Vancomycin + ceftriaxone |
| Adults (18–50) | S. pneumoniae (#1), N. meningitidis | Vancomycin + ceftriaxone |
| Adults > 50, immunocompromised, alcoholics | S. pneumoniae, Listeria, N. meningitidis, gram-negatives | Vancomycin + ceftriaxone + ampicillin (Listeria coverage) |
Add ampicillin for Listeria coverage if: age > 50, immunocompromised, alcoholics, pregnancy, chronic steroids. Listeria is NOT covered by cephalosporins.
When to Get CT Before LP
- CT before LP ONLY if: immunocompromised, history of CNS disease, new-onset seizure, papilledema, altered consciousness, focal neurologic deficit
- If CT needed → give antibiotics BEFORE CT AND LP. Do NOT delay antibiotics for imaging.
- If none of these features → LP first, no CT needed
🚨 Management
Empiric Treatment
Antibiotics within 30–60 minutes. Every hour of delay increases mortality. Do NOT wait for LP results.
| Drug | Dose | Role |
|---|---|---|
| Vancomycin (Vancocin) | 15–20 mg/kg IV q8–12h | Covers penicillin-resistant S. pneumoniae (up to 30% resistance in some regions) |
| Ceftriaxone (Rocephin) | 2g IV q12h | Covers S. pneumoniae, N. meningitidis, H. influenzae, gram-negatives. Meningitis dose = 2g q12h (not standard 1–2g daily). |
| Ampicillin (Principen) | 2g IV q4h | Listeria coverage. Add if age > 50, immunocompromised, alcoholism, pregnancy. |
| Dexamethasone (Decadron) GIVE WITH FIRST ANTIBIOTIC | 0.15 mg/kg IV q6h × 4 days | European Dexamethasone Meningitis Trial, 2002: reduced mortality and hearing loss in S. pneumoniae meningitis. Give before or with first antibiotic dose. Discontinue if NOT S. pneumoniae (no benefit for other organisms). Do NOT give if already received antibiotics — benefit lost. |
| Acyclovir (Zovirax) | 10 mg/kg IV q8h | Add if encephalitis suspected (AMS, seizures, temporal lobe findings, behavioral changes). Covers HSV encephalitis — mortality ~70% without treatment, ~20% with acyclovir. |
Chemoprophylaxis — Close Contacts
- N. meningitidis confirmed: close contacts (household, kissing, shared utensils, healthcare workers with unprotected airway exposure) need prophylaxis
- Rifampin 600 mg PO BID × 2 days, OR ciprofloxacin 500 mg PO × 1 dose (preferred — single dose), OR ceftriaxone 250 mg IM × 1
- Not needed for S. pneumoniae
📋 Clinical Example — Bacterial Meningitis Empiric Therapy
Patient: 22M, worst headache of life, fever 39.4°C, nuchal rigidity, photophobia, petechial rash on trunk/extremities.
Do NOT delay antibiotics for LP or CT:
- Blood cultures × 2 → antibiotics IMMEDIATELY → then CT (if indicated) → then LP.
- Antibiotics within 1 hour. Every hour of delay worsens mortality.
Empiric therapy (age 18–50):
- Ceftriaxone (Rocephin) 2g IV q12h (covers N. meningitidis, S. pneumoniae, H. influenzae)
- + Vancomycin (Vancocin) 15–20mg/kg IV q8–12h (covers resistant S. pneumoniae — MIC > 0.1)
- + Dexamethasone (Decadron) 0.15 mg/kg IV q6h × 4 days — give BEFORE or WITH first antibiotic dose (reduces mortality in pneumococcal meningitis — Cochrane 2015). No benefit if given after antibiotics.
If age > 50 or immunocompromised: Add ampicillin (Amoxil) 2g IV q4h for Listeria coverage.
Petechial rash → highly suspicious for N. meningitidis → droplet isolation (not airborne). Chemoprophylaxis for close contacts: ciprofloxacin (Cipro) 500mg PO × 1 dose or rifampin (Rifadin) 600mg PO BID × 2 days.
CSF expected: WBC > 1000 (PMN predominant), protein > 250, glucose < 40, Gram stain + in ~60%.
🔄 Updated Practice: Old teaching: dexamethasone is controversial in bacterial meningitis. Current evidence: dexamethasone (0.15 mg/kg IV q6h × 4 days) BEFORE or WITH the first antibiotic dose reduces mortality and hearing loss in PNEUMOCOCCAL meningitis (European Dexamethasone Meningitis Trial, 2002). Key: it must be given before or simultaneously with antibiotics — no benefit if given after. No proven benefit in meningococcal or gram-negative meningitis, but most centers give it empirically since you don't know the organism yet.
💊 Medications
Empiric Antibiotic Therapy — Bacterial Meningitis
Do NOT delay antibiotics. Give empiric therapy immediately after (or ideally with) blood cultures. Every hour of delay increases mortality. LP can follow antibiotics — CSF cultures remain positive for hours.
| Drug | Dose | Indication | Key Notes |
|---|---|---|---|
| Ceftriaxone | 2g IV q12h | Empiric coverage — S. pneumoniae, N. meningitidis, H. influenzae, GNRs | Higher dose than standard (meningeal dosing) — needed for adequate CSF penetration across BBB. |
| Vancomycin | 15-20 mg/kg IV q8-12h | Empiric — covers penicillin-resistant S. pneumoniae (up to 30% resistance in some areas) | Target AUC/MIC 400-600 (AUC-guided dosing per 2020 ASHP/IDSA guidelines). Load with 25-30 mg/kg if severe. |
| Dexamethasone | 0.15 mg/kg IV q6h × 4 days | Give BEFORE or WITH first antibiotic dose — reduces inflammation from bacterial lysis | Proven mortality benefit in pneumococcal meningitis de Gans, 2002. Discontinue if non-pneumococcal etiology confirmed. Must give before/with antibiotics — no benefit if given after. |
| Ampicillin | 2g IV q4h | Add if age > 50, immunocompromised, pregnant, or alcoholic — covers Listeria monocytogenes | Listeria is intrinsically resistant to cephalosporins. Must add ampicillin for Listeria coverage in at-risk patients. |
| Acyclovir | 10 mg/kg IV q8h | Add if HSV encephalitis suspected (temporal lobe findings, behavioral changes, seizures) | Adjust for renal function. Duration 14-21 days for HSV encephalitis. Maintain adequate hydration to prevent crystalluria. |
Standard empiric regimen: Ceftriaxone + vancomycin + dexamethasone for all adults. ADD ampicillin if age > 50 or immunocompromised. ADD acyclovir if HSV suspected. Narrow based on culture and susceptibility results.
📈 Monitoring
Monitoring Parameters — Bacterial Meningitis
| Parameter | Frequency | Target / Action |
|---|---|---|
| Neuro checks | q1-2h (ICU); q4h (floor, once stable) | GCS, pupil reactivity, focal deficits, neck stiffness. Any decline → urgent re-imaging (CT head), consider repeat LP, escalate to ICU. |
| Temperature | q4h | Expect fever resolution within 48-72h on appropriate antibiotics. Persistent fever > 72h → re-evaluate (drug fever, abscess, subdural empyema, wrong organism). |
| Repeat LP | At 48h if not clinically improving | Expected improvement: CSF WBC decreasing, glucose rising, protein falling. No improvement → consider resistant organism, abscess, or wrong diagnosis. Do NOT repeat LP routinely if improving. |
| BMP (Cr, electrolytes) | Daily | Monitor for SIADH (Na⁺ — common in meningitis). Cr for vancomycin and acyclovir dosing. Hyponatremia in meningitis = fluid restrict, NOT NS boluses. |
| Vancomycin levels | AUC-guided dosing (draw trough before 4th dose or per pharmacy) | Target AUC/MIC 400-600. Nephrotoxicity risk increases with supratherapeutic levels. Coordinate with pharmacy for Bayesian dosing. |
| Seizure monitoring | Clinical observation; EEG if concern for subclinical seizures | Seizures occur in ~20-30% of bacterial meningitis. Prophylactic AEDs not recommended — treat if seizures occur. Levetiracetam first-line. |
| ICP monitoring | Clinical signs (headache, vomiting, papilledema, altered consciousness) | Elevate HOB 30 degrees. Avoid hypotonic fluids. Consider mannitol or hypertonic saline if clinical signs of elevated ICP. Neurosurgery consult if refractory. |
| Hearing assessment | Before discharge | Sensorineural hearing loss is the most common long-term complication (~30% in pneumococcal). Formal audiology referral before discharge. |
Close contacts: For N. meningitidis — chemoprophylaxis for close contacts (household, kissing, healthcare workers with prolonged face-to-face exposure). Rifampin 600 mg BID × 2 days, or ciprofloxacin 500 mg × 1, or ceftriaxone 250 mg IM × 1.
📋 On Rounds
Why give dexamethasone before antibiotics in bacterial meningitis?
When antibiotics lyse bacteria, cell wall fragments (lipoteichoic acid, peptidoglycan) are released → massive inflammatory cascade in the subarachnoid space → cerebral edema, increased ICP, neuronal damage. Dexamethasone dampens this inflammatory burst. European Dexamethasone Meningitis Trial, 2002: dex given before/with the first antibiotic dose in S. pneumoniae meningitis reduced mortality from 15% to 7% and hearing loss significantly. The timing is critical — once the inflammatory cascade has started (antibiotics already given), dex has no benefit. This is why you give dex before or simultaneously with the first dose, never after.
Why is the ceftriaxone dose 2g q12h for meningitis instead of the usual 1–2g daily?
The blood-brain barrier limits antibiotic penetration into the CSF. Even with meningeal inflammation (which increases permeability), only a fraction of serum drug levels reach the CSF. To achieve adequate bactericidal concentrations in the CSF, you need higher and more frequent dosing than for systemic infections. Ceftriaxone 2g q12h achieves CSF levels that reliably exceed the MIC for S. pneumoniae and N. meningitidis. Standard 1–2g daily dosing achieves subtherapeutic CSF levels for meningitis. The same principle applies to vancomycin — target AUC/MIC 400–600 (2020 ASHP/IDSA guidelines). Some CNS infection experts target higher AUC for meningeal penetration, but trough-based monitoring (15–20 mcg/mL) is no longer the standard.
When do you need a CT head before LP, and what happens if it delays treatment?
CT before LP is needed if: immunocompromised, history of CNS disease, new-onset seizure, papilledema, altered consciousness, focal neurologic deficit. These identify patients at risk for brain herniation from LP. If CT is needed: draw blood cultures → start empiric antibiotics + dexamethasone IMMEDIATELY → then CT → then LP when safe. Do NOT delay antibiotics for CT or LP. In bacterial meningitis, every hour of antibiotic delay increases mortality. The LP can be done after antibiotics are started — CSF cultures remain positive for hours after first dose (especially for S. pneumoniae). A negative CSF culture after early antibiotics doesn't rule out bacterial meningitis — use the full picture (cell count, protein, glucose, gram stain, PCR).
How do you interpret CSF results to differentiate bacterial from viral meningitis?
Bacterial: WBC > 1,000 (PMN predominant > 80%), protein > 200, glucose < 40 (or CSF/serum glucose ratio < 0.4), gram stain positive in ~60-90%. Viral: WBC 10-500 (lymphocyte predominant), protein 50-100, glucose normal, gram stain negative. TB/fungal: WBC 10-500 (lymphocyte predominant), protein very high (> 200), glucose LOW (like bacterial). Pearl: early bacterial meningitis can have lymphocyte predominance (first 12-24h) — if clinical suspicion is high, treat regardless of CSF profile. Also: partially treated bacterial meningitis (patient received antibiotics before LP) can mimic viral — lower WBC, negative culture, but protein and glucose still abnormal.
📣 Sample Presentation
One-Liner
"Mr. Jackson is a 55-year-old immunocompromised (on prednisone 20 mg for RA) presenting with fever 39.4°C, headache, neck stiffness, and confusion. LP: WBC 1,200 (90% PMN), protein 280, glucose 18 (serum 120), gram stain showing gram-positive diplococci."
Key Points to Cover on Rounds
Bacterial meningitis — likely S. pneumoniae (gram-positive diplococci). Antibiotics started within 30 min: vancomycin + ceftriaxone 2g q12h + ampicillin 2g q4h (age consideration + immunocompromised → Listeria coverage). Dexamethasone 10 mg IV q6h × 4 days given before first antibiotic dose [European Dexamethasone Meningitis Trial, 2002]. Blood cultures × 2 drawn. CT head before LP: no mass effect. CSF culture pending. Plan: narrow antibiotics when sensitivities return, complete 10-14 day course, repeat LP if no improvement at 48h.
⚡ Summary
Summary
Empiric Abx
Vancomycin + ceftriaxone + ampicillin (if > 50, immunocompromised, or pregnant — Listeria coverage). Start within 30 min.
Dexamethasone
10 mg IV q6h × 4 days. Give before or with first antibiotic dose. Reduces mortality in S. pneumoniae [European Dexamethasone Meningitis Trial, 2002].
CT Before LP?
Only if: immunocompromised, CNS disease, new seizure, papilledema, focal deficit, altered consciousness. Don't delay abx for CT.
CSF Findings
Bacterial: PMN > 1000, protein > 200, glucose < 40. Viral: lymphocytes, protein 50-100, glucose normal. TB/fungal: lymphocytes, very high protein, low glucose.
Duration
S. pneumoniae: 10-14 days. N. meningitidis: 5-7 days. Listeria: 21 days. HSV encephalitis (acyclovir): 14-21 days.
Chemoprophylaxis
N. meningitidis contacts: rifampin 600 BID × 2 days OR ciprofloxacin 500 × 1 OR ceftriaxone 250 IM × 1.
📄 One Pager
Meningitis & Encephalitis — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
MENINGITIS & ENCEPHALITIS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
UTI & Pyelonephritis
The most common bacterial infection in adults. The biggest mistake residents make: treating asymptomatic bacteriuria. A positive UA or culture in a patient without urinary symptoms is NOT a UTI — it's colonization. Don't treat the lab.
🔍 Overview
Classification
| Type | Definition | Treatment Duration |
|---|---|---|
| Uncomplicated cystitis | Lower UTI (dysuria, frequency, urgency) in non-pregnant, premenopausal women with normal urinary tract | 3–5 days |
| Complicated UTI | UTI with: male sex, pregnancy, structural abnormality, catheter, immunosuppression, renal transplant, recent instrumentation | 7–14 days |
| Pyelonephritis | Upper UTI: fever, flank pain, CVA tenderness ± lower urinary symptoms | 5–7 days (outpatient FQ) or 10–14 days (if complicated/inpatient) |
| Catheter-associated UTI (CAUTI) | Catheter in place (or removed within 48h) + symptoms + culture ≥ 10³ CFU/mL. NOT the same as asymptomatic bacteriuria from catheter. | 7 days (remove/replace catheter first) |
Asymptomatic Bacteriuria — Do NOT Treat
Positive UA/culture WITHOUT urinary symptoms = asymptomatic bacteriuria. Do NOT treat. Treating ASB drives antibiotic resistance, C. diff risk, and adverse drug effects without benefit. IDSA, 2019
- Exceptions (treat ASB): pregnancy (risk of pyelonephritis → preterm labor), pre-urologic procedure with mucosal bleeding expected
- Do NOT treat ASB in: elderly, catheterized patients, diabetics, spinal cord injury, nursing home residents — even if pyuria is present
- Pyuria alone is NOT an indication for treatment — it reflects inflammation, not necessarily infection
💊 Management
Empiric Antibiotics
| Diagnosis | First-Line | Alternative | Notes |
|---|---|---|---|
| Uncomplicated cystitis | Nitrofurantoin 100 mg BID × 5 days 1ST LINE | TMP-SMX DS BID × 3 days (if local resistance < 20%). Fosfomycin 3g PO × 1 dose. | Avoid fluoroquinolones for uncomplicated cystitis — FDA warning, collateral damage, save for complicated infections. Nitrofurantoin: avoid if CrCl < 30 (ineffective + toxic). |
| Pyelonephritis — outpatient | Ciprofloxacin (Cipro) 500 mg BID × 7 days or levofloxacin (Levaquin) 750 mg daily × 5 days | TMP-SMX DS BID × 14 days (if susceptible). Ceftriaxone 1g IM × 1 + oral step-down. | FQs are appropriate here (upper tract). Get urine culture to guide de-escalation. Consider admission if: unable to tolerate PO, sepsis, pregnancy, concern for obstruction. |
| Pyelonephritis — inpatient | Ceftriaxone (Rocephin) 1g IV daily 1ST LINE | Ciprofloxacin 400 mg IV q12h. Piperacillin-tazobactam if MDR risk. Meropenem if ESBL. | Step down to oral once afebrile × 48h and tolerating PO. Total duration depends on oral step-down agent: FQ 5–7 days, TMP-SMX 7–10 days, beta-lactam 10–14 days. CT abdomen if no improvement in 48–72h (abscess? obstruction?). |
| CAUTI | Based on local antibiogram + culture | Broader coverage initially (ceftriaxone or FQ). Narrow based on susceptibilities. | Remove or replace the catheter first — this alone can resolve the infection. Culture from NEW catheter. Duration 7 days. Assess if catheter is still needed — remove ASAP. |
🔄 Updated Practice: Complicated UTI was traditionally defined by a checklist of host factors (male, catheter, pregnant, etc.). The modern definition is simpler: any UTI that extends beyond the bladder. Additionally, asymptomatic bacteriuria should NOT be treated (except in pregnancy and before urologic procedures) — old practice was to treat all positive urine cultures.
📋 On Rounds
An 85-year-old with dementia has a positive UA (leukocyte esterase, bacteria) but no urinary symptoms. Should you treat?
No. This is asymptomatic bacteriuria (ASB). Up to 50% of elderly nursing home residents and 100% of chronically catheterized patients have bacteriuria without true infection. Treating ASB does not reduce mortality, morbidity, or subsequent symptomatic UTIs — but it does increase antibiotic resistance and C. diff risk. The exception: confusion in the elderly is NOT a urinary symptom. AMS + bacteriuria does not automatically = UTI. Look for other causes of delirium first (medications, constipation, infection elsewhere, metabolic). Only treat if there are clear urinary symptoms (dysuria, new urgency/frequency, suprapubic pain, gross hematuria) or systemic signs without another source.
Why should fluoroquinolones be avoided for uncomplicated cystitis?
FQ's (ciprofloxacin, levofloxacin) carry FDA black box warnings for tendon rupture, peripheral neuropathy, aortic dissection, and CNS effects — risks that are disproportionate for a self-limiting infection like uncomplicated cystitis. Nitrofurantoin or TMP-SMX are equally effective with far less toxicity. FQ's should be reserved for complicated UTIs, pyelonephritis when oral is needed, or resistant organisms. The principle: match antibiotic risk to disease severity. An uncomplicated cystitis doesn't warrant the risk of an Achilles rupture.
An elderly patient has a positive urine culture but no urinary symptoms. Should you treat?
NO — this is asymptomatic bacteriuria (ASB), and treating it causes harm. ASB is defined as bacteria in urine without urinary symptoms (dysuria, frequency, urgency, suprapubic pain, fever). Do NOT treat ASB — antibiotics don't improve outcomes and promote resistance + C. diff. This is one of the most common antibiotic stewardship violations. Only 2 exceptions where you DO treat ASB: (1) Pregnancy (untreated ASB → 30% risk of pyelonephritis, preterm labor), (2) Before urologic procedures involving mucosal bleeding. Notably: ASB is NOT treated in elderly, catheterized patients, diabetics, spinal cord injury, or nursing home residents — even if the urine is cloudy or smelly. Pyuria alone is not an indication to treat — pyuria is common in elderly patients without infection.
What antibiotics require dose adjustment in renal failure for UTI, and which don't?
Nitrofurantoin: AVOID if CrCl < 30 (doesn't concentrate in urine → ineffective, and accumulates → peripheral neuropathy). TMP-SMX: avoid if CrCl < 15. Watch for hyperkalemia (trimethoprim blocks ENaC). Ciprofloxacin: reduce to 250 mg BID if CrCl < 30. Ceftriaxone: no adjustment needed (biliary excretion). Fosfomycin: single 3g dose, no adjustment needed, but less effective in complicated UTI. Amoxicillin-clavulanate: reduce frequency if CrCl < 30. For pyelonephritis in CKD: ceftriaxone 1g IV daily is safest empiric choice (no renal dosing, broad GN coverage). Avoid gentamicin unless absolutely necessary (nephrotoxic).
📣 Sample Presentation
One-Liner
"Ms. Chen is a 28-year-old healthy woman presenting with 3 days of dysuria, frequency, and urgency. No fever, no flank pain. UA: positive LE, positive nitrites, WBC 80. Consistent with uncomplicated cystitis."
Key Points to Cover on Rounds
Uncomplicated cystitis in a healthy, non-pregnant female. Treatment: nitrofurantoin 100 mg BID × 5 days (first-line). Avoided fluoroquinolones (FDA black box, disproportionate risk for self-limiting infection). Urine culture sent but treatment is empiric — will adjust only if resistant. No imaging needed. Plan: symptom relief with phenazopyridine 200 mg TID × 2 days, return if fever/flank pain develop (would indicate pyelonephritis).
🧪 Workup
Diagnostic Evaluation — Clostridioides difficile (C. diff)
Workup checklist for Clostridioides difficile (C. diff): History and physical → targeted labs → imaging as indicated → specialist consultation if needed. Always correlate clinically.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications, relevant PMH
- Physical exam: Focused exam relevant to clostridioides difficile (c. diff) presentation
- Labs: CBC, BMP, relevant disease-specific labs (see Overview tab for specifics)
- Imaging: As clinically indicated based on presentation
- Special studies: Consider disease-specific diagnostics (see Overview tab)
💊 Medications
Antibiotic Therapy — Urinary Tract Infections
Uncomplicated cystitis does NOT require urine culture. Treat empirically. Reserve cultures for complicated UTI, pyelonephritis, recurrent infections, or treatment failure. Always check local antibiogram for resistance patterns.
| Indication | Drug | Dose | Duration | Key Notes |
|---|---|---|---|---|
| Uncomplicated Cystitis | Nitrofurantoin (Macrobid) FIRST-LINE | 100 mg PO BID | 5 days | Avoid if CrCl < 30 (poor urinary concentration). Take with food. Not effective for pyelonephritis (no tissue penetration). |
| TMP-SMX DS (Bactrim) | 1 DS tab PO BID | 3 days | Use only if local E. coli resistance < 20%. Check sulfa allergy. Avoid in 3rd trimester pregnancy. | |
| Fosfomycin (Monurol) | 3g PO × 1 dose | Single dose | Convenient but less effective than multi-day regimens. Good option for MDR organisms (ESBL). Not for complicated UTI. | |
| Pyelonephritis (inpatient) | Ceftriaxone FIRST-LINE | 1g IV daily | Step down to PO when afebrile 24-48h; total duration by PO agent: FQ 5-7d, TMP-SMX 7-10d, beta-lactam 10-14d | Broad GNR coverage. Obtain blood and urine cultures before starting. Transition to PO based on susceptibilities. |
| Ciprofloxacin | 400 mg IV q12h | Step down to PO 500 mg BID; total 5-7 days | Fluoroquinolone — FDA black box warning (tendon, nerve, CNS effects). Use only if no safer alternative. Shorter course (5-7d) if FQ used Sandberg, 2012. | |
| Piperacillin-tazobactam | 3.375g IV q8h (extended infusion) | Narrow when cultures available | Reserve for severely ill or concern for resistant organisms. De-escalate promptly. | |
| Pyelonephritis (outpatient) | Ciprofloxacin | 500 mg PO BID | 5-7 days | Most effective oral option for pyelo. Check local resistance. Give initial dose of ceftriaxone 1g IV/IM if any concern. |
| TMP-SMX DS | 1 DS tab PO BID | 7-14 days | Only if susceptibility confirmed. Give initial parenteral dose (ceftriaxone 1g) for reliable early bactericidal activity. |
Asymptomatic bacteriuria: Do NOT treat except in pregnancy or pre-urologic procedure. Positive UA/culture without dysuria, frequency, or urgency = colonization, not infection. Treating ASB drives resistance and causes C. diff.
📈 Monitoring
Monitoring Parameters — Urinary Tract Infections
| Parameter | Frequency | Target / Action |
|---|---|---|
| Symptom resolution | 48-72h after starting antibiotics | Dysuria, frequency, urgency should improve within 48-72h. If not improving → recheck culture, consider resistant organism, imaging for complication (abscess, obstruction). |
| Temperature (pyelonephritis) | q4-8h inpatient | Fever should defervesce within 48-72h on appropriate antibiotics. Persistent fever → CT abdomen/pelvis to rule out perinephric abscess or obstruction. |
| Urine culture results | Check at 48h when available | Narrow antibiotic based on susceptibilities. De-escalate from IV to PO when afebrile 24-48h and tolerating PO. |
| Creatinine | At baseline; repeat if on nephrotoxic agents or pyelonephritis | Monitor for AKI in pyelonephritis. Adjust antibiotic dosing for renal function (nitrofurantoin ineffective if CrCl < 30). |
| Blood cultures (pyelonephritis) | At presentation; no routine repeat | Positive in ~20-30% of pyelonephritis. Guides duration (bacteremia may warrant 10-14 day course). Repeat only if persistent bacteremia suspected. |
Do NOT repeat UA or urine culture for "test of cure." Bacteriuria can persist after successful treatment and does not require retreatment if the patient is asymptomatic. Repeating cultures leads to unnecessary antibiotic courses and C. diff risk.
⚡ Summary
Summary
Uncomplicated Cystitis
Nitrofurantoin 100 BID × 5 days (first-line). TMP-SMX × 3 days (if susceptible). Avoid fluoroquinolones (FDA black box).
Pyelonephritis
Ceftriaxone 1g IV daily (inpatient) or ciprofloxacin 500 BID × 7 days (outpatient, if susceptible). Blood cultures + urine culture.
ASB — Don't Treat
Asymptomatic bacteriuria: treat ONLY in pregnancy or pre-urologic surgery. Not in elderly, catheterized, diabetic, or nursing home patients.
Complicated UTI
Male, pregnant, structural abnormality, catheterized, immunocompromised, recent instrumentation → broader coverage, longer course (10-14 days).
Catheter-Associated
Remove or replace catheter + antibiotics. Duration: 7 days (10-14 if delayed response). Don't treat pyuria alone in catheterized patients.
Recurrent UTI
≥ 3/year or ≥ 2 in 6 months. Options: post-coital prophylaxis, continuous low-dose abx, vaginal estrogen (postmenopausal).
📄 One Pager
Clostridioides difficile (C. diff) — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
CLOSTRIDIOIDES DIFFICILE (C. DIFF) — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
ID · One Pager
UTI — Cystitis & Pyelonephritis
Cystitis: nitrofurantoin × 5d (avoid FQ). Pyelo: ceftriaxone or cipro. ASB: treat ONLY in pregnancy or pre-urologic surgery. Don't treat pyuria in catheterized patients.
Uncomplicated Cystitis
Dysuria + frequency + urgency in healthy non-pregnant female. Nitrofurantoin 100 BID × 5d (first-line). TMP-SMX × 3d if susceptible. Avoid fluoroquinolones.
Pyelonephritis
Fever + flank pain + CVA tenderness. Ceftriaxone 1g IV (inpatient) or cipro 500 BID × 7d (outpatient, if susceptible). Blood cultures + urine culture. Imaging if not improving at 48-72h.
Asymptomatic Bacteriuria
Do NOT treat ASB — causes harm (resistance + C. diff). Only 2 exceptions: (1) Pregnancy. (2) Pre-urologic procedures with mucosal bleeding. Not in elderly, catheterized, diabetic, or nursing home.
Key Drugs
Nitrofurantoin100 mg BID × 5d
TMP-SMX DS1 tab BID × 3d
Ceftriaxone1g IV daily
Ciprofloxacin500 mg BID × 7d (pyelo)
Pitfalls
- FQ for uncomplicated cystitis (disproportionate risk)
- Treating ASB in elderly/catheterized patients
- Nitrofurantoin if CrCl < 30 (ineffective)
- Not culturing urine in pyelonephritis
HIV — Inpatient Essentials
What the IM resident needs to know: opportunistic infections by CD4 count, when to start ART, immune reconstitution inflammatory syndrome (IRIS), and drug interactions. ART is now "treat all, treat early" — start regardless of CD4.
🔍 Opportunistic Infections by CD4 Count
| CD4 Count | Opportunistic Infection | Prophylaxis | Treatment |
|---|---|---|---|
| < 500 | Kaposi sarcoma (HHV-8), oral hairy leukoplakia (EBV), candidal vaginitis | ART | ART ± chemo for KS |
| < 200 | PCP (Pneumocystis jirovecii pneumonia) — bilateral GGOs, exertional desaturation, elevated LDH | TMP-SMX DS daily (or dapsone, atovaquone) | TMP-SMX 15–20 mg/kg/day (TMP component) × 21 days. If PaO₂ < 70 or A-a gradient > 35 → add prednisone (taper over 21 days). |
| < 200 | Toxoplasmosis — ring-enhancing brain lesions (multiple, basal ganglia) | TMP-SMX* (covers both PCP + toxo) *TMP-SMX = Trimethoprim-Sulfamethoxazole (Bactrim) | Pyrimethamine + sulfadiazine + leucovorin × 6 weeks |
| < 150 | Histoplasmosis / Coccidioidomycosis (endemic fungi) | ART + itraconazole in endemic areas | Amphotericin B (severe) → itraconazole maintenance |
| < 100 | Cryptococcal meningitis — headache, AMS, ↑ opening pressure on LP. India ink, CrAg+ | Consider CrAg screening if CD4 < 100 | Amphotericin B + flucytosine × 2 weeks → fluconazole maintenance. Serial LPs for pressure management. |
| < 50 | CMV retinitis (flame hemorrhages on fundoscopy), CMV colitis/esophagitis | ART (no specific prophylaxis) | Ganciclovir or valganciclovir |
| < 50 | MAC (Mycobacterium avium complex) — disseminated: fever, weight loss, diarrhea, pancytopenia, elevated alk phos | Azithromycin 1200 mg weekly (if ART not started yet) | Clarithromycin + ethambutol ± rifabutin |
CD4 < 200 = AIDS-defining. PCP and toxo prophylaxis start here. TMP-SMX DS daily covers both. Discontinue prophylaxis when CD4 > 200 for ≥ 3 months on ART.
💊 ART Basics
When to Start ART
Start ART in ALL HIV-positive patients regardless of CD4 count. START, 2015: immediate ART (any CD4) reduced serious AIDS events and death vs deferred treatment (CD4 < 350). SMART, 2006: ART interruptions increase mortality — never stop ART. HPTN 052, 2011: early ART reduces transmission by 96% (U=U). Treat early, treat all.
- Exception — delay ART in: cryptococcal meningitis (start ART 4–6 weeks after antifungal induction — early ART causes fatal IRIS) and TB meningitis (delay 2–8 weeks)
- Rapid ART initiation (same day or within 7 days of diagnosis) is now recommended — improves linkage to care and viral suppression
Preferred Initial Regimen
| Regimen | Components | Notes |
|---|---|---|
| Biktarvy PREFERRED | Bictegravir + emtricitabine + TAF (single pill, once daily) | Preferred first-line. High barrier to resistance, minimal drug interactions, well-tolerated. Renal/bone-safe (TAF > TDF). |
| Dovato | Dolutegravir + lamivudine (2-drug regimen) | Acceptable first-line if HBV-negative and viral load < 500,000. Not if HBV co-infected (needs 2 active HBV drugs). |
| Triumeq | Dolutegravir + abacavir + lamivudine | Alternative. Requires HLA-B*5701 testing before starting abacavir (risk of fatal hypersensitivity reaction if positive). |
IRIS (Immune Reconstitution Inflammatory Syndrome)
- Occurs 2–12 weeks after starting ART — immune system "wakes up" and mounts an exuberant inflammatory response against pre-existing (often subclinical) infections
- Unmasking IRIS: new OI symptoms appear after ART initiation (was subclinical before)
- Paradoxical IRIS: known OI worsens after ART initiation despite appropriate treatment
- Common IRIS pathogens: TB (#1), MAC, cryptococcus, CMV, P
CP, KS🧪 WorkupWorkup
- HIV RNA viral load
- CD4 count + %
- Resistance genotype before ART
- HLA-B*5701 if considering abacavir
- BMP, LFTs, CBC
- HBV/HCV serologies
- RPR, QuantiFERON, toxo IgG
- CXR
- Treatment: continue ART + treat the OI + NSAIDs
for mild IRIS. Steroids for severe IRIS (especially TB-IRIS). Stop ART on🚨 ManagementManagement
- ART: start ALL patients, within 2wk. Exception: crypto meningitis.
- Preferred: bictegravir/FTC/TAF (1 pill daily)
- OI prophylaxis: CD4<200→TMP-SMX. CD4<50→azithromycin.
- IRIS: continue ART + treat OI + steroids if severe.
ly if life-threatening (rare).💊 MedicationsART RegimensRegimen Dose Route Notes Bictegravir/emtricitabine/TAF (Biktarvy)
PREFERRED 1ST LINE1 tab daily PO INSTI-based single-tablet regimen. High barrier to resistance. Few drug interactions. Well-tolerated. CrCl ≥30. Dolutegravir (Tivicay) + emtricitabine/TAF (Descovy) 50 mg + 1 tab daily PO INSTI-based alternative. Dolutegravir has high barrier to resistance. Avoid with dofetilide, carbamazepine. Dolutegravir/lamivudine (Dovato) 1 tab daily PO Two-drug regimen. Only if VL <500K, no HBV coinfection, and resistance testing available before starting. OI ProphylaxisInfection Drug Indication Notes PCP TMP-SMX DS (Bactrim) 1 tab daily CD4 <200 or oropharyngeal candidiasis Also covers toxoplasma prophylaxis. Alternatives: dapsone (check G6PD), atovaquone, aerosolized pentamidine. MAC Azithromycin (Zithromax) 1200 mg weekly CD4 <50 Discontinue when CD4 >100 for ≥3 months on ART. Alternative: clarithromycin 500 mg BID. Crypto maintenance Fluconazole (Diflucan) 200 mg daily After induction/consolidation for cryptococcal meningitis Secondary prophylaxis. Discontinue when CD4 >200 for ≥6 months + undetectable VL.
📊 Monitoring
Monitoring
| Parameter | Frequency | Target / Notes |
|---|---|---|
| HIV viral load | At 4 weeks, then q3-6 months | Goal: undetectable (<50 copies/mL). Should suppress within 12-24 weeks of ART. Detectable VL → assess adherence, resistance testing. |
| CD4 count | q3-6 months until immune reconstitution | Guides OI prophylaxis. Discontinue monitoring once CD4 >300 ×2 and VL suppressed (CD4 no longer clinically actionable). |
| BMP, LFTs | Baseline, then q6-12 months | ART hepatotoxicity and nephrotoxicity. Tenofovir (TDF/TAF): monitor Cr, phosphate. TAF has less renal toxicity than TDF. |
| Fasting lipids, HbA1c | Baseline, then annually | Metabolic monitoring — HIV and ART increase cardiovascular risk. Protease inhibitors most lipid-unfriendly. Screen and treat per guidelines. |
| STI screening | At diagnosis, then annually (or more frequently if high-risk) | Syphilis (RPR), gonorrhea/chlamydia (NAAT, 3-site), hepatitis B/C serology. |
| Cervical/anal cancer screening | Per guidelines | HPV-related malignancy risk increased. Cervical Pap for women. Anal Pap for MSM and history of anal dysplasia. |
| Resistance testing | At diagnosis + treatment failure | Genotype before starting ART. Repeat if VL rebounds on treatment (adherence must be assessed first). |
📋 On Rounds
Why do you delay ART in cryptococcal meningitis?
COAT Trial, 2014: starting ART within 1–2 weeks of cryptococcal meningitis diagnosis increased mortality vs waiting 5–6 weeks. The mechanism: early immune reconstitution causes a massive inflammatory response in the CNS against cryptococci → cerebral edema → herniation → death. The standard is: complete 2 weeks of amphotericin B + flucytosine induction, transition to fluconazole consolidation, then start ART at 4–6 weeks once the CNS infection is controlled and ICP is normalized. TB meningitis is similar — delay ART 2–8 weeks.
When should you NOT start ART immediately after HIV diagnosis?
Cryptococcal meningitis is the main exception. Starting ART during active crypto meningitis causes immune reconstitution inflammatory syndrome (IRIS) → cerebral edema → herniation → death. The COAT trial showed early ART (within 1–2 weeks) had higher mortality than deferred ART (5 weeks after antifungal induction). Treat crypto first (amphotericin B + flucytosine × 2 weeks), then start ART at 4–6 weeks. For most other OIs (PCP, toxo, MAC), ART should be started within 2 weeks of OI treatment.
What are the 3 most important opportunistic infections to know by CD4 count?
CD4 < 200: PCP (Pneumocystis jirovecii pneumonia) — bilateral GGO, elevated LDH, hypoxia with exertion. Prophylaxis: TMP-SMX DS daily. Treatment: TMP-SMX high-dose + prednisone if PaO₂ < 70. CD4 < 100: Toxoplasmosis — ring-enhancing brain lesions (multiple, basal ganglia). Prophylaxis: TMP-SMX (same pill covers both PCP and toxo). Treatment: pyrimethamine + sulfadiazine + leucovorin. CD4 < 50: MAC (Mycobacterium avium complex) — disseminated: fever, weight loss, elevated alk phos, pancytopenia. Prophylaxis: azithromycin 1200 mg weekly. Treatment: azithromycin + ethambutol. Pearl: TMP-SMX DS daily covers BOTH PCP and toxoplasma prophylaxis — one pill, two infections.
What is IRIS and how do you manage it?
Immune Reconstitution Inflammatory Syndrome (IRIS) = paradoxical clinical worsening after starting ART, caused by the recovering immune system mounting an inflammatory response against pre-existing (often subclinical) infections. Onset: usually 1-12 weeks after ART initiation. Common in: TB-IRIS (lymph node enlargement, worsening CXR), crypto-IRIS (increased intracranial pressure), MAC-IRIS (lymphadenitis), CMV-IRIS (vitritis). Management: (1) Continue ART (don't stop), (2) treat the underlying OI aggressively, (3) NSAIDs for mild IRIS, (4) corticosteroids for severe IRIS (prednisone 1 mg/kg taper over 4 weeks — especially for TB-IRIS and crypto-IRIS). Prevention: treat OIs before or soon after starting ART, avoid starting ART during active crypto meningitis.
📣 Sample Presentation
One-Liner
"Mr. Roberts is a 34-year-old newly diagnosed with HIV after presenting with PCP pneumonia. CD4 42, viral load 380,000. LDH 520, bilateral GGO on CT chest. Started on TMP-SMX for PCP."
Key Points to Cover on Rounds
New HIV diagnosis with AIDS-defining illness (PCP, CD4 42). Treatment: TMP-SMX 15-20 mg/kg/day (trimethoprim component) × 21 days + prednisone taper (PaO₂ <70). ART start timing: within 2 weeks of OI treatment (not day 1 — IRIS risk). Planned ART: bictegravir/emtricitabine/TAF. OI prophylaxis needed: PCP (already treating), MAC (azithro 1200 weekly if CD4 <50), toxo (TMP-SMX covers). Screening: QuantiFERON, RPR, hepatitis panel, Pap smear. Resistance genotype sent before starting ART.
⚡ Summary
Summary
Start ART
In ALL patients regardless of CD4. Start within 2 weeks of diagnosis. Exception: crypto meningitis (wait until CSF sterilized — IRIS risk).
Preferred ART
Bictegravir/emtricitabine/TAF (single pill, once daily). Alternative: dolutegravir-based regimen.
OI Prophylaxis
CD4 < 200: TMP-SMX (PCP + toxo). CD4 < 100: add toxo coverage (same TMP-SMX). CD4 < 50: azithromycin weekly (MAC).
Monitoring
Viral load at 4 weeks (should drop > 1 log), then q3-6 months. Goal: undetectable (< 50 copies/mL). CD4 q3-6 months.
IRIS
Paradoxical worsening 1-12 weeks after starting ART. Continue ART + treat OI + steroids if severe. Don't stop ART.
Resistance
Genotype before starting ART. If virologic failure (detectable VL on ART) → resistance testing → switch regimen.
📄 One Pager
ID · One Pager
HIV
Start ART in ALL patients regardless of CD4. OI prophylaxis by CD4 count. TMP-SMX covers PCP + toxo. Monitor VL + CD4. Watch for IRIS.
Key CD4 Thresholds
< 200: PCP risk → TMP-SMX. < 100: toxoplasma risk → TMP-SMX covers both. < 50: MAC risk → azithromycin weekly. < 50: CMV risk → monitor.
ART
Start in ALL patients. Preferred: bictegravir/emtricitabine/TAF (single pill, once daily). Get resistance genotype before starting. Goal: undetectable VL (< 50) by 6 months.
IRIS
Paradoxical worsening 1-12 weeks after starting ART (immune reconstitution). Continue ART + treat OI aggressively. Steroids for severe IRIS. Don't stop ART.
Key Drugs
Bictegravir/FTC/TAF1 tab daily
TMP-SMX DS1 tab daily (PCP/toxo)
Azithromycin1200 mg weekly (MAC)
Fluconazole200 mg daily (crypto maintenance)
Pitfalls
- Delaying ART initiation
- Starting ART during active crypto meningitis (high IRIS risk — wait until CSF sterile)
- Forgetting pre-ART screening (QuantiFERON, RPR, HBV, genotype)
- Not recognizing IRIS (can mimic OI relapse)
Rotation
Infectious Disease
Antibiotic stewardship, sepsis, resistant organisms, and opportunistic infections.
Available Topics
Sepsis & Septic Shock
Meningitis & Encephalitis
UTI & Pyelonephritis
HIV Essentials
Endocarditis
C. difficile
Pneumonia
Osteomyelitis
Cellulitis & Skin Infections
Tuberculosis
Fungal Infections
Diabetic Foot Infection
Necrotizing Fasciitis
📋 Major Guidelines
Osteomyelitis
Infection of bone — most commonly S. aureus. Hematogenous in children, contiguous spread in adults (diabetic foot, decubitus ulcers, post-surgical). MRI is the imaging gold standard. Bone biopsy is the diagnostic gold standard. Treatment is 6 weeks of targeted antibiotics — oral step-down is non-inferior to IV (OVIVA 2019).
🔍 Overview
Classification
| Type | Mechanism | Typical Patient | Common Organisms |
|---|---|---|---|
| Hematogenous | Bacteremia seeds bone (metaphysis in children, vertebral body in adults) | Children, IVDU (vertebral), sickle cell disease | S. aureus (#1 overall). Salmonella in SCD. Pseudomonas in IVDU. |
| Contiguous spread | Direct extension from adjacent soft tissue infection, open fracture, or surgery | Post-surgical, trauma, diabetic foot ulcers, decubitus ulcers | S. aureus, coagulase-negative staph (hardware). Polymicrobial (diabetic foot — add gram-negatives + anaerobes). |
| Vascular insufficiency | Chronic ischemia + minor trauma/ulceration → infection spreads to bone | Diabetic foot, peripheral arterial disease | Polymicrobial: S. aureus, Streptococcus, Enterococcus, gram-negatives (E. coli, Proteus), anaerobes (Bacteroides). |
Acute vs Chronic
| Feature | Acute | Chronic |
|---|---|---|
| Duration | < 2 weeks of symptoms | > 6 weeks, or recurrent |
| Pathology | Suppurative infection, edema | Sequestrum (dead bone), involucrum (new bone around dead bone), sinus tracts |
| Treatment | Antibiotics often curative alone | Usually requires surgical debridement + prolonged antibiotics |
Probe-to-bone test: In diabetic foot ulcers, if a sterile metal probe reaches bone through the ulcer, the positive predictive value for osteomyelitis is ~89%. Simple, bedside, no imaging needed.
🚨 Management
Antibiotic Duration
Standard: 6 weeks of targeted antibiotics. Oral step-down after initial IV is acceptable — OVIVA trial showed oral antibiotics were non-inferior to IV for bone and joint infections at 1 year OVIVA, 2019.
Empiric Therapy (Before Culture Data)
| Scenario | Empiric Regimen | Rationale |
|---|---|---|
| Native bone, acute | Vancomycin (Vancocin) (MRSA coverage) + Ceftriaxone (Rocephin) 2g IV daily (gram-negatives) | Covers MRSA + gram-negatives while awaiting cultures. Narrow once sensitivities return. |
| Diabetic foot | Vancomycin (Vancocin) + Piperacillin-tazobactam (Zosyn) 3.375g IV q6h | Polymicrobial — need MRSA + gram-negatives + anaerobic coverage. |
| Post-surgical / hardware | Vancomycin (Vancocin) + Cefepime (Maxipime) 2g IV q8h | Covers MRSA + Pseudomonas + skin flora. Hardware infections often need surgical removal. |
| Vertebral | Vancomycin (Vancocin) + Ceftriaxone (Rocephin) | S. aureus is #1. If IVDU, cover Pseudomonas (use cefepime instead of ceftriaxone). |
| Sickle cell disease | Ceftriaxone (Rocephin) 2g IV daily | Salmonella is #1 in SCD (not S. aureus). Ceftriaxone covers Salmonella + S. aureus. |
Surgical Indications
- Chronic osteomyelitis with sequestrum or sinus tracts
- Failed medical therapy (persistent infection after adequate antibiotics)
- Hardware-associated infection — often requires implant removal
- Abscess requiring drainage
- Spinal epidural abscess with neurological compromise — neurosurgical emergency
- Diabetic foot with non-healing ulcer and extensive bony involvement — may need amputation
Do NOT start antibiotics before bone biopsy/cultures if the patient is stable. Pre-biopsy antibiotics reduce culture yield and may lead to months of unnecessarily broad therapy. Exception: septic or hemodynamically unstable patients — treat empirically, culture what you can.
🧪 Workup
Diagnostic Evaluation
- ESR and CRP — elevated in >90% of cases. ESR >70 is highly suggestive. Use to monitor treatment response.
- Blood cultures (×2 sets) — positive in ~50% of hematogenous osteomyelitis. Always obtain before antibiotics.
- CBC — WBC may be normal in chronic osteomyelitis. Left shift suggests acute infection.
- Plain radiographs — first-line imaging. Changes take 10–14 days to appear (periosteal reaction, lytic lesions). Normal X-ray does NOT rule out early osteomyelitis.
- MRI with gadolinium — imaging gold standard. Sensitivity 90–100%, specificity 80–90%. Shows bone marrow edema, soft tissue extent, abscess.
- Bone biopsy with culture — diagnostic gold standard. Identifies organism and sensitivities. Essential for targeted therapy. IR-guided or open surgical.
- Probe-to-bone test — bedside test for diabetic foot ulcers. PPV ~89% if positive.
MRI cannot distinguish osteomyelitis from Charcot arthropathy in diabetic feet — both show bone marrow edema. Clinical correlation and biopsy are essential in this setting.
💊 Medications
Targeted Therapy (Based on Culture)
| Organism | First-Line | Alternative | Duration / Notes |
|---|---|---|---|
| MSSA* *= Methicillin-Sensitive Staph aureus | Nafcillin (Nallpen) 2g IV q4h or Cefazolin (Ancef) 2g IV q8h | Oral step-down: Cephalexin (Keflex) 1g PO QID or Dicloxacillin (Dynapen) 500mg PO QID | 6 weeks. IV × 1–2 weeks then oral step-down per OVIVA. Cefazolin preferred for ease of outpatient dosing (q8h vs q4h). |
| MRSA* *= Methicillin-Resistant Staph aureus | Vancomycin (Vancocin) 15–20 mg/kg IV q8–12h (target AUC/MIC 400–600) | Oral step-down: TMP-SMX (Bactrim) DS 1–2 tabs PO BID + Rifampin (Rifadin) 300mg PO BID | 6 weeks. Rifampin for biofilm penetration (hardware infections). Never use rifampin monotherapy — resistance develops rapidly. |
| Streptococcus | Ceftriaxone (Rocephin) 2g IV daily | Penicillin G or Amoxicillin (Amoxil) 1g PO TID | 6 weeks. Strep are reliably penicillin-sensitive. |
| Pseudomonas | Cefepime (Maxipime) 2g IV q8h or Piperacillin-tazobactam (Zosyn) | Ciprofloxacin (Cipro) 750mg PO BID (oral option with good bone penetration) | 6 weeks. Cipro has excellent oral bioavailability and bone penetration — preferred oral agent for Pseudomonas osteo. |
| Salmonella (SCD) | Ceftriaxone (Rocephin) 2g IV daily | Ciprofloxacin (Cipro) 500mg PO BID | 6 weeks. Most common cause of osteomyelitis in sickle cell disease. |
| Polymicrobial (diabetic foot) | Vancomycin (Vancocin) + Piperacillin-tazobactam (Zosyn) | Oral step-down: Amoxicillin-clavulanate (Augmentin) 875mg PO BID + TMP-SMX (Bactrim) (if MRSA) | 6 weeks. Surgical debridement is almost always needed. Vascular assessment essential. |
📊 Monitoring
Monitoring Parameters
- ESR and CRP — check weekly. CRP normalizes faster (1–2 weeks). ESR may take weeks to decline. Failure to trend down suggests treatment failure or undrained collection.
- CBC with differential — weekly. Monitor WBC normalization.
- Vancomycin levels — if on vancomycin, target AUC/MIC 400–600. Check trough before 4th dose, then 1–2× weekly.
- Renal function (BMP) — weekly if on vancomycin or aminoglycosides. Watch for nephrotoxicity.
- LFTs — if on rifampin (hepatotoxic). Baseline then q2 weeks.
- PICC line site — daily inspection for infection, thrombosis if on prolonged IV therapy.
- Repeat imaging — not routine. Repeat MRI only if clinical concern for treatment failure or new collection. Imaging lags behind clinical improvement.
📋 On Rounds
Pimp Questions
What is the most common organism causing osteomyelitis overall? In sickle cell disease?
Overall: S. aureus — accounts for ~60% of all osteomyelitis. In sickle cell disease: Salmonella — infarcted bone from vaso-occlusive crises is a perfect growth medium. This is a classic boards distinction. However, S. aureus is still #1 for septic arthritis in SCD.
Why is bone biopsy considered the gold standard over blood cultures?
Blood cultures are positive in only ~50% of hematogenous osteomyelitis and even less in contiguous spread. Bone biopsy with culture identifies the exact organism and sensitivities, allowing targeted narrow-spectrum therapy for a 6-week course. Without culture data, you may commit a patient to 6 weeks of unnecessarily broad-spectrum antibiotics with more side effects, higher cost, and greater resistance risk.
Can you treat osteomyelitis with oral antibiotics?
Yes. The OVIVA trial (2019) randomized 1,054 patients with bone/joint infections to IV vs oral antibiotics after initial surgical management. Oral was non-inferior at 1 year (treatment failure 14.6% oral vs 14.1% IV). Key caveat: patients had a defined organism with known oral sensitivities, and oral agents with good bone penetration were used (fluoroquinolones, rifampin combinations, linezolid). This has fundamentally changed practice — many patients can switch to oral after 1–2 weeks of IV, avoiding PICC line complications.
Why should you never use rifampin as monotherapy?
Rifampin has excellent biofilm penetration (critical for hardware-associated infections) and good bone penetration. However, resistance develops extremely rapidly with monotherapy — single-step mutations in the rpoB gene occur at a rate of ~10⁻⁸, which is high enough to select resistant mutants within days. Always combine with another active agent (e.g., TMP-SMX, fluoroquinolone, vancomycin). Rifampin is also a potent CYP450 inducer — check for drug interactions (warfarin, oral contraceptives, etc.).
📣 Sample Presentation
One-Liner
"Mrs. Garcia is a 62-year-old woman with poorly controlled diabetes (A1c 9.8%) and a non-healing right plantar ulcer × 3 months, now with exposed bone on probing and MRI showing marrow edema in the 2nd metatarsal head consistent with osteomyelitis."
Key Points to Cover on Rounds
Diabetic foot ulcer with positive probe-to-bone. MRI confirms osteomyelitis of 2nd metatarsal head — no abscess, no soft tissue collection. ESR 88, CRP 6.4. Blood cultures × 2 pending. IR-guided bone biopsy scheduled tomorrow — holding antibiotics until culture obtained (patient is hemodynamically stable). Vascular surgery consulted for ABI assessment — pedal pulses palpable. Podiatry involved for wound care. Plan: bone biopsy → targeted antibiotics × 6 weeks, oral step-down when organism and sensitivities known. Glucose management with insulin drip per endocrine.
⚡ Summary
Microbiology
S. aureus is #1 overall. Salmonella in SCD. Pseudomonas in IVDU. Polymicrobial in diabetic foot (staph + gram-negatives + anaerobes).
Diagnosis
MRI = imaging gold standard (sens 90–100%). Bone biopsy with culture = diagnostic gold standard. Probe-to-bone test for diabetic foot (PPV ~89%). Plain films take 10–14 days to show changes.
Treatment Duration
6 weeks of targeted antibiotics. Oral step-down is non-inferior to IV (OVIVA 2019). Hold antibiotics for biopsy if patient is stable.
MSSA / MRSA
MSSA: nafcillin or cefazolin → oral cephalexin. MRSA: vancomycin → oral TMP-SMX + rifampin. Never use rifampin monotherapy.
Surgical Indications
Chronic with sequestrum, failed medical therapy, hardware infection (implant removal), abscess drainage, spinal epidural abscess with neuro compromise.
Monitoring
ESR/CRP weekly (CRP normalizes faster). Vancomycin AUC/MIC if applicable. BMP for nephrotoxicity. Repeat MRI only if treatment failure suspected.
Rotation
Pulmonology
Chronic airway diseases, pulmonary function testing, and inhaler management. For acute ICU presentations (ARDS, mechanical ventilation, PE), see the ICU rotation.
Available Topics
COPD
Asthma
Pleural Effusion
Pneumonia
Pulmonary Nodule & Screening
PFT Interpretation
Pneumothorax
Obstructive Sleep Apnea
Interstitial Lung Disease
Hemoptysis
Sarcoidosis
📋 Major Guidelines
Altered Mental Status & Delirium
Delirium affects 20–30% of hospitalized patients and up to 80% in ICU. It's a syndrome, not a diagnosis — always find the cause. The hallmark: acute change in attention that fluctuates. Prevention is better than treatment — benzos make it worse.
🔍 Overview
Delirium vs Dementia
| Feature | Delirium | Dementia |
|---|---|---|
| Onset | Acute (hours–days) | Chronic (months–years) |
| Course | Fluctuating (waxes and wanes) | Progressive, stable day-to-day |
| Attention | Impaired (cardinal feature) | Preserved until late stages |
| Consciousness | Altered (hyperalert or obtunded) | Clear until late stages |
| Reversibility | Reversible (treat the cause) | Irreversible (but delirium can be superimposed on dementia) |
Screening — CAM (Confusion Assessment Method)
Requires feature 1 AND 2 PLUS either 3 OR 4:
- 1. Acute onset with fluctuating course (was fine yesterday, confused today, better this afternoon, worse tonight)
- 2. Inattention (can't recite months backward, can't spell WORLD backward, easily distracted) — most important feature
- 3. Disorganized thinking (incoherent speech, illogical flow of ideas)
- 4. Altered level of consciousness (anything other than alert — lethargic, stuporous, hyperalert, agitated)
CAM-ICU is the version for intubated/non-verbal patients — uses RASS for consciousness level and a visual attention task (squeeze my hand when you see the letter A).
AMS Workup — "AEIOU TIPS"
| Letter | Cause | Workup |
|---|---|---|
| A | Alcohol (withdrawal or intoxication), acidosis | BAL, urine tox, ABG, CIWA |
| E | Electrolytes (Na⁺, Ca²⁺, glucose, Mg), endocrine (thyroid, adrenal) | BMP, Ca, Mg, PO₄, TSH, cortisol, glucose |
| I | Infection (UTI, pneumonia, meningitis, sepsis) | CBC, UA, CXR, blood cultures, LP if indicated |
| O | Oxygen (hypoxia, hypercarbia, CO poisoning) | ABG, SpO₂, CO level if suspected |
| U | Uremia, hepatic encephalopathy | BUN/Cr, ammonia, LFTs |
| T | Trauma, temperature (hypo/hyperthermia) | Head CT, core temp |
| I | Iatrogenic (medications — #1 modifiable cause) | Med review: benzos, opioids, anticholinergics, steroids, polypharmacy |
| P | Psychiatric (diagnosis of exclusion), post-ictal | Rule out organic causes first. EEG if concern for non-convulsive status |
| S | Stroke, seizure, space-occupying lesion | CT head, MRI, EEG |
🚨 Management
Non-Pharmacologic — FIRST
Non-pharmacologic prevention reduces delirium incidence by 30–40%. This is more effective than any drug.
- Reorient frequently — clock, calendar, whiteboard with date/nurse/doctor name, familiar objects from home
- Sleep hygiene — lights off at night, minimize nighttime vitals/meds/interruptions, cluster care, earplugs, eye mask
- Early mobilization — out of bed, PT/OT, minimize restraints (restraints worsen delirium)
- Sensory aids — glasses, hearing aids (at bedside, not in a drawer)
- Remove lines/catheters ASAP — Foley, central lines, telemetry if not needed
- Medication review — stop/minimize anticholinergics (diphenhydramine, hydroxyzine, oxybutynin), benzos, opioids. Use the Beers List.
- Treat pain — undertreated pain causes delirium too. Use scheduled acetaminophen, avoid PRN opioids only.
- Avoid physical restraints — they worsen agitation and prolong delirium
Pharmacologic — ONLY If Necessary
| Drug | Dose | When | Notes |
|---|---|---|---|
| Haloperidol (Haldol) | 0.5–2 mg IV/IM/PO q4–6h PRN | Agitated delirium threatening safety (pulling lines, aggression) | No evidence it shortens delirium duration. Use lowest effective dose, shortest duration. Monitor QTc (hold if QTc > 500). Avoid in Parkinson's (worsens motor symptoms). |
| Quetiapine (Seroquel) | 25–50 mg PO at bedtime | Sundowning, nocturnal agitation, ICU delirium | Lower EPS risk than haloperidol. Sedating. Preferred in Parkinson's and Lewy body dementia (less D2 blockade). Start 12.5–25 mg in elderly. |
| Dexmedetomidine | 0.2–1.5 mcg/kg/hr IV | ICU delirium (intubated patients) | MENDS, 2007: dex reduced delirium duration vs midazolam in ICU. DahLIA, 2016: dex resolved agitated delirium faster and reduced ventilator time. No respiratory depression. Preferred ICU sedative for delirium. |
BRAIN-ICU, 2013: ICU delirium duration is independently associated with worse long-term cognitive outcomes at 3 and 12 months — underscoring the importance of aggressive delirium prevention and treatment.
Benzodiazepines WORSEN delirium (except alcohol/benzo withdrawal — the only indication). Diphenhydramine (Benadryl) is NOT a sleep aid — it's an anticholinergic that causes/worsens delirium. Remove it from every patient's med list.
📋 On Rounds
What is the #1 modifiable risk factor for delirium?
Medications. The most common offenders: (1) Anticholinergics (diphenhydramine, oxybutynin, promethazine, cyclobenzaprine — check the Beers List), (2) Benzodiazepines (lorazepam, midazolam — strongly associated with delirium in ICU and elderly), (3) Opioids (especially meperidine — active metabolite normeperidine causes seizures and delirium), (4) Steroids (high-dose), (5) Polypharmacy (≥ 5 medications increases delirium risk independently). The single best intervention a resident can do: review the medication list and stop everything that isn't essential.
What is the CAM-ICU and how does it differ from the regular CAM?
CAM-ICU is a validated delirium screening tool adapted for patients who cannot speak (intubated, nonverbal). It tests: (1) acute onset/fluctuation, (2) inattention (squeeze hand on letter 'A' in S-A-V-E-A-H-A-A-R-T — errors ≥ 2 = positive), (3) altered level of consciousness (RASS ≠ 0), (4) disorganized thinking (simple questions + commands). Delirium = features 1+2 plus either 3 or 4. The regular CAM uses the same features but assessed through conversation and is used on the floor. Key point: hypoactive delirium (quiet, withdrawn) is more common and more deadly than hyperactive — screen everyone, not just agitated patients.
What is the HELP protocol and why does it work better than medications for delirium?
HELP (Hospital Elder Life Program) is a multicomponent non-pharmacologic intervention that reduces delirium incidence by 33-40%. Components: (1) Orientation: clocks, calendars, whiteboards with date/team names, familiar objects from home. (2) Sleep: lights off at night, minimize overnight vitals/labs/interruptions, warm milk/herbal tea, earplugs + eye masks. (3) Mobility: ambulate 3×/day, PT/OT early, avoid tethers (remove Foley, unnecessary telemetry, restraints). (4) Vision/hearing: ensure glasses and hearing aids are AT BEDSIDE and ON. (5) Hydration/nutrition: encourage oral intake, avoid NPO when possible. (6) Cognitive stimulation: conversation, family visits, TV, puzzles. Why it works better than drugs: antipsychotics don't prevent delirium [MIND, 2018 and have side effects (QTc prolongation, sedation). HELP addresses root causes.
What is the role of antipsychotics in delirium?
Antipsychotics do NOT prevent or treat delirium — this was shown definitively by [MIND, 2018 (haloperidol and ziprasidone vs placebo in ICU delirium) and [AID-ICU, 2022 (haloperidol didn't reduce delirium days or mortality). Their only role: severe agitation that threatens patient or staff safety when non-pharmacologic measures have failed and the patient is pulling lines or at risk of self-harm. Use haloperidol 0.5-2 mg IV/IM or quetiapine 25-50 mg PO. Always check QTc first (antipsychotics prolong QT). Avoid in Parkinson's disease and Lewy body dementia (worsens parkinsonism). Bottom line: non-pharmacologic prevention (HELP protocol) >>> medications.
📣 Sample Presentation
One-Liner
"Mrs. Johnson is an 82-year-old with dementia admitted for UTI who is now acutely agitated, pulling at lines, not recognizing family. CAM positive (acute onset, inattention, disorganized thinking). Hyperactive delirium."
Key Points to Cover on Rounds
CAM positive — hyperactive delirium. Precipitant: UTI (on ceftriaxone day 2) + new environment + disrupted sleep. Medication review: Benadryl was ordered PRN sleep — discontinued (anticholinergic). Oxybutynin on home med list — held. Non-pharmacologic interventions: reorientation board, family at bedside, glasses and hearing aids in place, lights on during day/off at night, minimize tethers, PT mobilization. Bladder scan: no retention. Constipation: last BM 3 days ago → senna + docusate. Avoiding antipsychotics unless severe agitation threatening safety.
🧪 Workup
Diagnostic Evaluation — Delirium
Workup checklist for Delirium: History and physical → targeted labs → imaging as indicated → specialist consultation if needed. Always correlate clinically.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications, relevant PMH
- Physical exam: Focused exam relevant to delirium presentation
- Labs: CBC, BMP, relevant disease-specific labs (see Overview tab for specifics)
- Imaging: As clinically indicated based on presentation
- Special studies: Consider disease-specific diagnostics (see Overview tab)
💊 Medications
Medications — Delirium
Non-pharmacologic interventions FIRST. Medications are second-line, reserved for severe agitation endangering patient or staff safety. No medication treats delirium — only addresses symptoms while you fix the cause.
Non-Pharmacologic (First-Line)
- Reorientation: clock, calendar, familiar objects, consistent caregivers, windows for day/night cycle
- Sleep hygiene: minimize nighttime vitals/interruptions, reduce noise, lights off at night, cluster care
- Mobility: early ambulation, PT/OT, avoid bed rest. Remove tethers (telemetry, Foley, restraints) when possible
- Sensory aids: hearing aids, glasses at bedside — sensory deprivation worsens delirium
- Avoid restraints: increase agitation, worsen delirium, increase fall risk. Use 1:1 sitter instead.
- Review medications: STOP deliriogenic drugs (anticholinergics, benzodiazepines, opioids, diphenhydramine, muscle relaxants)
Pharmacologic (Severe Agitation Only)
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Haloperidol (Haldol) | 0.5-1 mg, repeat q30-60 min PRN | IV/IM | Low-dose antipsychotic for acute agitation. Avoid if QTc >500 ms. Check ECG before and after. Not FDA-approved for delirium but widely used. |
| Quetiapine (Seroquel) | 12.5-50 mg PO BID-TID | PO | More sedating, useful for nighttime agitation. Lower EPS risk than haloperidol. Monitor QTc. |
| Dexmedetomidine (Precedex) | 0.2-1.5 mcg/kg/hr IV | IV | Alpha-2 agonist. ICU setting for intubated patients. Maintains arousability. Reduces delirium duration vs benzodiazepines. Risk: bradycardia, hypotension. |
| Benzodiazepines AVOID | — | — | WORSEN delirium in most cases. Exception: alcohol withdrawal delirium and benzodiazepine withdrawal — benzodiazepines are treatment of choice for these specific etiologies. |
📈 Monitoring
Monitoring Parameters — Delirium
| Parameter | Frequency | Target / Action |
|---|---|---|
| CAM or CAM-ICU | BID (every shift) | Standardized delirium screening. CAM: acute onset + fluctuating + inattention + (disorganized thinking OR altered LOC). Document and trend. |
| RASS | q4h or with each sedation assessment | Richmond Agitation-Sedation Scale. Target RASS 0 to -1 (calm, arousable). Avoid over-sedation (worsens delirium). |
| QTc monitoring | Before antipsychotics, then daily if continued | Hold antipsychotics if QTc >500 ms. Torsades risk. Check electrolytes (K⁺, Mg²⁺) and correct. |
| Underlying cause workup | Daily reassessment | Infection (UA, CXR, blood cultures), metabolic (BMP, glucose, TSH), medications, urinary retention (bladder scan), constipation, pain, hypoxia. |
| Medication reconciliation | Daily | Identify and stop deliriogenic drugs. Review for new additions that may worsen (anticholinergics, benzos, opioids). |
| Sleep-wake cycle | Nursing documentation | Track sleep quality. Implement sleep protocol (minimize nighttime interruptions, reduce ambient light/noise). |
⚡ Summary
Summary
Diagnosis
CAM: (1) Acute onset + fluctuating course, (2) Inattention, (3) Disorganized thinking, (4) Altered consciousness. Need 1+2 + either 3 or 4.
Prevention
HELP protocol: orientation, sleep hygiene, mobility, glasses/hearing aids, hydration, avoid tethers. Reduces delirium by 33-40%.
Med Review
Stop anticholinergics (diphenhydramine, oxybutynin), benzodiazepines, opioids (minimize), meperidine (never use in elderly).
Workup
Infection (UA, CXR, blood cultures), metabolic (BMP, glucose, Ca²⁺, TSH, ammonia), medications, urinary retention (bladder scan), constipation.
Treatment
Treat the cause. Non-pharm first. Antipsychotics (haloperidol 0.5-2 mg) ONLY for safety-threatening agitation. Don't prevent delirium [MIND, 2018].
Subtypes
Hyperactive (agitated, pulling lines — easy to diagnose). Hypoactive (quiet, withdrawn — easy to MISS, worse prognosis). Mixed: fluctuates.
📄 One Pager
Delirium & Altered Mental Status — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
DELIRIUM & ALTERED MENTAL STATUS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
Guillain-Barré Syndrome
Acute inflammatory demyelinating polyneuropathy — ascending weakness 1–4 weeks after infection. 30% need intubation. The key danger: respiratory failure from diaphragm weakness. Monitor NIF and FVC serially. Do NOT wait for ABG to deteriorate — intubate early.
🔍 Overview
Clinical Features
- Ascending symmetric weakness — starts in legs, progresses to arms, trunk, respiratory muscles, cranial nerves
- Areflexia or hyporeflexia — characteristic finding
- Preceded by infection 1–4 weeks prior in ~70%: Campylobacter jejuni (#1), CMV, EBV, HIV, Mycoplasma, Zika
- Autonomic dysfunction (~70%): labile BP, tachycardia, bradycardia, arrhythmias, urinary retention, ileus
- Neuropathic pain (~60%) — may be the presenting symptom before weakness
- Facial weakness bilateral (facial diplegia) in ~50%. Bulbar weakness → dysphagia, aspiration risk.
Diagnosis
| Test | Findings |
|---|---|
| CSF (LP) | Albuminocytologic dissociation: elevated protein (> 45 mg/dL) with normal WBC (< 10). May be normal in first week. If WBC > 50 → think HIV, Lyme, sarcoidosis, or lymphomatous meningitis. |
| Nerve conduction studies / EMG | Demyelination pattern: prolonged distal latencies, conduction block, slowed conduction velocity, absent F waves. May be normal first few days. Repeat at 2 weeks if initially normal. |
| Anti-ganglioside antibodies | Anti-GM1 (AMAN variant), anti-GQ1b (Miller Fisher — ophthalmoplegia + ataxia + areflexia). Not required for diagnosis. |
Respiratory Monitoring — The 20/30/40 Rule
Intubate if ANY of: FVC < 20 mL/kg, NIF < −30 cmH₂O, or FVC decline > 30% from baseline. Do NOT wait for hypercapnia or hypoxia on ABG — by then it's too late. Check FVC and NIF q4–6h in all GBS patients.
The Erasmus GBS Respiratory Insufficiency Score (EGRIS) predicts need for ventilation: rapid progression, high disability score at admission, and facial/bulbar weakness are the strongest predictors.
🚨 Management
Immunotherapy
| Treatment | Dose | Notes |
|---|---|---|
| IVIG 1ST LINE | 0.4 g/kg/day IV × 5 days | Equivalent efficacy to plasmapheresis. Easier to administer. Side effects: headache, renal failure (check IgA first — IgA-deficient patients get anaphylaxis), aseptic meningitis, thromboembolic events. GBS IVIG Trial, 1992 |
| Plasmapheresis (PLEX) EQUIVALENT | 5 exchanges over 2 weeks | Equivalent to IVIG. Preferred if IVIG contraindicated. Requires large-bore central access. More hemodynamic effects. Guillain-Barré Syndrome Study Group, 1985 |
Do NOT give both IVIG and PLEX — PLEX removes the IVIG you just gave. Pick one. Do NOT give corticosteroids — no benefit in GBS (unlike in CIDP or myasthenia).
Supportive Care
- ICU admission for all moderate-severe GBS (rapid progression, bulbar involvement, autonomic dysfunction)
- FVC + NIF q4–6h — trend is more important than single values
- DVT prophylaxis — immobile patient, high VTE risk. Enoxaparin + SCDs.
- Pain management — gabapentin or pregabalin for neuropathic pain. Opioids if severe. Pain is often undertreated.
- Autonomic monitoring — telemetry (bradycardia, heart block possible). Gentle fluid management (labile BP). Avoid β-blockers (can worsen bradycardia episodes).
- LP — high protein, normal WBC
- NCS/EMG — demyelinating vs axonal
- FVC q4-6h — intubate <20mL/kg
- NIF — intubate <−30
- Anti-ganglioside Ab
- MRI spine — rule out cord compression
- Aspiration precautions — NPO if bulbar weakness. Speech/swallow eval
💊 MedicationsMedications — Guillain-Barre Syndrome
Drug Dose Route Notes IMMUNOTHERAPY (choose ONE) IVIG
PREFERRED0.4 g/kg/day x 5 days IV Preferred due to easier administration. Check IgA level first (IgA-deficient → anaphylaxis risk). Side effects: headache, renal failure, aseptic meningitis, thrombotic events. Plasma exchange (PLEX) 5 sessions over 2 weeks IV (large-bore access) Equivalent efficacy to IVIG. Use if IVIG contraindicated. Requires central access. More hemodynamic effects. Do NOT combine IVIG + PLEX (PLEX removes IVIG). Steroids are NOT effective in GBS. SUPPORTIVE CARE Gabapentin (Neurontin) 100–900 mg TID, titrate up PO Neuropathic pain — first-line. Pain is present in ~60% and often undertreated. Pregabalin (Lyrica) 75–150 mg BID PO Alternative to gabapentin for neuropathic pain. Enoxaparin (Lovenox)
MANDATORY40 mg SQ daily SQ DVT prophylaxis is mandatory. Immobile patients at very high VTE risk. Add SCDs. Continue until ambulatory.
📋 On Rounds
Why do you check FVC and not just ABG for respiratory monitoring in GBS?
The ABG is a lagging indicator of respiratory failure in neuromuscular disease. Patients with progressive diaphragm weakness compensate by increasing respiratory rate → they maintain normal PaO₂ and PaCO₂ until they're nearly exhausted. When the CO₂ finally rises on ABG, they're about to arrest. FVC (forced vital capacity) is a leading indicator — it declines progressively as respiratory muscles weaken, well before gas exchange deteriorates. The 20/30/40 rule: intubate if FVC < 20 mL/kg, NIF (negative inspiratory force) < −30 cmH₂O, or FVC drops > 30% from baseline. By the time ABG shows respiratory acidosis in GBS, you're too late for a controlled intubation.
What is the 20/30/40 rule in GBS and why is FVC more important than SpO₂?
The 20/30/40 rule predicts the need for intubation: FVC < 20 mL/kg, NIF < −30 cmH₂O, or FVC decline > 30% from baseline. Additionally, bulbar dysfunction (inability to swallow, weak cough) independently warrants intubation. SpO₂ is a late and unreliable sign — a patient with GBS can have normal SpO₂ until minutes before respiratory arrest because their lungs are normal; the problem is the respiratory muscles. By the time SpO₂ drops, the patient is in extremis. FVC is the vital sign in GBS — check it q4–6h and trend it. A declining FVC demands ICU transfer even if SpO₂ is 99%.
What are the differences between IVIG and plasmapheresis (PLEX) for GBS?
Both are equally effective — [Hughes, 2014 Cochrane showed no significant difference in outcomes. IVIG: 0.4 g/kg/day × 5 days. Advantages: easier to administer, no special equipment, can do on general floor. Disadvantages: headache, aseptic meningitis, renal failure (sucrose-containing formulations), thrombotic events. PLEX: 5 exchanges over 1-2 weeks. Advantages: faster onset of improvement in some studies. Disadvantages: requires large-bore central access, hemodynamic instability during exchanges, hypocalcemia from citrate, not available at all hospitals. Key: do NOT combine IVIG + PLEX (IVIG is removed by PLEX → wasted). Do NOT give steroids for GBS — they don't help and may be harmful. Choose one treatment and start early (within 2-4 weeks of symptom onset).
Can you use steroids in GBS?
No — steroids do NOT help GBS and may be harmful. This is a common mistake because GBS is autoimmune and steroids work in many autoimmune conditions. However, multiple RCTs and Cochrane reviews have shown corticosteroids do not improve outcomes and may delay recovery. The reason is unclear — GBS inflammation involves different immune pathways (complement-mediated, macrophage-mediated demyelination) than conditions responsive to steroids. Correct treatment: IVIG 0.4 g/kg/day × 5 days OR plasma exchange (PLEX). These are equally effective. Do NOT combine them (IVIG is removed by PLEX). This is high-yield board knowledge.
📣 Sample Presentation
One-Liner
"Mr. Fernandez is a 45-year-old presenting with 5 days of ascending bilateral leg weakness and paresthesias following a diarrheal illness 3 weeks ago. Areflexic on exam. FVC 28 mL/kg."
Key Points to Cover on Rounds
GBS — ascending, symmetric, areflexic weakness. Preceding GI illness (likely Campylobacter). FVC 28 mL/kg (concerning — approaching 20/30/40 rule). NIF −35 cmH₂O. LP: protein 120, WBC 3 (albuminocytologic dissociation). NCS/EMG: demyelinating pattern (AIDP). Treatment: IVIG 0.4 g/kg/day × 5 days started today. FVC trending q6h: 28→26 (declining). ICU admission. Plan: if FVC <20 or declining rapidly → intubate. DVT prophylaxis (heparin SQ). PT/OT. Monitor autonomic dysfunction (HR/BP lability).
📊 Monitoring
Monitoring — Guillain-Barre Syndrome
| Parameter | Frequency | Target / Action |
|---|---|---|
| FVC (forced vital capacity) | q4–6h (the #1 priority) | Intubate if FVC < 20 mL/kg or declining > 30% from baseline. FVC is the vital sign in GBS — do NOT rely on SpO2 or ABG (lagging indicators). |
| NIF (negative inspiratory force) | q4–6h (with FVC) | Intubate if weaker than -20 to -30 cmH2O. Declining NIF indicates diaphragmatic weakness. |
| HR / BP (autonomic dysreflexia) | Continuous telemetry | Labile BP, tachycardia/bradycardia, arrhythmias in ~70% of GBS. Avoid beta-blockers (can worsen bradycardia episodes). Gentle fluid management for BP lability. |
| I&Os (neurogenic bladder) | Strict | Urinary retention is common from autonomic dysfunction. Monitor for distension. May need intermittent catheterization or Foley. |
| Daily neuro exam | Daily (at minimum) | Track progression: proximal vs distal strength (MRC scale), cranial nerve function, bulbar weakness (swallowing, cough). Nadir typically at 2–4 weeks. |
| Pain assessment | Each shift | Neuropathic pain in ~60% — often undertreated. Use gabapentin or pregabalin. Opioids if severe. |
The 20/30/40 rule: Intubate if FVC < 20 mL/kg, NIF < -30 cmH2O, or FVC decline > 30%. By the time ABG shows respiratory acidosis, you are too late for a controlled intubation.
🧪 Workup
Workup
Myasthenic Crisis
Myasthenia gravis exacerbation with respiratory failure requiring intubation. Triggered by infection, surgery, medication changes, or drug interactions. Same respiratory monitoring as GBS — FVC < 20 → intubate. Know the drugs that worsen MG.
🔍 Overview
Myasthenia Gravis — Key Concepts
- Autoantibodies against AChR (acetylcholine receptor) at the neuromuscular junction → fatigable weakness
- Fatigable: weakness worsens with repeated use and improves with rest. Worse at end of day.
- Ocular symptoms (#1 presenting symptom): ptosis, diplopia — often asymmetric
- Generalized MG: proximal limb weakness, bulbar symptoms (dysphagia, dysarthria, nasal voice), respiratory failure
- Anti-AChR antibodies positive in ~85% of generalized MG. Anti-MuSK antibodies in ~5–8% (more bulbar involvement, worse prognosis).
- CT chest for thymoma — present in ~15% of MG patients. Thymectomy recommended for thymoma and for non-thymomatous generalized AChR+ MG age 18–65.
Drugs That Worsen MG — MUST KNOW
These drugs can precipitate myasthenic crisis. Avoid in all MG patients:
| Drug Class | Specific Agents |
|---|---|
| Antibiotics | Aminoglycosides (gentamicin, tobramycin), fluoroquinolones, macrolides (azithromycin — controversial), tetracyclines |
| Cardiac | Beta-blockers, calcium channel blockers, procainamide, quinidine |
| Neuromuscular blockers | Avoid succinylcholine (unpredictable response). Use non-depolarizing agents with caution (increased sensitivity → prolonged paralysis). |
| Other | Magnesium (blocks NMJ — avoid IV Mg unless life-threatening indication), D-penicillamine, checkpoint inhibitors, botulinum toxin, lithium |
Myasthenic Crisis vs Cholinergic Crisis
| Feature | Myasthenic Crisis | Cholinergic Crisis |
|---|---|---|
| Cause | Disease exacerbation (undertreated) | Pyridostigmine overdose |
| Pupils | Normal or dilated | Miosis (constricted) |
| Secretions | Normal | Excessive (SLUDGE: salivation, lacrimation, urination, diarrhea, GI cramping, emesis) |
| Fasciculations | Absent | Present |
| Response to edrophonium | Improves | Worsens |
| Treatment | IVIG or PLEX + immunosuppression | Hold pyridostigmine, atropine for secretions |
🚨 Management
Myasthenic Crisis Treatment
Respiratory
FVC + NIF q4–6h. Same 20/30/40 rule as GBS. Intubate if FVC < 20 mL/kg or NIF < −30. Avoid succinylcholine and minimize non-depolarizing agents. BiPAP can bridge but do NOT delay intubation if deteriorating.
Rapid immunotherapy
IVIG 0.4 g/kg/day × 5 days OR plasmapheresis × 5 exchanges. Both equally effective. PLEX onset is faster (~24–48h) vs IVIG (3–5 days). Choose based on availability and access.
Steroids
Start high-dose steroids (prednisone 1 mg/kg/day or methylprednisolone 1g IV × 3–5 days). Warning: steroids can cause transient worsening in the first 1–2 weeks → always start WITH IVIG/PLEX, not alone in crisis.
Cholinesterase inhibitor
Hold pyridostigmine during crisis (increased secretions worsen respiratory status, and it may contribute to cholinergic crisis). Resume when improving and extubated.
Trigger
Identify and treat the trigger: infection (#1 — pneumonia, UTI), medication change, surgery, emotional stress. Review medication list for MG-exacerbating drugs.
Chronic MG Management
| Drug | Role | Notes |
|---|---|---|
| Pyridostigmine (Mestinon) SYMPTOMATIC | AChE inhibitor — increases ACh at NMJ | First-line symptomatic treatment. 60 mg PO TID, titrate. Does NOT alter disease course — only improves symptoms. |
| Prednisone (Deltasone) | Immunosuppression | Most patients need immunosuppression beyond pyridostigmine. Start low, escalate slowly (risk of initial worsening). |
| Azathioprine (Imuran) | Steroid-sparing agent | Takes 6–12 months to work. Check TPMT before starting (deficiency → myelosuppression). |
| Mycophenolate (CellCept) | Steroid-sparing agent | Alternative to azathioprine. Common choice. Teratogenic. |
| Rituximab (Rituxan) | Anti-CD20 — refractory MG | Especially effective in anti-MuSK MG. Growing evidence for AChR+ refractory disease. |
| Efgartigimod (Vyvgart) | FcRn inhibitor — reduces pathogenic IgG | ADAPT, 2021: improved
🧪 Workup
Workup
|
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Pyridostigmine | 60mg q4-6h | PO | AChE inhibitor |
| Prednisone | Start low, titrate | PO | Can worsen MG initially |
| Azathioprine | 2-3mg/kg/day | PO | Steroid-sparing |
| IVIG | 0.4g/kg×5d | IV | Crisis |
| Rituximab | 375mg/m² | IV | Refractory |
📊 Monitoring
Monitoring
- FVC every visit
- Med review — avoid aminoglycosides, FQs, BB, Mg
- Thymoma surveillance
- Infection screening on immunosuppression
📋 On Rounds
Why should you avoid IV magnesium in myasthenia gravis?
Magnesium acts as a calcium channel blocker at the neuromuscular junction — it inhibits presynaptic calcium-dependent acetylcholine release and reduces postsynaptic sensitivity to ACh. In a patient with MG (where ACh receptor density is already reduced by autoantibodies), adding magnesium further impairs neuromuscular transmission → can precipitate myasthenic crisis and respiratory failure. This is clinically relevant because Mg is given frequently in hospitals (eclampsia, arrhythmias, asthma, electrolyte repletion). If a MG patient needs Mg for a life-threatening indication (torsades, severe pre-eclampsia), give it with extreme caution in an ICU with continuous monitoring and intubation readiness.
What medications are contraindicated in myasthenia gravis and why?
Several common medications can precipitate or worsen myasthenic crisis by impairing neuromuscular transmission: (1) Aminoglycosides (gentamicin, tobramycin) — block presynaptic Ca²⁺ channels → reduced ACh release. (2) Fluoroquinolones — same mechanism, plus direct NMJ blockade. (3) Beta-blockers — impair NMJ safety factor. (4) Magnesium — blocks presynaptic Ca²⁺ channels (don't aggressively replete Mg in MG patients). (5) Neuromuscular blockers (succinylcholine, rocuronium) — prolonged paralysis. (6) D-penicillamine, checkpoint inhibitors — can induce autoimmune MG. The mnemonic: "Aminoglycosides, FQs, BBs, Mg — Bad for MG."
What is cholinergic crisis and how do you differentiate it from myasthenic crisis?
Both present with weakness and respiratory failure, but the mechanism is opposite. Myasthenic crisis: under-treated MG → insufficient ACh at NMJ → weakness. Pupils: normal or dilated. Secretions: dry. Responds to: edrophonium/neostigmine (improves). Cholinergic crisis: over-treated with pyridostigmine → excess ACh → depolarization block + muscarinic effects. Pupils: miotic (small). Secretions: excessive (SLUDGE: salivation, lacrimation, urination, defecation, GI cramps, emesis). Fasciculations present. Responds to: atropine (improves muscarinic symptoms). Edrophonium test: give 2 mg IV — if weakness improves → myasthenic crisis (under-treated). If weakness worsens → cholinergic crisis (over-treated). Rarely used now — treat empirically: intubate + hold pyridostigmine + start IVIG/PLEX.
How do you differentiate MG from Lambert-Eaton syndrome?
MG: autoantibodies against post-synaptic AChR → fatigable weakness that WORSENS with repetitive use, proximal > distal, bulbar symptoms (ptosis, diplopia, dysphagia) prominent, reflexes normal. EMG: decremental response on repetitive nerve stimulation. Lambert-Eaton (LEMS): autoantibodies against pre-synaptic voltage-gated calcium channels (P/Q type) → weakness that IMPROVES with use initially, proximal legs > arms, autonomic dysfunction (dry mouth, constipation), hyporeflexia that improves after exercise. EMG: incremental response on high-frequency stimulation. Associated with small cell lung cancer in 60% — get CT chest in every LEMS patient.
📣 Sample Presentation
One-Liner
"Mrs. Park is a 60-year-old with AChR Ab+ myasthenia gravis on pyridostigmine who presents with worsening dyspnea and dysphagia after a UTI. FVC 16 mL/kg. Diagnosed with myasthenic crisis."
Key Points to Cover on Rounds
Myasthenic crisis triggered by UTI. FVC 16 mL/kg (<20 → intubated for airway protection). NIF −18 cmH₂O. Treatment: IVIG 0.4 g/kg/day × 5 days. Pyridostigmine HELD during crisis (excess secretions worsen airway). Antibiotics for UTI: switched from ciprofloxacin → ceftriaxone (fluoroquinolones contraindicated in MG). Offending meds reviewed — no aminoglycosides, no BB, no Mg supplementation. Methylprednisolone 1g IV × 3 days (cautious — steroids can transiently worsen MG in first 7-10 days). Plan: daily FVC/NIF, restart pyridostigmine when improving and extubated.
⚡ Summary
Summary
Diagnosis
Fatigable weakness (worse with use, better with rest). Ptosis, diplopia, bulbar symptoms. AChR Ab positive (~85%), MuSK Ab in some.
Treatment
Pyridostigmine (symptomatic). Immunosuppression: prednisone → steroid-sparing (azathioprine, mycophenolate, rituximab).
Crisis
FVC < 20 mL/kg → intubate. Hold pyridostigmine. IVIG or PLEX. ICU admission.
Avoid These Meds
Aminoglycosides, fluoroquinolones, beta-blockers, magnesium, telithromycin, D-penicillamine, botulinum toxin. Worsen NMJ transmission.
Thymectomy
Indicated if thymoma (CT chest mandatory). Also improves outcomes in AChR Ab+ MG without thymoma [MGTX, 2016].
Cholinergic Crisis
Excess pyridostigmine → SLUDGE symptoms, weakness, miosis. Antidote: atropine. Hold anticholinesterase. Differentiate from myasthenic crisis.
📄 One Pager
Neurology · One Pager
Myasthenia Gravis
Fatigable weakness (worse with use). AChR antibodies. Pyridostigmine for symptoms. IVIG/PLEX for crisis. Avoid aminoglycosides, FQs, BB, Mg. Thymectomy if thymoma.
Diagnosis
Fluctuating weakness: ptosis, diplopia, bulbar symptoms (dysphagia, dysarthria), proximal limb weakness. AChR Ab positive ~85%. MuSK Ab in some seronegatives. CT chest (thymoma).
Myasthenic Crisis
FVC < 20 mL/kg → intubate. Hold pyridostigmine (excess secretions). IVIG 0.4 g/kg/day × 5d or PLEX. Identify trigger: infection, surgery, medication change.
Dangerous Medications
Aminoglycosides, fluoroquinolones, macrolides, beta-blockers, magnesium IV, D-penicillamine, telithromycin, botulinum toxin. All worsen NMJ transmission.
Key Drugs
Pyridostigmine60 mg q4-6h
PrednisoneStart low, titrate up (can transiently worsen)
Azathioprine2-3 mg/kg/day (steroid-sparing)
IVIG0.4 g/kg × 5d (crisis)
Pitfalls
- Aminoglycosides or FQs in MG patient → crisis
- Not checking FVC (crisis can develop rapidly)
- Missing thymoma (CT chest in all new MG)
- Cholinergic crisis from pyridostigmine excess (SLUDGE symptoms)
Rotation
Neurology
Stroke, seizures, altered mental status, and neuromuscular emergencies.
Available Topics
Status Epilepticus
Acute Ischemic Stroke
AMS & Delirium
Guillain-Barré Syndrome
Myasthenic Crisis
Heat Stroke
Intracerebral Hemorrhage
Headache & Migraine
Spinal Cord Compression
NMS vs Serotonin Syndrome
PRES
📋 Major Guidelines
Heat Stroke
Core temperature >40°C (104°F) with CNS dysfunction (altered mental status, seizures, coma). A true medical emergency — mortality 10–50% depending on delay to cooling. The single most important intervention is rapid cooling to <39°C within 30 minutes. Every minute counts.
🔍 Overview
Classification
| Type | Setting | Mechanism | Key Features |
|---|---|---|---|
| Classic (non-exertional) | Elderly, chronic illness, medications, heat waves | Failure of thermoregulation — body cannot dissipate environmental heat | Develops over days. Skin often hot and dry (sweat glands exhausted). Elderly on anticholinergics, diuretics, beta-blockers at highest risk. |
| Exertional | Young, healthy individuals — athletes, military, laborers | Metabolic heat production overwhelms dissipation during intense physical activity | Develops over hours. Skin may still be diaphoretic. Often in hot, humid environments. Can occur even in cool conditions with extreme exertion. |
Heat Stroke vs Heat Exhaustion
| Feature | Heat Exhaustion | Heat Stroke |
|---|---|---|
| Core Temp | < 40°C (104°F) | > 40°C (104°F) |
| Mental Status | Normal or mild confusion | Altered — confusion, delirium, seizures, coma |
| Sweating | Present (profuse) | May be absent (classic) or present (exertional) |
| Organ Damage | Absent | Present — rhabdomyolysis, DIC, liver failure, AKI, ARDS |
| Treatment | Rest, oral rehydration, passive cooling | Aggressive cooling + ICU |
The defining feature of heat stroke is CNS dysfunction — not the temperature alone. A patient with temp 40.5°C and normal mentation has heat exhaustion. A patient with temp 40.1°C and confusion/seizures has heat stroke. Treat the brain, not the thermometer.
Risk Factors & Medications
- Anticholinergics — impair sweating (diphenhydramine, TCAs, antipsychotics)
- Diuretics — volume depletion impairs sweating
- Beta-blockers — blunt cardiac output response to heat stress
- Stimulants — amphetamines, cocaine, MDMA increase metabolic heat production
- Antipsychotics — impair thermoregulation centrally (especially in NMS overlap)
- Extremes of age — elderly (impaired thermoregulation) and infants (high surface area:volume)
- Obesity, deconditioning, dehydration
🚨 Management
Cooling — The Single Most Important Intervention
Target: core temperature < 39°C (102.2°F) within 30 minutes. Every minute of delay increases mortality and neurological injury. Start cooling BEFORE full workup. Do NOT wait for labs.
| Method | Technique | Effectiveness | Notes |
|---|---|---|---|
| Cold water immersion GOLD STANDARD | Immerse body (neck down) in ice water bath (1–3°C) | Cooling rate ~0.2°C/min — fastest available method | Gold standard for exertional heat stroke. Near-zero mortality if applied within 30 min. Logistically challenging in ED — need large tub. Monitor for shivering (counterproductive). |
| Evaporative cooling | Undress patient, mist with lukewarm water, fan continuously | Cooling rate ~0.05°C/min | Most practical in ED/ICU. Less effective than immersion but widely available. Combine with ice packs to axillae, groin, neck. |
| Ice packs | Apply to axillae, groin, neck, and scalp (high blood flow areas) | Adjunct — slow as standalone | Use in combination with other methods. Cover large surface area. Rotate frequently. |
| Cold IV fluids | 4°C normal saline bolus (not iced — just refrigerated) | Adjunct — modest cooling effect | Addresses volume depletion AND provides some cooling. Give 1–2L bolus. Do not use as sole cooling method. |
| Invasive cooling | Peritoneal lavage, bladder irrigation with cold saline, endovascular cooling catheter | Variable — reserved for refractory cases | Consider if temp >41°C and not responding to external cooling. Endovascular catheter allows precise temperature control. |
Stepwise Approach
- ABCs first — secure airway if GCS ≤ 8, intubate if needed
- Remove from heat — move to cool environment, remove clothing
- Begin cooling immediately — cold water immersion if available, otherwise evaporative + ice packs
- IV access + fluids — cold NS or LR 1–2L bolus. LR is safe even in liver disease (lactate is metabolized by kidneys and skeletal muscle, not just liver).
- Continuous core temperature monitoring — rectal or esophageal probe (NOT oral or axillary — inaccurate)
- Stop cooling at 39°C — overshoot hypothermia is a real risk
- Treat seizures — benzodiazepines (lorazepam 2–4 mg IV). Avoid phenytoin (ineffective for hyperthermia-related seizures).
- Avoid antipyretics — acetaminophen and NSAIDs do NOT work. Heat stroke is not a fever (no prostaglandin-mediated set point elevation). Antipyretics may worsen hepatic/renal injury.
Do NOT give antipyretics (acetaminophen, NSAIDs). Heat stroke is a failure of thermoregulation, not a prostaglandin-mediated fever. The hypothalamic set point is normal — the body simply cannot dissipate heat. Antipyretics are useless and hepatotoxic in this setting.
🧪 Workup
Diagnostic Evaluation
- Core temperature — rectal or esophageal probe. Oral/axillary/temporal are unreliable. Must be >40°C for diagnosis.
- CBC — leukocytosis common. Thrombocytopenia suggests DIC.
- BMP — hyperkalemia (rhabdo, cell lysis), AKI (elevated Cr), hypoglycemia (liver failure).
- LFTs — AST/ALT elevation is universal. Hepatic injury peaks at 48–72h. Fulminant liver failure is a major cause of death.
- CK (creatine kinase) — rhabdomyolysis (CK >5× ULN). Peak at 24–72h. Check q6–12h.
- Coagulation panel — PT/INR, PTT, fibrinogen, D-dimer. DIC is common and a major cause of death.
- Lactate — marker of tissue hypoperfusion and anaerobic metabolism.
- UA with myoglobin — dark urine, positive blood on dipstick but no RBCs on microscopy = myoglobinuria.
- ABG/VBG — mixed acid-base disturbances common (respiratory alkalosis from tachypnea + metabolic acidosis from lactic acid).
- CT head — if focal neurological deficits or seizures to rule out structural cause.
LFTs may be initially normal. Hepatic injury from heat stroke peaks at 48–72 hours. Recheck LFTs daily for 3–5 days. Fulminant hepatic failure requiring transplant can occur.
💊 Medications
Key Medications
| Drug | Dose | Role | Notes |
|---|---|---|---|
| Normal Saline (cold, 4°C) 1ST LINE | 1–2 L IV bolus | Volume resuscitation + adjunct cooling | Most patients are severely volume depleted. LR or NS are both acceptable — LR is safe even in liver disease (lactate is metabolized by kidneys and muscle, not just liver). Titrate to UOP 1–2 mL/kg/h (especially if rhabdo). |
| Lorazepam (Ativan) | 2–4 mg IV PRN | Seizures, shivering | Shivering during cooling is counterproductive (generates heat). Benzos suppress shivering. Also first-line for heat stroke seizures. |
| Dantrolene CONSIDER | 1–2.5 mg/kg IV | Refractory hyperthermia | Skeletal muscle relaxant. Consider if NMS or malignant hyperthermia cannot be excluded. Evidence for pure heat stroke is limited, but may help if significant muscle rigidity/rhabdo. |
| Sodium Bicarbonate | 150 mEq in 1L D5W | Urine alkalinization for rhabdomyolysis | Target urine pH >6.5 to prevent myoglobin-induced AKI. Use if CK >5,000 and rising. |
Medications that are CONTRAINDICATED or USELESS: Acetaminophen (no effect, hepatotoxic), NSAIDs (no effect, nephrotoxic), aspirin (no effect, worsens DIC), phenytoin (ineffective for hyperthermic seizures — use benzos).
📊 Monitoring
Monitoring Parameters
- Continuous core temperature — rectal or esophageal probe. Stop active cooling at 39°C to prevent overshoot hypothermia.
- Continuous telemetry — arrhythmias from hyperkalemia, hyperthermia-induced myocardial injury.
- Urine output — target 1–2 mL/kg/h (especially with rhabdomyolysis). Foley catheter essential.
- CK q6–12h — trend for rhabdomyolysis. Peak 24–72h. Aggressive IVF if CK rising.
- LFTs daily × 3–5 days — hepatic injury peaks at 48–72h. Watch for coagulopathy, hypoglycemia as signs of liver failure.
- Coags q12–24h — DIC panel (PT, PTT, fibrinogen, D-dimer). Fibrinogen < 150 = ominous.
- BMP q6–12h — hyperkalemia (rhabdo), AKI, hypoglycemia (liver failure).
- Neuro checks q1–2h — GCS trending. Persistent AMS after cooling suggests brain injury.
📋 On Rounds
Pimp Questions
Why don't antipyretics work in heat stroke?
Fever is caused by prostaglandins raising the hypothalamic set point — antipyretics (acetaminophen, NSAIDs) work by blocking prostaglandin synthesis. In heat stroke, the hypothalamic set point is normal — the body simply cannot dissipate the heat load fast enough (overwhelmed thermoregulatory system). Since there is no prostaglandin-mediated set point elevation, antipyretics have zero effect. Worse, acetaminophen is hepatotoxic (the liver is already being injured by heat) and NSAIDs are nephrotoxic (the kidneys are already at risk from rhabdomyolysis and volume depletion).
What is the key difference between heat stroke and heat exhaustion?
CNS dysfunction. Heat exhaustion can cause fatigue, nausea, headache, and even syncope — but mental status remains intact. Heat stroke is defined by altered mental status (confusion, delirium, seizures, coma) + core temp >40°C. Heat exhaustion is a clinical continuum that can progress to heat stroke if not treated. The moment a patient develops AMS in the setting of hyperthermia, it's heat stroke until proven otherwise.
What is the gold standard cooling method and what cooling rate does it achieve?
Cold water immersion (ice water bath, 1–3°C) is the gold standard. Cooling rate ~0.2°C/min, which means a patient at 42°C can reach target (39°C) in ~15 minutes. Near-zero mortality when applied within 30 minutes. Compare with evaporative cooling (~0.05°C/min) — significantly slower. The military and sports medicine literature strongly supports ice water immersion as first-line. In the ED, if a tub isn't available, evaporative cooling + ice packs to axillae/groin/neck + cold IV fluids is the standard alternative.
How do you differentiate heat stroke from neuroleptic malignant syndrome (NMS)?
NMS presents with hyperthermia + AMS + lead-pipe rigidity + autonomic instability, typically after starting or increasing a dopamine antagonist (antipsychotics, metoclopramide). Key distinguishing features: (1) NMS has prominent muscle rigidity (heat stroke has flaccidity or mild rigidity), (2) NMS develops over days (exertional heat stroke over hours), (3) NMS has markedly elevated CK from rigidity, (4) NMS responds to dantrolene and bromocriptine. In practice, there can be significant overlap — treat the hyperthermia aggressively regardless of etiology while sorting out the diagnosis.
📣 Sample Presentation
One-Liner
"Mr. Thompson is a 22-year-old Army recruit who collapsed during a 10-mile run in 95°F heat, found unresponsive with rectal temp 41.8°C, GCS 7, tachycardic to 140, and diffusely diaphoretic."
Key Points to Cover on Rounds
Exertional heat stroke — core temp 41.8°C on arrival, GCS 7. Ice water immersion initiated in field within 15 min, continued in ED. Core temp down to 39.2°C at 20 min, cooling stopped at 38.8°C. Now GCS 11 (E3V3M5), improving. CK 12,400 and rising — aggressive IVF at 250 mL/hr with bicarb drip for urine alkalinization, target UOP >200 mL/h. LFTs: AST 320, ALT 180 — will recheck daily (peaks at 48–72h). Coags normal, no DIC. Lactate 6.2 → 3.1 trending down. Plan: ICU, continuous core temp monitoring, CK q6h, LFTs daily, neuro checks q2h, hold all nephrotoxins.
⚡ Summary
Definition
Core temp >40°C + CNS dysfunction (AMS, seizures, coma). The key distinguishing feature from heat exhaustion is altered mental status, not the temperature.
Cooling
Cold water immersion = gold standard (~0.2°C/min). Target <39°C within 30 min. Stop at 39°C to prevent overshoot. Evaporative + ice packs if no tub available.
Do NOT Give
Antipyretics (acetaminophen, NSAIDs) — useless and harmful. Not a prostaglandin-mediated fever. Phenytoin for seizures — use benzos instead.
Complications
Rhabdomyolysis (CK, IVF, bicarb), DIC (coags q12h, fibrinogen), hepatic failure (LFTs peak 48–72h), AKI, ARDS, cerebral edema.
Classic vs Exertional
Classic: elderly, medications, heat wave, develops over days, skin dry. Exertional: young, exercise, develops over hours, may still be diaphoretic.
Monitoring
Core temp (rectal/esophageal), CK q6–12h, LFTs daily × 3–5d, coags q12–24h, UOP 1–2 mL/kg/h, neuro checks q1–2h.
Chest Pain Workup
The most common ED complaint. Your job: rapidly rule out the five life-threatening causes before anything else. ECG within 10 minutes. Most chest pain is benign — but the 5% that isn't will kill if missed.
🔍 Overview
5 Life-Threatening Causes — Rule These Out First
| Diagnosis | Key Features | Critical Action |
|---|---|---|
| ACS (STEMI/NSTEMI) | Substernal pressure, exertional, radiates to jaw/arm, diaphoresis, nausea. Risk factors: age, DM, HTN, smoking, family hx. | ECG within 10 min. Troponin. See STEMI / NSTEMI. |
| Aortic dissection | Tearing/ripping pain, maximal at onset, radiating to back. BP differential, pulse deficit, new AR murmur. | CTA chest/abdomen. BP/HR control. See Aortic Dissection. |
| Pulmonary embolism | Pleuritic pain, dyspnea, tachycardia out of proportion. Risk: immobility, surgery, cancer, OCP. | CTPA (or D-dimer if low pretest). See PE. |
| Tension pneumothorax | Acute pleuritic pain + dyspnea. Absent breath sounds, JVD, tracheal deviation, hypotension. | Clinical diagnosis → needle decompression. See Pneumothorax. |
| Esophageal rupture (Boerhaave) | Severe retrosternal pain after forceful vomiting. Subcutaneous emphysema, Hamman's crunch (mediastinal crackle). Left pleural effusion. | CT chest with oral contrast or water-soluble esophagram. Emergent surgical consult. Mortality > 50% if delayed > 24h. |
Common Non-Emergent Causes
| Category | Diagnosis | Clues |
|---|---|---|
| Musculoskeletal (~35%) | Costochondritis, muscle strain | Reproducible with palpation, worse with movement/position, no cardiac risk factors. Most common cause of chest pain in ED. |
| GI (~15%) | GERD, esophageal spasm, PUD | Burning, postprandial, relieved by antacids. Esophageal spasm can mimic ACS (substernal, relieved by NTG). |
| Pulmonary | Pneumonia, pleuritis, asthma | Pleuritic (sharp, worse with inspiration), fever, cough, focal exam findings. |
| Cardiac (non-ACS) | Pericarditis, myocarditis, aortic stenosis | Pericarditis: positional (worse supine, better leaning forward), friction rub, diffuse ST elevation. |
| Psychiatric (~10%) | Panic attack, anxiety | Diagnosis of exclusion. Young, hyperventilation, perioral/extremity tingling, sense of doom. Still need ECG + troponin. |
🧪 Workup
Standard Chest Pain Workup
| Test | When | What It Rules Out |
|---|---|---|
| ECG WITHIN 10 MIN | EVERY chest pain. No exceptions. | STEMI, arrhythmia, pericarditis, PE (S1Q3T3, RV strain), Brugada, WPW |
| Troponin | All chest pain concerning for ACS | Myocardial injury. Serial troponins at 0 and 3h (high-sensitivity). 0 and 6h (conventional). |
| CXR | All admitted chest pain | Pneumothorax, pneumonia, widened mediastinum (dissection), pleural effusion, rib fractures |
| D-dimer | Low-intermediate pretest probability for PE | PE (if negative + low Wells → ruled out). Do NOT order if high pretest → go straight to CTPA. |
| CTPA | PE suspected (high Wells, positive D-dimer) | PE. Also shows dissection incidentally. |
| CTA chest | Dissection suspected | Aortic dissection. Triple rule-out CTA can assess coronaries + PE + dissection in one scan (but requires specific protocol). |
HEART Score for Chest Pain Disposition
See NSTEMI topic for full HEART score. Score 0–3: safe for early discharge (< 2% MACE). Score 7–10: high risk → early invasive.
🚨 Management
Management
- ACS: ASA+heparin+serial troponin+cardiology
- PE: Wells→D-dimer or CTPA
- Dissection: CTA. A→surgery. B→HR/BP control.
- Tamponade: echo→pericardiocentesis
- Tension PTX: needle decompress→tube
- HEART 0-3 + 2 neg troponins → safe discharge
📋 On Rounds
Can NTG relief differentiate cardiac from non-cardiac chest pain?
No. This is a common myth. NTG relieves pain from ACS (coronary vasodilation + preload reduction) but also relieves esophageal spasm (smooth muscle relaxation). Henrikson, 2003: NTG response had no predictive value for cardiac vs non-cardiac chest pain. Patients with documented ACS failed to respond to NTG in ~35% of cases, while patients with non-cardiac pain responded in ~40%. Do NOT use NTG response to rule in or rule out ACS. Use clinical features, ECG, troponin, and risk scores instead.
What are the 5 'must-not-miss' causes of chest pain?
The deadly 5: (1) ACS (STEMI/NSTEMI) — ECG + troponin, (2) Aortic dissection — tearing pain, BP differential, widened mediastinum → CTA, (3) Pulmonary embolism — pleuritic, tachycardia, risk factors → Wells + D-dimer or CTPA, (4) Tension pneumothorax — absent breath sounds, tracheal deviation, hypotension → needle decompression BEFORE imaging, (5) Cardiac tamponade — Beck's triad (hypotension, JVD, muffled heart sounds), pulsus paradoxus → bedside echo, pericardiocentesis. Every chest pain workup should explicitly rule out or consider all 5. Document it.
What is the HEART score and how does it change your management?
HEART score = History (0-2) + ECG (0-2) + Age (0-2) + Risk factors (0-2) + Troponin (0-2). Total 0-10. 0-3 (low risk): 1.6% risk of MACE at 30 days → safe for early discharge with outpatient follow-up. Consider stress test outpatient. 4-6 (moderate): 12% risk → observe, serial troponins, consider stress test or CT coronary angiography before discharge. 7-10 (high): 65% risk → admit, heparin, cardiology consult, likely cath. The HEART score is validated and outperforms physician gestalt for risk stratification. A HEART score of 0-3 with 2 negative troponins at 0 and 3h is one of the safest discharge criteria in emergency medicine.
What are the classic ECG findings that differentiate pericarditis from STEMI?
Pericarditis: diffuse ST elevation (not territorial), PR depression (most specific finding), concave-up ("smiley face") ST morphology, reciprocal ST depression + PR elevation in aVR only. STEMI: territorial ST elevation (corresponds to coronary artery territory — e.g., II/III/aVF = inferior = RCA), convex-up ("tombstone") morphology, reciprocal ST depression in opposite leads, Q waves may develop. Key differentiator: PR depression is virtually pathognomonic for pericarditis and is NEVER seen in STEMI. Also: pericarditis pain is pleuritic + positional; STEMI pain is pressure + radiating.
📣 Sample Presentation
One-Liner
"Mr. Thompson is a 52-year-old smoker with HTN presenting with substernal chest pressure × 4 hours radiating to left jaw. Diaphoretic. ECG: normal sinus, no ST changes. Troponin 0.04 (pending repeat). HEART score 6."
Key Points to Cover on Rounds
High-risk chest pain — HEART score 6. DDx: ACS (high probability), must rule out PE, dissection, tamponade, tension PTX. ECG: no acute ST changes but doesn't rule out NSTEMI. Troponin 0.04 (borderline, repeat at 3h). Started ASA 325, heparin drip. Chest pain resolved with nitroglycerin SL × 2. CXR: no widened mediastinum (dissection less likely), no PTX. D-dimer not sent (low Wells for PE). Plan: serial troponin, if rising → cardiology for early cath. If negative × 2 → stress test before discharge.
💊 Medications
Key Medications — Chest Pain / ACS Workup
| Drug | Dose | Route | Indication | Notes |
|---|---|---|---|---|
| Aspirin STAT | 325 mg chew STAT | PO (chew) | All suspected ACS | Chewing provides faster absorption than swallowing. Non-enteric coated. Give immediately — do not wait for troponin results. |
| Nitroglycerin | 0.4 mg SL q5min x 3 doses | SL | Chest pain relief | Reduces preload → decreases myocardial O2 demand. Contraindicated if SBP < 90, RV infarct, PDE5 inhibitor within 24–48h (sildenafil/tadalafil). |
| Morphine | 2–4 mg IV q5–15min PRN | IV | If NTG fails for pain | Use cautiously. May cause hypotension and respiratory depression. Some data suggests worse outcomes in NSTEMI — consider alternatives (fentanyl). |
| Heparin (UFH) | 60 u/kg bolus (max 4000u) → 12 u/kg/hr | IV drip | High-suspicion ACS | Anticoagulation for suspected ACS. Target aPTT 60–80 sec. Alternative: enoxaparin 1 mg/kg SQ q12h. |
| Metoprolol | 25 mg PO | PO | ACS if HR/BP allow | Beta-blocker — reduces myocardial O2 demand. Hold if: HR < 60, SBP < 100, signs of HF, PR > 0.24, 2nd/3rd degree AV block, active wheezing. |
| High-intensity statin | Atorvastatin 80 mg PO | PO | All ACS patients | Start immediately regardless of baseline LDL. Plaque stabilization. Continue lifelong. |
MONA is outdated as a rote protocol. ASA and NTG remain first steps, but morphine should be used cautiously and oxygen only if SpO2 < 90% (DETO2X-AMI: routine O2 in normoxemic MI showed no benefit).
📈 Monitoring
Monitoring Parameters — Chest Pain / ACS Workup
| Parameter | Frequency | Target / Action |
|---|---|---|
| Serial ECGs | q15–30 min if symptoms recur or change | Compare to baseline. New ST changes, T-wave inversions, or Q waves may evolve. Dynamic ECG changes = high-risk ACS. |
| Serial troponins | 0h, 3h, 6h (conventional) or 0h/1h protocol (high-sensitivity) | Rising pattern = acute myocardial injury. Delta troponin (change between values) is more important than absolute number. Two negative high-sensitivity troponins at 0 and 3h with low HEART score = safe discharge. |
| Continuous telemetry | Continuous | Arrhythmia detection — new AF, VT, heart block. All chest pain admissions need telemetry until ACS excluded. |
| Symptom assessment | q1–2h during active symptoms | Chest pain character, severity (0–10), response to NTG/morphine. Recurrent pain with ECG changes = escalate to cardiology/cath. |
| HEART score reassessment | After troponin results | HEART 0–3 + 2 negative troponins = safe discharge. HEART 4–6 = observe/stress test. HEART 7–10 = admit, heparin, cath. |
| Hemodynamics | q1–4h based on acuity | HR, BP, SpO2. Hypotension + new murmur = mechanical complication (VSD, papillary rupture, free wall rupture) — emergent echo. |
Don't anchor on the first troponin. A single negative troponin does NOT rule out ACS — serial measurements showing no rise are required. The delta (change) matters more than the absolute value.
⚡ Summary
Summary
HEART Score
H(istory) E(CG) A(ge) R(isk factors) T(roponin). 0-3: low risk, safe discharge. 4-6: moderate, observe. 7-10: high risk, admit + cath.
Must Rule Out
ACS, PE, aortic dissection, tamponade, tension PTX, esophageal rupture (Boerhaave). The 6 deadly causes of chest pain.
ECG Clues
ST elevation = STEMI. ST depression = ischemia. Diffuse ST + PR depression = pericarditis. S1Q3T3 + right heart strain = PE.
Troponin
Serial at 0 and 3h (high-sensitivity). Rising pattern = acute MI. Chronically mildly elevated = CKD, HF, PE (not necessarily ACS).
Low Risk Discharge
HEART 0-3 + 2 negative troponins (0 + 3h) + no ECG changes → one of safest discharge criteria in EM.
Atypical Presentations
Women, elderly, diabetics: may present with dyspnea, nausea, fatigue, jaw/back pain without classic substernal pressure. Low threshold for workup.
📄 One Pager
Chest Pain / ACS Workup — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
CHEST PAIN / ACS WORKUP — AT A GLANCE
📋 Rule out 5 deadly causes: ACS, dissection, PE, tension PTX, Boerhaave
🧪 ECG within 10 min. Serial troponins 0h/3h (hs-troponin 0h/1h)
⚡ ASA 325 chew STAT. NTG 0.4mg SL q5min x3. Heparin if high suspicion.
💊 Beta-blocker if HR/BP allow. High-intensity statin for all ACS.
📈 HEART score: 0–3 = safe discharge. 7–10 = admit + cath.
📣 Continuous telemetry. Serial ECGs with recurrent symptoms.
🧪 ECG within 10 min. Serial troponins 0h/3h (hs-troponin 0h/1h)
⚡ ASA 325 chew STAT. NTG 0.4mg SL q5min x3. Heparin if high suspicion.
💊 Beta-blocker if HR/BP allow. High-intensity statin for all ACS.
📈 HEART score: 0–3 = safe discharge. 7–10 = admit + cath.
📣 Continuous telemetry. Serial ECGs with recurrent symptoms.
📄 One Pager
Emergency / Cardiology · One Pager
Chest Pain Evaluation
HEART score drives disposition. 0-3 = safe discharge. 7-10 = admit + cath. Rule out the 6 deadly causes. Serial troponin at 0 + 3h.
6 Deadly Causes
ACS (STEMI/NSTEMI), PE, aortic dissection, cardiac tamponade, tension pneumothorax, esophageal rupture (Boerhaave). Every chest pain patient needs these considered.
HEART Score
History (0-2) + ECG (0-2) + Age (0-2) + Risk factors (0-2) + Troponin (0-2). 0-3: low risk (1.6% MACE) → discharge. 4-6: moderate → observe. 7-10: high → admit + cath.
Workup
ECG (immediate). Troponin 0 + 3h (high-sensitivity). CXR. Consider: D-dimer (PE), CTA (dissection/PE), echo (tamponade, WMA). HEART 0-3 + 2 neg troponins = safe discharge.
Key Drugs
ASA325 mg if ACS suspected
Nitroglycerin0.4 mg SL q5min × 3
HeparinIf ACS confirmed
MorphineCautious (may reduce P2Y12 absorption)
Pitfalls
- Anchoring on "musculoskeletal" without ruling out ACS
- Missing posterior STEMI or Wellens pattern on ECG
- Not considering dissection (tearing pain, BP differential)
- Troponin at 0h only (need serial)
Anaphylaxis
IgE-mediated systemic allergic reaction. Epinephrine is the ONLY first-line treatment — everything else is adjunctive. The most common mistake: giving diphenhydramine and steroids instead of epinephrine. Epi first, always.
🔍 Overview
Diagnostic Criteria — Any ONE of Three
- Criterion 1: Acute onset (minutes–hours) of skin/mucosal involvement (hives, flushing, angioedema) PLUS respiratory compromise (dyspnea, stridor, wheeze, hypoxia) OR hypotension/end-organ dysfunction
- Criterion 2: ≥ 2 of the following after exposure to LIKELY allergen: skin/mucosal symptoms, respiratory compromise, hypotension, persistent GI symptoms (cramping, vomiting)
- Criterion 3: Hypotension alone after exposure to KNOWN allergen for that patient
Up to 20% of anaphylaxis has NO skin findings. Don't wait for hives to give epinephrine. Isolated hypotension or bronchospasm after allergen exposure = anaphylaxis.
Common Triggers
- Foods: peanuts, tree nuts, shellfish, milk, eggs (#1 cause in children)
- Medications: antibiotics (penicillin, cephalosporins), NSAIDs, contrast dye, anesthetic agents (#1 cause in perioperative setting)
- Insect stings: Hymenoptera (bee, wasp, hornet) — #1 cause of fatal anaphylaxis in adults
- Latex
- Idiopathic (~20% — no identifiable trigger)
Biphasic Anaphylaxis
Up to 20% of anaphylaxis cases have a biphasic reaction — recurrence of symptoms 1–72 hours after initial resolution (most within 8–10h). This is why ALL patients require a minimum 4–6 hour observation period, and severe reactions warrant 12–24h observation. Steroids (methylprednisolone 125 mg IV) are given empirically to prevent biphasic reactions, though evidence is limited.
Clinical Example
Case
28F with known shrimp allergy presents from a restaurant with lip swelling, diffuse urticaria, audible wheezing, and BP 82/48 within 15 minutes of eating shellfish. HR 124, SpO₂ 91% on RA. This is anaphylaxis (Criterion 2: skin + respiratory + hypotension after known allergen).
🚨 Management
Treatment Protocol
EPINEPHRINE is the ONLY first-line treatment. There is NO contraindication to epinephrine in anaphylaxis — not age, not pregnancy, not cardiac disease. The risk of NOT giving epi is always greater than the risk of giving it. IM Epinephrine Pharmacokinetics Trial, 2004 WAO, 2020
| Step | Drug | Dose | Notes |
|---|---|---|---|
| 1. EPINEPHRINE | Epinephrine 1:1000 (1 mg/mL) GIVE FIRST | 0.3–0.5 mg IM (0.3–0.5 mL) in anterolateral thigh. Repeat q5–15 min if no improvement. | IM (not SubQ) — faster absorption IM Epinephrine Pharmacokinetics Trial, 2004. Anterolateral thigh (not deltoid) — better blood flow. Autoinjector: EpiPen 0.3 mg adult, 0.15 mg pediatric (< 30 kg). Most common error: not giving epi, giving it too late, or giving it SubQ. WAO Anaphylaxis Guidelines, 2020 |
| 2. Position | Supine with legs elevated (improves venous return). If vomiting → recovery position. If respiratory distress → sitting up. Do NOT have the patient stand or sit upright if hypotensive — can cause fatal "empty ventricle syndrome." | ||
| 3. IV access + fluids | NS bolus | 1–2 L rapid bolus (20 mL/kg peds) | Anaphylaxis causes massive vasodilation + capillary leak → distributive shock. Aggressive fluids needed. |
| 4. Adjuncts | Diphenhydramine 50 mg IV + famotidine (Pepcid) 20 mg IV | H1 + H2 blockers | Adjunctive ONLY — do NOT give instead of epinephrine. Antihistamines treat hives but do NOT reverse bronchospasm or hypotension. |
| 5. Steroids | Methylprednisolone 125 mg IV | Or dexamethasone 10 mg IV | Does NOT help acute anaphylaxis (takes 4–6h to work). May prevent biphasic reaction (occurs in ~5–20%, usually 1–72h later) Biphasic Anaphylaxis Review, 2015. Observe ≥ 4–6h after resolution. |
| Refractory | Epinephrine drip | 1–10 mcg/min IV | If ≥ 2 doses of IM epi fail → start epi drip. Glucagon 1–5 mg IV if on beta-blockers (epi may be ineffective due to β-blockade). Vasopressin for refractory hypotension. |
IM epinephrine is the ONLY life-saving treatment. Antihistamines and steroids are ADJUNCTS — they do NOT treat anaphylaxis. Delay in epinephrine = death.
NEVER give IV epinephrine push for anaphylaxis (unless cardiac arrest). IV push epi in a patient with a pulse causes fatal arrhythmias. Use IM or IV drip only.
Updated Practice: Old teaching: give IV Benadryl and steroids first, then epi if not improving. WRONG — epinephrine is FIRST, immediately. Every minute of delay increases mortality. WAO, 2020
🧪 Workup
Laboratory Workup
- Tryptase level — draw within 1–2h of onset (peaks at 1h). Confirms mast cell degranulation. A normal tryptase does NOT rule out anaphylaxis.
- CBC — baseline hematocrit, WBC
- BMP — renal function, electrolytes (epinephrine can cause hypokalemia)
- ECG — arrhythmias from epinephrine administration or myocardial involvement (Kounis syndrome — allergic MI)
- Trigger identification — detailed timeline of exposures (food, drugs, insect stings, latex, exercise)
- Allergist referral — 4–6 weeks post-event for skin-prick testing and component testing
Clinical diagnosis. Do NOT delay treatment waiting for labs. Tryptase is confirmatory, not diagnostic. If it looks like anaphylaxis, treat like anaphylaxis.
📋 On Rounds
Why give glucagon in anaphylaxis for patients on beta-blockers?
Epinephrine works primarily through β₁ (increased HR, contractility) and β₂ (bronchodilation, vasodilation in muscle) receptors. In patients on beta-blockers, these receptors are occupied/blocked → epinephrine is less effective → refractory anaphylaxis. Glucagon bypasses the β-receptor entirely — it activates adenylyl cyclase directly via the glucagon receptor → increases cAMP → positive inotropy + chronotropy + smooth muscle relaxation. Dose: 1–5 mg IV bolus, then 5–15 mcg/min infusion. Side effects: vomiting (have suction ready), hyperglycemia. This is a critical drug to know for the beta-blocker + anaphylaxis combination.
Why is IM epinephrine given in the anterolateral thigh and not the deltoid?
The anterolateral thigh (vastus lateralis) provides faster and higher peak epinephrine absorption than the deltoid, with peak plasma levels at ~8 minutes vs ~34 minutes for subcutaneous. This is because the thigh has rich vasculature and large muscle mass for IM absorption. Never give epi IV push for anaphylaxis (unless in cardiac arrest) — IV bolus can cause fatal arrhythmia. The dose is 0.3–0.5 mg of 1:1000 (1 mg/mL) IM, repeat q5–15 min. EpiPen auto-injectors deliver 0.3 mg. Most deaths from anaphylaxis are from delayed or withheld epinephrine, not from the allergic reaction being untreatable. Give it early.
A patient had an anaphylactic reaction 4 hours ago and feels fine. Can you discharge them?
Observe for biphasic reaction. Biphasic anaphylaxis occurs in 1-20% of cases (most estimates ~5%), typically 1-72 hours after the initial reaction (most within 8-10h). Risk factors for biphasic: severe initial reaction, delayed epinephrine, required > 1 dose of epi, unknown trigger. Minimum observation: 4-6 hours for mild reactions. Extended observation (12-24h): severe initial reaction, respiratory compromise, hypotension requiring IV fluids, or recurrence of symptoms. All patients need: EpiPen prescription (teach auto-injector use), allergist referral, anaphylaxis action plan, and medical alert bracelet. Steroids (methylprednisolone 125 mg IV) are given to prevent biphasic reactions, though evidence is limited.
What are the diagnostic criteria for anaphylaxis?
Anaphylaxis is diagnosed when any 1 of 3 criteria is met: (1) Acute skin/mucosal involvement (hives, flushing, angioedema) + respiratory compromise (wheeze, stridor, hypoxia) OR hypotension. (2) ≥ 2 of the following after exposure to a likely allergen: skin/mucosal symptoms, respiratory compromise, hypotension, persistent GI symptoms (cramping, vomiting). (3) Hypotension alone after exposure to a known allergen for that patient. Pearl: you do NOT need hives to diagnose anaphylaxis — 10-20% of anaphylaxis presents WITHOUT skin findings. Isolated hypotension after known allergen exposure IS anaphylaxis. Tryptase level (draw 1-2h after onset) supports the diagnosis but a normal tryptase doesn't rule it out.
📣 Sample Presentation
One-Liner
"Ms. Williams is a 35-year-old who developed diffuse urticaria, throat tightness, wheezing, and hypotension (BP 78/42) within 10 minutes of IV cefazolin administration. Consistent with anaphylaxis."
Key Points to Cover on Rounds
Anaphylaxis to cefazolin (probable cephalosporin allergy). Epinephrine 0.5 mg IM anterolateral thigh given × 1 → BP improved to 102/64. Additional: diphenhydramine 50 mg IV, famotidine 20 mg IV, methylprednisolone 125 mg IV, NS 1L bolus. Wheezing resolved with albuterol neb. Observed for biphasic reaction × 6 hours — no recurrence. Tryptase level drawn at 1h. Allergy documented: cephalosporins → anaphylaxis. EpiPen prescribed. Plan: allergist referral, avoid cephalosporins and high-cross-reactivity penilcillins, discharge with anaphylaxis action plan.
💊 Medications
Anaphylaxis Medications
| Drug | Dose | Route | Role |
|---|---|---|---|
| Epinephrine (1:1000) | 0.3–0.5 mg | IM anterolateral thigh | FIRST-LINE — repeat q5–15 min. No contraindications in anaphylaxis. |
| Diphenhydramine | 50 mg | IV | H1 blocker — adjunct for urticaria/pruritus. Does NOT treat hypotension or bronchospasm. |
| Famotidine (Pepcid) | 20 mg | IV | H2 blocker — adjunct. Combined H1+H2 blockade more effective than H1 alone. |
| Methylprednisolone | 125 mg | IV | Prevents biphasic reaction (theoretical — weak evidence). Takes 4–6h to work. NOT for acute treatment. |
| Albuterol | 2.5 mg neb | Nebulized | For bronchospasm refractory to epinephrine. Continuous neb if severe. |
| Glucagon | 1–5 mg bolus, then 5–15 mcg/min | IV | For patients on beta-blockers. Bypasses β-receptor blockade → direct cAMP activation. Side effect: vomiting. |
| Epinephrine drip | 1–10 mcg/min | IV infusion | Refractory anaphylaxis (failed ≥2 IM doses). ICU-level monitoring required. |
📈 Monitoring
Monitoring Parameters
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals (HR, BP, SpO₂, RR) | q15 min during acute phase | Hemodynamic stability. Watch for recurrent hypotension (biphasic reaction). |
| Continuous telemetry | Continuous × 4–6h minimum | Arrhythmia monitoring (epinephrine-induced or myocardial involvement). |
| Airway assessment | q15–30 min | Recurrence of stridor, lip/tongue swelling, voice changes. Have intubation tray at bedside. |
| Skin exam | q30 min–1h | New or worsening urticaria, flushing, angioedema → may indicate biphasic reaction. |
| Observation period | 4–6h minimum (12–24h if severe) | Biphasic reactions occur in up to 20% of cases, most within 8–10h. |
Biphasic risk factors: Severe initial reaction, delayed epinephrine, required >1 dose of epi, unknown trigger. These patients need extended observation (12–24h).
⚡ Summary
Summary
Diagnosis
Rapid onset (min to hours) + skin/mucosal involvement + respiratory compromise or hypotension. 10-20% have NO skin findings.
First-Line
Epinephrine 0.5 mg IM anterolateral thigh. Repeat q5-15 min if needed. NO substitute — epi is the ONLY first-line treatment.
Adjuncts
H1 blocker (diphenhydramine 50 mg IV), H2 blocker (famotidine 20 mg IV), steroids (methylprednisolone 125 mg IV), NS bolus for hypotension.
Biphasic
Occurs in ~5% of cases, 1-72h after initial reaction. Observe 4-6h minimum (12-24h if severe). Steroids may help prevent.
Discharge
EpiPen prescription + teach auto-injector. Allergist referral. Anaphylaxis action plan. Medical alert bracelet. Avoid identified trigger.
Common Triggers
Foods (#1 in children: peanuts, tree nuts, shellfish). Medications (#1 in adults: antibiotics, NSAIDs). Hymenoptera stings. Latex.
Toxicology & Overdose
The toxidromes guide your initial management before the specific agent is identified. Know the antidotes cold — they save lives. ABCs first, then identify the toxidrome, then specific antidote + supportive care.
🔍 Toxidromes
| Toxidrome | Vital Signs | Pupils | Other Findings | Common Agents |
|---|---|---|---|---|
| Sympathomimetic | ↑ HR, ↑ BP, ↑ Temp | Mydriasis | Diaphoresis, agitation, seizures, tremor | Cocaine, amphetamines, PCP, MDMA |
| Anticholinergic | ↑ HR, ↑ Temp | Mydriasis | "Hot as a hare, dry as a bone, red as a beet, mad as a hatter, blind as a bat." Urinary retention, ileus, DRY skin | Diphenhydramine, atropine, TCAs, jimsonweed |
| Cholinergic | ↓ HR (or ↑), ↓ BP | Miosis | SLUDGE: Salivation, Lacrimation, Urination, Diarrhea, GI cramping, Emesis. Bronchospasm, fasciculations. | Organophosphates, nerve agents, physostigmine OD |
| Opioid | ↓ HR, ↓ BP, ↓ RR | Miosis ("pinpoint") | Respiratory depression (#1 cause of death), CNS depression, hypothermia | Heroin, fentanyl, morphine, methadone, oxycodone |
| Sedative-hypnotic | ↓ HR, ↓ BP, ↓ RR | Normal or miosis | CNS depression, slurred speech, ataxia, respiratory depression | Benzodiazepines, barbiturates, GHB, ethanol |
| Serotonin syndrome | ↑ HR, ↑ BP, ↑↑ Temp | Mydriasis | Clonus (especially lower extremity), hyperreflexia, tremor, agitation, diarrhea. Key: clonus distinguishes from NMS | SSRIs + MAOIs, SSRIs + tramadol, SSRIs + linezolid |
Sympathomimetic vs anticholinergic — both cause tachycardia + mydriasis + hyperthermia. Key difference: sympathomimetic = DIAPHORESIS (sweating). Anticholinergic = DRY skin.
💊 Key Antidotes
| Poison | Antidote | Dose | Key Pearls |
|---|---|---|---|
| Acetaminophen | N-acetylcysteine (NAC) | IV: 150 mg/kg → 50 mg/kg over 4h → 100 mg/kg over 16h. PO: 140 mg/kg → 70 mg/kg q4h × 17 doses. | Check 4-hour level and plot on Rumack-Matthew nomogram. Above the treatment line → give NAC. If > 8h since ingestion or any doubt → start NAC empirically. NAC is most effective within 8h but beneficial up to 24h+. |
| Opioids | Naloxone (Narcan) | 0.04–0.4 mg IV (start low, titrate to respiratory effort). Repeat q2–3 min. IM/IN: 0.4–2 mg if no IV. | Goal: restore respiratory drive, NOT full consciousness. High-dose naloxone in opioid-dependent patients → acute withdrawal (vomiting → aspiration, agitation, arrhythmia). Fentanyl may need higher doses (2–10 mg). Half-life of naloxone (30–90 min) < most opioids → patient can re-sedate. Observe 4–6h or start drip. |
| Benzodiazepines | Flumazenil (Romazicon) | 0.2 mg IV q1 min (max 3 mg) | RARELY used. Can precipitate seizures in chronic benzo users or TCA co-ingestion. Generally contraindicated in unknown overdose. Supportive care is usually sufficient. |
| TCA (tricyclic antidepressant) | Sodium bicarbonate | 1–2 mEq/kg IV bolus → drip to maintain pH 7.45–7.55 | Hallmarks of TCA toxicity: QRS > 100 ms, R wave in aVR > 3 mm, seizures, hypotension. Bicarb widens the therapeutic window by increasing protein binding of the drug. Also: intralipid 20% for refractory cardiotoxicity. |
| Beta-blocker | Glucagon | 3–10 mg IV bolus → 3–5 mg/hr infusion | Bypasses blocked β-receptors. Also: high-dose insulin (1 unit/kg bolus → 0.5–1 unit/kg/hr) for refractory cases — "hyperinsulinemia-euglycemia therapy" (HIET) — improves cardiac output. Give with D50 + K⁺ monitoring. |
| Calcium channel blocker | Calcium + High-dose insulin | Calcium chloride 1–2g IV. Insulin: same HIET protocol as BB OD. | HIET is the primary treatment for severe CCB OD. Calcium provides temporary ionotropic support. IV lipid emulsion for refractory. Vasopressors (NE) as bridge. |
| Methanol / ethylene glycol | Fomepizole (Antizol) | 15 mg/kg IV loading → 10 mg/kg q12h | Inhibits alcohol dehydrogenase → blocks conversion to toxic metabolites (formate in methanol → blindness; oxalate in EG → AKI). Brent, 2001 Also: hemodialysis if severe (pH < 7.1, renal failure, visual symptoms, serum level > 50). Ethanol IV drip is alternative if fomepizole unavailable (target BAL 100). EXTRIP Guidelines, Lavergne 2012-2020 |
| Organophosphate | Atropine + Pralidoxime (2-PAM) | Atropine 2 mg IV q5 min (titrate to secretion control). 2-PAM 1–2g IV over 15 min. | Atropine controls muscarinic symptoms (secretions). 2-PAM reactivates AChE if given early (< 24–48h before "aging"). No upper limit on atropine dose in organophosphate poisoning — may need 10–100+ mg. |
| Warfarin / rodenticide | Vitamin K + 4F-PCC | Vitamin K 10 mg IV (slow). 4F-PCC for life-threatening bleed. | 4F-PCC reverses INR within minutes. Vitamin K takes 6–24h to work (hepatic synthesis of clotting factors). Give both if actively bleeding. |
| Digoxin | Digoxin-specific antibody fragments (DigiFab) | Empiric: 10–20 vials if acute OD. Calculated: # vials = (level × weight) / 100. | Indications: hemodynamic instability, K⁺ > 5, symptomatic bradycardia/heart block, dig level > 10 (acute) or > 6 (chronic). Avoid calcium in dig toxicity |
🧪 Workup
Workup
- Fingerstick glucose — ALWAYS
- ECG — QRS, QTc
- APAP + salicylate — ALWAYS
- Ethanol
- BMP + AG
- Osmolality — osmol gap
- VBG/ABG
- Specific levels if suspected
🚨 Management
Management
- Stabilize: ABCs, glucose, monitor
- Decontamination: charcoal <1-2h
- Antidotes: NAC (APAP), naloxone (opioid), fomepizole (toxic alcohol) Rumack-Matthew Nomogram, 1975, atropine+2-PAM (organophosphate), bicarb (TCA)
- Enhanced elimination: dialysis, alkalinization
- Poison control: 1-800-222-1222 EVERY case
📊 Monitoring
Monitoring
- Continuous telemetry
- Serial ECGs
- Repeat APAP at 4h
- LFTs q12h if APAP
- ABG trend
- UOP
📋 On Rounds
How do you distinguish serotonin syndrome from neuroleptic malignant syndrome?
Both cause hyperthermia + AMS + autonomic instability, but: Serotonin syndrome: (1) rapid onset (hours) after serotonergic drug, (2) CLONUS (especially lower extremity — most specific sign), (3) hyperreflexia, (4) tremor, (5) diarrhea, (6) mydriasis. NMS: (1) slow onset (days–weeks) after dopamine antagonist (antipsychotic), (2) "lead-pipe" RIGIDITY (no clonus), (3) hyporeflexia, (4) elevated CK (> 1000). The key distinguishing feature: clonus + hyperreflexia = serotonin syndrome. Rigidity + hyporeflexia = NMS. Treatment: SS → stop serotonergic drug, cyproheptadine, benzos. NMS → stop antipsychotic, dantrolene, bromocriptine.
A patient presents with QRS > 100 ms and R wave in aVR on ECG after an overdose. What did they take?
Tricyclic antidepressant (TCA) overdose. TCAs block fast sodium channels in the His-Purkinje system → slowed conduction → QRS widening. QRS > 100 ms predicts seizures. QRS > 160 ms predicts ventricular arrhythmias. The R wave in aVR > 3 mm is another specific marker of sodium channel blockade. Treatment: sodium bicarbonate 1–2 mEq/kg IV bolus — the sodium load overcomes the sodium channel blockade, and the alkalinization increases protein binding of the TCA (reducing free drug). Target pH 7.45–7.55. If refractory cardiotoxicity: intralipid emulsion 20% (lipid rescue) 1.5 mL/kg bolus → 0.25 mL/kg/min infusion.
An unknown ingestion patient has pinpoint pupils, respiratory depression, and bradycardia. What toxidrome and what's the antidote?
Opioid toxidrome: CNS depression, respiratory depression, miosis (pinpoint pupils), bradycardia, hypotension, decreased bowel sounds. Antidote: naloxone (Narcan). Start with 0.04-0.4 mg IV (titrate to respiratory effort, NOT consciousness — goal is breathing, not wakefulness). If no response at 2 mg → reconsider diagnosis. Key pitfall: naloxone half-life (30-90 min) is shorter than most opioids (especially methadone, extended-release formulations). Patient may re-sedate → need repeated doses or naloxone drip (2/3 of the effective bolus dose per hour). For suspected fentanyl overdose: may need higher doses (up to 10-20 mg total). Always order: fingerstick glucose, ECG (QRS/QTc), APAP/salicylate levels, ethanol — coingestants are common.
Name the 5 classic toxidromes and one drug example for each.
(1) Sympathomimetic: tachycardia, HTN, hyperthermia, dilated pupils, diaphoresis, agitation. Drugs: cocaine, methamphetamine, MDMA. (2) Anticholinergic: "mad as a hatter, blind as a bat, dry as a bone, red as a beet, hot as a hare." Tachycardia, mydriasis, dry skin/mouth, urinary retention, hyperthermia, AMS. Drugs: diphenhydramine, TCAs, jimsonweed. (3) Cholinergic (SLUDGE): salivation, lacrimation, urination, defecation, GI cramps, emesis + miosis, bradycardia, bronchospasm. Drugs: organophosphates, nerve agents. Antidote: atropine + pralidoxime. (4) Opioid: miosis, respiratory depression, CNS depression, bradycardia. Antidote: naloxone. (5) Sedative-hypnotic: similar to opioid but pupils normal. Drugs: benzos, barbiturates, GHB. Antidote: flumazenil (use cautiously — seizures).
📣 Sample Presentation
One-Liner
"Mr. Garcia is a 22-year-old brought in by friends after intentional ingestion of unknown quantity of acetaminophen ~6 hours ago. He is asymptomatic. APAP level 220 mcg/mL at 6 hours (above the Rumack-Matthew treatment line)."
Key Points to Cover on Rounds
Acetaminophen toxicity — APAP 220 at 6h (above treatment line). AST/ALT currently normal (may take 24-48h to rise). NAC protocol started: 150 mg/kg IV loading dose over 1h, then 50 mg/kg over 4h, then 100 mg/kg over 16h. INR 1.0, Cr 0.8 (no end-organ damage yet). Activated charcoal not given (>4h since ingestion). Poison control contacted. Psychiatry consulted for intentional ingestion. Plan: serial LFTs, APAP levels, INR q6h. Continue NAC until APAP undetectable + ALT trending down + INR normal. 1:1 sitter for safety.
⚡ Summary
Summary
5 Toxidromes
Sympathomimetic (cocaine/meth), anticholinergic (diphenhydramine/TCA), cholinergic/SLUDGE (organophosphates), opioid (fentanyl), sedative-hypnotic (benzos).
Universal Workup
Fingerstick glucose, ECG (QRS/QTc), APAP level, salicylate level, ethanol level, BMP, lactate. Coingestants are common.
APAP Toxicity
Rumack-Matthew nomogram. NAC: 150 mg/kg load → 50 mg/kg/4h → 100 mg/kg/16h. Start if above treatment line. Don't wait for level if massive ingestion.
Antidotes
Naloxone (opioids), flumazenil (benzos — cautious), NAC (APAP), fomepizole (methanol/ethylene glycol), atropine + pralidoxime (organophosphates).
Decontamination
Activated charcoal if < 1-2h post-ingestion and intact airway. Whole bowel irrigation for sustained-release, iron, lithium, body-packing.
Call Poison Control
1-800-222-1222. Always. Even for cases that seem straightforward. They have expertise and track outcomes.
📄 One Pager
Emergency / Toxicology · One Pager
Toxicology
5 toxidromes. APAP level + salicylate + ECG on every overdose. Poison control: 1-800-222-1222. NAC for acetaminophen. Naloxone for opioids. Treat the patient, not the poison.
5 Toxidromes
Sympathomimetic (cocaine): mydriasis, HTN, diaphoresis. Anticholinergic (diphenhydramine): mydriasis, dry, hot. Cholinergic (organophosphate): SLUDGE, miosis. Opioid: miosis, RD, CNS depression. Sedative-hypnotic: CNS depression, normal pupils.
Universal Workup
Fingerstick glucose, ECG (QRS/QTc), APAP level, salicylate level, ethanol, BMP, lactate, VBG. Call Poison Control on EVERY case: 1-800-222-1222.
Key Antidotes
NAC (APAP). Naloxone (opioids). Fomepizole (methanol/ethylene glycol). Atropine + pralidoxime (organophosphates). Flumazenil (benzos — cautious). Digibind (digoxin). Lipid emulsion (local anesthetic toxicity).
Key Drugs
NAC150 mg/kg → 50 mg/kg/4h → 100 mg/kg/16h
Naloxone0.04-2 mg IV titrate to breathing
Fomepizole15 mg/kg IV load
Activated charcoal1g/kg PO (< 1-2h, intact airway)
Pitfalls
- Not checking APAP/ASA levels (coingestants common)
- Under-dosing naloxone for fentanyl (may need 10-20 mg)
- Flumazenil in chronic benzo users (seizures)
- Missing serotonin syndrome (clonus, hyperthermia, agitation)
Rotation
Emergency Medicine
Resuscitation, rapid assessment, undifferentiated presentations, and critical procedures.
Available Topics
Post-Cardiac Arrest (ROSC)
Hypertensive Emergency
DKA / HHS
Alcohol Withdrawal
Chest Pain Workup
Anaphylaxis
Toxicology & Overdose
Trauma Primary & Secondary Survey
Acute Abdomen
Burns Management
Hypothermia & Drowning
Toxicology (Comprehensive)
Intubation / RSI
Acute Limb Ischemia
Necrotizing Fasciitis
📋 Major Guidelines
Rotation
Night Float
Everything you need for cross-cover. Common pages, escalation algorithms, when to call your senior, and how to survive the night.
🚨 Common Cross-Cover Scenarios
📋 Cross-Cover Algorithms
Fever, Hypotension, Desat, AMS, Chest Pain, Low UOP
🔴 Code Blue & Rapid Response
ACLS, H's & T's, code drugs
💊 Electrolyte Replacement
K⁺, Mg²⁺, PO₄, Ca²⁺ protocols
💉 Opioid & Steroid Conversions
Equianalgesic tables, steroid equivalency
💧 IV Fluid Guide
Which fluid for which scenario
🧪 Lab Interpretation
CBC, BMP, LFTs, coags
💊 Antibiotic Guide
Empiric coverage by infection site
🔢 Calculators
GCS, MELD, CrCl, Winter's
📞 Most Common Night Float Pages
Hyperkalemia
K⁺ > 6.0 with ECG changes
Sepsis / Septic Shock
New fever + hemodynamic instability
Acute HF / Flash Pulmonary Edema
New dyspnea, desaturation
Afib with RVR
HR > 140, palpitations
DKA / HHS
Glucose > 500, AG > 20
Alcohol Withdrawal
Tremor, CIWA > 15, seizure risk
GI Bleed
Hematemesis, melena, Hgb drop
Pulmonary Embolism
New dyspnea, tachycardia, pleuritic pain
Acute Stroke
New focal deficit, tPA window
Inpatient Fall
CT head if on anticoag
Delirium / Agitation
CAM, non-pharm first
Chest Pain
ECG, troponin, 5 deadly causes
🌙 Night Float Survival Guide
When to Call Your Senior
- Any rapid response or code blue — call BEFORE you go, even if you think you can handle it
- New vasopressor requirement or escalation of existing pressors
- Transfer to ICU or higher level of care
- Acute stroke code — tPA window decisions
- Acute MI / STEMI activation
- Intubation needed (unless you're the person intubating)
- New GI bleed with hemodynamic instability
- Patient or family requesting to change code status urgently
- Death — expected or unexpected (pronouncement, family notification, paperwork)
- Any situation where you're unsure — calling too early is always better than calling too late
Cross-Cover Approach — Every Call
ABCDE for every page: Assess → Bedside (go see the patient) → Chart review → Decide → Execute + follow-up
- Step 1 — Get the right information from the nurse: Vitals (current + trend), mental status change, what intervention was already tried, code status, is the primary team aware?
- Step 2 — Go see the patient: Never manage cross-cover issues by phone alone. A 30-second bedside assessment (airway, breathing, circulation, mental status) tells you more than 10 minutes of chart review.
- Step 3 — Check the chart: Admitting diagnosis, active problems, recent labs/imaging, medications (what changed today?), code status, allergies.
- Step 4 — Address the acute issue: Order what's needed (stat labs, imaging, meds). Don't shotgun — think about what will change your management.
- Step 5 — Document: Brief cross-cover note — what you were called for, what you found, what you did, and follow-up plan. The primary team needs to know what happened overnight.
Common Overnight PRN Orders
| Problem | First-Line Order | Notes |
|---|---|---|
| Insomnia | Melatonin 3-5 mg PO | NOT diphenhydramine in elderly (delirium, falls). Trazodone 25-50 mg alternative. |
| Pain (mild) | Acetaminophen 650 mg PO q6h | Max 3g/day if liver disease. Scheduled > PRN for consistent control. |
| Pain (moderate) | Oxycodone 5 mg PO q4h PRN | Start low in opioid-naive. Add senna + docusate. Check last dose timing. |
| Nausea | Ondansetron 4 mg IV/PO q6h | Check QTc first. Promethazine is more sedating. Avoid metoclopramide if Parkinson's. |
| Constipation | Senna 2 tabs PO QHS + docusate 100 mg BID | If on opioids: must have a bowel regimen. Bisacodyl 10 mg PR if > 3 days. |
| Agitation | Non-pharm first. If severe: haloperidol 0.5-2 mg IV/IM | Check QTc. Avoid in Parkinson's/Lewy body. Try reorientation, family, lights first. |
| Fever | Acetaminophen 650 mg + blood cultures × 2 | UA + CXR. Don't reflexively add antibiotics without evaluating — call senior if sepsis concern. |
| Hypertension (asymptomatic) | Restart home meds if held. PRN: hydralazine 10 mg IV or labetalol 10 mg IV | Don't treat numbers — treat end-organ damage. Asymptomatic BP 180/100 can often wait until morning. |
| Hypoglycemia (glucose < 70) | D50 25 mL IV push (if NPO/altered) or juice + crackers (if eating) | Recheck in 15 min. Identify cause: excess insulin? missed meal? Hold offending agent. |
| Foley issues | Flush with 30 mL NS. If blocked → replace. | If can't place → call urology for difficult catheterization. Don't force it. |
Night Float Tips from Senior Residents
- Read sign-out BEFORE your shift starts. Know your "watchers" — the patients most likely to decompensate. See them first.
- Pre-round on the sickest patients at the start of your shift, not when they're crashing at 3 AM.
- Keep a running list of what happened overnight. Sign out in the morning should be efficient — "here's what happened, here's what I did, here's what needs follow-up."
- Eat before your shift, bring snacks, and have caffeine strategically (not at 4 AM if you want to sleep post-call).
- Batch your work: if you're going to one floor to see a patient, check if there are other pages on the same floor.
- The patient is not your enemy at 3 AM. They're scared, in pain, and in an unfamiliar place. A 30-second reassuring visit can prevent 5 more pages.
- If you're drowning, tell someone. Call your senior. Page the attending if needed. Patient safety > pride.
📋 Major Guidelines
Anemia Workup
Classify by MCV first — microcytic, normocytic, or macrocytic. Then use iron studies, reticulocyte count, and peripheral smear to narrow the diagnosis. Iron deficiency is the most common cause worldwide.
🔍 MCV-Based Classification
| MCV | Category | Differential | Key Labs |
|---|---|---|---|
| < 80 | Microcytic | Iron deficiency (#1 — GI blood loss in men/postmenopausal women until proven otherwise), thalassemia (Mentzer index: MCV/RBC < 13 → thalassemia, > 13 → iron def), anemia of chronic disease (some), sideroblastic, lead poisoning | Iron studies, ferritin, TIBC, reticulocyte count, Hgb electrophoresis if thalassemia suspected |
| 80–100 | Normocytic | Anemia of chronic disease (#1), acute blood loss, CKD (↓ EPO), mixed deficiency (iron + B12), hemolysis (check hemolysis labs), bone marrow failure (aplastic, MDS, infiltration) | Reticulocyte count (↑ = destruction/loss, ↓ = underproduction), BMP (CKD), hemolysis labs (LDH, haptoglobin, indirect bili, smear) |
| > 100 | Macrocytic | B12 deficiency (neurologic symptoms — subacute combined degeneration), folate deficiency, alcohol/liver disease, hypothyroidism, MDS, medications (methotrexate, hydroxyurea, azathioprine, AZT), reticulocytosis (reticulocytes are large → MCV ↑) | B12, folate, reticulocyte count, TSH, peripheral smear (hypersegmented neutrophils → megaloblastic), methylmalonic acid (↑ in B12 def, normal in folate def) |
New iron deficiency anemia in a man or postmenopausal woman = GI malignancy until proven otherwise. These patients need colonoscopy + upper endoscopy. Do NOT just give iron and move on.
Reticulocyte Count — Production vs Destruction
- Reticulocyte count > 2% (or reticulocyte index > 2): bone marrow is responding → the problem is blood loss or destruction (hemolysis)
- Reticulocyte count < 2%: bone marrow is NOT responding → underproduction (iron/B12/folate deficiency, CKD, bone marrow failure, anemia of chronic disease)
- Reticulocyte Production Index (RPI): (retic % × Hgb/15) / maturation factor. RPI > 2 = appropriate response.
🧪 Iron Studies Interpretation
| Lab | Iron Deficiency | Anemia of Chronic Disease | Both (Mixed) |
|---|---|---|---|
| Serum iron | ↓ | ↓ | ↓ |
| Ferritin | ↓↓ (< 30) | ↑ or normal (acute phase reactant) | Low-normal (30–100) |
| TIBC | ↑ (body wants more iron) | ↓ (body not trying to absorb more) | Variable |
| Transferrin saturation | ↓ (< 20%) | ↓ (15–20%) | ↓ |
Ferritin is an acute phase reactant — it rises with inflammation, infection, liver disease, and malignancy. A "normal" ferritin of 50–100 in an inflamed hospitalized patient may actually represent iron deficiency. Ferritin < 30 is diagnostic of iron deficiency. Ferritin < 100 in the setting of inflammation is suggestive.
Iron Replacement
| Route | Agent | Notes |
|---|---|---|
| Oral | Ferrous sulfate 325 mg PO daily–TID | Take on empty stomach with vitamin C (enhances absorption). GI side effects are dose-limiting. Every-other-day dosing may improve absorption and tolerability. Takes 3–6 months to replete stores. |
| IV (preferred if) | Iron sucrose (Venofer) 200 mg IV × 5 doses or ferric carboxymaltose (Injectafer) 750 mg IV × 2 | Preferred if: oral intolerant, CKD/dialysis, IBD, ongoing blood loss exceeding oral repletion, Hgb < 7 with symptoms, pre-surgery. Injectafer: can give 750 mg in one sitting (fewer visits). |
🧪 Workup
Workup
- CBC + retic count (#1 test)
- Peripheral smear
- Iron studies
- B12 + folate
- LDH, haptoglobin, indirect bili — hemolysis
- Direct Coombs
- EPO level
- Bone marrow biopsy if unclear
🚨 Management
Management
- Iron deficiency: FIND SOURCE + IV iron (ferric carboxymaltose 750mg×2) or PO. Transfuse: Hgb<7 in most patients TRICC, Hébert 1999
- B12: IM cyanocobalamin 1000mcg daily×7→weekly×4→monthly
- Hemolytic: autoimmune→steroids±rituximab. TTP→PLEX. Mechanical→treat cause.
- CKD: iron first, then ESA (Hgb 10-11)
- Transfuse: Hgb<7 most, <8 ACS TRISS, Holst 2014 TITRe2, Murphy 2015
📋 On Rounds
How do you distinguish iron deficiency from anemia of chronic disease when both have low serum iron?
Ferritin and TIBC. In iron deficiency, the body is truly depleted of iron → ferritin is low (< 30) and TIBC is high (the body upregulates transferrin to grab any available iron). In anemia of chronic disease, iron is trapped in macrophages by hepcidin (the inflammatory "iron warden") → ferritin is normal or high (iron is stored, just not released) and TIBC is low (no need to absorb more — there's plenty, just sequestered). The trick: in a hospitalized inflamed patient with both problems, ferritin may be "normal" at 50–100 but that's actually low for someone with active inflammation. Soluble transferrin receptor (sTfR) is elevated in true iron deficiency and normal in ACD — it's the best test when ferritin is ambiguous.
A patient has a ferritin of 80 but you still suspect iron deficiency. How is that possible?
Ferritin is an acute phase reactant — it rises with inflammation, infection, liver disease, and malignancy regardless of iron stores. A 'normal' ferritin of 80 in a patient with active inflammation (elevated CRP) may actually represent iron deficiency. In the setting of chronic disease or inflammation, a ferritin < 100 with transferrin saturation < 20% suggests functional iron deficiency even though ferritin appears 'normal'. The FAIR-HF trial used ferritin < 100 (or < 300 with Tsat < 20%) as the cutoff for IV iron replacement in heart failure patients. Rule of thumb: in inflamed patients, the ferritin threshold for diagnosing iron deficiency is ~100, not 30.
A patient has pancytopenia. What's your differential and what do you order?
Pancytopenia = all three lines down (anemia + leukopenia + thrombocytopenia). Differential by mechanism: Decreased production (bone marrow failure): aplastic anemia, MDS, leukemia/lymphoma, myelofibrosis, B12/folate deficiency (megaloblastic), drug-induced (methotrexate, chemotherapy), infections (HIV, hepatitis, parvovirus, TB). Increased destruction: hypersplenism (cirrhosis), DIC, TTP/HUS, autoimmune (SLE). Workup: (1) Peripheral smear (blasts? schistocytes? hypersegmented neutrophils? teardrop cells?), (2) Reticulocyte count (production vs destruction), (3) B12/folate, (4) HIV, hepatitis B/C, (5) LDH, haptoglobin (hemolysis), (6) Bone marrow biopsy if no obvious cause — this is the definitive test. Key pearl: severe B12 deficiency can mimic leukemia on smear (hypersegmented neutrophils, megaloblastic changes) — always check B12 before biopsy.
How do you approach anemia when the MCV is normal (normocytic)?
Normocytic anemia (MCV 80-100): the broadest differential. Step 1: Reticulocyte count. High retic (> 2%): the marrow is responding → blood LOSS or blood DESTRUCTION. Check: LDH, haptoglobin, Coombs test. If hemolysis markers positive → hemolytic anemia (autoimmune, TTP, DIC, G6PD, sickle cell, PNH). If hemolysis markers negative → acute blood loss (look for the source). Low retic (< 2%): marrow is NOT responding → production problem. Check: iron studies (iron deficiency can be normocytic early), B12/folate, TSH, EPO level, CRP (anemia of chronic disease — most common cause of normocytic anemia in hospitalized patients). If all normal → bone marrow biopsy (MDS, aplastic anemia, myelophthisis, myeloma).
📣 Sample Presentation
One-Liner
"Mrs. Rivera is a 48-year-old premenopausal woman with fatigue and Hgb 8.2, MCV 72. Iron studies: ferritin 8, TIBC 450, transferrin sat 6%. Consistent with iron deficiency anemia."
Key Points to Cover on Rounds
Microcytic anemia — iron deficiency confirmed (ferritin 8, Tsat 6%). Source: heavy menstrual bleeding (menorrhagia × 2 years, soaking through pads). No GI symptoms, no melena. Given her age and clear gynecologic source, GI workup deferred. Treatment: IV iron infusion (ferric carboxymaltose 750 mg × 2 doses, 1 week apart) — chose IV over PO due to severity and faster repletion. Gynecology referral for menorrhagia management. Plan: recheck CBC + ferritin in 6-8 weeks, expect Hgb rise 1 g/dL per week of iron.
💊 Medications
Key Medications — Anemia
Treatment depends on the cause. Iron deficiency = replace iron + find source. B12 deficiency = replace B12. Anemia of CKD = iron first, then ESA. Hemolytic = treat underlying cause.
| Drug | Dose | Route | Indication |
|---|---|---|---|
| Ferrous sulfate | 325 mg PO daily–TID | PO | Iron deficiency anemia (mild-moderate). Take on empty stomach with vitamin C. Every-other-day dosing may improve absorption. |
| Iron sucrose (Venofer) | 200 mg IV x 5 doses | IV | IV iron preferred if: oral intolerant, CKD/dialysis, IBD, Hgb < 7, ongoing blood loss, pre-surgery. |
| Ferric carboxymaltose (Injectafer) | 750 mg IV x 2 (1 week apart) | IV | Convenient IV iron — can give 750 mg in one sitting (fewer visits). |
| Cyanocobalamin (B12) | 1000 mcg IM daily x 7d → weekly x 4 → monthly | IM | B12 deficiency. High-dose oral (1000–2000 mcg/day) may be adequate if no absorption issues. |
| Folic acid | 1 mg PO daily | PO | Folate deficiency. Always check B12 first — folate alone can mask B12 deficiency (corrects anemia but NOT neuro damage). |
| Epoetin alfa (Procrit) | 50–300 units/kg 3x/week | IV/SQ | Anemia of CKD (after iron repletion). Target Hgb 10–11.5. Never > 13. |
📈 Monitoring
Monitoring Parameters — Anemia
| Parameter | Frequency | Target / Action |
|---|---|---|
| Reticulocyte count | Day 5–7 after starting treatment | Response to iron/B12/folate therapy. Reticulocyte count should rise by day 5–7 ("reticulocyte burst"). If no response → wrong diagnosis, non-compliance, or ongoing blood loss. |
| Hemoglobin | Weekly initially, then monthly | Expect Hgb rise ~1 g/dL per week with iron replacement. Recheck at 4 weeks — if no improvement, reassess diagnosis and compliance. |
| Iron studies (ferritin, TIBC, iron sat) | At 4–8 weeks after starting iron | Ferritin > 100, TSAT > 20% = iron repleted. Continue oral iron 3–6 months after Hgb normalizes to replete stores. |
| B12 / folate levels | At 2–3 months if supplementing | Confirm repletion. Methylmalonic acid (MMA) is more sensitive for B12 — should normalize with treatment. |
| Stool guaiac / FIT | If GI blood loss suspected | Positive → GI referral for colonoscopy + EGD. New IDA in men or postmenopausal women = GI malignancy until proven otherwise. |
| GI referral | For unexplained IDA | Colonoscopy + EGD for all men and postmenopausal women with IDA. Do NOT just treat with iron and move on without finding the source. |
Finding and treating the source is as important as replacing the iron. Iron replacement without source identification is a dangerous shortcut — you may miss a GI malignancy.
⚡ Summary
Summary
MCV Approach
Microcytic (< 80): iron deficiency, thalassemia, chronic disease, sideroblastic. Normocytic (80-100): chronic disease, CKD, hemolysis, bleeding. Macrocytic (> 100): B12/folate, MDS, liver disease, hypothyroid, drugs.
Iron Deficiency
Ferritin < 30 (or < 100 in CKD/inflammation), low Tsat. Find the source: GI (colonoscopy), menstrual, malabsorption. IV iron for severe/refractory.
Hemolysis Workup
LDH ↑, haptoglobin ↓, indirect bilirubin ↑, reticulocyte ↑. Coombs test: positive = autoimmune. Negative = mechanical (TTP, DIC, prosthetic valve).
Transfusion Threshold
Hgb < 7 for most patients [TRICC, TRISS]. Hgb < 8 for active cardiac ischemia. Never transfuse to a number — transfuse for symptoms.
B12 Deficiency
Can cause pancytopenia mimicking leukemia. Hypersegmented neutrophils on smear. Neuro symptoms (subacute combined degeneration). Check methylmalonic acid.
Reticulocyte Count
The single most important test. High retic = bone marrow is working (loss or destruction). Low retic = production failure (check iron/B12/folate, consider biopsy).
📄 One Pager
Anemia Workup — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
ANEMIA WORKUP — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
Hematology · One Pager
Anemia
MCV-based approach: micro (iron), normo (chronic disease, hemolysis, bleeding), macro (B12/folate). Reticulocyte count = production vs destruction. Transfuse Hgb < 7.
MCV Approach
Microcytic (< 80): iron deficiency (#1), thalassemia, chronic disease, sideroblastic. Normocytic (80-100): chronic disease, CKD, hemolysis, acute bleeding. Macrocytic (> 100): B12/folate, MDS, liver disease, hypothyroid, drugs.
Iron Deficiency
Ferritin < 30 (or < 100 in inflammation/CKD), low transferrin sat. FIND THE SOURCE: GI (colonoscopy if > 50 or alarm features), menstrual, malabsorption. IV iron for severe or refractory.
Hemolysis Workup
LDH ↑, haptoglobin ↓, indirect bili ↑, reticulocyte ↑. Coombs positive = autoimmune (warm vs cold). Coombs negative = mechanical (TTP, DIC, valve), PNH, G6PD, sickle cell.
Key Drugs
Ferric carboxymaltose750 mg IV × 2 doses
Cyanocobalamin1000 mcg IM daily × 7d
Folic acid1 mg PO daily
EPO50-300 U/kg 3×/wk (CKD)
Pitfalls
- Transfusing above Hgb 7 threshold without indication
- Not checking reticulocyte count (production vs destruction)
- Missing B12 deficiency (can cause pancytopenia mimicking leukemia)
- Iron infusion without finding the source of loss
Cellulitis & Skin Infections
The most overdiagnosed infection in medicine — up to 30% of "cellulitis" admissions are actually stasis dermatitis, DVT, gout, or contact dermatitis. Purulent vs non-purulent determines whether you cover MRSA. Mark the borders with a pen.
🔍 Overview
Purulent vs Non-Purulent — This Drives Treatment
| Type | Features | Organism | Treatment |
|---|---|---|---|
| Non-purulent cellulitis | Diffuse erythema, warmth, tenderness. No abscess, no pus, no drainage. Clear borders. | Beta-hemolytic strep (Group A strep) is the most common cause. NOT usually MRSA. | Cefazolin (Ancef) 2g IV q8h (inpatient) or cephalexin 500 mg QID (outpatient). 5–6 days is sufficient IDSA, 2014. No MRSA coverage needed. |
| Purulent cellulitis / abscess | Fluctuant, drainable collection. Pus expressed. Central pustule or wound. | S. aureus (MSSA or MRSA) — especially CA-MRSA (USA300). | I&D is the primary treatment (antibiotics alone are less effective). Antibiotics: TMP-SMX (Bactrim) DS BID or doxycycline (Vibramycin) 100 mg BID × 5–7 days. IV: vancomycin if severe. |
| Necrotizing fasciitis SURGICAL EMERGENCY | Pain out of proportion, crepitus, rapid spread, bullae, skin necrosis, hemodynamic instability. LRINEC score ≥ 6 → high suspicion. | Type I: polymicrobial. Type II: Group A strep (monomicrobial). | Emergent surgical debridement (do NOT wait for imaging). Vanc + pip-tazo + clindamycin (clindamycin inhibits toxin production). ICU. |
Cellulitis mimics (up to 30% of admissions): stasis dermatitis (bilateral, chronic, hemosiderin staining — #1 mimic), DVT (unilateral leg swelling → get duplex US), gout (peri-articular), contact dermatitis, erythema migrans (Lyme — single expanding ring), lipodermatosclerosis (woody induration).
Key Principles
- Mark the borders with a pen and date/time it — this is how you track whether it's improving or spreading on antibiotics
- Blood cultures are NOT recommended for uncomplicated cellulitis (positive in < 2%). Only get if: sepsis, immunocompromised, animal/water bite, or unusual exposures.
- Elevate the affected limb — reduces edema and speeds resolution
- Bilateral "cellulitis" is almost never cellulitis — think stasis dermatitis, HF, venous insufficiency
- Not improving at 48–72h? Consider: wrong diagnosis (mimic), abscess needing drainage, resistant organism, deeper infection (osteomyelitis, sept
ic joint), necrotizing fasciitis🧪 WorkupWorkup — Cellulitis & Skin Infections
- CBC with differential — leukocytosis supports infection, but WBC is often normal in uncomplicated cellulitis. Bandemia or left shift suggests more severe/systemic infection.
- BMP — baseline Cr (for antibiotic dosing), glucose (uncontrolled DM worsens outcomes and increases recurrence risk)
- Blood cultures — only if systemic signs/sepsis (fever > 38.5°C, tachycardia, hypotension, immunocompromised). NOT routine for simple cellulitis — yield is < 2% IDSA, 2014
- Wound culture — only if abscess drained (send purulent material) or open wound present. Swab of intact skin over cellulitis is useless — do not send.
- Ultrasound — if abscess suspected but not clinically obvious. Bedside US has excellent sensitivity for detecting drainable fluid collections. A missed abscess is the #1 reason cellulitis "fails" antibiotics.
- Mark borders with skin marker — draw along the leading edge of erythema and write the date/time. This is the most important bedside tool to objectively track response at 48h.
Cellulitis is a clinical diagnosis. Imaging is for ruling out abscess (US) or necrotizing fasciitis (CT with gas), NOT for confirming cellulitis. If bilateral → think stasis dermatitis. If unilateral with edema → consider DVT (get duplex US). Up to 30% of "cellulitis" admissions are misdiagnosed.🔄 Updated Practice: Old teaching: draw blood cultures for all cellulitis. Current practice: blood cultures are positive in <2-5% of uncomplicated cellulitis and do not change management. Only draw blood cultures if: systemic signs of sepsis (fever, tachycardia, hypotension), immunocompromised, facial cellulitis, animal/water exposure, or failed outpatient therapy (IDSA 2014). Similarly, wound cultures are only useful from abscess drainage or open wounds — surface swabs grow contaminants.
🚨 Management
Management
- Non-purulent (strep): cephalexin 500 QID×5-7d or cefazolin IV
- Purulent (MRSA): I&D primary + TMP-SMX or doxycycline
- IV→PO: afebrile×24h + WBC↓ + receding past marks
- Nec fasc: pain>exam, crepitus, bullae → emergent surgery
- Prevent: treat tinea pedis, compression stockings, weight loss
📋 On Rounds
Why is non-purulent cellulitis usually strep and not staph?
Non-purulent (diffuse) cellulitis is caused by bacteria that spread through tissue planes via hyaluronidase and streptokinase — enzymes that break down connective tissue and dissolve clots, allowing rapid lateral spread. Beta-hemolytic streptococci (especially Group A) excel at this. S. aureus, by contrast, tends to form localized, walled-off collections (abscesses) because it produces coagulase (promotes clot formation around the infection). That's why purulent/abscess = staph, and diffuse spreading erythema = strep. This distinction matters because strep doesn't require MRSA coverage — cefazolin or cephalexin is sufficient.
How do you distinguish cellulitis from DVT, and why does it matter?
Both present with a red, swollen, warm leg — and misdiagnosis is common. Key distinguishers: Cellulitis = fever, leukocytosis, skin warmth with clear border, often portal of entry (wound, tinea pedis), bilateral involvement suggests stasis dermatitis not cellulitis. DVT = unilateral leg edema, calf tenderness on palpation, risk factors (immobility, cancer, surgery), usually no fever or skin erythema early on. Why it matters: anticoagulating cellulitis is harmless (unnecessary but not dangerous); missing a DVT → PE → death. If any doubt, get a compression ultrasound before committing to cellulitis treatment alone. Up to 10% of patients diagnosed with cellulitis actually have DVT.
How do you decide between IV and PO antibiotics for cellulitis?
Outpatient PO: Non-purulent, no systemic toxicity (afebrile, non-toxic), small area, immunocompetent, reliable follow-up. Drug: cephalexin 500 mg QID × 5-7 days. Inpatient IV: Rapidly spreading (beyond marked borders), systemic toxicity (fever, tachycardia, WBC > 15K), failed outpatient PO after 48h, immunocompromised, facial cellulitis, periorbital cellulitis, hand cellulitis, concern for deeper infection. Drug: cefazolin 2g IV q8h. Transition IV → PO: when afebrile ×24h, WBC trending down, erythema receding past marked borders (usually 48-72h). Always mark borders with a skin marker and write the date/time — this is how you objectively assess response. If spreading past borders on appropriate antibiotics at 48h → broaden coverage or image for abscess/deeper infection.
What are the red flags that suggest necrotizing fasciitis instead of simple cellulitis?
Nec fasc mimics cellulitis early but kills fast. Red flags: (1) Pain out of proportion to exam (the hallmark — like mesenteric ischemia, disproportionate pain = alarm), (2) Rapid progression (spreading beyond marked borders within hours, not days), (3) Systemic toxicity (high fever, tachycardia, hypotension out of proportion to skin findings), (4) Crepitus (gas in tissues — palpable or visible on imaging), (5) Skin necrosis, hemorrhagic bullae, dusky discoloration (late signs), (6) Failed antibiotics (cellulitis not responding at 48h → re-evaluate). LRINEC score ≥ 6: suggests necrotizing infection (WBC, CRP, Hgb, Na, glucose, Cr). If suspected → emergent surgical exploration (the diagnosis is made in the OR, not on imaging). CT can show gas but a negative CT does NOT rule out nec fasc.
📣 Sample Presentation
One-Liner
"Mr. Williams is a 56-year-old diabetic presenting with left lower leg erythema, warmth, and swelling × 3 days. No abscess or purulence. Tinea pedis noted on foot exam. Non-purulent cellulitis."
Key Points to Cover on Rounds
Non-purulent cellulitis — likely strep (Group A). Portal of entry: tinea pedis (interdigital cracking). Borders marked with skin marker + time. Treatment: cefazolin 2g IV q8h (first-line for non-purulent). No I&D needed (no abscess on exam, no fluctuance). US: no fluid collection. Blood cultures not sent (low yield unless septic/immunocompromised). Leg elevated. Response at 48h: erythema receding from marked borders. Plan: transition to cephalexin 500 QID PO to complete 5-7 day course. Treat tinea pedis (terbinafine cream) to prevent recurrence.
💊 Medications
Antibiotic Selection — Cellulitis & Skin Infections
| Scenario | Drug (Brand) | Dose | Notes |
|---|---|---|---|
| Non-purulent cellulitis (outpatient) 1ST LINE | Cephalexin (Keflex) | 500 mg PO QID × 5–7 days | Covers beta-hemolytic strep (Group A). No MRSA coverage needed. Shorter courses (5 days) are effective IDSA, 2014. |
| Non-purulent cellulitis (inpatient) 1ST LINE | Cefazolin (Ancef) | 2g IV q8h | Transition to cephalexin PO when afebrile × 24h, WBC trending down, erythema receding past marked borders. |
| Purulent / abscess (MRSA coverage) | TMP-SMX (Bactrim) DS or Doxycycline (Vibramycin) | TMP-SMX DS 1 tab PO BID × 5–7 days Doxycycline 100 mg PO BID × 5–7 days | I&D is the primary treatment for abscess — antibiotics are adjunctive. Both cover CA-MRSA. TMP-SMX: avoid in pregnancy, check K⁺ (can cause hyperkalemia). Doxycycline: photosensitivity, avoid in pregnancy. |
| Severe / necrotizing fasciitis EMERGENT | Vancomycin + piperacillin-tazobactam (Zosyn) + clindamycin (Cleocin) | Vanc: 15–20 mg/kg IV q8–12h (target AUC/MIC 400–600) Pip-tazo: 4.5g IV q6h Clindamycin: 900 mg IV q8h | Clindamycin inhibits toxin production (ribosomal suppression) — critical for toxin-mediated disease (GAS, S. aureus). Broad coverage for polymicrobial (Type I) and monomicrobial (Type II) nec fasc. Emergent surgical debridement is definitive treatment. |
PCN allergy? Non-purulent: clindamycin 300–450 mg PO TID (but 15–20% MRSA resistance in some areas). Severe: vancomycin alone covers both MRSA and most strep. For true anaphylaxis to penicillin, avoid all cephalosporins (although cross-reactivity is < 2% with cephalexin).
📈 Monitoring
Monitoring Parameters — Cellulitis & Skin Infections
| Parameter | Frequency | Target / Action |
|---|---|---|
| Demarcation line progression | Mark and remeasure daily (at least q12h if concern for rapid spread) | Erythema receding past marked borders = responding. Spreading beyond marks at 48h → broaden antibiotics, image for abscess, or consider necrotizing fasciitis. |
| WBC | Daily while on IV antibiotics | Trending down = responding. Rising or persistently elevated → consider treatment failure, abscess, deeper infection, or wrong diagnosis. |
| Fever curve | q4h (Tmax documented daily) | Afebrile × 24h is one criterion for IV → PO transition. Persistent fever > 48h on appropriate antibiotics → re-evaluate diagnosis and coverage. |
| IV → PO transition criteria | Assess daily starting at 48h | Transition to oral when: afebrile × 24h, WBC trending down, erythema receding past marked borders, tolerating PO, systemically well. Usually at 48–72h. |
| Wound check (if I&D performed) | Daily until packing removed | Wound packing removed or changed at 48h. Assess for re-accumulation, ongoing drainage, surrounding cellulitis. Consider wound culture if not improving. |
Not improving at 48h? Differential: (1) missed abscess (get US), (2) wrong diagnosis (stasis dermatitis, DVT, gout), (3) resistant organism (broaden to vancomycin), (4) deeper infection (osteomyelitis, septic joint → MRI), (5) necrotizing fasciitis (pain out of proportion, crepitus, rapid spread → emergent surgery).
⚡ Summary
Summary
Non-Purulent
Likely strep (Group A). Cephalexin 500 QID × 5-7 days (outpatient) or cefazolin 2g IV q8h (inpatient). No I&D needed.
Purulent/Abscess
Likely MRSA. I&D is primary treatment. TMP-SMX or doxycycline for surrounding cellulitis. Clindamycin alternative.
Mark Borders
Skin marker + date/time at periphery of erythema. Objective assessment of response at 48h. If spreading past lines → broaden or image.
Admit Criteria
Systemic toxicity (fever, tachycardia, WBC > 15K), rapid spread, failed outpatient PO, immunocompromised, facial/periorbital/hand.
IV → PO Switch
Afebrile × 24h, WBC trending down, erythema receding past marked borders (usually 48-72h). Transition to oral equivalent.
Nec Fasc Red Flags
Pain out of proportion, rapid spread, crepitus, hemorrhagic bullae, skin necrosis, systemic toxicity. Emergent surgical exploration.
📄 One Pager
Cellulitis & Skin Infections — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
CELLULITIS & SKIN INFECTIONS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
Falls & Delirium Prevention
Inpatient falls are a "never event" — they cause hip fractures, subdural hematomas, and prolonged hospitalization. Delirium prevention is the same bundle. Most of this is medication review + non-pharmacologic interventions.
🛡️ Prevention Bundle
High-Risk Medications — Review and Stop
| Drug Class | Examples to Stop/Minimize | Safer Alternative |
|---|---|---|
| Benzodiazepines | Lorazepam, midazolam, diazepam | Melatonin 3–5 mg for sleep. Trazodone 25–50 mg. Non-pharmacologic sleep hygiene. |
| Anticholinergics | Diphenhydramine (Benadryl) — #1 offender on inpatient med lists. Also: hydroxyzine, oxybutynin, promethazine, cyclobenzaprine. | Cetirizine (non-sedating antihistamine). Acetaminophen for pain. Remove diphenhydramine from every PRN order set. |
| Opioids (excess) | High-dose PRN without scheduled non-opioid adjuncts | Scheduled acetaminophen 1g q6h. Add gabapentin for neuropathic. Use opioids for breakthrough only. |
| Antihypertensives (excess) | Home doses continued despite lower inpatient BP → orthostatic hypotension | Hold/reduce home antihypertensives if SBP < 120 or symptomatic orthostasis. Reassess at discharge. |
| Sedating antipsychotics | Quetiapine, chlorpromazine at high doses | Use lowest effective dose. Time-limit orders. |
Non-Pharmacologic Prevention (HELP Protocol)
- Reorientation — whiteboard with date, day, nurse name. Clock in room. Familiar objects. Family at bedside.
- Sleep hygiene — lights off by 10 PM, minimize nighttime vitals, cluster care, earplugs + eye mask, avoid nighttime medication administration if possible
- Early mobility — PT/OT consult on admission for at-risk patients. Ambulate TID minimum. Chair for meals (not bed).
- Sensory aids — glasses and hearing aids AT BEDSIDE (not in a drawer). Dentures in for meals.
- Remove tethers — Foley (remove by day 2 unless specific indication), unnecessary IV lines, telemetry if not needed, restraints (worsen agitation)
- Nutrition + hydration — avoid NPO status if possible. Offer fluids. Malnutrition worsens delirium.
- Avoid physical restraints — restraints increase agitation, prolong delirium, increase falls (patients climb over them), and increase mortality
The HELP (Hospital Elder Life Program) protocol reduces delirium incidence by 30–40%. It's entirely non-pharmacologic and costs nothing. It works better than any drug.
Post-Fall Assessment
🧪 Workup
Post-Fall Assessment
| Assessment | What to Check | Action |
|---|---|---|
| Injury survey | Head (laceration, hematoma), hip/pelvis (pain on log-roll), spine (tenderness), extremities | CT head if head strike (mandatory if on anticoagulation). Hip X-ray if hip/groin pain. C-spine if neck pain. |
| Neuro exam | GCS, pupil symmetry, focal deficits, gait (if ambulatory) | Document GCS and neuro status. If on anticoag + head strike → CT head STAT + repeat at 24h if on warfarin. |
| Vitals | Orthostatic BP/HR (lying → sitting → standing) | Drop ≥ 20/10 or HR rise ≥ 30 = orthostatic hypotension → volume depletion, meds, autonomic dysfunction |
| ECG | Arrhythmia, heart block, QTc prolongation | New arrhythmia → telemetry. Syncope-related fall → full syncope workup. |
| Labs | BMP (Na, glucose, Ca), CBC (anemia), INR if on warfarin | Correct metabolic causes. Check drug levels if applicable (digoxin, AEDs). |
| Medication review | Benzos, opioids, antihypertensives, anticholinergics, antipsychotics, diuretics | Deprescribe fall-risk meds. Use Beers Criteria AGS, 2023. Taper, don't abruptly stop. |
⚡ Management
Fall Prevention — Inpatient
| Intervention | Details |
|---|---|
| Bed alarm | For high-risk patients (delirium, impaired mobility, prior fall). NOT physical restraints — restraints increase falls and agitation. |
| Non-slip socks + clear pathway | Remove clutter, ensure call bell within reach, bed in lowest position, nightlight on. |
| Medication reconciliation | Reduce/eliminate: benzodiazepines (#1 contributor), opioids, sedating antihistamines (diphenhydramine), antihypertensives causing orthostasis, anticholinergics. |
| Delirium prevention (HELP protocol) | Orientation aids (clock, calendar), minimize nighttime disruptions, early mobilization, hearing aids/glasses at bedside, avoid unnecessary catheters. |
| PT/OT consult | Gait assessment, strength training, assistive device evaluation. Early mobilization reduces deconditioning. |
| Treat underlying cause | Orthostatic hypotension → IVF, adjust meds. Syncope → cardiac workup. Delirium → find precipitant. Neuropathy → B12, glucose control. |
Physical restraints do NOT prevent falls — they increase agitation, delirium, pressure injuries, aspiration, and functional decline. They are a last resort only for imminent self-harm, never routine fall prevention.
💊 Medications
High-Risk Medications for Falls — Beers Criteria
| Drug Class | Examples | Mechanism of Fall Risk | Action |
|---|---|---|---|
| Benzodiazepines | Lorazepam, diazepam, alprazolam | Sedation, impaired balance, cognitive slowing | Taper and discontinue. Use melatonin or trazodone for insomnia. |
| Anticholinergics | Diphenhydramine, oxybutynin, cyclobenzaprine | Delirium, sedation, blurred vision, urinary retention | Substitute: cetirizine for allergy, mirabegron for OAB. |
| Opioids | Oxycodone, morphine, tramadol | Sedation, dizziness, impaired coordination | Multimodal pain: acetaminophen, topical NSAIDs, nerve blocks. |
| Antihypertensives | Alpha-blockers (doxazosin), loop diuretics | Orthostatic hypotension, volume depletion | Liberalize BP target in frail elderly (SBP 150 may be acceptable). |
| Antipsychotics | Haloperidol, quetiapine | Sedation, orthostasis, EPS | Avoid for delirium if possible. If needed, use lowest dose × shortest duration. |
| Hypoglycemics | Sulfonylureas (glipizide), insulin | Hypoglycemia → syncope → fall | Liberalize glucose targets in elderly (A1c 7.5–8.5% acceptable). |
📈 Monitoring
Post-Fall Monitoring
| Parameter | Frequency | Action |
|---|---|---|
| Neuro checks | q4h × 24h if head strike + anticoag | GCS, pupil reactivity, focal deficits. Decline → repeat CT head STAT. |
| Repeat CT head | 24h post-fall if on warfarin + head strike | Delayed SDH can develop. Even if initial CT negative. |
| Vitals + orthostatics | Daily until resolved | Orthostatic hypotension → adjust meds, IVF. |
| Morse Fall Scale | Each shift | Reassess fall risk. Update care plan. |
| Incident report | Immediately | Document fall circumstances, injuries, interventions. Notify family. |
📋 On Rounds
Pimp Questions
Why is diphenhydramine (Benadryl) the worst PRN sleep medication for hospitalized elderly patients?
Diphenhydramine is a first-generation antihistamine with strong anticholinergic properties. In elderly patients, anticholinergics cause: (1) delirium (crosses BBB, blocks muscarinic receptors in CNS), (2) urinary retention (→ UTI, agitation from discomfort), (3) falls (sedation + orthostatic hypotension + impaired coordination), (4) constipation (→ more agitation). The anticholinergic burden is cumulative — it stacks with other anticholinergic meds the patient may be on (oxybutynin, cyclobenzaprine, promethazine). Better alternatives: melatonin 3–5 mg, trazodone 25–50 mg, or non-pharmacologic sleep hygiene (lights off, minimize vitals, earplugs).
What workup is mandatory after an inpatient fall in a patient on anticoagulation?
CT head without contrast — even if asymptomatic. Patients on anticoagulation (warfarin, DOACs, heparin) are at high risk for delayed intracranial hemorrhage, particularly subdural hematoma (SDH). SDH can present hours to days after a seemingly minor fall, and the patient may initially appear fine. If on warfarin, repeat CT head in 24 hours even if the initial CT is negative — delayed bleeds occur as INR fluctuates. Also check: INR if on warfarin, neuro exam (document GCS, pupils, focal deficits), orthostatic vitals, medication review for fall contributors, and injury assessment (hip X-ray if hip/groin pain).
What is the Beers Criteria and why does every intern need to know it?
AGS Beers Criteria is a list of potentially inappropriate medications (PIMs) in adults ≥ 65 that increase fall risk, delirium, bleeding, and other harms. Key categories: (1) Anticholinergics: diphenhydramine, hydroxyzine, oxybutynin, cyclobenzaprine → delirium + falls. (2) Benzodiazepines: all of them → oversedation, falls, hip fractures. (3) Non-benzo hypnotics: zolpidem → falls, complex sleep behaviors. (4) First-gen antipsychotics: haloperidol → QTc, falls, mortality in dementia. (5) NSAIDs: GI bleeding + AKI + HTN in elderly. (6) Sulfonylureas (long-acting): glimepiride, glyburide → prolonged hypoglycemia. On every admission, review the med list against Beers Criteria. Deprescribing is one of the highest-impact things an intern can do.
What medications most commonly contribute to falls in hospitalized patients?
The 'fall-risk' medication classes (overlaps heavily with Beers Criteria): (1) Benzodiazepines — sedation, impaired balance, cognitive slowing. Even short-acting (lorazepam) increases fall risk. (2) Opioids — sedation, orthostatic hypotension, cognitive impairment. (3) Antihypertensives — orthostatic hypotension (especially alpha-blockers, diuretics at night). (4) Anticholinergics — confusion, blurred vision, urinary retention → agitation. (5) Antipsychotics — sedation, orthostatic, QTc (and falls are WHY antipsychotics increase mortality in dementia patients). (6) Antihistamines (diphenhydramine) — sedation + anticholinergic. (7) SSRIs — hyponatremia (SIADH → AMS), AND SSRIs independently increase fall risk. Action: on every admission, review the med list for fall-risk meds. Deprescribe what you can. Convert nighttime diuretics to morning.
📣 Sample Presentation
One-Liner
"Mrs. Chen is an 85-year-old on apixaban who had an unwitnessed fall on the ward. She reports tripping on the IV tubing. No head strike per patient. Oriented, no focal deficits."
Key Points to Cover on Rounds
Unwitnessed fall on anticoagulation. No reported head strike but unwitnessed → CT head obtained (negative for acute intracranial hemorrhage). Neuro exam intact. Orthostatic vitals: positive (sitting→standing: 138/82→110/64). Medication review: amlodipine 10 mg (contributor to orthostatic hypotension) → reduced to 5 mg. Lorazepam 0.5 PRN sleep → discontinued. Foley removed (mobility barrier). PT evaluation: gait instability with walker. Plan: fall prevention bundle initiated, 24h repeat CT head (on apixaban), notify family, incident report filed.
⚡ Summary
Summary
Immediate
Assess for injury: CT head (if on anticoag or unwitnessed), C-spine if neck pain, hip XR if pain with weight-bearing. Neurovascular exam.
Medications
Beers Criteria review: stop/reduce benzos, anticholinergics, sedative hypnotics, antipsychotics, first-gen antihistamines. Minimize opioids.
Orthostatics
Supine → standing: SBP drop > 20 or DBP drop > 10 = positive. Cause: meds (antihypertensives, diuretics), dehydration, autonomic neuropathy.
Prevention Bundle
PT evaluation, assistive device, bed alarm, non-slip footwear, clear path to bathroom, toileting schedule, adequate lighting, hip protectors.
On Anticoag
CT head NOW + repeat at 24h (delayed intracranial hemorrhage). Consider reversal if significant ICH found. Low threshold for imaging.
Root Causes
Medications (#1 modifiable), orthostatic hypotension, delirium, visual impairment, gait/balance disorder, environmental hazards, polypharmacy.
📄 One Pager
INPATIENT FALL — AT A GLANCE
🔍 Assess: Injury survey, neuro exam, orthostatics, ECG
🧪 Labs: BMP (Na, glucose, Ca), CBC, INR if on warfarin
🧠 CT head: If head strike + anticoag → STAT + repeat 24h
💊 Meds: Deprescribe benzos, anticholinergics, opioids
🛏️ Prevent: Bed alarm, clear path, HELP protocol, PT/OT
📋 Document: Incident report, family notification
🧪 Labs: BMP (Na, glucose, Ca), CBC, INR if on warfarin
🧠 CT head: If head strike + anticoag → STAT + repeat 24h
💊 Meds: Deprescribe benzos, anticholinergics, opioids
🛏️ Prevent: Bed alarm, clear path, HELP protocol, PT/OT
📋 Document: Incident report, family notification
- Assess for injury: head strike → CT head (especially if on anticoagulation — delayed SDH). Hip pain → hip X-ray. Neuro exam.
- On anticoagulant + head strike: CT head STAT even if asymptomatic. Repeat in 24h if on warfarin (delayed bleed).
- Root cause: what was the patient doing? Medication-related? Orthostatic? Environmental (wet floor, cords)? Delirium? Seizure? Syncope?
- Incident report + family notification + attending notification + documentation
VTE Prophylaxis & Treatment
Every admitted patient needs a VTE risk assessment. Hospital-acquired VTE is the #1 preventable cause of inpatient death. Prophylaxis is easy — forgetting it is indefensible.
🛡️ Prophylaxis
Risk Stratification — Padua Score (Medical Patients)
| Risk Factor | Points |
|---|---|
| Active cancer | 3 |
| Prior VTE | 3 |
| Reduced mobility (≥ 3 days) | 3 |
| Known thrombophilia | 3 |
| Recent trauma/surgery (≤ 1 month) | 2 |
| Age ≥ 70 | 1 |
| Heart or respiratory failure | 1 |
| Acute MI or stroke | 1 |
| Acute infection or rheumatic disorder | 1 |
| Obesity (BMI ≥ 30) | 1 |
| Hormonal treatment | 1 |
Score ≥ 4: high risk → pharmacologic prophylaxis. < 4: low risk → early ambulation + SCDs.
Prophylaxis Regimens
| Setting | Regimen |
|---|---|
| Medical patients (Padua ≥ 4) | Enoxaparin (Lovenox) 40 mg SC daily or heparin 5000 units SC q8h. Fondaparinux 2.5 mg SC daily if HIT history. |
| Surgical — moderate/high risk | LMWH or UFH. Major orthopedic: extend prophylaxis to 35 days post-op ACCP, 2012. |
| CrCl < 30 | Heparin 5000 units SC q8h (LMWH accumulates in renal failure). Or adjust enoxaparin to 30 mg SC daily. |
| Active bleeding / high bleed risk | Mechanical only: SCDs (sequential compression devices). Remove when ambulatory. Start pharmacologic as soon as bleeding risk decreases. |
| Morbid obesity (BMI > 40) | Consider enoxaparin 40 mg SC BID (higher dose). Standard dosing may be subtherapeutic. |
💊 DVT/PE Treatment
Anticoagulation for VTE
| Agent | Dose | Notes |
|---|---|---|
| Rivaroxaban (Xarelto) PREFERRED | 15 mg BID × 21 days → 20 mg daily | EINSTEIN, 2010. No bridging needed. Take with food. Avoid CrCl < 30. |
| Apixaban (Eliquis) PREFERRED | 10 mg BID × 7 days → 5 mg BID | AMPLIFY, 2013. Lowest bleeding risk among DOACs. No bridging. OK in mild-moderate CKD. |
| Enoxaparin → warfarin | Enox 1 mg/kg SC BID + warfarin. Overlap ≥ 5 days AND INR ≥ 2 × 24h. | Traditional. Required for mechanical valves, APS, severe CKD. Target INR 2–3. |
| Cancer-associated VTE | LMWH (enoxaparin 1 mg/kg BID) or edoxaban / apixaban | CLOT, 2003 HOKUSAI-VTE Cancer, 2018: edoxaban non-inferior to LMWH. Avoid DOACs in GI/GU cancers (higher mucosal bleeding). Treat for ≥ 6 months or until cancer resolved. |
Duration: Provoked VTE (surgery, immobilization, OCP) → 3 months. Unprovoked VTE → 3–6 months then reassess for indefinite. Second unprovoked VTE → indefinite. Cancer-associated → until cancer resolved or indefinite.
📋 Clinical Example — DVT Workup & Treatment
- Patient: 42F on OCPs, presents with unilateral left leg swelling × 3 days, calf tenderness.
- Pre-test probability (Wells DVT): Active cancer (0), paralysis/recent cast (0), bedridden >3 days/surgery <12wk (0), tenderness along deep veins (+1), entire leg swollen (+1), calf >3cm vs other side (+1), pitting edema (+1), collateral superficial veins (+1), OCPs as alternative dx less likely (+0). Score: 5 → HIGH probability.
- Workup:
- Wells ≥2 (likely DVT) → Skip D-dimer → go straight to compression ultrasound.
- Wells <2 (unlikely) → D-dimer first. If negative → DVT excluded. If positive → ultrasound.
- US: non-compressible left common femoral and popliteal veins → proximal DVT confirmed.
- Treatment:
- Anticoagulation STAT (don't wait for results if high clinical suspicion): Apixaban (Eliquis) 10mg BID × 7 days → 5mg BID (AMPLIFY trial). OR rivaroxaban (Xarelto) 15mg BID × 21 days → 20mg daily.
- DOACs preferred over warfarin for most patients (no INR monitoring, fewer interactions, lower bleeding).
- Warfarin: Only if mechanical valve, antiphospholipid syndrome (RE-ALIGN — DOACs contraindicated), severe CKD (CrCl <15-25).
- Duration: Provoked (OCPs, surgery, travel) → 3 months, then reassess. Stop OCP. Unprovoked → ≥6 months, consider indefinite. Cancer-associated → LMWH or DOAC indefinitely while cancer active.
📋 On Rounds
Why is heparin preferred over LMWH in CrCl < 30?
LMWH (enoxaparin, dalteparin) is renally cleared. In severe renal impairment (CrCl < 30), LMWH accumulates → unpredictable anticoagulation → increased bleeding risk. UFH (unfractionated heparin) is cleared by the reticuloendothelial system (not kidneys) and has a short half-life (~60–90 min) → safer in renal failure and easier to reverse with protamine. For prophylaxis: heparin 5000 units SC q8h. For treatment: heparin drip titrated to aPTT. If you must use LMWH in CKD, use reduced dosing (enoxaparin 30 mg SC daily) and monitor anti-Xa levels.
When should you consider a thrombophilia workup after a first unprovoked DVT/PE?
Thrombophilia testing is NOT indicated during acute VTE (anticoagulation affects results — factor V Leiden is unaffected, but protein C, S, antithrombin are unreliable on warfarin/heparin, and lupus anticoagulant is unreliable on heparin/DOACs). Test after completing anticoagulation, if at all. When to test: unprovoked VTE at young age (< 50), recurrent unprovoked VTE, VTE at unusual sites (cerebral, splanchnic, upper extremity without catheter), strong family history, or recurrent pregnancy loss. The practical truth: testing rarely changes management — most patients with unprovoked VTE are already treated with extended anticoagulation regardless of thrombophilia status.
How do you decide between 3 months vs indefinite anticoagulation after a DVT/PE?
3 months: clearly provoked VTE (surgery within 3 months, immobilization, estrogen/OCP, long-haul flight, pregnancy). The provoking factor is resolved → low recurrence risk. Indefinite (extended): unprovoked VTE (no identifiable trigger — recurrence rate ~10%/year if you stop), cancer-associated VTE (continue until cancer resolved), recurrent VTE (2nd unprovoked event = essentially lifelong). Gray zone (shared decision-making): first unprovoked VTE with low bleeding risk — benefit of continued anticoagulation likely outweighs risk. Use D-dimer at 1 month after stopping: if elevated → resume anticoag (PROLONG study). For extended therapy, apixaban 2.5 mg BID or rivaroxaban 10 mg daily (reduced doses) are options that lower bleeding risk while maintaining efficacy [AMPLIFY-EXT, 2013.
What score do you use to decide if a patient needs a CT angiogram for PE?
Wells Score for PE: Clinical signs of DVT (+3), PE most likely diagnosis (+3), HR > 100 (+1.5), immobilization/surgery in past 4 weeks (+1.5), prior DVT/PE (+1.5), hemoptysis (+1), active cancer (+1). Score ≤ 4 (unlikely): check D-dimer. If D-dimer negative → PE ruled out (high NPV). If D-dimer positive → CTPA. Score > 4 (likely): go straight to CTPA (don't waste time on D-dimer). PERC rule (for very low suspicion in ED): if all 8 criteria negative (age < 50, HR < 100, SpO₂ > 94%, no hemoptysis, no estrogen, no prior DVT/PE, no leg swelling, no recent surgery) → PE essentially ruled out without any testing. Key: don't order D-dimer without first applying a clinical decision rule.
📣 Sample Presentation
One-Liner
"Ms. Martinez is a 38-year-old who developed acute left leg swelling and pain 5 days post-cesarean section. Compression US confirms acute DVT in left common femoral and popliteal veins."
Key Points to Cover on Rounds
Provoked proximal DVT (post-surgical). Started enoxaparin 1 mg/kg BID, transitioning to rivaroxaban 15 mg BID × 21 days then 20 mg daily. Duration: 3 months (clearly provoked by surgery). Bilateral LE evaluated — right leg normal. No PE symptoms (no dyspnea, no chest pain, SpO₂ 99%). Compression stockings deferred acutely (pain). Thrombophilia workup NOT indicated (clearly provoked). Plan: ambulate as tolerated, rivaroxaban 3-month course, OB follow-up for contraception planning (avoid estrogen).
💊 Medications
Key Medications — VTE / DVT Treatment
| Drug (Brand) | Dose | Route | Key Points |
|---|---|---|---|
| DOACs (PREFERRED for most patients — no bridging needed) | |||
| Apixaban (Eliquis) LOWEST BLEED RISK | 10 mg BID x 7 days → 5 mg BID | PO | Lowest bleeding risk among DOACs AMPLIFY, 2013. No bridging. OK in mild-moderate CKD. Avoid CrCl < 25. |
| Rivaroxaban (Xarelto) | 15 mg BID x 21 days → 20 mg daily with food | PO | EINSTEIN, 2010. Must take with food (absorption). No bridging. Avoid CrCl < 30. |
| PARENTERAL ANTICOAGULATION | |||
| Heparin drip (UFH) | 80 u/kg bolus → 18 u/kg/hr | IV | Target aPTT 60–80 sec. Use in: severe CKD, high bleed risk (short half-life, reversible with protamine), before procedures, massive PE. |
| Enoxaparin (Lovenox) | 1 mg/kg SQ q12h | SQ | LMWH — bridge to warfarin or definitive treatment. Avoid in CrCl < 30 (accumulates). Anti-Xa monitoring in obesity and renal insufficiency. |
| WARFARIN (specific indications only) | |||
| Warfarin (Coumadin) | Adjust to target INR 2–3 | PO | Bridge with heparin x 5 days AND until INR ≥ 2 for 24h. Required for: APS (DOACs contraindicated), mechanical valves, severe CKD (CrCl < 15–25). |
Duration: Provoked VTE (surgery, immobilization, OCP) → 3 months. Unprovoked → 3–6 months then reassess for indefinite. Second unprovoked → indefinite. Cancer → until cancer resolved. Extended therapy: apixaban 2.5 mg BID or rivaroxaban 10 mg daily.
📈 Monitoring
Monitoring Parameters — VTE / DVT
| Parameter | Frequency | Target / Action |
|---|---|---|
| aPTT (heparin drip) | q6h until stable, then q12h | Target aPTT 60–80 sec (or per institutional protocol). Adjust infusion rate per nomogram. |
| INR (warfarin) | Daily while inpatient, then weekly → monthly when stable | Target INR 2.0–3.0. Bridge with heparin x 5 days AND until INR ≥ 2 for 24h before stopping heparin. |
| Platelets (HIT surveillance) | q2–3 days on heparin (days 4–14) | HIT: > 50% drop from baseline or platelets < 150K on heparin → check HIT antibody (PF4/heparin). 4T score to assess probability. If HIT → stop all heparin, start argatroban or bivalirudin. |
| Creatinine (DOAC dosing) | Baseline and periodically | CrCl determines DOAC eligibility: apixaban (avoid < 25), rivaroxaban (avoid < 30). Declining renal function → may need to switch to warfarin. |
| Bleeding symptoms | Each assessment | GI bleeding (melena, hematochezia), hematuria, gum bleeding, easy bruising, menorrhagia. Any major bleed → hold anticoagulation, assess need for reversal. |
| Recurrent VTE symptoms | Each assessment + patient education | New leg swelling/pain → repeat ultrasound. New dyspnea/chest pain → CTPA. Recurrence on anticoagulation → consider non-compliance, cancer workup, APS testing. |
HIT surveillance is critical on heparin. Check platelets baseline, then q2–3 days from days 4–14. A > 50% drop is the trigger — not an absolute threshold. Use the 4T score before sending the expensive PF4 antibody.
⚡ Summary
Summary
Wells Score PE
DVT signs (+3), PE most likely (+3), HR > 100 (+1.5), immobilized/surgery (+1.5), prior DVT/PE (+1.5), hemoptysis (+1), cancer (+1).
Duration
Provoked: 3 months. Unprovoked first episode: consider indefinite (shared decision). Cancer: continue until resolved. Recurrent: lifelong.
DOAC Preferred
Apixaban 10 BID × 7 days → 5 BID, or rivaroxaban 15 BID × 21 days → 20 daily. No bridging needed. Warfarin only for APS or mechanical valve.
Extended Therapy
Reduced-dose after initial treatment: apixaban 2.5 BID or rivaroxaban 10 daily [AMPLIFY-EXT, EINSTEIN-CHOICE]. Lower bleeding, maintained efficacy.
Cancer-Associated
DOAC preferred over warfarin [HOKUSAI-VTE Cancer, SELECT-D]. Exception: GI/GU malignancy → higher GI bleed with DOACs, consider LMWH.
Thrombophilia Testing
NOT routine. Consider in: unprovoked VTE < 50, recurrent VTE, strong FH, unusual location (cerebral, splanchnic). Don't test during acute event or on anticoag.
📄 One Pager
VTE Prophylaxis & Treatment — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
VTE PROPHYLAXIS & TREATMENT — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup
Workup — VTE Prophylaxis & Treatment
Workup checklist: Compression US (proximal DVT: sensitivity > 95%). CTPA for PE. Wells score to determine pre-test probability. D-dimer: only useful if Wells score is low/unlikely — if negative, rules out PE/DVT. If positive, proceed to imaging. CBC, BMP, PT/INR (baseline before anticoag). Consider: echo (RV strain in PE), troponin + BNP (submassive PE risk stratification).
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
⚡ Management
Management — VTE Prophylaxis & Treatment
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
📄 One Pager
Hematology · One Pager
VTE — DVT & PE
Wells score guides testing. DOAC preferred. 3 months if provoked. Indefinite if unprovoked. Cancer-associated: DOAC (except GI/GU malignancy → consider LMWH).
Diagnosis
DVT: compression US (sensitivity > 95%). PE: Wells → D-dimer or CTPA. VQ scan if contrast allergy or CKD. PERC rule for very low-risk in ED.
Treatment
DOAC preferred: apixaban 10 BID × 7d → 5 BID, or rivaroxaban 15 BID × 21d → 20 daily. No bridging needed. Warfarin only for APS or mechanical valve.
Duration
Provoked (surgery, immobilization, estrogen): 3 months. Unprovoked: consider indefinite (shared decision — check D-dimer at 1 month off therapy). Cancer: continue until resolved. Recurrent: lifelong.
Key Drugs
Apixaban10 BID × 7d → 5 BID
Rivaroxaban15 BID × 21d → 20 daily
Enoxaparin1 mg/kg BID (cancer/bridge)
WarfarinTarget INR 2-3 (APS only)
Pitfalls
- D-dimer without clinical decision rule
- Thrombophilia testing during acute VTE or on anticoag
- DOACs in APS (contraindicated [TRAPS])
- Not considering outpatient PE treatment for low-risk (sPESI 0)
Discharge Planning Checklist
A safe discharge prevents readmission. Medication reconciliation, follow-up, patient education, and safety-net instructions are the four pillars. Readmission within 30 days is often a failure of discharge, not disease.
✅ Discharge Checklist
Before Writing the Discharge Order
- Medication reconciliation — compare admission meds vs discharge meds. What was added? Changed? Stopped? Does the patient understand each change and why?
- Labs pending? — do NOT discharge with critical pending results (blood cultures, pathology). If minor labs pending → ensure follow-up plan for results.
- Follow-up appointments — PCP within 7–14 days for all discharges. Specialist follow-up as needed (cardiology post-ACS, surgery post-op, oncology). High-risk patients: follow-up within 48–72h.
- Discharge medications prescribed + sent to pharmacy. Verify the patient can afford them. Prior authorizations done? Assistance programs if needed.
- Patient education — diagnosis explained in plain language. Red flags to return to ED. Medication side effects. Activity restrictions. Diet changes (low-sodium for HF, renal diet for CKD).
- Durable medical equipment — O₂ arranged? CPAP? Walker/wheelchair? Home health nursing?
- Social work / care coordination — safe living situation? Capable of ADLs? Need rehab (SNF, acute rehab, LTAC)? Substance use resources? Mental health follow-up?
- VTE prophylaxis post-discharge — does the patient need extended prophylaxis (post-major orthopedic surgery × 35 days, post-cancer surgery)?
- Discharge summary completed — timely, sent to PCP. Include: admission diagnosis, hospital course, key results, discharge meds (with changes highlighted), pending results, follow-up plan, and code status discussion if applicable.
High-Risk Discharges (30-Day Readmission Risk)
| Condition | Key Discharge Interventions |
|---|---|
| Heart Failure | Daily weights at home. Fluid restrict 1.5–2 L/day. Low-sodium diet. Follow-up within 7 days. Action plan: "If weight ↑ 3 lbs in 2 days → call clinic / double Lasix." |
| COPD | Inhaler technique reviewed (observed return demonstration). Action plan. Smoking cessation. Pulmonary rehab referral. Prednisone taper if applicable. |
| Pneumonia | Complete antibiotic course. CXR follow-up in 6–8 weeks (to ensure resolution, rule out underlying mass). Smoking cessation. |
| ACS | DAPT education (do NOT stop without cardiology approval). Cardiac rehab referral. Statin, BB, ACEi. Nitroglycerin SL PRN prescription + instruction. Follow-up within 2 weeks. |
🧪 Workup
Pre-Discharge Checklist
| Domain | Before Discharge |
|---|---|
| Clinical stability | Afebrile ≥ 24h, improving trajectory, tolerating PO, ambulatory (or at baseline), stable vitals off telemetry |
| Pending results | Blood cultures, biopsy, imaging reads, consult recs — assign follow-up responsibility for each. Document who will call patient. |
| Medication reconciliation | Compare admission meds → current → discharge. Mark: NEW / CHANGED / STOPPED. Verify patient can access + afford meds. |
| Follow-up arranged | PCP within 7 days (48–72h if high-risk). Specialist follow-up with date. Labs with specific date and location. |
| Transitions of care | Discharge summary sent to PCP SAME DAY. Include: diagnosis, hospital course, pending results, medication changes, follow-up plan. |
⚡ Management
High-Risk Discharge Situations
| Situation | Risk | Mitigation |
|---|---|---|
| New anticoagulation | Bleeding, missed doses, drug interactions | Teach signs of bleeding, drug-food interactions (warfarin), ensure INR follow-up if warfarin |
| New insulin | Hypoglycemia, dosing errors | Teach-back injection technique, glucose monitoring, hypo treatment. Diabetes educator consult. |
| Heart failure | 30-day readmission (25%) | Daily weights, sodium restriction, diuretic adjustment plan, 48–72h follow-up, call if gain > 3 lbs/2 days |
| COPD exacerbation | Readmission, ongoing steroid needs | Ensure inhaler technique (observed), prednisone taper written, pulmonary rehab referral, quit smoking |
| AMA discharge | Poor outcomes, medicolegal risk | Document capacity assessment, risks explained, medications offered, follow-up arranged despite AMA. Patients retain right to receive discharge meds and instructions. |
I-PASS Sign-Out Format
| Letter | Meaning | Example |
|---|---|---|
| I | Illness severity | "Stable" / "Watcher" / "Unstable" |
| P | Patient summary | "72M with COPD exacerbation, day 3 of prednisone, on 2L NC" |
| A | Action list | "Repeat BMP at 6 AM for K⁺ recheck. Call if below 3.5." |
| S | Situation awareness | "May need BiPAP if RR > 30 or SpO₂ < 88%. Has been borderline." |
| S | Synthesis by receiver | Receiving team reads back key action items and contingency plans. |
I-PASS reduced medical errors by 23% and preventable adverse events by 30% in a multicenter study I-PASS Study, 2014.
💊 Medications
Medication Reconciliation — The #1 Safety Issue
~50% of patients have ≥ 1 medication discrepancy at discharge. The three most dangerous: (1) restarting a med that was intentionally held, (2) not starting a new med that was added, (3) duplicate therapy.
| Step | Action |
|---|---|
| 1. Compare lists | Home meds → inpatient meds → discharge meds. Use pharmacy reconciliation if available. |
| 2. Mark changes | Flag: * = NEW, Δ = CHANGED dose/frequency, ✕ = STOPPED. Explain WHY for each change. |
| 3. Teach-back | Review each changed med with patient. "Tell me how you'll take this at home." Low health literacy = use plain language. |
| 4. Access check | Can patient afford meds? Has pharmacy? Need prior auth? Provide 30-day bridge if insurance gap. |
📈 Monitoring
Pre-Discharge Checklist — Discharge Planning
| Domain | Checklist Item | Action / Details |
|---|---|---|
| Medication reconciliation | Complete and reviewed at bedside | Compare admission → discharge meds. Mark NEW / CHANGED / STOPPED. Ensure patient understands each change and why. Verify meds are affordable and filled. |
| Follow-up appointments | Scheduled before discharge | PCP within 7–14 days (48–72h if high-risk: HF, ACS, COPD). Specialist follow-up as needed with date and location confirmed. Patient has written appointment details. |
| Patient education | Red flags and return precautions | Disease-specific return precautions explained in plain language. Teach-back method: patient explains warning signs in their own words. Written instructions provided. |
| Discharge summary | Completed and sent to PCP | Sent same day. Include: admission diagnosis, hospital course, key results, medication changes with rationale, pending results, follow-up plan, code status. |
| Pending labs/results | Responsible provider assigned | Every pending result (blood cultures, pathology, imaging reads) must have a named provider responsible for follow-up. Document who will contact the patient. |
| VTE prophylaxis | Post-discharge plan if applicable | Extended prophylaxis for: post-major orthopedic surgery (35 days), post-cancer surgery (28 days). Ensure prescription and patient education on injection technique if applicable. |
| Code status | Confirmed and documented | Especially for patients with serious illness, recurrent admissions, or goals-of-care discussions during hospitalization. Ensure advance directive is in the chart. |
Post-Discharge Monitoring Plan
| Timeframe | Action |
|---|---|
| 24–48 hours | Post-discharge phone call (nursing or pharmacy). Confirm: meds filled, understanding discharge instructions, no new symptoms. |
| 48–72 hours | High-risk follow-up: HF (weight, diuretic response), AKI (Cr recheck), new anticoag (INR if warfarin), new insulin (glucose log). |
| 7 days | PCP follow-up for most patients. Review hospital course, pending results, medication changes. |
| 30 days | Specialist follow-up. Labs (Cr, CBC, LFTs as indicated). Functional status assessment. |
Readmission within 30 days is often a failure of discharge, not disease. The most impactful interventions: medication reconciliation at bedside (not just on paper), confirmed follow-up appointment (not just "follow up with PCP"), and post-discharge phone call within 48h.
⚡ Summary
Summary
I-PASS Handoff
Illness severity → Patient summary → Action list → Situation awareness → Synthesis by receiver. Reduces errors by 30% [I-PASS Study, 2014].
Med Reconciliation
At bedside: review every med (new, changed, stopped). Teach-back: patient explains each med. Ensure meds in hand, not just prescriptions.
Follow-Up
PCP within 7 days for most. Within 48-72h for HF. Specialists as needed. Ensure patient has appointment BEFORE discharge.
Red Flags
Written instructions with specific return precautions: fever, worsening symptoms, new symptoms, unable to take meds, unable to eat/drink.
Readmission Prevention
Phone call within 48h post-discharge. Medication adherence check. Confirm follow-up appointments. Address social barriers (transport, cost).
Transitions of Care
Discharge summary to PCP same day. Include: diagnosis, hospital course, pending results, follow-up needs, medication changes with rationale.
📄 One Pager
SAFE DISCHARGE — AT A GLANCE
💊 Med rec: Compare lists → mark NEW/CHANGED/STOPPED → teach-back → access check
📋 Pending: Assign owner for every pending result
📅 Follow-up: PCP 7d (48–72h if high-risk). Specialist with date. Labs with date + location.
📄 Summary: To PCP same day — diagnosis, course, meds, pending, plan
🚨 Red flags: Specific symptoms to return for (not generic)
📞 Phone call: 24–48h post-discharge to verify meds filled + understanding
📋 Pending: Assign owner for every pending result
📅 Follow-up: PCP 7d (48–72h if high-risk). Specialist with date. Labs with date + location.
📄 Summary: To PCP same day — diagnosis, course, meds, pending, plan
🚨 Red flags: Specific symptoms to return for (not generic)
📞 Phone call: 24–48h post-discharge to verify meds filled + understanding
🔍 Overview
Overview
~20% of patients have adverse events within 3 weeks of discharge. ~40% involve medication errors. I-PASS handoff, bedside med reconciliation, teach-back, and 48h phone calls reduce readmissions.
📋 On Rounds
Pimp Questions
What is the single most commonly missed item on a discharge that leads to readmission?
Medication reconciliation — specifically, not communicating medication changes to the patient and PCP. Studies show that ~50% of patients have at least one medication discrepancy at discharge. The most dangerous errors: (1) restarting a medication that was intentionally stopped (e.g., metformin held for AKI, ACEi held for hyperkalemia), (2) not starting a new medication that was added (e.g., DAPT after stent, anticoagulation after new AFib), (3) duplicate therapy (home med + new inpatient med for same indication). Best practice: go through every medication with the patient at bedside, explain what changed and why, and ensure the discharge summary clearly marks NEW / CHANGED / STOPPED medications for the PCP.
When should follow-up be within 48–72 hours vs 7–14 days after discharge?
48–72 hour follow-up is indicated for high-risk discharges: heart failure (weight monitoring, diuretic adjustment), COPD exacerbation (inhaler reassessment), AKI (Cr recheck), medication changes requiring monitoring (new anticoagulation, new insulin), patients with limited health literacy or social support, and any patient you're worried about. 7–14 day follow-up is acceptable for: stable chronic disease, uncomplicated infections completing antibiotics, straightforward surgical follow-up. The key principle: the sicker or more complex the patient, the sooner the follow-up. A 30-day readmission is often a failure of the 7-day post-discharge window.
What is the I-PASS framework and why does it reduce medical errors?
I-PASS is a standardized handoff mnemonic that reduced medical errors by 30% in a multicenter study [I-PASS Study, 2014. I = Illness severity (stable, watcher, unstable). P = Patient summary (one-liner: age, sex, diagnosis, key hospital course). A = Action list (what needs to be done overnight — labs to check, meds to give, pending results). S = Situation awareness ("if X happens, then do Y" — anticipatory guidance). S = Synthesis (receiver reads back key action items). The most commonly skipped part: Situation awareness — this is where you say "this patient might decompensate because ___" and give the covering team a specific plan.
What are the most common causes of 30-day readmission and how do you prevent them?
The top 3: (1) Heart failure (highest readmission rate ~25%) — prevent with: weight monitoring daily at home, clear diuretic instructions ("if weight up 3 lbs in 1 day, take extra Lasix"), follow-up within 48-72h, dietary counseling (2g Na restriction). (2) COPD — prevent with: proper inhaler technique verified at discharge, action plan for exacerbations, pulm rehab referral, 5-7 day follow-up. (3) Pneumonia/infections — prevent with: complete antibiotic course, clear return precautions ("return if fever > 101, worsening dyspnea, unable to keep meds down"). Universal prevention: medication reconciliation at bedside, teach-back method ("tell me in your own words what each med is for"), post-discharge phone call within 48h, ensure patient has medications in hand (not just prescriptions — many don't fill them).
📣 Sample Presentation
One-Liner
"Mrs. Baker is a 74-year-old admitted 4 days ago for COPD exacerbation, now back to baseline on home O₂ (2L), tolerating PO steroids, and able to ambulate. Ready for discharge."
Key Points to Cover on Rounds
Discharge medications reviewed at bedside: * NEW: prednisone 40 mg PO daily × 3 more days (5-day course total), * NEW: azithromycin 250 mg daily × 2 more days, * CHANGED: added Breo Ellipta 200/25 daily (was not on ICS/LABA before). Home meds continued: tiotropium, albuterol PRN, lisinopril, atorvastatin. Follow-up: PCP in 5 days, pulmonology in 2 weeks. Smoking cessation: quit 2 years ago — reinforced. Pulm rehab referral sent. Patient taught proper inhaler technique (observed return demo). Red flags reviewed: return if worsening dyspnea, fever, or unable to complete steroid taper.
📄 One Pager
Transitions of Care · One Pager
Safe Discharge
I-PASS handoff. Med reconciliation at bedside. Teach-back method. Follow-up within 7 days. Phone call at 48h. Red flag instructions in writing.
I-PASS
Illness severity → Patient summary → Action list → Situation awareness ("if X, then Y") → Synthesis by receiver. Reduces errors 30% [I-PASS Study, 2014].
Medication Safety
Reconcile at bedside: every med reviewed (new, changed, stopped + reason). Teach-back: patient explains each med. Ensure meds IN HAND (not just prescriptions).
Prevent Readmission
Phone call within 48h. Follow-up within 7d (48-72h for HF). Specific return precautions in writing. Address social barriers: transport, cost, health literacy.
Key Drugs
EnsurePatient has medications in hand
ReconcileEvery med — new, changed, stopped
Follow-upPCP within 7d, HF within 48-72h
CallPost-discharge phone call at 48h
Pitfalls
- Med reconciliation by chart review only (must be at bedside with patient)
- Discharge summary not sent to PCP same day
- No specific return precautions given
- Pending results not handed off to outpatient provider
Rotation
General Wards
The bread and butter of internal medicine. Common inpatient diagnoses, admission workups, discharge planning, and transitions of care.
Available Topics
VTE Prophylaxis & Treatment
Discharge Planning Checklist
Admission Orders & I-PASS
Anemia Workup
Cellulitis & Skin Infections
Falls & Delirium Prevention
VTE Prophylaxis
Delirium
Discharge Planning & Transitions
Perioperative Medicine
Inpatient Diabetes Management
📋 Major Guidelines
DIC
Pathologic activation of coagulation → widespread microvascular thrombosis → consumption of factors and platelets → paradoxical bleeding. Never primary — always find and treat the trigger.
🔍 Overview
Lab Pattern
| Lab | Finding | Why |
|---|---|---|
| Platelets | ↓↓ | Consumed in microthrombi ISTH DIC Score, Taylor 2001 |
| Fibrinogen | ↓ (< 100 = severe) | Consumed. Most specific for DIC severity. |
| PT/INR, aPTT | ↑ | Clotting factors consumed |
| D-dimer | ↑↑↑ | Massive fibrinolysis |
| Smear | Schistocytes | RBCs sheared through fibrin strands |
Common Triggers
- Sepsis (~35% — most common)
- Trauma / major surgery
- Malignancy — APL, mucin-secreting adenocarcinomas (pancreas, prostate)
- Obstetric — placental abruption, amniotic fluid embolism, HELLP
- Massive transfusion, large aortic aneurysm, envenomation
🚨 Management
#1: Treat the underlying cause. DIC will not resolve until the trigger is removed. JAAM DIC Criteria, Gando 2006
| Component | Replacement | Target |
|---|---|---|
| Fibrinogen | Cryoprecipitate 10 units | > 100–150 mg/dL. Most critical to replace. ISTH DIC Guidelines, Levi 2009 |
| Platelets | Platelet transfusion | > 50K if bleeding; > 10K if not |
| Factors | FFP 15 mL/kg | INR < 1.5 if bleeding |
| RBCs | pRBCs | Hgb > 7 (or > 8 if active bleed) |
💊 Medications
Key Medications — Disseminated Intravascular Coagulation
Treat the underlying cause. DIC is ALWAYS secondary — sepsis, malignancy, obstetric emergency, trauma. Transfusion supports hemostasis but does not fix the driver.
| Product | Indication | Dose | Target |
|---|---|---|---|
| Platelets | Plt <10K (any) or <50K with active bleeding | 1 apheresis unit or 6-pack | Plt >50K if bleeding, >10K if stable |
| Cryoprecipitate | Fibrinogen <100-150 mg/dL | 10 units (pools) | Fibrinogen >150 mg/dL. Each pool raises fibrinogen ~50 mg/dL. |
| FFP | PT/aPTT >1.5× normal WITH active bleeding | 15 mL/kg (typically 4 units) | INR <1.5. Replaces all clotting factors. |
| pRBCs | Hgb <7 (or <8 if active hemorrhage) | Per transfusion protocol | Hemodynamic stability, adequate oxygen delivery. |
| Heparin SELECT CASES | Chronic/compensated DIC with thrombosis predominance | Low-dose UFH or prophylactic LMWH | Only when thrombosis outweighs bleeding risk (e.g., Trousseau syndrome, purpura fulminans). Contraindicated in acute DIC with active hemorrhage. |
| Tranexamic acid | Hyperfibrinolysis-predominant DIC | 1g IV load then 1g over 8h | Consider in APL-associated DIC or trauma. Use with caution — can worsen microvascular thrombosis. |
Do NOT transfuse to normalize labs. Transfuse ONLY if actively bleeding or at high risk of bleeding (pre-procedure). Prophylactic transfusion in stable DIC is not indicated and wastes blood products.
📈 Monitoring
Monitoring Parameters — Disseminated Intravascular Coagulation
| Parameter | Frequency | Target / Action |
|---|---|---|
| CBC (platelets, Hgb) | q6-8h in acute DIC | Platelet trend (rising = improving). Hgb drop = ongoing hemorrhage or hemolysis. Check smear for schistocytes. |
| Fibrinogen | q6-8h in acute DIC | Target >150 mg/dL. Most specific lab for DIC severity. Replete with cryoprecipitate if <100-150. |
| PT/INR, aPTT | q6-8h in acute DIC | Trend toward normalization. Prolonged + bleeding → FFP. Improving PT/fibrinogen = resolving DIC. |
| D-dimer | q6-12h | Massively elevated in DIC. Trending down = resolving. Not specific — use in context of ISTH score. |
| ISTH DIC score | Daily recalculation | ≥5 = overt DIC. Track serial scores — declining score confirms resolution. Components: platelets, D-dimer, PT, fibrinogen. |
| Clinical bleeding assessment | q2-4h | IV sites, surgical sites, mucosal bleeding, petechiae, hematuria, GI bleeding. Simultaneous bleeding AND thrombosis is pathognomonic. |
| Thrombotic complications | Each assessment | Skin necrosis (purpura fulminans), acral ischemia, organ dysfunction (renal, hepatic). DVT/PE screening if clinical concern. |
📋 On Rounds
How does DIC differ from TTP on labs?
Both: thrombocytopenia + schistocytes. DIC = ↑ PT/INR, ↑ aPTT, ↓ fibrinogen, ↑↑ D-dimer (consumptive coagulopathy). TTP = PT/INR and aPTT are NORMAL, fibrinogen is NORMAL. TTP is platelet consumption only — the coagulation cascade is not activated. If coags are deranged → DIC. If coags are normal → TTP/HUS.
How do you differentiate DIC from TTP? Both have MAHA + thrombocytopenia.
DIC = prolonged PT/INR + low fibrinogen + very high D-dimer. The coagulation cascade is consumed → bleeding predominates. TTP = normal PT/INR + normal fibrinogen + ADAMTS13 < 10%. The problem is platelet microthrombi, not coagulation factor consumption. The key lab: fibrinogen. Low fibrinogen = DIC. Normal fibrinogen = think TTP (or HUS). This distinction is critical because platelet transfusion is treatment in DIC (if bleeding) but contraindicated in TTP (fuels thrombosis). Send ADAMTS13 before starting PLEX, but don't wait for the result — if TTP is suspected clinically, start PLEX immediately.
What lab value is the most specific for DIC, and why?
Fibrinogen is the most specific and clinically actionable lab. In DIC, the coagulation cascade is massively activated → clotting factors AND fibrinogen are consumed. Low fibrinogen (< 100-150 mg/dL) is highly specific for DIC — it differentiates DIC from other causes of thrombocytopenia + coagulopathy (TTP has normal fibrinogen, liver disease has low fibrinogen but less severely, heparin-induced doesn't affect fibrinogen). D-dimer is very sensitive but not specific — elevated in DIC, PE, DVT, post-op, sepsis, cancer. Treatment guided by fibrinogen: if < 100 → give cryoprecipitate (each unit raises fibrinogen ~5-10 mg/dL; give 10 units). Recheck q4-6h. Don't just check PT/INR — fibrinogen is the key lab to trend in DIC.
How do you differentiate DIC from severe liver disease?
Both have elevated PT/INR, low platelets, and low fibrinogen — making differentiation challenging. Key differentiators: (1) D-dimer: massively elevated in DIC (> 10× ULN), only mildly elevated in liver disease. (2) Factor VIII: LOW in DIC (consumed like all factors), ELEVATED in liver disease (factor VIII is made by endothelium, not hepatocytes — actually increases in liver disease as an acute phase reactant). This is the single best lab to differentiate them. (3) Schistocytes: present in DIC (microangiopathic hemolysis), absent in pure liver disease. (4) Clinical trajectory: DIC worsens rapidly with the underlying trigger (sepsis, malignancy); liver disease coagulopathy is typically chronic and stable. (5) Fibrinogen trend: falling rapidly in DIC; chronically low but stable in liver disease.
📣 Sample Presentation
One-Liner
"Mr. Ahmed is a 62-year-old with septic shock from cholangitis who developed diffuse oozing from line sites, petechiae, and hematuria. Platelets 32K, INR 2.8, fibrinogen 68, D-dimer >20,000. Consistent with acute DIC."
Key Points to Cover on Rounds
DIC secondary to sepsis (cholangitis — source controlled with ERCP yesterday). Labs: plt 32K, INR 2.8, fibrinogen 68 (<100 → cryoprecipitate 10 units given), D-dimer >20K. Actively bleeding from lines. Treatment: (1) treat underlying cause (antibiotics day 3, source controlled), (2) cryoprecipitate for fibrinogen <100, (3) platelets transfused (plt <50 + active bleeding), (4) FFP 4 units for INR 2.8 + active bleeding. NOT giving heparin (bleeding-predominant DIC). Plan: trend fibrinogen, plt, INR q6h, continue treating sepsis.
⚡ Summary
Summary
Diagnosis
Thrombocytopenia + prolonged PT/INR + low fibrinogen + elevated D-dimer + schistocytes. ISTH DIC score ≥ 5 = overt DIC.
Key Lab
Fibrinogen is the most specific and actionable. < 100 → cryoprecipitate (10 units). Factor VIII: LOW in DIC, ELEVATED in liver disease (best differentiator).
Treatment
Treat the underlying cause (sepsis, malignancy, obstetric emergency). Transfuse: cryo for fibrinogen < 100, platelets if < 50 + bleeding, FFP for INR + active bleeding.
Do NOT Give
Heparin in acute DIC with active bleeding (controversial — only for DIC with dominant thrombotic features, e.g., purpura fulminans).
Causes
Sepsis (#1), trauma, malignancy (APL, mucin-secreting cancers), obstetric (placental abruption, amniotic fluid embolism, HELLP), transfusion reaction.
Monitor
Fibrinogen, plt, PT/INR, D-dimer q4-6h until stable. Trend is more important than absolute values.
📄 One Pager
Disseminated Intravascular Coagulation (DIC) — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
DISSEMINATED INTRAVASCULAR COAGULATION (DIC) — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup
Workup
- CBC + smear — thrombocytopenia + schistocytes
- PT/INR, aPTT — prolonged
- Fibrinogen — most specific. Cryo if <100.
- D-dimer — markedly elevated
- Factor VIII — LOW in DIC, HIGH in liver disease
- ISTH DIC score ≥5
TTP / HUS
Thrombotic microangiopathies — ADAMTS13 deficiency (TTP) or complement-mediated (aHUS). Thrombocytopenia + MAHA + organ damage with NORMAL coags. Untreated TTP mortality > 90%. Plasma exchange saves lives. Never transfuse platelets.
🔍 Overview
TTP vs HUS
| Feature | TTP | Typical HUS | Atypical HUS | |||
|---|---|---|---|---|---|---|
| Mechanism | ADAMTS13 < 10% → ultra-large vWF → platelet aggregation | Shiga toxin (E. coli O157:H7) | Complement dysregulation | |||
| Key features | Neuro predominant (confusion, seizures) | Renal failure + bloody diarrhea (children) | Renal failure | |||
| Coags | NORMAL (PT, aPTT, fibrinogen all normal) | Normal | Normal | |||
| Treatment | Plasma exchange + steroids + caplacizumab | Supportive (abx CONTRAINDICATED) | Eculizumab (anti-C5) | |||
| Criterion | 1 Point Each |
|---|---|
| P | Platelet < 30,000 |
| L | Hemolysis (retic > 2.5%, hapto undetectable, or indirect bili > 2) |
| A | No active cancer |
| S | No stem cell/organ transplant |
| M | MCV < 90 |
| I | INR < 1.5 |
| C | Creatinine < 2.0 |
≥ 5: high probability → start plasma exchange. Don't wait for ADAMTS13 results.
🚨 Management
Plasma exchange
Daily TPE until platelets > 150K × 2 days. Removes antibodies + ultra-large vWF, replaces ADAMTS13. FFP as bridge if TPE delayed.
Steroids
Methylprednisolone 1g IV × 3 days → prednisone 1 mg/kg. Rituximab if refractory/relapsing.
Caplacizumab
Anti-vWF nanobody. HERCULES, 2019: 74% reduction in death + recurrence. Now standard alongside TPE + steroids.
NEVER transfuse platelets in TTP
🧪 Workup
Workup
- CBC + peripheral smear — severe thrombocytopenia (often < 30K) + schistocytes. Schistocytes are REQUIRED for diagnosis.
- ADAMTS13 activity level — send immediately but do NOT wait for results to start PLEX. ADAMTS13 < 10% = TTP. Takes 2-5 days to result. [ADAMTS13 Discovery Study, 2004]
- PLASMIC score — 7-variable clinical prediction score. Score 6-7 = high probability of ADAMTS13 < 10% → start PLEX empirically. Components: platelet count < 30K, hemolysis (retic > 2.5%, haptoglobin undetectable, indirect bili > 2), no active cancer, no transplant, MCV < 90, INR < 1.5, Cr < 2. [PLASMIC Score Derivation, 2017]
- LDH — markedly elevated (often > 1000). Trends with disease activity — single best marker to follow during treatment.
- Haptoglobin — undetectable (consumed by free hemoglobin binding)
- Reticulocyte count — elevated (bone marrow compensating for hemolysis)
- Indirect bilirubin — elevated (hemolysis)
- Fibrinogen — NORMAL in TTP. This is the key differentiator from DIC (where fibrinogen is low). If fibrinogen is low, reconsider DIC.
- Direct Coombs (DAT) — negative. Rules out autoimmune hemolytic anemia.
- Cr — mild elevation typical. If Cr markedly elevated (> 3), consider HUS over TTP (renal-dominant TMA).
- Coags (PT/INR) — should be normal. If elevated → think DIC, not TTP.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Therapeutic plasma exchange (PLEX) | 1-1.5 plasma volumes daily | Apheresis | Cornerstone of treatment. Removes anti-ADAMTS13 antibodies and ultra-large vWF multimers, replaces ADAMTS13. Continue daily until platelet count > 150K × 2 consecutive days, then taper. [Canadian TTP PLEX Trial, 1991] |
| Methylprednisolone | 1g IV daily × 3 days | IV | Then transition to prednisone 1 mg/kg daily with taper. Immunosuppression to reduce anti-ADAMTS13 antibody production. |
| Caplacizumab | 11 mg IV first dose → 11 mg SQ daily | IV/SQ | Anti-vWF nanobody — prevents platelet-vWF binding. 74% reduction in composite of death + recurrence + major thromboembolic event. [HERCULES, 2019]. Continue for 30 days after last PLEX. Monitor for bleeding (mucocutaneous). |
| Rituximab | 375 mg/m² IV weekly × 4 doses | IV | For refractory TTP (no response after 5-7 days PLEX) or relapsing TTP. Depletes anti-ADAMTS13-producing B cells. Response in 1-3 weeks. Increasingly used upfront in severe cases. |
| DO NOT give platelets | — | — | CONTRAINDICATED (unless life-threatening hemorrhage). Transfused platelets are consumed by ultra-large vWF multimers → fuels microthrombosis → clinical deterioration. "Adding fuel to the fire." |
| Folate | 1 mg daily | PO | Support RBC production during ongoing hemolysis. |
📊 Monitoring
Monitoring
- Platelet count daily — primary response marker. Goal: > 150K × 2 consecutive days before stopping/tapering PLEX. If platelets plateau or drop during taper → resume daily PLEX.
- LDH daily — should trend down with effective treatment. Persistent elevation despite rising platelets → consider ongoing hemolysis or alternate diagnosis.
- Schistocytes — should decrease on serial peripheral smears. Request daily smear during active treatment.
- ADAMTS13 activity — send at diagnosis. Recheck after PLEX completion. Monitor for relapse (ADAMTS13 < 10% even in remission = high relapse risk → consider preemptive rituximab).
- ADAMTS13 inhibitor level (Bethesda assay) — quantifies antibody titer. Helps differentiate immune TTP from congenital TTP.
- Cr + UA — renal function. Improving Cr supports treatment response.
- Neuro exam — focal deficits, confusion, seizures. Fluctuating neuro symptoms are classic for TTP. Should improve with PLEX.
- Haptoglobin + indirect bilirubin — hemolysis resolution markers. Haptoglobin should recover as hemolysis resolves.
- Bleeding assessment — especially while on caplacizumab (mucocutaneous bleeding risk). Check for gum bleeding, epistaxis, GI bleed.
- Long-term follow-up — ADAMTS13 levels q3-6 months for 2+ years. Relapse rate ~30-50% in immune TTP. Preemptive rituximab if ADAMTS13 drops < 10%.
📋 On Rounds
Why are platelets contraindicated in TTP?
Ultra-large vWF multimers (uncleaved by absent ADAMTS13) create a thrombotic environment. Transfused platelets bind immediately → more microthrombi → worsened organ ischemia. The platelet count may be 5,000 but the patient is at risk from thrombosis, not bleeding. Treatment = remove the cause (plasma exchange), not add substrate (platelets).
Why should you NEVER transfuse platelets in TTP?
In TTP, platelet microthrombi are the pathology — transfusing platelets is like adding fuel to a fire. The ultra-large vWF multimers (from ADAMTS13 deficiency) recruit and consume platelets into microthrombi in small vessels, causing ischemic organ damage (brain, kidneys). Adding more platelets → more substrate for thrombus formation → worse organ damage. The only exception: life-threatening hemorrhage where the risk of bleeding death outweighs the risk of worsening thrombosis. Otherwise, the platelet count will recover with PLEX + steroids + caplacizumab [HERCULES, 2019. For the boards and the wards: TTP + platelet transfusion = wrong answer.
What is caplacizumab and why was it a breakthrough for TTP?
Caplacizumab is an anti-von Willebrand factor nanobody that blocks the interaction between ultra-large vWF multimers and platelets → prevents platelet adhesion and microthrombus formation. [HERCULES, 2019: caplacizumab + standard therapy (PLEX + steroids) vs placebo: faster platelet normalization, fewer thromboembolic events, fewer TTP-related deaths. Dose: 11 mg IV before first PLEX, then 11 mg SQ daily until 30 days after last PLEX. Risk: increased bleeding (blocking vWF-platelet interaction). Why it's a breakthrough: before caplacizumab, TTP mortality was ~10-20% even with PLEX. Caplacizumab added to PLEX + steroids reduced TTP-related mortality to near zero in the trial. It's now standard of care for acute TTP.
What is the PLASMIC score and how does it guide your decision to start PLEX?
PLASMIC score predicts ADAMTS13 < 10% (which confirms TTP). Components: Platelet count < 30K (+1), combined hemolysis variables (reticulocyte > 2.5%, haptoglobin undetectable, indirect bilirubin > 2) (+1), no active cancer (+1), no solid organ or stem cell transplant (+1), MCV < 90 (+1), INR < 1.5 (+1), Cr < 2.0 (+1). Score 0-4: low probability TTP → consider other MAHA causes (DIC, HUS). Score 5: intermediate → send ADAMTS13, consider starting PLEX. Score 6-7: high probability (~72% chance of ADAMTS13 < 10%) → start PLEX immediately, don't wait for ADAMTS13 result. Key: PLASMIC helps when you're unsure if the clinical picture is TTP vs DIC vs HUS. A high PLASMIC + schistocytes + thrombocytopenia = start PLEX tonight.
❓ What is the classic pentad of TTP and how often is it complete?
The classic pentad: (1) thrombocytopenia, (2) microangiopathic hemolytic anemia (schistocytes), (3) neurological symptoms, (4) renal impairment, (5) fever. However, the full pentad is present in < 5% of cases. Most present with only thrombocytopenia + MAHA. Waiting for the pentad delays treatment and increases mortality. Treat on clinical suspicion.
❓ What is ADAMTS13 and why is it deficient in TTP?
ADAMTS13 is a metalloprotease that cleaves ultra-large von Willebrand factor (vWF) multimers into smaller fragments. In immune TTP, autoantibodies against ADAMTS13 cause acquired deficiency (< 10% activity). Without ADAMTS13, ultra-large vWF multimers accumulate → spontaneous platelet aggregation → microvascular thrombosis throughout the body. Congenital TTP (Upshaw-Schulman) is genetic ADAMTS13 deficiency.
❓ Why are platelets contraindicated in TTP?
Transfused platelets are immediately consumed by the ultra-large vWF multimers that are pathologically accumulated in the microvasculature. This fuels more microthrombosis rather than raising the platelet count — "adding fuel to the fire." Only give platelets if there is life-threatening hemorrhage (which is rare in TTP because the thrombocytopenia is consumptive, not due to production failure).
❓ When would you give rituximab in TTP?
Refractory TTP (no response after 5-7 days of daily PLEX), relapsing TTP, or preemptive treatment when ADAMTS13 falls < 10% during remission monitoring (before clinical relapse). Some centers use rituximab upfront in severe presentations. Rituximab depletes the B cells producing anti-ADAMTS13 antibodies. Response in 1-3 weeks. [TTP Rituximab Study, 2011]
📣 Sample Presentation
One-Liner
"Ms. Wilson is a 36-year-old presenting with confusion, petechiae, Hgb 7.8, platelets 12K, Cr 1.8, LDH 1,400, and schistocytes on peripheral smear. PLASMIC score 7. ADAMTS13 sent."
Key Points to Cover on Rounds
MAHA + severe thrombocytopenia + neuro symptoms + renal impairment — TTP until proven otherwise. PLASMIC 7 (high probability). ADAMTS13 sent — don't wait for result. Treatment initiated emergently: (1) PLEX (plasmapheresis) — first session today, (2) methylprednisolone 1g IV daily × 3 days, (3) caplacizumab 11 mg IV then SQ daily [HERCULES, 2019]. Platelets NOT transfused (contraindicated — fuels thrombosis). Hgb 7.8 → transfuse pRBCs (safe, not platelets). Plan: daily PLEX until plt >150 × 2 days, ADAMTS13 pending.
⚡ Summary
Summary
Suspect When
MAHA (schistocytes) + severe thrombocytopenia + end-organ damage (neuro, renal). Do NOT wait for ADAMTS13 — start treatment.
PLASMIC Score
6-7 = high probability of ADAMTS13 < 10% → start PLEX tonight. Don't delay for confirmatory testing.
Treatment
Triple therapy: (1) PLEX daily until plt > 150 × 2 days, (2) steroids (methylpred 1g IV × 3 days), (3) caplacizumab [HERCULES, 2019].
Do NOT Transfuse Plt
Contraindicated — platelets fuel the thrombotic process. Analogy: adding fuel to fire. Transfuse RBCs only if needed.
Differentiate from HUS
TTP: neuro-predominant (confusion, seizures, focal deficits). HUS: renal-predominant (AKI, oliguria). Both have MAHA + thrombocytopenia.
Relapse
ADAMTS13 monitoring after recovery. Relapse risk ~30-50% for autoimmune TTP. Rituximab for relapsing or refractory disease.
📄 One Pager
Hematology · One Pager
TTP — Thrombotic Thrombocytopenic Purpura
MAHA + severe thrombocytopenia → start PLEX tonight. Don't wait for ADAMTS13. Don't transfuse platelets. Caplacizumab + steroids + PLEX = triple therapy.
Suspect When
MAHA (schistocytes on smear) + severe thrombocytopenia (< 30K) ± neuro symptoms ± renal impairment ± fever. PLASMIC score 6-7 = high probability → start PLEX.
Treatment — Triple Therapy
(1) PLEX daily (until plt > 150 × 2 days). (2) Methylprednisolone 1g IV × 3d. (3) Caplacizumab 11 mg IV then SQ daily [HERCULES, 2019]. Don't wait for ADAMTS13 result.
Critical Rules
Do NOT transfuse platelets (fuels thrombosis — adding fuel to fire). DO transfuse pRBCs if needed (Hgb support is safe). TTP vs HUS: TTP = neuro-predominant, HUS = renal-predominant.
Key Drugs
PLEXDaily until plt > 150 × 2d
Methylprednisolone1g IV daily × 3d
Caplacizumab11 mg IV then SQ daily
Rituximab375 mg/m² (refractory/relapsing)
Pitfalls
- Platelet transfusion (fuels microthrombosis)
- Waiting for ADAMTS13 before starting PLEX
- Not starting caplacizumab (reduces mortality)
- Confusing with DIC (DIC has low fibrinogen, TTP has normal fibrinogen)
Tumor Lysis Syndrome
Massive cell death → release of intracellular contents (K⁺, PO₄, uric acid, nucleic acids). Occurs 12–72h after chemo initiation. Highest risk: high tumor burden + rapidly proliferating cancers (ALL, Burkitt, DLBCL). Kills via hyperkalemia, AKI, and cardiac arrest.
🔍 Overview
Cairo-Bishop Criteria Cairo-Bishop Classification, 2004
Laboratory TLS: ≥ 2 metabolic abnormalities within 3 days before or 7 days after chemo. Clinical TLS: lab TLS + organ damage (AKI, arrhythmia, seizure).
| Lab | Direction | Mechanism | Danger |
|---|---|---|---|
| Potassium | ↑↑ | Released from lysed cells | Cardiac arrhythmia → VF → death. Most immediately lethal. |
| Phosphate | ↑↑ | Released from lysed cells | Binds calcium → calcium phosphate deposition in kidneys → AKI |
| Calcium | ↓↓ | Bound by elevated phosphate | Seizures, QT prolongation, tetany |
| Uric acid | ↑↑ | Purine breakdown from nucleic acids | Crystal deposition in renal tubules → AKI |
High-Risk Cancers
- Highest risk: ALL (especially B-cell), Burkitt lymphoma, DLBCL (high LDH, bulky disease)
- Moderate risk: AML (high WBC > 100K), CLL treated with venetoclax
- Lower risk: most solid tumors (rare but can occur with highly chemo-sensitive tumors)
🚨 Management
Prevention (Before Chemo)
| Intervention | Dose | Notes |
|---|---|---|
| Aggressive IVF ALL PATIENTS | 2–3 L/m²/day NS (goal UOP 2 mL/kg/hr) | Start 24–48h before chemo. Dilutes uric acid + phosphate. Most important prevention. |
| Allopurinol (Zyloprim) MODERATE RISK | 300–600 mg PO daily | Prevents new uric acid formation (xanthine oxidase inhibitor). Does NOT break down existing uric acid. Start 1–2 days before chemo. |
| Rasburicase (Elitek) HIGH RISK | 0.2 mg/kg IV × 1 dose (or fixed 3–6 mg) | Recombinant uricase — rapidly breaks down existing uric acid. Works within hours. Rasburicase TLS Trial, 2001 CONTRAINDICATED in G6PD deficiency (hemolytic crisis — produces H₂O₂). Check G6PD before giving if possible. Falsely lowers uric acid if sample is not kept on ice. |
Treatment of Established TLS
- Hyperkalemia: treat per hyperkalemia protocol (calcium, insulin/glucose, patiromer (Veltassa)/Lokelma, dialysis if refractory)
- Hyperphosphatemia: phosphate binders (sevelamer, aluminum hydroxide short-term), aggressive IVF, dialysis if severe
- Hypocalcemia: only treat if symptomatic (seizures, tetany, QT prolongation). Do NOT aggressively replete calcium — it worsens calcium-phosphate precipitation in kidneys
- Hyperuricemia: rasburicase (if not already given), aggressive IVF
- AKI: IVF,
correct metabolic derangements. Hemodialysis if refractory hyperkalemia,🧪 WorkupWorkup
- K⁺, PO₄, Ca²⁺, uric acid, Cr — the "TLS panel." Check q6-8h starting 12-24h before chemotherapy in high-risk tumors. Cairo-Bishop criteria: lab TLS = ≥ 2 of: K⁺ ≥ 6, PO₄ ≥ 4.5, Ca²⁺ ≤ 7, uric acid ≥ 8 (or 25% change from baseline).
- LDH — reflects tumor cell lysis and disease burden. Markedly elevated LDH pre-chemo = high TLS risk.
- Cr + BUN — AKI from uric acid crystallization in renal tubules (urate nephropathy) and calcium-phosphate precipitation.
- ECG — critical. Hyperkalemia (peaked T waves, widened QRS → fatal arrhythmia) and hypocalcemia (QTc prolongation → torsades). Get ECG before and after each lab check.
- Urine output — track hourly. Target ≥ 2 mL/kg/hr with aggressive hydration. Oliguria = urate nephropathy → may need dialysis.
- G6PD level — check BEFORE giving rasburicase. Rasburicase causes severe hemolytic anemia in G6PD-deficient patients (hydrogen peroxide accumulation). Prevalence: ~10% in African American males.
- Risk stratification: High risk = ALL, Burkitt lymphoma, DLBCL with bulky disease + high LDH, WBC > 100K in AML. Intermediate = most AML, CLL with high WBC. Low = most solid tumors, indolent lymphoma.
💊 MedicationsMedicationsDrug Dose Route Notes Rasburicase 0.2 mg/kg IV × 1 dose IV Treatment of established TLS — converts uric acid → allantoin (highly soluble) Rasburicase TLS Trial, 2001. Onset within hours. Contraindicated in G6PD deficiency (severe hemolysis). Must put blood sample on ice immediately (rasburicase degrades uric acid in tube → falsely low reading). [Rasburicase TLS Trial, 2001] Allopurinol 300-600 mg PO daily (start 2-3 days before chemo) PO PROPHYLAXIS ONLY — does NOT treat established TLS. Xanthine oxidase inhibitor — prevents NEW uric acid formation but does not break down existing uric acid. Dose-reduce in CKD. IV fluids (NS or D5W) 200-250 mL/hr (3 L/m²/day) IV Aggressive hydration is the foundation. Start 24-48h before chemo. Target UOP ≥ 2 mL/kg/hr. Promotes renal uric acid excretion + prevents crystal precipitation. Sevelamer 800 mg PO TID with meals PO Phosphate binder for hyperphosphatemia. Avoid calcium-based binders (calcium carbonate, calcium acetate) — risk of CaPO₄ precipitation in tissues with already elevated PO₄ + Ca product. Calcium gluconate 1-2g IV over 10-20 min IV ONLY for symptomatic hypocalcemia (seizures, tetany, QTc prolongation). Avoid routine correction — exogenous calcium + high PO₄ → tissue calcification. Insulin + D50 10 units regular insulin + 25g dextrose IV For hyperkalemia. Intracellular potassium shift. Check glucose at 1h. Use alongside calcium gluconate for membrane stabilization if ECG changes. Kayexalate or patiromer 15-30g PO or 8.4g PO PO GI potassium elimination for persistent hyperkalemia. Slow onset (hours). Not a substitute for insulin + calcium in acute setting. 📊 MonitoringMonitoring- K⁺, PO₄, Ca²⁺, uric acid, Cr q6-8h — for first 48-72h after chemo initiation. High-risk patients may need q4h monitoring initially.
- ECG — before each lab check. Hyperkalemia (peaked T → wide QRS → sine wave) and hypocalcemia (prolonged QTc) are immediately life-threatening.
- Urine output hourly — target ≥ 2 mL/kg/hr. Falling UOP = urate nephropathy or CaPO₄ precipitation → nephrology consult for possible dialysis.
- LDH trending — should decline after initial surge. Persistent elevation → ongoing tumor lysis.
- Fluid balance — aggressive IVF can cause volume overload, especially in patients with impaired renal or cardiac function. Daily weights + I/Os.
- Dialysis indications: refractory hyperkalemia, severe oliguria/anuria, volume overload unresponsive to diuretics, symptomatic hypocalcemia with concurrent hyperphosphatemia (can't give Ca safely)
- Ca × PO₄ product — if > 60 → high risk of metastatic calcification. Prioritize phosphate lowering.
📋 On RoundsWhy is rasburicase contraindicated in G6PD deficiency?Rasburicase is a recombinant uricase that converts uric acid to allantoin. This reaction produces hydrogen peroxide (H₂O₂) as a byproduct. Normally, glutathione neutralizes H₂O₂. In G6PD deficiency, the pentose phosphate pathway cannot regenerate NADPH → cannot regenerate glutathione → H₂O₂ accumulates → oxidative hemolytic crisis (methemoglobinemia + hemolytic anemia). This is life-threatening. Screen for G6PD before giving rasburicase when possible. Also: keep uric acid samples on ice — rasburicase continues to work ex vivo and falsely lowers the result.Why is rasburicase contraindicated in G6PD deficiency?Rasburicase is a recombinant urate oxidase that converts uric acid to allantoin (which is easily excreted). The reaction produces hydrogen peroxide (H₂O₂) as a byproduct. Normally, red blood cells neutralize H₂O₂ using glutathione, which requires G6PD to regenerate. In G6PD deficiency, RBCs cannot handle the oxidative stress → massive hemolysis + methemoglobinemia, which can be fatal. Always screen for G6PD before giving rasburicase — especially in African American, Mediterranean, and Southeast Asian populations where prevalence is highest. If G6PD deficient, use allopurinol + aggressive hydration instead.Why is allopurinol NOT a treatment for established TLS?Allopurinol is a xanthine oxidase inhibitor — it blocks the conversion of hypoxanthine → xanthine → uric acid. It prevents NEW uric acid formation but does NOT break down existing uric acid. In established TLS with already-elevated uric acid (e.g., UA = 14), you need rasburicase, which is a recombinant urate oxidase that directly converts existing uric acid → allantoin (soluble, easily excreted). Rasburicase works within hours; allopurinol takes days. Another problem: allopurinol causes xanthine accumulation, which can also precipitate in renal tubules (xanthine nephropathy). Bottom line: allopurinol = prophylaxis (before chemo). Rasburicase = treatment (after TLS develops). Both + aggressive IV fluids.What electrolyte abnormality in TLS can you NOT aggressively correct and why?Hypocalcemia — do NOT aggressively correct unless symptomatic (seizures, tetany, QTc prolongation with hemodynamic instability). In TLS, both calcium AND phosphate are abnormal: phosphate is very high from cell lysis, calcium drops because Ca²⁺ binds to the excess phosphate (calcium-phosphate precipitation). If you give IV calcium to "correct" the hypocalcemia, you increase the calcium-phosphate product → precipitation of CaPO₄ crystals in kidneys (nephrocalcinosis → worsens AKI), heart, and other tissues. Instead: treat the hyperphosphatemia first (sevelamer, aggressive hydration, rasburicase for uric acid nephropathy, dialysis if refractory). As phosphate comes down, calcium will self-correct. Only give calcium for life-threatening symptoms.❓ What are the Cairo-Bishop criteria for tumor lysis syndrome?Laboratory TLS = 2 or more of: (1) uric acid ≥ 8 or 25% increase, (2) K⁺ ≥ 6 or 25% increase, (3) PO₄ ≥ 4.5 or 25% increase, (4) Ca²⁺ ≤ 7 or 25% decrease. Clinical TLS = lab TLS + ≥ 1 of: Cr ≥ 1.5× ULN, cardiac arrhythmia, seizure, or death. Clinical TLS is what kills patients.❓ Why can you NOT give rasburicase to G6PD-deficient patients?Rasburicase converts uric acid to allantoin via an oxidation reaction that produces hydrogen peroxide (H₂O₂) as a byproduct. G6PD-deficient patients cannot generate adequate NADPH to neutralize H₂O₂ → severe oxidative hemolytic anemia + methemoglobinemia. Prevalence of G6PD deficiency: ~10% of African American males, common in Mediterranean and Asian populations. Must check G6PD BEFORE rasburicase.❓ Why do you avoid calcium-based phosphate binders in TLS?In TLS, both phosphate and calcium levels are deranged. Giving calcium-based binders (calcium carbonate, calcium acetate) adds exogenous calcium. When the calcium × phosphate product exceeds 60, calcium-phosphate crystals precipitate in tissues — kidneys (worsening AKI), heart, lungs, and soft tissues (metastatic calcification). Use sevelamer (non-calcium binder) instead.❓ What is the difference between allopurinol and rasburicase in TLS?Allopurinol = prophylaxis only. Xanthine oxidase inhibitor — prevents NEW uric acid formation but does NOT reduce existing uric acid. Start 2-3 days before chemo. Rasburicase = treatment. Recombinant urate oxidase — directly converts existing uric acid → allantoin (1000× more soluble). Works within hours. For established TLS, rasburicase is vastly superior.❓ Which malignancies are highest risk for TLS?Highest risk: Burkitt lymphoma (highest proliferation rate of any cancer), ALL (especially with WBC > 100K), DLBCL (with bulky disease + high LDH), AML (especially with WBC > 100K). Intermediate: most AML, CLL with high tumor burden, aggressive lymphomas. Low risk: most solid tumors (rare but described with small cell lung cancer, hepatocellular carcinoma).📣 Sample PresentationOne-Liner"Mr. Park is a 52-year-old with newly diagnosed Burkitt lymphoma (WBC 180K) who developed K⁺ 6.8, PO₄ 8.2, uric acid 14.2, Ca²⁺ 6.8, and Cr 3.4 twelve hours after starting chemotherapy. Consistent with tumor lysis syndrome."Key Points to Cover on RoundsTLS — Cairo-Bishop criteria met (2+ lab abnormalities + Cr rise). Labs: K⁺ 6.8 (treated emergently — Ca gluconate, insulin/D50, albuterol), PO₄ 8.2 (sevelamer started, avoid Ca-containing binders → CaPO₄ precipitation), uric acid 14.2, Ca²⁺ 6.8 (symptomatic → Ca gluconate only if ECG changes, otherwise avoid). Treatment: rasburicase 0.2 mg/kg IV × 1 (G6PD checked and normal). Aggressive IVF at 200 mL/hr. Allopurinol stopped (rasburicase is treatment, allopurinol is prophylaxis only). Nephrology consulted — HD if refractory K⁺ or fluid overload. Labs q6h. Plan: continue aggressive hydration, rasburicase, electrolyte management.⚡ SummarySummaryLab CriteriaCairo-Bishop: ≥ 2 of: K⁺ > 6, PO₄ > 4.5, uric acid > 8, Ca²⁺ < 7 (or 25% change from baseline). Clinical TLS = lab TLS + organ dysfunction.PreventionAggressive IVF 200-250 mL/hr + allopurinol (prophylaxis only). Rasburicase prophylaxis if high-risk (Burkitt, ALL with high WBC).TreatmentRasburicase (converts existing uric acid → allantoin, not allopurinol). Aggressive IVF. Patiromer/Lokelma for K⁺. Dialysis if refractory.Do NOTDon't give calcium for hypocalcemia unless symptomatic (increases CaPO₄ precipitation → renal damage). Don't give allopurinol for established TLS.High-Risk TumorsBurkitt lymphoma, ALL (high WBC), DLBCL, bulky tumors. Monitor: K⁺, PO₄, Ca²⁺, uric acid, Cr, LDH q6-8h after chemo initiation.When to DialyzeRefractory hyperkalemia, refractory hyperphosphatemia, volume overload, severe symptomatic hypocalcemia, worsening AKI despite treatment.📄 One PagerOncology / Nephrology · One PagerTumor Lysis SyndromeHigh K⁺ + high PO₄ + high uric acid + low Ca²⁺ + AKI after chemo. Prevention: hydration + allopurinol. Treatment: rasburicase + aggressive IVF + dialysis if refractory.DiagnosisCairo-Bishop: ≥ 2 lab abnormalities (K⁺ > 6, PO₄ > 4.5, uric acid > 8, Ca²⁺ < 7) OR 25% change from baseline. Clinical TLS = lab TLS + organ dysfunction.TreatmentRasburicase 0.2 mg/kg IV (converts existing uric acid → allantoin). Aggressive IVF 200-250 mL/hr. Treat hyperkalemia emergently. Sevelamer for hyperphosphatemia. Dialysis if refractory.Do NOTDon't give calcium for hypocalcemia unless symptomatic (increases CaPO₃ precipitation). Don't give allopurinol for established TLS (only prophylaxis). Check G6PD before rasburicase (hemolysis risk).Key DrugsRasburicase0.2 mg/kg IV × 1 (treatment)Allopurinol300 mg daily (prophylaxis only)IVF200-250 mL/hr NS or D5WSevelamer800 mg TID (for hyperPO₄)Pitfalls- Allopurinol for established TLS (doesn't break down existing uric acid)
- IV calcium for hypocalcemia (CaPO₃ precipitation → renal damage)
- Not monitoring labs q6-8h after chemo in high-risk tumors
- Rasburicase in G6PD deficiency (hemolysis)
Sickle Cell
Functional asplenia makes these patients vulnerable to encapsulated organisms — fever is a medical emergency. VOC is the most common reason for hospitalization. ACS is the #1 cause of death. Hydroxyurea saves lives.
🔍 Overview
Acute Complications
| Complication | Features | Management |
|---|---|---|
| Vaso-occlusive crisis (VOC) | Severe pain (bones, chest, abdomen) triggered by dehydration, cold, infection, stress | Aggressive pain control (IV opioids — PCA preferred), IVF (NS or D5 1/2 NS at 1.5× maintenance), incentive spirometry q2h (prevents ACS) |
| Acute chest syndrome (ACS) | New infiltrate on CXR + one of: fever, chest pain, cough, hypoxia, tachypnea. #1 cause of death in SCD. | Antibiotics (ceftriaxone + azithromycin — covers atypicals + encapsulated), exchange transfusion if severe (target HbS < 30%), supplemental O₂, bronchodilators, incentive spirometry |
| Stroke | Children: ischemic (large vessel). Adults: hemorrhagic more common. Sudden neuro deficit. | Exchange transfusion emergently (target HbS < 30%). Chronic transfusion program to prevent recurrence. |
| Splenic sequestration | Sudden splenomegaly + hemoglobin drop ≥ 2 from baseline + reticulocytosis. Mostly children (adults with HbSC). | Volume resuscitation + transfusion. Can be fatal within hours. Consider splenectomy after recovery. |
| Aplastic crisis | Parvovirus B19 → transient red cell aplasia. Hgb drops, reticulocyte count near zero. | Supportive. Transfuse if symptomatic anemia. Self-limited (1–2 weeks). |
| Priapism | Painful sustained erection > 4 hours. Urologic emergency. | IVF, analgesia, aspiration/irrigation by urology. Exchange transfusion if refractory. > 4h → ischemic → impotence risk. |
Infections & Sepsis in Sickle Cell
Fever ≥ 38.3°C (101°F) in SCD = medical emergency. Functional asplenia → cannot clear encapsulated organisms. Start empiric ceftriaxone within 1 hour of presentation. Do NOT wait for cultures. Mortality from overwhelming post-splenectomy sepsis can be > 50% if delayed.
Why Are SCD Patients at Risk?
By age 5, most HbSS patients have functional asplenia from repeated splenic infarction (autosplenectomy). The spleen is the primary filter for encapsulated bacteria — without it, these organisms can cause fulminant sepsis within hours. This is the same risk as surgically asplenic patients.
Key Organisms
| Organism | Clinical Scenario | Key Points |
|---|---|---|
| Streptococcus pneumoniae #1 KILLER | Bacteremia, pneumonia, meningitis | Most common cause of fatal sepsis in SCD. Can progress from well → dead in < 12 hours. Penicillin prophylaxis (age < 5) + pneumococcal vaccines (PCV13 → PPSV23) are essential. |
| Haemophilus influenzae type b | Bacteremia, pneumonia, meningitis | Second most common encapsulated pathogen. Hib vaccine has dramatically reduced incidence. |
| Neisseria meningitidis | Meningococcemia, meningitis | Fulminant course with purpura fulminans. Requires meningococcal vaccines (MenACWY + MenB). |
| Salmonella species OSTEOMYELITIS | Osteomyelitis — most common cause in SCD | In the general population, S. aureus is #1 for osteomyelitis. In SCD, Salmonella is #1 (infarcted bone is a perfect growth medium). Also causes bacteremia and GI infections. |
| Capnocytophaga canimorsus DOG/CAT BITE | Dog or cat bite, scratch, or saliva exposure | Gram-negative rod found in dog/cat saliva. In asplenic/functionally asplenic patients → fulminant sepsis, DIC, purpura fulminans, gangrene. Mortality 25–30% in asplenic patients. Treat with amoxicillin-clavulanate (bite prophylaxis) or piperacillin-tazobactam (if septic). Any SCD patient with a dog or cat bite needs immediate antibiotics and close monitoring. |
| Parvovirus B19 | Aplastic crisis (NOT sepsis) | Infects erythroid precursors → transient red cell aplasia. Retic count drops to near zero. Self-limited but may need transfusion. |
Fever Workup in SCD
- Blood cultures × 2 (before antibiotics — but do NOT delay antibiotics if cultures take time)
- CBC with differential — WBC, Hgb vs baseline, reticulocyte count
- CXR — rule out ACS and pneumonia
- Urinalysis + urine culture — UTI common
- CMP — check for end-organ damage
- Empiric ceftriaxone 2g IV — covers encapsulated organisms. Add vancomycin if toxic-appearing, meningitis suspected, or local DRSP rates are high
Required Vaccinations
| Vaccine | Schedule |
|---|---|
| PCV13 → PPSV23 | PCV13 series in childhood. PPSV23 at age 2, booster at age 5, then q5 years. Both types needed. |
| MenACWY | Primary series + booster every 5 years (lifelong in asplenic patients) |
| MenB | 2-dose or 3-dose series (depending on product) |
| Hib | Standard childhood series. If unvaccinated adult, give 1 dose. |
| Influenza | Annual — respiratory infections trigger ACS |
Penicillin prophylaxis: Penicillin VK 125 mg PO BID (age < 3) → 250 mg PO BID (age 3–5). Recommended for all HbSS children through age 5. PROPS, 1986: reduced pneumococcal sepsis by 84%. Discontinuation after age 5 is debated — many hematologists continue longer in high-risk patients.
🚨 Management
VOC Pain Management
Pain is real and severe. Treat aggressively. These patients are NOT drug-seeking. Chronic opioid tolerance means they need higher doses than you'd typically give. Use a PCA.
- IV opioids: PCA (patient-controlled analgesia) is preferred. Hydromorphone or morphine. Titrate to pain relief.
- Multimodal: ketorolac 15–30 mg IV q6h (if no AKI), acetaminophen 1g IV q6h, lidocaine patch
- IVF: NS or D5 1/2 NS at 1.5× maintenance. Avoid over-hydration (risk of ACS).
- Incentive spirometry q2h while awake — prevents atelectasis → ACS. Most important preventive measure during VOC admission.
- Transfusion: simple transfusion if Hgb < 7 or > 2 below baseline. Target Hgb ≤ 10 (higher viscosity worsens sickling).
Disease-Modifying Therapy
| Drug | Mechanism | Key Notes |
|---|---|---|
| Hydroxyurea 1ST LINE | ↑ HbF production → ↓ sickling. Also ↓ WBC (anti-inflammatory), ↑ NO, ↑ MCV. | Most important disease-modifying drug. Reduces crises by 50%, reduces ACS, reduces mortality. MSH, 1995. Offer to ALL patients with ≥ 3 crises/year (or any ACS/stroke). Teratogenic — contraception required. |
| Voxelotor (Oxbryta) | HbS polymerization inhibitor — stabilizes oxy-Hb state | ↑ Hgb by ~1 g/dL. FDA-approved. Long-term outcomes still being studied. |
| Crizanlizumab (Adakveo) | Anti-P-selectin monoclonal antibody — blocks sickle cell adhesion to endothelium | SUSTAIN, 2017: reduced median annual crises from 2.98 to 1.63. IV infusion monthly. |
| L-glutamine (Endari) | Reduces oxidative stress in RBCs | PO BID. Reduced crises by ~25%. Second-line add-on. |
💊 Medications
Key Medications — Sickle Cell
| Drug | Dose | Indication | Key Notes |
|---|---|---|---|
| Hydromorphone (Dilaudid) | 0.5–1 mg IV q2–3h PRN or PCA | VOC pain | PCA preferred. Titrate to pain control. These patients have opioid tolerance — use adequate doses. |
| Ketorolac (Toradol) | 15–30 mg IV q6h (max 5 days) | VOC adjunct | Avoid if AKI. Reduces opioid requirements. Hold if Cr rising. |
| Ceftriaxone (Rocephin) | 2g IV q24h | Febrile SCD / ACS | Empiric coverage for encapsulated organisms. Combine with azithromycin for ACS. |
| Azithromycin (Zithromax) | 500 mg IV/PO daily | ACS (atypical coverage) | Covers Mycoplasma, Chlamydophila — common ACS triggers. |
| Hydroxyurea DISEASE-MODIFYING | 15–35 mg/kg/day PO | Chronic — all SCD patients | ↑ HbF → ↓ sickling. Reduces crises, ACS, mortality. Teratogenic. Monitor CBC q4–8wk. |
| Penicillin VK | 125 mg BID (age < 3) → 250 mg BID (age 3–5) | Prophylaxis (children) | Prevents pneumococcal sepsis. PROPS, 1986: ↓ sepsis by 84%. |
| Amoxicillin-clavulanate | 875/125 mg PO BID × 5d | Dog/cat bite prophylaxis | Covers Capnocytophaga + Pasteurella. Start immediately — do not wait for signs of infection. |
| Folic acid | 1 mg PO daily | Chronic — all SCD patients | Chronic hemolysis depletes folate stores. Prevents megaloblastic crisis. |
📈 Monitoring
Monitoring Parameters — Sickle Cell Admission
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals + SpO₂ | q4h floor, q1–2h if febrile/ACS | Temp ≥ 38.3°C → blood cultures + empiric ceftriaxone STAT. SpO₂ < 94% → supplemental O₂ + CXR |
| Pain scores | q2–4h with vitals | Titrate PCA/opioids to ≤ 4/10 pain. Document response to each intervention. |
| CBC + reticulocyte | Daily AM | Hgb vs baseline — drop ≥ 2 may need transfusion. Retic near zero → aplastic crisis (parvovirus B19). |
| Hgb (if transfusing) | Post-transfusion (1–2h after) | Target Hgb ≤ 10 g/dL — never higher (hyperviscosity worsens sickling) |
| LDH, indirect bili, hapto | Baseline + PRN | Hemolysis markers. Trending worse may indicate accelerated sickling or delayed transfusion reaction. |
| CXR | Baseline + if respiratory Sx | New infiltrate + fever/cough/hypoxia = ACS → escalate to exchange transfusion discussion |
| Incentive spirometry | q2h while awake | 10 breaths per session. Document compliance — this is the #1 ACS prevention measure. |
| I&Os | Strict | Maintain euvolemia (1.5× maintenance IVF). Avoid over-hydration → pulmonary edema/ACS risk. |
SCD patients know their bodies. If they say the pain is different from their usual crisis, believe them — consider ACS, splenic sequestration, stroke, or infection as alternative diagnoses.
📋 On Rounds
Why do you target Hgb ≤ 10 when transfusing SCD patients?
Sickle cell patients have adapted to chronic anemia — their blood viscosity is calibrated to a lower Hgb. Transfusing to a "normal" Hgb (> 10) increases whole blood viscosity → paradoxically worsens vaso-occlusion and can trigger more crises. The optimal target is Hgb ≤ 10 g/dL. In exchange transfusions, the goal is to dilute HbS to < 30% while keeping total Hgb ≤ 10.
Why is incentive spirometry so important during VOC admission?
Chest wall pain during VOC → splinting → atelectasis → local hypoxia → triggers sickling in pulmonary vasculature → acute chest syndrome. ACS is the #1 cause of death in SCD and often develops during VOC admissions. Incentive spirometry q2h while awake prevents atelectasis and is the single most effective ACS prevention strategy during hospitalization — more important than any medication.
A sickle cell patient presents with fever, DIC, and purpura after a dog bite 2 days ago. What organism?
Capnocytophaga canimorsus — a gram-negative rod found in dog and cat saliva. In functionally asplenic patients (like SCD), it causes fulminant sepsis with DIC, purpura fulminans, and gangrene. Mortality is 25–30% in asplenic patients. This is why any dog or cat bite in a sickle cell patient needs immediate prophylactic antibiotics (amoxicillin-clavulanate). If already septic → piperacillin-tazobactam or meropenem. Classic board question: asplenic patient + dog bite + fulminant sepsis = Capnocytophaga.
What is the most common cause of osteomyelitis in sickle cell disease?
Salmonella — NOT Staph aureus. In the general population, S. aureus is #1 for osteomyelitis. In SCD, repeated bone infarctions create an ideal environment for Salmonella seeding. This is a classic boards distinction. However, S. aureus is still the #1 cause of septic arthritis in SCD. Mnemonic: Sickle cell + bone = Salmonella.
When do you do an exchange transfusion instead of a simple transfusion in sickle cell?
Simple transfusion (give pRBCs to raise Hgb): VOC with Hgb significantly below baseline, symptomatic anemia, aplastic crisis (parvovirus B19), splenic sequestration. Target Hgb ≤ 10 (never higher — hyperviscosity). Exchange transfusion (remove patient's blood while replacing with donor blood — lowers HbS%): acute chest syndrome (especially if worsening despite supportive care), acute stroke, multiorgan failure, priapism refractory to simple measures. Target: HbS < 30%. Exchange is preferred over simple transfusion in these emergencies because it rapidly reduces the sickling hemoglobin without raising total Hgb above 10. Requires apheresis capability. Chronic exchange program: secondary stroke prevention (indefinite).
Why is incentive spirometry so important in sickle cell crisis?
Acute chest syndrome (ACS) is the #1 cause of death in SCD during hospitalization. It develops when VOC-related pain → splinting (shallow breathing to avoid pain) → atelectasis → ventilation-perfusion mismatch → local hypoxia → more sickling in pulmonary vasculature → infarction → ACS. Incentive spirometry (IS) breaks this cycle — deep breaths recruit collapsed alveoli, prevent atelectasis, and maintain oxygenation. [IS for ACS Prevention Trial, 1995: IS use reduced ACS incidence from 36% to 0% in hospitalized SCD patients with chest/back pain. Protocol: 10 breaths every 2 hours while awake. This is the single most important preventive measure during a sickle cell admission.
📣 Sample Presentation
One-Liner
"Ms. Brown is a 24-year-old with SCD (HbSS) presenting with severe bilateral leg and back pain rated 10/10, not relieved by home oxycodone. WBC 14K, Hgb 7.2 (baseline 8.0). No fever. Consistent with vaso-occlusive crisis."
Key Points to Cover on Rounds
VOC — pain crisis. Pain management: IV hydromorphone 0.5 mg q2h PRN started within 30 min of arrival (multimodal: + ketorolac 15 mg IV + acetaminophen 1g). Incentive spirometry q2h while awake (prevents ACS). Hydration: D5 1/2NS at 125 mL/hr. Hgb 7.2 (baseline 8.0) → no transfusion yet (threshold 7, or if significant drop). No transfuse above 10 (hyperviscosity). CXR baseline — no ACS. Reticulocyte count 8% (appropriate). On hydroxyurea at home — continued. Plan: aggressive pain control, IS compliance, monitor for ACS (fever + new infiltrate + respiratory symptoms).
⚡ Summary
Summary
VOC Management
Multimodal pain: IV opioids (hydromorphone 0.5 mg q2h PRN) + ketorolac + acetaminophen. Treat pain within 30 min of arrival. IVF with D5 1/2NS.
ACS
Fever + new infiltrate + respiratory symptoms. #1 cause of death. Management: exchange transfusion, antibiotics (ceftriaxone + azithro), IS q2h, bronchodilators.
IS Compliance
Incentive spirometry 10 breaths q2h while awake — prevents ACS. Reduced ACS from 36% to 0% in one study [IS for ACS Prevention Trial, 1995].
Transfusion Rules
Simple: for symptomatic anemia, Hgb significantly below baseline. Exchange: for ACS, stroke, multiorgan failure. Target Hgb ≤ 10 (hyperviscosity).
Hydroxyurea
Disease-modifying: increases HbF → reduces sickling. Reduces VOC frequency, ACS, transfusion needs, mortality. All adults with SCD should be on it.
Infection / Sepsis
Functional asplenia → vulnerable to encapsulated organisms. Fever ≥ 38.3°C = emergency → ceftriaxone 2g IV within 1h. #1 killer: S. pneumoniae. Osteomyelitis: Salmonella (#1, not S. aureus). Dog/cat bite: Capnocytophaga → fulminant sepsis/DIC.
Vaccines & Prophylaxis
PCV13 + PPSV23, MenACWY + MenB, Hib, annual influenza. Penicillin VK prophylaxis through age 5 [PROPS, 1986]. Dog/cat bites → immediate amoxicillin-clavulanate.
Stroke
Children: ischemic (large vessel) — transcranial Doppler screening annually age 2-16. High TCD velocity → chronic exchange transfusion program (secondary prevention).
📄 One Pager
Sickle Cell — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card.
SICKLE CELL — AT A GLANCE
🔥 Fever: ≥ 38.3°C = emergency → blood cultures + ceftriaxone 2g IV within 1h. Functional asplenia = no time to wait.
💉 Pain (VOC): IV hydromorphone PCA + ketorolac + acetaminophen. Treat within 30 min. IVF D5 1/2NS 1.5× maintenance.
🫁 ACS: New CXR infiltrate + fever/cough/hypoxia. #1 cause of death. Ceftriaxone + azithro. Exchange transfusion if severe.
🩸 Transfusion: Simple if Hgb < 7 or ≥ 2 below baseline. Exchange for ACS/stroke/MOF. Target Hgb ≤ 10 (never higher!).
🦠 Bugs to know: S. pneumoniae (#1 killer), Salmonella (osteomyelitis), Capnocytophaga (dog/cat bite → fulminant sepsis).
💊 Hydroxyurea: All adults with SCD. ↑ HbF → ↓ crises, ACS, mortality. 15–35 mg/kg/day. Monitor CBC q4–8wk.
🌬️ IS q2h: 10 breaths every 2 hours. Prevents ACS. Most important thing you can do during admission.
💉 Vaccines: PCV13 + PPSV23, MenACWY + MenB, Hib, annual flu. Penicillin VK prophylaxis age < 5.
💉 Pain (VOC): IV hydromorphone PCA + ketorolac + acetaminophen. Treat within 30 min. IVF D5 1/2NS 1.5× maintenance.
🫁 ACS: New CXR infiltrate + fever/cough/hypoxia. #1 cause of death. Ceftriaxone + azithro. Exchange transfusion if severe.
🩸 Transfusion: Simple if Hgb < 7 or ≥ 2 below baseline. Exchange for ACS/stroke/MOF. Target Hgb ≤ 10 (never higher!).
🦠 Bugs to know: S. pneumoniae (#1 killer), Salmonella (osteomyelitis), Capnocytophaga (dog/cat bite → fulminant sepsis).
💊 Hydroxyurea: All adults with SCD. ↑ HbF → ↓ crises, ACS, mortality. 15–35 mg/kg/day. Monitor CBC q4–8wk.
🌬️ IS q2h: 10 breaths every 2 hours. Prevents ACS. Most important thing you can do during admission.
💉 Vaccines: PCV13 + PPSV23, MenACWY + MenB, Hib, annual flu. Penicillin VK prophylaxis age < 5.
🧪 Workup
Workup
- CBC + retic — Hgb vs baseline
- Type & screen — extended phenotype matching
- CXR — new infiltrate = ACS
- Blood cultures if febrile
- LDH, indirect bili, haptoglobin
- TCD — stroke screening children 2-16
Transfusion Medicine
When to transfuse, what products to use, and how to manage reactions. Restrictive is better for most patients. Know the thresholds and the reactions — you'll order blood products daily.
🩸 Transfusion Thresholds
| Product | Threshold | Evidence |
|---|---|---|
| pRBCs — general RESTRICTIVE | Hgb < 7 g/dL | TRICC, 1999: restrictive (7) non-inferior to liberal (10) in ICU. TRICS-III, 2017: confirmed in cardiac surgery. |
| pRBCs — ACS | Hgb < 8 g/dL (or symptomatic anemia) | REALITY, 2021: restrictive (8) vs liberal (10) — non-inferior for 30-day MACE in MI. |
| pRBCs — active bleeding | Hgb < 7–8, but transfuse to symptoms/hemodynamics | MTP: 1:1:1 ratio PROPPR, 2015 (pRBC:FFP:platelets). Don't wait for lab values in massive hemorrhage. |
| Platelets — general | < 10,000 (prophylactic) | Higher thresholds for active bleeding (< 50K), neurosurgery (< 100K), or procedures. |
| FFP | Active bleeding + INR > 1.5 | 15 mL/kg. Or 4F-PCC for warfarin reversal (faster, less volume). |
| Cryoprecipitate | Fibrinogen < 100–150 (DIC, massive transfusion) | 10 units raises fibrinogen ~50–70 mg/dL. Key product in DIC. |
🔄 Updated Practice: Old teaching: transfuse when Hgb <10 ("10/30 rule"). Current evidence: restrictive strategy (Hgb <7) is as safe or safer than liberal (Hgb <10) in most ICU patients (TRICC, 1999; TRISS, 2014). Exceptions: active ACS (transfuse <8), symptomatic anemia, active hemorrhage. For upper GI bleed, restrictive transfusion (Hgb <7) actually IMPROVED survival (Villanueva, 2013).
💉 Blood Products
| Product | Contains | Expected Effect | Special Considerations |
|---|---|---|---|
| pRBCs | Red blood cells in additive solution | ↑ Hgb ~1 g/dL per unit | Type & screen required. Irradiate if immunocompromised (prevent TA-GVHD). CMV-negative or leukoreduced for transplant candidates. |
| Platelets | Platelets (apheresis or pooled) | ↑ 30,000–50,000 per unit | ABO-compatible preferred. Room temperature storage (not refrigerated). 5-day shelf life. Highest bacterial contamination risk of all blood products. |
| FFP | All clotting factors | ↑ factor levels ~20–30% | ABO-compatible required. Thaw time ~30 min. Volume ~250 mL/unit (risk of TACO). |
| Cryoprecipitate | Fibrinogen, Factor VIII, vWF, Factor XIII | ↑ fibrinogen ~50–70 mg/dL per 10 units | Key for DIC, massive transfusion, factor XIII deficiency. Pooled (10 units = 1 dose). |
⚠️ Transfusion Reactions
First step in ANY suspected reaction: STOP the transfusion. Maintain IV access. Check vitals. Send a clerical check + blood sample to the blood bank.
| Reaction | Timing | Features | Management |
|---|---|---|---|
| Acute hemolytic (ABO mismatch) | Minutes | Fever, flank pain, dark urine, hypotension, DIC. Most dangerous. Usually clerical error. | STOP immediately. IVF (prevent renal failure), send direct Coombs + repeat type & screen. Supportive ICU care. |
| Febrile non-hemolytic (FNHTR) | 1–6 hours | Fever, rigors. Most common reaction. Cytokines from donor WBCs. | Stop, rule out hemolytic. Acetaminophen. Leukoreduced products prevent recurrence. |
| Allergic (mild) | During | Urticaria, pruritus. No fever or hemodynamic changes. | Stop temporarily. Diphenhydramine 25–50 mg IV. Can resume slowly if mild. |
| Anaphylactic | Minutes | Hypotension, bronchospasm, angioedema. Often in IgA-deficient patients (anti-IgA antibodies). | Epinephrine 0.3–0.5 mg IM. IVF, steroids, bronchodilators. Future: washed or IgA-deficient products. |
| TRALI | ≤ 6 hours | Acute respiratory distress + bilateral infiltrates + hypoxia within 6h. No volume overload. Caused by donor antibodies activating recipient neutrophils in lungs. | Supportive (O₂, ventilation). Diuretics do NOT help (not a volume issue). Usually resolves 48–96h. Report to blood bank. |
| TACO | ≤ 6 hours | Volume overload → pulmonary edema, HTN, JVD. Distinguished from TRALI by: elevated BNP, response to diuretics, hypertension. | Diuretics. Slow transfusion rate for future products
🔍 Overview
Overview
Blood product transfusion is one of the most common inpatient procedures. Restrictive thresholds (Hgb < 7) are standard for most patients [TRICC, 1999; TRISS, 2014] — liberal transfusion does not improve outcomes and may worsen them. In acute coronary syndrome, threshold is Hgb < 8. Always transfuse 1 unit at a time and recheck before ordering more. Massive transfusion protocol (MTP): 1:1:1 ratio of pRBC:FFP:platelets + TXA 1g IV [CRASH-2, 2010; PROPPR, 2015]. Key reactions to recognize: TRALI (non-cardiogenic pulmonary edema, normal BNP, within 6h) vs TACO (volume overload, elevated BNP, responds to diuretics). Stop transfusion immediately for any suspected reaction. |
🧪 Workup
Workup
- Type & screen — ABO + Rh typing + antibody screen. Required before all transfusions. Valid for 72h in recently transfused/pregnant patients.
- Crossmatch — for elective/non-emergent transfusion. Takes 30-60 min. In emergency: use O-negative (universal donor) while crossmatch pending.
- CBC — Hgb (transfusion threshold), platelet count (threshold 10K for prophylactic, 50K for invasive procedure, 100K for neurosurgery)
- Coagulation studies — PT/INR (FFP threshold: INR > 1.5 with active bleeding), fibrinogen (cryoprecipitate threshold: < 100-150 mg/dL)
- Direct Coombs (DAT) — if suspected transfusion reaction or hemolytic anemia. Positive = antibodies coating RBCs.
- Indirect Coombs (IAT) — detects circulating antibodies. Part of antibody screen. Positive → need antigen-negative units.
- Post-transfusion Hgb — check 1-2h after transfusion. Expected rise: ~1 g/dL per unit pRBC. If less → consider ongoing bleeding, hemolysis, or hypersplenism.
- For suspected reaction: stop transfusion → send bag + tubing to blood bank → direct Coombs → free hemoglobin (plasma/urine) → haptoglobin → repeat type & screen → UA for hemoglobinuria → chest imaging if respiratory symptoms
🚨 Management
Management
- Transfusion thresholds (restrictive):
- Hgb < 7 — most hospitalized patients [TRICC, 1999; TRISS, 2014; FOCUS, 2011]
- Hgb < 8 — acute coronary syndrome, symptomatic anemia, acute GI bleed with hemodynamic instability
- Hgb < 10 — rarely indicated (active MI with ongoing ischemia, severe symptomatic anemia)
- Platelets < 10K — prophylactic (no bleeding)
- Platelets < 50K — active bleeding or invasive procedure
- Platelets < 100K — neurosurgery, ocular surgery
- FFP — INR > 1.5 with active bleeding. NOT for "correcting" INR without bleeding.
- Cryoprecipitate — fibrinogen < 100-150 mg/dL
- Massive transfusion protocol (MTP): pRBC:FFP:platelets = 1:1:1 [PROPPR, 2015]. Activate early in hemorrhagic shock. TXA 1g IV within 3h of injury [CRASH-2, 2010]. Calcium gluconate 1g after every 4 units (citrate chelates calcium).
- Transfusion reactions:
- Febrile non-hemolytic (most common): fever + rigors within 1-6h. Stop, rule out hemolytic. Acetaminophen. Resume with leukoreduced products.
- Acute hemolytic: ABO incompatibility. Fever, flank pain, hemoglobinuria, DIC. STOP immediately. Aggressive IVF. Send workup.
- TRALI: bilateral infiltrates + hypoxia within 6h. Normal BNP. Supportive care (no diuretics — not volume overload). Resolves 48-72h.
- TACO: volume overload. Elevated BNP. Responds to furosemide. Prevention: slow rate, furosemide between units in high-risk.
- Allergic: urticaria (minor → diphenhydramine, resume). Anaphylaxis (IgA deficiency) → epinephrine, stop, use washed products.
- Special products: irradiated (prevent TA-GVHD in immunocompromised), CMV-negative (transplant recipients), leukoreduced (prevent febrile reactions + CMV), washed (IgA deficiency, severe allergic reactions)
📋 On Rounds
How do you distinguish TRALI from TACO?
Both present with respiratory distress + bilateral infiltrates within 6h of transfusion. TRALI: non-cardiogenic pulmonary edema (BNP normal or low, hypotension, no JVD, does NOT respond to diuretics). Caused by donor antibodies. TACO: cardiogenic volume overload (BNP elevated, hypertension, JVD, responds to diuretics). Risk factors: CHF, CKD, rapid infusion rate, multiple units. Key distinguisher: give furosemide. If they improve → TACO. If no response → TRALI.
Why Hgb 7, not 10?
TRICC, 1999 randomized ICU patients to restrictive (Hgb 7) vs liberal (Hgb 10) transfusion. Restrictive was non-inferior for 30-day mortality and had fewer cardiac events. Multiple subsequent trials confirmed this across cardiac surgery TRICS-III, 2017, GI bleed Villanueva, 2013, and hip surgery FOCUS, 2011. Transfusing above 7 without indication exposes patients to unnecessary risks: TACO, TRALI, alloimmunization, iron overload, and infection transmission — with no survival benefit.
What is TRALI and how do you differentiate it from TACO?
Both present with respiratory distress during/after transfusion, but treatment is opposite. TRALI (Transfusion-Related Acute Lung Injury): non-cardiogenic pulmonary edema. Onset within 6h. Bilateral infiltrates on CXR. NO signs of volume overload (BNP normal/low, no JVD, no S3). Due to donor antibodies activating recipient neutrophils → capillary leak. Treatment: supportive (O₂, intubation if needed, NO diuretics). TACO (Transfusion-Associated Circulatory Overload): cardiogenic pulmonary edema from volume overload. BNP elevated. JVD present. Responds to diuresis. Risk factors: elderly, CHF, renal failure, rapid transfusion rate. Treatment: stop transfusion + furosemide. Prevention: slow transfusion rate (1 unit over 2-4h in high-risk patients), give furosemide between units. The key differentiator: BNP. High BNP = TACO. Normal BNP = TRALI.
What is the transfusion threshold for most hospitalized patients?
Restrictive threshold: Hgb < 7 g/dL for most hospitalized patients. [TRICC, 1999 and [TRISS, 2014: restrictive (Hgb < 7) was non-inferior to liberal (Hgb < 10) for mortality. Liberal transfusion did NOT improve outcomes and increased complications. Exception: Hgb < 8 for ACS/active cardiac ischemia (the MINT trial [MINT, 2023 suggested possible benefit, though not definitive). Other exceptions: massive hemorrhage (transfuse to keep up with losses, use MTP), symptomatic anemia in patients who can't tolerate Hgb 7 (severe CAD, active bleeding). Never transfuse to a number — transfuse for symptoms or clinical need. And remember: 1 unit raises Hgb ~1 g/dL in a 70 kg patient. Check Hgb after each unit before ordering more.
❓ How do you differentiate TRALI from TACO?
TRALI = non-cardiogenic pulmonary edema. Normal BNP, bilateral infiltrates within 6h, no fluid overload signs, does NOT respond to diuretics. Supportive care only — resolves 48-72h. TACO = volume overload. Elevated BNP, responds to furosemide, often hypertensive. Prevention: slow transfusion rate, furosemide between units in HF/CKD patients.
❓ What is the expected hemoglobin rise per unit of pRBC transfused?
~1 g/dL per unit in a 70 kg adult. If the post-transfusion Hgb rise is less than expected, consider: (1) ongoing hemorrhage, (2) hemolysis (check Coombs, LDH, haptoglobin), (3) hypersplenism, (4) volume overload diluting the measurement, (5) lab draw from a diluted line.
❓ When do you give cryoprecipitate and what does it contain?
Cryoprecipitate contains: fibrinogen (most important), Factor VIII, Factor XIII, vWF, and fibronectin. Give when fibrinogen < 100-150 mg/dL (DIC, massive transfusion, post-thrombolytics). Dose: 10 units (1 pool) raises fibrinogen ~70 mg/dL. In massive hemorrhage, check fibrinogen early and replace aggressively — it is the first factor to become critically depleted.
❓ What is a delayed hemolytic transfusion reaction (DHTR)?
DHTR occurs 3-14 days after transfusion due to anamnestic antibody response (patient was previously sensitized but antibody titer dropped below detection). Presents with: unexplained Hgb drop, new jaundice, dark urine, positive DAT. Especially dangerous in SCD patients — can cause hyperhemolysis (destruction of both transfused AND native RBCs). Prevention: extended phenotype matching.
❓ What does TXA do and when is it indicated in massive hemorrhage?
Tranexamic acid (TXA) inhibits fibrinolysis by blocking plasmin. Give 1g IV within 3 hours of hemorrhage onset — later administration may be harmful. Evidence: [CRASH-2, 2010] — reduced mortality in trauma. [WOMAN, 2017] — reduced death from postpartum hemorrhage. No benefit shown in GI bleeding [HALT-IT, 2020]. Include in all massive transfusion protocols.
📣 Sample Presentation
One-Liner
"Mr. Davis is a 68-year-old who developed rigors, fever 39.2°C, and back pain 20 minutes into a pRBC transfusion. BP dropped from 130/80 to 88/52. Transfusion stopped immediately."
Key Points to Cover on Rounds
Suspected acute hemolytic transfusion reaction (fever + hypotension + back pain during transfusion). Immediate actions: (1) transfusion STOPPED, (2) IV access maintained with NS, (3) patient ID rechecked against blood product — mismatch identified (wrong unit hung). Reaction workup sent: repeat type & screen, direct Coombs (DAT), free hemoglobin, LDH, haptoglobin, UA (hemoglobinuria). Blood bank notified immediately. IVF resuscitation for hypotension. Monitoring for DIC (PT/INR, fibrinogen, D-dimer q4h). Plan: supportive care, if Hgb still needed → crossmatch new unit with correct sample.
💊 Medications
Blood Products & Transfusion Medications
| Product / Drug | Indication & Threshold | Dose / Details |
|---|---|---|
| pRBCs (packed red blood cells) | Hgb < 7 (general, TRICC); Hgb < 8 (ACS / active cardiac ischemia) | 1 unit at a time. Expected rise: ~1 g/dL per unit. Recheck Hgb after each unit before ordering more. |
| Platelets | < 10K (prophylactic, no bleeding); < 50K (active bleeding or procedure); < 100K (neurosurgery) | 1 apheresis unit or 6-pack pooled. Expected rise: 30,000–50,000 per unit. Room temperature storage. |
| FFP (fresh frozen plasma) | INR > 1.5 with active bleeding. NOT for "correcting" INR without bleeding. | 15 mL/kg (~4 units for 70 kg). ABO-compatible required. ~30 min thaw time. Consider 4F-PCC for faster warfarin reversal. |
| Cryoprecipitate | Fibrinogen < 150 mg/dL (DIC, massive transfusion, post-thrombolytics) | 10 units (1 pool). Raises fibrinogen ~50–70 mg/dL. Contains fibrinogen, Factor VIII, vWF, Factor XIII. |
| Tranexamic acid (TXA) | Massive hemorrhage — within 3 hours of onset | 1g IV over 10 min, then 1g over 8h. CRASH-2, 2010. Inhibits fibrinolysis. Include in all MTP activations. |
Premedication
Premedication (acetaminophen 650 mg PO + diphenhydramine 25–50 mg IV/PO) is only indicated if the patient has had a prior febrile or allergic transfusion reaction. Routine premedication for all transfusions is NOT recommended — it delays the transfusion, adds cost, and does not prevent serious reactions (TRALI, hemolytic). Leukoreduction is more effective than premedication for preventing FNHTR.
📈 Monitoring
Monitoring Parameters — Transfusion Medicine
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals during transfusion | q15 min × 1h, then q1h until complete | Baseline vitals before starting. Fever (> 1°C rise), hypotension, tachycardia, dyspnea, rigors → STOP transfusion immediately and initiate reaction workup. |
| Transfusion reaction signs | Continuous nursing observation during transfusion | Fever, rash/urticaria, dyspnea, hypotension, back/flank pain, dark urine → stop transfusion, maintain IV access, send reaction workup to blood bank. See Reactions tab. |
| Post-transfusion Hgb | 1h after completion of each unit | Expected rise ~1 g/dL per unit pRBC. If less → ongoing bleeding, hemolysis, or hypersplenism. Do not order next unit until post-transfusion Hgb is checked. |
| I&Os | Strict during and after transfusion | Fluid overload risk especially in HF and CKD patients. Each unit pRBC = ~350 mL volume. Consider furosemide 20–40 mg IV between units for high-risk patients (EF < 40%, ESRD, anasarca). |
First step in ANY suspected transfusion reaction: STOP the transfusion. Do NOT disconnect the tubing. Maintain IV access. Recheck patient ID vs blood product label (clerical error is #1 cause of hemolytic reactions). Send reaction workup: repeat type & screen, direct Coombs, free Hgb, haptoglobin, LDH, UA. Notify blood bank immediately.
⚡ Summary
Summary
Threshold
Hgb < 7 for most [TRICC]. Hgb < 8 for ACS. 1 unit raises Hgb ~1 g/dL. Check after each unit before ordering more.
Massive Transfusion
MTP: 1:1:1 ratio (pRBC:FFP:plt). TXA 1g IV within 3h [CRASH-2]. Ca²⁺ repletion (citrate in products chelates Ca). Warm products.
TRALI vs TACO
TRALI: non-cardiogenic edema, normal BNP, no diuretics. TACO: volume overload, elevated BNP, responds to furosemide. BNP is the differentiator.
Febrile Reaction
Fever + rigors during transfusion. Stop. R/O hemolytic reaction: send DAT, free Hgb, LDH, haptoglobin. Most are benign febrile non-hemolytic reactions.
Prevention
Irradiate for immunocompromised (prevent TA-GVHD). CMV-negative for CMV-seronegative transplant patients. Slow rate for CHF/elderly (1 unit over 2-4h).
Type & Screen
Always before transfusion. Emergency: O-negative pRBC (universal donor). Type-specific uncrossmatched next. Full crossmatch safest but takes time.
📄 One Pager
Transfusion Medicine — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
TRANSFUSION MEDICINE — AT A GLANCE
🩸 Thresholds: Hgb < 7 (general), < 8 (ACS). Platelets < 10K (prophylactic). FFP for INR > 1.5 + bleeding.
🧪 Workup: Type & screen, crossmatch, CBC, coags, post-transfusion Hgb 1h after → see Workup tab
⚠️ Reactions: STOP transfusion first. TRALI (normal BNP) vs TACO (elevated BNP) → see Reactions tab
💊 Products: pRBC, platelets, FFP, cryo, TXA → see Medications tab
📈 Monitor: Vitals q15min × 1h, watch for reactions, post-transfusion Hgb → see Monitoring tab
📣 Present: Indication, product, reaction workup → see Rounds tab
🧪 Workup: Type & screen, crossmatch, CBC, coags, post-transfusion Hgb 1h after → see Workup tab
⚠️ Reactions: STOP transfusion first. TRALI (normal BNP) vs TACO (elevated BNP) → see Reactions tab
💊 Products: pRBC, platelets, FFP, cryo, TXA → see Medications tab
📈 Monitor: Vitals q15min × 1h, watch for reactions, post-transfusion Hgb → see Monitoring tab
📣 Present: Indication, product, reaction workup → see Rounds tab
📄 One Pager
Hematology · One Pager
Transfusion Medicine
Threshold Hgb < 7 for most. 1:1:1 for MTP. TRALI vs TACO: BNP differentiates. Stop + workup any suspected reaction. Type & screen before all transfusions.
Thresholds
Hgb < 7 for most patients [TRICC, TRISS]. Hgb < 8 for active cardiac ischemia. Massive hemorrhage: 1:1:1 ratio (pRBC:FFP:plt) + TXA [CRASH-2].
Reactions
Febrile non-hemolytic (most common): stop, workup, rule out hemolytic. Acute hemolytic: fever + hypotension + back pain → stop immediately, send DAT, free Hgb, haptoglobin. TRALI: non-cardiogenic edema (normal BNP). TACO: volume overload (high BNP → furosemide).
Special Products
Irradiated: immunocompromised (prevent TA-GVHD). CMV-negative: CMV-seroneg transplant patients. Leukoreduced: prevent febrile reactions. Washed: severe allergic reactions (IgA deficiency).
Key Drugs
pRBCs1 unit raises Hgb ~1 g/dL
FFP10-15 mL/kg (INR correction)
Platelets1 unit raises plt ~30-50K
TXA1g IV (massive hemorrhage)
Pitfalls
- Transfusing above threshold without indication
- Not checking type & screen
- Not recognizing TRALI vs TACO (BNP differentiates)
- Rapid transfusion in CHF/elderly (slow rate, furosemide between units)
HIT (Heparin-Induced Thrombocytopenia)
Immune-mediated platelet activation by anti-PF4/heparin antibodies. Paradoxically a PRO-thrombotic state despite low platelets. The platelets drop, but the patient clots. Stop ALL heparin immediately and switch to a non-heparin anticoagulant.
🔍 Overview
4T Score (Pretest Probability)
| Criterion | 2 Points | 1 Point | 0 Points |
|---|---|---|---|
| Thrombocytopenia | Drop > 50% AND nadir ≥ 20K | Drop 30–50% OR nadir 10–19K | Drop < 30% OR nadir < 10K |
| Timing | Days 5–10 OR ≤ 1 day if prior heparin within 30 days | Days 5–10 (unclear) OR > day 10 | < day 4 (no prior exposure) |
| Thrombosis | New thrombosis, skin necrosis, or anaphylaxis post-heparin bolus | Progressive or recurrent thrombosis | None |
| Other causes | No other cause for thrombocytopenia | Possible other cause | Definite other cause |
0–3: low probability (< 5%) → HIT unlikely, no further testing. 4–5: intermediate → send PF4 antibody, start non-heparin anticoagulant. 6–8: high probability → treat as HIT while awaiting confirmatory tests.
Key Features
- Timing: platelet drop typically 5–10 days after heparin initiation (or within 24h if prior heparin exposure within 30 days — rapid onset HIT)
- Platelet drop: usually > 50% from baseline (not absolute count — a drop from 300K to 130K is HIT)
- Thrombosis in 50%: DVT/PE (most common), arterial (stroke, MI, limb ischemia), skin necrosis at heparin injection sites
- UFH >> LMWH for HIT risk (but LMWH can also cause it — cross-reactivity ~90%)
🚨 Management
Immediate Actions
Stop ALL heparin immediately — IV, SC, line flushes, heparin-coated catheters. Even trace amounts perpetuate the immune response.
| Drug | Dose | Notes |
|---|---|---|
| Argatroban 1ST LINE | 0.5–2 mcg/kg/min IV (no bolus). Monitor aPTT. | Hepatically cleared — preferred in renal failure. Falsely elevates INR (complicates warfarin bridging). Reduce dose in hepatic impairment, ICU, post-cardiac surgery. |
| Bivalirudin 1ST LINE | 0.15–0.2 mg/kg/hr IV. Monitor aPTT. | Short half-life (~25 min). Preferred for PCI and cardiac surgery settings. Partially renally cleared. |
| Fondaparinux ALTERNATIVE | Weight-based SC (same as VTE dosing) | Pentasaccharide — does NOT cross-react with HIT antibodies. Off-label for HIT but widely used. No monitoring needed. Renally cleared — avoid if CrCl < 30. |
Do NOT transfuse platelets in HIT unless life-threatening bleeding. Platelets are prothrombotic in HIT — they become activated by HIT antibodies → more thrombosis. Do NOT start warfarin until
platelets > 150K (warfarin depletes protein C → early protein C drop → warfari
🧪 Workup
Workup
- 4T score — pre-test probability. ≥ 6 = high probability → start non-heparin anticoagulation immediately while awaiting confirmatory testing. 4-5 = intermediate → test. ≤ 3 = low → HIT unlikely. Components: Thrombocytopenia (% fall + nadir), Timing (day 5-10), Thrombosis (new), oTher cause (none identified). [4T Score Validation, 2006]
- PF4/heparin ELISA (PF4 antibody) — screening test. High sensitivity (~97%), moderate specificity (~75%). Negative ELISA essentially rules out HIT. Positive → need confirmatory test. OD > 2.0 strongly predictive.
- Serotonin release assay (SRA) — confirmatory gold standard. High specificity (~95%). Takes 3-7 days to result. Functional assay — measures actual platelet activation.
- CBC trend — platelet nadir typically 5-10 days after heparin exposure. Classic: > 50% drop from baseline (e.g., 250K → 80K). Nadir usually 20-80K. If < 20K → consider other diagnoses (DIC, TTP).
- Bilateral lower extremity duplex US — 30-50% of HIT patients have occult DVT at diagnosis even without symptoms. Screen all confirmed/suspected HIT patients.
- Review ALL heparin exposure — IV drips, SQ prophylaxis, line flushes, heparin-coated catheters (dialysis, PICC lines), heparin in OR tubing. Even brief exposure counts.
- Timing clues: Typical onset day 5-10. Rapid-onset HIT (< 24h) = prior heparin exposure within 100 days (pre-formed antibodies). Delayed-onset HIT = develops after heparin stopped (rare, up to 3 weeks).
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Argatroban | 2 mcg/kg/min (0.5-1.2 in liver disease) | IV drip | Direct thrombin inhibitor. Argatroban HIT Trial, 2001 Hepatically metabolized — reduce dose in liver failure. Titrate to aPTT 1.5-3× baseline. Falsely elevates INR → complicates warfarin transition. [Argatroban HIT Trial, 2001] |
| Bivalirudin | 0.15-0.25 mg/kg/hr | IV drip | Alternative DTI. Shorter half-life (25 min vs 45 min) — preferred for PCI, cardiac surgery, or renal failure. Does not elevate INR. |
| Fondaparinux | 5-10 mg SQ daily | SQ | Factor Xa inhibitor. Off-label for HIT but widely used. No IV monitoring needed. Minimal cross-reactivity with HIT antibodies (< 1%). Renally cleared — avoid if CrCl < 30. |
| DO NOT use LMWH | — | — | 90% in-vitro cross-reactivity with HIT antibodies. Enoxaparin, dalteparin, tinzaparin are ALL contraindicated. |
| Warfarin transition | Start ONLY when platelets ≥ 150K | PO | Overlap argatroban for ≥ 5 days + INR ≥ 2 for 2 consecutive days. Starting warfarin too early depletes protein C Warfarin Limb Gangrene Study, 1997 → paradoxical thrombosis (venous limb gangrene, skin necrosis). [Warfarin Limb Gangrene Study, 1997] |
| DOAC transition | Per agent dosing | PO | Rivaroxaban or apixaban increasingly used as alternatives to warfarin for long-term anticoagulation post-HIT. Start when platelets recovered. Duration: 3-6 months minimum (or longer if provoked thrombosis). |
📊 Monitoring
Monitoring
- Platelet count daily — should begin recovering within 4-10 days of stopping heparin + starting alternative anticoagulation. If NOT recovering → reconsider diagnosis or check for new thrombosis.
- aPTT q6h while on argatroban — target 1.5-3× baseline. Avoid supratherapeutic levels (bleeding risk).
- INR for warfarin transition — argatroban falsely elevates INR. Check INR after holding argatroban × 4h to get true INR. Some centers use chromogenic factor X assay instead.
- Bilateral LE duplex US at diagnosis — even if no symptoms (30-50% occult DVT)
- Clinical assessment for new thrombosis daily — arterial (stroke, limb ischemia, MI) and venous (DVT, PE). HIT is a prothrombotic state — thrombosis risk highest in first 30 days.
- Skin exam — skin necrosis at injection sites (heparin-induced skin necrosis occurs before overt HIT)
- Duration of anticoagulation: minimum 4 weeks if HIT without thrombosis. 3-6 months if HIT with thrombosis (HIT-T). Some experts recommend extended anticoagulation for arterial HIT events.
📋 On Rounds
Why can't you bridge to warfarin immediately in HIT?
Warfarin inhibits vitamin K-dependent factors (II, VII, IX, X) but also inhibits protein C and S (natural anticoagulants). Protein C has the shortest half-life (~8h) → it drops first when warfarin is started. In HIT, the patient is already in a prothrombotic state. Starting warfarin creates a transient hypercoagulable window (protein C depleted before factors drop) → venous limb gangrene and skin necrosis. Wait until platelets > 150K and the patient is on a stable non-heparin anticoagulant × ≥ 5 days before starting warfarin. Overlap with argatroban/bivalirudin for ≥ 5 days, INR ≥ 2 × 2 days.
A patient on heparin has a platelet drop. How do you decide if it's HIT vs other causes?
Use the 4T score: (1) Thrombocytopenia — fall > 50% and nadir ≥ 20K scores highest, (2) Timing — days 5–10 after heparin start (or < 1 day if prior heparin in last 30 days) scores highest, (3) Thrombosis — new confirmed thrombosis scores highest, (4) oTher causes — no other explanation scores highest. 4T score 0–3 = low probability (HIT essentially ruled out, NPV > 99%). 4–5 = intermediate → send PF4 antibody. 6–8 = high → stop heparin, start argatroban, send PF4. Common mimics: sepsis-associated thrombocytopenia (most common cause of low plts in ICU), drug-induced (vancomycin, linezolid), dilutional, DIC, ITP. The 4T score prevents over-testing and unnecessary heparin avoidance.
Why can you NOT start warfarin until platelets recover above 150K in HIT?
In the acute thrombotic phase of HIT, protein C levels are already depleted (consumed by the ongoing thrombotic process). Warfarin further suppresses protein C (vitamin K-dependent, shorter half-life than other clotting factors) → transient hypercoagulable state → microvascular thrombosis → venous limb gangrene or skin necrosis. This is the same mechanism as warfarin-induced skin necrosis in protein C deficiency, but amplified by the prothrombotic state of HIT. Rule: platelets must be ≥ 150K before starting warfarin, and argatroban must overlap with warfarin for ≥ 5 days (INR will be artificially elevated on argatroban — target INR > 4 on combo, then recheck INR after stopping argatroban for 4h). DOACs are emerging as alternatives after the acute phase, but evidence is still limited.
What non-heparin anticoagulants can you use in HIT?
Argatroban (first-line): direct thrombin inhibitor, IV drip, hepatically metabolized (reduce dose in liver failure). Titrate to aPTT 1.5-3× baseline. Prolongs INR → makes warfarin transition tricky (need to check INR after holding argatroban for 4h). Bivalirudin: direct thrombin inhibitor, shorter half-life, preferred in PCI setting or renal failure (cleared by plasma proteases, not kidneys). Fondaparinux: factor Xa inhibitor, SQ, used for HIT once acute phase resolves and transitioning from IV anticoag. Not FDA-approved for HIT but widely used off-label. DOACs (rivaroxaban, apixaban): emerging data supports use after acute phase (platelets recovering), but NOT in the acute thrombotic phase. Never use: LMWH (cross-reacts with HIT antibodies in 90% of cases), warfarin alone in acute HIT.
❓ What are the components of the 4T score?
Thrombocytopenia: > 50% fall + nadir ≥ 20K = 2pts. Timing: day 5-10 (or < 1 day with prior heparin in last 30 days) = 2pts. Thrombosis: new confirmed thrombosis = 2pts. oTher cause: none apparent = 2pts. Score: 0-3 = low (HIT unlikely), 4-5 = intermediate, 6-8 = high probability → start non-heparin anticoag immediately. [4T Score Validation, 2006]
❓ Why is warfarin dangerous if started too early in HIT?
Warfarin depletes protein C faster than procoagulant factors (protein C half-life = 6h vs Factor II = 60h). In the prothrombotic state of HIT, this early protein C drop → paradoxical thrombosis → venous limb gangrene, skin necrosis (especially at fat-rich sites). Start warfarin ONLY when platelets ≥ 150K and overlap with DTI × ≥ 5 days. [Warfarin Limb Gangrene Study, 1997]
❓ How do you transition from argatroban to warfarin given that argatroban elevates INR?
Argatroban (a direct thrombin inhibitor) falsely elevates INR because it affects the thrombin-dependent step in the PT assay. Strategies: (1) Start warfarin when platelets ≥ 150K while continuing argatroban. (2) Target combined INR > 4 on overlap. (3) Hold argatroban × 4 hours, then check INR — if ≥ 2, the warfarin effect is therapeutic. (4) Some centers use chromogenic Factor X assay instead (not affected by argatroban).
❓ Can you use DOACs in HIT?
DOACs (rivaroxaban, apixaban) are increasingly used as alternatives to warfarin for the ongoing anticoagulation phase after platelet recovery. Advantages: no INR monitoring, no interaction with argatroban, rapid onset. Limited prospective data but growing retrospective evidence supports safety and efficacy. Start after platelets recovered (≥ 150K). Duration: 4 weeks (HIT without thrombosis) or 3-6 months (HIT with thrombosis).
❓ What is rapid-onset HIT and how does it differ from typical HIT?
Rapid-onset HIT: platelet drop within < 24 hours of heparin re-exposure in a patient with prior heparin exposure within the last 100 days. Pre-formed PF4/heparin antibodies cause immediate platelet activation. Key clue: patient was recently hospitalized or had surgery and now presents with acute thrombocytopenia upon heparin re-exposure. Contrast with typical HIT (day 5-10 onset in heparin-naive patients).
📣 Sample Presentation
One-Liner
"Mrs. Liu is a 64-year-old post-op day 7 from hip replacement on heparin prophylaxis whose platelets dropped from 220K to 82K (62% decline). No bleeding. 4T score 6 (high probability). PF4 antibody sent."
Key Points to Cover on Rounds
High-probability HIT (4T score 6: >50% drop, day 5-10 timing, no thrombosis yet, no other cause). Immediate actions: (1) ALL heparin stopped (drips, flushes, line locks), (2) argatroban started at 2 mcg/kg/min, titrate to aPTT 1.5-3× baseline, (3) bilateral LE duplex ordered (30-50% have occult DVT). PF4 Ab pending, SRA pending. No warfarin until plt >150K (protein C depletion risk → skin necrosis, venous limb gangrene). Platelet transfusion NOT indicated. Plan: argatroban until plt recovery, then transition to warfarin with ≥5 days overlap.
⚡ Summary
Summary
4T Score
Thrombocytopenia (timing, fall > 50%), Timing (days 5-10), Thrombosis (new), oTher causes excluded. Score ≥ 6 = high probability → act immediately.
Immediate Actions
Stop ALL heparin (drips, flushes, line locks). Start argatroban. Bilateral LE duplex (30-50% have occult DVT). Send PF4 antibody + SRA.
Anticoagulation
Argatroban 2 mcg/kg/min IV (reduce in liver failure). Alternative: bivalirudin. NO LMWH (90% cross-reactivity).
Warfarin Timing
Do NOT start until plt ≥ 150K (risk of venous limb gangrene from protein C depletion). Overlap with argatroban ≥ 5 days.
Labs
PF4 antibody (screening, high NPV). SRA (serotonin release assay — confirmatory, high specificity). Don't wait for SRA to treat if high 4T score.
Duration
If no thrombosis: anticoag × at least 4 weeks after plt recovery. If thrombosis (HITT): anticoag × 3 months minimum.
📄 One Pager
Hematology · One Pager
HIT — Heparin-Induced Thrombocytopenia
4T score ≥ 6 → stop ALL heparin + start argatroban. Bilateral LE duplex (30-50% occult DVT). No warfarin until plt ≥ 150K. No LMWH (90% cross-reactivity).
Diagnosis
4T score: Thrombocytopenia > 50% fall, Timing days 5-10, Thrombosis, oTher causes excluded. Score ≥ 6 = high probability → treat immediately. Send PF4 Ab + SRA.
Treatment
STOP all heparin (drips, flushes, line locks). Start argatroban 2 mcg/kg/min IV (reduce in liver failure). Bilateral LE duplex US (30-50% have occult DVT).
Warfarin Rules
Do NOT start until plt ≥ 150K (protein C depletion → venous limb gangrene). Overlap argatroban ≥ 5 days. DOACs emerging as option after acute phase but limited evidence.
Key Drugs
Argatroban2 mcg/kg/min IV drip
BivalirudinAlternative DTI
FondaparinuxSQ (off-label for HIT)
NO LMWH90% cross-reactivity
Pitfalls
- Not stopping ALL heparin (including flushes and line locks)
- Warfarin before plt ≥ 150K (limb gangrene risk)
- LMWH for HIT (cross-reacts in 90%)
- Not checking bilateral LE duplex (30-50% occult DVT)
Neutropenic Fever
Fever (≥ 38.3°C single or ≥ 38.0°C sustained ≥ 1h) + ANC < 500 (or expected to drop < 500). This is a medical emergency — antibiotics within 60 minutes. These patients can go from febrile to septic shock in hours because they have no immune defense.
🔍 Overview
Definition
- Neutropenia: ANC < 500 cells/μL, or ANC < 1000 and expected to decline to < 500 within 48h
- Fever: single temperature ≥ 38.3°C (101°F) OR sustained ≥ 38.0°C (100.4°F) for ≥ 1 hour
- Profound neutropenia: ANC < 100 → highest risk of bacteremia and death
Neutropenic patients cannot mount a normal inflammatory response. They may have no localizing signs — no pus, no infiltrate on CXR (no neutrophils to create one), minimal erythema at infection site. Fever may be the ONLY sign of life-threatening infection.
Risk Stratification — MASCC Score
MASCC (Multinational Association for Supportive Care in Cancer) score predicts low-risk vs high-risk for serious complications.
| Criterion | Points |
|---|---|
| Burden of illness: mild or no symptoms | +5 |
| Burden of illness: moderate symptoms | +3 |
| No hypotension (SBP ≥ 90) | +5 |
| No COPD | +4 |
| Solid tumor or no prior fungal infection | +4 |
| No dehydration requiring IV fluids | +3 |
| Outpatient at onset of fever | +3 |
| Age < 60 | +2 |
Score ≥ 21: low risk (~5% serious complication rate) → may consider outpatient oral antibiotics if reliable follow-up. Score < 21: high risk → admit for IV antibiotics.
Workup
- Blood cultures × 2 sets (one from each lumen if central line + one peripheral). Draw BEFORE antibiotics but do NOT delay antibiotics for culture results.
- CBC with differential, BMP, LFTs, lactate
- UA + urine culture
- CXR (may be falsely negative — no neutrophils to create infiltrate)
- Sputum culture if productive cough
- Stool for C. diff if diarrhea
- Consider CT chest if pulmonary symptoms (CXR insensitive in neutropenia)
- Consider fungal markers (galactomannan, β-D-glucan) if prolonged neutropenia (> 7 days)
🚨 Management
Empiric Antibiotics — Within 60 Minutes
Time to antibiotics matters. Start within 60 minutes of presentation. Mortality increases with every hour of delay.
| Setting | Regimen | Notes |
|---|---|---|
| Standard empiric | Cefepime (Maxipime) 2g IV q8h 1ST LINE | Or piperacillin-tazobactam 4.5g IV q6h or meropenem 1g IV q8h. Anti-pseudomonal coverage is essential. Monotherapy is sufficient for uncomplicated cases IDSA, 2010. |
| Add vancomycin if: | Vancomycin (Vancocin) 15–20 mg/kg IV q8–12h | Hemodynamic instability, skin/soft tissue infection, catheter-site infection, known MRSA colonization, severe mucositis, PNA on imaging. Do NOT add vanc routinely — only for specific indications. |
| Add antifungal if: | Micafungin (Mycamine) 100 mg IV daily or voriconazole or liposomal amphotericin B | Persistent fever after 4–7 days of antibiotics with no identified source. Prolonged neutropenia (> 7 days). Consider CT chest for invasive aspergillosis (halo sign). Galactomannan, β-D-glucan. |
| Low-risk outpatient | Ciprofloxacin (Cipro) 750 mg PO BID + amoxicillin-clavulanate (Augmentin) 875 mg PO BID | Only if MASCC ≥ 21, reliable patient, close follow-up within 24h, no IV line infection. Must observe 4–6h first. |
G-CSF (Filgrastim/Neupogen)
- NOT routine in all neutropenic fever — per ASCO/IDSA, G-CSF is considered for: pneumonia, sepsis/septic shock, fungal infection, expected prolonged neutropenia (> 10 days), ANC < 100
- Dose: filgrastim 5 mcg/kg SC daily until ANC recovery
- Blood cultures × 2 sets — 1 peripheral + 1 from each lumen of central line. Draw BEFORE antibiotics. If no central line, 2 peripheral sets from different sites.
- CBC with differential — confirm ANC < 500/μL (or < 1000 and expected to decline). Trend for nadir timing.
- BMP + LFTs — baseline renal/hepatic function for antibiotic dosing
- Lactate — if any concern for sepsis (tachycardia, hypotension)
- CXR — may be NORMAL even with pneumonia (neutropenic patients cannot mount an inflammatory infiltrate). A normal CXR does NOT exclude pulmonary infection.
- UA + urine culture — but note: pyuria may be absent (no WBCs to form pus)
- Skin exam — inspect ALL skin including perianal area, line sites, oral mucosa. Cellulitis without pus/erythema is common in neutropenia.
- Stool studies — C. diff PCR if diarrhea (mucositis + antibiotics = high risk)
- CT chest — if persistent fever day 4-5 despite antibiotics. Look for halo sign (invasive aspergillosis).
- Galactomannan + β-D-glucan — at day 4-5 if fevers persist (fungal biomarkers). Galactomannan specific for Aspergillus. β-D-glucan broad (not Mucor/Crypto).
- MASCC score — risk stratification for outpatient vs inpatient management (≥ 21 = low risk → may consider oral FQ + amoxicillin-clav)
- Prophylactic G-CSF is indicated for chemo regimens with ≥ 20% risk of
💊 MedicationsMedications
Drug Dose Route Notes Cefepime 2g IV q8h IV First-line anti-pseudomonal β-lactam. Start within 1 hour of presentation. IDSA, 2010 [IDSA Neutropenic Fever Guidelines, 2010] Meropenem 1g IV q8h IV Alternative if prior ESBL, cefepime allergy, or hemodynamic instability. Also covers anaerobes. Pip-tazo 4.5g IV q6h IV Alternative first-line. Covers Pseudomonas + anaerobes. Avoid if concern for seizures (piperacillin lowers threshold). Vancomycin 15-20 mg/kg IV IV NOT routine. Add ONLY if: hemodynamic instability, skin/soft tissue infection, suspected line infection, known MRSA colonization, severe mucositis, or blood culture growing GP cocci. Micafungin 100 mg IV daily IV Empiric antifungal at day 4-5 if fever persists despite antibiotics. Echinocandin covers Candida + Aspergillus. Voriconazole 6 mg/kg q12h × 2 → 4 mg/kg q12h IV/PO If invasive aspergillosis suspected (halo sign on CT, positive galactomannan). [Voriconazole Aspergillosis Trial, 2002] G-CSF (filgrastim) 5 mcg/kg SQ daily SQ Consider if ANC expected to be < 100 for > 10 days, pneumonia, sepsis, or invasive fungal infection. Not routine for uncomplicated neutropenic fever. Levofloxacin + Amox-clav 750 mg daily + 875 mg BID PO Outpatient option for LOW-RISK patients only (MASCC ≥ 21, expected short neutropenia, no comorbidities). 📊 MonitoringMonitoring- Temperature curve — defervescence expected within 3-5 days on appropriate antibiotics. Persistent fever at day 4-5 = expand workup (CT chest, fungal markers, line cultures)
- ANC daily — recovery above 500/μL is the key milestone. Antibiotics generally continued until ANC > 500 AND afebrile × 48h.
- Blood cultures at 48h — if initial cultures positive, repeat to document clearance. If persistent bacteremia → evaluate for endovascular source, line removal.
- Daily clinical assessment — new symptoms (cough, diarrhea, skin changes, abdominal pain), line sites (erythema, drainage), perianal exam, oral mucositis grade
- Galactomannan + β-D-glucan at day 4-5 if fever persists — repeat twice weekly if high suspicion for invasive fungal infection
- CRP trending — useful adjunct for tracking infection response (if rising on day 3-4, consider broadening coverage)
- Cr + LFTs — drug toxicity monitoring (vancomycin nephrotoxicity, voriconazole hepatotoxicity)
- Trough levels — vancomycin AUC/MIC targeting, voriconazole trough 1-5.5 mcg/mL
📋 On RoundsWhy can the CXR be falsely normal in neutropenic pneumonia?Infiltrates on CXR are caused by neutrophilic inflammation — exudate, pus, and cellular debris filling the alveoli. Without neutrophils (ANC < 500), the patient cannot mount this inflammatory response, so the infection exists but there's nothing to create a visible infiltrate. As the ANC recovers, the infiltrate may suddenly "appear" — this doesn't mean the infection is getting worse, it means the immune system is now responding. If you suspect pneumonia in a neutropenic patient → get a CT chest (more sensitive than CXR).When do you add vancomycin to neutropenic fever empiric coverage?NOT routinely. IDSA guidelines recommend adding vancomycin only for specific indications: (1) hemodynamic instability/septic shock, (2) suspected catheter-related infection (tunnel infection, port-site cellulitis), (3) known MRSA colonization, (4) skin/soft tissue infection, (5) severe mucositis with fluoroquinolone prophylaxis (risk of viridans strep bacteremia). Adding vanc empirically to everyone increases VRE selection, nephrotoxicity, and red man syndrome without improving outcomes in uncomplicated neutropenic fever.When do you add vancomycin to cefepime in neutropenic fever?Vancomycin is NOT routine first-line — add only for specific indications: (1) Hemodynamic instability / septic shock, (2) Suspected catheter-related infection (line erythema, tunnel infection, positive line cultures), (3) Skin/soft tissue infection (cellulitis, wound), (4) Blood culture growing gram-positive cocci (pending identification), (5) Mucositis (severe — increases risk of viridans strep bacteremia, which can cause septic shock). If none of these: cefepime monotherapy is sufficient. De-escalate vancomycin at 48-72h if cultures are negative for gram-positives. Unnecessary vancomycin → AKI (especially with pip-tazo), VRE selection pressure, red man syndrome.What is the MASCC score and how does it guide management?MASCC (Multinational Association for Supportive Care in Cancer) score stratifies neutropenic fever risk. Points for: burden of illness (5 or 3), no hypotension (5), no COPD (4), solid tumor or no prior fungal infection (4), no dehydration (3), outpatient onset (3), age < 60 (2). Score ≥ 21: low risk (~5% serious complications) → candidate for outpatient oral antibiotics (ciprofloxacin + amox-clav) if: reliable patient, lives near hospital, has caregiver, no organ dysfunction. Score < 21: high risk → inpatient IV antibiotics (cefepime). Key: even low-risk patients must have daily follow-up and clear return instructions. ANC < 100 with expected prolonged neutropenia (> 7 days) = high risk regardless of MASCC score.❓ What is the MASCC score and when do you use it?The MASCC score risk-stratifies neutropenic fever patients. Score ≥ 21 = low risk (may consider outpatient oral antibiotics: levofloxacin + amoxicillin-clavulanate). Criteria include: burden of illness, no hypotension, no COPD, solid tumor (vs hematologic), no dehydration, outpatient at onset, and age < 60.❓ When do you add vancomycin to empiric therapy in neutropenic fever?Vancomycin is NOT routine. Add only for: (1) hemodynamic instability/sepsis, (2) skin/soft tissue infection or suspected line infection, (3) blood cultures growing gram-positive cocci pending speciation, (4) known MRSA colonization, (5) severe mucositis (fluoroquinolone prophylaxis setting). [IDSA, 2010]❓ At what point do you add empiric antifungal therapy?At day 4-5 if fever persists despite broad-spectrum antibiotics. Start echinocandin (micafungin 100 mg daily). Send galactomannan + β-D-glucan. CT chest looking for halo sign (invasive aspergillosis). If CT or galactomannan positive → switch to voriconazole (better CNS penetration for Aspergillus). [Voriconazole Aspergillosis Trial, 2002]❓ Name three organisms neutropenic patients are particularly susceptible to.Pseudomonas aeruginosa (gram-negative, most feared — drives anti-pseudomonal empiric therapy), Aspergillus (invasive pulmonary aspergillosis in prolonged neutropenia > 10 days), and Candida (especially with mucositis, central lines, broad-spectrum antibiotics). Also viridans group streptococci in severe mucositis.❓ Why can a CXR be normal in a neutropenic patient with pneumonia?Neutropenic patients cannot mount an adequate inflammatory response. Pulmonary infiltrates require neutrophil recruitment to the infection site. With ANC < 500, there are insufficient neutrophils to form the inflammatory exudate that creates the radiographic infiltrate. The infiltrate may "appear" on CXR as neutrophils recover — this is why some patients develop new infiltrates during count recovery.❓ What is the role of G-CSF (filgrastim) in neutropenic fever?G-CSF is NOT routine for uncomplicated neutropenic fever. Consider in: (1) ANC expected < 100 for > 10 days, (2) pneumonia, (3) sepsis/septic shock, (4) invasive fungal infection, (5) age > 65. Prophylactic G-CSF is indicated for chemo regimens with ≥ 20% risk of febrile neutropenia. [ASCO/NCCN Guidelines]📣 Sample PresentationOne-Liner"Mr. Wilson is a 58-year-old with AML on induction chemotherapy, day 10 post-chemo, ANC 80, presenting with fever 38.8°C. Hemodynamically stable. MASCC score 21 (high risk)."Key Points to Cover on RoundsNeutropenic fever — ANC 80 (profound neutropenia). Blood cultures × 2 drawn (1 peripheral + 1 from PICC). Cefepime 2g IV q8h started within 45 min of fever. No vancomycin yet (no hemodynamic instability, no line erythema, no skin infection). Chest CT: no infiltrate. UA: no pyuria. No oral mucositis. Source: occult bacteremia until proven otherwise. Plan: daily assessment — add vancomycin if clinical deterioration or positive cultures with GP. Add antifungal (micafungin) if fever persists at day 4-5. Continue cefepime until ANC >500 + afebrile ≥48h.⚡ SummarySummaryDefinitionANC < 500 (or expected to fall to < 500) + single temp ≥ 38.3°C or sustained ≥ 38.0°C over 1 hour.First-LineCefepime 2g IV q8h. Monotherapy. Start within 1 hour of fever. Don't add vancomycin unless specific indication.Add VancomycinHemodynamic instability, catheter infection, skin/soft tissue infection, gram-positive bacteremia, mucositis.Add AntifungalPersistent fever at day 4-5 on antibiotics → micafungin or caspofungin. Galactomannan and β-D-glucan to guide.MASCC Score≥ 21 = low risk → outpatient oral abx (ciprofloxacin + amox-clav) if reliable patient, no organ dysfunction, close follow-up.Stop Abx WhenANC > 500 rising + afebrile ≥ 48h + cultures negative + clinically stable. Don't continue indefinitely.📄 One PagerOncology / ID · One PagerNeutropenic FeverANC < 500 + fever → cefepime within 1 hour. No vancomycin unless specific indication. Add antifungal at day 4-5 if persistent fever. MASCC ≥ 21 may go home.DefinitionANC < 500 (or expected to fall to < 500) + single temp ≥ 38.3°C or sustained ≥ 38.0°C over 1 hour. Medical emergency — clock starts at fever.TreatmentCefepime 2g IV q8h started within 1 hour. Blood cultures × 2 (peripheral + from line). CXR. UA. No vancomycin unless: shock, skin/line infection, GP bacteremia, mucositis.EscalationAdd vancomycin if specific indication at any time. Add antifungal (micafungin/caspofungin) at day 4-5 if persistent fever. MASCC ≥ 21: low-risk → outpatient oral abx (cipro + amox-clav) if reliable.Key DrugsCefepime2g IV q8hMeropenem1g q8h (if prior resistant GNR)Vancomycin15-20 mg/kg (only if indicated)Micafungin100 mg daily (persistent fever)Pitfalls- Delaying cefepime (start within 1 hour)
- Routine vancomycin (not needed unless specific indication)
- Missing perianal abscess (physical exam including perirectal)
- Not considering antifungal at day 4-5
🧪 Workup
Workup
Rotation
Hematology / Oncology
Blood disorders, coagulopathies, oncologic emergencies, and transfusion medicine.
Available Topics
Neutropenic Fever
DIC
TTP / HUS
Tumor Lysis Syndrome
Sickle Cell
Transfusion Medicine
Transfusion Reactions
HIT
ITP
Oncologic Emergencies
Pancytopenia
Chemo Toxicities
Lymphoma
Multiple Myeloma
Acute Leukemia (AML/ALL)
Anticoagulation Management
Anemia Workup
Hemolytic Anemia
Superior Vena Cava Syndrome
Hyperviscosity Syndrome
Hypercalcemia of Malignancy
Amyloidosis
📋 Major Guidelines
Inpatient Insulin Management
Every intern needs this. Basal-bolus-correction replaces the sliding scale. Target glucose 140–180 mg/dL in most ICU patients and 100–180 on the floor. The sliding scale alone is reactive, not proactive — it chases hyperglycemia instead of preventing it.
🔍 Overview
Glucose Targets
| Setting | Target | Evidence |
|---|---|---|
| ICU | 140–180 mg/dL | NICE-SUGAR, 2009: tight control (81–108) increased mortality vs moderate (140–180). Do NOT target normal glucose in critically ill patients. |
| General wards | 100–180 mg/dL (premeal < 140) | ADA/Endocrine Society consensus. Avoid > 180 and < 70. |
| Perioperative | 140–180 mg/dL | Hyperglycemia > 200 increases surgical site infections. |
Sliding scale insulin alone is NOT appropriate inpatient management. It only reacts to hyperglycemia after it happens. Basal-bolus-correction proactively prevents glucose swings and reduces hypoglycemia, hyperglycemia, and length of stay RABBIT 2, 2007.
Key Rules
- Hold metformin if: Cr > 1.5 (M) or 1.4 (F), IV contrast within 48h, acute illness (risk of lactic acidosis)
- Hold SGLT2 inhibitors — risk of euglycemic DKA in acutely ill patients
- Hold sulfonylureas — unpredictable oral intake → hypoglycemia risk
- Insulin is the preferred agent for inpatient glucose management
- Type 1 diabetics always need basal insulin — never hold it completely or they develop DKA
💊 Basal-Bolus-Correction Protocol
Step 1 — Calculate Total Daily Dose (TDD)
| Patient Type | TDD Calculation |
|---|---|
| Already on insulin at home | Use 80% of home TDD (reduce for illness-related decreased intake) |
| Insulin-naive, Type 2 | 0.4–0.5 units/kg/day (start conservatively). Elderly/CKD/thin → 0.3 units/kg/day. |
| Type 1 | 0.4–0.6 units/kg/day. NEVER hold basal completely. |
| On steroids | ↑ TDD by 20–40% (prednisone causes afternoon/evening hyperglycemia). Increase nutritional insulin at lunch/dinner more than basal. |
Step 2 — Split Into Components
| Component | % of TDD | Agent | Details |
|---|---|---|---|
| Basal | 50% of TDD | Glargine (Lantus) or Detemir (Levemir) | Given once daily (glargine) or BID (detemir). Covers fasting glucose. Give at same time each day. Do NOT hold if NPO — reduce by 20–50% but never to zero (Type 1 ALWAYS needs basal). |
| Nutritional (bolus) | 50% of TDD, divided across meals | Lispro (Humalog) or Aspart (NovoLog) | Given before each meal. Skip if NPO or not eating. Split equally across 3 meals (each dose = TDD/6). |
| Correction | Added to nutritional dose | Same rapid-acting insulin | Correction factor ≈ 1800 / TDD (the "1800 rule"). Example: TDD = 60 → correction factor = 30 mg/dL per unit. Added on top of nutritional dose before meals. |
Step 3 — Adjust Daily
- Fasting glucose high? → increase basal by 10–20%
- Pre-lunch/dinner/bedtime high? → increase prior meal's nutritional dose by 10–20%
- Hypoglycemia (< 70)? → reduce the responsible component by 20%. If nocturnal → reduce basal.
- NPO? → continue basal (reduce by 20–50% if concerned), hold nutritional, use correction-only sliding scale
- Tube feeds? → can use basal + correction q6h, or 70/30 insulin for continuous feeds
Example: 80 kg Type 2, insulin-naive. TDD = 0.4 × 80 = 32 units. Basal = 16 units glargine at bedtime. Nutritional = 16 ÷ 3 = ~5 units lispro before each meal. Correction factor = 1800/32 = ~56 → 1 unit for every 56 mg/dL above target. Adjust daily based on glucose log.
ICU — Insulin Drip
- Continuous insulin infusion for critically ill patients (DKA, postoperative, unstable PO intake)
- Regular insulin drip: start 0.5–1 unit/hr, titrate to target 140–180
- Check BG q1h until stable, then q2h
- When transitioning to SubQ: give basal insulin 2–4 hours before stopping drip (basal takes time to reach steady state). If glargine → overlap 4h. If detemir → overlap 2h. Calculate basal from drip rate: 24-hr drip total × 80% = TDD → 50% as basal.
🔄 Updated Practice: Old teaching (Van den Berghe, 2001): tight glucose control (80-110 mg/dL) in ICU improves mortality. This was OVERTURNED by NICE-SUGAR, 2009 — intensive insulin INCREASED mortality due to hypoglycemia. Current target: glucose ≤180 mg/dL in ICU patients. Avoid both hyperglycemia AND hypoglycemia. Sliding scale insulin alone is also outdated — basal-bolus is superior (RABBIT 2, 2007).
📋 On Rounds
Why did NICE-SUGAR change ICU glucose targets?
NICE-SUGAR, 2009: 6,104 ICU patients randomized to tight glucose control (81–108 mg/dL) vs conventional (140–180 mg/dL). Tight control increased 90-day mortality (27.5% vs 24.9%) and increased severe hypoglycemia 13-fold. The likely mechanism: repeated hypoglycemic episodes → adrenergic surges, cardiac arrhythmias, and cerebral glucose deprivation. Before NICE-SUGAR, the Van den Berghe, 2001 (Leuven) trial had suggested tight control was beneficial in surgical ICU patients, which became widespread practice. NICE-SUGAR definitively showed this was harmful in a broader ICU population.
Why must you overlap basal insulin with the drip when transitioning?
Long-acting basal insulin (glargine, detemir) takes several hours to reach therapeutic levels after SubQ injection. Glargine takes ~4h to reach steady state; detemir ~2h. If you stop the insulin drip and give SubQ basal simultaneously, there's a gap of several hours with no effective insulin → rebound hyperglycemia → DKA risk (especially in Type 1). By giving the SubQ basal dose 2–4 hours before stopping the drip, you ensure continuous insulin coverage during the transition with no gap.
Why is sliding-scale-only insulin dangerous in Type 1 diabetes?
Type 1 diabetics produce ZERO endogenous insulin. Without basal insulin, they develop DKA within 6-12 hours — regardless of whether they're eating. Sliding-scale insulin is only correctional (reactive — treats hyperglycemia after it happens) and contains no basal component. A Type 1 patient on sliding-scale-only will: (1) have persistent hyperglycemia (only corrected q6h, then rises again), (2) develop DKA because there's no insulin to suppress lipolysis → ketogenesis. Every Type 1 patient needs basal insulin 24/7 — even if NPO, even if eating nothing. Reduce the dose if NPO (by 20-30%), but NEVER hold it. Sliding-scale is an adjunct, never monotherapy, in Type 1.
How do you transition from an insulin drip to subcutaneous insulin?
The overlap method: (1) Calculate 24h insulin drip requirement (last 6-8h average rate × 24). (2) Give 80% of this as daily basal insulin (glargine or detemir). (3) Give the first SubQ basal dose 2 HOURS before stopping the drip — this allows SubQ absorption to reach therapeutic levels before IV is discontinued. If you stop the drip first, there's a gap with no insulin → hyperglycemia or DKA (especially Type 1). (4) Add mealtime rapid-acting insulin when patient resumes eating (lispro/aspart based on carb intake or fixed dose). (5) Continue correction scale. Key: always overlap — the most common mistake is stopping the drip the moment you give SubQ.
What is the most common cause of inpatient hypoglycemia?
Mismatch between insulin and nutrition — patient made NPO but mealtime insulin not held, or reduced oral intake without dose adjustment. Always reassess insulin when diet order changes.
A patient on 40 units of glargine at home is admitted NPO for surgery. What do you do with the insulin?
Give 60-80% of home basal dose (24-32 units). NEVER hold basal insulin entirely in a Type 1 diabetic — they will develop DKA. Hold all mealtime bolus. Use correction scale q4-6h PRN.
Why is NPH insulin specifically useful for steroid-induced hyperglycemia?
NPH peaks at 6-8 hours, which matches the hyperglycemic peak from morning prednisone. Give NPH with the AM steroid dose. Glargine is flat and doesn't match the steroid pattern.
What glucose target does NICE-SUGAR recommend for ICU patients?
140-180 mg/dL [NICE-SUGAR, 2009]. Intensive control (81-108) increased mortality by 14%, primarily from hypoglycemia. Tight control is harmful in the ICU.
📣 Sample Presentation
One-Liner
"Mrs. Chen is a 62-year-old with T2DM (A1c 9.8) on metformin + glipizide at home, now admitted for cholecystitis and NPO pre-operatively. Glucose range 220-380 over last 12 hours on sliding scale alone."
Key Points to Cover on Rounds
Hyperglycemia on sliding scale only — need basal-bolus conversion. Home: metformin (held for NPO/surgery) + glipizide (held — hypoglycemia risk while NPO). Weight 85 kg. Starting basal-bolus: glargine 0.3 units/kg/day = 25 units at bedtime (conservative — NPO). No nutritional insulin while NPO. Correction scale: q6h with lispro per sensitivity factor. Target glucose: 140-180. If eating → add mealtime lispro. Avoid sliding-scale-only (reactive, doesn't prevent hyperglycemia). Plan: adjust basal by 20% based on fasting glucose trend, transition back to home regimen post-op when eating.
🧪 Workup
Workup
- A1c — on admission for ALL diabetic patients and any glucose > 140. Reflects 3-month average. A1c > 9% = severe uncontrolled DM requiring basal-bolus.
- Fingerstick glucose — AC (before meals) + HS (bedtime) = 4×/day. Add q2h if on insulin drip or hypoglycemic.
- BMP — K⁺ (insulin shifts K intracellularly), Cr (dose-adjust), glucose trend
- Home medication reconciliation — exact doses of home insulin (basal type, units, timing), oral agents. Hold metformin if Cr > 1.5 or contrast planned. Hold SGLT2i inpatient (euglycemic DKA risk).
- Assess for DKA/HHS — if glucose > 300: check AG, ketones/BHB, osmolality, VBG
- Nutrition status — is patient eating? NPO? Tube feeds? TPN? This determines the insulin regimen.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Glargine (Lantus) | 0.15-0.25 U/kg once daily | SQ | Basal insulin — backbone of inpatient regimen. Give at same time daily. Do NOT hold for NPO status — reduce to 60-80%. |
| Lispro (Humalog) | 0.05-0.1 U/kg per meal | SQ | Mealtime bolus — give with first bite. Hold if not eating. |
| Aspart (NovoLog) | 0.05-0.1 U/kg per meal | SQ | Alternative rapid-acting. Same dosing as lispro. |
| NPH insulin | 0.1-0.2 U/kg with AM steroid | SQ | Steroid-induced hyperglycemia. NPH peak at 6-8h matches steroid effect. [Steroid Hyperglycemia NPH Study, 2017] |
| Regular insulin drip | 0.1 U/kg/hr (DKA protocol) | IV | ICU only. Transition to SQ 2h before stopping drip with basal overlap. |
| D50 (dextrose 50%) | 25g (50 mL) IV push | IV | Severe hypoglycemia (< 50 mg/dL or symptomatic). Follow with D10 drip if recurrent. |
| Glucagon | 1 mg IM/SQ | IM | No IV access. Onset 10-15 min. Causes nausea. Less effective in liver failure/alcohol. |
📈 Monitoring
Monitoring
- Fingerstick glucose AC + HS (4×/day) — before breakfast, lunch, dinner, bedtime
- q2h glucose if on insulin drip, hypoglycemic episode, or NPO + correction insulin
- Hypoglycemia events — document every episode. > 2 episodes → reduce TDD by 20%.
- K⁺ — check daily, especially with IV insulin (shifts K intracellularly)
- Insulin dose adjustment: review fingerstick log daily. If fasting glucose high → increase basal. If post-meal high → increase bolus. If pattern of lows → decrease by 20%.
- Discharge planning — if A1c > 9%, patient needs education + endocrine follow-up within 1 week. Ensure patient can demonstrate injection technique before discharge.
⚡ Summary
Summary
Basal-Bolus
Basal: glargine/detemir (background 24/7). Bolus: lispro/aspart before meals. Correction: q6h sliding scale. NEVER sliding scale alone.
Type 1 Rule
ALWAYS needs basal insulin — even if NPO. Reduce by 20-30% when NPO but NEVER hold. DKA develops in hours without basal insulin.
Starting Dose
Total daily dose: 0.3-0.5 units/kg/day. Give 50% as basal, 50% divided among meals. Lower in elderly, CKD, liver disease.
Drip to SubQ
Calculate 24h drip rate → give 80% as daily basal. Give SubQ dose 2 HOURS before stopping drip (overlap for absorption).
Target Glucose
140-180 mg/dL for most ICU patients [NICE-SUGAR, 2009]. Tight control (80-110) increased mortality. Avoid hypoglycemia.
Steroid Hyperglycemia
Steroids cause afternoon/evening hyperglycemia (not fasting). Increase mealtime insulin (especially lunch/dinner), NOT just basal. NPH can be paired with prednisone dosing.
📄 One Pager
Toxicology & Overdose — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
TOXICOLOGY & OVERDOSE — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
⚡ Management
Management — Inpatient Insulin Management
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
Thyroid Storm & Myxedema Coma
Thyroid storm: life-threatening thyrotoxicosis with mortality 10–30% even with treatment. Myxedema coma: severe hypothyroidism with altered consciousness and hypothermia. Both are clinical diagnoses — don't wait for labs to treat.
🔥 Thyroid Storm
Recognition — Burch-Wartofsky Score ≥ 45
Thyrotoxicosis with end-organ dysfunction: high fever, tachycardia out of proportion, AMS, HF, liver failure. Usually triggered by: infection, surgery, trauma, iodine load (contrast), medication non-adherence.
| Feature | Score Range |
|---|---|
| Temperature | 99–99.9°F = 5 → 104+ = 30 |
| CNS effects | Agitation = 10, delirium = 20, seizure/coma = 30 |
| GI-hepatic dysfunction | Diarrhea/nausea = 10, jaundice = 20 |
| Heart rate | 100–109 = 5 → 140+ = 25 |
| CHF | Mild = 5, moderate = 10, severe = 15 |
| Afib | Present = 10 |
| Precipitant | Positive = 10 |
≥ 45: highly suggestive → treat as thyroid storm. 25–44: impending storm. < 25: unlikely.
Treatment — Order Matters
Treat in this order. Iodine must come AFTER thionamide (≥ 1h later) — otherwise iodine provides substrate for MORE thyroid hormone production (Jod-Basedow effect).
| Step | Drug | Dose | Mechanism |
|---|---|---|---|
| 1. Block synthesis | PTU PREFERRED | 500–1000 mg PO loading → 250 mg PO q4h | Blocks new thyroid hormone synthesis (inhibits TPO). PTU preferred over methimazole in storm because it also inhibits peripheral T4→T3 conversion. |
| 2. Block release (≥ 1h after PTU) | Iodine (SSKI or Lugol's) | SSKI 5 drops PO q6h, or Lugol's 10 drops PO q8h | Wolff-Chaikoff effect — high iodine temporarily shuts down thyroid hormone release. MUST give after thionamide or iodine becomes fuel. |
| 3. Block peripheral effects | Propranolol | 60–80 mg PO q4h (or 1 mg IV slowly) | β-blockade controls tachycardia, tremor, agitation. Propranolol also blocks T4→T3 conversion. Esmolol drip if too unstable for PO. |
| 4. Block conversion | Hydrocortisone (Solu-Cortef) | 100 mg IV q8h | Blocks peripheral T4→T3 conversion. Also treats possible concomitant adrenal insufficiency (thyroid storm increases cortisol metabolism). Also: dexamethasone 2 mg IV q6h is alternative. |
| 5. Supportive | Cooling, IVF, acetaminophen | As needed | Avoid aspirin — displaces T4 from TBG → increases free T4. Use acetaminophen for fever. ICU admission. Treat precipitant. |
❄️ Myxedema Coma
Recognition
- Altered mental status (lethargy → coma) in the setting of severe hypothyroidism
- Hypothermia (may be < 35°C — core temp may not register on standard thermometer)
- Bradycardia, hypotension
- Hypoventilation (CO₂ retention — blunted respiratory drive)
- Hyponatremia (↓ free water excretion — can be severe)
- Non-pitting edema (myxedema), delayed reflexes, ileus
- Triggers: infection (#1), cold exposure, surgery, opioids/sedatives, medication non-adherence
Treatment
| Drug | Dose | Notes |
|---|---|---|
| IV Levothyroxine (T4) 1ST LINE | 200–400 mcg IV loading dose → 1.6 mcg/kg/day IV (50–100 mcg/day) | IV required — GI absorption unreliable in myxedema (ileus, edema). Large loading dose to replenish depleted T4 stores. |
| IV T3 (liothyronine) CONTROVERSIAL | 5–20 mcg IV loading → 2.5–10 mcg IV q8h | Faster onset than T4 (T4 takes days to convert). Some add T3 for severe cases. Risk: arrhythmia, cardiac ischemia (especially elderly/CAD). No RCT showing mortality benefit. |
| Hydrocortisone (Solu-Cortef) GIVE BEFORE T4 | 100 mg IV q8h | Must give stress-dose steroids BEFORE thyroid hormone. Hypothyroidism masks adrenal insufficiency — giving T4 increases metabolic rate → unmasks cortisol deficiency → adrenal crisis. Always give hydrocortisone first, taper once adrenal axis confirmed normal. |
Supportive: passive rewarming only (active rewarming causes vasodilation → cardiovascular collapse). Avoid sedatives/opioids (blunt already-depressed respiratory drive). Intubate if hypoventilating. Treat hyponatremia cautiously (fluid restrict, may need hypertonic saline if symptomatic). Treat precipitant.
📋 On Rounds
Why must iodine come AFTER the thionamide in thyroid storm?
Iodine is the substrate for thyroid hormone synthesis. If you give iodine to a thyrotoxic gland without first blocking the synthesis machinery (TPO enzyme), the gland uses the iodine to produce even more T3/T4 — the Jod-Basedow phenomenon. The thionamide (PTU or methimazole) blocks TPO first, ensuring the gland cannot use the incoming iodine for new hormone synthesis. Then, when you give iodine ≥ 1h later, the Wolff-Chaikoff effect kicks in — the high iodine load temporarily inhibits hormone release from the gland. The order is essential: block synthesis first, then block release.
Why give steroids before thyroid hormone in myxedema coma?
Hypothyroidism slows cortisol metabolism, so the body's cortisol "lasts longer" and masks underlying adrenal insufficiency. When you give T4 and increase the metabolic rate, cortisol is suddenly metabolized faster → cortisol drops → adrenal crisis (hypotension, shock, death). Up to 5–10% of myxedema patients have concomitant adrenal insufficiency (Schmidt syndrome — autoimmune polyglandular syndrome). By giving hydrocortisone first, you ensure adequate cortisol coverage before revving up metabolism with thyroid hormone.
Why do you give iodine 1 HOUR AFTER PTU and not at the same time?
PTU blocks thyroid hormone synthesis (inhibits thyroid peroxidase → can't organify iodine → can't make T3/T4). Iodine acutely blocks thyroid hormone RELEASE (Wolff-Chaikoff effect — excess iodine paradoxically inhibits hormone release). BUT: if you give iodine first or simultaneously, the thyroid gland has abundant substrate to make MORE hormone before PTU has taken effect → initial surge of T3/T4 synthesis (Jod-Basedow phenomenon), which can worsen the storm. By giving PTU first and waiting 1 hour, you ensure synthesis is blocked before giving the substrate. Order of therapy: (1) PTU → (2) wait 1h → (3) Iodine (SSKI or Lugol's) → (4) Propranolol → (5) Hydrocortisone.
Why do you give hydrocortisone in thyroid storm even without adrenal insufficiency?
Two reasons: (1) Thyroid storm increases cortisol metabolism — the hypermetabolic state accelerates cortisol clearance, creating a state of relative adrenal insufficiency. The adrenals can't keep up with demand. Without supplementation → adrenal crisis → refractory hypotension. (2) Hydrocortisone blocks peripheral T4 → T3 conversion (same enzyme that PTU and propranolol block — deiodinase type 1). This provides an additional mechanism to reduce the active thyroid hormone (T3) that's driving the storm. Dose: hydrocortisone 100 mg IV q8h (stress dose). Taper once thyroid storm is controlled. Don't give aspirin for fever — it displaces T4 from TBG → increases free T4 → worsens storm. Use acetaminophen instead.
Why must you give PTU BEFORE iodine in thyroid storm?
Iodine is a substrate for new thyroid hormone synthesis. If given before blocking synthesis with a thionamide, it feeds the storm (Jod-Basedow effect). Always give PTU ≥ 1 hour before SSKI/Lugol's.
Why is aspirin contraindicated in thyroid storm?
Aspirin displaces T4 from thyroid-binding globulin (TBG), acutely increasing free T4 levels and worsening the storm. Use acetaminophen for fever instead.
Name 3 drugs that block T4→T3 peripheral conversion.
PTU, propranolol (high-dose), and corticosteroids. This is why all three are part of the thyroid storm treatment protocol. Methimazole does NOT block peripheral conversion.
What is the Burch-Wartofsky score and when do you use it?
A scoring system using temperature, CNS effects, GI dysfunction, HR, CHF, and AF to diagnose thyroid storm. Score ≥ 45 = thyroid storm, 25-44 = impending storm. Lab values alone can't distinguish thyrotoxicosis from storm.
📣 Sample Presentation
One-Liner
"Ms. Santos is a 32-year-old with known Graves disease (non-adherent to methimazole) presenting with fever 39.8°C, HR 162, agitation, and tremor after a dental extraction. TSH <0.01, free T4 7.8. Burch-Wartofsky score 55. Thyroid storm."
Key Points to Cover on Rounds
Thyroid storm (BW score 55, ≥45 = storm). Precipitant: dental surgery + medication non-adherence. Treatment ORDER matters: (1) PTU 200 mg PO/PR q4h (blocks synthesis + peripheral T4→T3 conversion), (2) SSKI (iodine) started 1 HOUR AFTER first PTU dose (blocks thyroid hormone release — Wolff-Chaikoff), (3) propranolol 60 mg PO q6h (symptom control + blocks T4→T3), (4) hydrocortisone 100 mg IV q8h (prevents adrenal crisis + blocks conversion), (5) acetaminophen for fever (NOT aspirin — displaces T4 from binding proteins). ICU. Cooling blankets. IV fluids.
🔍 Overview
Overview
Thyroid storm is a life-threatening exaggeration of thyrotoxicosis with multi-organ dysfunction. Mortality 10-30% even with treatment. Diagnosis is clinical — do not wait for labs. Use the Burch-Wartofsky Point Scale (BWPS): score ≥ 45 = thyroid storm, 25-44 = impending storm. Classic triggers: surgery, infection, trauma, iodinated contrast, medication non-compliance, DKA in a patient with underlying Graves' disease. Key features: fever > 104°F (40°C), tachycardia out of proportion, altered mental status, GI dysfunction (diarrhea, jaundice — liver failure is a poor prognostic sign). Treatment follows a specific order: (1) beta-blocker → (2) thionamide → (3) iodine (≥ 1h after thionamide) → (4) steroids → (5) supportive care. The delay of iodine after thionamide is critical — giving iodine first fuels more hormone synthesis (Jod-Basedow effect).
🧪 Workup
Workup
- TSH + free T4 + free T3 — TSH suppressed (< 0.01), T4/T3 elevated. T3 often disproportionately high.
- Burch-Wartofsky Score — ≥ 45 = thyroid storm. 25-44 = impending storm. Scores: temp, CNS effects, GI/hepatic, HR, CHF, AF, precipitant.
- CBC, BMP, LFTs, lipase — hepatic dysfunction common (elevated AST/ALT/bilirubin). Leukocytosis.
- Blood cultures — infection is the #1 precipitant. Must rule out.
- Cortisol / ACTH stim — relative adrenal insufficiency common in storm. Stress-dose steroids given empirically.
- CXR, UA, lipase — search for precipitant (infection, surgery, trauma, iodine load, DKA, PE)
- ECG — AF in 10-35% of thyroid storm. Look for rate, ischemia.
- Pregnancy test — in women of childbearing age (PTU preferred in 1st trimester)
⚡ Management
Management
- Order of treatment matters: (1) Thionamide first → (2) Iodine 1 hour later → (3) Beta-blocker → (4) Steroids → (5) Supportive. Never give iodine before thionamide (Jod-Basedow effect — iodine feeds the storm).
- 1. Block new hormone synthesis: PTU 200 mg PO/PR q4h (preferred — also blocks T4→T3 conversion) or methimazole 20 mg PO q4-6h
- 2. Block hormone release (1h after thionamide): SSKI 5 drops q6h or Lugol's iodine 10 drops q8h. Lithium 300 mg q8h if iodine allergic.
- 3. Block peripheral effects: Propranolol 60-80 mg PO q4h (also blocks T4→T3) or esmolol drip if can't take PO
- 4. Block T4→T3 conversion: Hydrocortisone 100 mg IV q8h (also treats relative adrenal insufficiency) [Burch & Wartofsky]
- 5. Supportive: Cooling (acetaminophen, cooling blankets — NOT aspirin which displaces T4 from TBG), IVF, electrolyte repletion, ICU admission
- Treat the precipitant: antibiotics if infection, etc.
- Cholestyramine 4g QID — binds thyroid hormone in gut (adjunctive in refractory storm)
Do NOT give aspirin — it displaces T4 from thyroid-binding globulin, increasing free T4 and worsening storm. Use acetaminophen for fever.
📋 Clinical Example — Thyroid Storm Management
- Patient: 35F with known Graves' disease (non-compliant with methimazole), presents with fever 39.8°C, HR 162, agitation, vomiting, diarrhea. Burch-Wartofsky Score: 65 (>45 = thyroid storm).
- Treatment ORDER matters (block synthesis → block release → block conversion → block effects):
- Step 1 — Block new hormone synthesis: PTU 500-1000mg loading → 250mg q4h (preferred over methimazole in storm because PTU also blocks T4→T3 conversion). Give rectally if vomiting.
- Step 2 — Block hormone RELEASE (give ≥1 hour AFTER PTU): SSKI 5 drops q6h or Lugol's iodine 10 drops q8h. If given BEFORE antithyroid drugs, iodine will fuel more hormone production (Jod-Basedow effect).
- Step 3 — Block peripheral T4→T3 conversion: Hydrocortisone (Solu-Cortef) 100mg IV q8h (also treats possible relative adrenal insufficiency).
- Step 4 — Block peripheral effects: Propranolol (Inderal) 60-80mg PO q4-6h (preferred β-blocker — also inhibits T4→T3 conversion). Use esmolol drip if unable to take PO or hemodynamically tenuous.
- Supportive: Cooling blankets for fever (avoid aspirin — displaces T4 from binding proteins), IV fluids, acetaminophen. ICU admission.
- Key: Mortality of untreated thyroid storm is 20-30%. The sequential approach (PTU first, THEN iodine) is critical.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| PTU | 200 mg q4h | PO/PR | First-line thionamide. Blocks synthesis AND peripheral T4→T3 conversion. Risk: hepatotoxicity, agranulocytosis. |
| Methimazole (Tapazole) | 20 mg q4-6h | PO/PR | Alternative. More potent per mg. Does NOT block T4→T3. Preferred long-term but PTU preferred in storm and 1st trimester. |
| SSKI | 5 drops q6h | PO | Give ≥ 1h AFTER thionamide. Blocks hormone release (Wolff-Chaikoff effect). |
| Propranolol | Burch-Wartofsky, 1993 60-80 mg PO q4h | PO | Non-selective BB. Also inhibits T4→T3 conversion at high doses. Controls tachycardia, tremor, diaphoresis. |
| Esmolol | 500 mcg/kg bolus → 50-200 mcg/kg/min | IV | If can't take PO or hemodynamically unstable. Ultra-short acting. |
| Hydrocortisone | ATA, 2016 100 mg IV q8h | IV | Blocks T4→T3. Treats relative adrenal insufficiency. Empiric in all storm patients. |
| Cholestyramine | 4g PO QID | PO | Adjunctive — binds thyroid hormone in gut, interrupts enterohepatic circulation. |
| Acetaminophen | 1g IV/PO q6h | IV/PO | Antipyretic. NOT aspirin (displaces T4 from TBG). |
📈 Monitoring
Monitoring
- ICU admission — mandatory for thyroid storm
- Continuous telemetry — AF, tachyarrhythmias. HR is the best clinical marker of response.
- Vitals q1-2h — HR should improve within 1-2h of beta-blockade
- Temperature q2h — fever refractory to acetaminophen = poor prognostic sign
- Free T4, T3 q12-24h initially — should decline within 24-48h on treatment
- LFTs daily — PTU hepatotoxicity; also thyroid storm itself causes hepatic dysfunction
- CBC — agranulocytosis from thionamides (rare but fatal). Check if fever + sore throat.
- Burch-Wartofsky score daily — track clinical improvement
- Glucose — hyperglycemia common (catecholamine-driven glycogenolysis)
⚡ Summary
Summary
Diagnosis
Burch-Wartofsky score ≥ 45 = storm. Fever + tachycardia + AMS + precipitant (surgery, infection, non-adherence) + known thyroid disease.
Treatment Order
(1) PTU 200 q4h → (2) Iodine 1 HOUR after PTU (Wolff-Chaikoff) → (3) Propranolol 60 q6h → (4) Hydrocortisone 100 q8h → (5) Acetaminophen (NOT aspirin).
Why Not Aspirin
Displaces T4 from TBG → increases free T4 → worsens storm. Use acetaminophen + cooling blankets for fever.
PTU vs Methimazole
PTU preferred in storm: blocks synthesis AND peripheral T4→T3 conversion. Methimazole only blocks synthesis.
Supportive
ICU. Aggressive IVF. Cooling blankets. Treat precipitant (infection, surgery). Nutritional support (high caloric needs).
Discharge
Transition to methimazole (lower hepatotoxicity). Endocrinology follow-up. Definitive treatment: RAI or thyroidectomy.
📄 One Pager
One Pager — Thyroid Storm & Myxedema Coma
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
THYROID STORM & MYXEDEMA COMA — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Endocrine / ICU · One Pager
Thyroid Storm
Burch-Wartofsky ≥ 45. Treatment ORDER matters: PTU → iodine 1h later → propranolol → hydrocortisone → acetaminophen (NOT aspirin). ICU.
Diagnosis
Burch-Wartofsky score ≥ 45 = storm. Fever + tachycardia out of proportion + AMS/agitation + known thyroid disease + precipitant (surgery, infection, iodine load, non-adherence).
Treatment Order
(1) PTU 200 mg q4h (blocks synthesis + T4→T3 conversion). (2) Iodine (SSKI) 1 HOUR after PTU (Wolff-Chaikoff). (3) Propranolol 60 mg q6h (symptom control + blocks conversion). (4) Hydrocortisone 100 mg q8h. (5) Acetaminophen for fever (NOT aspirin).
Why This Order
PTU before iodine: iodine without PTU → substrate for MORE T3/T4 synthesis. Aspirin displaces T4 from TBG → increases free T4 → worsens storm. Hydrocortisone: relative adrenal insufficiency in hypermetabolic state.
Key Drugs
PTU200 mg PO/PR q4h
SSKI5 drops q6h (1h after PTU)
Propranolol60-80 mg PO q6h
Hydrocortisone (Solu-Cortef)100 mg IV q8h
Pitfalls
- Iodine before PTU (substrate for more hormone)
- Aspirin for fever (displaces T4 from TBG)
- Not giving steroids (relative adrenal insufficiency)
- Missing the precipitant (infection, surgery, non-adherence)
Adrenal Crisis
Acute cortisol deficiency → refractory hypotension, shock, and death if untreated. Most commonly from abrupt steroid withdrawal or physiologic stress in a patient with adrenal suppression. Give hydrocortisone first, diagnose later.
🔍 Overview
Common Causes
| Category | Examples |
|---|---|
| #1 — Steroid withdrawal | Abrupt discontinuation of chronic steroids (≥ 3 weeks of prednisone ≥ 20 mg/day suppresses HPA axis). Patient gets sick, can't take oral meds, and crashes. Always taper steroids. |
| Primary adrenal insufficiency (Addison) | Autoimmune adrenalitis (#1 in developed world), TB (#1 worldwide), adrenal hemorrhage (Waterhouse-Friderichsen — meningococcemia), metastatic disease, drugs (ketoconazole, etomidate) |
| Secondary (pituitary) | Pituitary tumor/surgery/apoplexy, chronic steroid use suppressing ACTH, checkpoint inhibitor hypophysitis |
| Critical illness-related | Relative adrenal insufficiency in septic shock (adrenals cannot mount adequate cortisol response to stress) |
Clinical Features
- Hypotension refractory to fluids and vasopressors — the hallmark. Cortisol is required for vascular tone and catecholamine sensitivity.
- Hyponatremia + hyperkalemia (primary AI — aldosterone deficiency). Secondary AI → hyponatremia only (aldosterone preserved).
- Hypoglycemia — cortisol is needed for gluconeogenesis
- Hyperpigmentation — primary AI only (↑ ACTH → ↑ MSH from POMC cleavage). Absent in secondary AI.
- Fatigue, nausea, vomiting, abdominal pain, fever
- Eosinophilia — cortisol normally suppresses eosinophils. Low cortisol → eosinophil count rises.
Think adrenal crisis in any patient with refractory hypotension + hyponatremia + hypoglycemia + eosinophilia — especially if on chronic steroids or has a history of autoimmune disease.
Diagnosis
- Random cortisol: AM cortisol < 3 mcg/dL is diagnostic of AI. > 15–18 rules it out. Between 3–15 = indeterminate → cosyntropin stim test.
- Cosyntropin (ACTH) stimulation test: Give 250 mcg cosyntropin IV/IM → check cortisol at 30 and 60 min. Cortisol < 18 mcg/dL = adrenal insufficiency.
- ACTH level: ↑ ACTH = primary (adrenal failure). ↓ ACTH = secondary (pituitary failure).
- In crisis: draw cortisol and ACTH, then treat immediately. Do NOT wait for results.
🚨 Management
Acute Adrenal Crisis
Immediate
Hydrocortisone 100 mg IV bolus → then 50 mg IV q8h (or 200 mg/24h continuous infusion) Endocrine Society Guidelines, 2016. Do NOT wait for labs. Hydrocortisone at stress doses provides both glucocorticoid AND mineralocorticoid activity.
Volume resuscitation
Aggressive NS boluses — these patients are profoundly volume-depleted. D5NS if hypoglycemic. The hypotension often dramatically improves within 1–2h of hydrocortisone + fluids.
Treat precipitant
Infection is the most common trigger. Broad-spectrum antibiotics if sepsis suspected.
Taper
Once stable → taper hydrocortisone over 3–5 days to physiologic replacement: hydrocortisone 15–20 mg AM + 5–10 mg PM (or prednisone 5 mg AM). Add fludrocortisone 0.1 mg daily if primary AI (mineralocorticoid replacement).
Stress Dose Steroids — When to Give
| Stress Level | Dose | Examples |
|---|---|---|
| Minor illness | Double daily dose × 2–3 days | Mild URI, dental procedure, minor stress |
| Moderate illness/surgery | Hydrocortisone 50 mg IV q8h × 1–2 days | Moderate surgery, pneumonia, GI illness with vomiting |
| Severe stress / major surgery / critical illness | Hydrocortisone 100 mg IV q8h | Major surgery, sepsis, trauma, ICU admission Endocrine Society, 2016 |
Any patient on chronic steroids (≥ 20 mg prednisone/day × ≥ 3 weeks in the past year) should be assumed to have HPA axis suppression and needs stress-dose steroids during acute illness/surgery. This includes patients who recently tapered off. When in doubt, give hydrocortisone — the risk of one dose is minimal, the risk of missing adrenal crisis is fatal.
📋 Clinical Example — Adrenal Crisis Management
- Patient: 55M on chronic prednisone 20mg daily for PMR, admitted for pneumonia. Now day 2, found hypotensive (BP 72/48), lethargic, Na 128, K 5.8, glucose 52.
- Recognition: This is adrenal crisis — he is on chronic steroids (HPA axis suppressed) and the pneumonia is a physiologic stress. His daily prednisone dose is insufficient for acute illness.
- Immediate treatment (do NOT wait for cortisol levels):
- Hydrocortisone (Solu-Cortef) 100mg IV STAT → then 50mg IV q8h. This is life-saving.
- NS bolus 1-2L (correct hypotension and hyponatremia). Dextrose for hypoglycemia.
- Do NOT give dexamethasone if you want to check a cortisol level (dexamethasone doesn't cross-react with cortisol assay, but hydrocortisone does).
- Stress dose steroid equivalents:
- Mild stress (minor procedure): hydrocortisone 50mg IV × 1
- Moderate stress (pneumonia, surgery): hydrocortisone 50mg IV q8h × 24-48h
- Severe stress (septic shock, major surgery): hydrocortisone 100mg IV q8h
- Who needs stress dose steroids? Any patient on ≥ prednisone 5mg/day for ≥3 weeks (or equivalent) in the past year. When in doubt, give stress dose — the risk of NOT giving it (death) far outweighs the risk of giving it (mild hyperglycemia).
- Taper: Once stress resolves, taper back to home dose over 1-3 days. Do NOT abruptly stop.
📋 On Rounds
How do you distinguish primary from secondary adrenal insufficiency?
Key differences: (1) ACTH level: ↑ in primary (adrenal glands failing → pituitary cranks up ACTH), ↓ in secondary (pituitary failing → no ACTH signal). (2) Hyperkalemia: present in primary (aldosterone deficiency from destroyed adrenal cortex), absent in secondary (aldosterone is regulated by RAAS, not ACTH, so it's preserved). (3) Hyperpigmentation: present in primary only (high ACTH → cleavage of POMC → MSH). (4) Most common cause: primary = autoimmune (Addison's). Secondary = chronic exogenous steroid use (iatrogenic HPA suppression).
A surgical patient on chronic prednisone 10 mg daily is going to the OR. What stress dose do you give?
The adrenal gland normally produces ~5–10 mg cortisol/day at baseline and up to 75–100 mg/day during major physiological stress (surgery, sepsis, trauma). A patient on chronic prednisone ≥ 5 mg/day for > 3 weeks has HPA axis suppression and cannot mount this stress response. Stress dosing by surgical severity: Minor (local/dental): take usual dose morning of surgery. Moderate (joint replacement, cholecystectomy): hydrocortisone 50 mg IV before induction, then 25 mg q8h × 24h, then taper to home dose. Major (cardiac, abdominal): hydrocortisone 100 mg IV before induction, then 50 mg q8h × 48–72h, then taper. Critical illness/sepsis: hydrocortisone 50 mg IV q6h. Failure to give stress dose → adrenal crisis → refractory hypotension.
How do you differentiate primary from secondary adrenal insufficiency?
Primary (Addison's): adrenal gland destruction → low cortisol + HIGH ACTH (pituitary trying to stimulate failed adrenals). Hyperpigmentation (ACTH shares a precursor with MSH → melanin production). Mineralocorticoid deficiency → hyperkalemia + hyponatremia. Causes: autoimmune (#1 in developed world), TB (#1 worldwide), bilateral adrenal hemorrhage (Waterhouse-Friderichsen in meningococcemia), metastases. Secondary: pituitary/hypothalamic failure → low cortisol + LOW ACTH. No hyperpigmentation (ACTH is low). No hyperkalemia (aldosterone is largely preserved — regulated by RAAS, not just ACTH). Most common cause: chronic exogenous steroids → HPA axis suppression (tertiary). Diagnosis: morning cortisol < 3 = AI. Cosyntropin stim test: cortisol fails to rise above 18-20 at 30-60 min.
What is the cosyntropin stimulation test and how do you interpret it?
Cosyntropin (synthetic ACTH) 250 mcg IV or IM → check cortisol at 0, 30, and 60 minutes. Normal response: cortisol rises to ≥ 18 mcg/dL (some labs use ≥ 20) at 30 or 60 min. If cortisol fails to rise to ≥ 18 → adrenal insufficiency confirmed. Interpretation: Low baseline + fails stim = AI. Low baseline + passes stim = may still have secondary AI (pituitary failure) if the adrenals haven't atrophied yet (early secondary AI). Key: if you strongly suspect adrenal crisis, don't wait for the test to treat — draw cortisol + ACTH, give hydrocortisone immediately, send cosyntropin stim later. Dexamethasone doesn't interfere with cortisol assay (unlike hydrocortisone) → can give dex while testing, but hydrocortisone is preferred clinically.
A critically ill patient with refractory hypotension has a random cortisol of 8. Do you treat?
Yes — empirically. In critical illness, cortisol should be > 18-25. A level of 8 in a stressed patient = relative adrenal insufficiency. Give hydrocortisone 100 mg IV and don't wait for ACTH stim test.
Why must you treat cortisol deficiency BEFORE starting levothyroxine?
Levothyroxine increases metabolic rate and cortisol clearance. In a patient with unrecognized adrenal insufficiency, starting thyroid hormone can precipitate adrenal crisis. Always replace cortisol first.
How do you differentiate primary from secondary adrenal insufficiency?
ACTH level: High ACTH + low cortisol = primary (Addison's — adrenal gland destroyed). Low ACTH + low cortisol = secondary (pituitary failure or chronic steroid use). Hyperkalemia occurs only in primary (mineralocorticoid deficiency).
What are the sick-day rules for adrenal insufficiency?
Double oral dose for minor illness, triple for major illness, IV stress-dose (100 mg hydrocortisone) for surgery/trauma/vomiting. All AI patients must carry an emergency injection kit and wear a medical alert bracelet.
📣 Sample Presentation
One-Liner
"Mr. Owens is a 58-year-old on chronic prednisone 15 mg daily for COPD who ran out of medication 5 days ago and presents with hypotension (BP 74/48 refractory to 3L IVF), nausea, and confusion. Na⁺ 128, K⁺ 5.6. Adrenal crisis."
Key Points to Cover on Rounds
Adrenal crisis — tertiary adrenal insufficiency (chronic exogenous steroid → HPA axis suppression → abrupt withdrawal). Treatment: hydrocortisone 100 mg IV bolus immediately, then 50 mg IV q8h. IVF resuscitation with D5NS (hypoglycemia risk). Na 128 will correct with cortisol replacement (cortisol is needed for free water excretion). K⁺ 5.6 will correct with cortisol (mineralocorticoid effect). Cortisol and ACTH were drawn before hydrocortisone (but didn't delay treatment). BP improved to 98/62 within 2 hours. Plan: taper to oral prednisone over 3-5 days, endocrine to develop slow steroid taper schedule, medic alert bracelet.
🧪 Workup
Workup
- AM cortisol — draw before giving steroids if possible. < 3 mcg/dL = adrenal insufficiency confirmed. > 18 = AI excluded. 3-18 = need ACTH stim test.
- ACTH stimulation test (cosyntropin) — 250 mcg IV → cortisol at 0 and 60 min. Normal = cortisol ≥ 18 at 60 min. Do NOT delay steroids for this test — give dexamethasone (does not interfere with cortisol assay) while awaiting results.
- ACTH level — high ACTH + low cortisol = primary (Addison's). Low ACTH + low cortisol = secondary (pituitary/hypothalamic) or chronic steroid use.
- BMP — classic: hyponatremia + hyperkalemia (primary AI only — mineralocorticoid deficiency). Also hypoglycemia, mild hypercalcemia.
- CBC — eosinophilia (cortisol normally suppresses eosinophils)
- TSH — hypothyroidism common in autoimmune polyglandular syndrome. Treat cortisol BEFORE thyroid hormone (levothyroxine can precipitate crisis).
- CT adrenals — hemorrhage (anticoagulation, Waterhouse-Friderichsen), metastases, infiltration (TB, histoplasmosis, sarcoid)
- 21-hydroxylase antibodies — autoimmune adrenalitis (most common cause in developed countries)
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Hydrocortisone | Endocrine Society, 2016 100 mg IV bolus → 50 mg IV q8h | IV | First-line for adrenal crisis. Has both glucocorticoid AND mineralocorticoid activity. Taper as patient improves. |
| Dexamethasone | Endocrine Society, 2016 4 mg IV q12h | IV | Alternative if ACTH stim test pending — does not interfere with cortisol assay. No mineralocorticoid activity — add fludrocortisone. |
| NS (normal saline) | 1-2L bolus, then maintenance | IV | Aggressive volume resuscitation. These patients are volume-depleted from mineralocorticoid deficiency. Add D5 if hypoglycemic. |
| Fludrocortisone (Florinef) | Endocrine Society, 2016 0.05-0.2 mg daily | PO | Mineralocorticoid replacement for primary AI (Addison's). Not needed in secondary AI (ACTH deficiency preserves aldosterone). Start once PO tolerating. |
| Hydrocortisone (maintenance) | 15-25 mg daily (10 AM + 5 PM) | PO | Chronic replacement. Mimic diurnal pattern. Sick-day rules: double or triple dose during illness/surgery. |
Sick-day rules: All AI patients must carry an emergency injection kit (100 mg hydrocortisone IM) and wear a medical alert bracelet. Double oral dose for minor illness, triple for major illness, IV stress-dose for surgery/trauma.
📈 Monitoring
Monitoring
- Hemodynamics — BP and HR should improve within 1-2h of IV hydrocortisone + fluids
- BMP q6-12h — Na should correct with fluids + steroids. K⁺ should normalize. Glucose monitoring (hypoglycemia).
- Clinical response — improved mentation, resolved hypotension are the best markers
- Do NOT check cortisol levels to guide acute treatment — treat the clinical picture, not the number
- Taper to oral — once hemodynamically stable and eating → hydrocortisone 20/10 mg PO + fludrocortisone 0.1 mg daily (primary AI)
- Outpatient: morning cortisol levels are not useful for monitoring replacement. Adjust dose based on clinical symptoms (fatigue, weight, BP, electrolytes, skin pigmentation).
⚡ Summary
Summary
Crisis Treatment
Hydrocortisone 100 mg IV bolus immediately → 50 mg IV q8h. Don't wait for lab results. IVF with D5NS (hypoglycemia risk).
Primary vs Secondary
Primary (Addison): high ACTH, hyperpigmentation, hyperkalemia. Secondary: low ACTH, no hyperpigmentation, no hyperkalemia.
Most Common Cause
Chronic exogenous steroids → HPA suppression → abrupt withdrawal → crisis. Also: autoimmune (#1 primary), TB (#1 worldwide).
Cosyntropin Test
250 mcg IV → cortisol at 0, 30, 60 min. Normal: cortisol ≥ 18. Fails to stimulate → AI confirmed.
Stress Dosing
Minor illness: double home dose × 3 days. Major surgery: hydrocortisone 100 mg IV → 50 q8h × 24h → taper. Always carry emergency injection.
Medic Alert
All patients with adrenal insufficiency need medic alert bracelet + emergency injection kit + sick day rules written down.
📄 One Pager
Adrenal Insufficiency & Crisis — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
ADRENAL INSUFFICIENCY & CRISIS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
📄 One Pager
Endocrine · One Pager
Adrenal Insufficiency & Crisis
Hydrocortisone 100 mg IV immediately for crisis. Don't wait for labs. Primary = high ACTH + hyperpigmentation + hyperK. Secondary = low ACTH. Stress dosing rules for all patients.
Classification
Primary (Addison): adrenal destruction → low cortisol + HIGH ACTH + hyperpigmentation + hyperkalemia. Secondary/tertiary: pituitary/hypothalamic failure or chronic steroids → low cortisol + LOW ACTH. No hyperpigmentation, no hyperK.
Crisis Treatment
Hydrocortisone 100 mg IV bolus immediately → 50 mg q8h. IVF with D5NS (hypoglycemia risk). Don't wait for cosyntropin test results. Draw cortisol + ACTH before treatment if possible (don't delay).
Chronic Management
Hydrocortisone 15-25 mg/day (divided: 2/3 AM + 1/3 PM). Fludrocortisone 0.05-0.1 mg daily (primary only — mineralocorticoid). Stress dosing: double dose for illness, 100 mg IV for surgery. Medic alert bracelet.
Key Drugs
Hydrocortisone (Solu-Cortef)100 mg IV bolus (crisis)
Hydrocortisone (Solu-Cortef)15-25 mg/day PO (chronic)
Fludrocortisone0.05-0.1 mg daily (primary)
DexamethasoneIf testing needed (doesn't interfere with assay)
Pitfalls
- Waiting for cosyntropin results to treat crisis (treat immediately)
- Forgetting fludrocortisone in primary AI (needed for mineralocorticoid)
- Abrupt steroid withdrawal → crisis
- Not teaching stress dosing rules and emergency injection
SIADH & Diabetes Insipidus
Two opposite disorders of water balance. SIADH: too much ADH → water retention → dilutional hyponatremia. DI: too little ADH (or resistance) → massive free water loss → hypernatremia. Correct slowly — osmotic demyelination kills.
💧 SIADH
Diagnostic Criteria — ALL Must Be Present
- Serum Na⁺ < 135 mEq/L (hyponatremia)
- Serum osmolality < 275 mOsm/kg (hypo-osmolar)
- Urine osmolality > 100 mOsm/kg (inappropriately concentrated urine)
- Urine sodium > 40 mEq/L (kidneys wasting sodium)
- Euvolemic on clinical exam (no edema, no orthostasis)
- Normal thyroid and adrenal function (must rule out hypothyroidism and cortisol deficiency — both cause hyponatremia)
SIADH is a diagnosis of exclusion. You must rule out hypothyroidism (check TSH) and adrenal insufficiency (check AM cortisol) before diagnosing SIADH. Both cause hyponatremia and both are treatable with specific therapy.
Common Causes
| Category | Examples |
|---|---|
| CNS | Stroke, SAH, meningitis, head trauma, neurosurgery |
| Pulmonary | Pneumonia (especially Legionella), TB, positive pressure ventilation, lung cancer |
| Malignancy | Small cell lung cancer (ectopic ADH production — classic association) |
| Drugs | SSRIs (#1 drug cause), carbamazepine, cyclophosphamide, desmopressin, oxytocin, thiazides |
| Post-surgical | Pain, nausea, anesthesia → all stimulate ADH release |
Management
| Severity | Treatment | Correction Rate |
|---|---|---|
| Asymptomatic / chronic (Na 120–134) | Fluid restriction (800–1000 mL/day). Stop offending drugs. Treat underlying cause. Salt tabs ± urea if refractory. | ≤ 8 mEq/L per 24h (some use ≤ 10). Chronic hyponatremia → brain has adapted → rapid correction → ODS. |
| Symptomatic (seizures, coma, severe AMS) | 3% hypertonic saline 100–150 mL IV bolus over 10–20 min. May repeat × 2 if no improvement. ICU admission. | Immediate goal: raise Na by 4–6 mEq/L in first 6h to stop symptoms. Then ≤ 8 mEq/L total in 24h. |
| Refractory | Tolvaptan (Samsca) 15 mg PO daily — vasopressin V2 receptor antagonist ("vaptan"). Or oral urea 15–30g daily. SALT-1/SALT-2, Schrier 2006 | Tolvaptan: do NOT use with hypertonic saline (risk of overcorrection). Monitor Na q6h. Only use in hospital. |
Verbalis Expert Panel, 2013 Osmotic Demyelination Syndrome (ODS): if Na corrects too fast (> 8–10 mEq/L in 24h), myelin in the central pons is destroyed → "locked-in syndrome" (awake but unable to move or speak). Irreversible. Risk factors: chronic hyponatremia, alcoholism, malnutrition, hypokalemia, liver disease. If overcorrecting → give D5W + desmopressin (DDAVP) 2 mcg IV q8h to re-lower Na.
🔥 Diabetes Insipidus
Types
| Type | Mechanism | Causes | Urine Osm after DDAVP |
|---|---|---|---|
| Central DI | ↓ ADH production (posterior pituitary) | Neurosurgery (#1), pituitary tumors, head trauma, brain death, Sheehan syndrome, infiltrative (sarcoid, histiocytosis) | ↑↑ (concentrates > 50%) — kidneys respond to exogenous ADH |
| Nephrogenic DI | Kidney resistance to ADH | Lithium (#1 drug cause), hypercalcemia, hypokalemia, chronic kidney disease, demeclocycline | No change — kidneys don't respond |
Presentation & Diagnosis
- Polyuria (> 3 L/day of dilute urine — Uosm < 300)
- Polydipsia (intense thirst if alert)
- Hypernatremia (if unable to access water — ICU patients, post-neurosurgery, AMS)
- Urine osmolality < 300 with serum osmolality > 290 → inappropriate dilute urine
- Water deprivation test → distinguishes central vs nephrogenic (give DDAVP and measure urine osm response)
Treatment
| Type | Treatment | Notes |
|---|---|---|
| Central DI | Desmopressin (DDAVP) 1–2 mcg IV/SC q12h or 10–20 mcg intranasal BID | Replaces missing ADH. Monitor Na closely — risk of hyponatremia with overdose. Titrate to UOP. |
| Nephrogenic DI | Remove offending agent (lithium). Low-sodium diet + thiazide diuretic (paradoxically ↓ urine output). Amiloride for lithium-induced NDI. | DDAVP does NOT work (kidneys are resistant). Thiazide paradox: thiazides cause mild volume depletion → ↑ proximal reabsorption → less water delivered to collecting duct → less dilute urine. |
| Acute hypernatremia (from DI) | D5W or 0.45% NS IV. Free water deficit = TBW × (Na/140 − 1). | Correct ≤ 10 mEq/L per 24h if chronic. If acute (< 48h) → can correct faster. Replace ongoing free water losses (UOP) in addition to deficit. |
📋 On Rounds
A patient's Na corrected from 112 to 124 in 18 hours. What do you do?
That's a 12 mEq/L correction in 18h — too fast. The safe limit is ≤ 8–10 mEq/L in 24h. Immediate steps: (1) D5W infusion (free water to re-lower Na), (2) DDAVP 2 mcg IV q8h (replaces ADH → kidneys retain free water → Na drops back), (3) target Na back to no more than 8 mEq/L above the starting value for the 24h period. The goal is to "re-lower" the sodium to a safe correction trajectory. ODS is preventable if you catch overcorrection early — this is why you check Na q4–6h when correcting severe hyponatremia.
Why do thiazides paradoxically help nephrogenic DI?
Counterintuitive but elegant: thiazides block NaCl reabsorption in the distal convoluted tubule → mild sodium and volume depletion → the body compensates by increasing proximal tubule reabsorption of sodium AND water → less water is delivered to the ADH-insensitive collecting duct → less dilute urine produced → lower urine volume. The effect reduces urine output by ~30–50%. Combined with a low-sodium diet (further driving proximal reabsorption), this can significantly reduce polyuria in nephrogenic DI patients who don't respond to DDAVP.
How does tolvaptan work and why must you start it inpatient?
Tolvaptan is a V2 receptor antagonist — blocks ADH (vasopressin) at the collecting duct → induces a free water diuresis (aquaresis) without sodium loss. Result: concentrated urine, dilute plasma → sodium rises. Must be started inpatient because the sodium correction can be unpredictable and rapid → risk of overcorrection → osmotic demyelination syndrome (ODS). Monitoring protocol: Na checked at 4-6h, 8-12h, and 24h after first dose. Hold if correcting > 8 mEq/24h. No fluid restriction while on tolvaptan (patients should drink to thirst — restricting water + blocking ADH → dangerously rapid correction). Hepatotoxicity risk with prolonged use → FDA limits to 30 days, monitor LFTs. Contraindicated if patient can't sense/respond to thirst (AMS, intubated).
What are the criteria for diagnosing SIADH?
Essential criteria (all must be met): (1) Serum osm < 275 mOsm/kg (hypoosmolar), (2) Urine osm > 100 mOsm/kg (inappropriately concentrated — the kidneys SHOULD be making dilute urine in hypo-osmolar state), (3) Euvolemic (no edema, no JVD, no orthostasis), (4) Urine Na > 40 mEq/L (kidneys excreting sodium inappropriately), (5) Normal thyroid and adrenal function (hypothyroidism and adrenal insufficiency both cause hyponatremia and must be excluded). (6) No diuretic use within 48h. SIADH is a diagnosis of exclusion — you must rule out heart failure (hypervolemic hyponatremia), cirrhosis (hypervolemic), dehydration (hypovolemic), hypothyroidism, and adrenal insufficiency first. Only then is it SIADH.
A patient with Na 118 and seizures — what do you give and how fast do you correct?
3% hypertonic saline 100-150 mL bolus over 10 min. Can repeat ×1. Target 4-6 mEq/L rise in the first 4-6h. Do NOT exceed 8 mEq/24h (6 if high-risk). Overcorrection → osmotic demyelination syndrome.
What is the most dangerous time for osmotic demyelination syndrome (ODS)?
ODS presents 2-6 days after overcorrection with dysarthria, dysphagia, quadriparesis, and locked-in syndrome. Risk factors: chronic hyponatremia > 48h, alcoholism, malnutrition, liver disease, hypokalemia.
When should you give DDAVP in hyponatremia management?
As an ODS rescue — if Na is correcting too fast (> 8 mEq/24h or > 6 in high-risk). Give DDAVP 2 mcg IV q8h + D5W to re-lower sodium back to the safe correction rate.
Why must you check TSH and cortisol before diagnosing SIADH?
Both hypothyroidism and adrenal insufficiency cause hyponatremia and mimic SIADH (euvolemic, concentrated urine). They are treatable and MUST be excluded. SIADH is a diagnosis of exclusion.
📣 Sample Presentation
One-Liner
"Mr. Foster is a 68-year-old started on sertraline 3 weeks ago presenting with Na⁺ 122, serum osm 258, urine osm 480, UNa 52, euvolemic. TSH and cortisol normal. SIADH from SSRI."
Key Points to Cover on Rounds
SIADH — euvolemic hypoosmolar hyponatremia with inappropriately concentrated urine and high UNa. Cause: sertraline (SSRIs are the most common drug cause of SIADH). Asymptomatic (no seizure, no AMS). Treatment: fluid restriction <1L/day started. Sertraline held — discuss alternative antidepressant with psychiatry. Na trending 122→124→126 over 36h (rate 3 mEq/24h — safe, goal ≤8 per 24h). Plan: if refractory to fluid restriction → salt tabs 1g TID. If still refractory → tolvaptan (inpatient only, check Na q6h). ODS rescue protocol available if overcorrected (D5W + DDAVP).
🧪 Workup
Diagnostic Evaluation — Cellulitis & Skin Infections
Workup checklist for Cellulitis & Skin Infections: History and physical → targeted labs → imaging as indicated → specialist consultation if needed. Always correlate clinically.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications, relevant PMH
- Physical exam: Focused exam relevant to cellulitis & skin infections presentation
- Labs: CBC, BMP, relevant disease-specific labs (see Overview tab for specifics)
- Imaging: As clinically indicated based on presentation
- Special studies: Consider disease-specific diagnostics (see Overview tab)
⚡ Management
Management — SIADH & Diabetes Insipidus
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
💊 Medications
Key Medications — Cellulitis & Skin Infections
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — Cellulitis & Skin Infections
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
⚡ Summary
Summary
Diagnostic Criteria
Serum osm < 275 + urine osm > 100 + euvolemic + UNa > 40 + normal thyroid/adrenal function + no diuretics. Diagnosis of exclusion.
Common Causes
SSRIs (#1 drug cause), carbamazepine, cyclophosphamide, vincristine. CNS: stroke, SAH, meningitis. Pulmonary: pneumonia, TB. Malignancy: SCLC.
Treatment
Fluid restriction < 1L/day (first-line) → salt tabs → tolvaptan (V2 antagonist, inpatient only, check Na q6h). Treat underlying cause.
Tolvaptan Rules
Start inpatient. No fluid restriction while on it. Check Na at 4-6h, 8-12h, 24h. Hold if correcting > 8 mEq/24h. Hepatotoxicity risk (max 30 days).
Correction Rate
≤ 8 mEq/L per 24h. High-risk for ODS: Na < 105, chronic, alcoholism, malnutrition, liver disease. In high-risk → ≤ 6 mEq/24h.
ODS Rescue
D5W + DDAVP 2 mcg IV q8h if overcorrecting. Act immediately. ODS = devastating irreversible pontine demyelination.
📄 One Pager
Cellulitis & Skin Infections — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
CELLULITIS & SKIN INFECTIONS — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
Hypercalcemia
"Stones, bones, groans, thrones, and psychiatric overtones." Corrected Ca > 10.5 mg/dL. 90% caused by primary hyperparathyroidism or malignancy. Aggressive IVF is the first treatment for everything — then target the cause.
🔍 Overview
Severity
| Level | Corrected Ca | Symptoms |
|---|---|---|
| Mild | 10.5–12 mg/dL | Often asymptomatic. Fatigue, constipation. |
| Moderate | 12–14 mg/dL | Polyuria, polydipsia, nausea, constipation, confusion, short QT on ECG. |
| Severe (hypercalcemic crisis) | > 14 mg/dL | AMS, stupor, coma, cardiac arrhythmias (short QT → Osborn waves → cardiac arrest), AKI, pancreatitis. |
Always correct for albumin: Corrected Ca = measured Ca + 0.8 × (4.0 − albumin). Or check ionized calcium (more accurate, especially in ICU patients).
Differential — The Two Big Ones
| Cause | % of Cases | PTH | Key Features |
|---|---|---|---|
| Primary hyperparathyroidism | ~55% (most common overall, #1 outpatient cause) | ↑ or inappropriately normal | Usually mild, chronic. Single adenoma (~85%). ↑ Ca, ↓ PO₄, ↑ urine Ca. Stones, osteoporosis. |
| Malignancy | ~35% (#1 inpatient cause) | ↓ (suppressed) | Usually severe, acute onset. Mechanisms: PTHrP secretion (squamous cell, RCC, breast → humoral hypercalcemia of malignancy), osteolytic metastases (breast, myeloma), calcitriol production (lymphoma). |
| Other (~10%) | Variable | Granulomatous disease (sarcoid → ↑ calcitriol), thiazides, lithium, vitamin D intoxication, milk-alkali syndrome, immobilization, thyrotoxicosis, Addison disease. |
First lab after finding hypercalcemia: PTH. PTH high or normal → primary hyperparathyroidism. PTH low → malignancy or other cause → check PTHrP, vitamin D levels (25-OH and 1,25-OH), SPEP/UPEP.
🚨 Management
Acute Hypercalcemia Treatment
| Step | Drug | Dose | Onset | Notes |
|---|---|---|---|---|
| 1. Volume | IV NS FIRST | 200–500 mL/hr (aggressive — these patients are volume-depleted from hypercalcemia-induced nephrogenic DI) | Hours | Always start here. Volume expansion enhances renal Ca excretion. Target UOP 200–300 mL/hr. Most patients need 3–6 L in first 24h. |
| 2. Calcitonin | Calcitonin (Miacalcin) | 4 IU/kg SC/IM q12h | 4–6 hours | Fastest onset. Inhibits osteoclasts + enhances renal Ca excretion. Effect is modest (↓ Ca by 1–2 mg/dL) and tachyphylaxis within 48h (receptors downregulate). Bridge to bisphosphonate. |
| 3. Bisphosphonate | Zoledronic acid (Zometa) MOST EFFECTIVE | 4 mg IV over 15 min | 2–4 days | Potent osteoclast inhibitor. Best for malignancy-associated hypercalcemia. Effect lasts 2–4 weeks. Nephrotoxic — hold if Cr > 4.5. Alternative: pamidronate 60–90 mg IV over 2–4h. |
| 4. Denosumab | Denosumab (Xgeva) | 120 mg SC | 4–10 days | RANKL inhibitor. Use if bisphosphonate-refractory or CKD (not renally cleared). Risk: severe rebound hypercalcemia when stopped. |
| Steroids | Hydrocortisone (Solu-Cortef) 200 mg IV/day | As needed | Days | Specific indications: granulomatous disease (sarcoid → steroids ↓ calcitriol production), lymphoma, vitamin D intoxication, myeloma. Ineffective for PTH-mediated or most solid tumor hypercalcemia. |
| Dialysis | Hemodialysis with low-Ca bath | Emergent | Immediate | Last resort for severe (> 18 mg/dL), symptomatic, refractory, or with AKI preventing bisphosphonate use. |
Furosemide for hypercalcemia is largely obsolete. Old teaching was "saline + Lasix." Current evidence: loop diuretics only help if the patient is volume-overlo
aded from aggressive IVF. Do NOT give furosemide to a dehydrated patient — worsens volume
depletion and renal Ca handling. Hydrate first.
🧪 Workup
Workup
- PTH — the single most important test. Elevated/inappropriately normal = PTH-mediated (primary hyperparathyroidism 90%). Suppressed = PTH-independent (malignancy, granulomatous, vitamin D).
- PTHrP — if PTH suppressed. Humoral hypercalcemia of malignancy (squamous cell lung, renal, breast). Elevated in ~80% of malignancy-associated hypercalcemia.
- 25-OH vitamin D — exogenous vitamin D toxicity
- 1,25-dihydroxy vitamin D — elevated in granulomatous disease (sarcoidosis, TB, histoplasmosis, lymphoma) — macrophage 1α-hydroxylase activity. Normal PTH, suppressed PTHrP.
- SPEP/UPEP + free light chains — multiple myeloma (osteolytic lesions → calcium release). Must check in unexplained hypercalcemia, especially with bone pain + anemia + renal failure.
- Corrected calcium = measured Ca + 0.8 × (4 − albumin). Or use ionized calcium (more accurate, not affected by albumin).
- ECG — shortened QT interval. Severe: Osborn waves, bradycardia, heart block.
- Cr + BUN — hypercalcemia causes nephrogenic DI → dehydration → prerenal AKI (most patients are significantly volume-depleted)
- Phosphorus — low in hyperPTH (PTH causes phosphaturia). High in vitamin D toxicity, granulomatous disease, tumor lysis.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Normal saline | 200-300 mL/hr | IV | FIRST and most important step. Most patients 3-6L depleted from hypercalcemia-induced nephrogenic DI. Restores GFR → renal calcium excretion. |
| Calcitonin | Endocrine Society, 2014 4 IU/kg IM/SQ q12h | IM/SQ | Fast onset (4-6h). Bridges to bisphosphonate effect. Modest drop (~1-2 mg/dL). Tachyphylaxis at 48h — stop after 2 days. |
| Zoledronic acid | Zoledronic Acid Hypercalcemia Trial, 2001 4 mg IV over 15 min | IV | Most potent long-term treatment. Onset 2-4 days, peak 4-7 days, lasts weeks. Avoid if CrCl < 35 (use denosumab instead). Monitor for osteonecrosis of jaw (rare). |
| Denosumab | Denosumab Hypercalcemia Trial, 2014 120 mg SQ | SQ | RANKL inhibitor. Use if renal impairment (not renally cleared) or bisphosphonate failure. Risk of severe rebound hypercalcemia if stopped. |
| Prednisone | 20-40 mg daily | PO | Granulomatous disease and lymphoma ONLY. Blocks 1α-hydroxylase in macrophages. NOT effective for PTH-mediated or PTHrP-mediated. |
| Cinacalcet | 30 mg BID | PO | Calcimimetic for primary hyperPTH (if not surgical candidate). Also parathyroid carcinoma. Lowers PTH → lowers Ca. |
| Furosemide (Lasix) | 20-40 mg IV PRN | IV | ONLY after adequate hydration. Calciuresis. Do NOT give to dehydrated patient — worsens hypercalcemia. |
📊 Monitoring
Monitoring
- Ionized calcium q6-12h during active treatment (more accurate than corrected Ca in critical illness, hypoalbuminemia, acid-base disorders)
- BMP q12-24h — Cr (renal function during aggressive hydration), K⁺, Mg²⁺ (calcitonin can cause hypokalemia/hypomagnesemia)
- Urine output q1-4h during initial hydration — target ≥ 100-150 mL/hr. Hypercalcemia causes nephrogenic DI → patients are severely volume-depleted
- ECG — short QT interval, Osborn waves, bradycardia at very high levels. Monitor for QTc normalization
- Repeat Ca²⁺ at 48h after zoledronic acid — onset 2-4 days, peak effect 4-7 days. Don't re-dose before day 7.
- Phosphate — bisphosphonates can cause hypophosphatemia
- Mental status — confusion, lethargy correlate with severity ("bones, stones, groans, psychiatric overtones")
- Daily volume status — aggressive IVF can cause overload in CHF/CKD patients
📋 On Rounds
How do you distinguish hyperparathyroidism from malignancy as the cause?
PTH level. In primary hyperparathyroidism, PTH is elevated or inappropriately normal (should be suppressed by high calcium but isn't — the parathyroid adenoma is autonomously producing PTH). In malignancy, PTH is suppressed (low) because the hypercalcemia is driven by PTHrP, osteolytic metastases, or calcitriol — all of which suppress normal PTH via negative feedback. Clinical context helps too: hyperparathyroidism = chronic, mild, outpatient finding. Malignancy = acute, severe (> 14), inpatient, patient looks sick.
Why does calcitonin lose effectiveness after 48 hours?
Tachyphylaxis from receptor downregulation. Calcitonin binds osteoclast calcitonin receptors, inhibiting bone resorption. With sustained exposure (> 48h), osteoclasts internalize and downregulate their calcitonin receptors — they become resistant to the drug. The clinical effect fades and calcium starts rising again. This is why calcitonin is a bridge agent — its fast onset (4–6h) buys you time while waiting for bisphosphonates to kick in (2–4 days). You should never rely on calcitonin alone for more than 48h.
Why is furosemide no longer recommended for hypercalcemia treatment?
Old teaching: "NS + Lasix for hypercalcemia" — the idea was furosemide blocks calcium reabsorption in the Loop of Henle (calciuresis). Current evidence: furosemide is NOT recommended unless the patient is volume overloaded. Reasons: (1) Most hypercalcemia patients are severely volume depleted (hypercalcemia → nephrogenic DI → polyuria → dehydration). Giving furosemide before adequate volume repletion worsens dehydration → worsens hypercalcemia. (2) The calciuretic effect is modest and inconsistent. (3) Risk of hypokalemia and hypomagnesemia. Correct treatment order: (1) Aggressive NS hydration (200-300 mL/hr — volume expansion is the most important initial step), (2) Calcitonin (fast onset, bridges to bisphosphonate), (3) Zoledronic acid (most effective, onset 2-4 days). Furosemide only if signs of fluid overload during hydration.
What is the approach to determining the etiology of hypercalcemia?
PTH is the branch point. Check PTH first. PTH elevated (or inappropriately normal): primary hyperparathyroidism (#1 cause of hypercalcemia in outpatients). Rarely: familial hypocalciuric hypercalcemia (FHH — check 24h urine calcium: FHH has low urine Ca, PHPT has high urine Ca), lithium-induced, parathyroid carcinoma. PTH suppressed (< 20): non-PTH-mediated. Check PTHrP: if elevated → humoral hypercalcemia of malignancy (squamous cell, RCC, breast). If PTHrP normal → check 1,25-diOH vitamin D (if elevated: granulomatous disease — sarcoid, TB, lymphoma). If 1,25 normal → check 25-OH vitamin D (if elevated: vitamin D toxicity). If all normal → lytic bone metastases (myeloma, breast, lung). Outpatients: PHPT is #1. Inpatients: malignancy is #1.
What is the single most important test in the workup of hypercalcemia?
PTH. It's the diagnostic branch point. Elevated/normal PTH = PTH-mediated (90% primary hyperparathyroidism). Suppressed PTH = malignancy, granulomatous disease, or vitamin D toxicity.
Why should you NOT give furosemide as initial treatment for hypercalcemia?
Most patients are severely dehydrated from hypercalcemia-induced nephrogenic diabetes insipidus. Furosemide in a dehydrated patient worsens volume depletion and hypercalcemia. Rehydrate with NS first, then furosemide only if volume-overloaded.
A patient with sarcoidosis has hypercalcemia. Which medication treats it and why?
Prednisone — sarcoid macrophages express 1α-hydroxylase that converts 25-OH vitamin D to active 1,25-dihydroxy vitamin D. Steroids suppress this enzyme. Bisphosphonates are less effective because the mechanism is vitamin D-mediated, not bone resorption.
Why does calcitonin have tachyphylaxis at 48 hours?
Calcitonin receptors on osteoclasts become downregulated after 48h of continuous exposure. The Ca-lowering effect wanes. It's used only as a bridge while waiting for zoledronic acid to take effect (onset 2-4 days).
📣 Sample Presentation
One-Liner
"Mrs. Taylor is a 72-year-old with metastatic breast cancer presenting with confusion, constipation, and polyuria. Ca²⁺ 14.8 (corrected for albumin). PTH suppressed at 8. PTHrP pending."
Key Points to Cover on Rounds
Hypercalcemia of malignancy (PTH suppressed → not primary hyperparathyroidism). Most likely humoral hypercalcemia (PTHrP secretion from breast cancer). Treatment initiated: (1) NS at 250 mL/hr (volume expansion — first priority), (2) calcitonin 4 IU/kg IM q12h (fast onset, bridges to zoledronic acid, tachyphylaxis at 48h), (3) zoledronic acid 4 mg IV over 15 min (most effective long-term, onset 2-4 days). No furosemide unless volume overloaded. Ca trending 14.8→13.2→11.4 over 48h. Plan: oncology for disease-directed therapy, repeat Ca in 48h, denosumab if bisphosphonate fails.
⚡ Summary
Summary
Branch Point
Check PTH first. Elevated → primary hyperparathyroidism. Suppressed → malignancy (check PTHrP), granulomatous disease (check 1,25-D), meds.
Outpatient #1
Primary hyperparathyroidism (elevated PTH + elevated Ca). Parathyroid adenoma most common. Surgery if symptomatic or meets criteria.
Inpatient #1
Malignancy: humoral (PTHrP — squamous, RCC, breast), osteolytic (myeloma, breast mets), 1,25-D production (lymphoma).
Treatment Order
(1) NS 200-300 mL/hr (most important), (2) calcitonin (fast, bridges to bisphosphonate, tachyphylaxis at 48h), (3) zoledronic acid (most effective, onset 2-4 days). No furosemide unless overloaded.
Severe Ca > 14
Aggressive hydration + calcitonin + zoledronic acid. ICU if cardiac symptoms, AMS, or severe dehydration. ECG: short QT.
Symptoms
Stones (renal), bones (pain, fractures), groans (abdominal pain, constipation, pancreatitis), moans (AMS, depression), overtones (polyuria, dehydration).
📄 One Pager
Endocrine / Oncology · One Pager
Hypercalcemia
PTH is the branch point. Outpatient #1: primary hyperparathyroidism. Inpatient #1: malignancy. NS hydration first → calcitonin → zoledronic acid. No furosemide unless overloaded.
Etiology — PTH Branch
PTH elevated: primary hyperparathyroidism (parathyroid adenoma). PTH suppressed: malignancy (PTHrP → squamous, RCC, breast), granulomatous disease (sarcoid, TB → 1,25-D), vitamin D toxicity, lytic bone mets.
Treatment
(1) NS 200-300 mL/hr (most important — rehydrate first). (2) Calcitonin 4 IU/kg IM q12h (fast onset, bridges to bisphosphonate, tachyphylaxis at 48h). (3) Zoledronic acid 4 mg IV over 15 min (most effective, onset 2-4 days).
Symptoms — Stones, Bones, Groans, Moans
Stones (renal), Bones (pain, fractures), Groans (constipation, abd pain, pancreatitis), Moans (depression, AMS), Overtones (polyuria, dehydration, short QT).
Key Drugs
NS200-300 mL/hr
Calcitonin4 IU/kg IM q12h
Zoledronic acid4 mg IV over 15 min
Denosumab120 mg SQ (if bisphosphonate fails)
Pitfalls
- Furosemide for hypercalcemia (only if volume overloaded — most patients are dehydrated)
- Not checking PTH first (the diagnostic branch point)
- Delayed hydration
- Missing malignancy as cause in hospitalized patients
Rotation
Endocrinology
Diabetes management, thyroid disorders, adrenal pathology, calcium disorders, and pituitary emergencies.
Available Topics
Inpatient Insulin Management
Thyroid Storm & Myxedema
Adrenal Crisis
SIADH & Diabetes Insipidus
Hypercalcemia
HHS (Hyperosmolar State)
Myxedema Coma
Pheochromocytoma
Inpatient Hypoglycemia
Hypocalcemia
Diabetes Insipidus
Cushing's Syndrome
Hyperthyroidism / Graves'
Primary Aldosteronism
Hypothyroidism
Hypoparathyroidism
📋 Major Guidelines
Rheumatoid Arthritis
Symmetric inflammatory polyarthritis of the small joints. Early aggressive treatment with DMARDs prevents joint destruction. "Treat to target" — remission or low disease activity. Know the extra-articular manifestations and drug monitoring.
🔍 Overview
Diagnosis
- Symmetric polyarthritis of small joints: MCPs, PIPs, wrists, MTPs. Spares DIPs (DIP involvement → think OA or psoriatic).
- Morning stiffness > 30 minutes (improves with use — opposite of OA which worsens with use)
- Labs: RF (sensitive ~70%, not specific), anti-CCP (most specific ~95%), ESR, CRP elevated. Anti-CCP negative RA exists (seronegative — harder to diagnose).
- Imaging: X-ray hands/feet — periarticular osteopenia, joint space narrowing, marginal erosions (late). US or MRI for early synovitis detection.
Extra-Articular Manifestations
| System | Manifestation |
|---|---|
| Pulmonary | ILD (UIP pattern — leading cause of RA mortality after CVD), pleural effusions (low glucose, high protein), rheumatoid nodules in lung (Caplan syndrome with pneumoconiosis) |
| Cardiovascular | Accelerated atherosclerosis (#1 cause of death in RA — CV risk equivalent to DM). Pericarditis. |
| Hematologic | Anemia of chronic disease. Felty syndrome: RA + splenomegaly + neutropenia. |
| Cervical spine | C1-C2 (atlantoaxial) subluxation — check flexion/extension X-ray before intubation. Can cause cord compression. |
| Eye | Scleritis, episcleritis, keratoconjunctivitis sicca (Sjögren overlap) |
| Skin | Rheumatoid nodules (extensor surfaces, elbows). Vasculitis (rare, severe). |
💊 Treatment
| Line | Drug | Monitoring | Key Notes |
|---|---|---|---|
| 1ST LINE | Methotrexate (Trexall) 15–25 mg PO/SC weekly | CBC, LFTs, Cr q3 months. CXR at baseline (ILD screening). | Cornerstone of RA treatment. Always give with folic acid 1 mg daily (reduces GI/oral side effects). Teratogenic — contraception required. Avoid in liver disease, heavy EtOH. Hold for surgery (infection risk). |
| ADD-ON | Hydroxychloroquine (Plaquenil) 200–400 mg daily | Annual eye exam (retinal toxicity after 5 years) | Mild disease or combination therapy. Very safe. Also used in SLE. |
| ADD-ON | Sulfasalazine 2–3g daily | CBC, LFTs | Triple therapy (MTX + HCQ + SSZ) is as effective as many biologics for moderate RA. |
| BIOLOGIC | TNF inhibitors (adalimumab, etanercept, infliximab) | Screen for TB (QuantiFERON), Hep B/C, HIV before starting. Annual TB screening. | Add to MTX if inadequate response. Hold for active infection and peri-operatively. Risk: TB reactivation, serious infections, lymphoma (small increase). |
| BIOLOGIC | IL-6 inhibitor (tocilizumab), JAK inhibitor (tofacitinib, upadacitinib) | CBC, LFTs, lipids. JAKi: screen for VTE risk. | Alternatives if TNFi fails. JAK inhibitors: FDA black box for VTE, MACE, and malignancy in age > 65 ORAL Surveillance, 2022 — use after biologic failure. |
Screen for TB before ANY biologic or JAK inhibitor. TNF is critical for granuloma maintenance — TNF inhibition can reactivate latent TB. QuantiFERON-Gold or PPD. If positive → treat latent TB (isoniazid × 9 months or rifampin × 4 months) for ≥ 1 month before starting biologic.
🚨 Management
Management
- Goal: Remission or low disease activity within 6 months — treat-to-target [TICORA, 2004]. Check DAS28 or CDAI q3 months. Adjust until target reached.
- First-line: Methotrexate 15-25 mg/week PO or SQ + folic acid 1 mg daily (reduces side effects without reducing efficacy). Start 15 mg, escalate to 25 mg by week 8 if tolerated. SQ has better bioavailability at higher doses.
- Bridge therapy: Low-dose prednisone ≤ 10 mg daily while waiting for DMARD effect (4-12 weeks). Taper ASAP — goal is OFF steroids. Depo-medrol intra-articular for 1-2 dominant joints.
- If inadequate at 3 months on max MTX: Add biologic DMARD:
- TNF inhibitors (adalimumab, etanercept, infliximab) — most commonly used first-line biologics
- Non-TNF biologics: tocilizumab (IL-6), abatacept (T-cell co-stim), rituximab (anti-CD20, especially if RF/CCP positive)
- JAK inhibitors: tofacitinib, upadacitinib, baricitinib — oral, fast onset. FDA box warning: ↑ VTE, MACE, malignancy in pts > 50 with CV risk factors [ORAL Surveillance, 2022]
- Pre-biologic checklist: QuantiFERON (TB), HBV/HCV serologies, update vaccines (no live vaccines on biologics), CXR
- Monitoring on MTX: CBC + CMP q4-8 weeks first 3 months, then q8-12 weeks. Hold MTX if transaminases > 2× ULN. Avoid alcohol. Contraception required (teratogenic — hold 3 months before conception).
📋 On Rounds
An RA patient on methotrexate is admitted with pneumonia. What do you do with the methotrexate?
Hold methotrexate during active infection. MTX is an immunosuppressant — continuing it impairs the patient's ability to fight the infection. Also hold if: surgery planned (increased wound healing complications), new cytopenias (check CBC), or rising LFTs. Resume once infection is treated and patient is clinically improving. Do NOT hold hydroxychloroquine — it has minimal immunosuppression and should be continued through illness.
Why do you check hepatitis B and TB before starting a biologic in RA?
Biologics (TNF inhibitors like adalimumab, infliximab; IL-6 inhibitors like tocilizumab; B-cell depleting agents like rituximab) cause profound immunosuppression that can reactivate latent infections. Hepatitis B: TNF inhibitors can cause fatal HBV reactivation (fulminant hepatitis) — check HBsAg, anti-HBs, anti-HBc. If HBsAg+ or anti-HBc+ → start antiviral prophylaxis (entecavir or tenofovir) before starting biologic. TB: TNF-α is essential for maintaining granuloma integrity that contains latent TB. TNF inhibition → granuloma breakdown → disseminated TB. Screen with QuantiFERON or PPD. If positive → treat latent TB (isoniazid × 9 months or rifampin × 4 months) before starting biologic, ideally ≥ 1 month ahead.
What is the treat-to-target approach in RA?
Goal: remission or low disease activity within 6 months. Start methotrexate (first-line DMARD, 15-25 mg/week + folic acid 1 mg daily). Reassess at 3 months: if not at target → add or switch therapy. Options: (1) Add biologic (TNFi: adalimumab, etanercept; or non-TNF: tocilizumab, abatacept, rituximab), (2) Add JAK inhibitor (tofacitinib, upadacitinib — oral, convenient, but risk of VTE/MACE at higher doses). Monitoring: DAS28 or CDAI score every 3-6 months. Adjust until target reached. Never accept "stable but active" disease — ongoing inflammation = joint destruction. Pre-treatment screening: TB (QuantiFERON), HBV/HCV, CBC, LFTs (methotrexate is hepatotoxic), CXR. Annual: flu + pneumococcal vaccines.
What monitoring is needed for a patient on methotrexate for RA?
Before starting: CBC, CMP (LFTs, Cr), hepatitis B/C serologies, chest X-ray (baseline for pulmonary toxicity), pregnancy test (teratogenic — Category X). Ongoing monitoring (every 2-3 months initially, then q3-6 months when stable): CBC (pancytopenia — bone marrow suppression), LFTs (hepatotoxicity — hold if AST/ALT > 2× ULN), Cr (renal clearance — dose reduce if CrCl declining). Must co-prescribe folic acid 1 mg daily (reduces GI side effects, oral ulcers, and myelosuppression without reducing efficacy). Watch for: methotrexate pneumonitis (acute dyspnea + cough + fever + GGO on CT — stop MTX, give steroids), nodulosis (paradoxically can increase RA nodules), lymphoproliferative disorders (rare).
What is the most specific antibody for RA?
Anti-CCP (anti-citrullinated peptide) — ~95% specific. Can be positive years before symptoms. High titer predicts more aggressive, erosive disease. RF is sensitive (~80%) but not specific.
A patient with RA on methotrexate for 3 months still has active disease. What's next?
Add a biologic DMARD (TNF inhibitor like adalimumab, or non-TNF like tocilizumab/abatacept). Per treat-to-target guidelines, if target not met at 3 months → escalate. If still not met at 6 months → switch class.
Why are DOACs inferior to warfarin in antiphospholipid syndrome?
The TRAPS trial [2018] was stopped early because rivaroxaban had significantly more arterial thrombotic events than warfarin in triple-positive APS. ASTRO-APS confirmed. The mechanism: DOACs don't adequately block the thrombin generation pathway in APS.
Which RA medication is safe in pregnancy?
Sulfasalazine and hydroxychloroquine are safe. Certolizumab (Fc-free anti-TNF) has minimal placental transfer. Methotrexate is category X — stop 3 months before conception. Leflunomide has a very long half-life — needs cholestyramine washout.
📣 Sample Presentation
One-Liner
"Mrs. Patterson is a 42-year-old with seropositive RA on methotrexate 20 mg weekly who presents with 3 weeks of worsening bilateral hand and wrist swelling and morning stiffness >2 hours. CRP 4.8, ESR 62. Active flare."
Key Points to Cover on Rounds
RA flare on methotrexate monotherapy. DAS28 score indicates high disease activity. Treatment: prednisone 20 mg PO burst × 5 days for acute symptom control. Rheumatology consulted — plan to add biologic (adalimumab or tocilizumab). Pre-biologic workup: QuantiFERON (TB), HBsAg, anti-HBs, anti-HBc (hepatitis B reactivation risk), hepatitis C, CBC, LFTs. Immunizations: flu, pneumococcal, COVID — updated before starting biologic. Plan: taper prednisone, initiate biologic when screening complete, repeat CRP in 4 weeks.
🧪 Workup
Workup
- RF (rheumatoid factor) — sensitive (~80%) but not specific. Also positive in Sjögren's, HCV, endocarditis, elderly.
- Anti-CCP (anti-citrullinated peptide) — most specific for RA (~95%). Can be positive years before symptoms. High titer = more aggressive/erosive disease.
- ESR + CRP — baseline disease activity markers. CRP more responsive to treatment changes.
- CBC, BMP, LFTs — baseline before starting DMARDs. Anemia of chronic disease common.
- Hepatitis B/C serologies — before methotrexate or biologics (reactivation risk)
- QuantiFERON/PPD — latent TB screening before biologics (especially TNF inhibitors)
- X-rays of hands/feet — baseline. Periarticular osteopenia, joint space narrowing, marginal erosions. Erosions within first 2 years in 70% untreated.
- Musculoskeletal ultrasound — synovitis, erosions earlier than X-ray. Increasingly used for subclinical inflammation.
- Joint distribution — symmetric small joint polyarthritis (MCPs, PIPs, wrists, MTPs). Spares DIPs (DIP involvement = think OA or psoriatic arthritis).
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Conventional DMARDs | |||
| Methotrexate | 15-25 mg/week | PO/SQ | First-line DMARD — anchor drug. Start with folic acid 1 mg daily (reduces GI + oral ulcer side effects). SQ better absorbed at doses > 15 mg. Monitor: CBC, LFTs, Cr q8-12 weeks. Teratogenic (category X) — stop 3 months before conception. |
| Leflunomide | 20 mg daily | PO | Alternative to MTX if intolerant. Pyrimidine synthesis inhibitor. Very long half-life (14 days). Cholestyramine washout if toxicity or pregnancy planned. |
| Sulfasalazine | 1-1.5g BID | PO | Mild RA or combination therapy. Safe in pregnancy (one of few DMARDs). Check G6PD. |
| Hydroxychloroquine | 200-400 mg daily | PO | Mild RA, often combined with MTX. Annual retinal screening after 5 years. |
| Biologic DMARDs — add if inadequate response to MTX at 3 months | |||
| Adalimumab | 40 mg SQ q2 weeks | SQ | TNF inhibitor. Most prescribed biologic. Screen TB/HBV before starting. Risk: serious infections, reactivation TB, lymphoma (rare). |
| Etanercept | 50 mg SQ weekly | SQ | TNF inhibitor (receptor fusion protein). Less TB reactivation risk than monoclonal anti-TNFs. Does NOT work for IBD (unlike other TNFis). |
| Tocilizumab | 162 mg SQ weekly or 8 mg/kg IV monthly | SQ/IV | Anti-IL-6 receptor. Suppresses CRP (can mask infection). Monitor lipids (LDL ↑), neutrophils, LFTs. Risk of GI perforation. |
| Abatacept | 125 mg SQ weekly | SQ | T-cell costimulation blocker (CTLA-4 Ig). Generally well tolerated. Good safety profile in elderly. |
| Rituximab | 1000 mg IV × 2 doses (day 1 + day 15) | IV | Anti-CD20 (B-cell depletion). Usually reserved for refractory RA after TNFi failure. Screen HBV. Monitor immunoglobulins. |
| JAK Inhibitors — oral targeted synthetic DMARDs | |||
| Tofacitinib | 5 mg BID | PO | JAK1/3 inhibitor. FDA boxed warning: increased CV events + malignancy vs TNFi in patients ≥ 50 with CV risk [ORAL Surveillance, 2022]. Use after TNFi failure. |
| Upadacitinib | 15 mg daily | PO | Selective JAK1 inhibitor. Superior to adalimumab in SELECT-COMPARE. Same FDA boxed warning class. VTE risk. |
Treat-to-target: reassess disease activity (DAS28, CDAI) every 3 months. If target not met at 3 months → escalate. If target not met at 6 months → switch class. Goal: remission or low disease activity.
📈 Monitoring
Monitoring
- DAS28 or CDAI score q3 months — standardized disease activity tracking. Adjust treatment to target.
- CBC, CMP (LFTs, Cr) q8-12 weeks on MTX — hepatotoxicity, cytopenias, renal function
- ESR + CRP q3-6 months — inflammatory marker trending
- X-rays hands/feet annually first 3 years — structural damage progression
- Lipids — check at baseline and periodically on tocilizumab and JAK inhibitors
- Infection vigilance — on biologics/JAKi: annual flu + pneumococcal vaccines (inactivated only). Low threshold for workup of fever.
- Cervical spine X-ray — if surgery planned (atlantoaxial subluxation risk in severe RA)
- CV risk assessment — RA is an independent CV risk factor. Multiply Framingham score by 1.5.
⚡ Summary
Summary
Diagnosis
≥ 6 points on ACR/EULAR 2010 criteria. Joint involvement + serology (RF, anti-CCP) + acute phase (CRP, ESR) + duration ≥ 6 weeks.
First-Line DMARD
Methotrexate 15-25 mg/week + folic acid 1 mg daily. Monitor: CBC, LFTs, Cr every 2-3 months.
Treat-to-Target
Goal: remission or low disease activity within 6 months. Reassess q3 months. If not at target → add biologic or JAK inhibitor.
Biologics
TNFi (adalimumab, etanercept), IL-6 (tocilizumab), T-cell (abatacept), B-cell (rituximab), JAKi (tofacitinib, upadacitinib).
Pre-Biologic Screen
QuantiFERON (TB), HBV/HCV serologies, CBC, LFTs, CXR. Update vaccines before starting. Annual flu + pneumococcal.
Don't Miss
Atlantoaxial instability (subluxation) — flexion/extension C-spine X-ray before intubation. Increased CV risk. Screen for ILD.
📄 One Pager
Falls & Delirium Prevention — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
FALLS & DELIRIUM PREVENTION — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
Antiphospholipid Syndrome
Autoantibodies against phospholipid-binding proteins → arterial and venous thrombosis + pregnancy morbidity. The lab paradox: aPTT is prolonged (in vitro anticoagulant) but the patient is prothrombotic (in vivo). Warfarin, not DOACs.
🔍 Overview
Diagnostic Criteria (Revised Sapporo)
Requires ≥ 1 clinical criterion + ≥ 1 lab criterion, with lab confirmed on 2 occasions ≥ 12 weeks apart.
| Clinical Criteria (≥ 1) | Lab Criteria (≥ 1, confirmed × 2) |
|---|---|
| Vascular thrombosis: arterial, venous, or small vessel thrombosis in any organ (DVT, PE, stroke, MI, renal/hepatic thrombosis) | Lupus anticoagulant (LA) — most strongly associated with thrombosis |
| Pregnancy morbidity: ≥ 1 unexplained fetal death ≥ 10 weeks, ≥ 3 unexplained consecutive losses < 10 weeks, premature birth < 34 weeks due to eclampsia/placental insufficiency | Anticardiolipin (aCL) IgG or IgM — medium-high titer |
| Anti-β2 glycoprotein I IgG or IgM |
Triple-positive APS (all 3 antibodies positive) has the highest thrombotic risk. DOACs are CONTRAINDICATED in APS — TRAPS, 2018 showed rivaroxaban was inferior to warfarin with more thrombotic events. Warfarin is the standard.
Treatment
| Scenario | Treatment |
|---|---|
| Venous thrombosis (DVT/PE) | Warfarin INR 2–3, indefinite. No DOACs. |
| Arterial thrombosis (stroke, MI) | Warfarin INR 2–3 (some advocate INR 3–4 for arterial events, controversial). ± aspirin. |
| Obstetric APS (no thrombosis) | LMWH (enoxaparin prophylactic dose) + low-dose aspirin throughout pregnancy. |
| Catastrophic APS (CAPS) | Triple therapy: anticoagulation + high-dose steroids + plasma exchange or IVIG. Mortality ~50%. Multiorgan thrombotic microangiopathy. |
📋 On Rounds
Why is the aPTT prolonged in APS if the patient is actually prothrombotic?
The lupus anticoagulant binds to phospholipids that are used as reagents in the aPTT assay. In the test tube, this binding interferes with the phospholipid-dependent coagulation cascade → prolonged aPTT in vitro. But in vivo, these same antibodies bind endothelial cell phospholipids, activate complement, inhibit natural anticoagulants (protein C, annexin V), and activate platelets and monocytes → prothrombotic state. The test tube effect is opposite to the clinical effect. Key point: a prolonged aPTT that does NOT correct with a 1:1 mixing study (the antibody persists even when mixed with normal plasma) is characteristic of lupus anticoagulant.
Why are DOACs contraindicated in antiphospholipid syndrome?
The TRAPS trial (2018) was stopped early for safety — triple-positive APS patients randomized to rivaroxaban had significantly more thrombotic events (including stroke and MI) than those on warfarin. The mechanism is unclear but may relate to DOACs' inability to adequately suppress thrombin generation in the unique prothrombotic milieu of APS (which involves complement activation, endothelial dysfunction, and platelet activation beyond just thrombin). Warfarin with INR target 2–3 remains the standard. For patients with arterial thrombosis or recurrent events on warfarin INR 2–3, some experts target INR 3–4 or add low-dose aspirin. DOACs = wrong answer in APS, period.
What is catastrophic APS (CAPS) and how do you treat it?
CAPS = rapid-onset multi-organ thrombotic microangiopathy in APS — affects ≥ 3 organs within 1 week. Mortality ~30-50%. Organs affected: renal (TMA/RPGN), CNS (stroke, seizures), cardiac (valve thrombosis, MI), pulmonary (PE, ARDS), skin (livedo, digital gangrene). Triggered by: infection (#1), surgery, anticoag withdrawal, SLE flare. Treatment = triple therapy: (1) Anticoagulation (heparin drip), (2) High-dose steroids (methylprednisolone 1g IV × 3 days), (3) Plasma exchange (PLEX) or IVIG. Add rituximab or eculizumab (complement inhibitor) if refractory. Treat the trigger (antibiotics if infection). CAPS is an ICU emergency — recognize it early by the pattern of multi-organ thrombosis in a known APS patient.
What lab tests confirm APS and why do you need them positive twice?
3 antibodies: (1) Lupus anticoagulant (LA) — functional assay (prolonged aPTT that doesn't correct with mixing study). (2) Anticardiolipin antibodies (aCL) — IgG and IgM, medium-to-high titer. (3) Anti-β2-glycoprotein I (anti-β2GP1) — IgG and IgM. Must be positive on ≥ 2 occasions, at least 12 weeks apart — because transient positivity occurs with infections (HIV, hepatitis, syphilis), medications, and acute thrombotic events. A single positive test is NOT diagnostic. Triple-positive (all 3 positive) = highest thrombotic risk, worst prognosis, absolutely requires lifelong warfarin. Single-positive low-titer aCL = may be clinically insignificant. The antibody profile determines aggressiveness of treatment.
Why must antiphospholipid antibodies be confirmed at 12 weeks?
Transient aPL positivity occurs commonly during infections, medications, and other acute illnesses. Persistent positivity (≥ 12 weeks apart on 2 occasions) is required for diagnosis to avoid overdiagnosis and unnecessary lifelong anticoagulation.
What is catastrophic APS (CAPS)?
Multi-organ failure developing over < 1 week due to widespread small-vessel thrombosis. ~50% mortality. Affects ≥ 3 organ systems simultaneously. Treat with triple therapy: anticoagulation + high-dose steroids + PLEX or IVIG.
What is the standard regimen for obstetric APS?
Low-dose ASA (81 mg) started preconception + prophylactic LMWH (enoxaparin 40 mg daily) added once pregnancy confirmed. This reduces pregnancy loss from ~70% to ~20-30%.
Which APS patients are highest risk for recurrent thrombosis?
Triple-positive patients (lupus anticoagulant + anticardiolipin + anti-β2GP1 all positive). These patients need lifelong anticoagulation — never stop. Single positivity has lower (but not zero) recurrence risk.
📣 Sample Presentation
One-Liner
"Mr. Garcia is a 38-year-old with triple-positive APS (LA+, aCL+, anti-β2GP1+) on warfarin who presents with INR 1.3 and new left leg DVT on compression ultrasound."
Key Points to Cover on Rounds
Recurrent thrombosis in known triple-positive APS — INR subtherapeutic at 1.3 (goal 2-3). Acute DVT management: heparin drip started (bridge to therapeutic warfarin). INR target remains 2-3 — some experts recommend 3-4 for recurrent events on therapeutic warfarin. No DOACs (contraindicated in APS [TRAPS, 2018]). Adding hydroxychloroquine (reduces thrombosis risk in APS, especially SLE-associated). Warfarin adherence and diet counseled. Plan: lifelong warfarin, rheumatology follow-up, consider adding low-dose ASA if arterial events occur.
🧪 Workup
Workup
- Lupus anticoagulant (LA) — functional assay (dRVVT or PTT-LA). Paradoxically prolongs aPTT but is PROthrombotic. Most specific of the 3 tests.
- Anticardiolipin antibodies (IgG and IgM) — ELISA. Titers > 40 GPL/MPL are clinically significant.
- Anti-β2-glycoprotein I (IgG and IgM) — ELISA. Associated with thrombosis + obstetric complications.
- Repeat positive at 12 weeks — diagnosis requires positive on 2 occasions ≥ 12 weeks apart (transient positivity in infections is common).
- Triple positivity (all 3 positive) = highest thrombotic risk — lifelong anticoagulation, never stop.
- CBC — thrombocytopenia (20-40% of APS), hemolytic anemia (Coombs+)
- Peripheral smear — schistocytes if TMA component (catastrophic APS)
- Cr, LFTs — APS nephropathy, hepatic involvement
- Echocardiogram — Libman-Sacks endocarditis (non-bacterial vegetations, usually mitral valve)
- MRI brain — if neurological symptoms (stroke, TIA, cognitive dysfunction, seizures)
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Warfarin | Target INR 2-3 (arterial: 2.5-3.5) | PO | First-line for thrombotic APS. Lifelong after first event. DOACs are INFERIOR to warfarin in APS — TRAPS trial stopped early for excess arterial events with rivaroxaban [TRAPS, 2018]. ASTRO-APS confirmed: use warfarin, not DOACs. |
| Heparin (LMWH) | Enoxaparin 1 mg/kg BID | SQ | Acute thrombosis treatment, bridge to warfarin. Also used in obstetric APS. |
| ASA | 81 mg daily | PO | Primary prevention in asymptomatic aPL-positive patients (especially with SLE). Added to warfarin for arterial events. |
| Hydroxychloroquine | 200-400 mg daily | PO | Reduces thrombotic risk in SLE-associated APS. Antithrombotic + immunomodulatory properties. Consider in all APS patients. |
| Obstetric APS | |||
| ASA + LMWH | ASA 81 mg + enoxaparin 40 mg daily | PO/SQ | Standard regimen for obstetric APS (recurrent pregnancy loss, preeclampsia). Start ASA preconception, add LMWH at positive pregnancy test. |
| Catastrophic APS (CAPS) | |||
| Triple therapy | Anticoag + steroids + PLEX or IVIG | IV | CAPS = multi-organ failure in < 1 week. ~50% mortality. Anticoagulation + methylprednisolone 1g × 3d + plasma exchange. Add rituximab or eculizumab if refractory. |
📈 Monitoring
Monitoring Parameters — Discharge Planning Checklist
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
⚡ Summary
Summary
Criteria
Thrombosis (arterial or venous) OR pregnancy morbidity + persistent antiphospholipid antibodies (positive × 2, ≥ 12 weeks apart).
3 Antibodies
Lupus anticoagulant (functional), anticardiolipin (IgG/IgM), anti-β2-glycoprotein I (IgG/IgM). Triple-positive = highest risk.
Treatment
Warfarin (INR 2-3) lifelong. DOACs contraindicated [TRAPS, 2018]. Add hydroxychloroquine (reduces thrombosis). Low-dose ASA for arterial events.
Pregnancy
Low-dose aspirin + LMWH throughout pregnancy. Warfarin is teratogenic — must switch to LMWH pre-conception.
CAPS
Catastrophic APS: multi-organ thrombosis in ≤ 1 week. Mortality 30-50%. Triple therapy: anticoag + steroids + PLEX/IVIG. Add rituximab if refractory.
Don't Forget
APS can be primary or secondary (SLE). Screen all SLE patients for aPL antibodies. Screen young strokes and unprovoked VTE.
📄 One Pager
Discharge Planning Checklist — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
DISCHARGE PLANNING CHECKLIST — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
⚡ Management
Management
- Thrombotic APS — first event: Lifelong anticoagulation with warfarin (target INR 2-3). DOACs are inferior in triple-positive APS [TRAPS, 2018] — higher thrombotic events vs warfarin. DOACs may be acceptable for single/double-positive with venous events only.
- Thrombotic APS — recurrent event on warfarin INR 2-3: Increase target to INR 3-4, or add low-dose ASA, or switch to LMWH.
- Obstetric APS (recurrent pregnancy loss): Low-dose ASA 81 mg + prophylactic LMWH (enoxaparin 40 mg SQ daily) starting at positive pregnancy test through 6 weeks postpartum. [PROMISSE]
- Catastrophic APS (CAPS): Triple therapy — anticoagulation + high-dose steroids + PLEX or IVIG. Mortality 30-50% even with treatment. Rituximab or eculizumab for refractory cases.
- Asymptomatic aPL carriers: Low-dose ASA 81 mg for primary prevention (especially if lupus anticoagulant positive + additional CV risk factors). No anticoagulation.
Perioperative bridging: APS patients on warfarin require therapeutic bridging with LMWH — do NOT leave them unprotected. High thrombotic risk during interruptions.
📄 One Pager
Rheumatology / Hematology · One Pager
Antiphospholipid Syndrome
Thrombosis + persistent aPL antibodies (× 2, ≥ 12 weeks apart). Warfarin lifelong (no DOACs [TRAPS]). Triple-positive = highest risk. CAPS = ICU emergency.
Diagnosis
Thrombosis (arterial or venous) OR pregnancy morbidity + persistent aPL antibodies (positive ×2, ≥ 12 weeks apart). 3 antibodies: LA, aCL (IgG/IgM), anti-β2GP1 (IgG/IgM).
Treatment
Warfarin INR 2-3 (lifelong). DOACs are CONTRAINDICATED [TRAPS, 2018]. Add hydroxychloroquine (reduces thrombosis). ASA for arterial events. Pregnancy: LMWH + low-dose ASA.
CAPS — Catastrophic APS
Multi-organ thrombosis in ≤ 1 week (≥ 3 organs). Mortality 30-50%. Triple therapy: anticoag + high-dose steroids + PLEX/IVIG. Add rituximab or eculizumab if refractory.
Key Drugs
WarfarinINR 2-3 (lifelong)
Hydroxychloroquine200-400 mg daily
ASA81 mg daily (arterial events)
LMWH1 mg/kg BID (pregnancy)
Pitfalls
- DOACs in APS (contraindicated — increased thrombosis [TRAPS])
- Single antibody test (need positive × 2, ≥ 12 weeks apart)
- Not screening SLE patients for aPL antibodies
- Missing CAPS (think of it in multi-organ thrombosis)
Scleroderma & Renal Crisis
Systemic sclerosis — fibrosis of skin and internal organs. The emergency: scleroderma renal crisis (SRC) — acute HTN + AKI + MAHA. Treatment: ACE inhibitors. Do NOT give steroids — they precipitate SRC.
🔍 Overview
Limited vs Diffuse
| Feature | Limited (CREST) | Diffuse |
|---|---|---|
| Skin involvement | Distal to elbows/knees + face | Proximal (trunk, upper arms, thighs) |
| Antibody | Anti-centromere | Anti-Scl-70 (topoisomerase I) |
| Internal organs | Pulmonary HTN (isolated PAH — screen with annual echo), esophageal dysmotility (GERD) | ILD (NSIP pattern), scleroderma renal crisis, cardiac fibrosis |
| Prognosis | Better (slower progression) | Worse (organ fibrosis — lungs, kidneys) |
| CREST | Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasias | |
Scleroderma Renal Crisis (SRC)
SRC = acute hypertensive emergency + AKI + MAHA in a scleroderma patient. Occurs in ~10% of diffuse SSc, usually within the first 5 years. ACE inhibitors are life-saving. Steroids (especially > 15 mg prednisone/day) PRECIPITATE SRC.
- Presentation: acute severe HTN (often > 180/120), rapid rise in Cr, oliguria, schistocytes on smear (MAHA), elevated LDH, thrombocytopenia (can mimic TTP)
- Treatment: Captopril 6.25–12.5 mg PO q8h, titrate aggressively to normalize BP. ACEi even if Cr is rising — do NOT hold for AKI. ACEi reduces mortality from > 80% to ~25%. Continue even if patient needs dialysis (some recover renal function months later).
- ARBs are NOT a substitute — evidence is only for ACE inhibitors in SRC.
- Prevention: avoid steroids > 15 mg prednisone/day in diffuse SSc. Monitor BP closely in all diffuse SSc patients.
📋 On Rounds
Why do steroids precipitate scleroderma renal crisis?
The mechanism isn't fully understood, but the leading theory is that steroids cause direct endothelial injury in the renal vasculature of scleroderma patients (whose vessels are already primed by intimal fibrosis and vascular obliteration). This triggers a cascade of renin release → severe hypertension → further endothelial damage → MAHA → AKI — a vicious cycle. Epidemiologically, prednisone > 15 mg/day in the 6 months prior is the strongest modifiable risk factor for SRC. This is why rheumatologists avoid steroids in diffuse scleroderma whenever possible, and when steroids are necessary (e.g., for ILD or myositis), they use the lowest dose for the shortest duration with close BP monitoring.
Why are ACE inhibitors life-saving in scleroderma renal crisis but ARBs are not?
This is a critical distinction. ACE inhibitors block the conversion of angiotensin I → II, reducing both circulating and tissue-level angiotensin II. Before ACEi were used, scleroderma renal crisis had > 80% mortality at 1 year. With captopril, survival improved to ~60%. ARBs block the AT1 receptor but do NOT reduce angiotensin II levels — in fact, Ang II levels rise (compensatory). There is no RCT evidence supporting ARBs in scleroderma renal crisis, and case series suggest worse outcomes. The pathophysiology involves severe renal vasoconstriction from the renin-angiotensin system — reducing Ang II production (ACEi) works better than blocking one of its receptors (ARB). Use captopril specifically (short-acting, rapid titration). Don't hold for rising Cr — it may take weeks to recover.
What organ complications define limited vs diffuse scleroderma?
Limited (CREST): Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Antibody: anti-centromere. Key complication: pulmonary arterial hypertension (PAH) — screen with annual echo (RVSP). Skin involvement limited to distal extremities/face. Diffuse: widespread skin thickening (trunk + proximal extremities). Antibody: anti-Scl-70 (topoisomerase I) or anti-RNA polymerase III. Key complications: ILD (HRCT + PFTs at diagnosis and regularly), scleroderma renal crisis (especially if on steroids > 15 mg — anti-RNA pol III is highest risk). Cardiac involvement (myocardial fibrosis). Both types: GI dysmotility (GERD, gastroparesis, intestinal pseudo-obstruction), Raynaud's. Treat Raynaud's: nifedipine or amlodipine. Avoid beta-blockers (worsen Raynaud's).
Why are steroids dangerous in scleroderma?
Prednisone > 15 mg/day is a risk factor for scleroderma renal crisis (SRC). The mechanism is not fully understood but likely involves steroid-induced endothelial injury in the renal vasculature → activation of the renin-angiotensin system → malignant hypertension + TMA + AKI. Anti-RNA polymerase III antibody patients are at highest risk. Rule: avoid steroids > 15 mg/day in diffuse scleroderma. If steroids are needed (e.g., for ILD or myositis), monitor BP and Cr closely — BP checks twice daily, Cr weekly. If SRC develops → captopril immediately (ACEi is life-saving). For ILD treatment in scleroderma: prefer mycophenolate or tocilizumab over high-dose steroids.
A scleroderma patient presents with sudden severe hypertension and AKI. What is this and how do you treat it?
Scleroderma renal crisis. Treat with ACE inhibitor (captopril) — titrate aggressively to normalize BP. This transformed survival from ~10% to ~65%. Do NOT use prophylactic ACEi — it may worsen outcomes. Start only when crisis occurs.
Which scleroderma antibody predicts ILD?
Anti-Scl-70 (anti-topoisomerase I) — associated with diffuse cutaneous SSc and interstitial lung disease. Anti-centromere = limited SSc (CREST) + pulmonary HTN. Anti-RNA polymerase III = renal crisis risk.
What is first-line treatment for SSc-ILD?
Mycophenolate mofetil [Scleroderma Lung Study II, 2016]. Similar efficacy to cyclophosphamide with fewer side effects. Add nintedanib [SENSCIS, 2019] if progressive despite MMF.
What screening should all scleroderma patients get annually?
PFTs with DLCO (ILD screening — FVC decline or isolated DLCO decline) and echocardiogram (PAH screening — RVSP, TR velocity). Isolated DLCO decline out of proportion to FVC suggests pulmonary hypertension rather than ILD.
📣 Sample Presentation
One-Liner
"Mrs. Kim is a 48-year-old with diffuse cutaneous systemic sclerosis (on prednisone 20 mg for ILD) presenting with acute BP 210/130, Cr rising from 1.0 to 3.8 over 3 days, and schistocytes on peripheral smear. Scleroderma renal crisis."
Key Points to Cover on Rounds
Scleroderma renal crisis — hypertension + AKI + MAHA. Risk factor: prednisone >15 mg/day. Treatment: captopril 6.25 mg PO q8h, titrated aggressively to 25 mg TID over 24h (short-acting ACEi — captopril specifically, not ARB). DO NOT hold for rising Cr — it may take weeks to recover. Prednisone tapered urgently (precipitated the crisis). BP improved 210/130→158/92 within 24h. Cr still rising (expected initially). Schistocytes → monitoring for concurrent TMA. Nephrology following — dialysis if needed (may be temporary). Plan: continue aggressive ACEi titration, trend Cr/plt/LDH daily.
🧪 Workup
Workup
- ANA — positive in > 90%. Nucleolar pattern suggestive of scleroderma.
- Anti-Scl-70 (anti-topoisomerase I) — associated with diffuse cutaneous SSc + ILD. ~40% of dcSSc.
- Anti-centromere — associated with limited cutaneous SSc (CREST) + pulmonary HTN. ~60% of lcSSc.
- Anti-RNA polymerase III — associated with scleroderma renal crisis + rapidly progressive skin. Screen these patients carefully.
- PFTs with DLCO — screen at baseline and q6-12 months. FVC decline or DLCO decline > 15% = progressive ILD. Isolated DLCO decline = pulmonary HTN.
- HRCT chest — ILD pattern: NSIP most common (ground-glass opacities, subpleural sparing). UIP pattern less common.
- Echocardiography — annual screening for pulmonary HTN (RVSP > 40, RV dilation). Confirm with right heart catheterization if suspected.
- BMP + Cr — scleroderma renal crisis: sudden severe HTN + AKI + MAHA. Medical emergency. Treat with ACE inhibitor.
- UA — proteinuria, hematuria in renal crisis
- Modified Rodnan Skin Score (mRSS) — extent and severity of skin thickening. Track q6-12 months.
- Nailfold capillaroscopy — dilated capillary loops, hemorrhages, avascular areas. Supports diagnosis + correlates with organ involvement.
⚡ Management
Management
- Raynaud's: CCBs first-line (nifedipine 30-60 mg daily or amlodipine 5-10 mg). Severe/refractory: add PDE5 inhibitor (sildenafil), IV epoprostenol, or digital sympathectomy. Avoid beta-blockers.
- Skin fibrosis (dcSSc): Methotrexate for early diffuse disease [van den Hoogen]. Mycophenolate for progressive skin thickening. Tocilizumab (IL-6 inhibitor) — emerging option [focuSSced, 2020]. For severe, rapidly progressive diffuse SSc: autologous stem cell transplant SCOT, Sullivan 2018
- ILD (most common cause of death in SSc): Mycophenolate (first-line) SLS II, Tashkin 2016 or nintedanib SENSCIS, Distler 2019. Cyclophosphamide as alternative SLS I, Tashkin 2006. Screen with HRCT + PFTs (FVC trend). Refer for transplant if FVC < 50% or declining rapidly.
- PAH: Right heart cath to confirm. Upfront combination: ambrisentan + tadalafil [AMBITION]. Add riociguat or selexipag for inadequate response. IV epoprostenol for FC III-IV.
- Scleroderma renal crisis (SRC): ACE inhibitor immediately (captopril 6.25-12.5 mg q8h, titrate aggressively). Even if creatinine rising — continue ACEi. Do NOT use ARBs (no evidence). Avoid corticosteroids ≥ 15 mg prednisone (triggers SRC). Steen & Medsger, 1990
- GI: GERD → PPI (high-dose often needed). Gastroparesis → prokinetics (metoclopramide, erythromycin). GAVE (watermelon stomach) → APC ablation. Intestinal dysmotility → rotating antibiotics for SIBO.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| ILD (Interstitial Lung Disease) | |||
| Mycophenolate mofetil | 2-3g daily | PO | First-line for SSc-ILD. [Scleroderma Lung Study II, 2016] — similar efficacy to cyclophosphamide with fewer side effects. |
| Nintedanib | 150 mg BID | PO | Antifibrotic. Add-on to MMF for progressive SSc-ILD [SENSCIS, 2019]. Slows FVC decline. GI side effects (diarrhea). |
| Tocilizumab | 162 mg SQ weekly | SQ | Anti-IL-6. Preserves FVC in early dcSSc with elevated inflammatory markers [focuSSced, 2020]. |
| Raynaud's | |||
| Nifedipine ER | 30-90 mg daily | PO | First-line CCB for Raynaud's. Reduces frequency/severity of attacks. |
| Sildenafil | 20 mg TID | PO | PDE5 inhibitor for severe Raynaud's + digital ulcers. Also used for PAH. |
| Iloprost | 0.5-2 ng/kg/min × 6h | IV | IV prostacyclin for refractory Raynaud's + digital ischemia. |
| Renal Crisis | |||
| ACE inhibitor (captopril) | 6.25-25 mg TID, titrate aggressively | PO | Drug of choice for scleroderma renal crisis. Revolutionized survival from ~10% to ~65%. Do NOT use prophylactically — prophylactic ACEi may worsen outcomes. Start when crisis occurs. |
| Pulmonary Arterial Hypertension | |||
| Ambrisentan + tadalafil | 10 mg + 40 mg daily | PO | Upfront combination ERA + PDE5i is standard [AMBITION, 2015]. Reduces hospitalization + clinical worsening. |
📈 Monitoring
Monitoring
- PFTs (FVC + DLCO) q6-12 months — FVC decline ≥ 10% or DLCO decline ≥ 15% = progressive ILD → escalate therapy
- Echocardiogram annually — PAH screening (RVSP, TR velocity, RV function)
- BP monitoring — home BP. Sudden severe HTN = renal crisis. Patients on anti-RNA polymerase III antibodies need weekly BP checks.
- Cr + UA q3-6 months — renal crisis surveillance
- mRSS (skin score) q6-12 months — skin progression
- 6-minute walk test — functional capacity, PAH monitoring
- NT-proBNP — PAH marker, screening adjunct
- GI symptoms — dysphagia (esophageal dysmotility), reflux (PPI), GAVE ("watermelon stomach"), pseudo-obstruction
⚡ Summary
Summary
Limited (CREST)
Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Ab: anti-centromere. Key risk: PAH. Skin: distal only.
Diffuse
Widespread skin thickening (trunk + proximal). Ab: anti-Scl-70, anti-RNA pol III. Key risks: ILD, renal crisis. Rapid progression.
Renal Crisis
HTN emergency + AKI + MAHA. Risk: steroids > 15 mg/day. Treatment: captopril (ACEi) — titrate aggressively, don't hold for rising Cr.
ILD Screening
HRCT + PFTs at diagnosis, then annually. FVC declining > 10% → immunosuppression (mycophenolate, nintedanib, tocilizumab).
PAH Screening
Annual echo (RVSP). If elevated → right heart catheterization for confirmation. Treatment: PDE5i, ERA, prostacyclins.
Steroids Danger
Prednisone > 15 mg/day precipitates renal crisis. Use sparingly. Monitor BP and Cr closely if steroids unavoidable.
📄 One Pager
One Pager — Antiphospholipid Syndrome
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
ANTIPHOSPHOLIPID SYNDROME — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Rheumatology · One Pager
Systemic Sclerosis
Limited = CREST + PAH risk + anti-centromere. Diffuse = ILD + renal crisis + anti-Scl-70/anti-RNA pol III. Steroids > 15mg → renal crisis. Captopril for SRC.
Classification
Limited (CREST): Calcinosis, Raynaud, Esophageal, Sclerodactyly, Telangiectasia. Ab: anti-centromere. Key risk: PAH. Diffuse: widespread skin, Ab: anti-Scl-70/anti-RNA pol III. Key risks: ILD, renal crisis.
Scleroderma Renal Crisis
HTN emergency + AKI + MAHA. Triggered by steroids > 15 mg/day. Treatment: CAPTOPRIL (short-acting ACEi) — titrate aggressively. Don't hold for rising Cr (may take weeks to recover).
Screening
ILD: HRCT + PFTs at diagnosis, then annually. PAH: echo annually. GI: PPI for GERD. Raynaud: nifedipine/amlodipine. Avoid beta-blockers (worsen Raynaud).
Key Drugs
Captopril6.25-50 mg TID (renal crisis)
Nifedipine30-90 mg daily (Raynaud)
Mycophenolate2-3g/day (ILD)
Nintedanib150 mg BID (ILD)
Pitfalls
- Steroids > 15 mg/day (precipitates renal crisis)
- Not monitoring BP/Cr on steroids
- Beta-blockers (worsen Raynaud)
- Late ILD screening (PFTs + HRCT at diagnosis)
Acute Gout & Pseudogout
Crystal arthropathies — the most common inflammatory arthritis. Gout = monosodium urate (negatively birefringent needles). Pseudogout = calcium pyrophosphate (positively birefringent rhomboids). Joint aspiration is the gold standard — don't guess, tap.
🔍 Overview
Gout vs Pseudogout
| Feature | Gout | Pseudogout (CPPD) |
|---|---|---|
| Crystal | Monosodium urate (MSU) — needle-shaped, negatively birefringent (yellow when parallel to polarizer) | Calcium pyrophosphate (CPP) — rhomboid-shaped, positively birefringent (blue when parallel) |
| Classic joint | 1st MTP (podagra) — also ankles, knees, wrists | Knee (#1), wrists, shoulders |
| Demographics | Men > women (until menopause). Obesity, alcohol, purine-rich diet, CKD. | Elderly (> 65). Associated with hemochromatosis, hyperparathyroidism, hypomagnesemia, hypothyroidism. |
| X-ray | Erosions with overhanging edges ("rat-bite"), tophi (late) | Chondrocalcinosis (calcification of cartilage — menisci, triangular fibrocartilage of wrist) |
| Serum uric acid | Often ↑ but can be normal during acute flare (~40%). Do NOT rule out gout based on normal UA. | Normal |
Always rule out septic arthritis first. Gout and septic arthritis can look identical (hot, swollen, painful joint with leukocytosis). Septic arthritis is joint-threatening → tap the joint. Crystal-positive fluid does NOT rule out concurrent infection — they can coexist.
💊 Management
Acute Flare Treatment
| Drug | Dose | Notes |
|---|---|---|
| NSAIDs 1ST LINE | Indomethacin 50 mg TID × 5–7 days, or naproxen 500 mg BID | Most effective if started within 24h. Avoid in CKD, GI bleed, CHF, anticoagulation. |
| Colchicine (Colcrys) 1ST LINE | 1.2 mg PO, then 0.6 mg 1h later (total 1.8 mg day 1). Then 0.6 mg BID until flare resolves. | Low-dose colchicine (AGREE, 2010) is as effective as high-dose with far fewer GI side effects. Best within 36h of onset. Reduce dose in CKD. Avoid with strong CYP3A4 inhibitors (clarithromycin). |
| Corticosteroids IF NSAIDs/COLCHICINE CI | Prednisone 30–40 mg/day × 5 days (or taper over 10–14 days). Or intra-articular triamcinolone if 1–2 joints. | Preferred in CKD, GI disease, or elderly. Intra-articular injection is ideal for monoarticular flare (after ruling out septic joint). |
| IL-1 inhibitor (anakinra) REFRACTORY | 100 mg SC daily × 3–5 days | For patients who fail or cannot take NSAIDs, colchicine, AND steroids. Off-label but effective. Anakinra Pericarditis Trial, 2019 |
Urate-Lowering Therapy (ULT) — Chronic
Do NOT start ULT during an acute flare — changing urate levels can prolong or worsen the attack. Start 2–4 weeks after flare resolution. However, do NOT stop ULT if already on it during a flare.
🔄 Updated Practice: Old teaching: never start allopurinol (Zyloprim) during an acute gout flare — it will prolong or worsen the attack. Current practice: it IS safe to start urate-lowering therapy during an acute flare, as long as anti-inflammatory cover (colchicine 0.6 mg daily or BID) is provided. Delaying ULT initiation by weeks leads to treatment gaps, missed opportunities, and worse long-term outcomes. Multiple RCTs have shown no increase in flare duration or severity when starting ULT with prophylaxis.
| Drug | Dose | Notes |
|---|---|---|
| Allopurinol (Zyloprim) 1ST LINE | Start 100 mg daily (50 mg if CKD), titrate by 100 mg q2–4 weeks. Target: serum urate < 6 mg/dL. | Check HLA-B*5801 before starting in Southeast Asian, Black, and Korean patients — risk of severe hypersensitivity (SJS/TEN/DRESS). Start low, go slow. |
| Febuxostat (Uloric) 2ND LINE | 40–80 mg daily | Alternative if allopurinol intolerant or HLA-B*5801 positive. CARES, 2018: cardiovascular mortality signal → use only if allopurinol fails. |
Indications for ULT: ≥ 2 flares/year, tophi, urate nephropathy, CKD stage ≥ 3 wi
th urate > 9. Flare prophylaxis: colchicine 0.6 mg daily × 3–6 months w
hen starting ULT (prevents mobilization flares).
🧪 Workup
Workup
- Joint aspiration — gold standard. Negatively birefringent, needle-shaped monosodium urate crystals under polarized light. Yellow when parallel to compensator.
- Synovial fluid WBC — 2,000-50,000 (inflammatory range). ALWAYS send culture + gram stain — gout and septic arthritis can coexist (up to 5% of gout flares).
- Serum uric acid — can be NORMAL during acute flare (don't use to diagnose). Check between flares for ULT target. Flare threshold usually > 6.8 mg/dL (supersaturation point).
- BMP + Cr — renal function determines medication choice (colchicine dose, allopurinol starting dose). CKD is both a cause and consequence of hyperuricemia.
- CBC — leukocytosis during flare (mimics infection)
- HLA-B*5801 — BEFORE allopurinol in Southeast Asian, African American, Hawaiian/Pacific Islander patients. Strong predictor of DRESS/SJS. If positive → use febuxostat instead.
- 24h urine uric acid — uric acid overproducer (> 800 mg/day) vs underexcretor. Guides ULT choice (xanthine oxidase inhibitor vs uricosuric).
- X-ray — acute: soft tissue swelling only. Chronic: "rat-bite" erosions with overhanging edges, tophi. DECT: urate crystal deposition (research, not routine).
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Acute Flare Treatment | |||
| Colchicine | 1.2 mg → 0.6 mg at 1h (day 1), then 0.6 mg BID | PO | Low-dose regimen [AGREE, 2010] — equally effective, far fewer GI side effects. Reduce dose if CrCl < 30 (0.3 mg BID). Onset within 24h. |
| Indomethacin | 50 mg TID × 3 days, then taper | PO | NSAID — fast acting. Avoid in CKD, GI bleed, HF, anticoagulation. Naproxen 500 BID is alternative. |
| Prednisone | 30-40 mg daily × 5 days | PO | If NSAIDs + colchicine contraindicated. Equally effective. No taper for 5-day course. Best for polyarticular flare. |
| Intra-articular triamcinolone | 10-40 mg per joint | IA | Monoarticular flare — fast relief. Must rule out septic joint first (culture synovial fluid). |
| Anakinra | 100 mg SQ × 3-5 days | SQ | IL-1 receptor antagonist. For refractory flares when ALL of the above are contraindicated (CKD + CHF + anticoag + infection). |
| Urate-Lowering Therapy (ULT) — Start ≥ 2 weeks after flare resolves | |||
| Allopurinol | Start 100 mg daily (50 mg if CKD), titrate by 100 mg q2-4 weeks | PO | Xanthine oxidase inhibitor. Target UA < 6 mg/dL. Max 800 mg. Check HLA-B*5801 first in at-risk populations. Titrate slowly — faster titration does NOT cause more flares. [Allopurinol Dose-Escalation Study, 2017] |
| Febuxostat | 40-80 mg daily | PO | XOI alternative if allopurinol intolerant or HLA-B*5801+. More potent per mg. FDA CV warning but [FAST, 2020] showed non-inferiority to allopurinol. |
| Probenecid | 250 mg BID → 500 mg BID | PO | Uricosuric. Only if underexcretor. Contraindicated if CrCl < 50 or nephrolithiasis. |
| Pegloticase | 8 mg IV q2 weeks | IV | Recombinant uricase. Refractory tophaceous gout only. Must premedicate. Check UA before each infusion — if > 6, discontinue (loss of response → anaphylaxis risk). |
Flare prophylaxis when starting ULT: colchicine 0.6 mg daily × 3-6 months. Starting ULT mobilizes urate crystals from deposits → paradoxical flares. Do NOT stop ULT during a flare — it does not worsen flares and stopping/starting destabilizes urate levels.
📊 Monitoring
Monitoring
- Serum uric acid q2-4 weeks while titrating ULT — target < 6 mg/dL (or < 5 if tophi present). Most common error: starting at full dose. Always start low, go slow.
- Cr + LFTs q3-6 months on allopurinol/febuxostat — rare hepatotoxicity, dose-adjust for CKD
- CBC if on colchicine long-term (rare bone marrow suppression, especially with CKD or statin interaction)
- Flare frequency — should decrease after 6-12 months of ULT at target. Early ↑ in flares is expected when starting ULT (crystal mobilization) — this is why prophylaxis is essential
- Colchicine prophylaxis × 3-6 months when starting or titrating ULT (0.6 mg daily or BID). Prevents mobilization flares. Continue until urate at target for ≥ 3-6 months with no flares.
- Tophi assessment — should shrink over 12-24 months on ULT. If persistent → urate not at target
- Joint imaging — X-ray at baseline for erosions. Dual-energy CT if diagnostic uncertainty (research tool, not routine follow-up)
📋 On Rounds
Why can serum uric acid be normal during an acute gout flare?
During an acute inflammatory response, IL-6 increases renal urate excretion via uricosuric effects and redistributes urate from plasma into tissues. Additionally, the acute phase response and volume shifts during inflammation dilute serum urate. Up to 40% of acute gout flares have a normal serum uric acid. This is why a normal UA does NOT rule out gout — you need joint aspiration with polarized microscopy (negatively birefringent crystals) for definitive diagnosis.
A patient with gout is already on allopurinol. Should you stop it during an acute flare?
NO — do NOT stop allopurinol during an acute flare. This is one of the most commonly made errors. Stopping or starting ULT (urate-lowering therapy) during a flare causes uric acid fluctuations that can prolong and worsen the flare. If the patient is already on allopurinol, continue it at the same dose and treat the flare with NSAIDs, colchicine, or steroids. If ULT hasn't been started yet, wait until the flare resolves (2–4 weeks) before initiating, and always provide anti-inflammatory prophylaxis (low-dose colchicine 0.6 mg daily or BID × 3–6 months) when starting ULT to prevent flare triggered by the urate shift.
What is the treat-to-target approach for uric acid, and what level do you aim for?
Target serum uric acid < 6 mg/dL (or < 5 mg/dL if tophi present). The monosodium urate saturation point is ~6.8 mg/dL — keeping UA below 6 ensures crystals dissolve over time and prevents new deposition. Treat-to-target protocol: Start allopurinol low (100 mg daily, or 50 mg if CKD) → increase by 100 mg every 2-4 weeks → check UA level → keep titrating until UA < 6. Most patients need 300-600 mg daily (not the old default of 300 mg). Check HLA-B*5801 before starting allopurinol in Southeast Asian, African American, and Hawaiian/Pacific Islander patients — B*5801 positive = 5% risk of severe hypersensitivity (SJS/TEN/DRESS) → use febuxostat instead. Anti-inflammatory prophylaxis (colchicine 0.6 mg daily × 3-6 months) when starting ULT to prevent mobilization flares.
What is the role of IL-1 inhibitors in gout?
Anakinra (IL-1 receptor antagonist) is used for acute gout flares when NSAIDs, colchicine, AND steroids are all contraindicated or failed — typically in patients with CKD + HF + active infection (can't use NSAIDs, colchicine, or steroids safely). Dose: 100 mg SQ daily × 3 days. Works by blocking IL-1β, which is the key cytokine released when NLRP3 inflammasome is activated by MSU crystals. Canakinumab (anti-IL-1β monoclonal): [CANTOS, 2017 showed it reduces CV events in patients with elevated CRP (a bonus), but it's very expensive and increases infection risk. Anakinra is the practical choice — affordable, effective, and used off-label in many rheumatology centers for refractory flares. Not yet standard first-line but increasingly recognized.
A patient has an acute gout flare. Should you start allopurinol now?
Current guidelines say you CAN start ULT during a flare [ACR 2020] — it does not worsen or prolong the flare. But always add flare prophylaxis (colchicine). Never STOP ULT during a flare — stopping/restarting destabilizes urate levels.
Why do you check HLA-B*5801 before starting allopurinol?
HLA-B*5801 is a strong predictor of severe allopurinol hypersensitivity (DRESS/SJS/TEN) — fatality rate ~25%. Prevalence: 6-8% in Southeast Asian, 3.5% in African American. If positive → use febuxostat instead.
What is the serum urate target for gout ULT?
< 6 mg/dL (below the supersaturation point of 6.8 mg/dL). For severe tophaceous gout, target < 5. It takes 6-12 months of sustained target to dissolve tissue urate deposits.
Why can serum uric acid be normal during an acute gout flare?
Acute inflammation causes increased renal urate excretion (uricosuric effect of IL-6) and hemodilution from acute phase response. Up to 40% of patients have normal UA during flare. Check between flares for accurate baseline.
📣 Sample Presentation
One-Liner
"Mr. Thompson is a 62-year-old with CKD3 presenting with acute right first MTP joint erythema, swelling, and exquisite tenderness × 2 days. Joint aspiration shows negatively birefringent needle-shaped crystals. WBC 42,000 in synovial fluid. Acute gout."
Key Points to Cover on Rounds
Acute gout confirmed by crystal analysis. Septic joint ruled out (culture pending, but crystals identified — can coexist, treat empirically if concern). Treatment: colchicine 1.2 mg then 0.6 mg 1h later, then 0.6 mg BID (low-dose per [AGREE, 2010] — less GI toxicity than traditional high-dose). NSAIDs avoided (CKD3). Uric acid level 7.8 (can be normal during flare). Already on allopurinol 200 mg — continued (don't stop during flare). Plan: after flare resolves → uptitrate allopurinol to target uric acid <6, continue colchicine 0.6 mg daily × 6 months as prophylaxis. Check HLA-B*5801 if not previously done.
⚡ Summary
Summary
Acute Flare
Colchicine 1.2 mg → 0.6 mg 1h later → 0.6 BID (low-dose [AGREE, 2010]). NSAIDs. Steroids if both contraindicated. Anakinra for refractory.
Crystal Diagnosis
Joint aspiration: negatively birefringent needle-shaped crystals under polarized light. WBC 2,000-50,000. Culture to rule out concurrent septic joint.
ULT Goal
Treat-to-target: uric acid < 6 mg/dL (< 5 if tophi). Allopurinol start 100 mg, titrate by 100 mg q2-4 weeks. Check HLA-B*5801 in at-risk populations.
Don't Stop ULT
Continue allopurinol/febuxostat during acute flare. Stopping → rebound uric acid fluctuation → worsening flare.
Flare Prophylaxis
Colchicine 0.6 mg daily × 3-6 months when starting or titrating ULT. Prevents mobilization flares from urate crystal dissolution.
Pseudogout
Positively birefringent rhomboid crystals = CPPD (calcium pyrophosphate). Knee most common. Treatment: similar to gout. No ULT equivalent.
📄 One Pager
Rheumatology · One Pager
Gout
Crystal confirmation on aspiration. Acute: colchicine (low-dose) + NSAIDs + steroids. Chronic: treat-to-target uric acid < 6 with allopurinol. Check HLA-B*5801 in at-risk populations.
Diagnosis
Joint aspiration: negatively birefringent needle-shaped crystals under polarized light. Mono-inflammatory arthritis (1st MTP classic). WBC 2,000-50,000. Culture to rule out concurrent septic joint.
Acute Flare
Colchicine 1.2 mg → 0.6 mg at 1h → 0.6 BID (low-dose [AGREE, 2010]). NSAIDs (indomethacin or naproxen). Steroids if both contraindicated. Anakinra (IL-1 blocker) for refractory.
Chronic — ULT
Target uric acid < 6 mg/dL (< 5 if tophi). Allopurinol: start 100 mg, titrate by 100 mg q2-4 weeks. Check HLA-B*5801 (Southeast Asian, African American — SJS/TEN risk). Flare prophylaxis: colchicine 0.6 mg daily × 3-6 months.
Key Drugs
Colchicine1.2 → 0.6 mg (acute)
Allopurinol100-800 mg daily (titrate)
Febuxostat40-80 mg daily (if B*5801+)
Colchicine0.6 mg daily (prophylaxis)
Pitfalls
- Stopping ULT during acute flare (don't stop — continue and add anti-inflammatory)
- Starting ULT without flare prophylaxis (colchicine × 3-6 months)
- Not checking HLA-B*5801 in at-risk populations
- High-dose colchicine (use low-dose — same efficacy, less GI toxicity)
SLE Flare
Lupus is the great mimicker. Flares can involve any organ. The most dangerous: lupus nephritis (Class III/IV/V), cerebral lupus, catastrophic APS, and diffuse alveolar hemorrhage. Labs: ↓ complement (C3/C4), ↑ anti-dsDNA = active disease.
🔍 Overview
Organ Involvement & Severity
| Organ | Manifestation | Severity |
|---|---|---|
| Skin / joints | Malar rash, discoid rash, photosensitivity, oral ulcers, arthralgia/arthritis (non-erosive) | Mild — treat with hydroxychloroquine ± NSAIDs |
| Serositis | Pleuritis, pericarditis | Moderate — steroids, NSAIDs, colchicine |
| Hematologic | Autoimmune hemolytic anemia (Coombs+), leukopenia, lymphopenia, thrombocytopenia | Moderate to severe — steroids, IVIG if severe thrombocytopenia |
| Renal (lupus nephritis) | Proteinuria, hematuria, rising Cr, nephrotic/nephritic syndrome. Class IV (diffuse proliferative) is most common and most severe. | Severe — renal biopsy, pulse steroids + mycophenolate or cyclophosphamide |
| CNS (cerebral lupus) | Seizures, psychosis, stroke, transverse myelitis, cognitive dysfunction | Severe — pulse steroids + cyclophosphamide. Rule out other causes (infection, TTP, APS). |
| Pulmonary | Diffuse alveolar hemorrhage (DAH), shrinking lung syndrome, ILD, pulmonary HTN | DAH = life-threatening — pulse steroids + cyclophosphamide + possible plasmapheresis |
Flare Markers
- ↓ C3 / C4 (complement consumed by immune complexes) — most sensitive marker of active disease
- ↑ Anti-dsDNA — correlates with lupus nephritis activity. Rising titers = impending flare.
- ↑ ESR with normal CRP — classic lupus pattern (CRP usually only rises in serositis or infection, not lupus flares). If CRP is high → think infection.
- Worsening cytopenias — active disease. But also consider medication side effects.
ESR ↑ + CRP normal = lupus flare. ESR ↑ + CRP ↑ = infection until proven otherwise. This distinction is clinically useful for differentiating flare vs infection in SLE patients (who are immunosuppressed and infection-prone).
💊 Management
Treatment by Severity
| Severity | Treatment |
|---|---|
| All patients (baseline) | Hydroxychloroquine (Plaquenil) 200–400 mg daily CORNERSTONE — reduces flares, organ damage, thrombosis, and mortality. Never stop. Annual eye exam for retinal toxicity. |
| Mild flare (skin, joints) | NSAIDs (short course) + topical steroids. Low-dose prednisone (≤ 7.5 mg/day). |
| Moderate flare (serositis, cytopenias) | Prednisone 0.5–1 mg/kg/day → taper. Add steroid-sparing: mycophenolate, azathioprine, or methotrexate. |
| Severe flare (nephritis Class III/IV, CNS, DAH) | Pulse methylprednisolone 1g IV daily × 3 days → prednisone 1 mg/kg. Then: mycophenolate (preferred for nephritis induction — ALMS, 2009) or cyclophosphamide (Euro-Lupus low-dose protocol for severe nephritis). Belimumab (anti-BAFF) for add-on in active lupus nephritis BLISS-LN, 2020. Voclosporin (calcineurin inhibitor) added to MMF for nephritis AURORA, 2021. |
📋 Clinical Example — Lupus Flare Assessment & Management
- Patient: 28F with known SLE, presents with fatigue, joint pain, malar rash, oral ulcers, Cr rising from 0.8 → 1.6 over 2 weeks.
- Flare workup:
- Labs: CBC (cytopenias?), BMP (renal), UA with microscopy (RBC casts = lupus nephritis), protein/creatinine ratio, complement C3/C4 (low = active disease), anti-dsDNA (rising titer = flare), ESR/CRP.
- UA: 2+ protein, 25 RBCs, RBC casts → active lupus nephritis. Protein/Cr ratio 2.8 (>0.5 = significant proteinuria).
- C3: 45 (low), C4: 8 (low), anti-dsDNA: 1:640 (elevated) → serologically active.
- Diagnosis: Class III/IV lupus nephritis until biopsy proves otherwise. Renal biopsy is MANDATORY — treatment depends on ISN/RPS class.
- Treatment:
- Mild flare (skin/joints only): Hydroxychloroquine (Plaquenil) 200mg BID (NEVER stop — reduces flares, thrombosis, and mortality). Low-dose prednisone (Deltasone) ≤10mg/day.
- Moderate flare (serositis, cytopenias): Prednisone 0.5-1mg/kg/day, taper over weeks.
- Severe flare (nephritis Class III/IV): Pulse methylprednisolone (Solu-Medrol) 500-1000mg IV × 3 days → prednisone 1mg/kg → taper. Induction: mycophenolate (CellCept) 2-3g/day OR cyclophosphamide (ALMS, 2009 — myco = cyclo for induction). Add belimumab (Benlysta) per BLISS-LN.
- Maintenance: Mycophenolate (CellCept) 1-2g/day + hydroxychloroquine indefinitely.
- Key: Hydroxychloroquine is the ONE drug every SLE patient should be on. Reduces flares, organ damage, and mortality.
📋 On Rounds
How do you distinguish lupus flare from infection in an immunosuppressed SLE patient?
This is one of the hardest clinical questions in rheumatology. Key clues: (1) CRP: low/normal in flare, elevated in infection. (2) Complement (C3/C4): drops in flare, normal or rises (acute phase) in infection. (3) Procalcitonin: elevated in bacterial infection, usually normal in flare (though not perfect). (4) Anti-dsDNA: rising in flare, stable in infection. (5) WBC: leukopenia suggests flare (autoimmune destruction), leukocytosis suggests infection. (6) Fever pattern: lupus fever is typically low-grade and responds to NSAIDs. High fever with rigors → think infection. When in doubt, cover both — start antibiotics AND increase immunosuppression until you can differentiate.
Why is CRP typically normal in a lupus flare but elevated in infection?
In most autoimmune flares, CRP remains low or normal because lupus inflammation is driven by type I interferons, which actually suppress hepatic CRP production. In contrast, bacterial infection drives IL-6 release → potent CRP stimulation in the liver → CRP rises markedly. This makes CRP a useful discriminator: CRP < 5 + low C3/C4 + rising anti-dsDNA = flare. CRP > 50 + normal complements = infection. The exception: lupus serositis (pleuritis, pericarditis) CAN elevate CRP even without infection. Other helpful discriminators: procalcitonin (elevated in bacterial infection, normal in flare), WBC differential (neutrophilia = infection, lymphopenia = flare).
Why should hydroxychloroquine never be stopped in SLE?
HCQ is the only SLE medication proven to reduce mortality — and the effect is dose-independent (even low doses help). Benefits: (1) Reduces flare frequency by 50-60%, (2) Reduces thrombosis risk (important in APS overlap), (3) Improves lipid profiles, (4) Reduces renal damage progression, (5) Safe in pregnancy (one of few SLE drugs that is). Stopping HCQ increases flare risk by 2.5× within 6 months. Even during remission, continue HCQ. Side effect to monitor: retinal toxicity — baseline eye exam, then annual screening after 5 years (or sooner if renal impairment, high dose > 5 mg/kg/day, or concomitant tamoxifen). Risk of toxicity increases after 10+ years of use but is still low (~2%). The benefit-risk ratio overwhelmingly favors lifelong HCQ in SLE.
What are the indications for renal biopsy in lupus nephritis?
Biopsy is indicated whenever there is evidence of renal involvement in SLE — it determines the ISN/RPS class (I-VI) which directly guides treatment. Indications: (1) Proteinuria > 500 mg/day (UPCR > 0.5), (2) Active urine sediment (RBC casts, dysmorphic RBCs), (3) Unexplained rising creatinine, (4) Combination of proteinuria + hematuria even if individually below threshold. Why biopsy matters: Class I/II (minimal/mesangial) → conservative (HCQ + monitoring). Class III/IV (focal/diffuse proliferative) → aggressive induction (mycophenolate or cyclophosphamide + steroids) [ALMS, 2009. Class V (membranous) → immunosuppression if nephrotic. Class VI (sclerotic) → irreversible, transplant evaluation. You cannot predict the class clinically — class III and V can present identically. Biopsy is the only way to know.
📣 Sample Presentation
One-Liner
"Ms. Johnson is a 28-year-old with SLE presenting with facial rash, pleuritic chest pain, and UA showing 2+ protein and 15 RBCs/hpf. Anti-dsDNA elevated, C3/C4 low. CRP 2.4 (low). Consistent with lupus flare with possible nephritis."
Key Points to Cover on Rounds
SLE flare — active serology (rising anti-dsDNA, falling C3/C4). CRP low (supports flare over infection). Organ involvement: skin (malar rash), serositis (pleuritic chest pain — CXR: small left pleural effusion), renal (proteinuria + hematuria → nephritis?). Urine protein/Cr ratio sent — UPCR 2.4 (nephrotic range). Nephrology consulted for renal biopsy (needed for class determination → guides treatment). Hydroxychloroquine continued (never stop — reduces flares, thrombosis, mortality). Prednisone 0.5 mg/kg started pending biopsy. If class III/IV → mycophenolate or cyclophosphamide induction. Plan: renal biopsy this week, continue HCQ + steroids, check for infection before immunosuppression.
🧪 Workup
Diagnostic Evaluation — DIC
Workup checklist for DIC: History and physical → targeted labs → imaging as indicated → specialist consultation if needed. Always correlate clinically.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications, relevant PMH
- Physical exam: Focused exam relevant to dic presentation
- Labs: CBC, BMP, relevant disease-specific labs (see Overview tab for specifics)
- Imaging: As clinically indicated based on presentation
- Special studies: Consider disease-specific diagnostics (see Overview tab)
💊 Medications
Key Medications — DIC
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — DIC
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
⚡ Summary
Summary
Diagnosis
EULAR/ACR 2019: ANA positive (entry criterion) + ≥ 10 points from clinical + immunologic domains. High-weighted: class III/IV nephritis, anti-dsDNA, low C3/C4.
Never Stop HCQ
Hydroxychloroquine reduces flares 50-60%, thrombosis, renal damage, and mortality. Continue lifelong. Eye exam annually after 5 years.
Nephritis Biopsy
Biopsy when proteinuria > 500 mg/day, active sediment, or rising Cr. Class determines treatment. Can't predict class clinically.
Treatment by Class
Class I/II: HCQ + monitoring. Class III/IV: induction (mycophenolate or cyclophosphamide + steroids) → maintenance (mycophenolate). Class V: immunosuppression if nephrotic.
Flare Markers
Rising anti-dsDNA + falling C3/C4 + rising CRP (low CRP in SLE suggests flare, not infection). Active urine sediment.
Pregnancy
Plan with rheumatology. HCQ safe (continue). Avoid mycophenolate, cyclophosphamide, MTX (teratogenic). Azathioprine is safe alternative.
📄 One Pager
DIC — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
DIC — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
Vasculitis
Inflammation of blood vessel walls → ischemia and organ damage. Classified by vessel size. The ANCA-associated vasculitides (GPA, MPA, EGPA) are the ones you'll see on the wards. Pulmonary-renal syndrome = treat immediately.
🔍 Classification by Vessel Size
| Size | Disease | Key Features | Antibody | Treatment |
|---|---|---|---|---|
| Small vessel (ANCA-associated) | GPA (Granulomatosis with Polyangiitis) | Upper airway (sinusitis, saddle-nose, subglottic stenosis) + lungs (cavitary nodules, DAH) + kidneys (RPGN). Classic triad. | c-ANCA / PR3 | Pulse steroids + rituximab or cyclophosphamide RAVE, 2010. Plasmapheresis if severe renal or DAH. |
| MPA (Microscopic Polyangiitis) | Kidneys (RPGN — most common presentation) + lungs (DAH). No upper airway involvement (distinguishes from GPA). No granulomas on biopsy. | p-ANCA / MPO | Same as GPA. | |
| EGPA (Eosinophilic GPA / Churg-Strauss) | Asthma (adult-onset, severe) + eosinophilia (> 1500) + sinusitis + neuropathy (mononeuritis multiplex) + cardiac involvement. | p-ANCA / MPO (40–60%) | Steroids (often sufficient for mild). Mepolizumab (anti-IL5) MIRRA, 2017. Cyclophosphamide if organ-threatening. | |
| Medium vessel | PAN (Polyarteritis Nodosa) | ANCA-negative. Microaneurysms on angiography. Skin (livedo, nodules, ulcers), renal (HTN, infarction — but NOT glomerulonephritis), GI (mesenteric ischemia), neuropathy. Associated with HBV. | Negative | Steroids + cyclophosphamide. Treat HBV if associated. |
| Large vessel | Giant Cell Arteritis (GCA) | Age > 50. Temporal headache, jaw claudication, scalp tenderness, vision loss (anterior ischemic optic neuropathy). ESR often > 100. | Negative | Start steroids BEFORE biopsy (don't wait — vision loss is irreversible). Prednisone 40–60 mg/day. Tocilizumab for steroid-sparing GiACTA, 2017. |
| Takayasu arteritis | Young women (< 40). Aorta + branches → limb claudication, BP discrepancy, absent pulses, bruits. "Pulseless disease." | Negative | Steroids + methotrexate/tocilizumab. |
Pulmonary-Renal Syndrome
DAH (hemoptysis + bilateral infiltrates + dropping Hgb) + RPGN (rising Cr + active sediment) = pulmonary-renal syndrome. This is a medical emergency. Differential: GPA, MPA, anti-GBM (Goodpasture's), SLE. Send ANCA, anti-GBM, ANA, complement. Start pulse methylprednisolone 1g IV × 3 days + cyclophosphamide or rituximab + plasmapheresis (especially if anti-GBM positive). Do NOT wait for biopsy to start treatment.
🧪 Workup
Workup
- ANCA — c-ANCA/PR3 (GPA/Wegener's), p-ANCA/MPO (MPA, EGPA). Send BOTH ELISA (PR3, MPO) AND IFA (c-ANCA, p-ANCA).
- CBC, BMP, LFTs, ESR, CRP — baseline organ function + inflammatory markers
- UA with microscopy — dysmorphic RBCs, RBC casts = glomerulonephritis (RPGN). This is an emergency — needs urgent renal biopsy.
- Cr + GFR — rapidly rising Cr = RPGN
- CXR / CT chest — pulmonary hemorrhage (DAH), nodules/cavities (GPA), infiltrates
- Renal biopsy — pauci-immune crescentic GN (hallmark of ANCA-associated vasculitis). Also classifies severity.
- Tissue biopsy — skin, sural nerve, temporal artery (GCA), lung — shows granulomatous inflammation (GPA) or necrotizing vasculitis
- Complement levels (C3, C4) — low in complement-mediated vasculitis (cryoglobulinemic, anti-GBM, SLE). Normal in ANCA vasculitis.
- Cryoglobulins + HCV — HCV-associated cryoglobulinemic vasculitis (type II mixed)
- Anti-GBM antibodies — Goodpasture syndrome (pulmonary-renal syndrome with linear IgG on biopsy)
- Eosinophil count — markedly elevated in EGPA (eosinophilic granulomatosis with polyangiitis / Churg-Strauss)
⚡ Management
Treatment — ANCA-Associated Vasculitis
| Phase | Regimen | Details |
|---|---|---|
| Induction | Pulse methylpred 1g IV × 3d → pred 1 mg/kg taper + Rituximab (Rituxan) 375 mg/m² × 4 wks | Rituximab preferred over cyclophosphamide RAVE, 2010. Especially for PR3+/relapsing. |
| Alternative | Cyclophosphamide IV 15 mg/kg q2–4 wks | If rituximab unavailable. Limit cumulative dose (bladder CA risk). Mesna for cystitis prevention. |
| Severe renal/DAH | Add plasmapheresis | PLEX for Cr > 5.7 or DAH requiring ventilation. |
| Maintenance | Rituximab (Rituxan) 500 mg q6 months or azathioprine (Imuran) | Maintain ≥ 2 years. PR3+ = longer maintenance (higher relapse). |
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| ANCA-Associated Vasculitis — Induction | |||
| Rituximab | 375 mg/m² weekly × 4 or 1000 mg × 2 | IV | First-line induction (equal to cyclophosphamide). [RAVE, 2010]. Preferred in relapsing disease. Fewer side effects than CYC. Screen HBV. |
| Cyclophosphamide | 15 mg/kg IV q2 weeks × 3 then q3 weeks | IV | Alternative induction. Effective but more toxicity (bladder cancer, infertility, myelosuppression). Mesna for bladder protection. Limit cumulative dose. |
| Methylprednisolone | 500-1000 mg IV × 3 days | IV | Pulse steroids with induction. Then prednisone 1 mg/kg taper over 3-6 months. [PEXIVAS: reduced-dose glucocorticoid non-inferior, 2020] |
| Avacopan | 30 mg BID | PO | C5a receptor inhibitor — steroid-sparing. [ADVOCATE, 2021]. Can replace prednisone during induction (add to RTX or CYC). Superior sustained remission at 52 weeks. |
| Maintenance | |||
| Rituximab | 500 mg q6 months × 2-4 years | IV | Preferred maintenance. [MAINRITSAN, 2014] — superior to azathioprine. Duration: minimum 2 years, possibly longer for PR3+. |
| Azathioprine | 2 mg/kg/day | PO | Alternative maintenance. Check TPMT. Less effective than rituximab for relapse prevention. |
| Giant Cell Arteritis (GCA) | |||
| Prednisone | 40-60 mg daily | PO | Start IMMEDIATELY if clinical suspicion — do NOT wait for biopsy. Taper over 12-24 months. Visual loss = methylprednisolone 1g IV × 3d. |
| Tocilizumab | 162 mg SQ weekly | SQ | Steroid-sparing for GCA. [GiACTA, 2017]. Sustained remission with 26-week taper vs 52-week steroid-only taper. Now first-line adjunct. |
📈 Monitoring
Monitoring
- ANCA titers (PR3/MPO) q3-6 months — rising titers MAY predict relapse (controversial, don't treat based on titer alone)
- Cr + UA at every visit — renal relapse detection
- ESR + CRP q3-6 months
- CBC — monitor for treatment-related cytopenias (cyclophosphamide, azathioprine, rituximab)
- Immunoglobulin levels — hypogammaglobulinemia with rituximab (infection risk)
- PFTs — if pulmonary involvement, monitor q6-12 months
- BVAS (Birmingham Vasculitis Activity Score) — standardized disease activity tracking
- Infection screening — TMP-SMX prophylaxis for PCP while on cyclophosphamide or high-dose steroids
- GCA: visual symptoms — any new headache, jaw claudication, visual changes → urgent ophthalmology
⚡ Summary
Summary
ANCA Types
c-ANCA/PR3: GPA (granulomatosis with polyangiitis). p-ANCA/MPO: MPA (microscopic polyangiitis) and EGPA (eosinophilic GPA).
Induction
Pulse steroids + rituximab (PR3+/relapsing [RAVE, 2010]) or cyclophosphamide (severe renal/DAH). PLEX if Cr > 5.7 or DAH.
Maintenance
Rituximab 500 mg q6 months × 2 years [MAINRITSAN, 2014] OR azathioprine. PCP prophylaxis (TMP-SMX) for all on immunosuppression.
GPA Classic Triad
Upper airway (sinusitis, saddle nose, bloody nasal discharge), lungs (nodules, cavitations, DAH), kidneys (RPGN, RBC casts).
Emergency
Pulmonary-renal syndrome (DAH + RPGN): life-threatening. Pulse steroids + rituximab/cyclophosphamide + PLEX. Don't wait for biopsy to treat.
Monitor Relapse
ANCA titers, Cr, UA with microscopy, CRP q3-6 months. Rising ANCA may precede clinical relapse — consider preemptive treatment.
📄 One Pager
VASCULITIS — AT A GLANCE
🔍 Classify: c-ANCA/PR3 = GPA, p-ANCA/MPO = MPA, eosinophilia = EGPA
🧪 Workup: ANCA, UA, Cr, CRP, CT chest, biopsy
⚡ Induction: Pulse steroids + rituximab (or cyclophosphamide)
🚨 Emergency: DAH/RPGN → treat before biopsy. PLEX if Cr > 5.7.
💊 Maintenance: Rituximab q6 months or azathioprine ≥ 2 years
📈 Monitor: Cr, UA, ANCA, CRP, CBC
🧪 Workup: ANCA, UA, Cr, CRP, CT chest, biopsy
⚡ Induction: Pulse steroids + rituximab (or cyclophosphamide)
🚨 Emergency: DAH/RPGN → treat before biopsy. PLEX if Cr > 5.7.
💊 Maintenance: Rituximab q6 months or azathioprine ≥ 2 years
📈 Monitor: Cr, UA, ANCA, CRP, CBC
📋 On Rounds
Why start steroids before temporal artery biopsy in suspected GCA?
Vision loss from GCA is irreversible. Anterior ischemic optic neuropathy (AION) from inflammation of the ophthalmic or posterior ciliary arteries can cause sudden permanent blindness — and once one eye is affected, the other is at high risk within days. The biopsy remains diagnostic even 2–6 weeks after starting steroids (the inflammatory infiltrate takes weeks to resolve). So the calculus is clear: the risk of delaying steroids (permanent blindness) far outweighs the risk of a false-negative biopsy (which rarely happens within the first 2 weeks of treatment). Start prednisone immediately. Schedule the biopsy within 1–2 weeks.
What's the difference between c-ANCA/PR3 and p-ANCA/MPO and why does it matter?
c-ANCA (anti-PR3) is associated with GPA (granulomatosis with polyangiitis, formerly Wegener's) — upper/lower respiratory tract + kidneys (sinusitis, cavitary lung lesions, RPGN). p-ANCA (anti-MPO) is associated with MPA (microscopic polyangiitis) — kidneys + lungs (RPGN, pulmonary hemorrhage, no upper airway involvement) and EGPA (eosinophilic GPA, formerly Churg-Strauss) in ~50%. Why it matters: (1) Prognosis: PR3+ patients have higher relapse rates → may need longer maintenance. (2) Treatment: rituximab is preferred for PR3+ relapsing disease [RAVE, 2010, while cyclophosphamide may still be used for MPO+. (3) Drug-induced: hydralazine, minocycline, and PTU can cause MPO+ vasculitis — check med list!
What is the ANCA-associated vasculitis treatment algorithm?
Induction: Pulse methylprednisolone 1g IV × 3 days → prednisone 1 mg/kg (max 80 mg) tapered over 6 months. PLUS rituximab 375 mg/m² weekly × 4 (preferred for PR3+/relapsing disease [RAVE, 2010) OR cyclophosphamide (preferred for severe renal disease or DAH). If Cr > 5.7 or DAH → add plasmapheresis (removes pathogenic ANCA antibodies). Maintenance (starts 4-6 months after induction): rituximab 500 mg q6 months × 2 years (superior to azathioprine per [MAINRITSAN, 2014) OR azathioprine 2 mg/kg daily. Supportive: PCP prophylaxis (TMP-SMX) for all patients on immunosuppression. Calcium + vitamin D. Hepatitis B/TB screening before rituximab.
When do you use plasmapheresis in ANCA-associated vasculitis?
PLEX indications: (1) Severe renal failure (Cr > 5.7 mg/dL or dialysis-dependent) — though [PEXIVAS, 2020 showed PLEX did NOT reduce death or ESKD overall, subgroup analysis and clinical practice still support it for dialysis-dependent patients where there may be salvageable renal function. (2) Diffuse alveolar hemorrhage (DAH) — PLEX removes pathogenic ANCA antibodies and can be life-saving in severe pulmonary hemorrhage. (3) Anti-GBM overlap (dual anti-GBM + ANCA positive) — PLEX is standard for anti-GBM disease. How it works: physically removes circulating ANCA antibodies from the blood — bridge therapy while immunosuppression (rituximab/cyclophosphamide) takes effect (days to weeks). Typically 7 exchanges over 14 days.
What is the initial treatment for suspected GCA with visual symptoms?
IV methylprednisolone 1g × 3 days IMMEDIATELY — do NOT wait for biopsy. Temporal artery biopsy can be done up to 2 weeks after starting steroids. Visual loss is often irreversible if treatment delayed even hours.
What drug has replaced cyclophosphamide as first-line induction for ANCA vasculitis?
Rituximab [RAVE, 2010] — equally effective for induction with fewer side effects. Preferred in relapsing disease. Cyclophosphamide still used but carries bladder cancer, infertility, and myelosuppression risks.
What is avacopan and why is it important?
C5a receptor inhibitor [ADVOCATE, 2021] — the first approved steroid-sparing agent for ANCA vasculitis. Can replace prednisone during induction (used with rituximab or cyclophosphamide). Superior sustained remission at 52 weeks.
How do you differentiate GPA from MPA?
GPA (Wegener's): upper + lower respiratory + renal. Cavitary lung nodules, sinusitis, saddle nose deformity. c-ANCA/PR3+. MPA: renal + pulmonary (DAH) without upper airway. No granulomas. p-ANCA/MPO+.
📣 Sample Presentation
One-Liner
"Mr. O'Connell is a 58-year-old presenting with hemoptysis, RPGN (Cr rising 1.2→4.8 in 4 days), and CT showing bilateral GGO. c-ANCA positive, anti-PR3 positive. Consistent with GPA (granulomatosis with polyangiitis)."
Key Points to Cover on Rounds
GPA with pulmonary-renal syndrome — c-ANCA/PR3+. Cr 4.8 (RPGN — UA showing RBC casts). CT chest: bilateral GGO (DAH). Hemoptysis — life-threatening. Treatment: (1) pulse methylprednisolone 1g IV × 3 days, (2) rituximab 375 mg/m² weekly × 4 weeks [RAVE, 2010] (preferred for PR3+ — lower relapse rate than cyclophosphamide for relapsing disease), (3) emergent plasmapheresis initiated (Cr >5.7 or DAH → PLEX indicated). Biopsy: renal biopsy scheduled but NOT delaying treatment. Plan: daily Cr, Hgb, CXR for DAH monitoring. PCP prophylaxis with TMP-SMX. Hepatitis B/TB screening (before rituximab infusion #2).
📄 One Pager
Rheumatology · One Pager
ANCA Vasculitis
c-ANCA/PR3 = GPA. p-ANCA/MPO = MPA/EGPA. Induction: steroids + rituximab or cyclophosphamide. PLEX for DAH or Cr > 5.7. Maintenance: rituximab q6 months.
Types
GPA (granulomatosis with polyangiitis): upper airway + lungs + kidneys. c-ANCA/PR3. MPA (microscopic polyangiitis): kidneys + lungs (no granulomas). p-ANCA/MPO. EGPA: asthma + eosinophilia + vasculitis. p-ANCA/MPO.
Induction
Pulse methylprednisolone 1g × 3d → prednisone taper. Rituximab 375 mg/m² × 4 weeks [RAVE, 2010] (PR3+/relapsing) OR cyclophosphamide (severe renal/DAH). PLEX if Cr > 5.7 or DAH.
Maintenance
Rituximab 500 mg q6 months × 2 years [MAINRITSAN, 2014] OR azathioprine. PCP prophylaxis (TMP-SMX). Calcium + vitamin D. Screen for TB/HBV before rituximab.
Key Drugs
Methylprednisolone1g IV × 3d
Rituximab375 mg/m² weekly × 4
Cyclophosphamide15 mg/kg q2wk × 3 then q3wk
TMP-SMXDS daily (PCP prophylaxis)
Pitfalls
- Waiting for biopsy to start treatment (life-threatening disease — treat empirically)
- Missing pulmonary-renal syndrome (DAH + RPGN = emergent)
- Not starting PCP prophylaxis on immunosuppression
- Missing relapse (monitor ANCA titers, Cr, UA q3-6 months)
Rotation
Rheumatology
Autoimmune diseases, vasculitis, crystal arthropathies, and immunosuppression management.
Available Topics
Gout & Pseudogout
SLE Flare
Vasculitis
Rheumatoid Arthritis
Antiphospholipid Syndrome
Scleroderma & Renal Crisis
Septic Arthritis
PMR & Giant Cell Arteritis
Dermatomyositis & Polymyositis
Spondyloarthropathies
📋 Major Guidelines
Hospice Eligibility Criteria
Hospice = comfort-focused care for patients with prognosis ≤ 6 months. It's a Medicare benefit, not giving up. Patients and families consistently say they wish hospice was offered earlier. Know the disease-specific criteria.
🕊️ Hospice Eligibility
General Criteria (All Diseases)
- Prognosis ≤ 6 months if disease runs its expected course (physician certification)
- Patient (or surrogate) elects comfort-focused care — no curative intent treatments
- General decline indicators: Karnofsky < 50% or PPS ≤ 50%, recurrent hospitalizations, progressive weight loss (> 10% in 6 months), declining functional status (increasing dependence in ADLs), albumin < 2.5
- "Surprise question": "Would you be surprised if this patient died in the next 6 months?" If no → hospice referral appropriate. SUPPORT Study, 1995
Disease-Specific Criteria
| Disease | Hospice-Eligible When |
|---|---|
| Heart Failure | NYHA Class IV at rest despite optimal therapy. EF ≤ 20%. Recurrent hospitalizations (≥ 3 in 6 months). Refractory to diuretics. Not a candidate for transplant/LVAD. Symptomatic hypotension limiting meds. |
| COPD / Pulmonary | FEV₁ < 30% predicted. Resting dyspnea on max therapy. O₂-dependent. Cor pulmonale / RHF. Recurrent exacerbations requiring hospitalization. pCO₂ > 50 or O₂ sat ≤ 88% on room air. |
| Dementia | FAST scale ≥ 7 (unable to ambulate, dress, bathe without assistance; < 6 intelligible words). Plus ≥ 1 complication in past 12 months: aspiration pneumonia, pyelonephritis, sepsis, decubitus ulcer stage III+, recurrent fever despite abx. |
| Cancer | Metastatic disease declining despite treatment or patient declines further disease-directed therapy. Poor performance status (ECOG 3–4). Progressive despite ≥ 2 lines of therapy. Hypercalcemia, malignant effusions, cachexia. |
| Liver disease | MELD ≥ 30 (not transplant candidate). Refractory ascites. SBP recurrence. HRS. Hepatic encephalopathy despite lactulose/rifaximin. Progressive jaundice. |
| Renal disease | CKD stage 5 (GFR < 15) and patient declines or discontinues dialysis. Creatinine clearance < 10 mL/min (CrCl < 15 for diabetics). Uremic symptoms not being treated with RRT. |
| Stroke / Neurologic | Coma or persistent vegetative state. Dysphagia with aspiration + declining to PEG. Progressive decline despite rehab. Recurrent aspiration pneumonia. |
What Hospice Provides
- Covered by Medicare Part A — no out-of-pocket cost to patient for hospice services
- Includes: RN visits (typically 1–3×/week), aide visits, social worker, chaplain, medications related to terminal diagnosis, DME (hospital bed, O₂, wheelchair), continuous care during crises, respite care (5 days), bereavement support for 13 months after death
- Does NOT mean stopping all meds. Comfort medications continue (pain, nausea, dyspnea, anxiety). Disease-modifying meds may continue if they provide symptom benefit. Temel et al., 2010
- Can be revoked at any time — patient can re-elect curative care if they change their mind
📋 On Rounds
Pimp Questions
A family asks: 'Does hospice mean you're giving up on my father?' How do you respond?
This is one of the most important conversations in medicine. The key reframe: 'Hospice isn't giving up — it's refocusing.' We're shifting from treatments that aren't working to treatments that improve quality of life. Hospice provides more care, not less: a nurse visits regularly, medications for comfort are covered, a chaplain and social worker support the family, and there's 24/7 phone access for crises. Patients on hospice often live longer than matched patients who continue aggressive treatment — this was shown in a landmark study of patients with metastatic lung cancer [Temel, 2010: early palliative care improved both quality of life AND survival by 2.7 months. Hospice can also be revoked at any time if the patient improves or changes their mind.
What is the difference between hospice and palliative care?
Palliative care can be provided at any stage of serious illness, alongside curative treatment. It focuses on symptom management, goals of care, and quality of life. There is no prognosis requirement. Hospice is a specific Medicare benefit for patients with prognosis ≤ 6 months who elect comfort-focused care (no curative-intent treatments). Think of it this way: all hospice is palliative care, but not all palliative care is hospice. A patient getting chemotherapy can receive palliative care simultaneously. A patient on hospice has chosen to focus entirely on comfort. The most common regret from families: 'We wish we had started hospice sooner.'
What are the general hospice eligibility criteria beyond disease-specific ones?
General LCD (Local Coverage Determination) criteria: (1) Prognosis ≤ 6 months if disease runs its usual course (certified by 2 physicians), (2) Patient has elected comfort-focused care (no curative-intent treatments), (3) Functional decline: PPS (Palliative Performance Scale) ≤ 50% or declining, increasing dependence in ADLs, spending > 50% of day in bed. (4) Nutritional decline: unintentional weight loss > 10% in 6 months, albumin < 2.5 (supportive, not required), declining oral intake. (5) Recurrent infections, hospitalizations, or ER visits despite optimal treatment. Disease-specific criteria exist for: cancer, CHF (NYHA IV, EF < 20%, refractory), COPD (FEV₁ < 30%, O₂-dependent, cor pulmonale), dementia (FAST ≥ 7, aspiration, recurrent infections), renal (not pursuing dialysis, CrCl < 10). Hospice can be revoked if patient improves — it's not a one-way door.
What symptoms can hospice patients still receive treatment for?
Hospice is NOT withdrawal of all treatment — it's refocusing on comfort. Hospice covers: (1) Pain: opioids, adjuvants (gabapentin, duloxetine, dexamethasone), nerve blocks, radiation for bone mets pain. (2) Dyspnea: morphine (first-line, low-dose), supplemental O₂ for comfort (not to chase SpO₂), fan directed at face, benzodiazepines if anxiety-related. (3) Nausea: ondansetron, haloperidol, metoclopramide, dexamethasone. (4) Secretions: glycopyrrolate or atropine drops (death rattle). (5) Agitation/delirium: haloperidol, lorazepam. (6) Constipation: senna, docusate, methylnaltrexone for opioid-induced. What hospice does NOT cover: curative-intent treatments (chemo, surgery for cure, dialysis for ESKD). Some palliative chemo/radiation IS covered if for symptom relief (bone pain, SVC obstruction). This is the most misunderstood part of hospice.
📣 Sample Presentation
One-Liner
"Mrs. Martinez is a 78-year-old with metastatic pancreatic cancer, declining PPS (30%), unable to eat or ambulate, with increasing pain and dyspnea. Oncology confirms no further disease-directed therapy. Family meeting held — patient and family electing hospice."
Key Points to Cover on Rounds
Goals of care discussion completed using REMAP framework. Patient priorities: comfort, being at home, no more ER visits. Prognosis: weeks to low months (PPS 30%, declining trajectory). Code status: DNR/DNI documented and in chart. Hospice eligibility: metastatic cancer with declining functional status despite treatment — meets LCD criteria. Hospice agency contacted — admission tomorrow. Comfort medications ordered: morphine 5 mg PO q4h PRN pain, lorazepam 0.5 mg SL q4h PRN anxiety, ondansetron 4 mg q6h PRN nausea, glycopyrrolate 0.2 mg SL q4h PRN secretions. Unnecessary meds stopped: statin, metformin, lisinopril. Hospital bed and O₂ arranged for home.
🧪 Workup
Diagnostic Evaluation — Tumor Lysis Syndrome
Workup checklist for Tumor Lysis Syndrome: History and physical → targeted labs → imaging as indicated → specialist consultation if needed. Always correlate clinically.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications, relevant PMH
- Physical exam: Focused exam relevant to tumor lysis syndrome presentation
- Labs: CBC, BMP, relevant disease-specific labs (see Overview tab for specifics)
- Imaging: As clinically indicated based on presentation
- Special studies: Consider disease-specific diagnostics (see Overview tab)
💊 Medications
Key Medications — Tumor Lysis Syndrome
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — Tumor Lysis Syndrome
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
⚡ Summary
Summary
Eligibility
Prognosis ≤ 6 months if disease runs its usual course. Patient elects comfort. Certified by 2 physicians. Can be revoked if patient improves.
Comfort Meds
Pain: morphine. Dyspnea: morphine + fan. Nausea: ondansetron, haloperidol. Secretions: glycopyrrolate/atropine. Agitation: lorazepam, haloperidol.
Stop Unnecessary
Statins, metformin, vitamins, screening tests, antihypertensives (if comfort-focused). Each med removed = reduced pill burden + side effects.
Hospice ≠ Giving Up
Hospice provides active symptom management, emotional/spiritual support, family bereavement, aide services, equipment, medications.
Prognostic Tools
PPS (Palliative Performance Scale): ≤ 50% supports hospice eligibility. Disease-specific criteria: CHF NYHA IV, COPD FEV₁ < 30%, dementia FAST ≥ 7.
Family Support
Caregiver burnout is real. Hospice provides: respite care (5 days), bereavement counseling × 13 months post-death, 24/7 nurse phone access.
📄 One Pager
Tumor Lysis Syndrome — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
TUMOR LYSIS SYNDROME — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
⚡ Management
Management — Vasculitis
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
📄 One Pager
Palliative Care · One Pager
Hospice
Prognosis ≤ 6 months. Comfort-focused. Active symptom management + family support. Can be revoked if patient improves. Hospice ≠ giving up.
Eligibility
Prognosis ≤ 6 months (certified by 2 physicians). Patient elects comfort care. PPS ≤ 50%. Declining functional status, nutritional decline, recurrent hospitalizations. Disease-specific criteria exist.
Comfort Medications
Pain: morphine (first-line). Dyspnea: morphine + fan at face. Nausea: ondansetron, haloperidol. Secretions: glycopyrrolate/atropine drops. Agitation: haloperidol, lorazepam.
What to Stop
Statins, metformin, vitamins, screening tests, antihypertensives (unless symptomatic). Each med removed = reduced pill burden + side effects. Focus on comfort and quality of life.
Key Drugs
Morphine2-5 mg PO/SL q2-4h PRN
Lorazepam0.5-1 mg SL q4h PRN
Ondansetron4 mg q6h PRN
Glycopyrrolate0.2 mg SL q4h PRN
Pitfalls
- Hospice = giving up (it's active symptom management + support)
- Continuing aggressive meds that add no comfort benefit
- Not offering hospice early enough (many patients referred too late)
- Not supporting caregivers (burnout is real — hospice provides respite care)
Opioid Rotation & Pain Management
When to rotate opioids, how to calculate the conversion, and the critical 25–50% dose reduction for incomplete cross-tolerance. Getting this wrong causes respiratory depression or undertreated pain.
💊 Opioid Rotation Protocol
When to Rotate
- Intolerable side effects (nausea, sedation, pruritus, myoclonus) despite dose adjustments
- Inadequate analgesia despite dose escalation (true tolerance vs ceiling effect)
- Renal failure (rotate away from morphine — M6G accumulates) McPherson et al., 2018
- Route change required (PO → IV, or vice versa)
4-Step Conversion Process
Step 1
Calculate total 24h dose of current opioid (scheduled + PRN breakthrough actually used). Example: morphine 30 mg PO q4h (scheduled) + 15 mg PO × 4 breakthrough = 210 mg PO morphine/24h.
Step 2
Convert to equianalgesic dose of new opioid using conversion table (see Opioid Conversions). 210 mg PO morphine ÷ 30 × 20 = 140 mg PO oxycodone/24h equivalent.
Step 3
Reduce by 25–50% for incomplete cross-tolerance. Different opioids bind to different μ-receptor subtypes → previous tolerance doesn't fully transfer. 140 × 0.75 = 105 mg PO oxycodone/24h. Use 50% reduction if: elderly, frail, renal/hepatic impairment, or switching to methadone.
Step 4
Split into scheduled + PRN. Scheduled: 105 ÷ 24h = ~4.4 mg/hr → oxycodone ER 45 mg q12h (or round to nearest available). PRN breakthrough: 10–15% of total 24h dose = oxycodone IR 10–15 mg q3h PRN.
ALWAYS reduce the calculated equianalgesic dose by 25–50%. Skipping this step is the #1 cause of opioid rotation overdose. The cross-tolerance reduction is non-negotiable. McPherson et al., 2018 For methadone conversions: ALWAYS consult pharmacy or palliative care — methadone conversion is non-linear and complex. CDC Opioid Prescribing Guideline, 2022
💊 Non-Opioid Adjuvants
| Pain Type | Agent | Notes |
|---|---|---|
| Neuropathic | Gabapentin (Neurontin) 100–300 mg TID → titrate to 1200 mg TID or pregabalin (Lyrica) 75 mg BID → 300 mg BID | First-line for neuropathic pain. Start low, titrate slow (sedation, dizziness). Reduce dose in CKD. Also: duloxetine 30–60 mg daily (good for diabetic neuropathy). |
| Bone metastases | Dexamethasone (Decadron) 4–8 mg daily + radiation therapy (single fraction effective) + NSAIDs if tolerated | Steroids reduce peri-tumor edema → rapid pain relief. Bisphosphonates/denosumab for skeletal events prevention. |
| Bowel obstruction | Dexamethasone (Decadron) 8–16 mg IV daily + octreotide (Sandostatin) 100–300 mcg SC TID + glycopyrrolate for secretions | Medical management for malignant bowel obstruction when surgery is not appropriate. |
| Visceral / somatic | Acetaminophen (Tylenol) 1g q6h (scheduled, not PRN) + NSAIDs (ibuprofen 400–600 mg TID or ketorolac 15 mg IV q6h × 5 days max) | Scheduled acetaminophen reduces opioid requirements by 20–30%. NSAIDs: avoid in CKD, GI bleed risk, CHF. Ketorolac: max 5 days (renal toxicity). |
| Muscle spasm | Baclofen 5–10 mg TID or tizanidine 2–4 mg TID | Avoid cyclobenzaprine in elderly (anticholinergic → delirium). Baclofen: reduce dose in CKD (renally cleared). |
🔄 Updated Practice: Old teaching: pain is the "5th vital sign" — treat aggressively with opioids. This contributed to the opioid epidemic. Current practice: multimodal analgesia first (acetaminophen + NSAIDs/ketorolac + gabapentin/pregabalin + regional/local anesthesia). Opioids are for severe pain refractory to multimodal therapy, at the lowest effective dose, for the shortest duration. For chronic non-cancer pain, opioids should generally be avoided — evidence shows minimal long-term benefit with significant harm (addiction, hyperalgesia, overdose).
📋 On Rounds
Pimp Questions
Why do you reduce the equianalgesic dose by 25–50% when rotating opioids?
Incomplete cross-tolerance. Different opioids bind to slightly different μ-opioid receptor subtypes and have different receptor binding profiles (μ1, μ2, δ, κ). When a patient develops tolerance to one opioid, that tolerance does NOT fully transfer to a new opioid — the new drug will be more potent than the conversion table suggests. Without the reduction, you're effectively giving an opioid-naive dose to a tolerant patient, but with the full equianalgesic potency of the new drug. This is the #1 cause of opioid rotation overdose. The 25% reduction is for straightforward rotations; use 50% for: elderly, hepatic/renal impairment, switching to methadone, or high-dose conversions.
When should you rotate opioids vs simply increase the dose of the current opioid?
Rotate (switch to a different opioid) when: (1) intolerable side effects despite dose adjustments (persistent nausea, myoclonus, pruritis, sedation — a different opioid may not cause the same side effect), (2) true analgesic tolerance with escalating doses and diminishing returns (switching resets cross-tolerance), (3) organ dysfunction requiring a different metabolism (e.g., morphine → hydromorphone in renal failure because morphine's M6G metabolite accumulates), (4) route change needed (PO no longer feasible → transdermal or parenteral). Increase the current dose when: pain is undertreated but the patient tolerates the drug well, or it's early in therapy and you haven't reached an adequate dose yet.
What is the most dangerous opioid rotation and why?
Rotation TO methadone is the most dangerous. Methadone has unique pharmacology that makes standard equianalgesic tables unreliable: (1) Long and variable half-life (15-60 hours) — steady state takes 5-7 days, so dose adjustments cause delayed toxicity. (2) Incomplete cross-tolerance is MORE pronounced with methadone than other opioids — the standard tables OVERESTIMATE the required methadone dose. (3) QTc prolongation — check ECG before starting and after dose changes. (4) NMDA receptor antagonism — gives analgesic benefit but also makes the conversion ratio non-linear (higher morphine doses convert to proportionally LESS methadone — not a simple ratio). Rule: use dedicated methadone conversion tables (not standard equianalgesic charts), reduce by ≥ 50-75%, start low and titrate slowly over days, and only prescribed by providers experienced with methadone.
What is the equianalgesic dose table and what are its limitations?
Key conversions (oral): Morphine 30 mg = Oxycodone 20 mg = Hydromorphone 6 mg = Hydrocodone 30 mg. IV conversions: Morphine 10 mg IV = Hydromorphone 1.5 mg IV. Oral-to-IV ratio: morphine 3:1 (30 mg PO = 10 mg IV), hydromorphone 5:1 (6 mg PO ≈ 1.5 mg IV). Limitations: (1) Tables are based on single-dose studies in opioid-naive patients — do NOT apply directly to chronic opioid patients. (2) Always apply 25-50% dose reduction for incomplete cross-tolerance. (3) Methadone and fentanyl have NON-LINEAR conversions (can't use a simple ratio). (4) Individual variation is huge — genetics (CYP2D6 polymorphisms), organ function, age all affect metabolism. The table is a starting point, not the answer — always titrate based on clinical response.
📣 Sample Presentation
One-Liner
"Mr. Lee is a 64-year-old with metastatic prostate cancer on sustained-release morphine 60 mg BID + morphine IR 15 mg q4h PRN (using 4 doses/day) being rotated to hydromorphone due to intolerable nausea, myoclonus, and pruritus."
Key Points to Cover on Rounds
Current 24h opioid: morphine SR 120 mg + IR 60 mg = 180 mg oral morphine/day. Equianalgesic conversion: oral morphine 180 mg → oral hydromorphone (÷5) = 36 mg/day. Apply 25% reduction for incomplete cross-tolerance → 27 mg/day. New regimen: hydromorphone ER 12 mg PO BID (24 mg scheduled) + hydromorphone IR 3 mg PO q3h PRN (10-15% of TDD for breakthrough). Bowel regimen continued: senna + docusate. Antiemetic PRN. Plan: monitor for first 48-72h, adjust based on pain scores and breakthrough use. Expect resolution of morphine-specific side effects.
🔍 Overview
Overview — Opioid Rotation & Pain Management
See the tabs above for the complete clinical reference: Workup, Management, Medications, Monitoring, Rounds, Summary, and One Pager.
🧪 Workup
Pre-Rotation Assessment — Opioid Rotation
- Pain assessment — numeric rating scale (0–10), functional goals ("What would you like to be able to do?"), pain quality (nociceptive vs neuropathic), exacerbating/relieving factors. The number alone is insufficient.
- Current opioid regimen — exact drug, dose, route, frequency (scheduled + PRN). Calculate total 24h opioid consumption including all breakthrough doses actually taken.
- Equianalgesic calculation — convert current total 24h dose to oral morphine equivalents (OME), then convert to the new opioid using equianalgesic table. Apply 25–50% reduction for incomplete cross-tolerance.
- Reason for rotation — intolerable side effects (nausea, myoclonus, pruritus, sedation), analgesic tolerance despite dose escalation, cost/formulary, route change needed (PO → IV or vice versa)
- Renal function (BMP, CrCl) — affects opioid metabolism. Morphine: avoid in CKD (active metabolite M6G accumulates → prolonged sedation/respiratory depression). Hydromorphone: safer in CKD but metabolite H3G can accumulate. Fentanyl: safest in renal failure (no active metabolites).
- Hepatic function (LFTs) — most opioids are hepatically metabolized (CYP3A4, CYP2D6). Severe liver disease → reduced clearance → dose reduce and extend intervals. Methadone especially affected.
⚡ Management
Management — Opioid Rotation
See the Rotation Steps tab above for the full 4-step conversion process with equianalgesic calculations and cross-tolerance reduction guidance.
💊 Medications
Equianalgesic Conversion Table
| Opioid | PO Dose (equianalgesic) | IV Dose | PO:IV Ratio | Notes |
|---|---|---|---|---|
| Morphine (MS Contin) | 30 mg | 10 mg | 3:1 | Reference standard. Avoid in CKD (M6G accumulates). IR: q4h. ER: q8–12h. |
| Hydromorphone (Dilaudid) | 6 mg | 1.5 mg | 4–5:1 | Preferred in renal impairment. 5× more potent than morphine PO. IR: q3–4h. ER: q12–24h. |
| Oxycodone (OxyContin) | 20 mg | N/A (no IV form) | — | 1.5× more potent than morphine PO. IR: q4–6h. ER: q12h. |
| Fentanyl patch (Duragesic) | 12 mcg/hr patch ≈ 30 mg PO morphine/24h | Variable | — | For stable opioid requirements ONLY (not acute pain). Takes 12–24h to reach peak effect. No active metabolites — safest in CKD/ESRD. |
| Methadone (Dolophine) | Non-linear conversion | Variable | ~2:1 | DANGER t½ = 15–60h. QTc prolongation. NMDA antagonist. Use dedicated methadone conversion tables — NOT the standard equianalgesic table. Consult pharmacy or palliative care. |
After calculating the equianalgesic dose, reduce the new opioid by 25–50% for incomplete cross-tolerance. This is non-negotiable. Use the 50% reduction for: elderly, hepatic/renal impairment, methadone conversions, or high-dose rotations (> 200 mg OME/day). Methadone has additional unique risks — always consult an experienced prescriber.
📈 Monitoring
Monitoring Parameters — Opioid Rotation
| Parameter | Frequency | Target / Action |
|---|---|---|
| Pain scores | q4h + 1h after each PRN dose | Target ≤ 4/10 or functional goals (e.g., able to ambulate, sleep). Track breakthrough use — if > 3 PRN doses/day, increase scheduled dose. |
| Sedation (Pasero Opioid-Induced Sedation Scale) | q4h with vitals (q1–2h first 24h post-rotation) | S = sleep, easy to arouse; 1 = awake, alert (acceptable); 2 = slightly drowsy (acceptable); 3 = frequently drowsy (hold dose, reduce); 4 = somnolent (hold, consider naloxone). Naloxone (Narcan) must be at bedside. |
| Respiratory rate | q4h (q1h first 24h of new opioid) | RR < 10 → hold opioid. RR < 8 or unresponsive → naloxone 0.04–0.4 mg IV (titrate to respirations, not consciousness). Monitor closely × 48–72h after rotation. |
| Bowel regimen | Daily assessment (BM frequency) | Start bowel regimen with ALL opioids — senna 8.6 mg + docusate 100 mg BID. No BM × 3 days → add bisacodyl or methylnaltrexone (Relistor) 12 mg SC if refractory. Tolerance does NOT develop to constipation. |
| Pruritus | Each assessment | Common opioid side effect (histamine release). Rotation may resolve it. Treat with low-dose nalbuphine 2.5 mg IV or hydroxyzine 25 mg PO. Avoid diphenhydramine (additive sedation). |
| Nausea | Each assessment | Often resolves with rotation. Ondansetron 4 mg IV/PO q8h PRN. Haloperidol 0.5–1 mg PO/IV for refractory opioid-induced nausea. |
| Functional status | Daily | Can the patient ambulate, participate in PT, perform ADLs? Pain management goal is function, not a number. Reassess total opioid requirements and consider multimodal adjuncts. |
Monitor closely × 48–72h after any opioid rotation. Incomplete cross-tolerance means the new opioid may be unexpectedly potent. Have naloxone (Narcan) at bedside for all patients on opioid drips or after recent rotation. Adjust based on pain scores, breakthrough use, and side effect profile.
⚡ Summary
Summary
Why Rotate
Tolerance, intolerable side effects (nausea, myoclonus, pruritus), renal failure (morphine metabolites accumulate), poor pain control.
Equianalgesic
Oral morphine 30 = oxycodone 20 = hydromorphone 6. IV morphine 10 = hydromorphone 1.5. Always apply 25-50% reduction for incomplete cross-tolerance.
Methadone Danger
Non-linear conversion. Long half-life (15-60h). QTc prolongation. Use dedicated methadone tables. Start low, titrate over days. Experienced prescribers only.
Fentanyl Patch
For stable opioid requirements only (not acute pain). Calculate 24h oral morphine equivalent → divide by 2 (approximately) = mcg/hr fentanyl.
Cross-Tolerance
Previous opioid exposure means partial tolerance — but cross-tolerance is INCOMPLETE between different opioids. Always reduce calculated dose by 25-50%.
Monitor After Rotation
Closely monitor × 48-72h after rotation. New opioid may be more or less potent than expected. Adjust based on pain scores and breakthrough use.
📄 One Pager
Opioid Rotation — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card.
OPIOID ROTATION — AT A GLANCE
📋 When to rotate: Intolerable side effects, tolerance, poor pain control, renal failure (morphine metabolites).
📊 Equianalgesic: PO morphine 30 = oxycodone 20 = hydromorphone 6. IV morphine 10 = hydromorphone 1.5.
⚠️ Cross-tolerance: Always reduce calculated dose by 25–50% — cross-tolerance is INCOMPLETE.
🚨 Methadone: Non-linear conversion, long t½ (15–60h), QTc risk. Use dedicated tables. Experienced prescribers only.
📈 Monitor: Closely × 48–72h after rotation. Pain scores, sedation, RR. Narcan at bedside.
📊 Equianalgesic: PO morphine 30 = oxycodone 20 = hydromorphone 6. IV morphine 10 = hydromorphone 1.5.
⚠️ Cross-tolerance: Always reduce calculated dose by 25–50% — cross-tolerance is INCOMPLETE.
🚨 Methadone: Non-linear conversion, long t½ (15–60h), QTc risk. Use dedicated tables. Experienced prescribers only.
📈 Monitor: Closely × 48–72h after rotation. Pain scores, sedation, RR. Narcan at bedside.
Goals of Care & Symptom Management
Palliative care is not hospice. It's about aligning treatment with the patient's values at any stage of illness. Every resident should be able to lead a goals-of-care conversation and manage common symptoms at end of life.
🤝 Goals of Care Conversation
When to Have the Conversation
- Any new serious diagnosis (advanced cancer, end-stage organ failure, severe dementia)
- Significant clinical deterioration or ICU admission
- Repeated hospitalizations for chronic progressive disease
- "Would you be surprised if this patient died in the next year?" — if no, initiate GOC discussion.
Framework — REMAP
| Step | What to Say |
|---|---|
| R — Reframe | "I want to step back and talk about the big picture of what's going on." |
| E — Expect emotion | Pause. Acknowledge. "I can see this is hard to hear." NURSE: Name, Understand, Respect, Support, Explore. |
| M — Map values | "What matters most to you?" "What does a good day look like?" "Are there things worse than death to you?" |
| A — Align | "Based on what you've told me — that being independent and not suffering are most important — I'd recommend..." |
| P — Plan | Concrete next steps. Document. Communicate with team. Revisit as things change. |
Code Status Discussion
- Avoid: "Do you want us to do everything?" (misleading — implies no CPR = giving up)
- Better: "If your heart were to stop, CPR involves chest compressions that often break ribs, a breathing tube, and electric shocks. In someone with your condition, the chance of surviving to leave the hospital is about ___%. Given what you've told me about what matters most to you, I would recommend..."
- Make a recommendation. Patients want guidance, not just options.
💊 Symptom Management
| Symptom | First-Line | Notes |
|---|---|---|
| Pain | Morphine (MS Contin) 2–5 mg IV/SC q2–4h PRN or oxycodone 5–10 mg PO q4h. Scheduled + PRN for constant pain. | Titrate to comfort. No ceiling for opioids in end-of-life care. Add adjuncts: acetaminophen (scheduled), gabapentin (neuropathic), dexamethasone (bone mets, inflammation). |
| Dyspnea | Morphine (MS Contin) 2–4 mg IV/SC q2–4h PRN. Fan to face. Oxygen if hypoxic. | Opioids are the most effective treatment for dyspnea in palliative care. They reduce the sensation of breathlessness centrally. Low doses are safe and don't hasten death Opioids for Dyspnea Trial, 2003. Anxiolytics (lorazepam 0.5–1 mg) if anxiety-driven. |
| Nausea / vomiting | Ondansetron (Zofran) 4–8 mg IV q6h or haloperidol 0.5–1 mg IV q6h (good for opioid-induced or chemical causes) | Match anti-emetic to mechanism: chemoreceptor trigger zone → haloperidol/ondansetron. GI dysmotility → metoclopramide. Raised ICP → dexamethasone. Vestibular → meclizine. |
| Terminal secretions ("death rattle") | Glycopyrrolate 0.2–0.4 mg IV/SC q4h or atropine drops 1% SL q4h | Anticholinergics reduce new secretion production. Suctioning is uncomfortable and often futile. Reposition to lateral. Reassure family — the sound is often more distressing to family than to the patient. |
| Terminal agitation / delirium | Haloperidol (Haldol) 1–2 mg IV/SC q4h. Add lorazepam 1–2 mg if refractory. | Rule out reversible causes first (urinary retention, constipation, pain, medication). If actively dying and refractory → palliative sedation with midazolam or phenobarbital infusion (requires palliative care consult + family discussion). |
🔍 Overview
Overview
Palliative care improves quality of life through symptom management, GOC discussions, and psychosocial support. Appropriate at any illness stage — concurrent with curative treatment. Palliative care ≠ hospice.
🧪 Workup
Workup
- ESAS symptom scores (0-10)
- Functional status — PPS, ECOG
- Prognostication — surprise question, PPI
- Advance directives review
- Psychosocial/spiritual screening
🚨 Management
Management
- Pain: WHO ladder + adjuvants (gabapentin, duloxetine, dexamethasone)
- Dyspnea: Morphine 2-5mg SL + fan at face + O₂ if hypoxic
- Nausea: Ondansetron, haloperidol, metoclopramide
- Delirium: Haloperidol 0.5-2mg. Treat reversible causes.
- GOC: REMAP framework
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Morphine | 2-5mg PO/SL q2-4h | PO/SL | Pain + dyspnea |
| Gabapentin | 100-900mg TID | PO | Neuropathic pain |
| Dexamethasone | 4-8mg daily | PO/IV | Bone mets, edema, obstruction |
| Haloperidol | 0.5-2mg q4-6h | PO/IV | Nausea + delirium |
| Glycopyrrolate | 0.2mg SL q4h | SL | Secretions |
| Lorazepam | 0.5-1mg SL q4h | SL | Anxiety, agitation |
📊 Monitoring
Monitoring
- ESAS scores daily
- Pain scale — goal functional
- Bowel regimen — all opioid patients
- Sedation level
- GOC reassessment with progression
📋 On Rounds
Pimp Questions
An attending asks you to 'make the patient comfortable' — what specific orders do you write?
This is a practical question that catches many interns off guard. A complete comfort care order set includes: (1) Pain: morphine 2–5 mg IV/SC q2h PRN (or current opioid equivalent). Scheduled if constant pain. (2) Dyspnea: morphine 2–4 mg IV/SC q2h PRN (opioids are first-line for dyspnea). (3) Anxiety/agitation: lorazepam 0.5–1 mg IV/SC q4h PRN. (4) Secretions (death rattle): glycopyrrolate 0.2 mg IV/SC q4h PRN or atropine 1% drops SL q4h. (5) Nausea: ondansetron 4 mg IV q6h PRN or haloperidol 0.5–1 mg IV q6h. (6) Fever: acetaminophen 650 mg PR q6h PRN. (7) Discontinue: labs, vitals (except comfort assessment), telemetry, unnecessary medications, fingerstick glucose, restraints. (8) Continue: mouth care, repositioning q2h, family presence, chaplain if desired.
How do you know when to give morphine for dyspnea vs when it will hasten death?
This is one of the most common misconceptions in medicine. Appropriately dosed opioids for dyspnea do NOT hasten death. This was definitively shown by Abernethy et al. (2003): low-dose morphine significantly improved dyspnea without affecting respiratory rate, oxygen saturation, or survival. The mechanism: opioids reduce the central perception of breathlessness by acting on μ-receptors in the brainstem respiratory center and limbic system — they change how the brain processes the sensation of air hunger, not how the lungs work. The principle of double effect applies: the intent is to relieve suffering (good effect), and any theoretical hastening of death (unintended effect) is ethically permissible when the primary intent is comfort. Start low (morphine 2 mg IV/SC q2h PRN) and titrate to effect. A comfortable patient often breathes better, not worse.
What is the REMAP framework for goals of care conversations?
Reframe — Set the stage: "I want to make sure we're on the same page about what's happening." Clarify medical reality without jargon. Expect emotion — Pause. Let silence work. Acknowledge: "I can see this is really hard." Don't fill silence with medical facts. Map values — "What matters most to your father?" "What would he say if he could tell us?" "Has he ever talked about what he would NOT want?" Align — "Based on what you're telling me he values, it sounds like focusing on comfort would be most in line with who he is." Make a recommendation aligned with their values. Plan — Concrete next steps: "Here's what I recommend we do..." Code status. Hospice referral if appropriate. Follow-up. The most common mistake: jumping straight to "do you want us to do CPR?" without mapping values first. Goals of care ≠ code status discussion.
How do you manage terminal dyspnea?
Dyspnea is the symptom patients and families fear most in the terminal phase. Management: (1) Morphine is first-line — 2-5 mg PO/SL/SQ q2-4h PRN. Reduces central perception of breathlessness without clinically significant respiratory depression at appropriate doses [Opioids for Dyspnea Trial, 2003. (2) Fan directed at face — stimulates V2 branch of trigeminal nerve → reduces sensation of air hunger. Evidence-based and free. (3) Supplemental O₂: for hypoxic patients. If SpO₂ is normal and patient still feels dyspneic, O₂ provides no additional benefit over room air fan [Fan for Dyspnea Trial, 2010. (4) Benzodiazepines: lorazepam 0.5-1 mg SL q4h for anxiety-related dyspnea (anxiety amplifies breathlessness perception). (5) Positioning: upright, leaning forward. (6) Discontinue unnecessary monitoring (SpO₂ alarms cause anxiety — turn them off in comfort care).
📣 Sample Presentation
One-Liner
"Mr. Washington is a 82-year-old with advanced dementia (FAST 7c), recurrent aspiration pneumonia × 3 admissions this year, and worsening functional status. Family requesting "everything" but primary team is concerned about escalating interventions."
Key Points to Cover on Rounds
Goals of care conversation needed. Current trajectory: advanced dementia with recurrent aspiration — antibiotics are treating the symptom, not the underlying cause. REMAP framework used: R (reframe: "his dementia is causing the pneumonias — antibiotics can't fix that"), E (expect emotion — family is grieving), M (map values: "what would he say if he could tell us?"), A (align), P (plan). Family shared that he previously said he "never wanted to be a burden." After discussion, family chose: comfort-focused care, treat symptoms (dyspnea with morphine 2 mg SL q2h PRN), no more antibiotics for aspiration, no intubation, no ICU. Hospice referral initiated. Palliative care following.
⚡ Summary
Summary
REMAP
Reframe → Expect emotion → Map values → Align → Plan. The gold standard framework for goals of care conversations.
Code Status ≠ GOC
Goals of care is about values and what matters. Code status is one small part. Don't lead with "do you want CPR?" — map values first.
Dyspnea
Morphine (first-line), fan at face, O₂ for hypoxic patients, benzodiazepines for anxiety component. Positioning. Discontinue SpO₂ alarms in comfort care.
Pain
WHO ladder: non-opioid → weak opioid → strong opioid. Adjuvants for neuropathic: gabapentin, duloxetine. Dexamethasone for bone pain, bowel obstruction, cerebral edema.
Prognostication
PPS, ECOG, disease-specific models. Clinicians overestimate survival by 3-5×. Use objective tools. Communicate uncertainty honestly.
When to Consult
Refractory symptoms, complex goals of care, family conflict, transition to hospice, existential/spiritual distress, withdrawal of life-sustaining treatment.
📄 One Pager
Palliative Care · One Pager
Palliative Care
REMAP framework for goals of care. Code status ≠ GOC. Morphine for dyspnea. Fan at face. Consult for refractory symptoms, complex GOC, family conflict.
REMAP Framework
Reframe (medical reality without jargon). Expect emotion (pause, acknowledge). Map values ("what matters most?"). Align (recommendation based on values). Plan (concrete next steps).
Symptom Management
Pain: WHO ladder (non-opioid → weak → strong opioid) + adjuvants (gabapentin, duloxetine). Dyspnea: morphine (first-line) + fan at face + O₂ if hypoxic. Nausea: ondansetron, haloperidol. Delirium: haloperidol, lorazepam.
When to Consult
Refractory symptoms despite standard management. Complex goals of care conversations. Family conflict. Transition to hospice. Withdrawal of life-sustaining treatment. Existential/spiritual distress.
Key Drugs
Morphine2-5 mg PO/SL q2-4h PRN (dyspnea + pain)
Gabapentin100-900 mg TID (neuropathic)
Dexamethasone4-8 mg daily (brain mets, obstruction)
Haloperidol0.5-2 mg q4-6h (nausea/delirium)
Pitfalls
- Jumping to code status without mapping values first
- Withholding morphine for dyspnea (effective and safe at appropriate doses)
- Not considering palliative care consult until patient is dying
- O₂ for non-hypoxic dyspnea (fan at face is equally effective [Fan for Dyspnea Trial, 2010])
Rotation
Palliative Care
Symptom management, goals of care conversations, pain at end of life, hospice criteria, and comfort-focused care.
Available Topics
Goals of Care & Symptom Management
Hospice Eligibility Criteria
Opioid Rotation & Pain
Code Status & Advance Directives
Family Meeting Framework
Prognostication Tools
Non-Opioid Symptom Management
Palliative Extubation
📋 Major Guidelines
Outpatient Diabetes Management
The treatment paradigm has shifted. It's no longer just about A1c — cardiorenal protection drives drug selection. SGLT2 inhibitors and GLP-1 agonists now have organ-protective benefits independent of glucose lowering.
💊 ADA 2024 Treatment Algorithm
Step 1 — All Type 2 DM
- Metformin (Glucophage) remains first-line for most patients (A1c reduction ~1.5%, weight neutral, cheap, CV benefit UKPDS, 1998)
- Lifestyle: 150 min/week moderate exercise, 5–7% weight loss target, medical nutrition therapy DPP, 2002
- A1c target: < 7% for most. < 6.5% if early disease, no hypoglycemia risk. < 8% if elderly, multiple comorbidities, limited life expectancy.
Step 2 — Add Based on Comorbidities (Not Just A1c)
| Comorbidity | Preferred Agent | Key Trial | Notes |
|---|---|---|---|
| ASCVD or high CV risk | GLP-1 RA (semaglutide, liraglutide, dulaglutide) PREFERRED | SUSTAIN-6, 2016 LEADER, 2016 | Reduce MACE (MI, stroke, CV death). Weight loss 5–15%. Weekly injection (semaglutide SC) or daily (liraglutide). GI side effects (nausea) limit titration. Also available PO (oral semaglutide). |
| Heart failure (HFrEF or HFpEF) | SGLT2i (empagliflozin, dapagliflozin) PREFERRED | EMPA-REG, 2015 DAPA-HF, 2019 | Reduce HF hospitalization and CV death — even in patients WITHOUT diabetes EMPEROR-Preserved, 2021. Now part of HF guideline-directed therapy. Also renal-protective. |
| CKD (eGFR 20–60 or albuminuria) | SGLT2i (dapagliflozin, empagliflozin) PREFERRED | DAPA-CKD, 2020 EMPA-KIDNEY, 2022 | Slow CKD progression by 30–40%. Can use down to eGFR 20 (initiate) or continue to dialysis. Glucose-lowering effect diminishes at low GFR but renal benefit persists. |
| Obesity (weight loss priority) | GLP-1 RA (semaglutide > others) or tirzepatide (dual GIP/GLP-1) | SURPASS, 2021 SURMOUNT, 2022 | Tirzepatide: most potent A1c reduction (~2.5%) and weight loss (~15–20%). Semaglutide 2.4 mg (Wegovy) FDA-approved for obesity regardless of DM. |
| Cost / simplicity priority | Sulfonylurea (glipizide, glimepiride) or pioglitazone | — | Very cheap. SU: hypoglycemia + weight gain risk. Pioglitazone: fluid retention (avoid in HF), fracture risk, bladder cancer concern. |
The key paradigm shift: drug selection is now driven by comorbidities (ASCVD, HF, CKD, obesity), not just A1c. A patient with DM + HF should be on an SGLT2i regardless of their A1c. A patient with DM + ASCVD should be on a GLP-1 RA.
📋 On Rounds
Why are SGLT2 inhibitors beneficial in HF even without diabetes?
The HF benefit of SGLT2i is independent of glucose lowering. Proposed mechanisms: (1) Osmotic diuresis + natriuresis → reduces preload and congestion without RAAS activation (unlike loop diuretics). (2) Improved cardiac energetics — shifts myocardial fuel from fatty acids to ketone bodies (more efficient substrate). (3) Reduced interstitial fibrosis and inflammation. (4) Improved endothelial function. (5) Nephroprotection → reduces tubuloglomerular feedback → lowers intraglomerular pressure. This is why DAPA-HF, 2019 and EMPEROR-Reduced, 2020 showed benefit in HFrEF patients both with and without diabetes, and why SGLT2i are now in the HF guidelines as a foundational therapy alongside ARNI, BB, and MRA.
Why are SGLT2 inhibitors given even in patients with A1c at goal?
SGLT2 inhibitors have organ-protective benefits independent of glucose lowering. EMPA-REG OUTCOME [EMPA-REG, 2015 showed empagliflozin reduced CV death by 38% in T2DM with ASCVD — a benefit too large and too fast to be explained by A1c reduction alone. DAPA-CKD showed dapagliflozin slowed CKD progression even in non-diabetic kidney disease. EMPEROR-Preserved showed benefit in HFpEF. The mechanisms: natriuresis → reduced preload, reduced intraglomerular pressure (afferent arteriole constriction), improved myocardial energetics (ketone body utilization), reduced inflammation. Bottom line: SGLT2i are now indicated for HF and CKD regardless of diabetes status. A1c at goal is NOT a reason to withhold them.
How do you choose between GLP-1 RA and SGLT2i when a patient has both ASCVD and CKD?
Start both — they work through different mechanisms and benefits are additive. If you must prioritize one: ASCVD-dominant → GLP-1 RA first (semaglutide, liraglutide — proven CV death reduction [SUSTAIN-6, LEADER). CKD-dominant → SGLT2i first (empagliflozin, dapagliflozin — proven renal protection [CREDENCE, DAPA-CKD, slow eGFR decline, reduce proteinuria). HF-dominant → SGLT2i first (reduce HF hospitalization in both HFrEF and HFpEF [DAPA-HF, EMPEROR-Preserved). Obesity-dominant → GLP-1 RA first (semaglutide 2.4 mg causes ~15% weight loss; SGLT2i only ~2-3 kg). Both agents have benefits beyond glucose lowering — which is why ADA guidelines now recommend them based on comorbidities, not A1c.
What is the 'legacy effect' in diabetes and why does early A1c matter?
The legacy effect (metabolic memory) refers to the long-term benefit of early intensive glucose control — even after control is later relaxed. [UKPDS, 1998 initially showed modest benefit of intensive control in newly diagnosed T2DM. But the 10-year post-trial follow-up showed the intensively-treated group continued to have lower rates of MI and death even though A1c had equalized between groups. Similarly, [DCCT/EDIC in T1DM: early intensive control reduced CV events and nephropathy DECADES later. Clinical implication: early, aggressive A1c control in NEWLY diagnosed diabetes has lasting benefits. In contrast, aggressively lowering A1c in LONG-STANDING diabetes with complications may cause harm (hypoglycemia → MI, falls) — [ACCORD, 2008 showed increased mortality targeting A1c < 6.0% in established T2DM. Bottom line: treat early and aggressively, but relax targets as disease progresses.
📣 Sample Presentation
One-Liner
"Mrs. Patel is a 54-year-old with T2DM (A1c 8.6), BMI 34, ASCVD (prior MI), and eGFR 52, currently on metformin 1000 BID only. Here for medication optimization."
Key Points to Cover on Rounds
A1c 8.6 (goal <7). BMI 34. ASCVD + CKD — drug selection driven by comorbidities, not just A1c. Changes: (1) Add semaglutide 0.25 mg SQ weekly, uptitrate to 1 mg (GLP-1 RA — proven CV benefit [SUSTAIN-6], weight loss, renal protection), (2) Add empagliflozin 10 mg daily (SGLT2i — proven CV + renal benefit [EMPA-REG, CREDENCE], even at eGFR 52), (3) Continue metformin 1000 BID. Screening: eye exam (overdue), foot exam done today (monofilament intact), UACR 180 (albuminuria — SGLT2i indicated). Statin confirmed (atorvastatin 80). Plan: recheck A1c in 3 months, titrate semaglutide, UACR in 6 months.
🧪 Workup
Workup — Goals of Care & Symptom Management
Workup for Goals of Care & Symptom Management: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
⚡ Management
Management — Goals of Care & Symptom Management
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
💊 Medications
Medications — Goals of Care & Symptom Management
Medication details for Goals of Care & Symptom Management are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Goals of Care & Symptom Management
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Drug Selection
ASCVD → GLP-1 RA first [SUSTAIN-6, LEADER]. CKD → SGLT2i [CREDENCE, DAPA-CKD]. HF → SGLT2i [DAPA-HF]. Obesity → GLP-1 RA. Continue metformin in most.
A1c Targets
< 7% for most. < 6.5% for newly diagnosed, young, no complications. < 8% for elderly, limited life expectancy, hypoglycemia risk, long-standing disease [ACCORD lesson].
Screening
Eye exam annually. Foot exam annually (monofilament). UACR annually if ≥ 5 years T1DM or at diagnosis T2DM. Lipid panel. BP every visit.
SGLT2i Caveats
Monitor for euglycemic DKA (especially in T1DM, surgery, fasting). Mycotic genital infections. AKI risk with dehydration. Avoid if eGFR < 20.
GLP-1 RA Caveats
GI side effects (titrate slowly). Pancreatitis risk (debated). Thyroid C-cell tumors (rodent data). Contraindicated in MEN2 or medullary thyroid cancer.
Legacy Effect
Early intensive control has lasting benefits decades later [UKPDS post-trial, DCCT/EDIC]. Treat early and aggressively. Relax targets as disease advances.
📄 One Pager
One Pager — Goals of Care & Symptom Management
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
GOALS OF CARE & SYMPTOM MANAGEMENT — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
Obesity Management & GLP-1 Agents
Obesity is a chronic disease, not a lifestyle choice. BMI ≥ 30 (or ≥ 27 with comorbidities) qualifies for pharmacotherapy. GLP-1 agonists and tirzepatide have transformed the field — 15–25% weight loss is now achievable.
💊 Anti-Obesity Medications
| Drug | Mechanism | Weight Loss | Key Notes |
|---|---|---|---|
| Semaglutide 2.4 mg (Wegovy) PREFERRED | GLP-1 receptor agonist → ↑ satiety, ↓ appetite, delayed gastric emptying | ~15% body weight STEP 1, 2021 | Weekly SC injection. Titrate slowly over 16 weeks (nausea management). Also reduces MACE by 20% SELECT, 2023 — CV benefit independent of diabetes. Contraindicated: personal/family history of medullary thyroid carcinoma, MEN2. |
| Tirzepatide (Zepbound) MOST EFFECTIVE | Dual GIP + GLP-1 receptor agonist | ~20–25% body weight SURMOUNT-1, 2022 | Weekly SC injection. Most potent weight loss agent available. Also FDA-approved for T2DM (as Mounjaro). Same GI side effects and contraindications as semaglutide. |
| Liraglutide 3.0 mg (Saxenda) | GLP-1 RA | ~5–8% | Daily SC injection. Less effective than semaglutide but first GLP-1 approved for obesity. Being replaced by weekly options. |
| Phentermine-topiramate ER (Qsymia) | Sympathomimetic + anticonvulsant (appetite suppression) | ~8–10% | Oral daily. Avoid in uncontrolled HTN, glaucoma, hyperthyroidism. Topiramate: teratogenic (REMS program), cognitive effects, metabolic acidosis, kidney stones. |
| Naltrexone-bupropion (Contrave) | Opioid antagonist + dopamine/NE reuptake inhibitor | ~5–6% | Oral. Good for patients with food cravings/binge eating. Avoid in seizure disorders, opioid use, uncontrolled HTN. Bupropion helps with smoking cessation too. |
| Orlistat (Xenical/Alli) | Lipase inhibitor (blocks fat absorption) | ~3–5% | GI side effects (oily stools, flatulence, fecal urgency) limit tolerability. OTC version (Alli 60 mg). Least effective. |
Bariatric Surgery
- Indications: BMI ≥ 40, or BMI ≥ 35 with obesity-related comorbidity (DM, HTN, OSA, NAFLD). ADA 2024: consider for BMI ≥ 30 with uncontrolled T2DM.
- Roux-en-Y gastric bypass: ~30% excess weight loss. DM remission in 60–80%. Malabsorptive → lifelong vitamin supplementation (B12, iron, calcium, folate, vitamin D).
- Sleeve gastrectomy: most commonly performed. ~25% excess weight loss. Fewer nutritional deficiencies than RYGB. GERD may worsen.
- Most effective long-term treatment for obesity and T2DM — superior to all medications for sustained weight loss and diabetes remission.
📋 On Rounds
Pimp Questions
Why do SGLT2 inhibitors cause weight loss while sulfonylureas cause weight gain?
SGLT2 inhibitors (empagliflozin, dapagliflozin) block sodium-glucose co-transporter 2 in the proximal tubule → glycosuria (urinating out ~70g glucose/day = ~280 kcal/day). This caloric loss drives ~2–3 kg weight loss. Additionally, osmotic diuresis causes initial fluid loss. Sulfonylureas (glipizide, glimepiride) stimulate pancreatic β-cells to release insulin regardless of glucose level → hyperinsulinemia → (1) drives glucose into cells including adipose tissue → fat storage, (2) causes hypoglycemia → patient eats more to compensate (defensive eating). This combination of anabolic insulin effects + compensatory eating causes 2–5 kg weight gain. This is why the ADA algorithm now favors SGLT2i and GLP-1 RA (weight loss + organ protection) over sulfonylureas (weight gain + hypoglycemia) for most patients.
A patient asks: 'Will I regain the weight if I stop semaglutide?' What's the evidence?
Unfortunately, yes — most patients regain ~2/3 of lost weight within 1 year of stopping GLP-1 agonists. The STEP 1 extension trial showed that after stopping semaglutide 2.4 mg, participants regained most of the weight they had lost. This is because GLP-1 agonists work by suppressing appetite centrally and slowing gastric emptying — when the drug is removed, appetite returns to baseline. This is analogous to stopping antihypertensives and having BP return to baseline — obesity is a chronic disease requiring chronic treatment. The key counseling points: (1) medication is one component alongside lifestyle changes, (2) long-term use is likely needed for sustained benefit, (3) even partial weight maintenance after stopping has metabolic benefits, (4) behavioral habits built during treatment may help mitigate some regain.
What are the criteria for bariatric surgery referral?
BMI ≥ 40 (regardless of comorbidities) OR BMI ≥ 35 with ≥ 1 obesity-related comorbidity (T2DM, HTN, OSA, NAFLD/NASH, GERD, OA, dyslipidemia). Some guidelines now support BMI ≥ 30 with uncontrolled T2DM. Types: Roux-en-Y gastric bypass (gold standard, ~30% excess weight loss), sleeve gastrectomy (most common currently, ~25% EWL), adjustable gastric band (declining use). Expected outcomes: 50-70% excess weight loss at 1 year, T2DM remission in 60-80% (especially RYGB), significant improvement in HTN, OSA, and NASH. Lifelong requirements: vitamin monitoring (B12, iron, calcium, D, folate), protein intake ≥ 60g/day, no NSAIDs (marginal ulcer risk), psychiatric support. Surgery is NOT "the easy way out" — it's the most effective long-term treatment for severe obesity.
What are the side effects of GLP-1 agonists that every prescriber should counsel about?
Most common (GI — dose-dependent, typically improve with slow titration): nausea (30-40%), vomiting, diarrhea, constipation, abdominal pain. Counsel: start low and titrate slowly, eat smaller meals, avoid fatty/fried foods. Serious but rare: (1) Pancreatitis: FDA warning, though causal link is debated. Stop if severe abdominal pain + elevated lipase. (2) Gallstones: rapid weight loss → bile stasis → cholelithiasis (same risk as any rapid weight loss). (3) Thyroid C-cell tumors: seen in rodents, not confirmed in humans. Contraindicated in personal/family history of medullary thyroid cancer or MEN2. (4) Gastroparesis/ileal obstruction: slowed gastric emptying can cause severe symptoms in predisposed patients. (5) Hypoglycemia: rare as monotherapy, but increased when combined with sulfonylureas or insulin — reduce those doses. (6) Injection site reactions. Aspiration risk: consider holding GLP-1 before elective surgery/anesthesia (delayed gastric emptying → aspiration).
📣 Sample Presentation
One-Liner
"Mr. Rodriguez is a 42-year-old with BMI 38, prediabetes (A1c 6.2), OSA on CPAP, and knee osteoarthritis. He has tried diet and exercise programs without sustained weight loss. Interested in pharmacotherapy."
Key Points to Cover on Rounds
BMI 38 with obesity-related comorbidities (prediabetes, OSA, OA). Prior weight loss attempts: commercial programs, lost 10 lbs but regained. Pharmacotherapy options discussed: (1) semaglutide 2.4 mg SQ weekly (most effective, ~15% weight loss [STEP 1]), (2) tirzepatide (dual GIP/GLP-1, ~20% weight loss [SURMOUNT-1]). Starting semaglutide 0.25 mg weekly, uptitrate monthly to 2.4 mg. Counseling: medication is one component alongside lifestyle (goal: 150 min/week moderate exercise, dietary changes). Insurance coverage checked. Bariatric surgery discussed as alternative (BMI ≥35 + comorbidities = eligible). Plan: monthly follow-up for dose titration, weight, and A1c monitoring.
🧪 Workup
Diagnostic Evaluation — HIT (Heparin-Induced Thrombocytopenia)
Workup checklist for HIT (Heparin-Induced Thrombocytopenia): History and physical → targeted labs → imaging as indicated → specialist consultation if needed. Always correlate clinically.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications, relevant PMH
- Physical exam: Focused exam relevant to hit (heparin-induced thrombocytopenia) presentation
- Labs: CBC, BMP, relevant disease-specific labs (see Overview tab for specifics)
- Imaging: As clinically indicated based on presentation
- Special studies: Consider disease-specific diagnostics (see Overview tab)
💊 Medications
Key Medications — HIT (Heparin-Induced Thrombocytopenia)
Refer to the Management tab for the full treatment algorithm with drug choices, dosing, and contraindications. Refer to the Antibiotic Guide if infectious etiology. Always check renal dosing and drug interactions.
- First-line agents: See Management tab for evidence-based recommendations with trial citations
- Renal adjustment: Check CrCl — see Antibiotic Guide renal dosing tab or Calculators for CrCl
- Drug interactions: See Drug Interactions reference
- Allergies: Always verify before prescribing. Document reaction type (rash vs anaphylaxis)
📈 Monitoring
Monitoring Parameters — HIT (Heparin-Induced Thrombocytopenia)
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | HR, BP, RR, SpO₂, Temp — notify for significant deviations |
| Labs (BMP, CBC) | Daily AM or as indicated | Trend Cr, K⁺, WBC, Hgb — adjust treatment based on trajectory |
| Disease-specific markers | Per clinical context | See Overview and Management tabs for condition-specific targets |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr. Net fluid balance guides diuresis or resuscitation. |
| Telemetry | Continuous if indicated | Arrhythmia detection. Discontinue when no longer indicated (reduces alarm fatigue). |
| Clinical response | Each assessment | Symptom improvement, functional status, appetite, mental status — the exam matters more than labs |
Don't just order labs — act on them. Every lab should have a clear clinical question. If you wouldn't change management based on the result, don't order it.
⚡ Summary
Summary
Pharmacotherapy
Semaglutide 2.4 mg SQ weekly (~15% weight loss [STEP 1]). Tirzepatide (~20% [SURMOUNT-1]). Titrate slowly to reduce GI side effects.
Bariatric Surgery
BMI ≥ 40 or ≥ 35 + comorbidity. Sleeve gastrectomy most common. RYGB gold standard. T2DM remission 60-80%. 50-70% excess weight loss.
Lifestyle
Foundation: 150 min/week moderate exercise + caloric deficit + behavioral counseling. Alone = ~5% weight loss. Needed alongside all pharmacotherapy.
Comorbidity Screening
OSA (STOP-BANG), NAFLD (LFTs, US), T2DM (A1c), dyslipidemia, HTN, GERD, OA, depression. Treat all identified comorbidities.
Post-Bariatric
Lifelong vitamin monitoring (B12, iron, calcium, D, folate). Protein ≥ 60g/day. No NSAIDs (marginal ulcer). Psychiatric support.
Not "Willpower"
Obesity is a chronic disease with genetic, hormonal, and environmental drivers. Frame treatment like any chronic disease — no blame, evidence-based management.
📄 One Pager
HIT (Heparin-Induced Thrombocytopenia) — Quick Reference Card
Print this page (Ctrl/Cmd + P) for a condensed reference card. All tabs will print on the same page for a complete topic summary.
HIT (HEPARIN-INDUCED THROMBOCYTOPENIA) — AT A GLANCE
📋 Diagnose: See Overview tab for criteria
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🧪 Workup: Focused labs + imaging → see Workup tab
⚡ Treat: Evidence-based algorithm → see Management tab
💊 Drugs: Key medications with dosing → see Medications tab
📈 Monitor: Disease-specific targets → see Monitoring tab
📣 Present: One-liner + key points → see Rounds tab
🔍 Overview
Overview — Obesity Management & GLP-1 Agents
See the tabs above for the complete clinical reference: Workup, Management, Medications, Monitoring, Rounds, Summary, and One Pager.
⚡ Management
Management — Obesity Management & GLP-1 Agents
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
📄 One Pager
Endocrine / Primary Care · One Pager
Obesity
BMI ≥ 30 = obesity. GLP-1 RAs are transformative (~15-20% weight loss). Bariatric surgery for BMI ≥ 40 or ≥ 35 + comorbidity. Lifestyle is foundation but insufficient alone for severe obesity.
Classification
BMI 25-29.9 = overweight. 30-34.9 = class I obesity. 35-39.9 = class II. ≥ 40 = class III. Screen for comorbidities: OSA, NAFLD, T2DM, HTN, dyslipidemia.
Pharmacotherapy
Semaglutide 2.4 mg SQ weekly (~15% weight loss [STEP 1]). Tirzepatide (dual GIP/GLP-1, ~20% [SURMOUNT-1]). Titrate slowly to minimize GI side effects. Lifestyle (150 min/week exercise + dietary changes) is always the foundation.
Bariatric Surgery
BMI ≥ 40 or ≥ 35 + comorbidity. Sleeve gastrectomy (most common). RYGB (gold standard). T2DM remission 60-80%. 50-70% excess weight loss. Lifelong vitamin monitoring required.
Key Drugs
Semaglutide0.25 → 2.4 mg SQ weekly
Tirzepatide2.5 → 15 mg SQ weekly
Phentermine-topiramate3.75/23 → 15/92 mg daily
Lifestyle150 min/week exercise + caloric deficit
Pitfalls
- "Just diet and exercise" for severe obesity (insufficient alone — like telling diabetic to "just eat better")
- Not screening for OSA, NAFLD, DM
- GI side effects at full dose (titrate slowly over weeks-months)
- GLP-1 RA before elective surgery (aspiration risk — hold per anesthesia guidelines)
Smoking Cessation
The single most impactful preventive intervention in medicine. Smoking cessation reduces all-cause mortality more than any drug you will ever prescribe. Ask every patient, every visit. Combination NRT + varenicline has the highest quit rate.
🚭 Pharmacotherapy
5 A's Framework
- Ask — about tobacco use at every visit
- Advise — to quit in a clear, personalized way ("Quitting is the single best thing you can do for your health")
- Assess — willingness to make a quit attempt
- Assist — offer medication + counseling (combination is most effective)
- Arrange — follow-up within 1 week of quit date
| Agent | Dose | Quit Rate | Notes |
|---|---|---|---|
| Varenicline (Chantix) MOST EFFECTIVE | 0.5 mg daily × 3 days → 0.5 mg BID × 4 days → 1 mg BID × 12 weeks. Can extend to 24 weeks. | ~30% at 1 year | Partial nicotine receptor agonist (reduces craving + blocks reward from smoking). FDA removed black box warning for neuropsych events EAGLES, 2016 — safe even in psychiatric patients. Start 1 week before quit date. GI side effects (nausea — take with food). Can combine with NRT for even higher efficacy. |
| NRT — patch | 21 mg/day × 6 wks → 14 mg × 2 wks → 7 mg × 2 wks (if > 10 cig/day). 14 mg start if < 10/day. | ~15–20% alone, ~25–30% combined | Apply to clean, hairless skin, rotate sites. Combine patch (sustained) + lozenge or gum (acute cravings) for best results — combination NRT is as effective as varenicline. |
| NRT — gum/lozenge | 2 mg or 4 mg (if first cigarette within 30 min of waking → 4 mg). Use q1–2h PRN. | ~15–20% | Best as add-on to patch for breakthrough cravings. Gum: "park and chew" technique. Lozenge: dissolve in mouth, don't chew. |
| Bupropion SR (Zyban) | 150 mg daily × 3 days → 150 mg BID × 12 weeks. Start 1–2 weeks before quit date. | ~20% | Also treats depression. Contraindicated in seizure disorders, eating disorders, MAOI use. Weight-neutral (unlike most cessation — patients often gain 5–10 lbs). Can combine with NRT. |
Highest quit rates: Varenicline + NRT patch (~35%), Varenicline alone (~30%), Combination NRT (patch + gum/lozenge, ~28%), Bupropion + NRT (~25%). All superior to counseling alone (~5–10%). Always combine pharmacotherapy with behavioral counseling (quitline: 1-800-QUIT-NOW).
📋 On Rounds
Pimp Questions
A patient says 'I've tried quitting before and it didn't work.' How do you respond?
This is actually encouraging, not discouraging. Most successful quitters have tried 6–8 times before finally quitting permanently. Each attempt teaches the patient about their triggers, cravings, and what strategies work or don't work for them. The response: 'That's actually great — it means you've been working at this. Most people need several attempts. Let's figure out what happened last time and try a different approach.' Then assess: (1) What method did they use? (many try cold turkey — medication doubles quit rates), (2) What triggered relapse? (stress, social situations, alcohol), (3) What worked, even briefly? Build on that. The most important thing: offer pharmacotherapy this time. Varenicline + NRT patch is the most effective combination (~35% 1-year quit rate). Behavioral counseling alone is only 5–10%.
Why is varenicline more effective than NRT alone?
Varenicline (Chantix) is a partial agonist at the α4β2 nicotinic acetylcholine receptor — the same receptor that nicotine binds. It works through a dual mechanism: (1) Agonist effect (~50% activation): provides a low level of dopamine release in the nucleus accumbens → reduces craving and withdrawal symptoms (similar to NRT but via the same receptor). (2) Antagonist effect (blocks full activation): if the patient smokes while on varenicline, nicotine cannot fully activate the receptor → the rewarding 'hit' from smoking is blunted → cigarettes become less satisfying. This combination of reducing withdrawal + blocking reward is more effective than NRT alone (which only addresses withdrawal). [EAGLES, 2016 confirmed varenicline's safety and superior efficacy, with ~30% 1-year quit rate vs ~20% for NRT.
What is the evidence for combining varenicline with NRT patch?
Combination therapy (varenicline + NRT patch) is the most effective smoking cessation strategy. A meta-analysis and the VARNIC trial showed ~35-40% quit rates at 12 weeks (vs ~25% for varenicline alone, ~20% for NRT alone, ~5-10% for counseling alone). Mechanism: varenicline provides partial agonism at the nicotinic receptor (reduces craving + blocks smoking reward), while the NRT patch provides steady-state nicotine replacement (further reduces withdrawal). Safety: [EAGLES, 2016 confirmed varenicline does NOT increase neuropsychiatric events (previous FDA black box was removed). Can be used in patients with psychiatric history. Start NRT patch (21 mg/day) on quit date while already on varenicline (started 1 week pre-quit). Continue both × 12 weeks. Consider extending to 24 weeks for heavy smokers.
What does the USPSTF say about e-cigarettes/vaping for smoking cessation?
USPSTF has NOT endorsed e-cigarettes for cessation — evidence is insufficient. While some studies show higher quit rates with e-cigs vs NRT (particularly the UK NIHR trial), concerns remain: (1) Dual use: many smokers vape AND smoke → no net benefit. (2) Long-term safety unknown: EVALI outbreak (2019) raised concerns, though most cases were linked to THC/vitamin E acetate, not nicotine e-cigs. (3) Nicotine addiction continues — just in a different form. Most patients don't transition off e-cigs. (4) Youth gateway effect: teen vaping has increased dramatically. Current recommendation: FDA-approved pharmacotherapy (varenicline, NRT, bupropion) remains the standard. If a patient is already using e-cigs and has quit combustible tobacco, acknowledge the harm reduction (vaping is likely less harmful than smoking) but encourage eventual nicotine cessation entirely.
📣 Sample Presentation
One-Liner
"Ms. Davis is a 52-year-old with 30-pack-year smoking history, COPD, and HTN. She wants to quit but has tried cold turkey twice and relapsed within 2 weeks both times. Ready to try medication."
Key Points to Cover on Rounds
Pack-year: 30. Prior quit attempts: 2 (cold turkey — no pharmacotherapy). Stage of change: preparation (ready to set quit date). Pharmacotherapy plan: varenicline 0.5 mg daily × 3 days → 0.5 mg BID × 4 days → 1 mg BID (start 1 week before quit date, continue × 12 weeks). Added NRT patch 21 mg/day for combination therapy (varenicline + NRT = highest quit rate ~35%). Quit date set: 2 weeks from today. Behavioral counseling: quitline referral (1-800-QUIT-NOW), trigger avoidance strategies discussed. LDCT lung cancer screening: eligible (50-80 yo, ≥20 pack-years) — ordered. Plan: follow-up call at 1 week post-quit date, office visit at 4 weeks.
🔍 Overview
Overview — Outpatient Diabetes Management
See the tabs above for the complete clinical reference: Workup, Management, Medications, Monitoring, Rounds, Summary, and One Pager.
🧪 Workup
Workup — Outpatient Diabetes Management
Workup for Outpatient Diabetes Management: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
⚡ Management
Management — Outpatient Diabetes Management
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
💊 Medications
Medications — Outpatient Diabetes Management
Medication details for Outpatient Diabetes Management are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Outpatient Diabetes Management
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Most Effective
Varenicline + NRT patch = highest quit rate (~35-40%). Start varenicline 1 week pre-quit date. NRT patch on quit date. Continue × 12 weeks.
Varenicline
0.5 mg daily × 3 days → 0.5 BID × 4 days → 1 mg BID. Safe in psychiatric patients [EAGLES, 2016]. FDA removed black box warning.
NRT Options
Patch (21/14/7 mg taper), gum, lozenge, inhaler, nasal spray. Patch for baseline + short-acting form for breakthrough cravings.
Bupropion
150 mg daily × 3 days → 150 BID. Start 1-2 weeks pre-quit. Also treats depression. Avoid in seizure history, eating disorders.
Lung Cancer Screening
Age 50-80 + ≥ 20 pack-years + current smoker or quit within 15 years → annual LDCT [USPSTF 2021]. Reduces mortality 20% [NLST].
Brief Intervention
5 A's: Ask (smoking status), Advise (quit), Assess (readiness), Assist (pharmacotherapy + counseling), Arrange (follow-up). Takes 3 minutes.
📄 One Pager
One Pager — Outpatient Diabetes Management
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
OUTPATIENT DIABETES MANAGEMENT — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
Preventive Care & Screening
The bread and butter of outpatient medicine. Know the USPSTF A/B recommendations cold — cancer screening, cardiovascular risk assessment, and immunizations. This is what keeps patients out of the hospital.
🔬 Cancer Screening (USPSTF)
| Cancer | Test | Age / Frequency | Key Notes |
|---|---|---|---|
| Breast | Mammography | 40–74, every 2 years (USPSTF 2024 update — lowered from 50 to 40) | Shared decision 40–49 in prior guidelines. Now routine. High-risk (BRCA, family hx) → may add MRI. |
| Cervical | Pap ± HPV | 21–65. Pap q3 years (21–29). Pap + HPV co-test q5 years or HPV alone q5 years (30–65). | Stop at 65 if adequate prior screening. No screening if hysterectomy (no cervix) for non-cancer indication. |
| Colorectal | Colonoscopy, FIT, Cologuard | 45–75. Colonoscopy q10 years, FIT annually, Cologuard q3 years. | USPSTF 2021 lowered from 50 to 45. 76–85 = selective. Family hx → start 10 years before youngest affected relative or age 40. |
| Lung | Low-dose CT (LDCT) | 50–80, ≥ 20 pack-years, current or quit within 15 years. Annual. | NLST, 2011: 20% mortality reduction. NELSON, 2020: confirmed. Shared decision-making required. |
| Prostate | PSA | 55–69: shared decision-making. USPSTF does NOT recommend routine screening. | PSA has high false-positive rate → unnecessary biopsies. Discuss benefits/harms. Not recommended > 70. |
Other Key Screenings
| Condition | Screening | Population |
|---|---|---|
| AAA | One-time abdominal US | Men 65–75 who ever smoked |
| Hepatitis C | Anti-HCV antibody | All adults 18–79 (one-time). USPSTF 2020. |
| HIV | HIV Ag/Ab combo | All adults 15–65 (one-time or more if high-risk). USPSTF 2019. |
| Diabetes | Fasting glucose, A1c, or OGTT | 35–70 with overweight/obesity. Screen q3 years. |
| Osteoporosis | DEXA scan | Women ≥ 65. Younger postmenopausal if FRAX 10-year hip fracture risk ≥ 3%. |
| Depression | PHQ-2 → PHQ-9 | All adults. USPSTF 2016. |
❤️ Cardiovascular Risk
Statin Therapy (ACC/AHA 2018)
| Group | Recommendation |
|---|---|
| 1. Clinical ASCVD (prior MI, stroke, PAD) | High-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) 4S, 1994. Target LDL < 70. Add ezetimibe if not at goal → add PCSK9 inhibitor if still not at goal. |
| 2. LDL ≥ 190 | High-intensity statin. Likely familial hypercholesterolemia. Lipid specialist referral. |
| 3. DM age 40–75, LDL 70–189 | Moderate-intensity statin (atorvastatin 10–20 mg, rosuvastatin 5–10 mg). High-intensity if 10-year ASCVD risk ≥ 7.5%. |
| 4. Non-DM, LDL 70–189, 10-yr ASCVD ≥ 7.5% | Moderate to high-intensity statin. If borderline (5–7.5%) → consider risk enhancers (family hx, CAC score, CRP, ABI). |
Hypertension (ACC/AHA 2017)
- Stage 1 HTN: 130–139/80–89. Lifestyle × 3–6 months first if ASCVD risk < 10%. Start medication if ≥ 10% risk or if not at goal after lifestyle.
- Stage 2 HTN: ≥ 140/90. Start 2-drug combination therapy. Reassess in 1 month.
- Target: < 130/80 for most adults SPRINT, 2015.
- First-line agents: ACEi/ARB (preferred if DM, CKD, proteinuria, HF), thiazide (chlorthalidone preferred), CCB (amlodipine). Start 2 of 3 for stage 2.
- Resistant HTN (≥ 3 drugs at max doses): screen for OSA, hyperaldosteronism, renal artery stenosis. Add spironolactone PATHWAY-2, 2015.
🏥 Rounds
Pimp Questions
USPSTF recently lowered the mammography screening start age. What changed and why?
In 2024, USPSTF lowered the recommended start age for mammography screening from 50 to 40, with biennial screening through age 74. The change was driven by rising breast cancer incidence in women under 50 — particularly Black women, who have higher rates of aggressive subtypes (triple-negative) and present at younger ages. The prior recommendation (50–74, with "individual decision" for 40–49) led to disparities in screening uptake. The updated recommendation makes screening routine for all average-risk women starting at 40, simplifying the message and reducing disparities.
A 52-year-old male with no history of heart disease has an LDL of 130 and a 10-year ASCVD risk of 8%. Does he need a statin?
This falls into ACC/AHA Group 4: non-DM, LDL 70–189, 10-year ASCVD risk 7.5–20% → moderate to high-intensity statin is recommended. At 8% risk, a statin is indicated. However, for borderline cases (5–7.5%), you'd use risk enhancers to guide the decision: family history of premature ASCVD, persistently elevated CRP (> 2), elevated Lp(a), South Asian ancestry, metabolic syndrome, or coronary artery calcium (CAC) score > 0. If risk enhancers are present → start statin. If none → can defer and recheck in 5 years. A CAC score of 0 is particularly useful to defer statin in borderline patients (very low event rate).
When do you start lung cancer screening with LDCT and who qualifies?
USPSTF 2021 recommendation: Annual LDCT for adults aged 50-80 with ≥ 20 pack-year smoking history who currently smoke OR quit within the last 15 years. This was expanded from the previous criteria (55-80, ≥ 30 pack-years) to capture more at-risk individuals. Stop screening when: the person has not smoked for 15 years, develops a health problem that limits life expectancy or willingness to have curative surgery, or turns 81. The NLST trial showed LDCT reduced lung cancer mortality by 20% compared to chest X-ray. Key counseling points: high false-positive rate (~25% will have a finding requiring follow-up, most are benign), radiation exposure is low (equivalent to ~15 CXRs), and this does NOT replace smoking cessation — screening + quitting is the best combination.
What cancer screenings are recommended by USPSTF and at what ages?
Breast: Mammography every 2 years, ages 40-74 (updated 2024 — lowered from 50). Cervical: Pap every 3 years ages 21-29, Pap + HPV co-test every 5 years ages 30-65. Colorectal: Start at 45 (updated from 50). Options: colonoscopy q10y, FIT annually, Cologuard q3y, CT colonography q5y, flex sig q5y. Lung: Annual LDCT ages 50-80 with ≥ 20 pack-year history + currently smoke or quit within 15 years. Prostate: Shared decision-making ages 55-69 (PSA screening — NOT universal recommendation). Not recommende
d: ovarian cancer screening (no effective test), pancreatic cancer screening (g
eneral population), thyroid cancer screening. Pearl: the single screening test
with the strongest mortality benefit relative to effort is colonoscopy — N
NS ~200 to prevent 1 CRC death over 10 years.
🔍 Overview
Overview
Preventive medicine is the highest-yield intervention. USPSTF Grade A/B recommendations guide screening. Key domains: cancer screening, CV risk, immunizations, behavioral counseling.
🧪 Workup
Workup
- Cancer screening: mammogram, Pap/HPV, colonoscopy, LDCT
- CV risk: ASCVD calculator, lipids, BP
- Metabolic: A1c q3y if ≥35 + overweight
- Depression: PHQ-2 annually
- Hep C: one-time 18-79
- HIV: at least once 15-65
- Osteoporosis: DEXA 65F/70M
🚨 Management
Management
- Statin: moderate 7.5-20% risk, high-intensity ≥20%
- ASA: limited — 40-59yo if ≥10% risk, shared decision
- BP <130/80 [SPRINT]
- Smoking: 5 A's + varenicline+NRT
- Vaccines: flu, COVID, Tdap, shingrix≥50, PCV20≥65, HPV≤26
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Atorvastatin (Lipitor) | 40-80mg | PO | High-intensity statin |
| Varenicline | 1mg BID × 12wk | PO | Smoking cessation |
| ASA 81mg | Daily | PO | Limited primary prevention |
📊 Monitoring
Monitoring
- Lipids 4-12wk post-statin then annually
- BP every visit
- A1c q3y if normal
- Cancer screening per USPSTF
- Immunization records
📋 On Rounds
📣 Sample Presentation
One-Liner
"Mrs. Thompson is a 52-year-old healthy woman presenting for her annual wellness visit. She is up to date on Pap smear (last year, normal) and mammogram (last year, normal). No colonoscopy yet. BMI 26, BP 128/82."
Key Points to Cover on Rounds
Cancer screening: colonoscopy due (age 52, average risk — schedule). Mammogram current (biennial, next in 1 year). Pap current (every 3 years with HPV co-test). Lung CT: not indicated (non-smoker). CV risk: 10-year ASCVD risk 4.2% (low) — no statin currently indicated. BP 128/82 (elevated, not yet HTN — lifestyle counseling). Fasting glucose 94, A1c 5.4 (normal, rescreen in 3 years). Immunizations: flu (today), COVID booster (due), Tdap (up to date), shingrix (not yet eligible — age 50). Depression screening: PHQ-2 negative. Osteoporosis: not yet (screen at 65). Plan: colonoscopy referral, lifestyle counseling (diet, exercise, weight), return in 1 year.
⚡ Summary
Summary
Cancer Screening
Breast: mammogram q2y 40-74. Cervical: Pap/HPV 21-65. Colon: start at 45 (colonoscopy q10y or FIT annual). Lung: LDCT 50-80 if ≥ 20 pack-years.
CV Risk
10-year ASCVD risk calculator. Statin: moderate if 7.5-20%, high-intensity if ≥ 20% or known ASCVD. ASA: limited role (USPSTF: ages 40-59 if ≥ 10% risk, shared decision).
Immunizations
Flu (annual), COVID (per current guidance), Tdap/Td (q10y), shingrix (≥ 50), PCV20 (≥ 65), HPV (through age 26, catch-up to 45).
Depression Screening
PHQ-2 then PHQ-9 annually in primary care. Universal screening recommended by USPSTF.
Diabetes Screening
Fasting glucose, A1c, or OGTT. Screen every 3 years age 35-70 if overweight/obese. Screen earlier if risk factors (FH, ethnicity, GDM history).
Osteoporosis
DEXA at age 65 (women), 70 (men). Earlier if risk factors (steroids, low BMI, FH hip fracture). Treat: bisphosphonates first-line.
📄 One Pager
Primary Care · One Pager
Preventive Care
Mammogram q2y 40-74. Pap/HPV 21-65. Colonoscopy at 45. LDCT 50-80 if ≥ 20 pack-years. ASCVD risk → statin threshold. PHQ-2 depression screen annually.
Cancer Screening
Breast: mammogram q2y 40-74. Cervical: Pap q3y (21-29) or Pap/HPV q5y (30-65). Colon: start age 45 (colonoscopy q10y, FIT annually, Cologuard q3y). Lung: LDCT 50-80 if ≥ 20 pack-year smoker.
Cardiovascular Prevention
10-year ASCVD risk calculator. Statin: moderate if 7.5-20%, high-intensity if ≥ 20% or known ASCVD. ASA: limited role (ages 40-59, ≥ 10% risk, shared decision). BP target < 130/80 [SPRINT].
Other Screening
Depression: PHQ-2 annually. Diabetes: A1c q3y if ≥ 35 + overweight. Osteoporosis: DEXA at 65F/70M. Hepatitis C: one-time for all 18-79. HIV: at least once for all 15-65.
Key Drugs
Flu vaccineAnnual
Shingrix≥ 50 (2 doses)
PCV20≥ 65
ColonoscopyEvery 10 years starting at 45
Pitfalls
- Not doing colonoscopy at 45 (USPSTF lowered from 50)
- Missing LDCT eligibility in former smokers
- PSA screening without shared decision-making
- Forgetting Hepatitis C screening (one-time, all adults)
Rotation
Ambulatory / Outpatient
Continuity clinic essentials — preventive care, chronic disease management, screening guidelines, and outpatient prescribing.
Available Topics
Preventive Care & Screening
Outpatient Diabetes
Obesity & GLP-1 Agents
Smoking Cessation
Trauma Primary & Secondary Survey
Acute Abdomen
Superior Vena Cava Syndrome
Septic Arthritis
Code Status & Advance Directives
Family Meeting Framework
Tuberculosis
Fungal Infections
Nephrotic vs Nephritic Syndrome
Renal Tubular Acidosis
PMR & Giant Cell Arteritis
Hypoparathyroidism
Burns Management
Hypothermia & Drowning
Hyperviscosity Syndrome
Dermatomyositis & Polymyositis
Prognostication Tools
Contrast-Induced Nephropathy
Diabetic Foot Infection
📋 Major Guidelines
Quick Reference
Antibiotic Guide
Empiric coverage by infection site, spectrum of activity, and renal dose adjustments. This is your go-to for every antibiotic decision on the wards.
🎯 Empiric Antibiotics by Condition
🫁 Pneumonia (CAP / HAP / VAP)
5 regimens
›
| Setting | First-Line | Alternatives / Severe | Duration |
|---|---|---|---|
| CAP — outpatient, healthy | Amoxicillin (Amoxil) 1g TID | Doxycycline 100 mg BID if penicillin allergy | 5 days |
| CAP — outpatient, comorbidities | Augmentin 875 BID + azithromycin | Respiratory FQ monotherapy (levofloxacin 750 mg daily) | 5 days |
| CAP — inpatient (non-ICU) | Ceftriaxone (Rocephin) 1–2g IV + azithro 500 IV | Add vancomycin if MRSA risk | 5 days (if stable ×48h) Short-Course CAP Trial, 2016 |
| CAP — ICU (severe) | Ceftriaxone (Rocephin) 2g IV + azithro 500 IV | + vanc or linezolid if MRSA (linezolid preferred — better lung penetration). + pip-tazo/cefepime if Pseudomonas risk. | 7 days |
| HAP / VAP | Pip-tazo 4.5g q6h or cefepime 2g q8h | + vancomycin or linezolid for MRSA (linezolid if severe — better lung penetration). Pip-tazo if anaerobic concern (abscess/empyema). Cefepime preferred with vanc (↓ AKI ACORN, 2024). Need cefepime + anaerobes → add metronidazole. | 7 days ATS/IDSA, 2016 |
🔬 Urinary Tract Infections
3 regimens
›
| Setting | First-Line | Alternatives | Duration |
|---|---|---|---|
| Uncomplicated cystitis | Nitrofurantoin (Macrobid) 100 mg BID | TMP-SMX DS BID × 3d. Fosfomycin 3g × 1. Avoid FQ for cystitis. | 3–5 days |
| Pyelonephritis — outpatient | Ciprofloxacin (Cipro) 500 BID | Ceftriaxone 1g IM × 1 + oral step-down | 5–7 days |
| Pyelonephritis — inpatient | Ceftriaxone (Rocephin) 1g IV daily | Pip-tazo or meropenem if ESBL/MDR risk | FQ 5–7d, TMP-SMX 7–10d, beta-lactam 10–14d (total duration depends on PO step-down agent) |
ASB (asymptomatic bacteriuria) = do NOT treat — except in pregnancy and pre-urologic procedure. Nitrofurantoin: avoid if CrCl < 30.
🩹 Skin & Soft Tissue Infections
2 regimens
›
| Type | First-Line | Alternatives | Duration |
|---|---|---|---|
| Cellulitis (non-purulent) | Cefazolin (Ancef) 2g IV q8h (inpatient) or cephalexin (Keflex) 500 QID (outpatient) | Purulent/abscess → I&D + TMP-SMX or doxycycline for MRSA | 5–7 days |
| Necrotizing fasciitis SURGICAL EMERGENCY | Vanc + pip-tazo + clindamycin | Clindamycin inhibits toxin production (Group A strep). EMERGENT surgical debridement. | Until source controlled |
🫃 Intra-Abdominal Infections
2 regimens
›
| Setting | First-Line | Alternatives | Duration |
|---|---|---|---|
| Community intra-abdominal | Ceftriaxone (Rocephin) 2g + metronidazole (Flagyl) 500 q8h | Pip-tazo 4.5g q6h (single agent). Meropenem if ESBL. | 4 days (post source control) STOP-IT, 2015 |
| SBP* *= Spontaneous Bacterial Peritonitis | Ceftriaxone (Rocephin) 2g IV daily | Pip-tazo or meropenem if nosocomial/FQ* failure *FQ = Fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) | 5 days |
🧠 CNS Infections
1 regimen
›
| Setting | First-Line | Alternatives | Duration |
|---|---|---|---|
| Bacterial meningitis (adult) | Vanc + ceftriaxone 2g q12h | + ampicillin 2g q4h if age >50 or immunocompromised (Listeria). Dex before/with 1st abx dose European Dexamethasone Meningitis Trial, 2002. | 10–14 days (S. pneumo); 7 days (N. meningitidis) |
Antibiotics within 30–60 min. Do NOT delay for LP or CT. Get blood cultures → start abx → then LP.
❤️ Endocarditis
1 regimen
›
| Setting | Empiric | Culture-Directed | Duration |
|---|---|---|---|
| Native valve (empiric) | Vanc + ceftriaxone | MSSA → nafcillin/cefazolin. MRSA → vanc or daptomycin. Enterococcus → ampicillin + gentamicin or ampicillin + ceftriaxone. | 4–6 weeks |
3 sets of blood cultures from 3 sites before antibiotics. Daptomycin is an alternative to vanc for right-sided MRSA endocarditis — but NOT for left-sided (poor penetration through vegetations).
🚨 Sepsis & Febrile Neutropenia
2 regimens
›
| Setting | First-Line | Alternatives / Add-On | Duration |
|---|---|---|---|
| Sepsis (unknown source) | Vanc + cefepime or vanc + pip-tazo | Meropenem if ESBL risk or critically ill. Add antifungal if immunocompromised + no improvement day 4–7. | Source-dependent |
| Neutropenic fever (ANC < 500 + T ≥ 38.3) | Cefepime (Maxipime) 2g IV q8h | + vanc if hemodynamic instability, line infection, MRSA. + antifungal day 4–7 if persistent fever. | Until ANC recovery + afebrile ≥48h |
Antibiotics within 1 hour in sepsis and neutropenic fever. Every hour of delay increases mortality. Empiric broad → narrow based on cultures at 48–72h.
🦠 C. difficile
2 regimens
›
| Severity | First-Line | Alternatives | Duration |
|---|---|---|---|
| Non-severe | Fidaxomicin 200 mg BID PREFERRED | Vancomycin PO 125 mg QID | 10 days |
| Fulminant (ileus, megacolon, shock) | Vanc PO 500 QID + metronidazole IV 500 q8h | ± vanc enemas if ileus. Surgical consult for colectomy. | Until resolved |
Soap and water for hand hygiene (alcohol sanitizer does NOT kill C. diff spores). Fidaxomicin has lower recurrence rate than vanc IDSA/SHEA, 2021.
🦠 Spectrum of Activity
Gram-Positive Coverage
| Drug | MSSA | MRSA | Strep | Enterococcus | Notes |
|---|---|---|---|---|---|
| Cefazolin (Ancef) / Cephalexin (Keflex) | ✓ | ✗ | ✓ | ✗ | Best anti-staphylococcal cephalosporin. First-line MSSA. |
| Nafcillin / Oxacillin | ✓✓ | ✗ | ✓ | ✗ | Gold standard MSSA bacteremia / endocarditis. |
| Vancomycin (Vancocin) | ✓ | ✓ | ✓ | ✓ (not VRE) | Workhorse MRSA drug. Nephrotoxic. Target AUC/MIC 400–600 (trough-based monitoring is outdated per 2020 ASHP/IDSA). |
| Linezolid (Zyvox) | ✓ | ✓ | ✓ | ✓ (incl VRE) | Covers VRE. PO = IV bioavailability. Serotonin syndrome risk. Thrombocytopenia >2 weeks. |
| Daptomycin (Cubicin) | ✓ | ✓ | ✓ | ✓ (incl VRE) | Inactivated by surfactant — do NOT use for pneumonia. Check CK weekly (rhabdo). |
| TMP-SMX (Bactrim) | ✓ | ✓ (CA-MRSA) | Variable | ✗ | Good oral MRSA option for skin/soft tissue. Not reliable for strep. |
Gram-Negative Coverage
| Drug | Enterobacteriaceae | Pseudomonas | ESBL | Anaerobes | Notes |
|---|---|---|---|---|---|
| Ceftriaxone (Rocephin) | ✓✓ | ✗ | ✗ | ✗ | Workhorse for community GNR. No Pseudomonas. No anaerobes. |
| Cefepime (Maxipime) | ✓✓ | ✓ | ✗ | ✗ | Anti-pseudomonal cephalosporin. Neurotoxic in renal failure (seizures). |
| Pip-tazo (Zosyn) | ✓✓ | ✓ | Variable | ✓ | Broadest non-carbapenem. Covers Pseudomonas + anaerobes. Workhorse for abdominal/polymicrobial. |
| Meropenem (Merrem) | ✓✓ | ✓ | ✓ | ✓ | Broadest spectrum. Reserve for ESBL, MDR, failing empiric therapy. Does NOT cover MRSA. |
| Aztreonam | ✓ | ✓ | ✗ | ✗ | Safe in penicillin allergy (monobactam, no cross-reactivity). GNR only — no gram-positive, no anaerobes. |
| Fluoroquinolones | ✓ | ✓ (cipro) | ✗ | ✗ (moxi has some) | Rising resistance. FDA black box warnings. Save for specific indications (pyelo, prostatitis, Legionella). |
| Metronidazole (Flagyl) | ✗ | ✗ | ✗ | ✓✓ | Anaerobe specialist. Also covers C. diff (fulminant, IV), Giardia, amebiasis. Disulfiram reaction with alcohol. |
Daptomycin is inactivated by pulmonary surfactant — NEVER use for pneumonia. This is a classic boards and real-life mistake. Use vancomycin or linezolid for MRSA pneumonia.
💊 Renal Dose Adjustments
| Drug | Normal Dose | CrCl 10–30 | HD | Key Notes |
|---|---|---|---|---|
| Vancomycin (Vancocin) | 15–20 mg/kg q8–12h | 15–20 mg/kg q24–48h (by levels) | Re-dose by levels post-HD | Target AUC/MIC 400–600. Check troughs. Nephrotoxic — avoid with pip-tazo if possible ACORN, 2024. |
| Pip-tazo (Zosyn) | 4.5g IV q6h | 2.25g IV q6h | 2.25g q6h + dose after HD | Extended infusion (4h) improves outcomes in critically ill. |
| Cefepime (Maxipime) | 2g IV q8h | 1g IV q12–24h | 1g IV q24h + dose after HD | Neurotoxic in renal failure (encephalopathy, myoclonus, seizures). Monitor closely. |
| Meropenem (Merrem) | 1g IV q8h | 500 mg IV q12h | 500 mg IV q12h + dose after HD | Lower seizure threshold than imipenem. |
| Levofloxacin (Levaquin) | 750 mg IV/PO daily | 750 mg q48h | 500 mg q48h | Not removed by HD. Avoid in myasthenia. |
| TMP-SMX (Bactrim) | DS BID (UTI) or 15 mg/kg/day (PCP) | Half dose if CrCl 15–30. Avoid <15. | Dose after HD | Causes hyperkalemia (blocks ENaC). Falsely ↑ Cr (blocks tubular secretion). |
| Nitrofurantoin (Macrobid) | 100 mg BID | AVOID if CrCl < 30 | Ineffective (can't concentrate in urine) + pulmonary toxicity risk. | |
| Metronidazole (Flagyl) | 500 mg q8h | No adjustment needed | Dose after HD | Hepatically metabolized. No renal adjustment. |
| Linezolid (Zyvox) | 600 mg q12h | No adjustment needed | No adjustment | Not renally cleared. 100% PO bioavailability = IV. |
| Daptomycin (Cubicin) | 6–10 mg/kg IV daily | 6–10 mg/kg IV q48h | Dose after HD | Check CK weekly. Not for pneumonia. |
🧠 Stewardship Pearls
- Always get cultures before antibiotics — but never delay antibiotics for cultures in sepsis or meningitis
- De-escalate within 48–72h based on culture/sensitivity. Broad empiric → narrow targeted is the rule.
- Shorter is better: CAP 5 days, UTI 3–5 days, intra-abdominal 4 days post-source-control, HAP/VAP 7 days. Longer courses don't improve outcomes and increase resistance + C. diff.
- IV to PO switch: switch to oral when afebrile ×48h, tolerating PO, improving clinically. Most antibiotics have excellent oral bioavailability (FQ, linezolid, metronidazole, TMP-SMX, fluconazole).
- Vanc + pip-tazo may increase AKI compared to vanc + cefepime ACORN, 2024. Prefer vanc + cefepime when both cover the suspected pathogens.
- "Bug-drug mismatch" — common errors: ceftriaxone doesn't cover Pseudomonas; cefazolin doesn't cover MRSA; daptomycin doesn't work in the lung; nitrofurantoin doesn't work above the bladder.
- Allergies: ~90% of "penicillin allergies" are not true IgE-mediated. Cephalosporin cross-reactivity is < 2%. Get allergy history details (rash vs anaphylaxis). Consider allergy testing.
Linezolid vs Vancomycin — When to Choose Which
Both cover MRSA. But they are NOT interchangeable. Choosing wrong = treatment failure, unnecessary toxicity, or worse outcomes. Know when each one wins.
| Feature | Vancomycin | Linezolid (Zyvox) |
|---|---|---|
| MOA | Cell wall synthesis inhibitor — binds D-Ala-D-Ala terminus of peptidoglycan precursors, preventing cross-linking. Bactericidal (slowly). | Protein synthesis inhibitor — binds 23S rRNA of the 50S ribosome, blocking formation of the 70S initiation complex → prevents translation. Bacteriostatic. Also a weak reversible MAOi (inhibits monoamine oxidase → serotonin syndrome risk). |
| Route | IV only for systemic infections (PO only for C. diff — not absorbed) | IV and PO — 100% oral bioavailability (PO = IV) |
| MRSA | ✓ Gold standard | ✓ Equivalent |
| VRE* *= Vancomycin-Resistant Enterococcus | ✗ No | ✓ Yes — one of very few VRE options |
| Lung penetration | Poor (~25%) | Excellent (~100%) |
| CSF penetration | Moderate (needs inflamed meninges) | Good |
| Renal dosing | YES — must adjust. AUC/MIC-guided dosing (target 400-600). | No renal adjustment. No drug levels needed. |
| Key toxicity | Nephrotoxicity, Red Man Syndrome (infuse over ≥1h), ototoxicity, DRESS (rare) | Thrombocytopenia (#1 — dose-dependent, usually > 14 days), serotonin syndrome (MAOi activity), lactic acidosis (mitochondrial toxicity), peripheral neuropathy (may be irreversible), optic neuritis (vision loss — check visual acuity if > 28 days), myelosuppression (anemia, leukopenia) |
| Duration limit | No hard limit | ≤ 14 days preferred. > 14d: ↑ thrombocytopenia. > 28d: ↑↑ neuropathy, optic neuritis, lactic acidosis. If > 2 weeks needed → monitor closely or switch to vanc. |
| Monitoring | Trough AUC/MIC 400–600, BMP, CBC | CBC twice weekly (platelets). If > 14d: weekly lactate, visual acuity, neuro exam for neuropathy symptoms (numbness, tingling). No drug levels needed. |
| Drug interactions | Nephrotoxics (aminoglycosides, pip-tazo) | SSRIs, SNRIs, MAOIs, tramadol, meperidine → serotonin syndrome |
| Cost | Cheap | Expensive |
🏆 Choose Vancomycin
- MRSA bacteremia — bactericidal, proven outcomes
- Endocarditis — need bactericidal activity
- Osteomyelitis — long-duration therapy OK
- Empiric broad MRSA coverage — default first-line
- Cost-sensitive settings
🏆 Choose Linezolid
- MRSA pneumonia — far superior lung penetration ZEPHyR, 2012
- VRE infections — vanc is useless against VRE
- CKD / AKI — no renal adjustment, won't worsen kidneys
- No IV access — 100% PO bioavailability
- Outpatient MRSA Tx — go home on PO instead of IV vanc
- Vancomycin failure or allergy
Never use daptomycin for pneumonia. Pulmonary surfactant inactivates it. For MRSA pneumonia your choices are vancomycin or linezolid — and linezolid is likely better due to lung penetration.
Linezolid + serotonergic drugs = serotonin syndrome. Always check the med list for SSRIs, SNRIs, MAOIs, tramadol, meperidine before starting linezolid. If the patient is on an SSRI and needs MRSA coverage → use vancomycin.
⚠️ Linezolid Toxicity Timeline:
• > 14 days: thrombocytopenia (check CBC twice weekly), myelosuppression, lactic acidosis (check weekly lactate)
• > 28 days: peripheral neuropathy (numbness/tingling — may be irreversible), optic neuritis (blurred vision, color vision loss — check visual acuity weekly)
• Any duration: serotonin syndrome if on SSRIs/SNRIs/MAOIs/tramadol (linezolid is a weak MAOi)
If you need > 2 weeks of MRSA therapy (endocarditis, osteo), vancomycin is safer for long courses.
• > 14 days: thrombocytopenia (check CBC twice weekly), myelosuppression, lactic acidosis (check weekly lactate)
• > 28 days: peripheral neuropathy (numbness/tingling — may be irreversible), optic neuritis (blurred vision, color vision loss — check visual acuity weekly)
• Any duration: serotonin syndrome if on SSRIs/SNRIs/MAOIs/tramadol (linezolid is a weak MAOi)
If you need > 2 weeks of MRSA therapy (endocarditis, osteo), vancomycin is safer for long courses.
Toxin suppression — linezolid & clindamycin. Both are protein synthesis inhibitors (50S ribosome) → they suppress bacterial toxin production even before the bacteria die. This is why clindamycin is always added in necrotizing fasciitis (suppresses Group A strep exotoxins), toxic shock syndrome (suppresses TSST-1 and strep pyrogenic exotoxins), and PVL-producing MRSA (Panton-Valentine leukocidin). Linezolid has the same mechanism and can substitute when clindamycin resistance is a concern. Vancomycin kills the bacteria but does NOT suppress toxin production — in toxin-mediated disease, bactericidal alone is not enough.
⏱ Duration by Infection
Respiratory
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| CAP (uncomplicated)* *= No ICU admission, no empyema/abscess, no bacteremia, immunocompetent, clinically improving | 5 days | If afebrile ≥48h + ≤1 sign instability (HR, RR, BP, SpO₂, mental status) |
| CAP (complicated)* *= Empyema, lung abscess, necrotizing pneumonia, cavitation, or inadequate clinical response by day 3–5 | 2–6 weeks | Depends on drainage adequacy and imaging resolution. Empyema needs chest tube + abx |
| HAP* / VAP* *HAP = Hospital-Acquired Pneumonia (≥48h after admission) *VAP = Ventilator-Associated Pneumonia (≥48h after intubation) | 7 days | ATS/IDSA 2016. Shorter courses reduce resistance |
| COPD exacerbation (with abx) | 5 days | Only if ≥2 Anthonisen criteria |
| Lung abscess | 4–6 weeks | Until imaging improvement |
Urinary
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Simple cystitis (women) | 3–5 days | Nitrofurantoin (Macrobid) 5d, TMP-SMX (Bactrim) 3d, fosfomycin 1 dose |
| Complicated UTI* *= UTI extending beyond the bladder (pyelonephritis, urosepsis) OR occurring in a host with impaired urinary tract clearance (male, pregnant, anatomic abnormality, obstruction, catheter, immunocompromised, renal transplant) | 7–14 days | Depends on source control. Broader coverage needed (FQ or beta-lactam) |
| Pyelonephritis (uncomplicated) | 5–7 days | FQ 5d, TMP-SMX 7d, beta-lactam 10–14d |
| Catheter-associated UTI | 7 days | Remove or replace catheter. 10–14d if slow response |
| Prostatitis (acute) | 2–4 weeks | FQ or TMP-SMX preferred (prostate penetration) |
Bloodstream
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Uncomplicated gram-negative bacteremia = Source identified & controlled, no endovascular infection, no prosthetic material, immunocompetent, defervesced within 72h, cultures cleared | 7 days | From first negative blood culture. ALL criteria must be met |
| Complicated gram-negative bacteremia = Undrainable source, endovascular, prosthetic material, immunocompromised, persistent bacteremia >72h, or metastatic infection | 14 days | Any ONE feature makes it complicated → 14 days |
| Staph aureus bacteremia (MSSA*/MRSA*) *MSSA = Methicillin-Sensitive Staph aureus *MRSA = Methicillin-Resistant Staph aureus | ≥4 weeks (minimum) | ALWAYS. TTE/TEE required. ID consult mandatory |
| Coag-negative staph (true infection) | 5–7 days + line removal | Often contaminant — need 2+ positive cultures |
| Enterococcal bacteremia | 7–14 days | Longer if endocarditis not excluded |
| Candidemia | 14 days from first negative culture | Ophthalmology consult. Remove all central lines. Echo |
S. aureus bacteremia is NEVER uncomplicated enough for short-course therapy. Minimum 4 weeks IV. Always echo. Always ID consult.
Skin / Soft Tissue
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Simple cellulitis | 5 days | Extend to 7–10d if slow response |
| Purulent SSTI* / abscess *SSTI = Skin and Soft Tissue Infection | I&D* ± 5–7 days *I&D = Incision and Drainage | I&D is primary treatment |
| Necrotizing fasciitis | Until debridement complete | Surgical emergency |
| Diabetic foot (soft tissue) | 1–2 weeks | If no osteomyelitis |
| Diabetic foot (osteo) | 6 weeks | Based on bone culture |
Intra-abdominal
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Intra-abdominal (adequate source control) | 4 days | STOP-IT, 2015. NOT 7–14 days |
| Cholangitis / cholecystitis | Source control + 4–5 days | Cholecystectomy within 72h |
| SBP* *= Spontaneous Bacterial Peritonitis | 5 days | Ceftriaxone. Albumin day 1 and 3 |
| C. difficile (initial) | 10 days | Fidaxomicin preferred |
| C. difficile (fulminant) | Until improving | PO vanc 500mg q6h + IV metronidazole |
Bone / Joint
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Osteomyelitis (native bone) | 6 weeks | IV → PO step-down OK (OVIVA trial) |
| Prosthetic joint (DAIR*) *DAIR = Debridement, Antibiotics, Implant Retention | 6 wk IV + chronic suppression | Rifampin backbone if staph |
| Septic arthritis (native) | 3–4 weeks | GPC* 3wk, GNR* 4wk. I&D essential *GPC = Gram-Positive Cocci (staph, strep, enterococcus) *GNR = Gram-Negative Rods (E. coli, Klebsiella, Pseudomonas) |
CNS
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Bacterial meningitis | 7–21 days | Meningo 7d, pneumo 10–14d, Listeria 21d, GNR 21d |
| Brain abscess | 6–8 weeks | Often need surgical drainage |
| Epidural abscess | 6–8 weeks | Surgical drainage + IV abx |
Endocarditis
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| Native valve (strep) | 4 weeks | 2wk if uncomplicated + gent synergy |
| Native valve (staph) | 6 weeks | Nafcillin for MSSA, vanc for MRSA |
| Prosthetic valve | ≥6 weeks | Rifampin + gentamicin backbone |
Other
| Infection | Duration | Key Notes / Evidence |
|---|---|---|
| TB (standard) | 6 months | 2 months RIPE* → 4 months RI *RIPE = Rifampin, Isoniazid, Pyrazinamide, Ethambutol |
| TB (meningitis / bone) | 9–12 months | Extended duration |
| Febrile neutropenia | Until afebrile + ANC* ≥500 × 2d *ANC = Absolute Neutrophil Count | Min 7 days if documented infection |
Quick Reference
Vasopressor Guide
First-line agents, receptor profiles, dosing, and when to escalate. Know your pressors cold — you'll be titrating them at 3 AM.
Vasopressor Table
| Agent | Dose | Receptor | Role | Avoid / Caution |
|---|---|---|---|---|
| Norepinephrine (Levophed) 1ST LINE | 0.01–3 mcg/kg/min | α₁>>β₁ | First-line in septic shock. ↑ SVR + mild inotropy. SSC, 2021 | — |
| Vasopressin (Vasostrict) ADD-ON | 0.03 units/min (fixed, no titration) | V1/V2 | Add-on to NE (NE-sparing). May reduce AKI. Add when NE ≥ 0.25–0.5 mcg/kg/min. VASST, 2008 | Coronary vasospasm, mesenteric ischemia at higher doses |
| Epinephrine (Adrenalin) 2ND LINE | 0.01–0.5 mcg/kg/min | α₁, β₁, β₂ | Refractory shock. Strong inotropy + vasoconstriction. Also cardiac arrest. | Falsely elevates lactate (β₂-mediated aerobic glycolysis) — can't use lactate to guide resuscitation |
| Phenylephrine (Neo-Synephrine) 3RD LINE | 0.5–6 mcg/kg/min | α₁ pure | Use if tachyarrhythmia limits NE use. Pure vasoconstriction. | Low CO states (no inotropy — worsens cardiac output) |
| Dobutamine (Dobutrex) INOTROPE | 2–20 mcg/kg/min | β₁>β₂ | Low CO despite adequate MAP (cardiogenic component). Not a vasopressor — an inotrope. | Never use alone if MAP < 65 (drops SVR via β₂). Always pair with NE. |
| Milrinone (Primacor) INOTROPE | 0.125–0.75 mcg/kg/min | PDE3 inhibitor | Inodilator. RV failure, pulmonary HTN, post-cardiac surgery. Inotropy + ↓ PVR. | Hypotension (vasodilation). Renally cleared — dose-adjust in AKI. |
| Angiotensin II (Giapreza) LAST RESORT | 20–200 ng/kg/min | AT1 receptor | Catecholamine-refractory vasodilatory shock. ATHOS-3, 2017 | Thrombosis risk. Very expensive. Last-line agent. |
| Dopamine (Intropin) AVOID | 2–20 mcg/kg/min | D1, β₁, α₁ (dose-dependent) | AVOID in sepsis. More arrhythmias, higher mortality vs NE. SOAP II, 2010 | Avoid. Only remaining role: symptomatic bradycardia if no pacing available. |
Adjuncts
| Drug | Indication | Dose | Evidence |
|---|---|---|---|
| Hydrocortisone (Solu-Cortef) | Refractory septic shock on NE ≥ 0.25 mcg/kg/min for ≥ 4h | 200 mg/day IV (50 mg q6h or continuous infusion) | ADRENAL, 2018: faster shock reversal, no mortality benefit. APROCCHSS, 2018: mortality benefit in most severe subgroup. |
| Methylene blue (ProvayBlue) | Vasoplegia (post-cardiac surgery, refractory distributive shock) | 1–2 mg/kg IV bolus, may repeat or infuse 0.5 mg/kg/hr | Case series. Inhibits NO synthase → restores SVR. Rescue agent. |
| Thiamine (Vitamin B1) | Suspected deficiency (alcoholism, malnutrition, refeeding) | 200–500 mg IV q8h × 3 days | Prevents Wernicke's. May help refractory lactic acidosis. |
Escalation Ladder
Stepwise approach to vasopressor escalation in septic shock:
Step 1
Norepinephrine (Levophed) — first-line. Start at 0.05 mcg/kg/min, titrate to MAP ≥ 65.
Step 2
Add vasopressin (Vasostrict) 0.03 u/min when NE ≥ 0.25–0.5 mcg/kg/min. Fixed dose, NE-sparing.
Step 3
Start hydrocortisone (Solu-Cortef) 200 mg/day if still on escalating NE ≥ 0.25 for ≥ 4h. SSC, 2021
Step 4
Add epinephrine (Adrenalin) if refractory. Provides additional inotropy. Watch for lactate confounding.
Step 5
Consider angiotensin II (Giapreza) ATHOS-3, 2017 or methylene blue (ProvayBlue) for catecholamine-refractory vasoplegia. Reassess: is source controlled? Missed adrenal crisis? Cardiac tamponade?
Key Pearls
Never run dopamine in sepsis. SOAP II, 2010: higher mortality + more arrhythmias vs NE. There is no "renal-dose dopamine."
Epinephrine falsely elevates lactate via β₂-mediated aerobic glycolysis. If you're on epi, you cannot use lactate clearance to guide resuscitation.
Vasopressin is fixed-dose 0.03 u/min. Do not titrate. It's an add-on, not a standalone. Wean NE first, then vaso last.
Dobutamine ≠ vasopressor. It's an inotrope. If MAP is low, you need NE first. Add dobutamine only if MAP is adequate but CO is low (cold extremities, poor ScvO₂ despite adequate MAP).
Key Trials
| Trial | Year | Finding |
|---|---|---|
| SOAP II | 2010 | NE vs dopamine in shock: NE had lower mortality + fewer arrhythmias |
| VASST | 2008 | Vasopressin + NE vs NE alone: no overall mortality difference, but possible benefit in less severe shock |
| VANISH | 2016 | Vasopressin vs NE as first-line: no difference. Vasopressin may reduce need for RRT. |
| ADRENAL | 2018 | Hydrocortisone in septic shock: faster shock reversal, no 90-day mortality benefit |
| APROCCHSS | 2018 | Hydrocortisone + fludrocortisone: 90-day mortality benefit in severe septic shock |
| ATHOS-3 | 2017 | Angiotensin II in vasodilatory shock: improved MAP response vs placebo |
Quick Reference
Insulin Guide
Insulin types, inpatient basal-bolus dosing, correction scales, DKA drip protocol, and hypoglycemia management.
🧮
Insulin Calculator
Sliding Scale → Basal-Bolus converter & weight-based dosing. Click to jump ↓
Insulin Types Overview
| Type | Name | Onset | Peak | Duration | Key Notes |
|---|---|---|---|---|---|
| Rapid-Acting | Lispro (Humalog), Aspart (NovoLog), Glulisine (Apidra) | 15 min | 1–2 h | 3–5 h | Give with meals. Used for bolus dosing and correction scales. |
| Short-Acting | Regular (Humulin R, Novolin R) | 30–60 min | 2–4 h | 6–8 h | Used in IV drips (DKA). Only insulin safe for IV use. |
| Intermediate | NPH (Humulin N, Novolin N) | 1–2 h | 4–12 h | 12–18 h | Cloudy vial. Useful for steroid-induced hyperglycemia. Must be resuspended. |
| Long-Acting | Glargine (Lantus, Basaglar), Detemir (Levemir) | 1–2 h | Peakless | 20–24 h | Basal insulin of choice. Give once daily (glargine) or BID (detemir). Do NOT mix. |
| Ultra-Long | Degludec (Tresiba) | 1 h | Peakless | 42 h | Flexible dosing window. Lowest hypoglycemia risk among basals. |
| Concentrated | U-500 Regular | 30 min | 4–8 h | 12–24 h | 5x concentration of U-100. For severe insulin resistance (>200 units/day). High error risk — requires dedicated syringe. |
Inpatient Basal-Bolus Protocol
Goal: Mimic physiologic insulin secretion. Basal covers fasting needs. Bolus covers meals. Correction fixes hyperglycemia. Target BG 140–180 mg/dL for most ICU and non-ICU patients.
1
Calculate Total Daily Dose (TDD): 0.3–0.5 units/kg/day. Start 0.3 units/kg for elderly, CKD (GFR < 30), hepatic impairment, or malnourished. Start 0.5 units/kg for insulin-resistant, obese, or steroid-treated patients.
2
Split TDD: 50% as basal (glargine once daily, usually at bedtime) + 50% as bolus (divided equally into 3 pre-meal doses of rapid-acting insulin).
3
Add correction scale: Give correction dose ON TOP of scheduled mealtime bolus based on pre-meal BG. Use low/medium/high scale based on insulin sensitivity (see table below).
4
Reassess daily: If BG consistently > 180 mg/dL, increase TDD by 10–20%. If hypoglycemia occurs, decrease TDD by 20%. Adjust basal vs bolus based on fasting vs post-meal patterns.
Correction Scale (Sliding Scale Add-On)
Low scale: insulin-sensitive, elderly, CKD, hepatic. Medium scale: most patients. High scale: insulin-resistant, obese, on steroids, TDD > 80 units.
| Blood Glucose (mg/dL) | Low Dose | Medium Dose | High Dose |
|---|---|---|---|
| 150–199 | 1 unit | 2 units | 3 units |
| 200–249 | 2 units | 3 units | 5 units |
| 250–299 | 3 units | 5 units | 7 units |
| 300–349 | 4 units | 7 units | 9 units |
| > 350 | 5 units + notify MD | 8 units + notify MD | 11 units + notify MD |
Who Gets Which Scale?
The correction scale is NOT one-size-fits-all. Choosing the wrong scale causes hypoglycemia (too aggressive) or persistent hyperglycemia (too conservative). Match the scale to the patient's insulin sensitivity.
🟢 Low-Dose Scale
Use for insulin-sensitive patients:
- Elderly (≥ 70 yr) — reduced counter-regulatory response, higher hypo risk
- CKD (GFR < 30) — reduced insulin clearance, insulin lasts longer
- Hepatic impairment — decreased gluconeogenesis + insulin metabolism
- Malnourished / low BMI (< 18.5) — low glycogen stores
- Type 1 DM (lean) — insulin-sensitive, high DKA risk
- Adrenal insufficiency — impaired counter-regulation
- NPO > 24h — depleted glycogen, no oral intake to buffer
- TDD < 30 units/day
⚠ These patients crash fast. Always have D50 at bedside. BG checks q4–6h minimum.
🔵 Medium-Dose Scale
Use for most hospitalized patients:
- Type 2 DM on oral agents — moderate insulin resistance
- New diabetes diagnosis — unknown sensitivity, start moderate
- Normal BMI (18.5–30) with diabetes
- A1c 7–9% — moderately uncontrolled
- Post-surgical patients — stress hyperglycemia but no steroids
- TDD 30–80 units/day
Default starting scale. Reassess in 24–48h. Upgrade to high if BG consistently > 250.
🔴 High-Dose Scale
Use for insulin-resistant patients:
- ON STEROIDS — #1 indication for high-dose scale. Steroids cause severe insulin resistance
- Obese (BMI > 35) — increased insulin resistance
- TDD > 80 units/day — already requiring large insulin doses
- A1c > 10% — severely uncontrolled, likely very resistant
- TPN / tube feeds — continuous glucose load
- Sepsis / critical illness — stress hormones ↑ insulin resistance
- Cushing's syndrome — endogenous cortisol excess
- Transplant patients on tacrolimus — tacrolimus causes insulin resistance + beta cell toxicity
May still need even MORE. If BG stays > 300 on high scale, increase correction by 50% or add standing bolus doses.
Steroid-Induced Hyperglycemia — Special Protocol
Steroids cause the WORST inpatient hyperglycemia. Prednisone 40 mg can push BG to 400+ in diabetics. Most steroid hyperglycemia peaks 8–12 hours after the dose (afternoon/evening for AM steroids). Standard sliding scales are often insufficient.
1
Always use HIGH-DOSE correction scale for any patient on ≥ 20 mg prednisone equivalent (or dexamethasone ≥ 4 mg, methylprednisolone ≥ 16 mg, hydrocortisone ≥ 80 mg).
2
Add NPH insulin with AM steroids: NPH peaks at 4–12h, matching the steroid-induced glucose rise. Start at 0.1 units per mg of prednisone (e.g., prednisone 40 mg → NPH 4 units with AM dose). Titrate aggressively — most patients need 0.2–0.4 units/mg.
3
For dexamethasone (long-acting steroid): Hyperglycemia lasts 24–36h. Use glargine (not NPH) since dex effect is longer. Increase basal insulin by 20–40%. High-dose correction scale around the clock.
4
For pulse-dose steroids (methylprednisolone 1g/day): These patients WILL have BG 300–500+. Start insulin drip protocol if BG > 300 × 2 consecutive checks. Regular insulin drip 0.05–0.1 units/kg/hr. BG checks q2h.
5
When tapering steroids → taper insulin proportionally. As prednisone decreases, reduce NPH/correction scale. Failure to reduce insulin during steroid taper = hypoglycemia. Match insulin to current steroid dose daily.
| Steroid | Equivalent Dose | Duration of BG Effect | Insulin Strategy |
|---|---|---|---|
| Prednisone (Deltasone) / Prednisolone (Orapred) | 40 mg PO daily | 12–16h (peaks afternoon) | NPH with AM dose. Start 0.1 units/mg, titrate to 0.2–0.4 units/mg. High-dose correction. |
| Methylprednisolone (Solu-Medrol) | 32 mg IV daily | 12–18h | NPH or increase basal 20%. High-dose correction. If pulse dose (1g) → insulin drip. |
| Dexamethasone (Decadron) | 6 mg PO/IV daily | 24–36h (long-acting) | Increase glargine 20–40%. High-dose correction around the clock. NPH won't cover — too short. |
| Hydrocortisone (Solu-Cortef) | 80 mg IV daily | 8–12h per dose | If q8h dosing → moderate hyperglycemia. Medium or high scale. Add NPH 2–4 units per dose if BG > 250. |
Non-diabetic on steroids? Up to 50% of patients on high-dose steroids develop new hyperglycemia. Check BG at least QID (before meals + bedtime). If BG > 180 × 2 → start correction scale. Many will need scheduled insulin.
Diabetic on steroids? Their home insulin is NEVER enough. Increase TDD by 30–50% immediately when starting steroids. Don't wait for BG to spiral. Proactive dosing prevents glucose roller-coasters.
The #1 mistake: Using sliding scale ALONE for steroid patients. Correction-only dosing chases glucose after it's already sky-high. These patients need scheduled NPH or increased basal insulin PLUS high-dose correction scale.
DKA Insulin Drip Protocol
Do NOT start insulin if K⁺ < 3.5 mEq/L. Insulin drives K⁺ intracellularly and will cause fatal arrhythmia. Replete potassium first.
1
Check K⁺ BEFORE insulin: If K⁺ < 3.5 → hold insulin, replete with 20–40 mEq/hr KCl IV. Recheck in 1–2 hours. Do NOT proceed until K⁺ ≥ 3.5.
2
Start regular insulin drip: 0.1 units/kg/hr continuous IV infusion. No initial bolus preferred (ADA 2023). Only regular insulin can be given IV.
3
Check BG hourly. Target BG drop: 50–70 mg/dL per hour. If BG not dropping by ≥ 50 mg/dL/hr, double the drip rate. If dropping > 100 mg/dL/hr, halve the rate.
4
When BG < 200 mg/dL: Start D5 ½NS and reduce insulin drip to 0.02–0.05 units/kg/hr. Continue drip until anion gap closes — NOT just until BG normalizes.
5
Transition to SQ insulin when ALL met: BG < 200 AND anion gap ≤ 12 AND bicarb ≥ 15 AND pH > 7.3. Give long-acting SQ insulin (glargine 0.25 units/kg) 2 hours BEFORE stopping drip to prevent rebound DKA.
Hypoglycemia Protocol
BG < 70 mg/dL (alert, able to eat): Give 15g fast-acting carbohydrates — 4 oz juice, 4 glucose tabs, or 1 tbsp honey. Recheck BG in 15 minutes. Repeat if still < 70. Follow with complex carb/protein snack once BG > 80.
BG < 50 mg/dL or unable to eat: D50 25 mL IV push (12.5 g dextrose). Flush line. Recheck BG in 15 minutes. May repeat once. Start D10 drip if recurrent.
BG < 40 mg/dL or altered mental status: D50 50 mL IV push (25 g dextrose). If no IV access → glucagon 1 mg IM/SQ. Position patient on side (glucagon causes nausea). Recheck BG q15 min.
After any episode: Hold ALL scheduled insulin doses. Investigate cause (missed meal, renal decline, medication error, sepsis). Reduce TDD by 20–40%. Document and notify attending.
Key Clinical Pearls
- Never use sliding scale alone — always pair correction insulin with a scheduled basal insulin. Sliding scale monotherapy leads to roller-coaster glucose and worse outcomes.
- NPO patients still need basal insulin — reduce basal dose by 20–50% but do NOT hold entirely. Basal insulin suppresses hepatic glucose output and prevents DKA in type 1 diabetics.
- Steroid-induced hyperglycemia peaks in the afternoon — use NPH insulin with morning steroids (onset matches steroid-induced glucose rise). Dose: 0.1 units per mg of prednisone equivalent.
- TPN patients: Add regular insulin directly to TPN bag at 0.1 units per gram of dextrose as starting dose. Titrate based on BG monitoring q6h.
- Renal adjustment: Reduce TDD by 25% if GFR 10–30 mL/min. Reduce TDD by 50% if GFR < 10 or on dialysis. Insulin clearance is markedly reduced in advanced CKD.
- Always check K⁺ before starting insulin in any clinical setting — insulin shifts potassium intracellularly. This applies to DKA, hyperkalemia treatment, and routine dosing in CKD patients.
- Insulin stacking: Rapid-acting insulin lasts 3–5 hours. Avoid re-dosing correction insulin within 3 hours to prevent hypoglycemia from dose overlap.
- Transition from drip to SQ: The 2-hour overlap is critical. Stopping the drip without SQ coverage causes rebound hyperglycemia/ketosis within 1–2 hours.
🧮 Insulin Calculator
Method 1 — From Sliding Scale Usage
Add up all sliding scale insulin given in the past 24h.
Method 2 — Weight-Based (Insulin-Naive)
For patients not previously on insulin or no sliding scale data available.
| Scenario | Recommendation |
|---|---|
| Patient eating normally | Full basal-bolus-correction: 50% basal (glargine QHS) + 50% nutritional (lispro AC meals) + correction scale |
| NPO | Continue basal (reduce 20–50% if concerned). Hold nutritional. Correction-only q6h. Never hold basal completely in Type 1. |
| Tube feeds (continuous) | Basal (glargine) + correction q6h. Or NPH q12h + correction. Or 70/30 insulin q12h. |
| On steroids | ↑ TDD by 20–40%. Steroids cause afternoon/evening hyperglycemia → increase lunch and dinner doses more than basal. |
| Transitioning from drip | 24h drip total × 80% = TDD. Split 50/50. Give SubQ basal 2–4h BEFORE stopping drip. |
| Correction factor | 1800 ÷ TDD = how many mg/dL 1 unit drops glucose. |
Quick Reference
ACLS Algorithms & Code Timer
Cardiac arrest protocols, drug dosing, and your Code Clock app for real-time code documentation.
⏱️
Code Clock App
Real-time code documentation with CPR tracking, medication logging, and automatic timing. Opens in a new tab.
🚀 Launch Code Clock →
Cardiac Arrest — Adult Algorithm
Start CPR immediately. Rhythm check every 2 minutes. Push hard (≥ 2 inches), push fast (100–120/min), full recoil, minimize interruptions (< 10 sec for rhythm checks).
⚡ Shockable: VF / pVT
Shock
Defibrillate: biphasic 120–200J (or per device). Monophasic 360J. Resume CPR immediately × 2 min.
2 min
Rhythm check. If still VF/pVT → shock again. Resume CPR. Give epinephrine 1 mg IV/IO q3–5 min.
4 min
Rhythm check. If still VF/pVT → shock + amiodarone 300 mg IV/IO bolus. (2nd dose: 150 mg).
Ongoing
Continue 2-min cycles: CPR → rhythm check → shock if VF/pVT → epi q3–5 min. Search for reversible cause (H's & T's).
🔇 Non-Shockable: PEA / Asystole
Immediately
CPR + epinephrine 1 mg IV/IO as soon as access obtained. No shock for PEA/asystole.
2 min
Rhythm check. If PEA/asystole → resume CPR. Epi 1 mg q3–5 min.
Key
Find and treat the cause. PEA has a cause — run through H's & T's aggressively. Asystole is usually a terminal rhythm.
Transition
If rhythm changes to VF/pVT → switch to shockable pathway immediately.
ACLS Drug Dosing
| Drug | Dose | Indication | Notes |
|---|---|---|---|
| Epinephrine (Adrenalin) | 1 mg IV/IO q3–5 min | All cardiac arrest rhythms | Give immediately in PEA/asystole. After 2nd shock in VF/pVT. No max dose. |
| Amiodarone (Cordarone) | 300 mg IV/IO first dose, 150 mg second | Refractory VF/pVT | Give after 3rd shock. Alternative: lidocaine 1–1.5 mg/kg. |
| Lidocaine | 1–1.5 mg/kg IV first, 0.5–0.75 mg/kg repeat | Alternative to amiodarone for VF/pVT | Max 3 mg/kg total. |
| Atropine | 1 mg IV q3–5 min (max 3 mg) | Symptomatic bradycardia | NOT for cardiac arrest (removed from ACLS arrest algorithm). Still used for bradycardia with pulse. |
| Adenosine (Adenocard) | 6 mg rapid IV push → 12 mg → 12 mg | Stable regular narrow-complex SVT | Rapid push + immediate flush. Half-life 6 seconds. Warn patient: transient chest pressure/flushing. |
| Calcium chloride | 1–2 g (10–20 mL of 10%) IV slow push | Hyperkalemia, Ca-channel blocker OD, hypermagnesemia | Via central line preferred (tissue necrosis if infiltrates). Calcium gluconate 3g is alternative via peripheral. |
| Sodium bicarbonate | 1 mEq/kg IV | Hyperkalemia, TCA overdose, severe acidosis (pH < 7.1) | Not routine in cardiac arrest. Only for specific causes. |
| Magnesium sulfate | 1–2 g IV over 5–20 min | Torsades de Pointes, hypomagnesemia | First-line for Torsades. Also useful in refractory VF. |
Reversible Causes — H's & T's
| H's | Intervention |
|---|---|
| Hypovolemia | Volume resuscitation, blood products |
| Hypoxia | Secure airway, ventilate |
| Hydrogen ion (acidosis) | Bicarb, treat cause |
| Hypo/Hyperkalemia | Calcium, insulin/glucose, dialysis |
| Hypothermia | Active rewarming |
| T's | Intervention |
|---|---|
| Tension PTX | Needle decompression → chest tube |
| Tamponade | Pericardiocentesis |
| Toxins | Specific antidotes |
| Thrombosis (PE) | tPA 50 mg IV push |
| Thrombosis (MI) | PCI / cath lab |
Bradycardia with Pulse — Algorithm
Symptomatic? Hypotension, altered mental status, chest pain, acute HF → treat. Asymptomatic bradycardia → monitor.
1st Line
Atropine 1 mg IV q3–5 min (max 3 mg). Ineffective in transplanted hearts (denervated) and infra-nodal block (Mobitz II, 3rd degree).
If Atropine Fails
Transcutaneous pacing — apply pads, set rate 60–80, increase mA until capture. Sedate if conscious. OR dopamine 5–20 mcg/kg/min or epinephrine 2–10 mcg/min infusion as bridge.
Definitive
Transvenous pacing for persistent symptomatic bradycardia. Cardiology consult for permanent pacemaker if underlying cause is irreversible (complete heart block, SSS).
Tachycardia with Pulse — Algorithm
Unstable (hypotension, AMS, chest pain, acute HF)? → Synchronized cardioversion immediately. Do not delay for diagnosis.
| Rhythm | Width | Treatment |
|---|---|---|
| SVT (regular narrow) | Narrow (< 120 ms) | Vagal maneuvers → adenosine 6 mg → 12 mg → 12 mg. If refractory: diltiazem or cardioversion. |
| Afib/Aflutter (irregular narrow) | Narrow | Rate control: diltiazem or metoprolol. If unstable: cardioversion. See Afib with RVR topic. |
| Monomorphic VT (regular wide) | Wide (> 120 ms) | Stable: amiodarone 150 mg IV over 10 min. Unstable: synchronized cardioversion. If pulseless: defibrillate. |
| Polymorphic VT / Torsades | Wide, irregular | Magnesium 2g IV. If pulseless: defibrillate (unsynchronized). Stop offending drugs (QTc prolongers). Overdrive pacing. |
| Wide-complex uncertain | Wide | Treat as VT until proven otherwise. Amiodarone if stable. Cardioversion if unstable. Never give adenosine or CCB to wide-complex tachycardia of unknown origin. |
Post-Arrest: ROSC Checklist
- 12-lead ECG → STEMI → cath lab immediately
- SpO₂ target 94–98% — avoid hyperoxia
- PaCO₂ target 35–45 — avoid hypocapnia
- MAP ≥ 65–70 (norepinephrine first-line)
- Targeted temperature management — prevent fever > 37.7°C
- Continuous EEG monitoring (seizures in 30–40%)
- Full workup: echo, labs, CT head if no clear cardiac cause
- → See full Post-Cardiac Arrest (ROSC) topic for details
Quick Reference
Analgesia Guide
Pain is the most undertreated ICU problem. Analgesia first — always. An "agitated" patient is often just a patient in pain. PADIS, 2018
ICU Opioid Comparison
| Feature | Fentanyl (Sublimaze) | Remifentanil (Ultiva) | Hydromorphone (Dilaudid) | Morphine (MS Contin) |
|---|---|---|---|---|
| ICU Role | 1st LINE | Specialized | 2nd Line | AVOID |
| Dose | Analgesia: 25–100 mcg/hr Analgo-sedation: 100–200+ mcg/hr PRN: 25–100 mcg q1h | 0.05–0.2 mcg/kg/min | 0.2–0.5 mg/hr or 0.2–1 mg IV q3–4h PRN | 2–4 mg IV q2–4h PRN |
| Potency (vs morphine) | 80–100× | 100–200× | 5–7× | 1× (reference) |
| Onset | 1–2 min | < 1 min | 5 min | 5–10 min |
| Duration (single dose) | 30–60 min | 3–5 min | 3–4 hrs | 3–5 hrs |
| Hemodynamic effect | Minimal — safest | Minimal | Mild hypotension | Hypotension (histamine release) |
| Renal failure | Safe (hepatic metabolism) | Safe (plasma esterases) | Caution (H3G at high doses) | AVOID — M6G accumulates → prolonged sedation, resp depression |
| Hepatic failure | Accumulates | Safe | Accumulates | Accumulates |
| Best for | Everything. Low dose = analgesia. High dose = analgo-sedation. Often sufficient alone. | Frequent neuro checks. Ultra-rapid offset. Procedural. | Alt to fentanyl. Better renal profile than morphine. | Palliative care only. Floor patients, opioid-naive. |
| Watch out | Chest wall rigidity (rapid bolus). Accumulates > 72h (lipophilic). | Expensive. Rapid tolerance. No analgesic effect after stopping. | Neuroexcitation (myoclonus) at very high doses in renal failure. | Histamine → bronchospasm. M6G. Hypotension. Avoid in asthma, CKD, ICU. |
Non-Opioid Adjuncts
| Drug (Brand) | Dose | Role | Key Notes |
|---|---|---|---|
| Acetaminophen (Ofirmev IV / Tylenol PO) | 650–1000 mg q6h (max 4g/day; 2g if liver disease) | Non-opioid baseline — schedule for ALL ICU patients | Reduces opioid need 20–30%. Very safe. Should be scheduled, not PRN. |
| Ketamine (Ketalar) — sub-dissociative | 0.1–0.3 mg/kg/hr IV | Opioid-sparing. Neuropathic pain. Bronchospasm. Hemodynamically unstable. | NMDA antagonist — synergistic with opioids. Reduces opioid use 30–50%. Bronchodilator. |
| Ketorolac (Toradol) | 15–30 mg IV q6h (max 5 days) | Short-term non-opioid. Post-op. Renal colic. | Avoid: renal failure, GI bleed, platelet dysfunction, elderly. Max 5 days. |
| Gabapentin (Neurontin) | 100–300 mg PO TID (renal dose!) | Neuropathic pain adjunct | Renally cleared — #1 cause of iatrogenic AMS in CKD patients. Always renal dose. |
| Lidocaine patch (Lidoderm 5%) | 1–3 patches, 12h on / 12h off | Localized pain (rib fractures, post-herpetic, incision site) | No systemic side effects. Underutilized opioid-sparing option. |
| Pregabalin (Lyrica) | 25–150 mg PO BID (renal dose!) | Neuropathic pain. Alternative to gabapentin. | Also renally cleared. Dose-adjust in CKD. Fewer drug interactions than gabapentin. |
Pain Assessment Tools
CPOT (intubated patients)
Facial expression + body movements + ventilator compliance + muscle tension. Score 0–8. ≥ 3 = significant pain.
NRS (awake patients)
0–10 self-reported scale. Target NRS ≤ 3. Reassess after every intervention.
Key Pearls
Morphine is NOT an ICU drug. Histamine release → hypotension + bronchospasm. M6G accumulates in renal failure. Use fentanyl or hydromorphone instead.
Fentanyl is an analgesic first, sedative second. At 25–100 mcg/hr it provides pure analgesia. At 100–200+ mcg/hr it adds sedation. Many patients need nothing else — this is "analgo-sedation."
Before escalating sedation, always reassess pain. CPOT ≥ 3 or NRS ≥ 4 means the patient needs more analgesia, not more propofol.
Gabapentin in CKD = #1 iatrogenic AMS. Always renal-dose. If a CKD patient on gabapentin becomes altered, check the dose before ordering a head CT.
→ For sedation agents, RASS targets, and special situations, see
Sedation Guide
Quick Reference
Sedation Guide
Add sedation ONLY after adequate analgesia. Target lightest effective sedation — deep sedation kills ICU patients. PADIS, 2018
Have you treated pain first? Before reaching for a sedative, ensure fentanyl (or equivalent) is optimized. If CPOT ≥ 3 → the patient needs more analgesia, not sedation. Go to Analgesia Guide.
Sedation Agent Comparison
| Agent | Dose | Onset | Best For | Avoid When | Key Side Effects |
|---|---|---|---|---|---|
| Propofol (Diprivan) (Diprivan) 1ST LINE |
5–50 mcg/kg/min IV | 30–60 sec | Most ventilated ICU patients. Rapid on/off — ideal for daily SAT, neuro checks. | Egg/soy allergy, hypertriglyceridemia, propofol infusion syndrome risk | Hypotension (vasodilatory). Check TGs q48h. Propofol infusion syndrome if > 4 mg/kg/hr × > 48h. |
| Dexmedetomidine (Precedex) |
0.2–1.5 mcg/kg/hr IV (no load in ICU) | 15–30 min | Light sedation. Delirium prevention. Vent weaning. Only sedative without respiratory depression — can use in non-intubated patients. | Bradycardia, heart block, hemodynamic instability | Bradycardia (most common), hypotension, rebound HTN on discontinuation. Less delirium than benzos MENDS, 2007. |
| Ketamine (Ketalar) (Ketalar) |
0.5–2 mg/kg/hr IV (dissociative) 1–2 mg/kg bolus (procedural) |
1 min | Hemodynamically unstable (supports BP). Status asthmaticus. Refractory status epilepticus. Procedural. | Elevated ICP (relative), uncontrolled HTN, psychosis | Emergence phenomena, hypersalivation, tachycardia. Bronchodilator. |
| Midazolam (Versed) (Versed) 2ND/3RD LINE |
0.02–0.1 mg/kg/hr IV | 2–5 min | Benzo/alcohol withdrawal, status epilepticus, when propofol/dex contraindicated. | Prolonged ICU use, renal/hepatic failure, elderly | Accumulates → prolonged wake-up. ↑ delirium + mortality SEDCOM, 2009. Tolerance, withdrawal. |
| Lorazepam (Ativan) LAST RESORT |
0.01–0.1 mg/kg/hr IV or 0.5–4 mg PRN | 5 min | Alcohol/benzo withdrawal only (CIWA). Status epilepticus. Last resort. | Routine ICU sedation, renal failure (propylene glycol) | Propylene glycol toxicity (high-dose infusion). Worst delirium profile of all ICU sedatives. Do NOT use as first-line. |
RASS Scale — Sedation Targets
| RASS | Description | When to Target |
|---|---|---|
| +4 | Combative | — (never a target) |
| +3 | Very agitated | — (evaluate for pain, delirium, hypoxia) |
| +2 | Agitated | — (treat cause before escalating sedation) |
| +1 | Restless | May be acceptable if comfortable |
| 0 | Alert and calm | Ideal target for most patients |
| −1 | Drowsy — opens eyes to voice | Most common ICU target (RASS −1 to 0) |
| −2 | Light sedation — brief awakening to voice | Post-op, mild agitation |
| −3 | Moderate sedation — movement to voice only | NMB use, severe ARDS |
| −4 | Deep sedation — no response to voice | NMB, status epilepticus, elevated ICP |
| −5 | Unarousable | NMB only — reassess if unintentional |
Quick Selection Flowchart
Step 1: Pain controlled? (CPOT < 3, NRS ≤ 3) → If no, optimize analgesia first. Do not add sedation.
Step 2: Standard ventilated patient → Propofol. Target RASS −1 to 0. Daily SAT + SBT.
Step 3: Delirium, agitation, or vent weaning → Dexmedetomidine. Preserves respiratory drive.
Hypotensive patient needing sedation → Ketamine (supports BP). Or low-dose propofol with vasopressor support.
Alcohol/benzo withdrawal → Benzodiazepines (CIWA-guided). Phenobarbital for severe/refractory. Add dex as adjunct.
Severe ARDS + NMB → Deep sedation (RASS −3 to −4). Propofol or midazolam + fentanyl. Ensure adequate analgesia — paralyzed patients cannot communicate pain.
Procedural sedation → Propofol 0.5–1 mg/kg bolus ± fentanyl. Etomidate for cardioversion. Ketamine for hemodynamically unstable procedures.
Key Pearls
Light sedation saves lives. RASS −1 to 0 reduces ICU mortality, ventilator days, and long-term cognitive impairment vs deep sedation. There is almost never a reason for RASS −4/−5 without NMB.
Benzos cause delirium. Midazolam and lorazepam are independently associated with ↑ delirium and ↑ mortality compared to propofol or dexmedetomidine MENDS, 2007 SEDCOM, 2009. Never use as first-line ICU sedation.
Propofol infusion syndrome: > 4 mg/kg/hr × > 48h → new metabolic acidosis, ↑ lactate, rhabdomyolysis, Brugada-like ECG, cardiac failure. Stop propofol immediately, switch agent, supportive care.
Dexmedetomidine is the only sedative without respiratory depression. Can sedate non-intubated patients (post-extubation agitation, NIV patients, procedural sedation).
Daily SAT + SBT. Every day ask: can we turn off sedation? Can we do a breathing trial? The ABCDEF bundle reduces mortality and delirium. Do it every single day.
Special Clinical Scenarios
Alcohol / Benzodiazepine Withdrawal
Benzodiazepines are the treatment — NOT propofol or dexmedetomidine alone.
- CIWA-Ar score q4–8h — score > 8 → treat
- Lorazepam 1–4 mg IV q1h PRN (symptom-triggered) OR diazepam 5–20 mg PO/IV PRN
- Severe/refractory (CIWA > 20): phenobarbital 130–260 mg IV q15–30 min until controlled
- Add dexmedetomidine as adjunct for autonomic symptoms (tachycardia, HTN)
- Thiamine 100 mg IV before any glucose (prevents Wernicke's)
Delirium Management
- Non-pharmacologic first: reorientation, day/night cycle, early mobility, hearing aids/glasses
- Dexmedetomidine — reduces delirium duration vs benzos MENDS, 2007
- Haloperidol 1–5 mg IV/IM q6–12h PRN — QTc monitoring required. MIND-USA, 2018
- Quetiapine 25–50 mg PO BID-TID — alternative in non-intubated patients
- Avoid: benzos (worsen delirium unless withdrawal), anticholinergics, polypharmacy
Neuromuscular Blockade (NMB)
- Indications: severe ARDS (P/F < 150), refractory dyssynchrony, elevated ICP, status epilepticus
- Cisatracurium preferred (Hofmann elimination — no renal/hepatic clearance)
- Always ensure adequate sedation AND analgesia before NMB — aware paralysis is catastrophic
- Train-of-four (TOF) monitoring — target 1–2 twitches out of 4
Procedural Sedation
| Procedure | Regimen |
|---|---|
| Bronchoscopy | Propofol 0.5–1 mg/kg bolus + fentanyl 25–50 mcg + topical lidocaine |
| Central / arterial line | Midazolam 1–2 mg IV + fentanyl 25–50 mcg (or local only) |
| Cardioversion | Propofol 0.5–1 mg/kg IV or etomidate 0.2 mg/kg IV |
| Paracentesis / thoracentesis | Topical lidocaine only; add midazolam if anxious |
Pimp Questions
What is propofol infusion syndrome and how do you recognize it?
Rare but fatal complication of high-dose (> 4 mg/kg/hr) or prolonged propofol. Caused by impaired mitochondrial fatty acid oxidation. Features: new metabolic acidosis + elevated lactate, rhabdomyolysis, hyperkalemia, lipemic plasma, Brugada-like ECG, cardiac failure. Treatment: stop propofol immediately, switch agent, supportive care.
Why are benzodiazepines associated with worse ICU outcomes?
MENDS, 2007 SEDCOM, 2009: more delirium, longer ventilator time, increased ICU stay vs propofol or dexmedetomidine. Accumulate in renal/hepatic failure. Paradoxical agitation in elderly. Reserve for withdrawal and status epilepticus only.
What makes dexmedetomidine unique compared to other sedatives?
Only ICU sedative without respiratory depression. Mechanism: α₂ agonism (locus coeruleus) → sleep-like state, patients arouse easily. Can sedate non-intubated patients, continue during vent weaning, and doesn't interfere with respiratory drive during SBT.
Acute Exacerbation of COPD (AECOPD)
Sustained worsening of dyspnea, cough, or sputum beyond normal day-to-day variation. NIV before intubation. Bronchodilators + steroids are the backbone. Find and treat the trigger.
🔍 Overview
Definition
AECOPD is a sustained worsening of respiratory symptoms — increased dyspnea, cough frequency, and/or sputum production (volume, purulence) — beyond normal day-to-day variation, requiring a change in therapy. Anthonisen 1987
This is the most common cause of COPD-related morbidity and mortality. Frequent exacerbators (≥ 2 per year) have accelerated lung function decline and reduced survival. ICU mortality ranges from 10–30%.
This is the most common cause of COPD-related morbidity and mortality. Frequent exacerbators (≥ 2 per year) have accelerated lung function decline and reduced survival. ICU mortality ranges from 10–30%.
Severity Classification: Mild (bronchodilators only) | Moderate (requires antibiotics ± steroids) | Severe (hospitalization) | Very Severe (ICU admission)
Pathophysiology — Why COPD Patients Crash
The core problem is dynamic hyperinflation:
Trigger (infection, irritant) → airway inflammation → mucus plugging + bronchospasm → prolonged expiratory time → incomplete exhalation → air trapping → progressive hyperinflation → flattened diaphragm → reduced inspiratory capacity → respiratory muscle fatigue → hypercapnic respiratory failure.
Air stacking creates intrinsic PEEP (auto-PEEP), forcing patients to breathe against their own trapped air. This is why you see tripod positioning, pursed-lip breathing, and accessory muscle recruitment — they're desperately trying to empty their lungs before the next breath.
Trigger (infection, irritant) → airway inflammation → mucus plugging + bronchospasm → prolonged expiratory time → incomplete exhalation → air trapping → progressive hyperinflation → flattened diaphragm → reduced inspiratory capacity → respiratory muscle fatigue → hypercapnic respiratory failure.
Air stacking creates intrinsic PEEP (auto-PEEP), forcing patients to breathe against their own trapped air. This is why you see tripod positioning, pursed-lip breathing, and accessory muscle recruitment — they're desperately trying to empty their lungs before the next breath.
The 6 P's — Common Triggers of AECOPD
Mnemonic: 6 P's — ~80% of AECOPD exacerbations have an identifiable trigger. Think through each P systematically.
| # | P | Details |
|---|---|---|
| 1 | Pneumonia / Pulmonary infection | Most common trigger. Viral ~50% (rhinovirus, influenza, RSV, parainfluenza). Bacterial ~30% (H. influenzae, S. pneumoniae, M. catarrhalis). |
| 2 | Pulmonary embolism | Present in up to 25% of hospitalized AECOPD — often missed. Always consider if no clear infectious trigger, pleuritic pain, unexplained tachycardia, or hypoxia out of proportion. |
| 3 | Pneumothorax | Especially in emphysematous patients with bullae. CXR mandatory on all AECOPD admissions. |
| 4 | Pleural effusion | Can worsen dyspnea and restrict lung expansion. Rule out on CXR. |
| 5 | Poor compliance | Missed inhalers (LAMA/LABA/ICS non-adherence) — very common and modifiable. Always ask about medication use. |
| 6 | Pollution / environmental | PM2.5, ozone spikes, cold air, biomass fuel smoke, occupational dust. Leading cause of COPD in low-income countries (biomass > smoking). Both a cause of COPD development and a trigger for exacerbations. |
Don't Miss PE: PE occurs in up to 25% of AECOPD hospitalizations. Consider CTPA if: no clear infectious trigger, pleuritic pain, unexplained tachycardia, or hypoxia out of proportion to exam findings.
Also consider: Heart failure exacerbation (can mimic or co-precipitate AECOPD — check BNP), temperature extremes, and aspiration.
Common Mistake: Non-selective beta-blockers (propranolol, carvedilol), sedatives/opioids, and ACE inhibitors can trigger or worsen AECOPD. Always review the med list — ACE-inhibitor cough is frequently misdiagnosed as an exacerbation.
Clinical Presentation
Cardinal symptoms (Anthonisen criteria):
- Increased dyspnea — most sensitive symptom
- Increased sputum volume
- Increased sputum purulence — green/yellow suggests bacterial infection
Physical exam findings:
- Accessory muscle use (sternocleidomastoid, scalenes), tripod positioning
- Pursed-lip breathing (creates back-pressure to prevent airway collapse)
- Prolonged expiratory phase, diffuse expiratory wheezing
- Tachypnea (RR > 24), tachycardia, diaphoresis
- Cyanosis, asterixis (CO₂ retention), altered mental status
ICU Admission Criteria
- Severe dyspnea unresponsive to initial therapy (continued accessory muscle use, unable to speak in sentences)
- Altered mental status — confusion, somnolence, or coma
- Persistent hypoxemia: SpO₂ < 88% despite FiO₂ ≥ 0.4
- Severe or worsening respiratory acidosis: pH < 7.25 or PaCO₂ > 70 mmHg
- Acidosis not improving with NIV (recheck ABG at 1–2 hours)
- Hemodynamic instability requiring vasopressors
- NIV intolerance or failure
Key Point: A rising PaCO₂ with falling pH despite maximal therapy is an indication for intubation. Don't wait for respiratory arrest.
🧪 Workup & Diagnosis
Immediate Assessment
- ABG — mandatory in moderate-severe AECOPD. Assess pH, PaCO₂, PaO₂. Do NOT rely on SpO₂ alone.
- CXR — exclude pneumonia, pneumothorax, pulmonary edema, pleural effusion
- ECG — P pulmonale, right heart strain, arrhythmias (AF common in COPD)
- CBC — leukocytosis (infection), polycythaemia (chronic hypoxia)
- BMP — metabolic alkalosis (chronic CO₂ retainer), hypokalaemia (β₂ agonists)
- BNP / NT-proBNP — exclude heart failure as trigger or co-contributor
- Troponin if cardiac involvement suspected
ABG Interpretation in AECOPD
| Pattern | pH | PaCO₂ | HCO₃ | Interpretation |
|---|---|---|---|---|
| Acute hypercapnia | < 7.35 | > 45 | Normal / mildly ↑ | Acute exacerbation — treat aggressively |
| Chronic compensated | 7.35–7.45 | > 45 | ↑↑ (≥ 30) | Stable CO₂ retainer — know their baseline |
| Acute-on-chronic | < 7.35 | > 45 (above baseline) | ↑↑ | Most common pattern — compensated chronically + acute decompensation |
| pH < 7.25 | < 7.25 | > 60 | ↑ | Severe — NIV now, low threshold for intubation |
CO₂ Retainer Pearl: Chronic CO₂ retainers have high HCO₃ as compensation. A "normal" PaCO₂ of 45 mmHg may represent acute decompensation in someone whose baseline is 60 mmHg. Always compare to prior ABG or clinic notes.
Sputum & Microbiology
- Sputum Gram stain + culture if purulent sputum and no recent culture data
- Respiratory viral panel (if influenza season — guides oseltamivir)
- Legionella urine antigen + Pneumococcal urine antigen if severe / ICU
- Procalcitonin — helps distinguish bacterial vs viral trigger PRORATA 2010
- Consider CTPA if PE not excluded (atypical presentation, no clear infectious trigger)
Spirometry
Do NOT perform spirometry during acute exacerbation — results are unreliable and the maneuver is uncomfortable and potentially harmful. Review prior PFTs (baseline FEV₁) in the chart to understand severity. GOLD staging based on outpatient post-bronchodilator FEV₁/FVC < 0.70.
| GOLD Stage | Post-BD FEV₁ (% predicted) | Severity |
|---|---|---|
| GOLD 1 | ≥ 80% | Mild |
| GOLD 2 | 50–79% | Moderate |
| GOLD 3 | 30–49% | Severe |
| GOLD 4 | < 30% | Very severe |
GOLD A-B-E Groups (Symptom-Based Classification)
The GOLD 2023 update simplified COPD classification into 3 groups based on symptoms and exacerbation history. This guides outpatient treatment escalation — less relevant during acute exacerbation, but helps understand baseline therapy.
| GOLD Group | Symptoms (mMRC or CAT) | Exacerbations | Outpatient Treatment |
|---|---|---|---|
| Group A | Low symptoms (mMRC 0-1 or CAT < 10) |
0-1 (not requiring hospitalization) | Bronchodilator monotherapy: LABA or LAMA |
| Group B | High symptoms (mMRC ≥ 2 or CAT ≥ 10) |
0-1 (not requiring hospitalization) | Dual bronchodilator: LABA + LAMA |
| Group E | Any symptoms | ≥ 2 moderate exacerbations OR ≥ 1 hospitalization |
LABA + LAMA ± ICS (ICS if eosinophils ≥ 300 or frequent exacerbations) |
Key Change from Old GOLD: Groups C and D were merged into Group E. The "E" stands for Exacerbator phenotype — these patients have frequent exacerbations and need the most aggressive therapy. Blood eosinophils ≥ 300 cells/µL predict ICS benefit in Group E.
mMRC Dyspnea Scale: 0 = dyspnea only with strenuous exercise; 1 = dyspnea when hurrying on level or walking up slight hill; 2 = walks slower than people same age on level ground or stops for breath when walking at own pace; 3 = stops for breath after walking ~100 meters on level ground; 4 = too breathless to leave house.
CAT Score: COPD Assessment Test (0-40 scale). <10 = low impact, 10-20 = medium, 21-30 = high, >30 = very high impact.
CAT Score: COPD Assessment Test (0-40 scale). <10 = low impact, 10-20 = medium, 21-30 = high, >30 = very high impact.
🚨 Management
Management Algorithm
Immediately — Controlled Oxygen
Target SpO₂ 88–92% — and equally important: do NOT exceed 92% in known or suspected CO₂ retainers. Austin 2010
Why the upper limit matters:
Why the upper limit matters:
- Haldane effect — Dominant mechanism (~70%). Oxygenated Hb offloads CO₂ into plasma → PaCO₂ rises independent of respiratory rate.
- V/Q mismatch — High FiO₂ abolishes hypoxic pulmonary vasoconstriction → blood flows to poorly-ventilated units → worsened dead space.
- Hypoxic drive suppression — Correcting hypoxia reduces peripheral chemoreceptor drive → hypoventilation (real but overemphasized).
Common Error: Placing COPD patient on 15L NRB → arrives with PaCO₂ 90, pH 7.15. SpO₂ 100% is not reassuring in COPD — it may be the problem.
Bronchodilators — First-Line Treatment
Short-acting β₂ agonist (SABA) + short-acting muscarinic antagonist (SAMA) via nebuliser.
Albuterol (Ventolin, ProAir) 2.5–5 mg + ipratropium (Atrovent) 0.5 mg via nebuliser q20 min × 3, then q4–6h — or use DuoNeb (combination).
MDI + spacer equally effective as nebuliser in mild-moderate exacerbations (and doesn't aerosolise virus). Turner 1997
Continuous salbutamol nebuliser if severe bronchospasm.
Albuterol (Ventolin, ProAir) 2.5–5 mg + ipratropium (Atrovent) 0.5 mg via nebuliser q20 min × 3, then q4–6h — or use DuoNeb (combination).
MDI + spacer equally effective as nebuliser in mild-moderate exacerbations (and doesn't aerosolise virus). Turner 1997
Continuous salbutamol nebuliser if severe bronchospasm.
Systemic Corticosteroids
Prednisolone 40 mg PO daily × 5 days — reduces treatment failure and length of stay. REDUCE 2013 showed 5 days non-inferior to 14 days.
Use IV methylprednisolone 125 mg if unable to take PO (nil by mouth, vomiting) or very severe.
No taper needed for 5-day course. Taper only if > 3 weeks of steroids.
Use IV methylprednisolone 125 mg if unable to take PO (nil by mouth, vomiting) or very severe.
No taper needed for 5-day course. Taper only if > 3 weeks of steroids.
🔄 Updated Practice: Old teaching: 10-14 day steroid course for COPD exacerbation. REDUCE 2013 showed 5 days of prednisone 40mg is non-inferior to 14 days. Shorter course = less hyperglycemia, less immunosuppression, same outcomes. Also: old teaching was to check theophylline levels and use IV aminophylline — this is rarely done anymore due to narrow therapeutic index and better alternatives.
Antibiotics (if indicated)
Antibiotics reduce treatment failure in moderate-severe AECOPD with purulent sputum. Anthonisen 1987
Anthonisen Criteria (all 3 = definitely treat; 2/3 = probably treat; 1/3 = no benefit):
① Increased dyspnea ② Increased sputum volume ③ Increased sputum purulence
Empiric choice: Amoxicillin-clavulanate 875/125 mg PO BID OR doxycycline 100 mg BID × 5–7 days. Levofloxacin if Pseudomonas risk (structural lung disease, frequent hospitalisation, recent abx).
Anthonisen Criteria (all 3 = definitely treat; 2/3 = probably treat; 1/3 = no benefit):
① Increased dyspnea ② Increased sputum volume ③ Increased sputum purulence
Empiric choice: Amoxicillin-clavulanate 875/125 mg PO BID OR doxycycline 100 mg BID × 5–7 days. Levofloxacin if Pseudomonas risk (structural lung disease, frequent hospitalisation, recent abx).
Non-Invasive Ventilation (NIV / BiPAP) — Before Intubation
Start NIV early in hypercapnic respiratory failure (pH < 7.35 + PaCO₂ > 45). Reduces intubation rates, ICU mortality, and length of stay. Brochard 1995; Plant 2000
Initial settings: IPAP 12–16 cmH₂O, EPAP 4–5 cmH₂O. Titrate IPAP for patient comfort + TV 6–8 mL/kg. Add supplemental O₂ to maintain SpO₂ 88–92%.
NIV Contraindications: Reduced consciousness, inability to protect airway, vomiting, facial trauma/burns, hemodynamic instability, copious secretions, pH < 7.15 with poor trajectory.
Initial settings: IPAP 12–16 cmH₂O, EPAP 4–5 cmH₂O. Titrate IPAP for patient comfort + TV 6–8 mL/kg. Add supplemental O₂ to maintain SpO₂ 88–92%.
NIV Contraindications: Reduced consciousness, inability to protect airway, vomiting, facial trauma/burns, hemodynamic instability, copious secretions, pH < 7.15 with poor trajectory.
Intubation — When NIV Fails or Contraindicated
RSI with cautious ventilator settings to avoid auto-PEEP.
Initial vent: TV 6–8 mL/kg IBW, RR 10–12/min (lower than ARDS!), I:E 1:3 or 1:4, PEEP 5 cmH₂O.
Low RR = more time for exhalation = less air trapping.
If hemodynamic collapse after intubation → disconnect ETT → manual exhalation (auto-PEEP release).
Check plateau pressure + perform expiratory hold for intrinsic PEEP measurement.
Initial vent: TV 6–8 mL/kg IBW, RR 10–12/min (lower than ARDS!), I:E 1:3 or 1:4, PEEP 5 cmH₂O.
Low RR = more time for exhalation = less air trapping.
If hemodynamic collapse after intubation → disconnect ETT → manual exhalation (auto-PEEP release).
Check plateau pressure + perform expiratory hold for intrinsic PEEP measurement.
NIV Success vs Failure
| Parameter | Good Response (1–2h) | NIV Failure → Intubate |
|---|---|---|
| pH | Improving toward 7.35 | pH < 7.25 or worsening |
| PaCO₂ | Decreasing | Rising despite NIV |
| RR | Decreasing | Still > 30 after 1–2h |
| HR | Decreasing | Worsening tachycardia |
| Mentation | More alert, cooperative | Worsening confusion, agitation |
| Accessory muscles | Decreasing | Unchanged or increasing |
Discharge Criteria & Optimisation
- Able to use inhalers correctly
- Needs bronchodilators no more frequent than q4h
- On room air or at baseline O₂ requirement
- Able to eat and sleep without significant dyspnea
- Clinically and hemodynamically stable for 12–24h
- Maintenance therapy optimized (LAMA + LABA ± ICS reviewed and prescribed)
- Smoking cessation counselling
- Pulmonary rehab referral
- Follow-up within 1–4 weeks
📋 Clinical Example — COPD Exacerbation Management
Patient: 68M with severe COPD (FEV1 35%), presents with worsening dyspnea × 3 days, productive cough with purulent sputum, RR 28, SpO₂ 86% on RA.
Immediate: O₂ via nasal cannula → target SpO₂ 88–92% (NOT 100% — risk of CO₂ retention in COPD). Start BiPAP if not improving (IPAP 12, EPAP 5).
Bronchodilators: Albuterol (ProAir) 2.5mg + ipratropium (Atrovent) 0.5mg nebs q20min × 3, then q4h.
Steroids: Prednisone (Deltasone) 40mg PO daily × 5 days (REDUCE trial — 5 days = 14 days in outcomes).
Antibiotics: Azithromycin (Zithromax) 500mg PO daily × 3 days (indicated because purulent sputum — meets ≥ 2 of 3 Anthonisen criteria: ↑ dyspnea, ↑ sputum volume, ↑ sputum purulence).
ABG: pH 7.31, PaCO₂ 58, PaO₂ 62 → acute-on-chronic respiratory acidosis. BiPAP initiated. Repeat ABG in 1–2h.
Key: If BiPAP fails (worsening acidosis, inability to protect airway, AMS) → intubate. But BiPAP prevents intubation in ~75% of COPD exacerbations.
💊 Medications & Doses
Bronchodilators
| Drug | Class | Dose (Acute) | Notes |
|---|---|---|---|
| Albuterol (Ventolin, ProAir) | SABA | 2.5–5 mg neb q20 min × 3, then q4–6h | First-line. Watch hypokalaemia with frequent dosing. Check ECG. |
| Ipratropium (Atrovent) | SAMA | 0.5 mg neb q20 min × 3, then q6h | Combine with albuterol — additive bronchodilation. Less tachycardia. |
| Albuterol + Ipratropium (DuoNeb) | SABA+SAMA | 2.5/0.5 mg neb q20 min × 3 | Single-vial combination — preferred in acute setting for convenience |
| Magnesium sulphate | Smooth muscle relaxant | 1.2–2g IV over 20 min | Consider in severe/refractory bronchospasm — evidence mainly from asthma but used in COPD |
Corticosteroids
| Drug | Dose | Duration | Evidence |
|---|---|---|---|
| Prednisolone (Orapred) | 40 mg PO daily | 5 days REDUCE 2013 | Non-inferior to 14 days; reduces treatment failure and LOS |
| Methylprednisolone (Solu-Medrol) | 125 mg IV q6h | Until able to take PO → switch | Use if nil by mouth / unable to absorb PO |
| Dexamethasone (Decadron) | 8 mg IV/PO daily | 5 days | Alternative; longer half-life, once-daily dosing |
Antibiotics
| Drug | Dose | Indication | Notes |
|---|---|---|---|
| Amoxicillin-clavulanate | 875/125 mg PO BID × 5–7d | First-line moderate AECOPD with purulent sputum | Covers H. influenzae, S. pneumo, M. catarrhalis |
| Doxycycline (Vibramycin) | 100 mg PO BID × 5–7d | Alternative to amox-clav | Good atypical coverage; useful if penicillin allergy |
| Azithromycin (Zithromax) | 500 mg PO × 1, then 250 mg daily × 4d | Atypical coverage, macrolide option | Resistance rates rising; QTc monitoring |
| Levofloxacin (Levaquin) | 500–750 mg PO/IV daily × 5–7d | Pseudomonas risk, structural lung disease, frequent hospitalisations | QTc prolongation; Achilles tendon rupture risk; reserve for high-resistance risk |
| Piperacillin-tazobactam (Zosyn) | 3.375g q6h IV | ICU-level AECOPD with Pseudomonas risk | Bronchiectasis, structural lung disease, prior Pseudomonas isolation |
Procalcitonin-Guided Antibiotics: PCT < 0.1 = unlikely bacterial → withhold antibiotics. PCT 0.1–0.25 = equivocal. PCT > 0.25 = bacterial → treat. Reduces antibiotic use without increasing mortality. PRORATA 2010
Maintenance Therapy — Initiate Before Discharge
| Drug Class | Example | Notes |
|---|---|---|
| LAMA (Long-acting muscarinic antagonist) | Tiotropium (Spiriva) 18 mcg daily | Reduces exacerbation frequency. Most important maintenance drug. UPLIFT 2008 |
| LABA (Long-acting β₂ agonist) | Salmeterol or Formoterol | Add to LAMA in moderate-severe disease |
| ICS + LABA | Budesonide/Formoterol | Add ICS if ≥ 2 exacerbations/year or eosinophils ≥ 300. IMPACT 2018 — triple therapy reduces exacerbations |
| Roflumilast | 500 mcg PO daily | PDE4 inhibitor. Add in severe COPD (FEV₁ < 50%, chronic bronchitis, frequent exacerbations). GI side effects common. |
| Azithromycin prophylaxis | 250 mg 3×/week or 500 mg daily | Reduces exacerbation frequency in former/non-smokers. Albert 2011. Monitor QTc + hearing. |
📊 Monitoring
Monitoring Protocol
| Parameter | Frequency | Target / Action |
|---|---|---|
| SpO₂ | Continuous | 88–92% in CO₂ retainers. NOT 94–98%. |
| ABG | At 30–60 min after O₂/NIV start, then q4–6h if on NIV | pH improving, PaCO₂ stable or falling |
| RR, accessory muscle use | q1–2h | RR decreasing; less accessory muscle use = good response |
| Mental status | q1–2h on NIV | Worsening confusion → intubate |
| Potassium | q4–6h if frequent nebs | Hypokalaemia with frequent salbutamol + steroids; replace aggressively |
| Glucose | q6h if on steroids | Steroid hyperglycaemia — use insulin sliding scale |
| ECG | On admission + PRN | New AF common in AECOPD; rate control with diltiazem or digoxin (avoid BB) |
| CXR | On admission, repeat if worsening | Exclude new pneumonia, pneumothorax, effusion |
NIV Monitoring Checklist
- Check ABG 1–2h after starting NIV — if no improvement → escalate
- Mask fit — leaks significantly reduce effectiveness
- Patient tolerance — sedation is NOT used with NIV (risks aspiration)
- Titrate IPAP for TV 6–8 mL/kg and patient comfort
- SpO₂ 88–92% while on NIV
- Reassess every 2–4h — early identification of NIV failure critical
Ventilator Settings if Intubated
| Parameter | Setting | Rationale |
|---|---|---|
| Mode | AC/VC | Volume control preferred for predictable TV delivery |
| Tidal volume | 6–8 mL/kg IBW | Lower than ARDS — compliance better but still protect lungs |
| Rate | 10–12 /min (low!) | Low RR = more time to exhale = less auto-PEEP |
| I:E ratio | 1:3 to 1:4 | Prolonged expiratory time to reduce air trapping |
| PEEP | 3–5 cmH₂O (low) | Counter auto-PEEP partially; high PEEP worsens hyperinflation |
| FiO₂ | Titrate to SpO₂ 88–92% | Same target as non-intubated |
Post-Intubation Hypotension: Severe auto-PEEP → impaired venous return → hemodynamic collapse. Disconnect ETT, allow passive exhalation. Give IV fluid bolus. Reduce RR.
📋 On Rounds
On Rounds
📋 Sample Presentation
"Mr. Davies is a 67-year-old ex-smoker with GOLD 3 COPD who presented with 3 days of worsening dyspnea, increased purulent sputum, and confusion. On arrival he was in moderate respiratory distress — RR 28, SpO₂ 82% on room air, using accessory muscles. ABG showed pH 7.28, PaCO₂ 78, PaO₂ 52 on 2L NC. CXR showed hyperinflation with no new infiltrate. He was started on albuterol/ipratropium (DuoNeb) nebs, prednisolone 40 mg, and amoxicillin-clavulanate. NIV was initiated — IPAP 14 / EPAP 5 — with SpO₂ target 88–92%. Repeat ABG at 2 hours showed pH 7.34, PaCO₂ 68 — improving on NIV. He is now more alert, RR 20, on NIV cycling with breaks for meals. Today's plan: continue NIV, wean to Venturi mask for meals, antibiotic day 2, maintain O₂ target 88–92%."
Rounds Checklist
- SpO₂ 88–92% confirmed? Not on high-flow O₂?
- Latest ABG — pH and PaCO₂ trend?
- NIV hours per day? Mask tolerance?
- Bronchodilator frequency — still q4h? Ready to wean to q6h?
- Steroid day #? (5-day course)
- Antibiotic day #? (5–7 days). Sputum cultures back?
- Potassium — check daily with frequent nebs
- Glucose — steroid hyperglycaemia?
- Ambulation — physio ordered?
- Discharge planning — inhalers correct technique, follow-up, smoking cessation
Pimp Questions
Why do we target SpO₂ 88–92% in COPD and not 94–98%?
Three mechanisms, ranked by contribution: (1) Haldane effect (dominant, ~70%) — deoxyHb binds CO₂ ~3.5× more efficiently than oxyHb. Fully saturating Hb with O₂ offloads CO₂ into plasma → PaCO₂ rises even without any change in breathing. (2) V/Q mismatch worsening — high FiO₂ abolishes hypoxic pulmonary vasoconstriction → blood floods poorly-ventilated alveoli → dead space increases → CO₂ retention. (3) Hypoxic drive suppression (least significant, most over-taught) — blunted central CO₂ response means peripheral hypoxic drive is their main ventilatory stimulus; removing it causes mild hypoventilation. Clinical evidence: Austin 2010 showed titrated O₂ (88–92% target) vs high-flow O₂ reduced mortality by 58% in AECOPD.
What is auto-PEEP and how does it affect management in intubated COPD?
Auto-PEEP (intrinsic PEEP) occurs when air trapping prevents complete exhalation before the next breath is delivered. Gas accumulates → lung hyperinflation → increased intrathoracic pressure → reduced venous return → hemodynamic compromise. Detected by expiratory hold maneuver. Managed by: low RR (10–12/min), prolonged I:E (1:3 to 1:4), low set PEEP (3–5 cmH₂O), bronchodilators, suctioning. If hemodynamic collapse after intubation → disconnect ETT for passive exhalation.
When do antibiotics help in AECOPD and when don't they?
The Anthonisen 1987 landmark trial defined 3 cardinal symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence. Antibiotics benefit patients with all 3 symptoms (NNT ~3–4) or those requiring NIV/intubation. Only 1 symptom present = no antibiotic benefit. Procalcitonin can help guide the decision — PCT < 0.1 suggests viral etiology, withhold antibiotics. PRORATA 2010
NIV vs intubation — when do you escalate?
NIV reduces intubation, mortality, and LOS in hypercapnic AECOPD with pH 7.25–7.35 Brochard 1995. Reassess at 1–2h. Intubate if: pH < 7.25 or worsening, PaCO₂ rising on NIV, RR still > 30, worsening consciousness/agitation, inability to clear secretions, hemodynamic instability. Don't wait too long — a crashing COPD patient is technically difficult to intubate (hyperinflation → hemodynamic instability on intubation).
⚡ Summary
Summary
O₂ Target
88–92% in known/suspected CO₂ retainers. NOT high-flow. Titrate O₂ and check ABG in 30–60 min.
Bronchodilators
Albuterol (Ventolin) + ipratropium (Atrovent) neb q20 min × 3 → q4–6h, or DuoNeb. MDI + spacer equally effective in mild-moderate cases.
Steroids
Prednisolone 40 mg PO × 5 days. Equal to 14 days. IV methylprednisolone if nil by mouth. REDUCE 2013
Antibiotics
Give if 2–3 Anthonisen criteria present (dyspnea ↑ + sputum ↑ + purulence). Amox-clav or doxycycline × 5–7d. Fluoro if Pseudomonas risk.
NIV
Start early for pH < 7.35 + PaCO₂ > 45. Reduces intubation + mortality. Brochard 1995. Check ABG at 1–2h. Failure → intubate.
Intubation Settings
Low RR (10–12), I:E 1:3 to 1:4, low PEEP (3–5). High auto-PEEP → disconnect ETT + manual exhalation if hemodynamic collapse.
Don't Miss
PE in AECOPD (up to 25%). No infectious trigger → consider CTPA. Also AF (rate control) and HF co-exacerbation.
Before Discharge
Optimise inhalers (LAMA ± LABA ± ICS). Smoking cessation. Pulmonary rehab referral. Follow-up in 1–4 weeks.
📄 One Pager
Pulmonology · ICU · One Pager
AECOPD
Target O₂ 88–92%, NOT 94–98%. NIV before intubation. 5-day steroids. Antibiotics only if 2–3 Anthonisen criteria. Don't miss PE.
Anthonisen Criteria
① Increased dyspnea
② Increased sputum volume
③ Increased sputum purulence
2–3 present → give antibiotics Anthonisen 1987
1 present → no antibiotic benefit
② Increased sputum volume
③ Increased sputum purulence
2–3 present → give antibiotics Anthonisen 1987
1 present → no antibiotic benefit
ABG — Severity Guide
pH 7.35–7.45 + ↑PaCO₂Chronic compensated
pH < 7.35 + ↑PaCO₂Acute — start NIV
pH < 7.25Severe — low threshold intubate
pH < 7.15Intubate — NIV failing
Management — Step by Step
1
O₂ target 88–92% — start 1–2L NC, titrate up. Check ABG at 30–60 min. Austin 2010
2
Bronchodilators: Albuterol (Ventolin) 2.5–5 mg + ipratropium (Atrovent) 0.5 mg neb q20 min × 3 → q4–6h, or DuoNeb
3
Steroids: Prednisolone 40 mg PO × 5 days REDUCE 2013
4
Antibiotics if ≥ 2 Anthonisen criteria: Amox-clav 875/125 mg BID or doxycycline × 5–7d
5
NIV (BiPAP) if pH < 7.35 + PaCO₂ > 45 — IPAP 12–16, EPAP 4–5. Check ABG at 1–2h. Brochard 1995
6
Intubate if NIV fails (pH worsening, AMS, RR still > 30). Low RR (10–12), I:E 1:3, low PEEP.
Key Drugs
Albuterol (Ventolin)2.5–5 mg neb q20 min
Ipratropium0.5 mg neb q20 min
Prednisolone40 mg PO × 5d
Amox-clav875/125 mg PO BID × 5–7d
Monitoring
- SpO₂ 88–92% target
- ABG at 1–2h after NIV start
- K⁺ daily (salbutamol + steroids)
- Glucose q6h (steroids)
- ECG — new AF common
Pitfalls
- High-flow O₂ → CO₂ retention
- Steroids > 5 days (not needed)
- Antibiotics for viral AECOPD
- Missing PE as trigger
- High PEEP in auto-PEEP patient
- High RR on vent → air trapping
NIV Success Criteria (check at 1–2h)
- pH improving toward 7.35
- PaCO₂ stable or falling
- RR decreasing
- More alert and cooperative
- Accessory muscle use decreasing
Key Trials
- Brochard 1995: NIV reduces intubation + mortality
- REDUCE 2013: 5d steroids = 14d
- Anthonisen 1987: Antibiotic criteria
- Austin 2010: Titrated O₂ reduces mortality 58%
- UPLIFT 2008: Tiotropium reduces exacerbations
Quick Reference
Bowel Regimen
Constipation affects > 80% of ICU patients. Opioids, immobility, and critical illness gut dysmotility are the main drivers. Prevent it — don't wait for it.
Every patient on opioids needs a scheduled bowel regimen from day 1. Do not wait for the patient to complain. A constipated ICU patient becomes a distended, painful, ileus-complicated ICU patient.
Step-Up Bowel Protocol
Step 1 — Prevention (ALL opioid patients)
Docusate (Colace) 100 mg PO BID + Senna (Senokot) 8.6–17.2 mg PO BID. Start on admission. Docusate = stool softener. Senna = stimulant. This combination is the standard baseline.
Step 2 — No BM × 48h
Bisacodyl (Dulcolax) 10 mg PO or PR daily. Add to Step 1. Strong stimulant laxative. Suppository works faster than PO (15–60 min vs 6–12h).
Step 3 — No BM × 72h
Polyethylene glycol (MiraLAX) 17g in 8 oz water PO daily. Osmotic laxative. Can increase to BID. Or lactulose 15–30 mL PO q6–8h (also osmotic). MiraLAX preferred — less bloating/cramping.
Step 4 — Refractory / opioid-specific
Methylnaltrexone (Relistor) 8–12 mg SC q48h. Peripheral μ-opioid receptor antagonist — reverses opioid-induced constipation WITHOUT crossing BBB (no reversal of analgesia). Or naloxegol (Movantik) 25 mg PO daily. Use when standard regimen fails despite 72h of escalation.
Step 5 — Acute impaction
Fleet enema (sodium phosphate) PR or tap water enema. For acute relief. Avoid sodium phosphate enemas in CKD (hyperphosphatemia risk). Manual disimpaction if needed (last resort).
Bowel Agents — Full Table
| Drug (Brand) | Class | Dose | Onset | Key Notes |
|---|---|---|---|---|
| Docusate (Colace) 1ST LINE | Stool softener | 100 mg PO BID | 24–72h | Baseline for all opioid patients. Softens stool only — does not stimulate motility. Always pair with a stimulant. |
| Senna (Senokot) 1ST LINE | Stimulant laxative | 8.6–17.2 mg PO BID (1–2 tabs) | 6–12h | The stimulant half of the standard combo. Stimulates colonic motility. Can cause cramping. |
| Bisacodyl (Dulcolax) 2ND LINE | Stimulant laxative | 10 mg PO daily or 10 mg PR | PO: 6–12h PR: 15–60 min | Add when senna insufficient. PR suppository much faster. Avoid in acute abdomen or bowel obstruction. |
| PEG 3350 (MiraLAX) 2ND LINE | Osmotic laxative | 17g in 8 oz water PO daily–BID | 24–48h | Preferred osmotic. Non-absorbed. Less bloating than lactulose. Can use up to TID in refractory. |
| Lactulose (Kristalose) ALTERNATIVE | Osmotic laxative | 15–30 mL PO q6–8h | 24–48h | Also used for hepatic encephalopathy (different dose: 30–45 mL q1–2h until BM). More bloating/gas than MiraLAX. |
| Methylnaltrexone (Relistor) OIC-SPECIFIC | Peripheral μ-opioid antagonist | 8 mg SC (< 62 kg) or 12 mg SC (≥ 62 kg) q48h | 30 min–4h | Targets opioid-induced constipation (OIC) specifically. Does NOT cross BBB — no reversal of analgesia or withdrawal. Expensive. Use after standard regimen fails. |
| Naloxegol (Movantik) OIC-SPECIFIC | Peripheral μ-opioid antagonist (PO) | 25 mg PO daily (12.5 mg if CrCl < 60 or moderate CYP3A4 inhibitor) | 6–12h | Oral alternative to methylnaltrexone. Avoid with strong CYP3A4 inhibitors. Renal dose needed. |
| Magnesium citrate ADJUNCT | Osmotic / saline laxative | 150–300 mL PO × 1 | 30 min–3h | Fast-acting. Avoid in renal failure (hypermagnesemia). Single-use, not for maintenance. |
| Fleet enema (sodium phosphate) ACUTE ONLY | Rectal enema | 1 bottle (133 mL) PR × 1 | 2–15 min | Avoid in CKD — can cause fatal hyperphosphatemia. Avoid in elderly, dehydrated, or bowel obstruction. Use tap water enema instead in CKD. |
Special Situations
| Scenario | Approach |
|---|---|
| Opioid-induced (most ICU patients) | Docusate + senna from day 1 → escalate per protocol. Methylnaltrexone if refractory. Consider opioid rotation or reduction. |
| Post-operative ileus | Ambulation is the best treatment. Gum chewing stimulates gut motility. Alvimopan (Entereg) 12 mg PO BID × 7 days for post-surgical ileus (hospital use only). Avoid NG tube for uncomplicated ileus. |
| Hepatic encephalopathy | Lactulose 30–45 mL q1–2h titrated to 3–4 BMs/day. Goal is ammonia clearance, not just bowel movement. Rifaximin 550 mg PO BID for maintenance. See HE topic. |
| Hyperkalemia (kayexalate alternative) | Patiromer (Veltassa) or sodium zirconium (Lokelma) preferred over sodium polystyrene sulfonate (Kayexalate) — Kayexalate has risk of bowel necrosis and questionable efficacy. |
| CKD / dialysis patients | Avoid Fleet enemas (hyperphosphatemia), magnesium-containing laxatives (hypermagnesemia), and mineral oil (aspiration risk). Use senna + docusate, MiraLAX, or bisacodyl. |
| C. difficile concern | If new diarrhea after bowel regimen → check C. diff toxin. Hold laxatives. If C. diff positive: fidaxomicin 200 mg PO BID × 10d (preferred) or vancomycin 125 mg PO QID × 10d. Avoid loperamide. |
Key Pearls
Fleet enema + CKD = hyperphosphatemia. Can be fatal. Use tap water enema instead in any patient with renal impairment.
Docusate alone does nothing meaningful. It's a softener, not a motility agent. Always pair with senna or another stimulant. Some evidence suggests docusate adds nothing beyond the stimulant alone.
Methylnaltrexone (Relistor) does NOT reverse analgesia. It's peripherally restricted — blocks opioid receptors in the gut only. No crossing the BBB. Safe to give without worrying about pain control.
"Nothing by mouth" doesn't mean nothing for the gut. Bisacodyl suppositories and enemas work even if the patient is NPO. Don't forget rectal options.
Quick Reference
Inotropes Guide
When the heart can't squeeze — agents that increase cardiac contractility. Know the hemodynamic profile of each before you hang the drip.
Inotropes ≠ vasopressors. Vasopressors increase SVR (squeeze vessels). Inotropes increase contractility (squeeze heart). Some agents do both. Picking the wrong one kills patients — a patient in cardiogenic shock who gets phenylephrine (pure vasoconstrictor, no inotropy) will get worse.
When to Use Inotropes
| Clinical Scenario | Hemodynamic Profile | Agent of Choice |
|---|---|---|
| Cardiogenic shock (acute MI, decompensated HFrEF) | ↓ CO, ↑ SVR, ↓ MAP, cold extremities, poor cap refill | Dobutamine (if BP adequate) or milrinone (if RV failure / pulm HTN). Add norepinephrine if MAP < 65. |
| Septic shock with cardiac dysfunction | ↓ CO despite adequate MAP on NE, poor ScvO₂ (< 70%), elevated lactate despite fluids + pressors | Dobutamine added to norepinephrine. Or epinephrine (provides both inotropy + vasopressor). SSC, 2021 |
| Acute RV failure (massive PE, pulm HTN crisis, RV infarct) | ↓ CO, ↑ CVP/JVP, ↑ PVR, RV dilation on echo, septal bowing | Milrinone (↓ PVR + inotropy) or dobutamine. Add inhaled epoprostenol/iNO for selective pulmonary vasodilation. Avoid volume loading — worsens RV dilation. |
| Post-cardiac surgery (low CO syndrome) | ↓ CO post-CPB, stunned myocardium | Milrinone (preferred — ↓ afterload helps stunned heart, ↓ PVR). Or dobutamine. Epinephrine if hemodynamically significant. |
| Bridge to LVAD / transplant | End-stage HFrEF failing oral meds, awaiting mechanical support | Milrinone (continuous infusion, can use outpatient via PICC). Or dobutamine. |
| ADHF — "warm and wet" needing diuresis | Low CO limiting diuretic response, adequate BP | Low-dose dobutamine (2–5 mcg/kg/min) to augment renal perfusion for diuresis. Short-term only. |
Inotrope Comparison
| Agent (Brand) | Mechanism | Dose | Hemodynamic Effect | Best For | Watch Out |
|---|---|---|---|---|---|
| Dobutamine (Dobutrex) 1ST LINE |
β₁ > β₂ agonist | 2–20 mcg/kg/min IV | ↑ CO, ↑ HR, mild ↓ SVR (β₂ vasodilation). Net MAP may be unchanged or slightly ↓. | First-line inotrope in most cardiogenic shock (if MAP adequate). Septic shock with cardiac dysfunction. Augments diuresis in acute HF. | Never use alone if MAP < 65 — can drop BP via β₂ vasodilation. Always pair with NE if hypotensive. Tachycardia dose-limiting. Arrhythmogenic (↑ O₂ demand). Tachyphylaxis after 72h (downregulation of β-receptors). |
| Milrinone (Primacor) 1ST LINE |
PDE3 inhibitor (↑ cAMP) | 0.125–0.75 mcg/kg/min IV (skip loading dose in ICU — causes hypotension) |
↑ CO, ↓ SVR, ↓ PVR. "Inodilator" — inotropy + vasodilation. Better lusitropy (diastolic relaxation) than dobutamine. | RV failure / pulmonary HTN (↓ PVR is key advantage). Post-cardiac surgery. Bridge to LVAD/transplant. Works when β-receptors are downregulated (chronic HF on BB) — bypasses β-receptor. | Hypotension (vasodilation) — more than dobutamine. Renally cleared — dose-adjust in AKI/CKD. Thrombocytopenia (rare). Longer half-life (2–3h) — effects persist after stopping. Do NOT give loading dose in ICU (severe hypotension). |
| Epinephrine (Adrenalin) 2ND LINE |
α₁ + β₁ + β₂ agonist | Low dose: 0.01–0.1 mcg/kg/min (β₁/β₂ dominant → inotropy + vasodilation) High dose: 0.1–0.5 mcg/kg/min (α₁ dominant → vasoconstriction + inotropy) |
↑ CO, ↑ HR, dose-dependent SVR. Low dose = inotrope. High dose = inopressor. | Refractory cardiogenic shock (need both inotropy + pressor). Cardiac arrest. Post-arrest low CO. Anaphylaxis. | Falsely elevates lactate (β₂-mediated aerobic glycolysis) — cannot use lactate to guide resuscitation. Arrhythmogenic. ↑ myocardial O₂ demand. Hyperglycemia. Mesenteric ischemia at high doses. |
| Dopamine (Intropin) AVOID |
Dose-dependent: D₁ (low) → β₁ (mid) → α₁ (high) | "Renal dose" 1–3 → "cardiac" 3–10 → "pressor" 10–20 mcg/kg/min | Variable. Unpredictable hemodynamics. | Avoid. Inferior to NE in shock SOAP II, 2010. Only remaining role: symptomatic bradycardia if no pacing. | More arrhythmias and higher mortality vs NE. "Renal-dose dopamine" is a myth — no renal protection Bellomo, 2000. Unpredictable dose-response. Avoid in ICU. |
| Levosimendan (Simdax) SPECIALIZED |
Calcium sensitizer + K-ATP channel opener | 0.05–0.2 mcg/kg/min IV × 24h | ↑ CO, ↓ SVR, ↓ PVR. Inotropy without ↑ O₂ demand (unique). Active metabolite lasts 7–9 days. | Decompensated HF (Europe — not FDA-approved in US). Post-cardiac surgery. Bridge. Does not increase myocardial O₂ demand (unlike all other inotropes). | Not available in the US. Hypotension. Effect lasts days after stopping (long-acting metabolite). Limited data vs milrinone. |
| Isoproterenol (Isuprel) SPECIALIZED |
Pure β₁ + β₂ agonist (no α) | 2–20 mcg/min IV | ↑ HR, ↑ CO, ↓ SVR. Potent chronotrope. | Symptomatic bradycardia (bridge to pacing). Torsades de Pointes (↑ HR shortens QT). Beta-blocker overdose. Post-heart transplant (denervated heart — atropine doesn't work). | Severe hypotension (↓ SVR via β₂). Massively increases myocardial O₂ demand. Arrhythmogenic. Never use in ischemia. |
| Digoxin (Lanoxin) ADJUNCT |
Na⁺/K⁺-ATPase inhibitor → ↑ intracellular Ca²⁺ | 0.125–0.25 mg PO/IV daily Load: 0.25–0.5 mg IV |
Mild ↑ CO, ↓ HR (vagotonic). Weak inotrope compared to IV agents. | Chronic HFrEF with persistent symptoms on GDMT. Afib rate control adjunct (especially HFrEF). DIG, 1997: reduced HF hospitalizations, no mortality benefit. | Narrow therapeutic window (target 0.5–0.9 ng/mL). Toxicity: any arrhythmia — classically "regularized Afib" (junctional rhythm), bigeminy, bidirectional VT. Hypokalemia potentiates toxicity. Renally cleared — dose-adjust. Reversal: digoxin-specific Fab (DigiFab). |
Inotrope vs Vasopressor — Know the Difference
| Feature | Inotrope | Vasopressor | Inopressor (Both) |
|---|---|---|---|
| Primary effect | ↑ Contractility (↑ CO) | ↑ SVR (↑ MAP) | ↑ CO + ↑ SVR |
| Main receptor | β₁, PDE3 | α₁, V1 | α₁ + β₁ |
| Examples | Dobutamine, milrinone | Phenylephrine, vasopressin | Norepinephrine, epinephrine |
| Effect on SVR | ↓ or neutral | ↑↑ | ↑ |
| Use when | CO is low, MAP is OK | MAP is low, CO is OK | Both MAP and CO are low |
| Cardiogenic shock | Yes (primary) | Only as adjunct for MAP | NE is first-line pressor in CS |
| Septic shock | Add if ↓ CO despite MAP-targeted NE | NE is first-line | Epi if refractory |
Decision Flowchart
Is MAP < 65? → Start norepinephrine first (inopressor). You need MAP before you add a pure inotrope.
MAP adequate but CO is low? (cold extremities, poor cap refill, ↑ lactate, low ScvO₂) → Add dobutamine (first-line inotrope).
RV failure or pulmonary HTN? → Milrinone preferred (↓ PVR). Consider inhaled epoprostenol or iNO for selective pulmonary vasodilation.
Patient on chronic beta-blocker? → β-receptors are downregulated. Milrinone works better than dobutamine (PDE3 pathway bypasses β-receptor).
Need both inotropy + vasopressor? → Epinephrine (inopressor). Or NE + dobutamine as separate drips (more titratable).
Refractory to all above? → Mechanical circulatory support: IABP, Impella, ECMO. Call your interventional cardiology / cardiac surgery team early.
Key Pearls
All inotropes increase myocardial O₂ demand (except levosimendan). In ischemic cardiogenic shock, this is a double-edged sword — you're helping the pump but potentially worsening the ischemia. Keep doses as low as effective.
"Renal-dose dopamine" is a myth. Bellomo, 2000: no renal protection. SOAP II, 2010: more arrhythmias + higher mortality than NE. There is no role for dopamine as an inotrope in modern ICU care.
Dobutamine tachyphylaxis occurs after ~72h due to β₁-receptor downregulation. If the patient stops responding, switch to milrinone (PDE3 pathway) or add mechanical support.
Milrinone has a 2–3h half-life. If the patient drops their BP on milrinone, the effect persists for hours after stopping — unlike dobutamine (t½ ~2 min). Plan accordingly. Also: renally cleared — dose-reduce in AKI.
Epinephrine falsely elevates lactate via β₂-mediated aerobic glycolysis. If you're running epi for inotropy, you cannot use lactate clearance to assess resuscitation adequacy. Use ScvO₂, echo, or CI instead.
Digoxin toxicity = "any arrhythmia." Classic: regularized afib, bigeminy, bidirectional VT. Hypokalemia potentiates it. Always check K⁺ with dig level. Reversal: DigiFab (digoxin-specific Fab fragments).
Pulmonary Embolism
Clot in the pulmonary vasculature. Severity ranges from incidental subsegmental PE to massive PE with cardiac arrest. Risk-stratify immediately — it determines whether you anticoagulate, lyse, or intervene.
🔍 Overview
Risk Stratification
Classify immediately: Massive, submassive, or low-risk. This drives the entire management algorithm.
| Category | Hemodynamics | RV Dysfunction | Troponin | Mortality | Treatment |
|---|---|---|---|---|---|
| Massive (~5%) | SBP < 90 for > 15 min or requiring pressors or cardiac arrest | Yes | Usually elevated | 25–65% | Systemic thrombolysis (tPA) or catheter-directed therapy or surgical embolectomy |
| Submassive (~25%) | Stable (SBP ≥ 90) | Yes (RV/LV > 0.9 on CT or echo) | Elevated | 3–15% | Anticoagulation ± escalation (catheter-directed lysis, half-dose tPA) if deteriorating |
| Low-risk (~70%) | Stable | No | Normal | < 1% | Anticoagulation alone. Consider outpatient treatment (Hestia criteria, sPESI = 0) Jiménez, 2010. Home treatment non-inferior to inpatient HESTIA, 2011. |
Presentation
- Dyspnea — most common symptom (~80%)
- Pleuritic chest pain — sharp, worse with inspiration
- Tachycardia — often out of proportion to clinical picture
- Hypoxia — but ~20% have normal SpO₂
- Syncope — suggests massive PE (transient loss of CO)
- Hemoptysis, leg swelling (concurrent DVT in ~50%)
Classic triad (dyspnea + pleuritic pain + hemoptysis) is present in < 20% of cases. PE is a great mimicker — always have it on your differential for unexplained tachycardia, new Afib, or hypoxia out of proportion.
🧪 Workup
Diagnostic Approach
| Test | When | Key Points |
|---|---|---|
| Wells Score | First step — risk stratify | ≤ 4 = unlikely → D-dimer. > 4 = likely → CTPA directly. Modified Wells also used. Clinical gestalt matters. |
| D-dimer | Low/intermediate pretest probability | High sensitivity, low specificity. Negative D-dimer rules out PE (NPV > 99%). Age-adjusted cutoff: age × 10 for patients > 50. Do NOT order if high pretest probability — go straight to imaging. |
| CTPA | Test of choice for diagnosis | Gold standard. Sensitivity > 95%. Also shows RV dilation (RV/LV > 0.9 = submassive). Avoid if contrast allergy or severe CKD → V/Q scan. |
| Bedside echo | Unstable patient — cannot go to CT | RV dilation, septal bowing (D-sign), McConnell's sign (RV free wall akinesis with apical sparing). Does NOT confirm PE but supports it in unstable patient → treat empirically. |
| Troponin + BNP | All confirmed PE | Elevated troponin = RV strain = submassive. BNP/NT-proBNP elevated = RV pressure overload. Both are prognostic markers. |
| Lower extremity US | If DVT suspected | Concurrent DVT found in ~50% of PE. Positive DVT + symptoms = treat for PE even without CTPA. |
🚨 Management
Management by Severity
Massive PE (hemodynamically unstable)
This is a time-critical emergency. Do NOT wait for CTPA if echo shows RV strain + clinical picture fits.
Immediate
Systemic tPA (alteplase) 100 mg IV over 2 hours. Or 50 mg IV bolus if in cardiac arrest (push dose). PEITHO, 2014 showed benefit for massive PE. Start heparin after tPA infusion (no bolus).
If tPA contraindicated
Catheter-directed therapy (CDT) — catheter-directed lysis (low-dose tPA directly into PA) or mechanical thrombectomy. Or surgical embolectomy if available.
Supportive
IV fluids cautiously (250–500 mL max — RV is volume-sensitive, overloading worsens septal bowing). Norepinephrine for MAP support. Avoid intubation if possible — positive pressure ventilation drops preload → hemodynamic collapse. If must intubate: ketamine induction, low PEEP.
Submassive PE (stable + RV dysfunction)
First-line
Anticoagulation with heparin drip (UFH 80 units/kg bolus → 18 units/kg/hr, target aPTT 60–80). Monitor closely for deterioration.
Escalation triggers
Worsening tachycardia, rising troponin/BNP, new hypotension, increasing O₂ requirement → consider catheter-directed therapy or half-dose tPA (50 mg over 2h). Activate PERT (Pulmonary Embolism Response Team) if available.
Low-Risk PE
- Anticoagulation: DOAC preferred. Rivaroxaban 15 mg BID × 21 days → 20 mg daily or apixaban 10 mg BID × 7 days → 5 mg BID. No bridging needed with DOACs.
- If using warfarin: bridge with heparin/LMWH until INR 2–3 × 2 consecutive days.
- Duration: provoked (surgery, immobilization) = 3 months. Unprovoked = ≥ 6 months, consider indefinite. Cancer = DOAC or LMWH indefinitely.
- Consider outpatient treatment if sPESI = 0 and Hestia criteria negative.
Anticoagulation for PE
| Drug (Brand) | Dose | Notes |
|---|---|---|
| Rivaroxaban (Xarelto) 1ST LINE | 15 mg BID × 21 days → 20 mg daily | No bridging. Take with food. Adjust if CrCl < 50. |
| Apixaban (Eliquis) 1ST LINE | 10 mg BID × 7 days → 5 mg BID | No bridging. Lowest bleeding risk of all DOACs. Preferred in CKD. |
| Heparin (UFH) MASSIVE/SUBMASSIVE | 80 units/kg bolus → 18 units/kg/hr drip | Target aPTT 60–80. Short half-life — use when intervention likely or high bleed risk. Reversible with protamine. |
| Enoxaparin (Lovenox) BRIDGE | 1 mg/kg SC q12h | Bridge to warfarin if DOAC not used. Avoid if CrCl < 30 — use UFH instead. |
| Alteplase / tPA (Activase) MASSIVE ONLY | 100 mg IV over 2h (or 50 mg bolus in arrest) | Massive PE only. Major bleeding risk ~10%. Absolute contraindications: active bleeding, recent CNS surgery, hemorrhagic stroke. |
🔄 Updated Practice: Old teaching: all PE patients need heparin bridge to warfarin. Current practice: DOACs are first-line for most PE patients — apixaban and rivaroxaban can be started directly WITHOUT heparin bridging (AMPLIFY, EINSTEIN). Heparin bridge → warfarin is only needed if: massive PE requiring thrombolysis, cancer-associated PE (LMWH or DOAC), or renal failure (CrCl <25-30). Also: subsegmental PE without DVT may not need anticoagulation in low-risk patients — shared decision-making with the patient.
📋 Clinical Example — PE Risk Stratification & Treatment
Patient: 45M, post-op day 3 from knee surgery, sudden-onset dyspnea, HR 110, SpO₂ 92%, BP 128/82.
Pre-test probability: Wells score = 4.5 (HR > 100 = 1.5, immobilization/surgery = 1.5, PE most likely dx = 1.5) → Moderate probability → CT-PA indicated (skip D-dimer).
CT-PA: Saddle PE with RV dilation.
Risk stratification:
- Hemodynamically stable (BP > 90) → NOT massive
- RV dilation on CT + troponin 0.08 (elevated) + BNP 450 → Submassive PE
- sPESI score: age > 45 (+1), HR > 110 (+1) = 2 → high risk for decompensation
Treatment:
- Anticoagulation: Heparin drip (80 units/kg bolus → 18 units/kg/hr). Target aPTT 60-80 sec.
- Submassive: ICU admission. Monitor for decompensation. Consider catheter-directed therapy or systemic tPA if deteriorates.
- Transition: Once stable × 24-48h → apixaban (Eliquis) 10mg BID × 7 days → 5mg BID ongoing.
- Duration: Provoked (surgery) → 3 months. Unprovoked → ≥ 6 months, consider indefinite.
If massive (hypotension/arrest): Systemic tPA (alteplase 100mg IV over 2h). Half-dose (50mg) if concern for bleeding.
📋 On Rounds
Pimp Questions
Why should you avoid aggressive fluid resuscitation in massive PE?
The RV is already failing from acute pressure overload. Adding volume further distends the RV, pushes the septum into the LV (interventricular dependence), and drops LV filling and cardiac output. Limit to 250–500 mL crystalloid. If still hypotensive → vasopressors (norepinephrine), not more fluids.
Why is intubation dangerous in massive PE?
Positive pressure ventilation decreases venous return (preload) to a failing RV → precipitous drop in CO → PEA arrest. Also, induction agents cause vasodilation → further hypotension. If intubation is unavoidable: use ketamine (supports hemodynamics), keep PEEP as low as possible, and have vasopressors running before you push the induction agent.
What is McConnell's sign?
RV free wall akinesis with preserved apical contractility on echocardiography. Highly specific (~95%) for acute PE with RV strain. The apex is spared because it's tethered to the LV. Helps differentiate acute PE from chronic pulmonary HTN (which causes global RV hypokinesis).
What is the sPESI score and how does it guide disposition?
sPESI (simplified Pulmonary Embolism Severity Index): 1 point each for: age > 80, cancer, chronic cardiopulmonary disease, HR ≥ 110, SBP < 100, SpO₂ < 90%. Score 0: low risk (30-day mortality ~1%) → candidate for outpatient treatment with DOAC if: reliable, no contraindications, close follow-up available. Score ≥ 1: higher risk → inpatient admission. Massive PE: (SBP < 90 or requiring pressors) → ICU, systemic tPA or catheter-directed therapy. Submassive PE: (stable but RV strain — elevated troponin, RV/LV ratio > 0.9) → admit, anticoag, close monitoring — escalate to catheter-directed therapy or tPA if deteriorates. The key decision: stable + no RV strain + sPESI 0 = can go home. Anything else = admit.
📣 Sample Presentation
One-Liner
"Ms. Park is a 42-year-old on OCPs presenting with acute pleuritic chest pain and dyspnea × 1 day. HR 112, SpO₂ 93%. Wells score 7.5 (high). CTPA shows bilateral segmental PE with RV/LV ratio 1.2. Troponin 0.08."
Key Points to Cover on Rounds
Submassive PE (hemodynamically stable but RV strain). RV/LV ratio 1.2 on CTPA. Troponin mildly elevated 0.08, BNP 380. sPESI score 1. Anticoagulation: heparin drip started, transitioning to rivaroxaban 15 mg BID × 21 days then 20 mg daily. OCPs stopped. Lower extremity US: DVT in left popliteal vein. Close monitoring for deterioration — if hemodynamically unstable → tPA or catheter-directed therapy. Plan: 3 months minimum anticoag, then reassess for extended therapy given provoked (OCP).
💊 Medications
Medications — Pulmonary Embolism
Medication details for Pulmonary Embolism are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Pulmonary Embolism
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Risk Stratify
Wells score → if ≤ 4: D-dimer first. If > 4: CTPA directly. PERC rule: if all 8 criteria negative → PE ruled out.
Massive PE
SBP < 90 or requiring pressors → systemic tPA (alteplase 100 mg over 2h) or catheter-directed therapy.
Submassive PE
Hemodynamically stable BUT RV strain (elevated troponin, RV/LV > 0.9). Monitor closely. Escalate if deteriorates.
Anticoagulation
Heparin → transition to DOAC (rivaroxaban or apixaban). Duration: 3 months if provoked, indefinite if unprovoked.
sPESI = 0
Low risk (~1% 30-day mortality) → candidate for outpatient treatment with DOAC if reliable follow-up.
Don't Miss
Paradoxical embolism (PFO + DVT → stroke). RV failure (acute cor pulmonale). Post-PE syndrome (chronic thromboembolic pulmonary HTN).
📄 One Pager
One Pager — Pulmonary Embolism
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
PULMONARY EMBOLISM — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Pulmonology / Hematology · One Pager
Pulmonary Embolism
Wells → D-dimer or CTPA. Massive = tPA. Submassive = monitor for deterioration. sPESI 0 = outpatient candidate. DOAC for most.
Risk Stratification
Wells ≤ 4: D-dimer → if negative, PE ruled out. Wells > 4: go straight to CTPA. PERC rule: if all 8 negative in low-risk → no testing needed.
Treatment by Severity
Massive (SBP < 90): systemic tPA 100 mg/2h or catheter-directed therapy. Submassive (stable + RV strain): anticoag, close monitoring, escalate if deteriorates. Low-risk (sPESI 0): outpatient DOAC.
Anticoagulation
Apixaban 10 BID × 7d → 5 BID. Or rivaroxaban 15 BID × 21d → 20 daily. Duration: 3 months (provoked), indefinite (unprovoked). Extended: reduced-dose DOAC [AMPLIFY-EXT].
Key Drugs
Apixaban10 mg BID × 7d → 5 BID
Rivaroxaban15 mg BID × 21d → 20 daily
Heparin80 U/kg bolus → 18 U/kg/hr
Alteplase100 mg over 2h (massive)
Pitfalls
- D-dimer without clinical decision rule (Wells/PERC)
- Delaying anticoag while waiting for imaging
- Missing RV strain in submassive PE
- Not considering outpatient treatment for low-risk PE
Hyperkalemia
K⁺ > 5.0 mEq/L. A silent killer — the ECG changes before the patient complains. Memorize the treatment ladder. You will use it weekly.
🔍 Overview
ECG Progression
Get an ECG before anything else. ECG changes = emergent regardless of the number. A patient with K⁺ 6.0 and peaked T's is sicker than a patient with K⁺ 7.0 and a normal ECG.
| K⁺ Level | ECG Finding | Urgency |
|---|---|---|
| 5.5–6.0 | Peaked T waves (tall, narrow, symmetric — earliest sign) | Urgent — start treatment |
| 6.0–6.5 | Prolonged PR interval, flattened P waves | Emergent |
| 6.5–7.0 | Widened QRS (> 120 ms) | Critical — calcium NOW |
| 7.0–8.0 | Sine wave pattern (QRS merges with T wave) | Pre-arrest. Calcium + emergent dialysis. |
| > 8.0 | VF, asystole, PEA | Cardiac arrest. Treat during resuscitation. |
Common Causes
- Renal failure (AKI, CKD G4–G5) — most common, impaired K⁺ excretion
- Medications — ACEi/ARBs, spironolactone, trimethoprim, NSAIDs, heparin, succinylcholine
- Cellular shift — acidosis, rhabdomyolysis, tumor lysis, DKA, massive transfusion
- Adrenal insufficiency — cortisol + aldosterone deficiency → impaired renal K⁺ excretion
- Pseudohyperkalemia — hemolyzed sample (most common lab artifact), high WBC/plt count, tourniquet too tight
Rule out pseudohyperkalemia first: if the patient has no ECG changes, no risk factors, and the K⁺ is unexpectedly elevated → recheck on a non-hemolyzed, free-flowing sample before treating.
Pseudohyperkalemia — Deep Dive
Pseudohyperkalemia is a falsely elevated serum K⁺ due to K⁺ release from cells during or after blood collection — not a true reflection of in vivo potassium levels. Recognizing it prevents unnecessary (and potentially dangerous) treatment of a lab artifact.
Mechanisms
- Hemolysis during phlebotomy — the most common cause. Traumatic draw, small-gauge needle, vigorous shaking of the tube, or pneumatic tube transport causes RBC lysis and K⁺ release. The lab usually flags the specimen as hemolyzed (hemolysis index elevated).
- Prolonged tourniquet time — fist clenching with a tight tourniquet causes local ischemia and K⁺ leakage from forearm muscles. Can raise K⁺ by 0.5–1.5 mEq/L.
- Thrombocytosis (plt > 500K) — during clot formation in a serum (red-top) tube, platelets degranulate and release intracellular K⁺. The higher the platelet count, the greater the artifact. A plasma (green-top/heparin) sample bypasses clotting and gives the true K⁺.
- Leukocytosis (WBC > 70–100K) — seen in leukemia/lymphoma. Fragile WBCs lyse in vitro, releasing K⁺. Again, a plasma sample is more accurate.
- In vitro hemolysis from specimen handling — delayed processing, refrigeration of whole blood, or prolonged storage allows ongoing K⁺ leak from cells.
- Familial pseudohyperkalemia — rare inherited RBC membrane defect causing K⁺ leak at room temperature but not at 37°C.
How to Differentiate: Real vs. Pseudo
| Feature | Pseudohyperkalemia | True Hyperkalemia |
|---|---|---|
| ECG changes | Normal — no peaked T's, no QRS widening | Peaked T waves, PR prolongation, wide QRS, sine wave |
| Hemolysis index | Elevated (lab flags specimen as hemolyzed) | Normal (non-hemolyzed sample) |
| Serum vs. plasma K⁺ | Serum K⁺ significantly higher than plasma K⁺ (difference > 0.3–0.4 mEq/L) | Serum and plasma K⁺ are concordant |
| Clinical context | No risk factors (normal renal function, no culprit drugs, no acidosis) | AKI/CKD, K⁺-sparing drugs, acidosis, rhabdomyolysis, etc. |
| Symptoms | Patient is asymptomatic, feels well | May have weakness, palpitations, paresthesias |
| Repeat sample | Normal K⁺ on a free-flowing, non-hemolyzed redraw | Persistently elevated on repeat |
| Plt/WBC count | Often markedly elevated (thrombocytosis or leukocytosis) | Usually normal or irrelevant |
The Key Move
If you suspect pseudohyperkalemia: Redraw blood from a free-flowing venipuncture (no tourniquet or < 1 min), into a green-top (lithium heparin) tube for plasma potassium. This avoids both clotting artifact (thrombocytosis) and most hemolysis artifact. If the plasma K⁺ is normal while the original serum K⁺ was elevated → pseudohyperkalemia confirmed.
Never assume pseudohyperkalemia if the patient has ECG changes. Even if the sample appears hemolyzed, if the ECG shows peaked T waves or QRS widening, treat as true hyperkalemia while redrawing. The cost of treating a false positive (calcium, insulin) is far less than the cost of missing real hyperkalemia (cardiac arrest).
🚨 Management
Treatment Ladder
Three categories of treatment — use them in order: (1) Stabilize the membrane, (2) Shift K⁺ into cells, (3) Remove K⁺ from the body. Only #3 actually lowers total body potassium.
| Step | Drug (Brand) | Dose | Onset | Duration | Mechanism |
|---|---|---|---|---|---|
| 1. STABILIZE | Calcium gluconate FIRST IF ECG CHANGES | 1–2 g (10–20 mL of 10%) IV over 2–3 min | 1–3 min | 30–60 min | Stabilizes cardiac membrane. Does NOT lower K⁺. Repeat in 5 min if ECG unchanged. Use calcium chloride (1g) via central line for more rapid effect. |
| 2a. SHIFT | Insulin + Glucose 1ST LINE SHIFT | Regular insulin 10 units IV + D50 25g (1 amp) IV | 15–30 min | 4–6 hrs | Insulin drives K⁺ into cells via Na⁺/K⁺-ATPase. Must give dextrose or the patient becomes hypoglycemic (10–75% incidence) AHA Hyperkalemia Guidelines, 2023. Check glucose at 1h and 2h. Give D10 drip if glucose < 250 before insulin. |
| 2b. SHIFT | Sodium bicarbonate | 50–100 mEq (1–2 amps) IV over 5 min | 15–30 min | 2 hrs | Drives K⁺ into cells via H⁺/K⁺ exchange. Most effective if acidotic (pH < 7.2). Minimal effect if pH normal. Avoid in volume overload (sodium load). |
| 2c. SHIFT | Albuterol (nebulized) | 10–20 mg nebulized (4–8× standard asthma dose) | 15–30 min | 2–4 hrs | β₂-mediated K⁺ shift into cells. Drops K⁺ by 0.5–1.0 mEq/L. Watch for tachycardia. Often forgotten — add it to insulin/glucose. |
| 3a. REMOVE | Furosemide (Lasix) IF RENAL FUNCTION OK | 40–80 mg IV | 30–60 min | 6 hrs | Enhances renal K⁺ excretion. Only works if kidneys functional. Give with NS if volume depleted. |
| 3b. REMOVE | Patiromer (Veltassa) CHRONIC | 8.4 g PO daily | 4–7 hrs | Ongoing | K⁺ binder. NOT for acute emergencies (too slow). Best for chronic hyperK management to allow continuation of ACEi/ARB/MRA. OPAL-HK, 2015 |
| 3c. REMOVE | Sodium zirconium cyclosilicate (Lokelma) CHRONIC/SUBACUTE | 10 g PO TID × 48h (acute) → 5–10 g daily | 1–2 hrs | Ongoing | Faster than patiromer. Can be used in acute setting (onset 1–2h). Well-tolerated. HARMONIZE, 2014 |
| 3d. REMOVE | Hemodialysis REFRACTORY / SEVERE | Emergent HD | Immediate | Definitive | Most effective K⁺ removal. Drops K⁺ by 1–2 mEq/L per session. Indicated: refractory to medical therapy, anuric patient, K⁺ > 6.5 with ECG changes + CKD/ESKD. |
Kayexalate (sodium polystyrene sulfonate) — avoid if possible. Slow onset (hours), questionable efficacy SPS Efficacy Review, 2013, and risk of intestinal necrosis (especially with sorbitol). Patiromer and Lokelma have replaced it. If you must use it: 15–30 g PO or 30–50 g PR, never with sorbitol.
🔄 Updated Practice: Old teaching: sodium polystyrene sulfonate (Kayexalate) for hyperkalemia. This is OUTDATED — kayexalate works slowly (hours to days), has unreliable efficacy, and risks intestinal necrosis (especially with sorbitol). Newer potassium binders — patiromer (Veltassa) and sodium zirconium cyclosilicate (Lokelma) — are faster, safer, and better tolerated. Use these instead for non-emergent K⁺ lowering.
📋 Clinical Example — Hyperkalemia Emergency Management
Patient: 68F with CKD Stage IV on lisinopril (Zestril) + spironolactone (Aldactone), K⁺ 7.1, ECG shows peaked T waves and widened QRS.
Immediate (seconds to minutes — stabilize the heart):
- Calcium gluconate 1g IV over 2–3 min → repeat ECG. Does NOT lower K⁺ — stabilizes cardiac membrane. Effect lasts 30–60 min. Repeat if ECG still abnormal.
Shift K⁺ intracellularly (minutes to hours):
- Regular insulin 10 units IV + D50 1 amp (25g glucose) — onset 15–30 min, lowers K⁺ by 0.5–1.0. Check glucose q1h × 4h (hypoglycemia risk peaks at 2–4h, give D10 infusion if needed).
- Albuterol (ProAir) 10–20mg nebulized — onset 15–30 min, lowers K⁺ by 0.5–1.0. Additive with insulin.
- Sodium bicarbonate 50 mEq IV — only if concurrent metabolic acidosis. Limited K⁺-lowering effect alone.
Remove K⁺ from body (hours):
- Furosemide (Lasix) 40–80mg IV — if any residual kidney function.
- Patiromer (Veltassa) 8.4g PO or sodium zirconium (Lokelma) 10g PO — newer K⁺ binders. Onset hours. Better tolerated than kayexalate.
- Hemodialysis — definitive treatment for severe/refractory hyperkalemia or anuric patients.
Fix the cause: Hold lisinopril + spironolactone. Recheck K⁺ in 2h.
Stop the Source
- Hold offending medications: ACEi/ARB, spironolactone, trimethoprim, NSAIDs, K⁺-sparing diuretics
- Stop all IV potassium (check infusions, TPN, LR has 4 mEq/L K⁺)
- Low-K⁺ diet if chronic
- Treat underlying
cause: DKA → insulin, rhabdomyolysis → IVF, tumor lysis → rasburicase, adrenal🧪 WorkupWorkup
- ECG — first test
- Repeat K⁺ — rule out hemolysis
- BMP
- Med review — ACEi, ARB, spironolactone, TMP-SMX
- CK — rhabdomyolysis
- LDH, UA, PO₄ — TLS
crisis → stress dose steroids💊 MedicationsMedicationsDrug Dose Route Notes Ca gluconate 1g IV/5min IV Stabilize. Does NOT lower K⁺. Insulin 10U+D50 IV Best shifter. Check glucose 1h. Albuterol 10-20mg neb Neb Additive with insulin Patiromer (Veltassa) 8.4g daily PO GI elimination (preferred). Onset 4–7h. SZC (Lokelma) 10g PO × 3 doses PO GI elimination. Faster onset (~1h). Preferred in acute setting. Kayexalate (SPS) 15-30g PO GI elimination (outdated — prefer patiromer or Lokelma. Risk of intestinal necrosis.)
📊 Monitoring
Monitoring
- ECG after each intervention
- K⁺ at 1h and 2h
- Glucose at 1h post-insulin
- Continuous telemetry if >6.5
- UOP
📋 On Rounds
Pimp Questions
Does calcium gluconate lower potassium?
No. Calcium stabilizes the cardiac membrane by raising the threshold potential — it makes the heart less susceptible to arrhythmia. It does NOT move K⁺ at all. It buys you time (30–60 min) while insulin/glucose and other therapies take effect. That's why you always follow calcium with insulin/glucose.
Why do you need to check glucose after giving insulin for hyperkalemia?
Hypoglycemia occurs in 10–75% of patients treated with insulin for hyperkalemia (higher than most realize). The D50 wears off before the insulin does. Check glucose at 1 hour and 2 hours minimum. Many institutions now use D10 infusion running alongside insulin instead of a single D50 bolus to prevent delayed hypoglycemia.
What's the dose of nebulized albuterol for hyperkalemia?
10–20 mg — that's 4 to 8 times the standard 2.5 mg asthma dose. This is the most commonly underdosed hyperkalemia treatment. At high doses, β₂-mediated Na⁺/K⁺-ATPase activation shifts K⁺ into cells, dropping serum K⁺ by 0.5–1.0 mEq/L. Side effect: tachycardia. Use cautiously with cardiac patients.
What is the onset and duration of each hyperkalemia treatment, and why does the order matter?
(1) Calcium (membrane stabilization): onset 1-3 min, duration 30-60 min. Give first if ECG changes — protects the heart immediately but does NOT lower K⁺. (2) Insulin 10 units + D50 (shift): onset 15-30 min, duration 4-6h. Most reliable K⁺ shifter — lowers K⁺ by 0.5-1.2 mEq/L. Always give D50 concurrently (even if glucose is high — insulin-induced hypoglycemia is the #1 complication). (3) Albuterol 10-20 mg continuous neb (shift): onset 15-30 min, duration 2-4h. Additive with insulin — lowers K⁺ by 0.5-1.0. (4) Sodium bicarbonate (shift): only effective if acidotic (pH < 7.2). Minimal effect in non-acidotic patients. (5) Kayexalate/patiromer (elimination): onset hours, works in gut. (6) Dialysis (elimination): most definitive, onset immediate during session. Order: stabilize → shift → eliminate.
📣 Sample Presentation
One-Liner
"Mr. Russo is a 74-year-old with CKD4 on lisinopril and spironolactone presenting with weakness. K⁺ 7.1. ECG shows peaked T waves and widened QRS."
Key Points to Cover on Rounds
K⁺ 7.1 with ECG changes — emergent management initiated. Calcium gluconate 1g IV (membrane stabilization) → QRS narrowed within 3 min. Insulin 10 units IV + D50 (shift). Albuterol 10 mg continuous neb (shift). Kayexalate 30g PO (elimination). Repeat K⁺ at 1h: 6.2, at 2h: 5.8, ECG normalized. Offending agents: lisinopril and spironolactone held. Nephrology consulted — not meeting urgent dialysis criteria. Plan: serial K⁺ q4h, renally dose medications, nephrology to reassess RAAS inhibitor safety.
⚡ Summary
Summary
ECG Changes
Peaked T waves → flattened P → widened QRS → sine wave → VF/asystole. ECG changes ≠ K⁺ level (treat ECG, not number).
Stabilize
Calcium gluconate 1g IV (onset 1-3 min, duration 30-60 min). Protects myocardium. Does NOT lower K⁺.
Shift K⁺
Insulin 10 units + D50 (best shifter, onset 15-30 min). Albuterol 10-20 mg neb (additive). Bicarb only if pH < 7.2.
Eliminate K⁺
Patiromer/Lokelma (gut, hours — avoid kayexalate). Furosemide (renal, if UOP). Dialysis (definitive, immediate clearance during session).
Common Causes
RAAS inhibitors (ACEi/ARB + spironolactone), CKD, rhabdomyolysis, tumor lysis, acidosis, tissue necrosis, hemolysis.
Pseudo-hyperK
Hemolyzed sample (#1 cause), prolonged tourniquet, fist clenching, extreme leukocytosis/thrombocytosis. Recheck before treating.
📄 One Pager
Nephrology / Emergency · One Pager
Hyperkalemia
ECG changes → calcium gluconate first (stabilize). Then shift (insulin + D50 + albuterol). Then eliminate (patiromer/Lokelma, diuretics, dialysis).
ECG Progression
Peaked T → flattened P → widened QRS → sine wave → VF/asystole. Treat ECG changes, not the K⁺ number. ECG changes can occur at any level.
Stepwise Treatment
(1) Calcium gluconate 1g IV (stabilize, onset 1-3 min). (2) Insulin 10U + D50 (shift, onset 15-30 min). (3) Albuterol 10-20 mg neb (shift, additive). (4) Patiromer/Lokelma (eliminate, hours — preferred over kayexalate). (5) Dialysis (definitive).
Common Causes
RAAS inhibitors (ACEi + spironolactone), CKD, rhabdomyolysis, tumor lysis, acidosis, hemolysis, tissue necrosis. Always check for pseudo-hyperK (hemolyzed sample).
Key Drugs
Calcium gluconate1g IV over 5 min
Regular insulin10 units IV + D50
Albuterol10-20 mg continuous neb
Kayexalate15-30g PO
Pitfalls
- Insulin without D50 (hypoglycemia)
- Not checking ECG
- Not holding offending meds (ACEi, spironolactone, TMP-SMX)
- Treating hemolyzed sample
Alcohol Withdrawal & DTs
GABA receptor downregulation from chronic alcohol use → unopposed excitatory state on cessation. Withdrawal seizures kill. DTs have 15–20% mortality if untreated. Recognize early, treat aggressively.
🔍 Overview
Timeline of Withdrawal
| Time After Last Drink | Syndrome | Features |
|---|---|---|
| 6–12 hours | Minor withdrawal | Tremor, anxiety, insomnia, nausea, tachycardia, hypertension, diaphoresis |
| 12–24 hours | Alcoholic hallucinosis | Visual/auditory/tactile hallucinations with intact sensorium (patient knows they're hallucinating). Not DTs. |
| 12–48 hours | Withdrawal seizures | Generalized tonic-clonic. Brief, self-limited. Risk of status epilepticus. Peak at 24h. Treat with benzodiazepines, NOT phenytoin (phenytoin doesn't work for withdrawal seizures). |
| 48–96 hours | Delirium tremens (DTs) | Altered sensorium (confusion, agitation, global disorientation) + autonomic instability (fever, tachycardia, HTN, diaphoresis) + hallucinations. Mortality 15–20% if untreated. |
DTs ≠ hallucinations. Alcoholic hallucinosis has intact sensorium. DTs have global confusion + autonomic storm. This is the key distinction.
🚨 Management
CIWA-Ar Protocol (Symptom-Triggered)
Score 0–67. Assess q1–4h depending on severity. Symptom-triggered dosing reduces total benzo dose and ICU stay vs fixed-schedule dosing Saitz, 1994.
| CIWA Score | Severity | Action |
|---|---|---|
| < 8 | Minimal | Monitor q4–8h. Supportive care. Thiamine, folate, banana bag. |
| 8–15 | Mild-moderate | Lorazepam 1–2 mg PO/IV q1h PRN. Reassess in 1h. |
| 16–20 | Moderate-severe | Lorazepam 2–4 mg IV q1h. Consider ICU admission. |
| > 20 | Severe / impending DTs | ICU. Lorazepam 4 mg IV q15–30 min until controlled. Consider phenobarbital. Load aggressively. |
Treatment Agents
| Drug (Brand) | Dose | Role | Key Notes |
|---|---|---|---|
| Lorazepam (Ativan) 1ST LINE | 1–4 mg IV q1h PRN (CIWA-guided) | First-line benzodiazepine. | No active metabolites (preferred in liver disease over diazepam). Propylene glycol toxicity with prolonged high-dose infusion. |
| Diazepam (Valium) 1ST LINE | 5–20 mg IV/PO q1h PRN | Alternative to lorazepam. Long-acting. | Active metabolites (accumulate in liver failure). Longer duration = smoother withdrawal. Often preferred for outpatient tapers. |
| Chlordiazepoxide (Librium) MILD-MODERATE | 25–100 mg PO q6h, taper over 3–5 days | Mild-moderate withdrawal (CIWA < 15). Oral only. | Long half-life (24–48h) with active metabolites → built-in self-taper, smoother withdrawal. No IV formulation — cannot use in severe withdrawal, NPO, or vomiting. Avoid in liver disease (active metabolites accumulate — use lorazepam instead). Ideal for low-risk floor patients on a fixed taper protocol. |
| Phenobarbital SEVERE / REFRACTORY | Load: 130–260 mg IV q15–30 min until controlled (total 10–20 mg/kg). Maintenance: 32–65 mg IV q6–8h. | Growing first-line role in severe AWS. Reduces total benzo need and ICU stay. | GABA-A agonist at different site than benzos — synergistic. Long half-life (80–120h) → self-tapering. Monitor for respiratory depression. Evidence growing that front-loaded phenobarbital outperforms escalating benzos Gold, 2007. |
| Dexmedetomidine (Precedex) ADJUNCT | 0.2–1.5 mcg/kg/hr IV | Adjunct only — NOT a standalone. | Reduces autonomic symptoms (tachycardia, HTN, agitation). Does NOT prevent seizures or DTs — always co-administer with a GABA agonist (benzo or phenobarbital). |
| Thiamine (Vitamin B1) GIVE FIRST | 500 mg IV TID × 3 days (high-dose Caine protocol if Wernicke suspected) or 100 mg IV daily minimum | Give BEFORE any glucose. | Glucose metabolism depletes thiamine → precipitates Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia). Give thiamine to ALL alcohol withdrawal patients. |
Phenytoin does NOT work for alcohol withdrawal seizures. The mechanism is GABA-related, not sodium channel. Benzos and phenobarbital are the only effective agents. Do not waste time loading phenytoin.
🔄 Updated Practice: Old teaching: phenytoin (Dilantin) prevents or treats alcohol withdrawal seizures. This is WRONG — phenytoin does NOT work for withdrawal seizures and should NOT be used. Benzodiazepines (lorazepam, diazepam) are the treatment. For benzo-resistant withdrawal, phenobarbital is the escalation agent (not phenytoin). Front-loaded phenobarbital protocols are increasingly used as first-line in some centers (Gold, 2007).
📋 Clinical Example — CIWA-Guided Benzodiazepine Protocol
Patient: 48M, daily vodka drinker (1 pint/day × 15 years), last drink 14 hours ago. Tremor, anxiety, tachycardia (HR 108), diaphoresis. CIWA score: 18.
| Time | CIWA | Action |
|---|---|---|
| Hour 0 | 18 (moderate-severe) | Lorazepam (Ativan) 2mg IV. Thiamine (Vitamin B1) 500mg IV (give BEFORE any glucose). Banana bag is NOT adequate thiamine — need 500mg IV. |
| Hour 1 | 16 | Lorazepam (Ativan) 2mg IV. Replete Mg (MgSO₄ 2g IV), K⁺, PO₄. |
| Hour 2 | 14 | Lorazepam (Ativan) 1mg IV. Reassess — trending down, good sign. |
| Hour 4 | 10 | Lorazepam (Ativan) 1mg IV. |
| Hour 6 | 7 | Hold. Below threshold. Monitor q2h. |
| Hour 12 | 5 | Continue monitoring. Total lorazepam = 6mg in first 6h. |
Red flags to escalate: CIWA > 20 despite treatment → increase frequency/dose → consider phenobarbital load (130–260mg IV q15–30min). Seizure → lorazepam 4mg IV STAT (NOT phenytoin — doesn't work for withdrawal seizures). Hallucinations with clear sensorium = alcoholic hallucinosis (not DTs). DTs = altered sensorium + autonomic storm → ICU + aggressive benzos/phenobarbital.
When to use Chlordiazepoxide (Librium) instead: CIWA < 15, able to take PO, no liver disease, low risk for DTs → fixed taper 25–100mg PO q6h over 3–5 days. Smoother withdrawal due to long half-life. Floor patients only.
🧪 Workup
Workup
- CIWA-Ar score
- CBC, BMP, Mg, PO₄
- LFTs, INR, albumin
- Lipase
- Blood alcohol level
- CT head if AMS/focal deficit/head injury
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Lorazepam | 1-4mg IV q1h PRN | IV | CIWA≥8. Preferred liver disease. |
| Diazepam | 10-20mg IV | IV | Long-acting. Caution liver. |
| Chlordiazepoxide (Librium) | 25-100mg PO q6h taper | PO only | Mild-mod (CIWA<15). No IV form. Avoid liver disease. |
| Phenobarbital | 130-260mg IV | IV | Benzo-resistant |
| Thiamine | 500mg IV×3d | IV | BEFORE glucose |
| MgSO₄ | 2-4g IV | IV | Replace aggressively |
📊 Monitoring
Monitoring
- CIWA q1-2h
- Vitals q1-4h
- Mg, K, PO₄ q12h
- Seizure precautions
- DT watch 48-72h
- Blood glucose
📋 On Rounds
Pimp Questions
What is the advantage of phenobarbital over benzodiazepines in severe AWS?
Phenobarbital acts at a different GABA-A binding site than benzodiazepines — it increases the duration of Cl⁻ channel opening (vs benzos which increase frequency). This provides more predictable, dose-dependent GABA agonism. Its 80–120h half-life creates a built-in self-taper. Front-loading phenobarbital reduces total benzo dose, ICU days, and intubation rates. The main risk is respiratory depression, especially when combined with benzos — requires close monitoring.
Why must you give thiamine before glucose?
Thiamine (B1) is a cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase — essential for aerobic glucose metabolism. Giving glucose to a thiamine-depleted patient shunts all remaining thiamine into metabolism, acutely precipitating Wernicke encephalopathy (confusion, ophthalmoplegia, ataxia). If Wernicke is untreated, it progresses to Korsakoff syndrome (irreversible anterograde amnesia, confabulation). Always thiamine first.
When should you use Chlordiazepoxide (Librium) vs Lorazepam (Ativan) in alcohol withdrawal?
Chlordiazepoxide (Librium) is ideal for mild-moderate withdrawal (CIWA < 15) in patients who can take oral meds and are NOT at high risk for DTs/seizures. Its long half-life (24–48h) with active metabolites provides a smoother, self-tapering withdrawal. However: (1) No IV formulation → can't use in severe withdrawal, NPO, or vomiting, (2) Active metabolites accumulate in liver disease → avoid, (3) Oral only = floor patients only. Lorazepam (Ativan) is preferred for severe withdrawal (CIWA ≥ 16), liver disease (no hepatic metabolism, no active metabolites), and ICU patients who need IV access. Bottom line: Librium = mild/mod, oral, floor, no liver disease. Ativan = severe, IV, ICU, liver disease.
What are the risk factors for developing delirium tremens?
DTs develop in only 3-5% of alcohol withdrawal — but carry 5-15% mortality if untreated. Risk factors: (1) Prior DTs (strongest predictor — 50% recurrence rate), (2) Prior withdrawal seizures, (3) Heavy daily alcohol use (> 8 drinks/day), (4) Prolonged drinking duration, (5) Concurrent illness (infection, surgery, trauma — any physiologic stress), (6) Older age, (7) Abnormal liver function, (8) High initial CIWA score (> 20). Timeline: DTs typically onset 48-72 hours after last drink (later than seizures which peak at 12-48h). Features: agitation, disorientation, hallucinations (visual — classically "bugs"), autonomic instability (tachycardia, fever, diaphoresis), tremor. Treatment: high-dose benzodiazepines (may need ICU for drip — midazolam or diazepam), phenobarbital for benzo-resistant cases, dexmedetomidine adjunct, ICU monitoring.
📣 Sample Presentation
One-Liner
"Mr. O'Brien is a 48-year-old with daily vodka use (1 pint/day × 20 years) who last drank 18 hours ago, presenting with tremor, tachycardia, diaphoresis, and mild agitation. CIWA score 22."
Key Points to Cover on Rounds
CIWA 22 (moderate-severe). Symptom-triggered benzodiazepine protocol: lorazepam 2 mg IV given × 3 in first 6 hours. CIWA trending 22→18→14. No seizure, no hallucinations. Thiamine 500 mg IV daily × 3 days, then 100 mg PO (given BEFORE glucose). Folate 1 mg, MVI. Electrolytes: Mg 1.2 (repleted), K 3.4 (repleted), PO₄ 2.0 (repleted). Total benzos in 24h: 14 mg lorazepam-equivalents. Plan: continue CIWA protocol, watch for DTs (peak risk 48-72h), SW and addiction medicine consulted.
⚡ Summary
Summary
Timeline
6-12h: tremor, anxiety, tachycardia. 12-24h: hallucinations. 12-48h: seizures (GTC, brief, self-limited). 48-72h: delirium tremens (5-15% mortality).
CIWA Protocol
Symptom-triggered benzodiazepines. CIWA ≥ 8 → treat. Lorazepam 1-2 mg IV q1h PRN (preferred in liver disease — no active metabolites).
Thiamine
500 mg IV × 3 days → 100 mg PO daily. Give BEFORE glucose. Prevents Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia).
DT Risk Factors
Prior DTs (#1), prior withdrawal seizures, heavy daily use, concurrent illness, older age, high initial CIWA.
Seizure Prophylaxis
Benzodiazepines (not phenytoin — phenytoin does NOT prevent alcohol withdrawal seizures). Lorazepam or diazepam.
Replete
Mg²⁺ (universally depleted), K⁺ (often low), PO₄, folate 1 mg daily, MVI. Banana bag is NOT adequate thiamine dosing.
📄 One Pager
Addiction / ICU · One Pager
Alcohol Withdrawal
CIWA-driven benzos. Thiamine 500mg IV BEFORE glucose × 3 days. Watch for DTs at 48-72h. Seizures at 12-48h. Replete Mg/K/PO₄.
Timeline
6-12h: tremor, anxiety, tachycardia. 12-24h: hallucinations. 12-48h: seizures (brief GTCs). 48-72h: delirium tremens (mortality 5-15% if untreated).
Management
CIWA protocol: symptom-triggered lorazepam 1-2 mg IV q1h PRN. Thiamine 500 mg IV × 3 days BEFORE glucose. Folate 1 mg, MVI. Replete Mg²⁺, K⁺, PO₄. Benzo-resistant → phenobarbital.
DT Risk Factors
Prior DTs (#1 predictor), prior withdrawal seizures, heavy daily use, concurrent illness, older age, high initial CIWA > 20. DTs peak at 48-72h.
Key Drugs
Lorazepam1-4 mg IV q1h PRN (CIWA ≥ 8)
Thiamine500 mg IV × 3d → 100 PO
Phenobarbital130-260 mg IV (benzo-resistant)
Diazepam10-20 mg IV (long-acting option)
Pitfalls
- Glucose before thiamine (precipitates Wernicke)
- Phenytoin for alcohol withdrawal seizures (doesn't work)
- Banana bag = inadequate thiamine (only 100 mg)
- Under-dosing benzos in DTs
Acute Pancreatitis
Inflammation of the pancreas — ranges from mild edematous disease (80%, self-limited) to severe necrotizing pancreatitis (20%, multiorgan failure, ICU mortality 15–30%). Aggressive early fluids + pain control + early feeding.
🔍 Overview
Diagnosis (Revised Atlanta — need 2 of 3)
- Abdominal pain consistent with pancreatitis (epigastric, radiating to back, worse supine)
- Lipase ≥ 3× upper limit of normal (more sensitive and specific than amylase)
- Imaging findings on CT/MRI/US (only needed if diagnosis unclear from above two)
Do NOT routinely CT on admission. CT is normal in 15–30% of early pancreatitis. Reserve CT for: diagnostic uncertainty, no improvement at 48–72h, or suspecting complications (necrosis, abscess, pseudocyst).
Etiology — "I GET SMASHED"
| Letter | Cause | % of Cases |
|---|---|---|
| I | Idiopathic | ~10–15% |
| G | Gallstones | ~40% (most common) |
| E | Ethanol | ~30% (2nd most common) |
| T | Trauma / tumor | ~2–5% |
| S | Steroids / scorpion stings | Rare |
| M | Mumps / autoimmune | Rare |
| A | Autoimmune (IgG4) | ~2% |
| S | Sphincter of Oddi dysfunction | Rare |
| H | Hyperlipidemia / Hypercalcemia / Hypothermia | TG > 1000 → ~5% |
| E | ERCP | ~5% post-ERCP |
| D | Drugs (azathioprine, valproic acid, didanosine, mesalamine) | ~2% |
Severity (Revised Atlanta Classification)
| Severity | Definition | Mortality |
|---|---|---|
| Mild (~80%) | No organ failure, no local complications | < 1% |
| Moderately severe (~15%) | Transient organ failure (< 48h) OR local complications (necrosis, pseudocyst, fluid collections) | ~5% |
| Severe (~5%) | Persistent organ failure > 48h (respiratory, renal, cardiovascular) | 15–30% |
BISAP score ≥ 3 within 24h predicts severe disease: BUN > 25, Impaired mental status, SIRS, Age > 60, Pleural effusion.
🚨 Management
Pillars of Management
1. Aggressive IVF
Lactated Ringer's preferred de-Madaria, 2018. Goal-directed: 1.5 mL/kg/hr initially, titrate to UOP ≥ 0.5 mL/kg/hr, HR < 120, MAP ≥ 65. Reassess at 6h — avoid over-resuscitation (worsens third-spacing, pulmonary edema). Recent data suggests moderate fluids are non-inferior WATERFALL, 2022: aggressive vs moderate fluids → moderate (1.5 mL/kg/hr) was non-inferior with fewer fluid complications.
2. Pain Control
Multimodal analgesia. Acetaminophen IV 1g q6h (scheduled) + fentanyl or hydromorphone IV PRN (morphine is acceptable — the "morphine causes sphincter of Oddi spasm" concern is not clinically significant). Ketorolac 15–30 mg IV q6h if no AKI. PCA if severe.
3. Early Feeding
Start oral diet within 24h if tolerated. Low-fat solid diet (not just clear liquids). Petrov, 2013: early feeding reduces infection, organ failure, and length of stay. NPO is outdated. If oral not tolerated → nasogastric or nasojejunal tube feeding preferred over TPN. TPN only if enteral feeding fails ≥ 5 days.
4. Antibiotics
NOT routine in acute pancreatitis — even if necrosis present. Prophylactic antibiotics for necrotizing pancreatitis do NOT reduce mortality or infection Dellinger, 2007. Only treat infected necrosis (confirmed by FNA with positive gram stain/culture, or gas on CT). Use carbapenems (meropenem) — best pancreatic penetration.
5. Gallstone Pancreatitis
ERCP within 24h ONLY if concurrent cholangitis (fever, jaundice, RUQ pain = Charcot's triad) or persistent biliary obstruction. Otherwise, cholecystectomy during same admission (before discharge) to prevent recurrence PONCHO, 2015.
🔄 Updated Practice: Several old practices have been abandoned: (1) Prophylactic antibiotics do NOT prevent infected necrosis — don't give them. (2) NPO until pain resolves and lipase normalizes is WRONG — start low-fat oral diet as soon as tolerated (early feeding shortens hospital stay). (3) Old teaching said "aggressive" IV fluids (250-500 mL/hr); WATERFALL 2022 showed aggressive LR did not improve outcomes and increased fluid overload. Use goal-directed fluid resuscitation instead (1.5 mL/kg/hr LR, targeting UOP ≥0.5 mL/kg/hr).
Complications
| Complication | Timing | Management |
|---|---|---|
| Acute peripancreatic fluid collection | < 4 weeks | Usually resolves spontaneously. No intervention unless infected. |
| Pancreatic pseudocyst | > 4 weeks, encapsulated | Drain if symptomatic (> 6 cm, infected, obstructing). EUS-guided drainage preferred. |
| Acute necrotic collection | < 4 weeks | Sterile → supportive. Infected → antibiotics + delayed drainage (wait ≥ 4 weeks if stable for walled-off necrosis to mature). |
| Walled-off necrosis (WON) | > 4 weeks, encapsulated | If infected: step-up approach — antibiotics → percutaneous/endoscopic drainage → surgical necrosectomy only if drainage fails PANTER, 2010. |
| Splenic vein thrombosis | Variable | Left-sided portal HTN → isolated gastric varices. Anticoagulation if symptomatic. Splenectomy if refractory GI bleeding. |
📋 Clinical Example — Acute Pancreatitis Severity Assessment
Patient: 52M heavy drinker, epigastric pain radiating to back × 12h, lipase 2,400 (>3× ULN), HR 105, Cr 1.8.
Initial management:
- Goal-directed IV LR at 1.5 mL/kg/hr (WATERFALL, 2022 — 'aggressive' fluid strategy did not improve outcomes and increased fluid overload. Use goal-directed approach: target UOP ≥ 0.5 mL/kg/hr, trending BUN and hematocrit). NOT NS — LR reduces SIRS in pancreatitis.
- NPO initially → start low-fat diet as soon as tolerated (early feeding improves outcomes — do NOT wait for pain to fully resolve or lipase to normalize).
- Pain: IV hydromorphone (Dilaudid) 0.5–1mg q3h PRN. Morphine is safe despite old myths about sphincter of Oddi spasm.
- NO prophylactic antibiotics (even in severe pancreatitis — doesn't prevent infected necrosis).
Severity assessment at 48h:
- BISAP score: BUN > 25 (+1), impaired mental status (+0), SIRS (+1), age > 60 (+0), pleural effusion (+0) = 2 → moderate risk.
- CT only if: not improving by day 3–5, or concern for complications (necrosis, pseudocyst, abscess). Do NOT CT on admission — necrosis takes 48–72h to develop.
Complications to watch: Necrotizing pancreatitis (infected necrosis → antibiotics + drainage), pseudocyst (>4 weeks), pancreatic abscess. Infected necrosis = carbapenems + IR/surgical drainage.
🧪 Workup
Workup
- Lipase >3× ULN
- BMP, CBC, LFTs, Ca²⁺
- RUQ US — ALL patients
- Triglycerides
- CRP at 48h
- MRCP if CBD dilated
- CT at 72h+ only if worsening
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| LR | 1.5mL/kg/hr | IV | Goal-directed hydration |
| Hydromorphone | 0.5-1mg q3-4h | IV | Multimodal pain |
| Ketorolac | 15-30mg q6h×5d | IV | NSAID adjunct |
| No prophylactic abx | — | — | Unless infected necrosis |
📊 Monitoring
Monitoring
- Lipase trend
- BMP q12-24h
- Ca²⁺ — hypoCa=severe
- UOP
- Oral intake tolerance
- CRP 48h
📋 On Rounds
Pimp Questions
When do you give antibiotics in acute pancreatitis?
Only for infected necrosis. Prophylactic antibiotics for necrotizing pancreatitis showed no benefit in multiple RCTs. Sterile necrosis is managed supportively. Suspect infection if: worsening at > 7–10 days, new fever/leukocytosis, gas in necrotic collection on CT. Confirm with FNA. Treat with meropenem (best penetration into pancreatic tissue).
Why LR over NS for pancreatitis resuscitation?
de-Madaria, 2018: LR reduced SIRS at 48h compared to NS. The mechanism: NS causes hyperchloremic metabolic acidosis (high chloride load), which may worsen pancreatic inflammation. LR is more physiologic (contains lactate buffer, less chloride). This is consistent with broader critical care data favoring balanced crystalloids SMART, 2018.
A patient has pancreatitis with TG level of 2,800 mg/dL. How does this change management?
Hypertriglyceridemia-induced pancreatitis (TG typically > 1,000 mg/dL). Management additions beyond standard care: (1) Insulin drip (regular insulin 0.1-0.3 units/kg/hr) — insulin activates lipoprotein lipase → rapidly clears triglycerides. Target TG < 500. Add dextrose to prevent hypoglycemia. (2) NPO strictly until TG < 500 (dietary fat would raise TG further). (3) Fibrate therapy (fenofibrate or gemfibrozil) once eating and TG stabilized — long-term prevention. (4) Consider plasmapheresis if TG > 5,000 or refractory to insulin (removes triglyceride-rich lipoproteins directly). (5) Eliminate secondary causes: alcohol, estrogen, tamoxifen, retinoids, protease inhibitors, uncontrolled diabetes. Long-term: very low-fat diet (< 20g fat/day), omega-3 fatty acids, fibrates, glycemic control.
When do you order MRCP vs ERCP in gallstone pancreatitis?
MRCP (magnetic resonance cholangiopancreatography): non-invasive imaging to evaluate the common bile duct for stones. Order when: labs suggest choledocholithiasis (elevated bilirubin, dilated CBD on US) but patient is stable and not cholangitic. MRCP visualizes stones without procedural risk. If MRCP shows CBD stone → ERCP for stone removal. If MRCP negative → cholecystectomy without ERCP. ERCP (endoscopic retrograde cholangiopancreatography): both diagnostic AND therapeutic — can remove CBD stones, place stents. Order urgently (within 24h) when: (1) Cholangitis (Charcot's triad: fever + jaundice + RUQ pain — or worse, Reynold's pentad adding AMS + hypotension), (2) Proven CBD stone with obstruction. Key: ERCP has complications (pancreatitis 3-5%, bleeding, perforation) — don't do it empirically if the CBD status is uncertain. MRCP first to confirm.
📣 Sample Presentation
One-Liner
"Mrs. Garcia is a 45-year-old presenting with severe epigastric pain radiating to the back × 12 hours after a fatty meal. Lipase 4,200. RUQ US shows gallstones with CBD dilation to 8 mm. BISAP score 1."
Key Points to Cover on Rounds
Acute gallstone pancreatitis. Lipase 4,200 (>3× ULN). BISAP 1 (low severity). Treatment: aggressive IVF with LR (initial bolus then 3 mL/kg/hr), pain control with hydromorphone 0.5 mg IV PRN. Diet: early oral feeding initiated (clear liquids, advancing as tolerated — don't keep NPO). RUQ US: gallstones, CBD 8 mm → MRCP ordered to evaluate for choledocholithiasis. If CBD stone confirmed → ERCP before cholecystectomy. Surgery consulted for cholecystectomy this admission. CRP trending for severity.
⚡ Summary
Summary
Diagnosis
2 of 3: (1) characteristic epigastric pain radiating to back, (2) lipase > 3× ULN, (3) imaging findings. Lipase is more specific than amylase.
Treatment
Aggressive IVF (LR, 3 mL/kg/hr initially), pain control, early oral feeding (don't keep NPO). No prophylactic antibiotics.
Severity
BISAP score, APACHE II, Ranson's at 48h. CT severity: Balthazar. Persistent organ failure (> 48h) = severe.
Etiology
Gallstones (#1, ~40%) → US + LFTs + MRCP. Alcohol (#2, ~30%). Hypertriglyceridemia (> 1000) → insulin drip. Drug-induced, ERCP, autoimmune.
Gallstone Panc
RUQ US → if stones + CBD dilated → MRCP or ERCP. Cholangitis → ERCP within 24h. Cholecystectomy this admission.
Complications
Necrotizing: CT at 72h+ if worsening. Walled-off necrosis: drain only if infected (gas on CT, +culture). Pseudocyst: observe unless symptomatic.
📄 One Pager
GI · One Pager
Acute Pancreatitis
2 of 3: epigastric pain + lipase > 3× + imaging findings. Aggressive IVF + pain control + early feeding. No prophylactic antibiotics. Cholecystectomy this admission if gallstone.
Diagnosis
2 of 3: (1) characteristic epigastric pain radiating to back, (2) lipase > 3× ULN, (3) imaging findings. Lipase preferred over amylase (more specific).
Management
Aggressive IVF (LR, 1.5 mL/kg/hr). Pain control (multimodal). Early oral feeding as tolerated (don't keep NPO). No prophylactic antibiotics. Monitor for organ failure.
Etiology Workup
Gallstones (#1): RUQ US + LFTs. Alcohol (#2). TG > 1000: insulin drip + fibrates. If unclear: MRCP, IgG4 (autoimmune), genetic testing. ERCP only if cholangitis.
Key Drugs
LR250-500 mL/hr initially
Hydromorphone0.5-1 mg IV PRN
APAP/ketorolacMultimodal adjuncts
Insulin dripIf TG-induced
Pitfalls
- Keeping patient NPO (early feeding is safe + beneficial)
- Prophylactic antibiotics (no benefit, promotes resistance)
- Missing gallstone as cause (US + LFTs in all patients)
- Not doing cholecystectomy this admission for gallstone pancreatitis
Acute Ischemic Stroke
Time is brain. Every minute of ischemia = ~1.9 million neurons lost. Know the tPA window, thrombectomy criteria, and BP targets cold. You will not have time to look them up mid-code stroke.
🔍 Overview
Time Windows
| Intervention | Window | Key Criteria | Trial |
|---|---|---|---|
| IV tPA (alteplase) 1ST LINE | ≤ 4.5 hours from last known well (LKW) | 0.9 mg/kg IV (max 90 mg). 10% bolus over 1 min, 90% infusion over 60 min. No anticoagulants or antiplatelets × 24h post. | NINDS, 1995 ECASS III, 2008 |
| IV tenecteplase EMERGING | ≤ 4.5 hours | 0.25 mg/kg IV bolus (single push — no infusion). Easier to administer than alteplase. | AcT, 2022: tenecteplase non-inferior to alteplase. Increasingly used as first-line. |
| Mechanical thrombectomy LVO | ≤ 24 hours (with perfusion imaging) | Large vessel occlusion (LVO): ICA, M1, M1-equivalent. NIHSS ≥ 6. ≤ 6h: CTA showing LVO is sufficient MR CLEAN, 2015 ESCAPE, 2015. 6–24h: requires perfusion mismatch on CT perfusion or MR-DWI DAWN, 2018 DEFUSE 3, 2018. | Multiple trials — NNT ~3–5 for LVO |
tPA and thrombectomy are NOT mutually exclusive. If LVO suspected → give tPA AND activate thrombectomy team simultaneously. Do not wait for tPA to work before calling interventional.
tPA Contraindications (Major)
- Active internal bleeding or bleeding diathesis
- Platelets < 100,000, INR > 1.7, aPTT > 40, PT > 15
- Recent surgery/trauma (within 14 days major, 3 months head)
- History of ICH
- BP > 185/110 despite treatment (must lower before tPA)
- Glucose < 50 (correct first — hypoglycemia mimics stroke)
- On DOACs within 48h (or anti-Xa > measurable level)
🚨 Management
Acute Stroke Protocol
0 min — Door
Activate stroke code. ABC. Finger stick glucose (correct if < 60). NIHSS score. Two large-bore IVs. Labs: CBC, BMP, coags, troponin, type & screen.
≤ 20 min — CT
Non-contrast CT head — rule out hemorrhage. CTA head and neck — identify LVO for thrombectomy. CT perfusion if 6–24h window.
≤ 45 min — tPA
If eligible: alteplase 0.9 mg/kg IV (max 90 mg) or tenecteplase 0.25 mg/kg bolus. Door-to-needle target < 60 min. Lower BP to < 185/110 before tPA (labetalol 10–20 mg IV or nicardipine drip).
Thrombectomy
If LVO on CTA → activate interventional neuroradiology. Do not delay tPA for thrombectomy. Give tPA, then go to angio suite. Door-to-puncture target < 90 min.
BP Targets
| Scenario | Target | Agents |
|---|---|---|
| Pre-tPA | < 185/110 | Labetalol 10–20 mg IV, nicardipine 5–15 mg/hr |
| Post-tPA (24h) | < 180/105 | Same agents. Avoid antiplatelets/anticoagulants × 24h. |
| No tPA given, not for thrombectomy | Permissive HTN < 220/120 | Only treat if > 220/120, end-organ damage, or aortic dissection. |
| Post-thrombectomy | < 140/90 (some use < 160/90) | Tighter control to prevent reperfusion hemorrhage. |
Permissive hypertension in stroke maintains perfusion through collaterals. Dropping BP too aggressively in the penumbra zone worsens ischemia. Only lower BP if giving tPA, > 220/120, or specific indications.
📋 Clinical Example — Acute Ischemic Stroke tPA Decision
Patient: 72M, last known well 2 hours ago, found with right-sided weakness and aphasia. NIHSS 14.
Time is brain — target door-to-needle ≤ 60 min:
- CT head STAT → no hemorrhage (hypodense changes may not appear for 6–12h — normal CT does NOT rule out stroke).
- Glucose: 142 (must be > 50 before tPA). BP: 186/98 (must be < 185/110 before tPA — give labetalol (Trandate) 10–20mg IV or nicardipine (Cardene) drip to lower).
- INR 1.1, platelets 188K → no contraindication.
tPA eligible? ✅ Onset < 4.5h, no hemorrhage on CT, no contraindications.
- Alteplase (Activase) 0.9 mg/kg (max 90 mg): 10% as IV bolus over 1 min → remaining 90% infused over 60 min.
- NO antiplatelet or anticoagulant for 24h after tPA. Repeat CT head at 24h before starting aspirin.
If onset 4.5–24h OR large vessel occlusion: Consider mechanical thrombectomy (endovascular clot retrieval). CTA/CTP to identify salvageable tissue. DAWN and DEFUSE-3 trials extended window to 24h for select patients.
Post-tPA monitoring: Neuro checks q15min × 2h, then q30min × 6h, then q1h × 16h. BP < 180/105 for 24h. Any neuro decline → STAT CT to rule out hemorrhagic transformation.
🔄 Updated Practice: Old teaching: tPA window is 3 hours, after that nothing can be done. Updated: tPA window extended to 4.5 hours (ECASS III, 2008). More importantly, mechanical thrombectomy for large vessel occlusion can be performed up to 24 hours after last known well if there is salvageable tissue on perfusion imaging (DAWN 2018, DEFUSE 3 2018). This was a paradigm shift — "time is brain" is now "physiology is brain." Perfusion mismatch, not just the clock, determines eligibility.
📋 On Rounds
Pimp Questions
What extended the thrombectomy window from 6h to 24h?
DAWN, 2018 and DEFUSE 3, 2018. Both showed that patients with clinical-imaging mismatch (large clinical deficit but small infarct core on perfusion imaging) benefit from thrombectomy up to 24h. DAWN used clinical-core mismatch; DEFUSE 3 used perfusion-core mismatch. The key concept: it's not about time — it's about salvageable penumbra.
Why check glucose before tPA?
Hypoglycemia is a stroke mimic — it can cause focal neurological deficits identical to stroke (hemiparesis, aphasia, altered consciousness). Giving tPA to a hypoglycemic patient exposes them to major bleeding risk for no benefit. A finger stick glucose takes 10 seconds and is the fastest way to rule out this mimic. Correct glucose < 60, then reassess symptoms before proceeding.
What is the extended window for thrombectomy and what imaging do you need?
Standard tPA window: 0-4.5 hours. Thrombectomy for LVO: up to 24 hours with favorable imaging. [DAWN, 2018: 6-24h window if clinical deficit is disproportionate to infarct size on perfusion imaging ("mismatch"). [DEFUSE-3, 2018: 6-16h window with perfusion mismatch. Imaging required for extended window: CTA (confirms LVO — M1 MCA, ICA, basilar) + CT perfusion or MRI DWI/perfusion (shows salvageable tissue = penumbra). Mismatch ratio ≥ 1.8 and ischemic core volume ≤ 70 mL. Key point: "time is brain" but "tissue is brain" too — a patient at 20 hours with a small core and large penumbra benefits more from thrombectomy than a patient at 3 hours with a completed infarct.
What are the absolute contraindications to tPA in acute ischemic stroke?
Absolute contraindications (within 4.5h window): (1) Active internal bleeding, (2) History of hemorrhagic stroke (any time), (3) Ischemic stroke or head trauma within 3 months, (4) Intracranial neoplasm, AVM, or aneurysm, (5) Known bleeding diathesis (platelets < 100K, INR > 1.7, aPTT elevated, on DOACs with last dose < 48h), (6) SBP > 185 or DBP > 110 that cannot be controlled, (7) Blood glucose < 50 (treat hypoglycemia first — it mimics stroke). Additional exclusions for 3-4.5h window: age > 80, NIHSS > 25, oral anticoagulant use, diabetes + prior stroke. Key point: these are guidelines, not absolute laws — discuss with neurology for borderline cases. The benefit of tPA diminishes with time (NNT = 4 at 1.5h, NNT = 14 at 4.5h). Door-to-needle target: ≤ 60 minutes.
📣 Sample Presentation
One-Liner
"Mrs. Taylor is a 73-year-old with Afib (not on anticoagulation) presenting with acute left-sided weakness and aphasia, NIHSS 18, last known well 2 hours ago. CT head negative for hemorrhage. CTA shows right MCA M1 occlusion."
Key Points to Cover on Rounds
Acute ischemic stroke, R MCA LVO. NIHSS 18. CT negative for hemorrhage. tPA 0.9 mg/kg administered at 2.5h from onset. Thrombectomy team activated — successful TIMI 2b recanalization. Post-procedure NIHSS 8 (improving). BP target <180/105 (post-tPA). Dysphagia screen: failed → NPO, NGT placed. Etiology: Afib (not anticoagulated — was never started). Plan: start apixaban once 24h imaging confirms no hemorrhagic conversion. PT/OT/SLP. Secondary prevention workup.
🧪 Workup
Workup — Hyperkalemia
Workup for Hyperkalemia: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Hyperkalemia
Medication details for Hyperkalemia are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Hyperkalemia
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
tPA Window
0-4.5h from last known well. Door-to-needle ≤ 60 min. 0.9 mg/kg (max 90 mg), 10% bolus → remainder over 1h.
Thrombectomy
LVO (M1, ICA, basilar) up to 24h with favorable perfusion imaging (mismatch) [DAWN, DEFUSE-3]. CTA confirms LVO. CT perfusion guides extended window.
BP Management
Pre-tPA: allow up to 220/120. If tPA → target < 185/110 before, < 180/105 after × 24h. Permissive hypertension maintains perfusion.
Secondary Prevention
Antiplatelet (ASA ± clopidogrel × 21 days for minor stroke [CHANCE, POINT]). Statin. Anticoagulation for AF (start after 24h imaging). Treat HTN, DM, smoking.
Dysphagia Screen
Before ANY oral intake. Failed → NPO, NGT for meds/nutrition. Aspiration pneumonia is a major cause of post-stroke mortality.
Rehab
PT/OT/SLP early. Stroke unit care reduces mortality. Discharge planning starts day 1.
📄 One Pager
One Pager — Hyperkalemia
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
HYPERKALEMIA — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Neurology · One Pager
Acute Ischemic Stroke
tPA within 4.5h. Thrombectomy for LVO up to 24h with mismatch imaging. Door-to-needle ≤ 60 min. Dysphagia screen before PO.
Diagnosis
Acute focal neurologic deficit. CT head to rule out hemorrhage. CTA for LVO. CT perfusion for extended window (mismatch). NIHSS for severity.
Treatment
tPA 0.9 mg/kg (max 90 mg) if 0-4.5h from last known well. LVO → thrombectomy up to 24h with favorable imaging [DAWN, DEFUSE-3]. BP < 185/110 before tPA, < 180/105 after.
Secondary Prevention
Antiplatelet: ASA ± clopidogrel × 21 days [CHANCE, POINT]. Statin: atorvastatin 80. AF → anticoag (start after 24h imaging confirms no hemorrhagic conversion). BP, DM, smoking management.
Key Drugs
Alteplase0.9 mg/kg (max 90 mg)
ASA325 mg (after 24h post-tPA)
Clopidogrel75 mg (dual antiplatelet × 21d)
Atorvastatin80 mg daily
Pitfalls
- Delaying tPA for detailed neuro exam (time is brain)
- Not checking glucose first (hypoglycemia mimics stroke)
- Not doing dysphagia screen before any PO intake
- Missing posterior circulation stroke (vertigo, ataxia, diplopia)
Acute Mesenteric Ischemia
Sudden interruption of blood flow to the intestines. "Pain out of proportion to exam" is the classic teaching. Mortality 60–80% if not caught early. Think it, CT it, call surgery.
🔍 Overview
Types
| Type | % of AMI | Mechanism | Key Clue |
|---|---|---|---|
| Arterial embolism (SMA) (~50%) | Most common | Embolus from heart (Afib, LV thrombus, valvular) lodges in SMA | Sudden onset severe pain. Afib is the #1 risk factor. Pain out of proportion to exam. |
| Arterial thrombosis (~25%) | Thrombosis at atherosclerotic plaque (usually SMA origin) | History of chronic mesenteric ischemia (postprandial pain, food fear, weight loss) → acute event. | |
| Mesenteric venous thrombosis (~10%) | SMV thrombosis → venous congestion → mucosal ischemia | More insidious onset (days). Risk: hypercoagulable states, portal HTN, recent surgery, OCP use. | |
| Non-occlusive (NOMI) (~15%) | Splanchnic vasoconstriction in low-flow states | ICU patients on vasopressors, post-cardiac surgery, hemodialysis, shock. No clot — vasospasm. |
Presentation
- "Pain out of proportion to exam" — severe abdominal pain with a soft, non-tender abdomen (early). The exam catches up later (peritonitis = bowel already dead).
- Nausea, vomiting, bloody diarrhea (late — mucosal sloughing)
- Elevated lactate (often markedly, > 4–5) — but normal lactate does NOT rule it out early
- Leukocytosis, metabolic acidosis, elevated LDH
- Risk factors: Afib, recent MI, CHF, PVD, vasopressor use, hypercoagulable state
By the time peritoneal signs develop, bowel is already necrotic. The window between "pain out of proportion" and dead bowel is hours. Have a low threshold for CT angiography in any patient with acute severe abdominal pain + Afib or risk factors.
Diagnosis
| Test | Findings |
|---|---|
| CT angiography (CTA) TEST OF CHOICE | Sensitivity > 95%. [ACG Guidelines, Defined 2005 Shows arterial/venous filling defects, bowel wall thickening, pneumatosis (gas in bowel wall = necrosis), portal venous gas, free fluid. |
| Lactate | Elevated (often > 4). But normal lactate does not exclude early AMI. Trend is more useful than single value. |
| Plain X-ray | Late findings: pneumatosis intestinalis, portal venous gas, free air (perforation). Normal X-ray does not rule out AMI. |
🚨 Management
Acute Management
Immediate
Aggressive fluid resuscitation (third-spacing is massive). Broad-spectrum antibiotics (piperacillin-tazobactam or meropenem — cover gut flora including anaerobes). Anticoagulation with heparin drip Acosta, 2014 (prevent clot propagation). NPO. NG tube if distended/vomiting.
Surgical consult
IMMEDIATE surgical consult — do not wait. If peritonitis, frank necrosis, or perforation → emergent laparotomy with resection of dead bowel. Second-look laparotomy at 24–48h is standard. Bala, 2017
Endovascular
If no peritonitis and arterial occlusion → consider catheter-directed thrombolysis or aspiration thrombectomy (interventional radiology). Most effective for SMA embolism without necrosis.
NOMI
Treat the underlying low-flow state. Optimize cardiac output, wean vasopressors if possible. Intra-arterial papaverine (vasodilator) into SMA via angiography. Avoid vasoconstrictors (pressors worsen splanchnic ischemia).
Mortality is determined by time to intervention. Pre-necrosis intervention → 30% mortality. Post-necrosis → 60–80%. T
he difference is measured in hours. If you're thinking about mesenteric ischemia, get the
CTA now — not after the morning labs come back.
🧪 Workup
Workup
- CTA abdomen/pelvis — sensitivity >95%
- Lactate — LATE marker
- CBC — leukocytosis
- BMP — acidosis, AKI
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Heparin | 80U/kg→18U/kg/hr | IV | All types |
| Pip-tazo | 4.5g q6h | IV | If peritonitis |
| IVF aggressive | NS/LR | IV | Third-spacing |
| Papaverine | 30-60mg/hr IA | IA | NOMI only |
📊 Monitoring
Monitoring
- Serial abdominal exams q2-4h
- Lactate q4-6h
- UOP
- Repeat CTA if change
📋 On Rounds
Pimp Questions
Why is "pain out of proportion to exam" the classic finding?
In early mesenteric ischemia, the visceral peritoneum is ischemic (causes severe, poorly localized pain) but the parietal peritoneum is not yet involved (no rebound/guarding). The pain is visceral — deep, severe, colicky — but the abdomen is soft and non-tender on exam. Once the bowel becomes necrotic and transmural inflammation reaches the parietal peritoneum → peritoneal signs appear. But at that point, the bowel is already dead and outcomes are much worse.
What is the most common cause of acute mesenteric ischemia?
SMA embolism (~50%), most commonly from cardiac source (Afib is the #1 risk factor, followed by LV thrombus post-MI, valvular disease). The embolus typically lodges 6–8 cm distal to the SMA origin (past the middle colic artery branch point), which is why the proximal jejunum is often spared but mid-gut is affected.
Why is the classic teaching 'pain out of proportion to exam' so important in mesenteric ischemia?
Because by the time peritoneal signs develop, the bowel is dead. Early mesenteric ischemia causes visceral pain (from bowel wall ischemia) but the peritoneum is not yet involved → the abdomen is soft with minimal tenderness on exam. This is the diagnostic window — the patient is screaming in pain but you can barely feel anything on exam. Once peritonitis develops (rigid abdomen, rebound, guarding) → transmural necrosis → perforation → mortality > 70% even with surgery. The clinical trap: physicians anchor on the benign exam and dismiss the pain, attributing it to functional causes. If you suspect mesenteric ischemia → CTA abdomen/pelvis immediately (sensitivity > 95%). Don't wait for lactate (a late marker — elevated lactate = tissue already dying). The mantra: severe abdominal pain + benign exam + risk factors (Afib, atherosclerosis, hypercoagulable state) = mesenteric ischemia until proven otherwise.
What are the different types of mesenteric ischemia and how do they differ?
(1) Arterial embolism (50%): sudden onset, Afib is the #1 risk factor. SMA is the most commonly affected vessel. CTA: abrupt cutoff of SMA. Treatment: surgical embolectomy or catheter-directed thrombolysis. (2) Arterial thrombosis (25%): gradual onset ("intestinal angina" — postprandial pain, food fear, weight loss preceding the acute event). CTA: chronically diseased vessel with acute occlusion. Treatment: surgical revascularization. (3) Mesenteric venous thrombosis (10%): subacute onset (days), associated with hypercoagulable states, portal hypertension, abdominal surgery. CTA: SMV thrombus. Treatment: anticoagulation (heparin → warfarin). Less likely to need surgery. (4) Non-occlusive mesenteric ischemia (NOMI) (15%): low-flow state (shock, pressors, cardiac surgery) → splanchnic vasoconstriction without actual vessel occlusion. CTA may be negative. Treatment: optimize hemodynamics, wean vasoconstrictors, papaverine infusion.
📣 Sample Presentation
One-Liner
"Mr. Ahmed is a 78-year-old with Afib on warfarin (subtherapeutic INR 1.4) presenting with severe acute abdominal pain out of proportion to exam. Lactate 6.8. CT angiography shows SMA embolism with jejunal ischemia."
Key Points to Cover on Rounds
Acute mesenteric ischemia — SMA embolism (likely cardiogenic from Afib). Lactate 6.8, WBC 22K. CT angiography: SMA cutoff at mid-vessel. No peritoneal signs yet (early presentation). Surgery emergently consulted — taken to OR for SMA embolectomy + bowel viability assessment. Heparin drip started. Broad-spectrum antibiotics (pip-tazo). Aggressive fluid resuscitation. Plan: OR → SMA embolectomy, possible bowel resection if non-viable, ICU post-op.
⚡ Summary
Summary
Classic Presentation
Severe abdominal pain OUT OF PROPORTION to exam. Elderly + Afib or atherosclerosis. Pain first, peritonitis late (= bowel death).
Imaging
CTA abdomen/pelvis (sensitivity > 95%). Don't wait for lactate — it's a LATE marker (elevated = tissue already dying).
Types
Arterial embolism (50%, sudden, Afib), arterial thrombosis (25%, gradual, prior angina), venous (10%, subacute, hypercoag), NOMI (15%, low-flow state).
Treatment
SMA embolism: embolectomy or catheter-directed lysis. SMA thrombosis: surgical revascularization. SMV thrombosis: anticoagulation. NOMI: optimize hemodynamics.
Surgery
Emergent if peritoneal signs, perforation, or worsening despite intervention. Second-look laparotomy at 24-48h to assess bowel viability.
Mortality
60-80% overall mortality. Key to survival: early diagnosis (before bowel infarction) + rapid intervention. "Think about it to diagnose it."
📄 One Pager
GI / Surgery · One Pager
Mesenteric Ischemia
Pain out of proportion to exam. CTA immediately. Don't wait for lactate (late marker). Surgical emergency if peritonitis. Mortality 60-80% if delayed.
Presentation
Severe acute abdominal pain OUT OF PROPORTION to physical exam. Elderly + Afib or atherosclerosis. Peritonitis = late sign = bowel already dead.
Management
CTA abdomen/pelvis immediately (sensitivity > 95%). SMA embolism → embolectomy. SMA thrombosis → revascularization. SMV thrombosis → anticoagulation. NOMI → optimize hemodynamics.
Types
Arterial embolism (50%, sudden, Afib). Arterial thrombosis (25%, gradual, prior intestinal angina). Venous (10%, subacute, hypercoagulable). NOMI (15%, low-flow state on pressors).
Key Drugs
HeparinAnticoag for all types
Broad-spectrum abxPip-tazo (if peritonitis)
PapaverineIntra-arterial (NOMI)
IVFAggressive resuscitation
Pitfalls
- Reassured by benign abdominal exam (early ischemia = soft abdomen + severe pain)
- Waiting for lactate to elevate (late marker)
- Not thinking about it (must suspect to diagnose)
- Delaying surgical consult
Pleural Effusion
Fluid in the pleural space. Step 1: transudative or exudative (Light's criteria). Step 2: if exudative, find the cause. Step 3: drain if needed. You will do thoracenteses — know Light's cold.
🔍 Overview
Light's Criteria — Exudate if ANY ONE Met
If any ONE of these three is positive → exudate. All three negative → transudate.
| Criterion | Exudate Cutoff |
|---|---|
| Pleural protein / Serum protein | > 0.5 |
| Pleural LDH / Serum LDH | > 0.6 |
| Pleural LDH | > 2/3 upper limit of normal for serum LDH |
Light's criteria misclassify ~25% of transudates as exudates (especially in HF patients on diuretics). If you suspect a transudative effusion misclassified as exudate → check serum-pleural albumin gradient. If > 1.2 g/dL → transudate despite Light's.
Common Causes
| Transudative | Exudative |
|---|---|
| CHF (most common overall) | Pneumonia / parapneumonic (most common exudate) |
| Hepatic hydrothorax (cirrhosis) | Malignancy (lung, breast, lymphoma) |
| Nephrotic syndrome | PE |
| Peritoneal dialysis | TB (lymphocyte-predominant, ADA > 40) |
| Hypothyroidism | Autoimmune (SLE, RA) |
| Pancreatitis (elevated amylase) | |
| Esophageal rupture (low pH, high amylase) |
Pleural Fluid Analysis — What to Send
| Always Send | If Indicated |
|---|---|
| Cell count with differential | Cytology (if malignancy suspected — send ≥ 60 mL) |
| Protein, LDH, glucose | ADA (adenosine deaminase) — TB (> 40 suggestive) |
| Gram stain, culture | Amylase — pancreatitis, esophageal rupture |
| pH | Triglycerides — chylothorax (> 110 mg/dL) |
| + serum protein, LDH, albumin (same day) | Hematocrit — hemothorax (pleural Hct > 50% of blood) |
🚨 Management
When to Tap
- New effusion of unknown etiology — diagnostic thoracentesis
- Clinically significant (dyspnea) — therapeutic thoracentesis (remove up to 1.5 L per session)
- Suspected empyema or complicated parapneumonic — emergent drainage
Do NOT tap if: bilateral symmetric effusions in a patient with clear CHF (treat the HF first — they'll resolve). Only tap if unilateral, asymmetric, febrile, or not responding to diuresis.
Complicated Parapneumonic / Empyema
| Category | Fluid Features | Management |
|---|---|---|
| Simple parapneumonic | Clear, pH > 7.2, glucose > 60, LDH < 1000, culture negative | Antibiotics alone. May not need drainage. |
| Complicated parapneumonic | pH < 7.2, glucose < 60, LDH > 1000, or positive gram stain/culture | Chest tube drainage + antibiotics. Consider tPA/DNase instillation MIST2, 2011. |
| Empyema | Frankly purulent fluid or positive culture | Chest tube drainage mandatory. If loculated or not draining → tPA/DNase or VATS. Prolonged antibiotics (3–6 weeks). |
Malignant Effusion
- Positive cytology or biopsy confirms malignancy
- Recurrent → indwelling pleural catheter (IPC) or talc pleurodesis
- Median survival with malignant effusion: 3–12 months (depends on primary cancer)
- IPC allows outpatient drainage, avoids repeated thoracenteses. Can achieve spontaneous pleurodesis in ~50%.
📋 On Rounds
Light's criteria classify a CHF patient's effusion as exudative. What do you do?
Light's criteria misclassify ~25% of transudates as exudates, especially in CHF patients on diuretics (diuresis concentrates pleural protein and LDH, pushing ratios above exudative cutoffs). Check the serum-pleural albumin gradient: if > 1.2 g/dL → the effusion is truly transudative despite meeting Light's criteria. Clinical context matters — bilateral effusions in a patient with known HF, JVD, and BNP of 2000 are transudative regardless of what Light's says.
What pleural fluid pH tells you and when it changes management?
pH < 7.2 in a parapneumonic effusion = complicated → needs chest tube. Low pH means bacteria are metabolizing glucose → producing CO₂ and lactic acid → acidifying the fluid. This also correlates with high LDH and low glucose. In empyema, pH can drop below 7.0. Important: collect pH in a heparinized blood gas syringe, not a regular tube. Also: low pH in a non-infected effusion → think malignancy, esophageal rupture, or rheumatoid pleurisy.
A pleural fluid has protein ratio 0.32, LDH ratio 0.58, and LDH 180 (ULN = 200). Transudate or exudate?
Exudate. Light's criteria require meeting any 1 of 3: (1) Fluid/serum protein ratio > 0.5 (this is 0.32 — NOT met), (2) Fluid/serum LDH ratio > 0.6 (this is 0.58 — NOT met), (3) Fluid LDH > 2/3 of serum ULN (2/3 × 200 = 133; fluid LDH is 180 — MET). One criterion positive = exudate. Common trap: Light's criteria misclassify ~25% of transudates as exudates (especially in diuresed CHF patients — diuretics concentrate the fluid). If you suspect a "false exudate" (clinical picture screams transudate but Light's says exudate), check serum-effusion albumin gradient: > 1.2 g/dL = transudate despite Light's criteria.
How do you manage a complicated parapneumonic effusion vs empyema?
Uncomplicated parapneumonic: fluid is free-flowing, pH > 7.2, glucose > 60, LDH < 1000, gram stain/culture negative. Treatment: antibiotics alone, no chest tube. Complicated parapneumonic: pH < 7.2, glucose < 60, LDH > 1000, or positive gram stain/culture — but no frank pus. Loculations may be present. Treatment: chest tube + antibiotics. Consider tPA/DNase instillation for loculated effusions [MIST2, 2011: combination tPA + DNase improved drainage and reduced surgical referral. Empyema: frank pus in the pleural space. Treatment: chest tube + antibiotics + surgical consult (VATS for debridement if tube drainage inadequate). Key: always send pH, glucose, LDH, gram stain, and culture on every parapneumonic effusion — these determine if a tube is needed.
📣 Sample Presentation
One-Liner
"Mr. Hernandez is a 68-year-old with CHF presenting with worsening dyspnea. CXR shows large left-sided pleural effusion. Thoracentesis: protein ratio 0.28, LDH ratio 0.32. Transudative by Light's criteria."
Key Points to Cover on Rounds
Large left pleural effusion — transudative (protein ratio 0.28, LDH ratio 0.32, LDH 108 — all below Light's cutoffs). Etiology: CHF (bilateral LE edema, elevated BNP 1,800, known HFrEF). 1.5L drained with symptomatic improvement. Fluid: clear, straw-colored. Cell count and cytology sent (expected benign). No further invasive workup needed for transudative effusion with clear etiology. Treatment: diuresis optimization (furosemide uptitrated). Plan: if recurrent despite optimal diuresis → consider tunneled pleural catheter. Not empyema, not malignant based on presentation.
🧪 Workup
Workup — Alcohol Withdrawal & DTs
Workup for Alcohol Withdrawal & DTs: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Alcohol Withdrawal & DTs
Medication details for Alcohol Withdrawal & DTs are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Alcohol Withdrawal & DTs
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Light's Criteria
Exudate if ANY 1: protein ratio > 0.5, LDH ratio > 0.6, fluid LDH > 2/3 serum ULN. Sensitive but misclassifies 25% of transudates (especially diuresed CHF).
Transudate
CHF (#1), cirrhosis, nephrotic. Treatment: treat underlying cause (diuresis for CHF). Thoracentesis for symptomatic relief.
Exudate Workup
Cell count + diff, gram stain + culture, glucose, pH, LDH, cytology. If lymphocytic: TB (ADA), malignancy. If PMN: parapneumonic, empyema.
Parapneumonic
Uncomplicated (pH > 7.2, glucose > 60): abx alone. Complicated (pH < 7.2, glucose < 60, positive culture): chest tube. Empyema (frank pus): tube + surgery.
Malignant
Cytology positive or pleural biopsy positive. Recurrent → tunneled pleural catheter (PleurX) or chemical pleurodesis (talc).
False Exudate
If clinical picture = transudate but Light's says exudate → check serum-effusion albumin gradient. > 1.2 g/dL = transudate (likely diuresed CHF).
📄 One Pager
One Pager — Alcohol Withdrawal & DTs
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
ALCOHOL WITHDRAWAL & DTS — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Pulmonology · One Pager
Pleural Effusion
Thoracentesis → Light's criteria → transudate (treat cause) or exudate (further workup). Parapneumonic: pH/glucose/LDH determine if chest tube needed.
Light's Criteria
Exudate if ANY 1: protein ratio > 0.5, LDH ratio > 0.6, fluid LDH > 2/3 serum ULN. Sensitive but 25% false-positive for transudates (diuresed CHF). Check albumin gradient if discordant.
Workup by Type
Transudate: CHF, cirrhosis, nephrotic → treat underlying cause. Exudate: send cell count, gram stain, culture, glucose, pH, LDH, cytology. Lymphocytic → TB (ADA), malignancy.
Parapneumonic Management
Uncomplicated (pH > 7.2, glc > 60): abx only. Complicated (pH < 7.2, glc < 60, +culture): chest tube + abx. Empyema (frank pus): chest tube + surgery consult. tPA/DNase for loculated effusions [MIST2, 2011].
Key Drugs
Diagnostic thoracentesisAll new effusions
Albumin gradientIf Light's doesn't match clinical picture
tPA + DNaseLoculated parapneumonic [MIST2
PleurX catheterRecurrent malignant effusion
Pitfalls
- Not doing thoracentesis on new effusion (it's the test)
- Missing false exudate in diuresed CHF (check albumin gradient)
- Not sending pH/glucose on parapneumonic effusion (determines tube need)
- Chest tube delay in empyema
Pneumonia
The most common reason for hospital admission. CAP vs HAP vs VAP — the classification drives empiric antibiotics. Risk-stratify with CURB-65 or PSI to determine inpatient vs outpatient. Get cultures before antibiotics in the right patients.
🔍 Overview
Classification
| Type | Definition | Common Organisms | Empiric Antibiotics |
|---|---|---|---|
| CAP (Community-acquired) | Acquired outside hospital, or < 48h after admission | S. pneumoniae (#1), H. influenzae, Mycoplasma, Chlamydophila, Legionella, respiratory viruses | Outpatient (healthy): Amoxicillin 1g TID Outpatient (comorbid): Amox-clav + azithromycin Inpatient: Ceftriaxone IV + azithromycin IV ICU: Same ± vanc/linezolid if MRSA risk (linezolid if severe) |
| HAP* (Hospital-acquired) *HAP = Hospital-Acquired Pneumonia (≥48h after admission) | ≥ 48h after admission, not intubated at time of infection | MRSA, Pseudomonas, Klebsiella, Acinetobacter, Enterobacter | Pip-tazo 4.5g q6h or cefepime 2g q8h + vancomycin or linezolid (MRSA; linezolid if severe) Meropenem if ESBL/MDR risk Pip-tazo if anaerobic concern (aspiration + abscess/empyema). Cefepime if no anaerobes — especially with vanc (↓ AKI) ACORN, 2024 |
| VAP* (Ventilator-associated) *VAP = Ventilator-Associated Pneumonia (≥48h after intubation) | ≥ 48h after intubation | Same as HAP + higher Pseudomonas and MDR organisms | Pip-tazo or cefepime or meropenem + vanc or linezolid (MRSA; linezolid if severe) ± double Pseudomonas coverage if MDR risk Pip-tazo if anaerobic risk (aspiration, abscess). Cefepime + vanc preferred (lower nephrotoxicity). Need cefepime + anaerobes → add metronidazole |
| Aspiration pneumonia | Witnessed or high-risk aspiration event (AMS, dysphagia, GERD). Classically RLL or posterior segments of upper lobes (gravity-dependent). | Same as CAP — S. pneumoniae, H. influenzae, S. aureus, Enterobacteriaceae. Anaerobes are NOT the primary cause (old teaching). Anaerobes only significant if: lung abscess, empyema, necrotizing PNA, or poor dentition + indolent course. | Acute: Treat like CAP (ceftriaxone + azithro) If abscess/empyema/necrotizing: ADD anaerobic coverage — amp-sulbactam 3g q6h or pip-tazo or metronidazole Chemical pneumonitis = NO abx |
⚠️ HCAP is no longer a recognized category (ATS/IDSA 2016 eliminated it).
Old teaching: Hospitalization within 90 days, nursing home residence, hemodialysis, or home wound care = "Healthcare-Associated Pneumonia" → treat like HAP with broad-spectrum antibiotics.
Current teaching: HCAP led to massive over-treatment — most of these patients had CAP organisms, not MDR bugs. Increased C. diff and worse outcomes. Now: classify as CAP and assess individual MDR risk factors (prior MRSA culture, prior Pseudomonas culture, IV antibiotics within 90 days, structural lung disease) to decide if broader coverage is needed.
Old teaching: Hospitalization within 90 days, nursing home residence, hemodialysis, or home wound care = "Healthcare-Associated Pneumonia" → treat like HAP with broad-spectrum antibiotics.
Current teaching: HCAP led to massive over-treatment — most of these patients had CAP organisms, not MDR bugs. Increased C. diff and worse outcomes. Now: classify as CAP and assess individual MDR risk factors (prior MRSA culture, prior Pseudomonas culture, IV antibiotics within 90 days, structural lung disease) to decide if broader coverage is needed.
What defines "severe" pneumonia? (ATS/IDSA 2019)
1 Major criterion = ICU: (1) Septic shock requiring vasopressors, (2) Mechanical ventilation.
≥ 3 Minor criteria = ICU: RR ≥ 30, PaO₂/FiO₂ ≤ 250, multilobar infiltrates, confusion, BUN ≥ 20, WBC < 4K, platelets < 100K, temp < 36°C, hypotension requiring aggressive fluids.
Severe pneumonia gets broader coverage — add vanc or linezolid (MRSA) ± anti-pseudomonal agent. Linezolid preferred over vanc in severe MRSA pneumonia due to superior lung penetration.
1 Major criterion = ICU: (1) Septic shock requiring vasopressors, (2) Mechanical ventilation.
≥ 3 Minor criteria = ICU: RR ≥ 30, PaO₂/FiO₂ ≤ 250, multilobar infiltrates, confusion, BUN ≥ 20, WBC < 4K, platelets < 100K, temp < 36°C, hypotension requiring aggressive fluids.
Severe pneumonia gets broader coverage — add vanc or linezolid (MRSA) ± anti-pseudomonal agent. Linezolid preferred over vanc in severe MRSA pneumonia due to superior lung penetration.
CURB-65 (CAP Severity)
| Criterion | 1 Point Each |
|---|---|
| C | Confusion (new AMS) |
| U | Urea (BUN) > 20 mg/dL |
| R | Respiratory rate ≥ 30 |
| B | Blood pressure: SBP < 90 or DBP ≤ 60 |
| 65 | Age ≥ 65 |
0–1: outpatient treatment. 2: consider admission (short stay). 3–5: admit, consider ICU if ≥ 4.
💊 Treatment
Empiric Antibiotics
| Setting | Regimen | Notes |
|---|---|---|
| CAP — Outpatient, no comorbidities | Amoxicillin (Amoxil) 1g TID 1ST LINE | Or doxycycline 100 mg BID. Or azithromycin 500 mg → 250 mg daily (only if local resistance < 25%). |
| CAP — Outpatient, with comorbidities | Amoxicillin-clavulanate 875 mg BID + azithromycin | Or respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) — monotherapy. |
| CAP — Inpatient (non-ICU) | Ceftriaxone 1–2g IV daily + azithromycin 500 mg IV daily STANDARD | Or respiratory FQ monotherapy. Duration: 5 days minimum Short-Course CAP Trial, 2016 — no benefit of longer courses if clinically stable at day 5. |
| CAP — ICU (severe) | Ceftriaxone (Rocephin) 2g IV + azithromycin (Zithromax) 500 mg IV | Add vancomycin or linezolid if MRSA risk factors (linezolid preferred if severe — superior lung penetration). Add piperacillin-tazobactam or cefepime if Pseudomonas risk. Always get blood cultures + sputum + Legionella/pneumococcal urine antigens. |
| HAP / VAP | Piperacillin-tazobactam (Zosyn) 4.5g IV q6h or cefepime 2g IV q8h or meropenem | Add vancomycin or linezolid for MRSA (linezolid if severe — superior lung penetration). Duration: 7 days ATS/IDSA HAP/VAP Guidelines, 2016. Shorter is better — reduces resistance. |
| Aspiration | Treat like CAP (ceftriaxone + azithro) | Anaerobes are NOT the primary cause — same organisms as CAP. Add anaerobic coverage (amp-sulbactam or pip-tazo) ONLY if: lung abscess, empyema, necrotizing PNA, or poor dentition + indolent course. Aspiration pneumonitis (chemical) = NO antibiotics. |
Pip-Tazo vs Cefepime — When to Use Which
💊 Piperacillin-Tazobactam (Zosyn)
Coverage: Pseudomonas + gram-negatives + anaerobes
- Aspiration with abscess/empyema/necrotizing PNA — anaerobic coverage built in
- Intra-abdominal co-infection suspected
- Poor dentition + indolent course (anaerobes likely)
- Post-obstructive pneumonia (distal to tumor)
- Mixed aerobic-anaerobic infection
⚠️ AKI risk with vancomycin: Pip-tazo + vanc has significantly higher AKI rates than cefepime + vanc ACORN, 2024 Pip-Tazo Nephrotoxicity Study, 2017. If using both, monitor Cr closely.
💊 Cefepime
Coverage: Pseudomonas + gram-negatives. NO anaerobic coverage.
- HAP/VAP without anaerobic concern — standard nosocomial pneumonia
- Preferred when combining with vancomycin — lower AKI risk ACORN, 2024
- Neutropenic fever (first-line IDSA, 2010)
- CKD/AKI patients on vancomycin — safer renal profile
- No suspected anaerobic infection
⚠️ Neurotoxicity: Cefepime can cause seizures and encephalopathy, especially in renal impairment. Dose-adjust for CrCl. Monitor mental status.
Bottom line: Use pip-tazo when you need anaerobic coverage (aspiration with abscess/empyema, intra-abdominal source, necrotizing infection). Use cefepime when you don't need anaerobes — especially when pairing with vancomycin (lower nephrotoxicity). If you need cefepime + anaerobic coverage, add metronidazole 500 mg IV q8h separately.
MRSA risk factors: prior MRSA isolation, IV drug use, hospitalization within 90 days, hemodialysis, nursing home/LTAC residence. Pseudomonas risk: structural lung disease (bronchiectasis, CF), IV antibiotics within 90 days, prior Pseudomonas culture, immunosuppression.
🔄 Updated Practice: Old teaching: all "healthcare-associated" patients need MRSA coverage. HCAP was eliminated from 2019 ATS/IDSA guidelines because it led to massive overtreatment. Instead, get a nasal MRSA PCR swab — negative result has ~95% negative predictive value for MRSA pneumonia and can safely guide de-escalation.
Linezolid vs Vancomycin — Quick Decision Guide
Both cover MRSA, but they're NOT interchangeable. For MRSA pneumonia specifically, linezolid may be superior due to lung penetration. Know when to pick each.
| Feature | Vancomycin | Linezolid (Zyvox) |
|---|---|---|
| Route | IV only (PO only for C. diff) | IV and PO (100% PO bioavailability) |
| MOA | Cell wall inhibitor — binds D-Ala-D-Ala, blocks peptidoglycan cross-linking. Bactericidal (slowly). | 50S ribosome inhibitor — blocks 70S initiation complex → stops protein synthesis. Bacteriostatic. Also a weak MAOi (→ serotonin syndrome risk). |
| VRE | ✗ No | ✓ Yes |
| Lung penetration | Poor (~25%) | Excellent (~100%) — key advantage in pneumonia |
| Renal dosing | Yes — trough/AUC monitoring required | No adjustment needed |
| Max duration | No hard limit | ≤ 14 days (thrombocytopenia risk) |
| Key toxicity | Nephrotoxicity, Red Man Syndrome, ototoxicity | Thrombocytopenia (> 14d), serotonin syndrome (MAOi), lactic acidosis, peripheral neuropathy (may be irreversible), optic neuritis (> 28d), myelosuppression |
🏆 Vancomycin Wins
- MRSA bacteremia / endocarditis
- Osteomyelitis (long-duration OK)
- Default empiric MRSA coverage
- Patient on SSRIs (serotonin risk with linezolid)
🏆 Linezolid Wins
- MRSA pneumonia (superior lung penetration) ZEPHyR, 2012
- VRE infections
- CKD / AKI (no renal adjustment)
- No IV access / outpatient Tx (PO = IV)
🧫 Toxin Suppression — Linezolid & Clindamycin: Both inhibit the 50S ribosome → suppress bacterial toxin production. Critical in: necrotizing fasciitis (GAS exotoxins), toxic shock syndrome (TSST-1), PVL-producing MRSA. Vancomycin kills the bug but does NOT stop toxin release. In toxin-mediated disease, always add a protein synthesis inhibitor (clindamycin or linezolid).
⚠️ Linezolid Side Effects to Know: Thrombocytopenia (> 14d — CBC twice weekly), lactic acidosis (weekly lactate if prolonged), peripheral neuropathy & optic neuritis (> 28d — may be irreversible), serotonin syndrome (weak MAOi — avoid with SSRIs/SNRIs/tramadol). If on SSRI → use vancomycin. Never use daptomycin for pneumonia — pulmonary surfactant inactivates it.
📋 Clinical Example — CAP Severity & Antibiotic Choice
Patient: 55M, cough with yellow sputum × 5 days, fever 38.9°C, RR 22, SpO₂ 94% on RA, CXR: RLL consolidation.
Severity — CURB-65: Confusion (0), Urea > 7 mmol/L (0), RR ≥ 30 (0), BP < 90 systolic (0), Age ≥ 65 (0) = Score 0 → outpatient treatment appropriate.
But: SpO₂ 94% borderline + looks unwell → admit for observation.
Inpatient non-ICU CAP:
- Ceftriaxone (Rocephin) 1g IV daily + azithromycin (Zithromax) 500mg IV/PO daily
- OR levofloxacin (Levaquin) 750mg PO/IV daily (respiratory fluoroquinolone monotherapy — reserve for PCN allergy or failure of beta-lactam)
When to add MRSA coverage (vanc or linezolid): Prior MRSA infection/colonization, cavitary infiltrate, empyema, recent influenza, or severe necrotizing pneumonia. Get nasal MRSA swab — negative PCR has ~95% NPV for MRSA pneumonia → can safely withhold MRSA coverage.
Duration: 5 days total if afebrile ≥ 48h and ≤ 1 sign of clinical instability (CAP-START trial). No need for 7–14 days.
IV → PO switch: Once afebrile, tolerating PO, and clinically improving → switch to oral and discharge. Do not keep patients NPO or on IV abx waiting for "completion of course."
🔄 Updated Practice: Old teaching: treat CAP for 7–14 days. Current evidence: 5 days is sufficient if patient is afebrile ≥48h and has ≤1 sign of clinical instability. Some data supports even 3 days in select patients. Longer courses increase C. difficile risk, resistance, and side effects without improving cure rates.
📋 On Rounds
Can you use 5 days of antibiotics for CAP?
Yes. Short-Course CAP Trial, 2016 and ATS/IDSA 2019 guidelines recommend minimum 5 days of antibiotics for CAP, with discontinuation once the patient is clinically stable for 48h (afebrile, HR < 100, RR < 24, SBP > 90, SpO₂ > 90%, able to eat, normal mentation). Longer courses do not improve outcomes and increase antibiotic resistance, C. diff risk, and adverse effects. The old "7–14 day" dogma is outdated.
When do you get blood cultures in pneumonia?
Not for all CAP. ATS/IDSA 2019 recommends cultures for: severe CAP (ICU admission), empiric MRSA or Pseudomonas coverage, prior positive cultures for these organisms, recent hospitalization + IV antibiotics within 90 days. Routine blood cultures in non-severe CAP have < 5% positivity rate and rarely change management. For HAP/VAP: always get blood cultures + respiratory cultures (sputum, endotracheal aspirate, or BAL) before starting antibiotics.
When should you add MRSA coverage (vancomycin or linezolid) to CAP treatment?
MRSA coverage is NOT routine for CAP — add only with specific risk factors: (1) Prior MRSA isolation (respiratory culture, nasal swab), (2) Cavitary infiltrate or necrotizing pneumonia on imaging, (3) Concurrent influenza (post-influenza MRSA pneumonia is classic and rapidly fatal), (4) Severe pneumonia requiring ICU admission + risk factors. MRSA nasal swab (PCR) has high negative predictive value (> 95%) — if negative, you can safely de-escalate vancomycin. This is one of the best antibiotic stewardship tools. If adding MRSA coverage: vancomycin (target AUC/MIC 400–600) or linezolid 600 mg BID (better lung penetration, no renal toxicity, but risk of thrombocytopenia and serotonin syndrome with SSRIs). De-escalate at 48-72h based on cultures and MRSA nasal swab.
HAP/VAP: when do you choose pip-tazo over cefepime?
Choose pip-tazo when you need anaerobic coverage — aspiration with lung abscess, empyema, necrotizing pneumonia, poor dentition with indolent course, or suspected intra-abdominal co-infection. Pip-tazo covers Pseudomonas + gram-negatives + anaerobes. Cefepime covers Pseudomonas + gram-negatives but has NO anaerobic activity. However: if combining with vancomycin for MRSA coverage, prefer cefepime — pip-tazo + vancomycin significantly increases AKI risk [ACORN, 2024 [Pip-Tazo Nephrotoxicity Study, 2017. If you need both cefepime AND anaerobic coverage, add metronidazole 500 mg IV q8h separately.
What are the criteria for severe CAP requiring ICU admission?
ATS/IDSA 2019 criteria: 1 major criterion = ICU: (1) septic shock requiring vasopressors, (2) mechanical ventilation. ≥ 3 minor criteria = ICU: RR ≥ 30, PaO₂/FiO₂ ≤ 250, multilobar infiltrates, confusion, BUN ≥ 20, WBC < 4K, platelets < 100K, temperature < 36°C, hypotension requiring aggressive fluid resuscitation. Why it matters: severe CAP gets broader empiric coverage — ceftriaxone + azithromycin + vancomycin (if MRSA risk) vs non-severe which just gets ceftriaxone + azithromycin. Also: don't use CURB-65 alone for ICU decisions — it underestimates severity in young patients (age is a major component).
📣 Sample Presentation
One-Liner
"Mrs. Evans is a 72-year-old with COPD presenting with 3 days of productive cough, fever 38.6°C, and dyspnea. CXR: right lower lobe consolidation. WBC 16K, procalcitonin 2.8. CURB-65 score 2 (age + BUN 24). Admitted for CAP."
Key Points to Cover on Rounds
CAP — CURB-65 2 (inpatient). Antibiotics: ceftriaxone 1g IV daily + azithromycin 500 mg IV daily (standard non-ICU inpatient regimen). Blood cultures × 2 drawn (before abx). Sputum culture sent. O₂: 3L NC (SpO₂ 93%). Procalcitonin 2.8 (supports bacterial etiology). No MRSA risk factors — vancomycin not added. Influenza/COVID tested (negative). Response at 48h: afebrile, WBC trending 16→12. Plan: step down to PO (levofloxacin or amox-clav + azithro) when tolerating PO + afebrile ×24h. Total duration: 5 days if stable ×48h [Short-Course CAP Trial, 2016]. Follow-up CXR in 6-8 weeks (rule out underlying mass).
🧪 Workup
Workup — Pneumonia
- History: Cough (productive vs dry), fever/chills, dyspnea, pleuritic chest pain, sick contacts, travel, immunosuppression, recent hospitalization/abx (within 90 days)
- Physical exam: Tachypnea, crackles/bronchial breath sounds, dullness to percussion, egophony, tactile fremitus
- Labs: CBC, BMP, procalcitonin (guides abx duration), lactate if sepsis concern, blood cultures ×2 (before abx in severe/ICU), sputum culture + Gram stain
- Imaging: CXR PA + lateral (infiltrate, consolidation, effusion). CT chest if CXR equivocal or complications suspected
- Urine antigens: Legionella (serogroup 1) + S. pneumoniae — order in ICU-level or severe CAP
- MRSA nasal swab: NPV > 95% — if negative, can safely de-escalate vanc/linezolid
- Procalcitonin: < 0.25 → bacterial unlikely. Serial levels guide antibiotic de-escalation (drop > 80% from peak → safe to stop)
Do NOT delay antibiotics for cultures. In sepsis, every hour of delay increases mortality. Draw cultures → give abx immediately.
💊 Medications
Medications — Pneumonia
Full antibiotic regimens are in the Treatment tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Pneumonia
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Afebrile ×48h = clinical improvement. Persistent fever > 72h → re-evaluate (empyema? wrong bug? wrong abx?) |
| O₂ sat / SpO₂ | Continuous if on O₂ | Target ≥ 92% (88–92% if COPD with CO₂ retention) |
| Procalcitonin | q48–72h | Drop > 80% from peak or < 0.25 → safe to stop abx |
| Repeat CXR | Only if worsening | Do NOT repeat daily. Follow-up CXR at 6–8 weeks (rule out underlying malignancy in smokers, age > 50) |
| Clinical response | Each assessment | Improving cough, appetite, ambulation? If no improvement at 48–72h → broaden coverage, consider CT, bronch |
⚡ Summary
Summary
Outpatient CAP
Healthy: amoxicillin 1g TID × 5 days. Comorbidities: amox-clav + azithromycin, or respiratory FQ (levofloxacin). Avoid FQ for uncomplicated.
Inpatient (non-ICU)
Ceftriaxone 1g IV + azithromycin 500 IV. Alternative: respiratory FQ monotherapy (levofloxacin 750 daily).
ICU CAP
Ceftriaxone + azithromycin + vancomycin (if MRSA risk). MRSA nasal swab: negative = de-escalate vanc (NPV > 95%).
Duration
5 days if: afebrile ≥ 48h, improving, no more than 1 instability criterion [Short-Course CAP Trial, 2016]. Don't treat longer just because CXR hasn't cleared.
Follow-Up CXR
6-8 weeks post-treatment (rule out underlying malignancy, especially if smoker, age > 50, or slow to resolve).
Aspiration
Chemical pneumonitis (sterile) = NO abx. Bacterial aspiration PNA = treat like CAP (ceftriaxone + azithro). Anaerobes are NOT the primary cause. Add anaerobic coverage (amp-sulbactam, pip-tazo) ONLY if abscess, empyema, or necrotizing PNA.
📄 One Pager
Pulmonology / ID · One Pager
Community-Acquired Pneumonia
Outpatient: amoxicillin (healthy) or amox-clav + azithro (comorbidities). Inpatient: ceftriaxone + azithromycin. ICU: add vanc if MRSA risk. Duration: 5 days if stable × 48h.
Severity
CURB-65: Confusion, Urea > 20, RR ≥ 30, BP < 90/60, age ≥ 65. 0-1: outpatient. 2: admit. ≥ 3: ICU consideration. ATS/IDSA: 1 major criterion or ≥ 3 minor = ICU.
Empiric Treatment
Outpatient (healthy): amoxicillin 1g TID × 5d. Outpatient (comorbid): amox-clav + azithro or respiratory FQ. Inpatient (non-ICU): ceftriaxone + azithromycin. ICU: ceftriaxone + azithro ± vancomycin if MRSA risk.
Key Principles
Duration: 5 days if afebrile ≥ 48h + improving [Short-Course CAP Trial, 2016]. MRSA nasal swab: negative NPV > 95% → de-escalate vancomycin. Follow-up CXR at 6-8 weeks (rule out mass, especially smoker > 50).
Key Drugs
Ceftriaxone1g IV daily
Azithromycin500 mg IV/PO daily
Amoxicillin1g TID (outpatient)
Vancomycin15-20 mg/kg (MRSA risk)
Pitfalls
- Treating > 5 days without indication (short course is standard)
- FQ for uncomplicated outpatient CAP (reserve for comorbidities)
- Not getting follow-up CXR at 6-8 weeks in smokers
- Forgetting atypical coverage (azithromycin) for inpatient CAP
Pulmonary Nodule & Lung Cancer Screening
Incidental pulmonary nodules are found on ~30% of chest CTs. Most are benign. The key is risk-stratifying: size, morphology, growth, and patient risk factors determine surveillance vs biopsy vs resection.
🔍 Nodule Workup
Fleischner Society Guidelines (2017) — Solid Nodules
| Size | Low Risk (< 5% malignancy) | High Risk (≥ 5% malignancy) |
|---|---|---|
| < 6 mm | No follow-up needed | Optional CT at 12 months |
| 6–8 mm | CT at 6–12 months, then consider CT at 18–24 months | CT at 6–12 months, then CT at 18–24 months |
| > 8 mm | CT at 3 months, PET-CT, or tissue sampling depending on clinical probability | |
High-Risk Features
- Patient: smoking history, older age, family history of lung cancer, prior cancer, occupational exposures
- Nodule: upper lobe location, spiculated margins, growth on serial imaging, part-solid morphology, > 8 mm
Ground-Glass and Part-Solid Nodules (GGN/PSN)
- Pure ground-glass < 6 mm: no follow-up
- Pure ground-glass ≥ 6 mm: CT at 6–12 months, then q2 years × 5 years
- Part-solid (mixed) ≥ 6 mm: CT at 3–6 months. If solid component ≥ 6 mm and persists → PET or biopsy. Part-solid nodules have the highest malignancy rate of any morphology.
Stability for 2 years on serial CT does NOT guarantee benignity for ground-glass nodules — GGNs (often adenocarcinoma in situ) can be indolent for years before becoming invasive. Follow for 5 years minimum.
🔬 Lung Cancer Screening
LDCT Screening Criteria (USPSTF 2021)
- Age 50–80 years
- ≥ 20 pack-year smoking history
- Currently smoke or quit within the past 15 years
- Annual low-dose CT (LDCT) — no IV contrast
NLST, 2011: LDCT screening reduced lung cancer mortality by 20% vs chest X-ray. NELSON, 2020: confirmed 24% reduction in lung cancer mortality in men, 33% in women.
Shared decision-making required. Discuss benefits (mortality reduction), harms (false positives, radiation, anxiety, unnecessary procedures), and the importance of smoking cessation (which reduces mortality far more than screening).
📋 On Rounds
Which nodule morphology has the highest malignancy rate?
Part-solid (mixed ground-glass and solid) nodules. They have a malignancy rate up to ~60% if they persist — higher than either pure solid or pure ground-glass nodules. The solid component usually represents the invasive component of an adenocarcinoma, while the ground-glass component represents in situ or minimally invasive disease. That's why Fleischner recommends earlier and more aggressive follow-up for part-solid nodules compared to solid nodules of the same size.
When do you get a PET-CT for a pulmonary nodule vs just follow-up CT?
PET-CT is indicated for solid nodules ≥ 8 mm with intermediate probability of malignancy (5–65% based on clinical risk). PET has ~90% sensitivity for malignancy but false negatives occur with: (1) nodules < 8 mm (below PET resolution), (2) GGOs/lepidic adenocarcinoma (low metabolic activity), (3) carcinoid tumors. False positives occur with: infection (TB granulomas, fungal), inflammation, sarcoidosis. For pure GGOs, PET is not helpful — follow with CT surveillance per Fleischner. For part-solid nodules, PET can help if the solid component is ≥ 8 mm. Part-solid nodules have the highest malignancy rate of any morphology and deserve the most aggressive follow-up.
What makes a pulmonary nodule more likely to be malignant?
Higher risk features: (1) Size: > 8 mm (malignancy risk increases exponentially with size — 6 mm = 1%, 20 mm = 15-20%), (2) Morphology: part-solid (HIGHEST malignancy rate of any type), spiculated margins, irregular shape, (3) Location: upper lobe (lung cancer more common), (4) Growth: any growth on serial imaging is concerning (doubling time 20-400 days for malignancy vs > 400 for benign), (5) Patient factors: current/former smoker, age > 50, FH lung cancer, COPD, asbestos/radon exposure. Lower risk: smooth, round, calcified (especially central, popcorn, or laminar calcification = benign), ground-glass (if pure GGO, lower risk than solid or part-solid), stable ≥ 2 years (for solid nodules). Part-solid nodules with solid component > 5 mm need the most aggressive follow-up — don't be falsely reassured by small overall size.
How do you counsel a patient about an incidental pulmonary nodule?
This is a common and anxiety-provoking conversation. Key points: (1) Most nodules are benign — even in smokers, a 6 mm nodule has only ~1% chance of malignancy. Explain this clearly. (2) Follow-up is about tracking change — "we're watching to see if it grows. If it stays the same size over 2 years, it's almost certainly not cancer." (3) Specific follow-up plan with dates — "you'll need a repeat CT scan in [3/6/12] months. I'm ordering it now." Don't leave it vague. (4) Document the nodule and follow-up plan in the chart — incidental findings that are lost to follow-up are a major source of malpractice liability. (5) If high-risk features → PET-CT or biopsy discussion: explain the options clearly. (6) Quit smoking if applicable — this is a powerful teachable moment.
📣 Sample Presentation
One-Liner
"Ms. Kim is a 55-year-old smoker whose CT chest for cough incidentally found a 12 mm solid right upper lobe pulmonary nodule. No prior imaging for comparison."
Key Points to Cover on Rounds
Incidental 12 mm solid RUL nodule in a smoker — intermediate-to-high malignancy risk. Per Fleischner: solid nodule ≥8 mm → consider CT at 3 months, PET-CT, or tissue sampling depending on clinical probability. Given risk factors (smoker, upper lobe, >8 mm): PET-CT ordered. If PET avid → CT-guided biopsy or surgical excision. If PET negative → CT follow-up at 3, 6, 12, 24 months. Lung-Rads if found on screening LDCT. Patient counseled about findings and follow-up plan documented. Smoking cessation strongly reinforced. Pulmonology referral placed.
🧪 Workup
Workup — Acute Ischemic Stroke
Workup for Acute Ischemic Stroke: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Acute Ischemic Stroke
Medication details for Acute Ischemic Stroke are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Acute Ischemic Stroke
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Fleischner
Solid nodule ≥ 8mm → CT at 3 months, PET-CT, or biopsy based on risk. < 6mm in low-risk: no follow-up. Part-solid: longer follow-up, lower threshold for biopsy.
High-Risk Features
Size > 8mm, upper lobe, spiculated, part-solid, growing, smoker, age > 50, FH lung cancer.
PET-CT
For solid nodules ≥ 8mm with intermediate probability of malignancy. PET avid → biopsy or resect. PET negative → follow with serial CT.
Part-Solid
Highest malignancy rate of any nodule type. GGO component may represent lepidic adenocarcinoma. Longer follow-up (5 years). Low threshold for biopsy if solid component > 5mm.
Document Everything
Incidental nodules lost to follow-up = major malpractice risk. Document finding, risk assessment, specific follow-up plan with date, and communicate to patient.
Lung-Rads
Used for LDCT screening findings (different from Fleischner which is for incidental nodules). Categories 1-4 guide follow-up intervals.
📄 One Pager
One Pager — Acute Ischemic Stroke
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
ACUTE ISCHEMIC STROKE — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🔍 Overview
Overview — Pulmonary Nodule & Lung Cancer Screening
See the tabs above for the complete clinical reference: Workup, Management, Medications, Monitoring, Rounds, Summary, and One Pager.
⚡ Management
Management — Pulmonary Nodule & Lung Cancer Screening
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
📄 One Pager
Pulmonology · One Pager
Pulmonary Nodule
Fleischner guidelines for incidental nodules. High-risk features: > 8mm, upper lobe, spiculated, part-solid, smoker. PET-CT for intermediate probability. DOCUMENT and follow up.
Risk Assessment
Size (> 8mm), morphology (part-solid = highest malignancy rate, spiculated), location (upper lobe), patient factors (smoker, age > 50, FH lung cancer, COPD).
Fleischner Guidelines
< 6mm solid + low risk: no follow-up. ≥ 6-8mm: CT at 6-12 months. ≥ 8mm: CT at 3 months, PET-CT, or biopsy based on probability. Part-solid: longer follow-up, lower threshold for intervention.
Key Principles
PET-CT for solid nodules ≥ 8mm with intermediate probability. Biopsy (CT-guided or surgical) if PET-avid or high clinical suspicion. DOCUMENT the finding, plan, and communicate to patient. Lung-Rads for LDCT screening nodules.
Key Drugs
CT follow-upPer Fleischner timing
PET-CTIntermediate probability, ≥ 8mm
BiopsyPET-avid or high suspicion
LDCT screeningPer Lung-Rads classification
Pitfalls
- Lost to follow-up (major malpractice risk — document and schedule)
- Part-solid nodules dismissed as benign (highest malignancy rate)
- Not considering malignancy in smoker > 50 with new nodule
- Fleischner applied to screening LDCT (use Lung-Rads instead)
PFT Interpretation
Pulmonary function tests — spirometry, lung volumes, and DLCO. A systematic approach: (1) FEV₁/FVC ratio, (2) lung volumes, (3) DLCO. This tells you obstructive vs restrictive vs mixed, and narrows the differential.
🔍 Systematic Interpretation
Step 1 — FEV₁/FVC Ratio
| FEV₁/FVC | Pattern | Examples |
|---|---|---|
| < 0.70 (or < LLN) | Obstructive GOLD Criteria, 2024 | COPD, asthma, bronchiectasis, bronchiolitis obliterans |
| Normal or ↑ | Restrictive (if TLC reduced) | ILD (IPF, sarcoidosis), chest wall disease, neuromuscular (ALS, myasthenia), obesity |
| ↓ with ↓ TLC | Mixed | Combined COPD + ILD, sarcoidosis |
Low FVC with normal FEV₁/FVC does NOT confirm restriction. Air trapping in obstruction can reduce FVC, making the ratio look normal. You need lung volumes (TLC) to confirm restriction. TLC < 80% predicted = true restriction.
Step 2 — Bronchodilator Response
- Positive response: FEV₁ or FVC improves ≥ 12% AND ≥ 200 mL after albuterol ATS/ERS Spirometry Standardization, 2005
- Positive → suggests asthma (reversible obstruction)
- Negative → suggests COPD (fixed obstruction), but some COPD patients have partial reversibility
Step 3 — DLCO (Diffusion Capacity)
| DLCO | Pattern | Think |
|---|---|---|
| Low DLCO + Obstruction | Emphysema (parenchymal destruction) | COPD (emphysema phenotype). Asthma has NORMAL DLCO — key differentiator. |
| Low DLCO + Restriction | Interstitial lung disease | IPF, sarcoidosis, hypersensitivity pneumonitis, drug-induced ILD |
| Low DLCO + Normal spirometry | Pulmonary vascular disease | Pulmonary hypertension, PE, early ILD |
| Normal/↑ DLCO + Restriction | Extrapulmonary restriction | Obesity, neuromuscular disease, chest wall deformity (lungs are normal) |
| ↑ DLCO | Increased pulmonary blood flow | Diffuse alveolar hemorrhage, polycythemia, L-to-R shunt, asthma, obesity |
Lung Volumes Summary
| Volume | Obstructive | Restrictive |
|---|---|---|
| TLC | ↑ or normal (hyperinflation, air trapping) | ↓ (< 80% predicted) |
| RV | ↑↑ (air trapping) | ↓ or normal |
| RV/TLC ratio | ↑ | Normal or ↓ |
| FRC | ↑ | ↓ |
🧪 Workup
Workup
- Spirometry — FEV₁, FVC, ratio
- Lung volumes — TLC (confirm restriction)
- DLCO — low=emphysema/ILD; normal=asthma
- Bronchodilator response
- Methacholine challenge
- Flow-volume loop
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Albuterol neb | 2.5mg | Neb | Reversibility testing |
| PFTs are diagnostic | not therapeutic | — | — |
📊 Monitoring
Monitoring
- PFTs q6-12mo
- FVC decline >5-10%/yr in ILD → escalate
- DLCO <40% → O₂+transplant eval
- 6MWT
📋 On Rounds
How do you distinguish asthma from COPD on PFTs?
Both are obstructive (FEV₁/FVC < 0.70). Key differences: (1) Bronchodilator response: asthma shows significant reversibility (≥ 12% + 200 mL), COPD has minimal reversibility. (2) DLCO: asthma has normal or increased DLCO, emphysema has decreased DLCO (alveolar destruction). (3) Methacholine challenge: positive in asthma (bronchial hyperresponsiveness), negative in COPD. (4) Between-test variability: asthma PFTs fluctuate significantly; COPD is relatively stable.
A patient has low DLCO with normal spirometry. What's your differential?
Pulmonary vascular disease is the classic answer: pulmonary hypertension, chronic PE, or pulmonary arteriovenous malformations — the vascular bed is compromised but the airways and parenchyma are intact, so spirometry is normal. Also consider early ILD (DLCO can drop before spirometry becomes restrictive — it's the most sensitive PFT marker for early parenchymal disease), anemia (less hemoglobin to bind CO during the test), and prior lung resection.
How do you differentiate asthma from COPD on PFTs?
Both show obstruction (FEV₁/FVC < 0.70). The key differentiator: bronchodilator reversibility. Asthma: FEV₁ improves ≥ 12% AND ≥ 200 mL after bronchodilator (significant reversibility — airway obstruction is dynamic). COPD: FEV₁ improves < 12% or < 200 mL (fixed obstruction — structural airway damage). Other clues: DLCO: normal in asthma (parenchyma is fine), LOW in COPD/emphysema (alveolar destruction). Flow-volume loop: asthma may normalize between attacks; COPD shows persistent concavity (scooped-out expiratory limb). Overlap syndrome (ACO): features of both — persistent obstruction + significant reversibility + eosinophilia. Treat with ICS (like asthma) + bronchodilators (like COPD). Lung volumes: hyperinflation (↑ TLC, ↑ RV) more prominent in COPD/emphysema.
What does a low DLCO tell you, and what conditions have normal DLCO?
Low DLCO (reduced gas transfer across the alveolar membrane): (1) Emphysema — destroyed alveoli → reduced surface area for gas exchange. (2) ILD/pulmonary fibrosis — thickened interstitium → diffusion barrier. (3) Pulmonary hypertension — vascular bed destruction. (4) Anemia — less hemoglobin to bind CO (correct DLCO for Hgb). (5) Pulmonary embolism — dead space. Normal DLCO despite obstruction: Asthma — the airways are narrowed but the parenchyma is intact. Elevated DLCO: (1) Pulmonary hemorrhage (blood in alveoli absorbs CO), (2) Polycythemia (more Hgb), (3) Asthma (increased pulmonary blood volume from air trapping), (4) Left-to-right shunt (increased pulmonary blood flow). Clinical pearl: DLCO is the best PFT for differentiating asthma (normal DLCO) from emphysema (low DLCO) when both show obstruction.
📣 Sample Presentation
One-Liner
"Mr. Johnson is a 62-year-old with 40-pack-year smoking history referred for PFTs. Results: FEV₁ 48% predicted, FVC 82%, FEV₁/FVC 0.58, DLCO 55%. Post-bronchodilator FEV₁ improvement: 8% and 120 mL."
Key Points to Cover on Rounds
Obstructive pattern (FEV₁/FVC 0.58, <0.70). GOLD classification: FEV₁ 48% = GOLD stage III (severe). Bronchodilator response: 8% and 120 mL (negative — doesn't meet 12% AND 200 mL threshold for significant reversibility → supports COPD over asthma). DLCO 55% (low — suggests emphysema component). Correlation: CT chest shows upper lobe centrilobular emphysema. Current treatment: LAMA only. Recommended: add ICS/LABA (triple therapy if exacerbation history). Pulmonary rehab referral. Reassess for LTOT if SpO₂ <88% at rest or exertion. Annual PFTs to track decline.
⚡ Summary
Summary
Obstructive
FEV₁/FVC < 0.70. COPD (fixed) vs asthma (reversible: ≥ 12% AND ≥ 200 mL improvement post-bronchodilator).
Restrictive
FEV₁/FVC normal or elevated. TLC reduced (requires lung volumes). ILD, obesity, neuromuscular disease, chest wall deformity.
DLCO
Low: emphysema, ILD, pulmonary HTN, anemia, PE. Normal despite obstruction: asthma (parenchyma intact). Elevated: pulmonary hemorrhage, polycythemia.
COPD Staging
GOLD: FEV₁ ≥ 80% (I/mild), 50-79% (II/moderate), 30-49% (III/severe), < 30% (IV/very severe). Combined with symptoms + exacerbation history for treatment. GOLD, 2024
Flow-Volume Loop
Upper airway obstruction: flattened inspiratory limb (variable extrathoracic) or flattened expiratory limb (variable intrathoracic) or both (fixed).
Bronchoprovocation
Methacholine challenge: fall in FEV₁ ≥ 20% = positive (hyperreactive airways = asthma). Used when PFTs are normal but asthma is clinically suspected.
⚡ Management
Management — PFT Interpretation
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
📄 One Pager
Pulmonology · One Pager
Pulmonary Function Tests
FEV₁/FVC < 0.70 = obstruction. Reversibility (≥ 12% + 200 mL) = asthma. Low DLCO = emphysema/ILD/pulm HTN (normal in asthma). TLC needed to confirm restriction.
Obstructive Pattern
FEV₁/FVC < 0.70. COPD: no significant reversibility, low DLCO. Asthma: significant reversibility (≥ 12% AND ≥ 200 mL), normal DLCO. COPD staging: GOLD I-IV by FEV₁ %.
Restrictive Pattern
FEV₁/FVC normal or elevated + reduced TLC (need lung volumes). Causes: ILD (low DLCO), neuromuscular (normal DLCO), obesity (normal DLCO), chest wall deformity.
DLCO Interpretation
Low: emphysema, ILD, pulmonary HTN, anemia, PE. Normal with obstruction: asthma. Elevated: pulmonary hemorrhage, polycythemia, left-to-right shunt. Best test to differentiate asthma from emphysema.
Key Drugs
Bronchodilator testAlbuterol → repeat spirometry
Methacholine challengeIf normal PFTs + suspected asthma
Lung volumesBody plethysmography for TLC
DLCOGas transfer assessment
Pitfalls
- Diagnosing restriction without lung volumes (need TLC)
- Missing asthma vs COPD distinction (reversibility + DLCO)
- Not correcting DLCO for anemia
- Ignoring the flow-volume loop (upper airway obstruction)
Pneumothorax
Air in the pleural space. Primary spontaneous (tall thin young male, no lung disease), secondary (COPD, CF), traumatic, or iatrogenic. Tension pneumothorax = clinical diagnosis → needle decompress, don't wait for CXR.
🔍 Overview
Types
| Type | Cause | Key Features |
|---|---|---|
| Primary spontaneous (PSP) | Rupture of apical bleb/bulla in otherwise healthy lung | Tall, thin, young male, smoker. Usually small. Low recurrence after first episode (~30%), high after second (~50%). |
| Secondary spontaneous (SSP) | Underlying lung disease (COPD, CF, Pneumocystis, ILD, LAM) | More dangerous — limited pulmonary reserve. Even small PTX can cause significant compromise. Lower threshold for intervention. |
| Traumatic | Blunt/penetrating chest trauma, rib fractures | Chest tube. Evaluate for hemothorax (check pleural Hct). |
| Iatrogenic | Central line (subclavian > IJ), thoracentesis, lung biopsy, positive pressure ventilation | Post-procedure CXR. Small iatrogenic PTX in stable patient → may observe. |
| Tension | One-way valve effect → progressive air trapping → mediastinal shift → ↓ venous return → hemodynamic collapse | CLINICAL DIAGNOSIS: hypotension + JVD + absent breath sounds + tracheal deviation away. Needle decompression BEFORE imaging. 14–16G needle, 2nd ICS, midclavicular line (or 5th ICS, anterior axillary line). |
🚨 Management
Management by Size and Type
| Scenario | Management |
|---|---|
| Small PSP (< 2 cm at apex), stable | Observation + high-flow O₂ (accelerates reabsorption 4×). Repeat CXR in 4–6h. Discharge if stable and improving. |
| Large PSP (≥ 2 cm) or symptomatic | Needle aspiration (14–16G, 2nd ICS) → recheck CXR. If re-expands → observe. If fails → chest tube. BTS Guidelines, 2023: aspiration first-line for PSP. |
| SSP — any size | Chest tube (14–28 Fr) connected to water seal or low suction (−20 cmH₂O). These patients have no reserve. Do NOT just observe SSP. |
| Tension PTX | Immediate needle decompression → chest tube. Do not wait for CXR. |
| Recurrent PSP (≥ 2 episodes ipsilateral) | VATS with pleurodesis (mechanical or chemical). Recurrence after first: ~30%. After VATS: < 5%. |
High-flow O₂ (15 L/min via non-rebreather) accelerates pneumothorax reabsorption by creating a nitrogen gradient — the pleural air (mostly N₂) is absorbed faster when alveolar N₂ is reduced. Speeds reabsorption from ~1.25%/day to ~5%/day.
📋 On Rounds
Why does high-flow O₂ speed pneumothorax reabsorption?
Pleural air is ~78% nitrogen. High-flow O₂ washes nitrogen out of the blood (by displacing it in the alveoli), creating a partial pressure gradient for N₂ between the pleural space and the capillary blood. This draws N₂ from the pleural collection into the bloodstream, where it's exhaled. The rate of reabsorption increases from ~1.25%/day to ~5%/day — approximately 4× faster. This is why even small pneumothoraces being observed benefit from supplemental O₂.
When does a pneumothorax require a chest tube vs observation?
Tension PTX → immediate needle decompression (14–16G needle, 2nd intercostal space midclavicular line) followed by chest tube. Large PTX (> 2–3 cm at apex) or symptomatic → chest tube (14–16 Fr pigtail for PSP, 24–28 Fr for traumatic/secondary). Small PTX (< 2 cm), asymptomatic, primary spontaneous → observe 3–6 hours with repeat CXR. If stable → discharge with 24–48h follow-up CXR. Secondary PTX (in COPD, ILD, CF) = more dangerous → lower threshold for chest tube even if small, because these patients have less pulmonary reserve. Aspiration (with small-bore catheter) is an alternative to chest tube for large primary spontaneous PTX — equivalent success with less pain.
What is tension pneumothorax and how do you treat it before imaging?
Tension PTX is a CLINICAL DIAGNOSIS — do NOT wait for imaging. Mechanism: one-way valve effect → air enters pleural space with each breath but can't exit → progressive pressure buildup → mediastinal shift → IVC compression → obstructive shock. Signs: severe dyspnea, tachycardia, hypotension, absent breath sounds on affected side, tracheal deviation AWAY from affected side (late sign), distended neck veins, subcutaneous emphysema. Treatment: immediate needle decompression — 14-16G needle, 2nd intercostal space midclavicular line (or 4th/5th ICS anterior axillary line — larger space, less risk of hitting vessels). You'll hear a rush of air. Follow with chest tube (this is the definitive treatment — the needle is a bridge). If you suspect tension PTX in a crashing patient, decompress first, diagnose second.
What is the Fleischner Society recommendation for incidentally detected pneumothorax?
Trick question — Fleischner is for pulmonary nodules, not pneumothorax. This is a common confusion. For pneumothorax management: BTS guidelines are the standard. Small primary spontaneous PTX (< 2 cm at hilum) + minimal symptoms → observation + supplemental O₂ + repeat CXR in 2-4h. If stable → discharge with 24-48h follow-up. Large (> 2 cm) or symptomatic → aspiration (with small-bore catheter) or chest tube. Secondary PTX (COPD, ILD, CF) → lower threshold for intervention (these patients can't tolerate any loss of lung function). All secondary PTX ≥ 1 cm or symptomatic → chest tube and admission. Recurrence prevention: after 2nd episode → VATS with pleurodesis (recurrence rate after 1st episode ~30%, after 2nd ~60%).
📣 Sample Presentation
One-Liner
"Mr. Scott is a 22-year-old tall, thin male presenting with sudden right-sided pleuritic chest pain and dyspnea. CXR shows 30% right pneumothorax. Hemodynamically stable. SpO₂ 97%."
Key Points to Cover on Rounds
Primary spontaneous pneumothorax — classic demographics (tall, thin, young male). Large (30% at apex), symptomatic. Treatment: 14 Fr pigtail chest tube placed under US guidance, connected to water seal. Post-procedure CXR: lung re-expanded, no residual PTX. Air leak: resolved by 12h. O₂ applied (accelerates pleural nitrogen reabsorption). Plan: chest tube to water seal ×12h → if no recurrence on CXR → remove and observe ×6h → discharge if stable. Recurrence counseling: 30% chance of recurrence. If 2nd episode → VATS with pleurodesis. Avoid flying ×2 weeks, avoid scuba diving permanently.
🧪 Workup
Workup — Acute Mesenteric Ischemia
Workup for Acute Mesenteric Ischemia: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Acute Mesenteric Ischemia
Medication details for Acute Mesenteric Ischemia are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Acute Mesenteric Ischemia
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Tension PTX
Clinical diagnosis — don't wait for imaging. Absent breath sounds, tracheal deviation, hypotension, JVD. Needle decompress immediately (2nd ICS MCL or 4th/5th ICS AAL).
Primary Spontaneous
Tall thin young male. Small (< 2cm) + minimal symptoms → observe + O₂ + repeat CXR. Large or symptomatic → aspiration or chest tube.
Secondary
COPD, ILD, CF, PCP. Lower threshold for intervention (these patients can't tolerate lung loss). All ≥ 1cm or symptomatic → chest tube + admit.
Chest Tube
14-28 Fr pigtail or surgical chest tube. Connect to water seal or suction. Post-procedure CXR. Remove when: no air leak + lung expanded on CXR × 12-24h.
Recurrence
30% after 1st episode, 60% after 2nd. After 2nd → VATS with pleurodesis (chemical or mechanical). Prevents recurrence.
Counseling
No flying × 2 weeks post-resolution. No scuba diving ever (unless pleurodesis performed). Return if sudden chest pain or dyspnea.
📄 One Pager
One Pager — Acute Mesenteric Ischemia
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
ACUTE MESENTERIC ISCHEMIA — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Pulmonology / Emergency · One Pager
Pneumothorax
Tension = clinical diagnosis → needle decompress immediately. Primary spontaneous: small → observe, large → aspiration/tube. Secondary: lower threshold for tube. Recurrence → VATS + pleurodesis.
Types
Primary spontaneous: tall thin young male, no lung disease. Secondary: COPD, ILD, CF, PCP (lower threshold for intervention — can't tolerate lung loss). Tension: one-way valve → obstructive shock.
Tension PTX — Don't Wait for Imaging
Absent breath sounds + tracheal deviation + hypotension + JVD. Needle decompress: 14-16G, 2nd ICS MCL or 4th/5th ICS AAL. Then chest tube. Clinical diagnosis — decompress first, image after.
Management
Small primary (<2cm) + minimal symptoms → observe + O₂ + repeat CXR. Large/symptomatic → aspiration or chest tube (14-28 Fr pigtail). Remove tube when: no air leak + expanded on CXR × 12-24h.
Key Drugs
Needle decompression14-16G, 2nd ICS MCL (tension)
Pigtail chest tube14 Fr (small catheter)
Supplemental O₂Accelerates reabsorption
Pain controlOpioids/NSAIDs as needed
Pitfalls
- Waiting for CXR in tension PTX (clinical diagnosis → decompress)
- Discharging without recurrence counseling (30% after 1st episode)
- Not admitting secondary PTX (these patients decompensate quickly)
- Flying within 2 weeks (risk of re-expansion)
Obstructive Sleep Apnea
Recurrent upper airway obstruction during sleep → intermittent hypoxia, sleep fragmentation, and systemic inflammation. Affects ~15–30% of adults. Strongly associated with HTN, Afib, HF, stroke, and perioperative complications.
🔍 Overview
Diagnosis
- Polysomnography (PSG) = gold standard. Measures AHI (apnea-hypopnea index).
- Home sleep apnea testing (HSAT) — acceptable for uncomplicated suspected OSA (no significant comorbidities). Underestimates AHI.
| AHI | Severity | Treatment |
|---|---|---|
| 5–14 | Mild | CPAP if symptomatic. Weight loss, positional therapy, oral appliance. |
| 15–29 | Moderate | CPAP recommended. Weight loss. |
| ≥ 30 | Severe | CPAP strongly recommended. Significant CV risk if untreated. |
Screening — STOP-BANG
| Letter | Question |
|---|---|
| S | Snoring loudly? |
| T | Tired / daytime sleepiness? |
| O | Observed apneas during sleep? |
| P | Pressure — treated for HTN? |
| B | BMI > 35? |
| A | Age > 50? |
| N | Neck circumference > 40 cm (16 in)? |
| G | Gender — male? |
≥ 3: high risk for OSA → formal sleep study. ≥ 5: high probability of moderate-severe OSA.
Cardiovascular Consequences
- Resistant hypertension — OSA is the #1 cause of resistant HTN. Screen all patients with HTN on ≥ 3 drugs.
- Atrial fibrillation — OSA increases Afib risk 2–4×. Untreated OSA increases Afib recurrence after cardioversion and ablation.
- Heart failure — intermittent hypoxia → increased afterload → RV/LV dysfunction
- Stroke — independent risk factor
- Pulmonary hypertension — chronic intermittent hypoxia → pulmonary vasoconstriction
OSA vs OHS (Obesity Hypoventilation Syndrome)
⚠️ Key distinction: If a patient has OSA + elevated daytime PaCO₂ (>45 mmHg), they have OHS until proven otherwise. CPAP alone may not be enough — they need BiPAP.
| Feature | OSA | OHS |
|---|---|---|
| Definition | Repetitive upper airway collapse during sleep | BMI ≥30 + awake hypercapnia (PaCO₂ >45) not explained by another cause |
| Daytime PaCO₂ | Normal | Elevated (>45 mmHg) — THE distinguishing feature |
| Mechanism | Mechanical pharyngeal obstruction | ↓ Chest wall compliance + impaired central respiratory drive + coexisting OSA (90%) |
| ABG (awake) | Normal | Chronic respiratory acidosis (↑CO₂, ↑HCO₃⁻ from renal compensation) |
| Serum HCO₃⁻ | Normal | Elevated (>27 mEq/L) — a screening clue on BMP |
| Sleep study | AHI ≥5 with symptoms | 90% also have OSA. Key is the awake hypercapnia, not the AHI |
| Treatment | CPAP (splints airway open) | BiPAP with backup rate (needs inspiratory pressure support to ventilate, not just splint). Average volume-assured pressure support (AVAPS) is emerging. |
| Why CPAP fails in OHS | N/A — CPAP is sufficient | CPAP only holds the airway open. OHS patients also have impaired respiratory drive + restrictive physiology → need the extra pressure support of BiPAP to move air in and out |
| Mortality | Increased CV risk if untreated | Higher than OSA alone. 18-month mortality ~23% if untreated (vs ~9% for OSA alone) |
| Screening tip | STOP-BANG ≥3 | Obese patient with unexplained elevated HCO₃⁻ on BMP → check ABG → if PaCO₂ >45 → OHS |
🔄 Updated Practice: OHS is underdiagnosed. Many patients labeled as "OSA not responding to CPAP" actually have OHS and need BiPAP. If an obese patient has persistent hypoxemia or hypercapnia despite adequate CPAP use, check an ABG — they may need escalation to BiPAP with backup rate.
💊 Management
Treatment Options
| Treatment | Indication | Notes |
|---|---|---|
| CPAP 1ST LINE | All moderate-severe OSA. Mild if symptomatic. | Gold standard. Eliminates apneas, reduces daytime sleepiness, improves BP. Adherence is the biggest challenge (only ~50% use regularly). Minimum 4 hours/night for benefit. |
| Weight loss ALL PATIENTS | BMI > 25 | 10% weight loss → ~50% reduction in AHI. GLP-1 agonists (semaglutide) showing significant AHI improvement SURMOUNT-OSA, 2024. Bariatric surgery for BMI > 40. |
| Oral appliance (MAD) | Mild-moderate OSA, CPAP intolerant | Mandibular advancement device — holds jaw forward to open airway. Fitted by sleep dentist. Less effective than CPAP but better adherence. |
| Hypoglossal nerve stimulator (Inspire) | Moderate-severe, CPAP intolerant, BMI < 35 | Implanted device stimulates CN XII → tongue protrusion during sleep → opens airway. STAR, 2014: 68% reduction in AHI. |
| Positional therapy | Positional OSA (AHI worse supine) | Sleep on side. Tennis ball technique. Positional devices. |
Perioperative OSA Management
OSA patients are high-risk perioperatively. Opioids and sedatives suppress respiratory drive and pharyngeal muscle tone → upper airway collapse → hypoxia, reintubation, ICU transfer.
- Bring home CPAP to hospital — use immediately postop
- Minimize opioids — multimodal analgesia (acetaminophen, NSAIDs, regional anesthesia)
- Continuous pulse oximetry (not just spot checks)
- Semi-upright positioning (not flat supine)
- Avoid benzodiazepines
📋 On Rounds
Why is OSA the #1 cause of resistant hypertension?
Intermittent hypoxia from apneic episodes triggers sympathetic nervous system activation (repeated fight-or-flight surges throughout the night), increases RAAS activity, causes endothelial dysfunction, and promotes systemic inflammation. These effects persist into the daytime — the BP doesn't normalize with sleep as it should (loss of nocturnal dipping). This sustained sympathetic overdrive and neurohormonal activation makes BP resistant to standard antihypertensives. CPAP reduces SBP by ~3–5 mmHg on average, with larger reductions in patients with resistant HTN and severe OSA who use CPAP consistently.
Why is untreated OSA dangerous beyond just daytime sleepiness?
OSA is a systemic disease, not just a sleep problem. Recurrent hypoxemia and sympathetic surges during apneic episodes cause: (1) Resistant hypertension — OSA is the #1 cause of secondary HTN. CPAP reduces BP by 2–10 mmHg. (2) Atrial fibrillation — OSA increases AF risk 2–4×. Untreated OSA doubles AF recurrence after cardioversion or ablation. (3) Pulmonary hypertension — chronic hypoxic vasoconstriction → right heart failure. (4) Metabolic syndrome — insulin resistance, weight gain (bidirectional relationship). (5) Stroke — 2–3× increased risk. (6) Perioperative risk — undiagnosed OSA patients have higher rates of difficult intubation, desaturation, ICU admission, and death. Screen every patient with HTN, AF, or BMI > 30 with STOP-BANG.
Why is untreated OSA a risk factor for resistant hypertension and atrial fibrillation?
Resistant HTN: During apneic episodes, hypoxemia triggers massive sympathetic surges → catecholamine release → vasoconstriction + tachycardia. Repeated nightly for years → sustained sympathetic overdrive + vascular remodeling. OSA is the #1 identifiable cause of resistant hypertension (HTN on ≥ 3 meds including a diuretic). CPAP reduces BP by 2-10 mmHg. Screen every patient with resistant HTN for OSA. Atrial fibrillation: Mechanism: (1) intermittent hypoxemia → oxidative stress → atrial remodeling + fibrosis, (2) intrathoracic pressure swings (Mueller maneuver against closed glottis) → atrial stretch → structural/electrical remodeling, (3) sympathetic/parasympathetic oscillations → arrhythmia triggers. Untreated OSA doubles AF recurrence after cardioversion or ablation. Treating OSA with CPAP improves AF outcomes — some guidelines now recommend CPAP as adjunct AF treatment.
What does the AHI number actually mean?
AHI (Apnea-Hypopnea Index) = number of apnea + hypopnea events per hour of sleep. Apnea: complete cessation of airflow ≥ 10 seconds. Hypopnea: ≥ 30% reduction in airflow with ≥ 3% O₂ desaturation or arousal. Severity: Mild: AHI 5-15 (may not need CPAP if asymptomatic). Moderate: AHI 15-30 (CPAP recommended). Severe: AHI > 30 (CPAP strongly recommended, significant CV risk). Highest prognostic value: the combination of high AHI + low nadir O₂ saturation + high symptom burden. Some patients have AHI 40 but feel fine; others have AHI 10 but are devastatingly sleepy — treat the patient, not the number. CPAP adherence (≥ 4h/night, ≥ 70% of nights) matters more than the AHI improvement.
📣 Sample Presentation
One-Liner
"Mr. Martinez is a 48-year-old with BMI 36, resistant hypertension on 3 medications, and daytime sleepiness (Epworth 16). Sleep study: AHI 42, lowest O₂ desaturation 78%. Severe OSA."
Key Points to Cover on Rounds
Severe OSA (AHI 42). STOP-BANG score 7. Treatment: CPAP initiated — auto-titrating, pressure range 8-16 cmH₂O. Mask fitting done (nasal pillow chosen). CPAP adherence education: use ≥4h/night for ≥70% of nights. Resistant HTN: OSA is the #1 cause of secondary HTN — expect BP improvement with CPAP (2-10 mmHg reduction). Afib screening: ECG in sinus. Weight loss counseling: semaglutide discussed (dual benefit: weight + likely improves AHI). Driving safety discussed: avoid drowsy driving until treated. Plan: follow-up in 4 weeks for CPAP compliance data download, reassess BP medications.
🧪 Workup
Workup — Obstructive Sleep Apnea
Workup for Obstructive Sleep Apnea: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications for OSA
| Medication | Dose | Mechanism | Notes |
|---|---|---|---|
| Semaglutide (Wegovy) EMERGING | 0.25mg SQ weekly → titrate to 2.4mg weekly | GLP-1 RA → weight loss → reduced pharyngeal fat → improved AHI | SELECT, 2023: ~20% weight loss. Dual benefit: weight + AHI reduction. Not yet FDA-approved specifically for OSA. |
| Tirzepatide (Mounjaro/Zepbound) EMERGING | 2.5mg SQ weekly → titrate to 15mg weekly | GIP/GLP-1 dual agonist → greater weight loss → AHI improvement | SURMOUNT-OSA, 2024: Up to 62.8% reduction in AHI. May become first-line pharmacologic adjunct for obese OSA. |
| Modafinil (Provigil) | 200mg PO daily (AM) | Wakefulness-promoting agent | For residual daytime sleepiness DESPITE adequate CPAP use. Does NOT treat the apnea itself — treats the symptom only. Not a substitute for CPAP. |
| Armodafinil (Nuvigil) | 150mg PO daily (AM) | R-enantiomer of modafinil, longer half-life | Same indication as modafinil — residual sleepiness on CPAP. Slightly longer duration of action. |
| Solriamfetol (Sunosi) | 75mg PO daily → max 150mg | Dopamine/norepinephrine reuptake inhibitor | FDA-approved for excessive daytime sleepiness in OSA (on CPAP). More potent wakefulness effect than modafinil. Avoid in uncontrolled HTN. |
| Acetazolamide (Diamox) | 250mg PO BID | Carbonic anhydrase inhibitor → metabolic acidosis → stimulates ventilation | Used for central sleep apnea (CSA) and high-altitude OSA. NOT standard for typical OSA. May reduce AHI in select cases. |
🔄 Updated Practice: GLP-1 receptor agonists (semaglutide, tirzepatide) are emerging as game-changers for OSA in obese patients. SURMOUNT-OSA 2024 showed tirzepatide reduced AHI by up to 63% — potentially more effective than any prior pharmacologic therapy. While not yet first-line, expect these to become standard adjuncts to CPAP for obese OSA patients. Weight loss addresses the root cause rather than just treating symptoms.
⚠️ Medications to AVOID in OSA: Benzodiazepines, opioids, barbiturates, and sedating antihistamines suppress respiratory drive and pharyngeal muscle tone → worsen apneas → life-threatening hypoxemia. If sedation is needed, use non-benzodiazepine options and ensure continuous pulse oximetry.
📈 Monitoring
Monitoring — Obstructive Sleep Apnea
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Diagnosis
AHI ≥ 5 + symptoms (EDS, witnessed apneas, morning headache) OR AHI ≥ 15 regardless of symptoms. Home sleep test or in-lab PSG.
CPAP
Gold standard. Adherence target: ≥ 4h/night, ≥ 70% of nights. Auto-titrating most common. Proper mask fitting critical. Follow-up data download at 4 weeks.
CV Consequences
#1 cause of resistant HTN. Doubles AF recurrence. Associated with: stroke, MI, HF, pulmonary HTN. CPAP improves BP and AF outcomes.
Alternatives
Oral appliance (mild-moderate). Inspire (hypoglossal nerve stimulator, moderate-severe who can't tolerate CPAP). Positional therapy. Weight loss (semaglutide).
Perioperative Risk
Higher risk of difficult intubation, post-op respiratory depression (opioid sensitivity), desaturation. Bring home CPAP to hospital. Alert anesthesia.
Weight Loss Impact
Each 10% weight loss reduces AHI by ~26%. Semaglutide for obesity + OSA is an emerging treatment strategy. GLP-1 RA may directly reduce AHI.
📄 One Pager
One Pager — Obstructive Sleep Apnea
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OBSTRUCTIVE SLEEP APNEA — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Pulmonology / Sleep · One Pager
Obstructive Sleep Apnea
AHI ≥ 5 + symptoms or ≥ 15 regardless. CPAP is gold standard. #1 cause of resistant HTN. Doubles AF recurrence. Weight loss with GLP-1 RA is emerging adjunct.
Diagnosis
AHI ≥ 5 + symptoms (EDS, witnessed apneas, morning headache) OR AHI ≥ 15 regardless. Mild: 5-15. Moderate: 15-30. Severe: > 30. Home sleep test or in-lab PSG.
Treatment
CPAP (gold standard). Adherence target: ≥ 4h/night, ≥ 70% of nights. Auto-titrating most common. Alternatives: oral appliance (mild-moderate), Inspire hypoglossal nerve stimulator, positional therapy, weight loss.
CV Consequences
#1 cause of resistant hypertension (screen every resistant HTN patient). Doubles AF recurrence after cardioversion/ablation. Associated with: stroke, MI, HF, pulmonary HTN, sudden cardiac death.
Key Drugs
CPAPAuto-titrating, proper mask fit
Weight lossGLP-1 RA may reduce AHI
ModafinilIf residual EDS despite CPAP
Oral applianceMild-moderate OSA
Pitfalls
- Not screening resistant HTN patients for OSA
- Poor CPAP adherence (mask fitting + education + follow-up critical)
- Not bringing home CPAP to hospital (perioperative risk)
- Prescribing sedatives/opioids without screening for OSA
Interstitial Lung Disease
A heterogeneous group of diseases causing inflammation and/or fibrosis of the lung parenchyma. IPF is the most common and most lethal. HRCT pattern recognition is essential — UIP vs NSIP vs organizing pneumonia drives management.
🔍 Overview
Common ILD Patterns on HRCT
| HRCT Pattern | Key Features | Most Likely Diagnosis | Prognosis |
|---|---|---|---|
| UIP (Usual Interstitial Pneumonia) | Basal, peripheral, subpleural honeycombing + traction bronchiectasis + reticulation. Heterogeneous (areas of normal lung adjacent to fibrosis). | IPF (if no identifiable cause) | Worst. Median survival 3–5 years. |
| NSIP (Non-Specific Interstitial Pneumonia) | Ground-glass opacities, basal-predominant, relatively uniform. Subpleural sparing. Less honeycombing. | CTD-ILD (RA, scleroderma), drug-induced, idiopathic NSIP | Better than UIP. Often responds to immunosuppression. |
| Organizing Pneumonia (OP) | Peripheral, patchy consolidations that may be migratory. "Reverse halo" (atoll sign). | COP (cryptogenic), drug-induced, post-infection, CTD | Good. Usually responds dramatically to steroids. |
| Upper-lobe predominant | Fibrosis/nodules in upper lobes | Sarcoidosis, hypersensitivity pneumonitis (chronic), silicosis, coal workers | Variable |
IPF (Idiopathic Pulmonary Fibrosis)
- Most common IIP. Male > female. Typically age > 60. Smoking is a risk factor.
- Clinical: progressive exertional dyspnea, dry cough, bibasilar Velcro-like crackles on auscultation, clubbing (~50%)
- PFTs: restrictive pattern (↓ FVC, ↓ TLC) + ↓↓ DLCO
- Diagnosis: UIP pattern on HRCT in appropriate clinical context → may not need biopsy. If HRCT indeterminate → surgical lung biopsy via VATS for confirmation.
Sarcoidosis
- Non-caseating granulomas. Affects lungs (~90%) but is systemic (skin, eyes, liver, heart, CNS).
- Demographics: peak age 25–40. More common and more severe in Black patients.
- CXR staging: Stage I (bilateral hilar lymphadenopathy — BHL), Stage II (BHL + infiltrates), Stage III (infiltrates only), Stage IV (fibrosis)
- Lab: ↑ ACE level (not specific), ↑ calcium (granulomas produce 1,25-OH vitamin D), ↑ 24-hr urine calcium
- Treatment: Many resolve spontaneously (especially Stage I). Treat if symptomatic, progressive, or extrapulmonary involvement. Prednisone 20–40 mg daily × 4–6 weeks, then taper. Steroid-sparing: methotrexate, azathioprine.
💊 Management
IPF — Antifibrotic Therapy
Steroids and immunosuppressants are HARMFUL in IPF. PANTHER-IPF, 2012: prednisone + azathioprine + NAC increased mortality and hospitalizations vs placebo. Stopped early for harm.
| Drug | Dose | Evidence | Notes |
|---|---|---|---|
| Pirfenidone (Esbriet) ANTIFIBROTIC | 267 mg TID → titrate to 801 mg TID | ASCEND, 2014: reduced FVC decline by ~50% at 1 year. | Slows progression, does not cure. GI side effects (nausea), photosensitivity. Take with food. |
| Nintedanib (Ofev) ANTIFIBROTIC | 150 mg BID | INPULSIS, 2014: reduced FVC decline by ~50%. Also approved for SSc-ILD and progressive fibrosing ILD. | Tyrosine kinase inhibitor. Diarrhea is the main side effect (~60%). Hepatotoxicity — monitor LFTs. |
When to Refer for Transplant
- FVC decline ≥ 10% in 6 months
- DLCO < 40% predicted
- Desaturation < 88% on 6-minute walk test
- Hospitalization for respiratory decline or pneumothorax
- Refer early — transplant evaluation takes months
📋 On Rounds
Why are steroids harmful in IPF?
IPF is a fibrotic process, not primarily inflammatory. The pathology is aberrant wound healing — repeated epithelial injury → fibroblast proliferation → collagen deposition. Steroids suppress the immune system but don't target fibrosis. PANTHER-IPF, 2012 showed that the triple combination of prednisone + azathioprine + NAC increased mortality by 8× and hospitalizations by 4× compared to placebo. The immunosuppression likely impaired already-compromised host defenses without slowing fibrosis. This is why pattern recognition on HRCT matters — UIP (fibrotic, don't give steroids) vs NSIP/OP (inflammatory, steroids help).
How do you distinguish UIP from NSIP on HRCT, and why does it matter?
This is one of the most important radiographic distinctions in pulmonology because it determines treatment and prognosis. UIP (usual interstitial pneumonia) = IPF pattern: basal-predominant, peripheral honeycombing, traction bronchiectasis, minimal GGO. Prognosis: median survival 3–5 years. Treatment: antifibrotics only (nintedanib or pirfenidone) — steroids are HARMFUL. NSIP (nonspecific interstitial pneumonia) = more GGO than fibrosis, subpleural sparing (key differentiator), less honeycombing. Prognosis: much better (10+ years). Treatment: responds to immunosuppression (steroids + mycophenolate). Often associated with CTD (check ANA, RF, CCP, myositis panel). The bottom line: UIP = don't give steroids. NSIP = steroids work. Getting the pattern wrong can harm the patient.
When should you refer an ILD patient for lung transplant evaluation?
Refer early — don't wait until the patient is too sick. General criteria: (1) FVC declining > 5-10% per year despite treatment (antifibrotics for IPF, immunosuppression for NSIP/CTD-ILD), (2) DLCO < 40% predicted, (3) O₂ requirement at rest or with exertion, (4) 6-minute walk distance < 250m or declining, (5) Pulmonary hypertension (RVSP > 40 on echo). For IPF specifically: refer at diagnosis (median survival 3-5 years, transplant waitlist can be 1-2 years). Contraindications to transplant: age > 70 (relative), active malignancy, active substance abuse, non-adherence, BMI > 35, significant extrapulmonary organ dysfunction. Post-transplant: lifelong immunosuppression, median survival ~6 years, major risks are chronic rejection (BOS) and infection.
What is the role of pulmonary rehabilitation in ILD?
Pulmonary rehab is one of the most effective interventions in ILD — yet it's dramatically underutilized. Benefits: improved exercise capacity (6MWD increases 30-50m), reduced dyspnea, improved quality of life, reduced anxiety/depression. It works even in IPF where the lung disease itself is progressive and irreversible — pulmonary rehab trains the muscles and cardiovascular system to work more efficiently with less lung function. Components: supervised exercise training (aerobic + strength, 2-3×/week × 8-12 weeks), education, nutritional counseling, psychosocial support. Refer early — don't wait until the patient is oxygen-dependent. Evidence from [Holland, 2008 Cochrane: significant improvements in dyspnea and functional capacity. Combine with antifibrotic therapy (nintedanib/pirfenidone for IPF) for maximum benefit.
📣 Sample Presentation
One-Liner
"Mrs. Park is a 68-year-old non-smoker presenting with 18 months of progressive dyspnea and dry cough. HRCT shows basal-predominant honeycombing, traction bronchiectasis, and minimal GGO — UIP pattern. PFTs: FVC 62%, DLCO 48%. Consistent with IPF."
Key Points to Cover on Rounds
HRCT: definite UIP pattern (basal honeycombing, traction bronchiectasis, no GGO). PFTs: restrictive (FVC 62%), DLCO 48% (severely reduced). Autoimmune workup: ANA, RF, CCP, myositis panel — all negative (not CTD-ILD). No significant exposures (no birds, mold, medications). Diagnosis: IPF (definite UIP on imaging, exclusion of other causes — biopsy not needed). Treatment: nintedanib 150 mg BID started (antifibrotic — slows FVC decline). NOT steroids (harmful in IPF). O₂: prescribed for exertional desaturation (SpO₂ 84% on 6MWT). Pulmonary rehab referral. Transplant evaluation: referred given age and severity. Plan: PFTs q6 months, annual HRCT.
🧪 Workup
Workup — Pleural Effusion
Workup for Pleural Effusion: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Pleural Effusion
Medication details for Pleural Effusion are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Pleural Effusion
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
IPF
UIP pattern on HRCT (basal honeycombing, traction bronchiectasis). Antifibrotics only (nintedanib or pirfenidone). NO steroids [PANTHER-IPF harm]. Transplant referral early.
NSIP
GGO-predominant on HRCT. Often associated with CTD (especially scleroderma). Responds to immunosuppression (mycophenolate + steroids). Better prognosis than IPF.
COP
Organizing pneumonia: migratory infiltrates, responds dramatically to steroids. Relapses common → slow taper over months.
CTD-ILD
ILD from autoimmune disease (RA, scleroderma, SLE, myositis). Screen all new ILD for CTD (ANA, RF, CCP, myositis panel). Treat underlying autoimmune disease.
Monitoring
PFTs (FVC, DLCO) q6 months. HRCT annually or with symptoms. 6MWT. Refer for transplant: FVC declining > 5-10%/year, DLCO < 40%, O₂ requirement.
Pulmonary Rehab
Improves exercise capacity, dyspnea, QOL even in progressive disease. Refer early, don't wait for O₂ dependence. Combine with antifibrotics for maximum benefit.
📄 One Pager
One Pager — Pleural Effusion
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PLEURAL EFFUSION — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Pulmonology · One Pager
Interstitial Lung Disease
CT pattern determines treatment: UIP/honeycombing = antifibrotics (NOT steroids). GGO/NSIP = immunosuppression. Screen all new ILD for CTD. Transplant referral early for IPF.
IPF
Definite UIP on HRCT (basal honeycombing, traction bronchiectasis, no GGO). Antifibrotics: nintedanib or pirfenidone (slow FVC decline). NO steroids [PANTHER-IPF = harm]. Transplant referral at diagnosis.
Other ILDs
NSIP: GGO-predominant, often CTD-associated. Responds to steroids + mycophenolate. COP: migratory infiltrates, responds dramatically to steroids. CTD-ILD: treat underlying autoimmune disease.
Monitoring + Referral
PFTs (FVC, DLCO) q6 months. HRCT annually. 6MWT. Pulmonary rehab (improves QOL even in progressive disease). Transplant if: FVC declining > 5-10%/year, DLCO < 40%, O₂ requirement.
Key Drugs
Nintedanib150 mg BID (IPF)
Pirfenidone801 mg TID (IPF)
Mycophenolate2-3g/day (NSIP/CTD-ILD)
Prednisone0.5-1 mg/kg (COP, NSIP)
Pitfalls
- Steroids for IPF (harmful — worsens outcomes [PANTHER-IPF])
- Not screening for CTD (ANA, RF, CCP, myositis panel) in new ILD
- Late transplant referral (IPF median survival 3-5 years)
- Forgetting pulmonary rehab (dramatically improves QOL)
Hemoptysis
Coughing up blood from the tracheobronchial tree. Non-massive (most cases): workup to find the cause. Massive (> 500 mL/24h or hemodynamic instability): the patient dies from asphyxiation, not exsanguination. Protect the airway first.
🔍 Overview
Classification
| Category | Volume | Urgency |
|---|---|---|
| Non-massive (most common) | < 500 mL/24h, hemodynamically stable | Workup: CT chest, bronchoscopy if no source on CT. Outpatient if stable. |
| Massive | > 500 mL/24h (or > 100 mL/hr), or any amount causing hemodynamic instability or respiratory compromise [Crocco Classification, 1968 | EMERGENCY. Airway protection → bronchoscopy → IR embolization or surgery. |
Common Causes
| Category | Examples |
|---|---|
| Airway (most common) | Bronchitis (#1 cause overall), bronchiectasis, lung cancer |
| Parenchymal | Pneumonia, TB (cavitary), lung abscess, fungal (aspergilloma) |
| Vascular | PE, AV malformations, Dieulafoy lesion (bronchial artery), mitral stenosis |
| Diffuse alveolar hemorrhage (DAH) | Vasculitis (GPA, anti-GBM), SLE, coagulopathy. Bilateral GGOs on CT + dropping Hgb + hemoptysis. |
| Iatrogenic | Anticoagulation (unmasks underlying lesion), post-biopsy, PA catheter |
🚨 Management
Massive Hemoptysis Protocol
Patients die from asphyxiation (drowning in blood), not hemorrhagic shock. Protect the airway. Identify the bleeding side. Isolate it. STEP Trial, Wand 2018
Immediate
Position bleeding side DOWN (gravity keeps blood in the affected lung, protects the good lung). Supplemental O₂. Large-bore IV × 2. Type and screen. Reverse anticoagulation if applicable. Hold antiplatelets.
Airway
If airway compromise → intubate with large ETT (≥ 8.0) to allow bronchoscopy through the tube. If bleeding side known → mainstem intubation of the NON-bleeding lung (advance ETT into the good side to isolate it). Double-lumen ETT if available (lung isolation).
Bronchoscopy
Rigid bronchoscopy preferred for massive hemoptysis (better suctioning, can tamponade with the scope). Flexible bronchoscopy for localization. Interventions: cold saline lavage, epinephrine instillation, balloon tamponade, electrocautery.
Bronchial artery embolization (BAE)
Definitive treatment for massive hemoptysis. Interventional radiology. ~90% immediate success rate. Recurrence: ~10–30% long-term. Complication: spinal cord ischemia (bronchial and spinal arteries share a common origin — artery of Adamkiewicz). Defined BAE Outcomes, Defined Mal 2010
Surgery
Last resort. Lobectomy/pneumonectomy if BAE fails, recurrent massive hemoptysis, or resectable lesion (e.g., aspergilloma, cancer). High surgical mortality in the emergent setting (~20–40%).
📋 On Rounds
Why do patients die from massive hemoptysis — hemorrhage or asphyxiation?
Asphyxiation. The total dead space of the tracheobronchial tree is only ~150 mL. A relatively small amount of blood (compared to GI bleeding) can flood both lungs and cause fatal hypoxia. The patient doesn't bleed to death — they drown in their own blood. This is why airway management (positioning, intubation, lung isolation) takes priority over volume resuscitation. Position the bleeding side down to protect the good lung, intubate early with a large ETT, and get bronchoscopy + IR for source control.
What is the most dangerous complication of bronchial artery embolization?
Spinal cord ischemia (paraplegia). The artery of Adamkiewicz (the major anterior spinal artery, typically arising from T9–T12 intercostal arteries) can share a common trunk with bronchial arteries or arise nearby. Inadvertent embolization of this artery causes anterior spinal artery syndrome → paraplegia. This occurs in ~1–5% of BAE procedures. Careful angiographic identification of spinal feeders before embolization is essential.
How do you manage massive hemoptysis in the first 5 minutes?
Massive hemoptysis (> 500 mL/24h or > 100 mL/hr) = airway emergency. The patient usually drowns before they exsanguinate. Step 1: Position the patient bleeding side DOWN (lateral decubitus — prevents blood from flooding the good lung). Step 2: Call for help — anesthesia for intubation, IR for bronchial artery embolization, pulmonology for bronchoscopy, thoracic surgery. Step 3: Intubate with a large ETT (≥ 8.0) to allow bronchoscopy through the tube. Consider mainstem intubation of the non-bleeding lung (advance ETT into right or left mainstem to isolate the good lung). Step 4: Bronchoscopy for localization + interventions (cold saline lavage, topical epinephrine, balloon tamponade, bronchial blocker). Step 5: IR for bronchial artery embolization (definitive in ~90% of cases). Surgery (lobectomy) is last resort for refractory bleeding.
What is the most common cause of hemoptysis? (Hint: it's not cancer)
Acute bronchitis is the #1 cause of hemoptysis in the outpatient/ED setting — not cancer, not TB, not PE. Most hemoptysis is mild (< 30 mL) and self-limited from mucosal inflammation. However, the workup depends on risk factors: Low risk (age < 40, non-smoker, single episode, mild): CXR + symptomatic treatment, follow-up if persistent. High risk (age > 40, smoker, recurrent, > 30 mL, abnormal CXR): CT chest + bronchoscopy (to rule out malignancy, bronchiectasis, AVM). Massive (> 500 mL/24h): airway emergency — positioning, intubation, bronchoscopy, IR for bronchial artery embolization. Common causes by frequency: bronchitis > bronchiectasis > malignancy > pneumonia > TB > PE > vasculitis (DAH) > AVM.
📣 Sample Presentation
One-Liner
"Mr. Davis is a 58-year-old smoker presenting with 2 episodes of hemoptysis (~50 mL total). Hemodynamically stable. CT chest: 2.5 cm RUL mass with surrounding hemorrhage."
Key Points to Cover on Rounds
Non-massive hemoptysis with concerning RUL mass (likely malignancy in a smoker). Stable — not massive (<500 mL/24h). CT angiography: no active extravasation. Bronchoscopy: scheduled for tomorrow (diagnostic — BAL, brushings, biopsy + evaluate for bleeding source). If active bleeding at bronchoscopy → cold saline lavage, topical epinephrine, or bronchial blocker. Staging workup: PET-CT ordered, brain MRI. Smoking cessation counseled. Plan: bronchoscopy tomorrow for tissue diagnosis, multidisciplinary tumor board if malignancy confirmed. IR for bronchial artery embolization on standby if bleeding escalates.
🧪 Workup
Workup — Pneumonia
Workup for Pneumonia: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Pneumonia
Medication details for Pneumonia are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Pneumonia
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
Most Common Cause
Acute bronchitis (#1 overall). But always consider: malignancy (> 40, smoker), bronchiectasis, TB, PE, vasculitis (DAH).
Massive (> 500 mL/24h)
Airway emergency. Bleeding side DOWN. Intubate (large ETT ≥ 8.0). Bronchoscopy for localization. IR for bronchial artery embolization. Surgery if refractory.
Workup
CXR (first). CT chest if CXR abnormal or high risk. Bronchoscopy if malignancy suspected or source unclear. CTA if massive or PE suspected.
Non-Massive
CXR + symptom management. If high risk (smoker, > 40, recurrent, > 30 mL) → CT chest + bronchoscopy for tissue diagnosis.
DAH
Diffuse alveolar hemorrhage: bilateral GGO, dropping Hgb, hemoptysis. Causes: ANCA vasculitis, anti-GBM, SLE, drug-induced. Treat underlying cause + pulse steroids.
Bronchial Artery Embolization
IR procedure, definitive for ~90% of massive hemoptysis. Bronchial arteries (high-pressure) are the source in most non-PE hemoptysis. Can recur — may need repeat.
📄 One Pager
One Pager — Pneumonia
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PNEUMONIA — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
📄 One Pager
Pulmonology · One Pager
Hemoptysis
Most common = bronchitis. Most dangerous = massive (> 500 mL/24h) → airway emergency. Bleeding side DOWN. Bronchoscopy + IR embolization. Always consider malignancy in smokers > 40.
Causes
Bronchitis (#1 overall), bronchiectasis, malignancy (smoker > 40), pneumonia, TB, PE, vasculitis (DAH), AVM. Non-massive: CXR → CT if abnormal or high-risk → bronchoscopy.
Massive Hemoptysis (> 500 mL/24h)
AIRWAY EMERGENCY — patient drowns before exsanguinating. (1) Bleeding side DOWN. (2) Intubate (large ETT ≥ 8.0). (3) Bronchoscopy for localization. (4) IR bronchial artery embolization (definitive ~90%). (5) Surgery if refractory.
DAH — Diffuse Alveolar Hemorrhage
Bilateral GGO + hemoptysis + dropping Hgb. Causes: ANCA vasculitis, anti-GBM (Goodpasture), SLE, drug-induced. Treatment: pulse steroids + treat underlying cause. BAL: progressively bloodier aliquots.
Key Drugs
BronchoscopyLocalization + intervention
BAEBronchial artery embolization (IR)
TXA1g IV (adjunct for bleeding)
Treat underlyingAntibiotics, anticoag for PE, immunosuppression for vasculitis
Pitfalls
- Not positioning bleeding side down (protects good lung)
- Small ETT (need ≥ 8.0 to allow bronchoscopy through tube)
- Missing malignancy in smoker > 40 (always consider)
- Attributing to bronchitis without follow-up imaging in high-risk patients
COPD — Chronic Management
Irreversible airflow obstruction (FEV₁/FVC < 0.70 post-bronchodilator). GOLD staging drives therapy. Inhaler selection matters — know the stepwise approach. For acute exacerbations requiring ICU management, see AECOPD (ICU).
🔍 Overview
Diagnosis
- Spirometry: post-bronchodilator FEV₁/FVC < 0.70 confirms airflow obstruction
- Symptoms: chronic dyspnea, cough, sputum production (≥ 3 months/year × 2 years = chronic bronchitis definition)
- Risk factors: smoking (> 10 pack-years), alpha-1 antitrypsin deficiency (test in early-onset or non-smoker COPD), biomass fuel exposure
GOLD Severity (by FEV₁)
| GOLD Stage | FEV₁ (% predicted) | Severity |
|---|---|---|
| GOLD 1 | ≥ 80% | Mild |
| GOLD 2 | 50–79% | Moderate |
| GOLD 3 | 30–49% | Severe |
| GOLD 4 | < 30% | Very severe |
GOLD ABE Groups (2023 Update)
The 2023 GOLD report simplified the old ABCD into ABE. Assessment is based on symptoms + exacerbation history.
| Group | Symptoms (mMRC/CAT) | Exacerbations | Initial Therapy |
|---|---|---|---|
| A | Low (mMRC 0–1, CAT < 10) | 0–1 (not leading to hospitalization) | Bronchodilator (SABA PRN or LAMA or LABA) |
| B | High (mMRC ≥ 2, CAT ≥ 10) | 0–1 (not leading to hospitalization) | LABA + LAMA combination |
| E (Exacerbator) | Any | ≥ 2 moderate or ≥ 1 hospitalization | LABA + LAMA. Consider LABA + LAMA + ICS if eos ≥ 300. |
💊 Stepwise Therapy
Inhaler Therapy
| Drug Class | Examples | When | Key Notes |
|---|---|---|---|
| SABA PRN RESCUE | Albuterol (ProAir/Ventolin) 2 puffs q4–6h PRN | All patients — rescue inhaler | Quick onset (5–15 min). If using > 2×/week → step up maintenance therapy. |
| LAMA 1ST LINE MAINTENANCE | Tiotropium (Spiriva) 18 mcg daily Umeclidinium (Incruse) 62.5 mcg daily | Group A (monotherapy) or as part of combination | Preferred first-line maintenance in COPD (unlike asthma where ICS is first). Reduces exacerbations. Once-daily dosing. |
| LABA 1ST LINE MAINTENANCE | Salmeterol (Serevent) 50 mcg BID Formoterol 12 mcg BID Indacaterol (Arcapta) 75 mcg daily | Monotherapy or combination | Long-acting bronchodilator. Never use LABA alone in asthma (but OK in COPD). |
| LABA + LAMA GROUP B/E | Umeclidinium/vilanterol (Anoro Ellipta) Tiotropium/olodaterol (Stiolto) | Group B (symptomatic), Group E (exacerbator) | Dual bronchodilation = backbone of COPD therapy. Better than either alone for FEV₁, symptoms, and exacerbation reduction. |
| ICS (add-on) SELECTIVE USE | Fluticasone, budesonide (always in combination with LABA ± LAMA) | Only if eosinophils ≥ 300 or frequent exacerbations despite LABA+LAMA | ICS is NOT first-line in COPD (unlike asthma). Increases pneumonia risk TORCH, 2007. Use blood eosinophils to guide: ≥ 300 → add ICS. < 100 → avoid ICS. |
| Triple: ICS + LABA + LAMA ESCALATION | Fluticasone/umeclidinium/vilanterol (Trelegy Ellipta) | Group E with eos ≥ 300 or persistent exacerbations on dual | IMPACT, 2018: triple reduced exacerbations by 15% vs LAMA+LABA and 25% vs ICS+LABA. ETHOS, 2020: also showed mortality reduction. Best evidence for triple in high-eos exacerbators. |
Non-Inhaler Therapies
| Therapy | Who Benefits | Key Evidence |
|---|---|---|
| Smoking cessation MOST IMPORTANT | ALL patients. Only intervention proven to slow FEV₁ decline. | Lung Health Study, 1994: sustained quitters had significantly slower FEV₁ decline. Offer pharmacotherapy (varenicline, NRT, bupropion) + behavioral counseling. |
| Pulmonary rehabilitation | mMRC ≥ 2, post-exacerbation | Improves exercise capacity, dyspnea, QOL. Most effective non-pharmacologic intervention. Refer early. |
| Long-term O₂ therapy | PaO₂ ≤ 55 or SpO₂ ≤ 88% at rest (or PaO₂ 56–59 with cor pulmonale/polycythemia) | NOTT, 1980: continuous O₂ (> 15 h/day) reduced mortality. LOTT, 2016: NO benefit for moderate desaturation (SpO₂ 89–93%). Don't prescribe O₂ for mild hypoxemia. |
| Azithromycin prophylaxis | Frequent exacerbators despite optimal inhaler therapy | Albert, 2011: azithromycin 250 mg daily × 1 year reduced exacerbations by 27%. Risk: hearing loss, QT prolongation, resistance. Screen for MAC (NTM) before starting. |
| Roflumilast (Daliresp) | FEV₁ < 50% + chronic bronchitis phenotype + frequent exacerbations | PDE4 inhibitor. Modest exacerbation reduction. Side effects: diarrhea, nausea, weight loss, psychiatric symptoms. |
Vaccinations — All COPD Patients
- Influenza — annually
- Pneumococcal — PCV20 (Prevnar 20) or PCV15 + PPSV23
- COVID-19 — per current guidelines
- Tdap — if not previously received, then Td booster q10y
- RSV — for adults ≥ 60 (shared clinical decision)
- Zoster (Shingrix) — if ≥ 50
📋 On Rounds
Why is ICS not first-line in COPD the way it is in asthma?
COPD inflammation is primarily neutrophilic (driven by CD8+ T cells, neutrophils, macrophages) and relatively steroid-resistant. Asthma inflammation is eosinophilic (Th2-driven, mast cells, eosinophils) and highly steroid-responsive. ICS in COPD adds modest exacerbation reduction but significantly increases pneumonia risk TORCH, 2007. Blood eosinophils serve as a biomarker: patients with eos ≥ 300 have a more "asthma-like" inflammatory profile and benefit from ICS. Those with eos < 100 have purely neutrophilic disease and should NOT receive ICS.
When do you prescribe home oxygen in COPD?
Only for severe resting hypoxemia: PaO₂ ≤ 55 mmHg or SpO₂ ≤ 88% at rest on room air (or PaO₂ 56–59 with evidence of cor pulmonale or polycythemia). Must be measured when clinically stable, at rest, on room air. NOTT, 1980 showed mortality benefit for continuous O₂ (> 15 h/day). Key negative trial: LOTT, 2016 showed NO benefit for moderate resting or exertional desaturation (SpO₂ 89–93%). Do not prescribe home O₂ for mild hypoxemia — it doesn't help and adds burden.
What changed from GOLD ABCD to ABE?
The 2023 GOLD update merged groups C and D into a single group E (Exacerbator). Previously, C = low symptoms + frequent exacerbations, D = high symptoms + frequent exacerbations — but they had the same initial treatment (LABA+LAMA ± ICS), so the distinction was clinically unnecessary. Now: A = low symptoms/low exacerbations, B = high symptoms/low exacerbations, E = any symptoms with ≥ 2 moderate or ≥ 1 hospitalized exacerbation. Simpler, more practical for treatment decisions.
When do you prescribe long-term oxygen therapy (LTOT) in COPD and what's the evidence?
Indications for LTOT (≥ 15h/day): (1) Resting PaO₂ ≤ 55 mmHg or SpO₂ ≤ 88%, (2) PaO₂ 56-59 with evidence of cor pulmonale, polycythemia (Hct > 55%), or RHF. Evidence: [NOTT, 1980 and [MRC, 1981 showed LTOT ≥ 15h/day reduces mortality in COPD with severe resting hypoxemia. Continuous O₂ (> 18h/day) was better than nocturnal-only. What about moderate hypoxemia? [LOTT, 2016: supplemental O₂ for STABLE COPD with moderate resting desaturation (SpO₂ 89-93%) or exercise desaturation showed NO mortality benefit. Bottom line: O₂ saves lives in severe resting hypoxemia (SpO₂ ≤ 88%). It does NOT help moderate desaturation — don't reflexively prescribe it.
📣 Sample Presentation
One-Liner
"Mr. Williams is a 66-year-old with COPD (GOLD stage II, FEV₁ 62%, Group E — 2 exacerbations last year), currently on tiotropium only. Here for medication optimization."
Key Points to Cover on Rounds
COPD GOLD II, Group E (≥2 exacerbations/year). Current: LAMA only (tiotropium). Undertreated. Recommended per GOLD 2024: escalate to triple therapy (LAMA + LABA + ICS) given eosinophils 320 (>300 supports ICS). Prescription: fluticasone furoate/umeclidinium/vilanterol (Trelegy) 100/62.5/25 one puff daily. Rescue: albuterol PRN. Azithromycin 250 mg MWF for exacerbation prevention (eosinophils >100 + frequent exacerbations). Vaccinations: pneumococcal (PCV20), flu, COVID, RSV — all updated. Pulmonary rehab: referred. Smoking: quit 3 years ago — reinforced. LDCT screening: current. Plan: PFTs in 3 months, reassess.
🧪 Workup
Workup — Pulmonary Nodule & Lung Cancer Screening
Workup for Pulmonary Nodule & Lung Cancer Screening: Targeted H&P → disease-specific labs → imaging as indicated → specialist consultation if needed.
- History: Onset, duration, severity, associated symptoms, prior episodes, medications
- Physical exam: Focused exam relevant to presentation
- Labs: CBC, BMP + disease-specific labs (see Overview tab)
- Imaging: As clinically indicated
💊 Medications
Medications — Pulmonary Nodule & Lung Cancer Screening
Medication details for Pulmonary Nodule & Lung Cancer Screening are in the Management tab with evidence-based dosing and trial citations. Check Drug Interactions and renal dosing before prescribing.
📈 Monitoring
Monitoring — Pulmonary Nodule & Lung Cancer Screening
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h ICU | Notify for significant deviations from baseline |
| Labs | Daily AM or PRN | Trend disease-specific markers (see Overview) |
| I&Os | Strict if volume-sensitive | UOP ≥ 0.5 mL/kg/hr |
| Clinical response | Each assessment | Symptoms improving? Functional status? Appetite? |
⚡ Summary
Summary
GOLD Classification
Spirometry: GOLD I-IV by FEV₁ %. Group A/B/E by symptoms + exacerbation history. Group E (≥ 2 exacerbations/year) = most aggressive treatment.
Inhaler Ladder
Group A: SABA PRN. Group B: LABA or LAMA. Group E: LAMA + LABA + ICS (triple therapy) if eos ≥ 300. If eos < 300: LAMA + LABA without ICS.
Exacerbation Rx
Prednisone 40 mg × 5 days + antibiotics (azithromycin or doxycycline) if purulent sputum + bronchodilators + O₂ target 88-92%.
LTOT
SpO₂ ≤ 88% or PaO₂ ≤ 55 at rest → O₂ ≥ 15h/day reduces mortality [NOTT, MRC]. Moderate desaturation (89-93%): no benefit [LOTT, 2016].
Exacerbation Prevention
Triple therapy (ICS/LABA/LAMA), azithromycin 250 MWF, roflumilast (eos ≥ 300), pulmonary rehab, smoking cessation, vaccinations.
Vaccines
PCV20, flu (annual), COVID, RSV (≥ 60), Tdap. All reduce exacerbation-related hospitalization.
📄 One Pager
One Pager — Pulmonary Nodule & Lung Cancer Screening
Print this page (Ctrl/Cmd + P) for a complete reference card. All tab content prints together.
PULMONARY NODULE & LUNG CANCER SCREENING — AT A GLANCE
📋 Diagnose: See Overview
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
🧪 Workup: See Workup tab
⚡ Treat: See Management tab
💊 Drugs: See Medications tab
📈 Monitor: See Monitoring tab
📣 Present: See Rounds tab
⚡ Management
Management — COPD — Chronic Management
See the Management section above for the full treatment algorithm with evidence-based recommendations and trial citations.
📄 One Pager
Pulmonology · One Pager
COPD
GOLD staging by FEV₁ + symptoms + exacerbations. Triple therapy (ICS/LABA/LAMA) for Group E. LTOT if SpO₂ ≤ 88%. Pulmonary rehab reduces hospitalizations. Vaccinations for all.
Classification
Spirometry: GOLD I-IV by FEV₁ %. Group A: few symptoms, 0-1 exacerbations. Group B: more symptoms, 0-1 exacerbations. Group E: ≥ 2 exacerbations/year or ≥ 1 hospitalization.
Acute Exacerbation
Prednisone 40 mg × 5 days + antibiotics (azithromycin or doxycycline if purulent sputum) + bronchodilators + O₂ target 88-92% (avoid O₂-induced hypercapnia). BiPAP for hypercapnic respiratory failure.
Chronic Management
Group A: SABA PRN. Group B: LABA or LAMA. Group E: LAMA + LABA + ICS (triple, if eos ≥ 300). Azithromycin 250 MWF (exacerbation prevention). LTOT if SpO₂ ≤ 88% [NOTT, MRC]. Pulmonary rehab. Vaccinations.
Key Drugs
Trelegy ElliptaICS/LAMA/LABA (triple)
Tiotropium18 mcg daily (LAMA)
Prednisone40 mg × 5d (exacerbation)
Azithromycin250 mg MWF (prevention)
Pitfalls
- O₂ target > 92% in COPD (risk of hypercapnia — target 88-92%)
- ICS without LABA (ICS monotherapy not recommended in COPD)
- Missing OSA overlap (common, worsens outcomes)
- Not referring for pulmonary rehab (most effective non-pharmacologic intervention)
Asthma
Reversible airway obstruction with eosinophilic inflammation and bronchial hyperresponsiveness. Chronic management is stepwise ICS-based. Acute exacerbations can kill — the "quiet chest" is the most dangerous sign.
🚨 Acute Exacerbation
Severity Assessment
| Severity | Features | PEF | Management |
|---|---|---|---|
| Mild-Moderate | Can speak in sentences, RR < 30, HR < 120, SpO₂ > 92% | > 50% predicted | Albuterol nebs + oral steroids. May discharge if responsive. |
| Severe | Speaking in words only, RR ≥ 30, HR ≥ 120, SpO₂ 90–92%, accessory muscle use | 25–50% | Continuous albuterol + ipratropium + IV steroids + Mg sulfate. Admit. |
| Life-threatening | "Silent chest" (no air movement), drowsy/confused, bradycardia, cyanosis | < 25% | ICU. Continuous nebs, IV Mg, consider IV terbutaline, ketamine, heliox. Prepare for intubation. |
"Silent chest" = the patient is too tight to wheeze. This is NOT improvement — it means air is not moving. This patient is about to arrest. Act immediately.
Acute Treatment Protocol
Immediate
Albuterol 2.5–5 mg nebulized q20 min × 3 (or continuous 10–15 mg/hr for severe). Add ipratropium (Atrovent) 0.5 mg to first 3 nebs — reduces hospitalizations Rodrigo, 2005.
Within 1 hour
Systemic corticosteroids: prednisone 40–60 mg PO or methylprednisolone 125 mg IV. Give early — takes 4–6h to work. Rowe, 2001: steroids within first hour reduced hospitalizations.
If severe / no response
Magnesium sulfate 2g IV over 20 min (smooth muscle relaxation). Goodacre, 2013 (3Mg Trial): improved PEF in severe exacerbations. Epinephrine 0.3–0.5 mg IM if anaphylaxis component or imminent arrest.
Refractory / ICU
IV terbutaline (selective β₂ agonist). Ketamine 0.5–1 mg/kg IV (bronchodilator properties). Heliox (80:20 helium:oxygen — reduces work of breathing in severe obstruction). BiPAP — may avoid intubation. Intubation is LAST RESORT — asthma patients are extremely difficult to ventilate (air trapping, high airway pressures, dynamic hyperinflation).
Intubation in status asthmaticus is dangerous: post-intubation dynamic hyperinflation (breath stacking) → auto-PEEP → hemodynamic collapse. Settings: low RR (8–12), prolonged I:E ratio (1:4–1:5), permissive hypercapnia. If peri-arrest hypotension post-intubation → disconnect from vent for 30–60 sec to allow exhalation.
Disposition
- Discharge if: PEF > 70% predicted, symptom improvement, can speak in full sentences, SpO₂ > 94% on RA. Send with: prednisone 40 mg × 5 days (no taper needed for ≤ 5 days), albuterol PRN, step up controller if needed.
- Admit if: PEF < 50% after treatment, persistent hypoxia, unable to speak in sentences, prior near-fatal asthma, high-risk features.
💊 Chronic Stepwise Therapy (GINA 2023)
Stepwise Approach
Key 2023 GINA change: SABA-only rescue is no longer recommended as monotherapy for ANY severity. All patients should have an ICS-containing regimen — either as-needed ICS-formoterol (Track 1) or regular low-dose ICS + SABA rescue (Track 2).
| Step | Track 1 (Preferred) | Track 2 (Alternative) | Notes |
|---|---|---|---|
| Step 1 (Mild intermittent) | As-needed low-dose ICS-formoterol (e.g., budesonide-formoterol PRN) | Low-dose ICS whenever SABA used | No more SABA-only. SYGMA, 2018: PRN budesonide-formoterol was superior to SABA alone for severe exacerbation prevention. |
| Step 2 (Mild persistent) | As-needed low-dose ICS-formoterol | Daily low-dose ICS + SABA PRN | ICS reduces exacerbations, hospitalizations, and death from asthma. This is the foundation. |
| Step 3 (Moderate) | Low-dose ICS-formoterol maintenance + reliever (MART) | Low-dose ICS-LABA + SABA PRN | MART = Maintenance And Reliever Therapy (same inhaler for both). Reduces exacerbation risk. |
| Step 4 (Moderate-severe) | Medium-dose ICS-formoterol maintenance + reliever | Medium/high-dose ICS-LABA + SABA PRN | Consider adding LAMA (tiotropium) if uncontrolled. |
| Step 5 (Severe) | Refer to specialist. High-dose ICS-LABA + LAMA. Phenotype: eosinophilic → add biologic (anti-IgE, anti-IL5, anti-IL4R). Low-dose OCS as last resort. | Biologics: omalizumab (anti-IgE), mepolizumab/benralizumab (anti-IL5), dupilumab (anti-IL4R), tezepelumab (anti-TSLP). | |
Asthma vs COPD — Key Differences
| Feature | Asthma | COPD |
|---|---|---|
| Age of onset | Usually childhood/young adult | Usually > 40, smoker |
| Reversibility | Reversible (FEV₁ improves ≥ 12% + 200 mL post-bronchodilator) | Irreversible (FEV₁/FVC stays < 0.70) |
| Inflammation | Eosinophilic (Th2, IgE-mediated) | Neutrophilic (CD8+, macrophages) |
| ICS role | Cornerstone of therapy | Add-on only if eos ≥ 300 |
🔍 Overview
Overview
Chronic inflammatory airway disease with reversible obstruction. ~8% adults. Variable wheeze/cough/dyspnea worse at night. Diagnosis: spirometry with reversibility (≥12% AND ≥200mL).
🧪 Workup
Workup
- Spirometry — FEV₁/FVC <0.70 + reversibility
- Peak flow variability >20%
- Methacholine challenge — if normal PFTs + suspected asthma
- FeNO >25ppb → eosinophilic inflammation
- CBC eosinophils — biologic selection
- IgE — omalizumab candidacy
- Allergy testing
- CXR to exclude other diagnoses
🚨 Management
Management
- Step 1: PRN low-dose ICS-formoterol
- Step 2: Daily low-dose ICS
- Step 3: Low-dose ICS/LABA
- Step 4: Medium/high ICS/LABA ± LAMA
- Step 5: Biologic by phenotype
Before escalating: check technique, adherence, triggers, comorbidities (GERD, sinusitis, VCD).
🔄 Updated Practice: Old teaching: step 1 asthma treatment is SABA PRN alone (albuterol as needed). Current practice: GINA 2019+ no longer recommends SABA-only treatment for ANY asthma severity. Even mild intermittent asthma should use as-needed low-dose ICS-formoterol (SYGMA 1 & 2 trials). SABA-only use without ICS increases the risk of severe exacerbations and death. The paradigm shift: every puff of a bronchodilator should come with an anti-inflammatory.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Fluticasone/salmeterol | 100-500/50 BID | DPI | ICS/LABA Steps 3-4 |
| Budesonide/formoterol | 80-160/4.5 | DPI | SMART strategy |
| Tiotropium Respimat | 2.5mcg 2 puffs daily | Inhaler | LAMA add-on Step 4-5 |
| Prednisone | 40-60mg × 5d | PO | Exacerbation — no taper |
| Mepolizumab | 100mg q4wk | SQ | Anti-IL-5 (eos asthma) |
| Dupilumab | 200-300mg q2wk | SQ | Anti-IL-4/13 |
📊 Monitoring
Monitoring
- Spirometry at dx, 3-6mo, then q1-2y
- ACT ≤19 = not controlled
- Exacerbation frequency
- FeNO trending
- Inhaler technique — observe every visit
- Adherence — refill records
📋 On Rounds
Why can't you give a LABA alone in asthma?
SMART Trial, 2006 (Salmeterol Multicenter Asthma Research Trial) was stopped early because salmeterol monotherapy increased asthma-related deaths. The mechanism: LABAs provide bronchodilation but do NOT address the underlying eosinophilic inflammation. Patients feel better (less bronchospasm) but the inflammation silently worsens → sudden severe exacerbation → death. LABAs must ALWAYS be paired with ICS in asthma. This is why combination inhalers (ICS-LABA) are standard. In COPD, LABA monotherapy is safe because the pathophysiology is different (neutrophilic, not as ICS-responsive).
What is the biggest danger of intubating an asthmatic?
Dynamic hyperinflation (breath stacking → auto-PEEP → hemodynamic collapse). Severe bronchospasm means air goes in but can't get out fast enough before the next breath. Each breath adds to the trapped volume (auto-PEEP) → intrathoracic pressure rises → venous return drops → cardiac output crashes → PEA arrest. Prevention: low respiratory rate (8–12), prolonged expiratory time (I:E 1:4 to 1:5), permissive hypercapnia (accept high CO₂). If they crash post-intubation: disconnect from ventilator for 30–60 seconds → manually compress the chest → allows trapped air to escape → hemodynamics recover.
Why did GINA remove SABA-only as first-line rescue?
SYGMA 1 & 2, 2018 showed that PRN budesonide-formoterol (ICS-formoterol used only as rescue) reduced severe exacerbations by 64% compared to SABA-only. SABA treats bronchospasm but not the underlying inflammation — patients using only SABA have worse outcomes even if they feel fine between episodes. The paradigm shift: even the mildest asthma has ongoing airway inflammation that needs anti-inflammatory therapy. Using ICS with every rescue dose ensures inflammation is treated at every symptomatic episode.
A patient on maximum ICS/LABA still has poorly controlled asthma. What are the next steps before adding a biologic?
Before escalating to Step 5 (biologics), always reassess the basics — "treatable traits": (1) Inhaler technique: 70-80% of patients use inhalers incorrectly — observe return demonstration. Spacer for MDIs. (2) Adherence: check refill records — are they actually using the controller? (3) Triggers: allergens (pets, dust mites, mold), occupational exposures, GERD, sinusitis, NSAID/ASA sensitivity. (4) Confirm the diagnosis: consider vocal cord dysfunction, COPD, cardiac asthma. (5) Add-on before biologics: tiotropium (Spiriva Respimat — add LAMA to ICS/LABA), LTRA (montelukast — less effective). If truly refractory → biologic evaluation: check eosinophils, FeNO, IgE. High eos → mepolizumab, benralizumab. High IgE + allergic → omalizumab. Type 2 inflammation (high eos + FeNO) → dupilumab, tezepelumab.
📣 Sample Presentation
One-Liner
"Ms. Brown is a 24-year-old with moderate persistent asthma on medium-dose ICS/LABA (Advair 250/50 BID) presenting to clinic with continued nocturnal symptoms 3×/week and rescue inhaler use 4×/week. Poorly controlled."
Key Points to Cover on Rounds
Poorly controlled asthma on Step 4 therapy. Before escalating: (1) Inhaler technique assessed — incorrect MDI technique identified, corrected with spacer education and observed return demo. (2) Adherence: admits missing doses 2-3×/week — counseled. (3) Trigger assessment: cat at home (allergen), no mattress encasement (dust mites), GERD symptoms (omeprazole started). (4) Spirometry today: FEV₁ 72%, 15% improvement post-bronchodilator. If still uncontrolled after optimizing technique/adherence/triggers → Step 5: add tiotropium (Spiriva Respimat) or refer for biologic evaluation (check eosinophils, FeNO, IgE). Asthma Action Plan provided. Plan: return in 6 weeks.
⚡ Summary
Summary
Step Therapy
Step 1: PRN low-dose ICS-formoterol. Step 2: daily low-dose ICS. Step 3: medium ICS/LABA. Step 4: high ICS/LABA. Step 5: add LAMA, biologic, or OCS.
Before Escalating
Check: inhaler technique (70-80% incorrect), adherence, trigger avoidance, comorbidities (GERD, sinusitis, VCD). Fix these first.
Biologics
High eos → mepolizumab, benralizumab. High IgE + allergic → omalizumab. Type 2 inflammation → dupilumab, tezepelumab.
Acute Exacerbation
Albuterol neb q20 min × 3, ipratropium, systemic steroids (prednisone 40-60 mg × 5 days). MgSO₄ 2g IV if severe. Assess peak flow.
Action Plan
Green (well): continue controller. Yellow (worsening): increase ICS, start OCS, use rescue. Red (emergency): call 911, albuterol, start OCS.
Asthma vs COPD
Asthma: reversible obstruction, normal DLCO, younger, atopic. COPD: fixed obstruction, low DLCO, older, smoking. ACO: features of both → treat with ICS + bronchodilators.
📄 One Pager
Pulmonology · One Pager
Asthma
Step therapy: low-dose ICS → ICS/LABA → add LAMA → biologic. Before escalating: check technique, adherence, triggers. Acute: albuterol + steroids. Action plan for all patients.
Diagnosis
Variable airflow obstruction + symptoms (wheeze, dyspnea, cough, chest tightness). Spirometry: FEV₁/FVC < 0.70 with significant reversibility (≥ 12% AND ≥ 200 mL). Normal DLCO distinguishes from emphysema.
Acute Exacerbation
Albuterol neb q20 min × 3 + ipratropium. Systemic steroids: prednisone 40-60 mg × 5 days. MgSO₄ 2g IV if severe. Peak flow or FEV₁ to assess response. If not improving → ICU.
Stepwise Chronic Management
Step 1: PRN low-dose ICS-formoterol. Step 2: daily low-dose ICS. Step 3: medium ICS/LABA. Step 4: high ICS/LABA ± LAMA. Step 5: add biologic (based on eos, FeNO, IgE). Before escalating: fix technique + adherence + triggers.
Key Drugs
Albuterol2 puffs q4-6h PRN
Fluticasone/salmeterol250/50 BID
Prednisone40-60 mg × 5d (exacerbation)
Dupilumab200-300 mg SQ q2wk (biologic)
Pitfalls
- Incorrect inhaler technique (70-80% use incorrectly — observe return demo)
- SABA-only treatment (all persistent asthma needs a controller)
- Not checking eos/FeNO before biologics
- Missing VCD (vocal cord dysfunction mimics asthma)
Evidence Base
RCT Library
Key trials behind every recommendation in Rounds. Click any trial for full details.
⌕
AECOPD
Albert et al. Azithromycin COPD Trial
Does daily azithromycin reduce COPD exacerbations?
Positive (with caveats)
Anthonisen Criteria Trial
Do antibiotics benefit patients with AECOPD?
Positive (symptom-guided)
Austin et al. Oxygen Titration Trial
Does titrated O₂ (SpO₂ 88–92%) reduce mortality vs high-flow O₂ in AECOPD?
Positive — practice changing
Brochard et al. NIV in AECOPD
Does NIV (BiPAP) reduce intubation and mortality in AECOPD with respiratory failure?
Positive — landmark trial
IMPACT Trial
Does triple therapy (ICS/LABA/LAMA) reduce exacerbations vs dual therapy in symptomatic COPD?
Positive for high-risk patients
Plant et al. NIV on General Wards
Is early NIV feasible and beneficial for AECOPD with mild-moderate acidosis on general wards?
Positive — NIV effective on wards
REDUCE Trial
Is 5-day prednisone non-inferior to 14-day course for AECOPD?
5 days = 14 days — use 5 days
Soriano et al. AECOPD Triggers
What are the common infectious triggers of AECOPD?
Observational
Turner et al. MgSO₄ in Acute Bronchospasm
Does IV magnesium sulphate improve lung function in acute severe asthma/bronchospasm?
Positive (asthma); extrapolated to AECOPD
UPLIFT Trial
Does tiotropium slow lung function decline and reduce exacerbations in COPD?
Positive for exacerbation prevention
ARDS
ACURASYS Trial
Does early cisatracurium infusion improve outcomes in moderate-severe ARDS?
Positive
EOLIA Trial
Does early VV-ECMO reduce 60-day mortality in very severe ARDS?
Negative (trend to benefit)
FACTT Trial
Does conservative vs liberal fluid strategy improve outcomes in ARDS?
Conservative strategy preferred
OSCILLATE Trial
Does HFOV improve outcomes in moderate-severe ARDS?
Negative — HFOV harmful
PROSEVA Trial
Does prone positioning reduce 28-day mortality in severe ARDS?
Positive — practice changing
ROSE Trial
Does early cisatracurium improve outcomes in ARDS when lighter sedation is standard?
Negative — NMB not routinely recommended
ARDS / Ventilation
ARDSnet ARMA Trial
Does low tidal volume ventilation (6 mL/kg IBW) reduce mortality in ARDS?
Positive — practice changing
Cardiogenic Shock
IABP-SHOCK II Trial
Does IABP reduce 30-day mortality in cardiogenic shock complicating MI?
Negative — practice changing
SHOCK Trial
Does early revascularization reduce mortality in cardiogenic shock complicating MI?
Early revascularization preferred
DKA / Glucose
ADA Standards of Care 2023
What are the recommended targets for inpatient glycemic management?
Guideline
Hepatic Encephalopathy
RFHE Trial (Rifaximin in Hepatic Encephalopathy)
Does rifaximin prevent recurrence of overt hepatic encephalopathy?
Positive
Airway & Ventilator Management / Sedation
ABC Trial (Awakening & Breathing Coordination)
Does pairing spontaneous awakening trials with spontaneous breathing trials improve outcomes?
Positive — ABCDEF bundle foundation
ABC Trial (Awakening & Breathing Coordination)
Does pairing spontaneous awakening trials with spontaneous breathing trials improve outcomes?
Positive — ABCDEF bundle foundation
Post-Cardiac Arrest
Kilgannon et al. Hyperoxia Post-Arrest
Is arterial hyperoxia associated with worse outcomes after cardiac arrest?
Avoid hyperoxia post-arrest
TTM-2 Trial
Does targeted hypothermia (33°C) reduce mortality vs targeted normothermia (37.5°C) post-arrest?
Normothermia non-inferior — major practice change
Sedation
MENDS Trial
Does dexmedetomidine reduce delirium vs lorazepam in mechanically ventilated patients?
Dexmedetomidine preferred
SEDCOM Trial
Does dexmedetomidine reduce delirium vs midazolam in mechanically ventilated patients?
Dexmedetomidine preferred
Sedation / Delirium
MIND-USA Trial
Do haloperidol or ziprasidone reduce delirium duration in critically ill patients?
Negative — antipsychotics don't treat ICU delirium
Sepsis
ADRENAL Trial
Does hydrocortisone reduce 90-day mortality in septic shock?
Neutral (faster reversal, no survival benefit)
ALBIOS Trial
Does albumin supplementation (target ≥30 g/L) reduce 28-day mortality in sepsis?
Negative
APROCCHSS Trial
Do hydrocortisone + fludrocortisone reduce 90-day mortality in septic shock?
Positive
CITRIS-ALI Trial
Does IV vitamin C reduce organ failure in sepsis-induced ARDS?
Neutral primary / signal secondary
PROWESS-SHOCK Trial
Does drotrecogin alfa (activated protein C) reduce mortality in septic shock?
Negative — drug withdrawn
Surviving Sepsis Campaign Guidelines
What are evidence-based recommendations for sepsis and septic shock management?
Guideline
Sepsis / Antibiotics
PRORATA Trial
Does procalcitonin-guided antibiotic discontinuation reduce use without harm?
Positive — supports PCT-guided de-escalation
Sepsis / Fluids
SMART Trial
Are balanced crystalloids superior to normal saline in critically ill adults?
Balanced crystalloids preferred in ICU
Sepsis / Vasopressors
SOAP II Trial
Is norepinephrine superior to dopamine as first-line vasopressor in shock?
Norepinephrine preferred
VASST Trial
Does adding vasopressin to norepinephrine reduce mortality in septic shock?
Neutral — vasopressin as catecholamine-sparing agent
Status Epilepticus
ESETT Trial
Which second-line agent is most effective for benzodiazepine-refractory status epilepticus?
Neutral — all equivalent
RAMPART Trial
Is IM midazolam non-inferior to IV lorazepam for prehospital status epilepticus?
IM midazolam preferred prehospital
Upper GI Bleed
TRIGGER Trial
Does liberal vs restrictive transfusion affect outcomes in upper GI bleed?
Restrictive strategy preferred
ACS / MI
ISIS-2 Trial
Does aspirin and/or streptokinase reduce mortality in acute MI?
Landmark Positive
PROVE IT–TIMI 22 Trial
Is intensive statin therapy better than standard therapy after ACS?
Positive — high-intensity statin after ACS
Cardiology / Lipids
4S Trial (Scandinavian Simvastatin Survival Study)
Does simvastatin reduce mortality in patients with CHD?
Landmark Positive — statins save lives
Stable CAD / Revascularization
COURAGE Trial
Does PCI beat optimal medical therapy in stable CAD?
Neutral — PCI did not beat medical therapy
SYNTAX Trial
PCI vs CABG for complex multivessel or left-main CAD?
CABG wins for complex disease
FREEDOM Trial
CABG vs PCI in diabetic patients with multivessel CAD?
Positive — CABG wins in diabetics
Heart Failure
SOLVD Treatment Trial
Does enalapril reduce mortality in HFrEF?
Landmark Positive — ACEi standard for HFrEF
RALES Trial
Does spironolactone reduce mortality in severe HFrEF?
Landmark Positive — MRA became HFrEF pillar
PARADIGM-HF Trial
Is sacubitril/valsartan superior to enalapril in HFrEF?
Landmark Positive — ARNI replaced ACEi
MADIT-II Trial
Does prophylactic ICD reduce mortality post-MI with low EF?
Positive — ICD for primary prevention
PLATO Trial
Is ticagrelor superior to clopidogrel in ACS?
Positive — ticagrelor preferred P2Y12
HEART Pathway Trial
Can HEART score safely identify low-risk chest pain for early ED discharge?
Positive — safe early discharge
TIMACS Trial
Does early (<24h) vs delayed (>36h) intervention improve outcomes in NSTEMI?
Positive in high-risk (GRACE >140)
ACORN Trial
Does cefepime cause less AKI than pip-tazo when combined with vancomycin?
Positive — cefepime preferred with vanc
Sepsis — Early Resuscitation
Rivers EGDT Trial
Does early goal-directed therapy improve survival in septic shock?
Landmark Positive — changed sepsis management
ProCESS Trial
Is protocolized EGDT superior to usual care?
Neutral — protocol not needed
CORTICUS Trial
Does hydrocortisone improve survival in septic shock?
Neutral — faster shock reversal, no survival benefit
Critical Care / Glucose
NICE-SUGAR Trial
Does intensive glucose control improve ICU outcomes?
Negative — tight control harms ICU patients
COVID-19
RECOVERY Dexamethasone Trial
Does dexamethasone reduce mortality in hospitalized COVID-19?
Landmark Positive
ACTT-1 Trial
Does remdesivir improve recovery in hospitalized COVID-19?
Positive — shortens recovery
BNT162b2 Pfizer-BioNTech Vaccine Trial
Is the BNT162b2 mRNA vaccine effective against COVID-19?
Landmark Positive — 95% efficacy
Diabetes
DCCT Trial
Does intensive glucose control reduce microvascular complications in T1DM?
Landmark Positive
UKPDS 34
Does metformin improve outcomes in overweight T2DM?
Landmark Positive — metformin first-line
ACCORD Trial
Does very intensive A1c lowering reduce CV events in T2DM?
Negative — increased mortality
ADVANCE Trial
Does intensive glucose control reduce events in T2DM?
Mixed — microvascular but not macrovascular
DPP (Diabetes Prevention Program)
Can lifestyle or metformin prevent T2DM?
Landmark Positive
EMPA-REG OUTCOME
Does empagliflozin reduce CV events in T2DM with CVD?
Landmark Positive — SGLT2i revolution
LEADER Trial
Does liraglutide reduce CV events in T2DM?
Positive — GLP-1 RA cardioprotective
Hypertension
SPRINT Trial
Does intensive BP control (<120) reduce CV events?
Positive — lower target saves lives
ALLHAT Trial
Which antihypertensive class is best?
Thiazide remains first-line
IV Fluids
SALT-ED Trial
Balanced crystalloids vs normal saline in non-critically ill adults?
Positive — balanced crystalloids preferred
HIV
START Trial (INSIGHT-START)
Should ART start immediately regardless of CD4?
Landmark Positive — treat all HIV immediately
SMART Trial
Can ART be safely interrupted based on CD4?
Negative — never stop ART
HPTN 052 Trial
Does early ART reduce HIV transmission?
Landmark Positive — U=U foundation
ACTG 076 Trial
Does zidovudine reduce vertical HIV transmission?
Landmark Positive — PMTCT became standard
Infectious Disease — Oral Step-Down
POET Trial
Can stable endocarditis switch from IV to oral antibiotics?
Positive — oral step-down safe
OVIVA Trial
Are oral antibiotics noninferior to IV for bone/joint infections?
Positive — oral sufficient
Oncology
IRIS Trial — Imatinib for CML
Is imatinib superior to interferon for CML?
Landmark Positive — targeted therapy
HERA Trial — Trastuzumab for HER2+ Breast Cancer
Does trastuzumab improve outcomes in HER2+ breast cancer?
Landmark Positive
CLEOPATRA Trial
Does adding pertuzumab to trastuzumab improve metastatic HER2+ breast cancer?
Positive — dual HER2 blockade
KEYNOTE-024 Trial
Is pembrolizumab better than chemo in high PD-L1 NSCLC?
Positive — immunotherapy era
FLAURA Trial
Is osimertinib superior to first-gen EGFR TKIs?
Positive — osimertinib first-line
SHARP Trial — Sorafenib for HCC
Does sorafenib improve survival in advanced HCC?
Positive — first systemic HCC therapy
IMbrave150 Trial
Is atezolizumab + bevacizumab superior to sorafenib in HCC?
Positive — new first-line for HCC
Hematology / VTE
CLOT Trial
Is LMWH better than warfarin for cancer-associated VTE?
Positive — LMWH beat warfarin
Transfusion
TRICC Trial
Restrictive vs liberal transfusion in critically ill patients?
Positive — restrictive became standard
Villanueva Restrictive Transfusion Trial
Restrictive vs liberal transfusion in acute upper GI bleeding?
Positive — restrictive is BETTER in GI bleed
Neurology / Stroke
NINDS tPA Trial
Does IV alteplase improve outcomes in acute ischemic stroke?
Landmark Positive — tPA changed stroke care
MR CLEAN Trial
Does thrombectomy improve outcomes in large vessel occlusion stroke?
Landmark Positive — thrombectomy standard for LVO
Procedures Guide
Step-by-step for the 5 core bedside procedures every resident must master. Landmarks, equipment, technique, and complications.
🩺 Central Venous Catheter
Site Selection
| Site | Pros | Cons | Preferred For |
|---|---|---|---|
| Right IJ | Most commonly used. Straight path to SVC. Low PTX risk with US. Easy for right-handed operators. | Neck motion limitation. Infection risk if tracheostomy nearby. | Dialysis catheters, Swan-Ganz, general access. |
| Subclavian | Lowest infection rate. Most comfortable for patient. Best for long-term use. | Highest PTX risk. Non-compressible if arterial puncture. Harder with US. | Long-term access, TPN, when lower infection risk critical. |
| Femoral | Easiest landmark access. No PTX risk. No airway compromise. | Highest infection rate. DVT risk. Can't use for CVP monitoring (inaccurate). Limits mobility. | Emergent access, codes, coagulopathy (compressible site). |
IJ — Step-by-Step (Ultrasound-Guided)
Prep
Consent, time-out, cap/mask/gown/gloves, full sterile drape. Position: Trendelenburg 15–20° (distends IJ). Head turned slightly contralateral. US with sterile probe cover.
Identify
IJ = lateral, round, compressible. Carotid = medial, pulsatile, non-compressible. Confirm with Doppler if unsure. Use short-axis (transverse) view for access.
Access
Lidocaine to skin. 18G finder needle at 45° angle into IJ under US. Aspirate dark non-pulsatile blood. Thread guidewire through needle (should pass easily — if resistance, reposition). Remove needle over wire.
Dilate
Nick skin with scalpel. Thread dilator over wire with twisting motion — only insert 2–3 cm (just enough to dilate the tract). Remove dilator.
Catheter
Thread catheter over wire. Right IJ: 15–17 cm depth (tip at cavoatrial junction). Left IJ: 17–19 cm. ALWAYS confirm wire out the back of the catheter before securing.
Confirm
Aspirate and flush all ports. Suture + sterile dressing. Post-procedure CXR to confirm tip position (at carina or slightly above) and rule out PTX.
NEVER lose control of the wire. Always have a hand on it. If the wire won't thread → reposition the needle, don't force. If you aspirate bright red pulsatile blood → you're in the carotid → remove needle, hold pressure × 10 min.
🩺 Arterial Line
Sites & Technique
| Site | Notes |
|---|---|
| Radial (1st choice) | Most common. Superficial, easy to access. Modified Allen test before (check ulnar collateral — though evidence for utility is weak). Wrist extension 30° on roll. US-guided preferred. 20G catheter-over-needle. Angle 15–30°. |
| Femoral (2nd) | Larger artery, easier to access in shock (radial may be pulseless). Below inguinal ligament, lateral to femoral vein (NAVEL: Nerve-Artery-Vein-Empty-Lymphatics). |
| Brachial / dorsalis pedis | Alternative sites. Brachial is an end-artery → higher ischemia risk. |
Indications
- Continuous BP monitoring (vasopressor titration, hemodynamic instability)
- Frequent ABG sampling (respiratory failure, vent management)
- Intra-aortic balloon pump monitoring
🩺 Paracentesis
Technique
Position
Supine or slight lateral decubitus (fluid pools to dependent side). Empty bladder first (or confirm with US).
Landmark
Left lower quadrant, 2 fingerbreadths medial and 2 cephalad to ASIS. Avoids the inferior epigastric artery (runs in the rectus sheath). US-guided preferred — mark the pocket with the deepest fluid and no underlying bowel.
Access
Sterile prep. Lidocaine track down to peritoneum (you'll feel a "pop"). 18G needle or 15–18G catheter-over-needle (preferred for large volume). Z-track technique: pull skin 2 cm caudally before inserting → prevents persistent leak after removal.
Drain
Diagnostic: 60–100 mL (send cell count, albumin, protein, culture in blood bottles). Therapeutic: drain to dryness (up to 8–10 L). If > 5 L → give albumin 6–8 g per liter removed.
INR and platelets are NOT contraindications. Bleeding rate < 1% even with coagulopathy. Do NOT transfuse before paracentesis in cirrhotic patients.
🩺 Thoracentesis
Technique
Position
Sitting upright, leaning forward over bedside table (arms resting on pillow). Maximizes dependent pooling and intercostal space width.
Landmark
US-guided mandatory (reduces PTX from ~10% to < 1%). Mark site with largest fluid pocket, ≥ 10 mm depth, no lung sliding. Insert 1–2 intercostal spaces below the fluid meniscus. Go OVER the top of the rib (neurovascular bundle runs under each rib — intercostal artery, vein, nerve).
Access
Sterile prep + drape. Lidocaine to skin → deeper → walk over the top of the rib → into the pleural space (you'll aspirate fluid). Insert 16–18G catheter-over-needle or thoracentesis kit (safe-T-centesis). Attach tubing to vacuum bottles.
Drain
Diagnostic: 50–60 mL. Therapeutic: up to 1.5 L maximum per session (risk of re-expansion pulmonary edema if > 1.5 L). Stop if: cough, chest tightness, or pleuritic pain (lung against chest wall).
Post-procedure CXR is NOT routinely needed if US-guided and uncomplicated. Only get CXR if: air aspirated, symptoms develop, or multiple needle passes.
🩺 Lumbar Puncture
Technique
Position
Lateral decubitus (fetal position — knees to chest, chin tucked) or seated upright leaning forward. Lateral decubitus is required for accurate opening pressure measurement.
Landmark
L3–L4 or L4–L5 interspace. Find the iliac crests (a line between them = Tuffier's line = approximately L4 vertebral body). Palpate the spinous processes. Spinal cord ends at L1–L2 in adults — always go below L2.
Access
Sterile prep + drape. Lidocaine skin to deeper tissues. 22G spinal needle with stylet, bevel up (parallel to the longitudinal dural fibers). Aim slightly cephalad (toward the umbilicus). Advance slowly — feel a "pop" through the ligamentum flavum and dura. Remove stylet to check for CSF flow.
Collect
Opening pressure first (attach manometer — patient must be in lateral decubitus with legs slightly extended for accurate reading). Normal: 6–20 cmH₂O. Collect 4 tubes (~1–2 mL each): Tube 1 = cell count, Tube 2 = glucose + protein, Tube 3 = Gram stain + culture, Tube 4 = cell count (to distinguish traumatic tap from SAH — RBC should decrease from tube 1 to 4 in traumatic tap).
When to Get CT Before LP
- CT first if: immunocompromised, CNS disease history, new seizure, papilledema, focal neuro deficit, altered consciousness
- None of these → LP without CT is safe. Do NOT delay antibiotics for imaging if meningitis suspected.
Post-LP headache (~10%): positional (worse upright, better supine). Treat with caffeine, IV fluids, analgesics. Refractory → epidural blood patch. Use atraumatic needles (Sprotte/Whitacre) when available — 50% lower headache rate vs cutting needles.
ECG Interpretation
A systematic approach to every ECG. Rate → rhythm → axis → intervals → ST-T changes. Learn the patterns that can kill — STEMI, hyperkalemia, PE, WPW, and long QT.
📐 Systematic ECG Reading
Step 1 — Rate
- Regular rhythm: 300 ÷ (number of large boxes between R-R). Or: 300, 150, 100, 75, 60, 50 for 1, 2, 3, 4, 5, 6 large boxes.
- Irregular rhythm: count QRS complexes in a 6-second strip (30 large boxes) × 10
- Normal: 60–100 bpm. Bradycardia < 60. Tachycardia > 100.
Step 2 — Rhythm
- Regular vs irregular? (march out R-R intervals with calipers or paper)
- P waves present? Upright in II = sinus origin. Absent = Afib/junctional. Flutter waves (sawtooth) = Aflutter.
- P:QRS relationship? 1:1 = sinus. More P's than QRS = AV block. No relationship = complete heart block.
Step 3 — Axis
| Lead I | Lead aVF | Axis |
|---|---|---|
| ↑ | ↑ | Normal (−30° to +90°) |
| ↑ | ↓ | Left axis deviation (think: LAFB, LVH, inferior MI) |
| ↓ | ↑ | Right axis deviation (think: RVH, PE, LPFB, lateral MI) |
| ↓ | ↓ | Extreme/indeterminate (think: ventricular rhythm, lead misplacement) |
Step 4 — Intervals
| Interval | Normal | If Abnormal |
|---|---|---|
| PR | 120–200 ms (3–5 small boxes) | Long (> 200): 1st degree AV block. Short (< 120): WPW (look for delta wave), junctional rhythm. |
| QRS | < 120 ms (3 small boxes) | 120–150: incomplete BBB, IVCD. > 150: LBBB, RBBB. > 200: hyperkalemia, TCA OD, severe conduction disease. |
| QTc | M < 450 ms, F < 470 ms | > 500 ms: high risk for torsades de pointes. Causes: drugs (haloperidol, ondansetron, amiodarone, FQ), electrolytes (↓K, ↓Mg, ↓Ca), congenital LQTS. |
Step 5 — ST Segment & T Waves
- ST elevation: STEMI, pericarditis (diffuse + PR depression), Brugada, early repolarization, LV aneurysm
- ST depression: ischemia (demand or NSTEMI), digoxin ("scooped"), LVH strain pattern, reciprocal changes
- T wave inversion: ischemia, Wellens pattern (LAD critical stenosis), PE (right precordial), LVH strain, intracranial event (deep cerebral T waves)
- Peaked T waves: hyperkalemia (#1), early STEMI (hyperacute T waves), benign early repolarization
⚡ Must-Know Patterns
| Pattern | ECG Findings | Clinical Significance |
|---|---|---|
| Hyperkalemia progression | Peaked T waves → prolonged PR → loss of P waves → wide QRS → sine wave → VFib/asystole | Give calcium immediately if QRS widening. The most lethal ECG pattern you'll see. See Hyperkalemia. |
| STEMI | ST elevation ≥ 1 mm in ≥ 2 contiguous limb leads, or ≥ 2 mm in precordial leads. Reciprocal ST depression. See STEMI Criteria tab. | Cath lab activation. |
| De Winter T waves | Upsloping ST depression + peaked T waves in V1–V6. No ST elevation. | LAD STEMI-equivalent. Activate cath lab even without classic STE. |
| Wellens syndrome | Type A: biphasic T waves in V2–V3. Type B: deep symmetric T wave inversions in V2–V3. | Critical LAD stenosis. Patient may be pain-free when ECG obtained. Do NOT stress test → send to cath lab. |
| PE | Sinus tachycardia (#1), S1Q3T3 (not sensitive), right axis deviation, RBBB, right precordial T inversions (V1–V4), P pulmonale | ECG is often normal in PE. Most reliable sign: sinus tachycardia. |
| WPW | Short PR (< 120 ms) + delta wave (slurred QRS upstroke) + wide QRS | Avoid AV nodal blockers (adenosine, CCB, digoxin, BB) in Afib + WPW → can cause VFib. Use procainamide or cardioversion. |
| Brugada | Type 1: coved ST elevation > 2 mm + T wave inversion in V1–V3 (pseudo-RBBB). | Risk of sudden cardiac death. Unmasked by fever, Na-channel blockers. Treatment: ICD. |
| TCA overdose | QRS > 100 ms + R wave in aVR > 3 mm + right axis + sinus tachycardia | Sodium bicarbonate. QRS > 160 = VT risk. See Toxicology. |
| Complete heart block | Regular P waves marching through at one rate, QRS at a slower rate. No PR relationship. AV dissociation. | Transcutaneous pacing → transvenous pacing. Atropine may help if junctional escape (narrow QRS). Atropine does NOT work if infranodal block (wide QRS). |
| Pericarditis | Diffuse ST elevation (concave-up, "smiley face") + PR depression (best in II) + Spodick's sign (downsloping TP segment) | Distinguish from STEMI: diffuse (not territorial), PR depression, no reciprocal changes, concave-up morphology. |
❤️ STEMI Localization
| Territory | STE Leads | Reciprocal Δ | Coronary Artery | Complications |
|---|---|---|---|---|
| Anterior | V1–V4 | II, III, aVF | LAD | LV dysfunction, CHF, VT/VF, anterior wall aneurysm |
| Lateral | I, aVL, V5, V6 | III, aVF | LCx or diagonal | Mitral regurgitation (papillary muscle) |
| Inferior | II, III, aVF | I, aVL | RCA (85%) or LCx (15%) | Bradycardia, heart block (RCA supplies AV node). Check right-sided leads (V4R) for RV infarct. |
| RV infarct | V4R ≥ 1 mm STE | — | Proximal RCA | Preload-dependent → fluids, NO nitrates/diuretics/morphine. |
| Posterior | ST depression V1–V3 (mirror image) + tall R wave V1 | — | PDA or LCx | Often missed. Get posterior leads (V7–V9): STE ≥ 0.5 mm confirms. |
New LBBB is no longer an automatic STEMI-equivalent. Use Sgarbossa criteria: (1) concordant STE ≥ 1 mm = 5 pts, (2) ST depression ≥ 1 mm in V1–V3 = 3 pts, (3) discordant STE ≥ 5 mm = 2 pts (modified: use proportional ratio > 0.25 of preceding S wave). Score ≥ 3 → STEMI despite LBBB.
Code Blue & Rapid Response
Your pocket card for running or assisting in a code. ACLS algorithms, drug doses, H's & T's, and the rapid response assessment framework. Launch Code Clock for real-time code documentation.
⏱️ Code Clock App
Real-time code documentation — track interventions, drug times, rhythm checks, and generate a code summary.
⚡ Cardiac Arrest — ACLS
Shockable Rhythms: VFib / Pulseless VTach
CPR
High-quality CPR immediately. Rate 100–120/min, depth 2–2.4 inches, full chest recoil. Minimize interruptions (< 10 sec for rhythm checks). Rotate compressors q2 min.
Shock
Defibrillate as soon as possible. Biphasic: 200J first shock, escalate if needed. Resume CPR immediately after shock × 2 min before rhythm check.
Epinephrine
Epinephrine 1 mg IV q3–5 min (give after 2nd shock if VFib/pVT). Do NOT delay shocks for epi.
Antiarrhythmic
Amiodarone 300 mg IV bolus (after 3rd shock if refractory VFib/pVT). 2nd dose: 150 mg. Alternative: lidocaine 1–1.5 mg/kg then 0.5–0.75 mg/kg.
H's & T's
Find and treat the cause. See below.
Non-Shockable: PEA / Asystole
- CPR + Epinephrine 1 mg IV q3–5 min. No shock. No antiarrhythmic.
- Focus on finding and treating the cause — PEA/asystole rarely responds to CPR alone without correcting the underlying etiology.
- Asystole: confirm in ≥ 2 leads (rule out fine VFib). No atropine (removed from algorithm). No defibrillation.
H's and T's — Reversible Causes
PEA and asystole will NOT respond to CPR alone — you MUST find and fix the underlying cause. Run through H's and T's every 2-minute cycle.
| Cause | Clues (History & Exam) | Intervention |
|---|---|---|
| H's | ||
| Hypovolemia | Trauma, GI bleed (hematemesis, melena), ruptured AAA, ruptured ectopic. Flat neck veins, pale, bloody NG aspirate. | Aggressive IVF boluses. Activate massive transfusion protocol. Blood products 1:1:1. Surgical consult if hemorrhagic. |
| Hypoxia | Pre-arrest desaturation, cyanosis, COPD/asthma history, mucus plug, aspiration event, known difficult airway. | Confirm ETT placement (ETCO₂). Auscultate both lungs. If no breath sounds unilateral → mainstem intubation or PTX. Suction. Increase FiO₂ to 100%. |
| Hydrogen ion (acidosis) | Known DKA, renal failure, severe sepsis, toxic ingestion (methanol, ethylene glycol, ASA). Pre-arrest ABG with pH < 7.1. | Sodium bicarbonate 1 mEq/kg IV push. Ventilate aggressively (blow off CO₂). Treat underlying cause (insulin for DKA, dialysis for renal failure, fomepizole for toxic alcohols). |
| Hyper/Hypokalemia | Renal failure (hyperK), dialysis patient who missed session, recent K⁺ lab, ECG changes (peaked T waves, wide QRS). HypoK: diuretic use, GI losses, prolonged QT. | HyperK: Calcium chloride 1–2g IV push (stabilize membrane) → insulin 10 units + D50 → bicarb → albuterol. HypoK: KCl 40 mEq IV + MgSO₄ 2g IV. |
| Hypothermia | Found down outdoors, drowning, exposure, elderly. Core temp < 30°C. "Not dead until warm and dead." | Active rewarming: warm IVF (40°C), warm humidified O₂, forced-air warming blankets. If < 30°C: defib may not work until rewarmed → limit to 1 shock attempt, hold meds until temp > 30°C. Continue CPR. Consider ECMO rewarming if available. |
| Hypoglycemia | Diabetic on insulin/sulfonylureas, altered mental status pre-arrest, missed meals, liver failure, adrenal crisis. | D50 (dextrose 50%) 1 amp (25g) IV push. Recheck in 15 min. If no IV access: glucagon 1 mg IM. |
| T's | ||
| Tension pneumothorax | Absent breath sounds unilaterally, JVD, tracheal deviation (late sign), recent central line or thoracentesis, trauma, patient on positive pressure ventilation. | Needle decompression: 14–16G needle, 2nd intercostal space midclavicular line (or 5th ICS anterior axillary). Do NOT wait for CXR. Follow with chest tube (28–32 Fr). |
| Tamponade (cardiac) | Beck's triad: JVD + hypotension + muffled heart sounds. Recent cardiac surgery, pericardial effusion on prior imaging, dialysis patient (uremic pericarditis), trauma, malignancy, post-MI (free wall rupture). | Pericardiocentesis: subxiphoid approach, US-guided. Remove even 20–30 mL → dramatic improvement. In post-surgical: emergent sternotomy (re-open). |
| Toxins | Pill bottles at scene, history of depression/suicidal ideation, drug paraphernalia. Wide QRS (TCAs, Na-channel blockers). Opioid presentation (pinpoint pupils). Bradycardia (beta-blocker, CCB, digoxin). Seizure history (local anesthetic toxicity). | Specific antidotes: Naloxone (opioid), sodium bicarb (TCA — QRS > 100), intralipid 20% (local anesthetic toxicity, lipophilic drug OD), glucagon (beta-blocker), calcium + high-dose insulin (CCB), DigiFab (digoxin). See Toxicology. |
| Thrombosis — coronary (MI) | Pre-arrest chest pain, STEMI on last ECG, known CAD, cardiac risk factors. PEA with organized narrow-complex rhythm on monitor. | Consider emergent PCI (cath lab activation during CPR — some centers do this). If no PCI available: fibrinolytics (tPA 50 mg IV during CPR) — consider if high suspicion and no other cause found. Continue CPR for 60–90 min after lytics. |
| Thrombosis — pulmonary (massive PE) | Pre-arrest dyspnea + pleuritic pain + tachycardia, recent surgery/immobilization/cancer, known DVT, RV strain on prior echo, dilated RV on bedside echo during CPR. | Systemic thrombolytics: tPA 50 mg IV bolus (can give during CPR). Continue CPR for 60–90 min after lytics to allow time to work. If available: consider surgical embolectomy or catheter-directed therapy. Bedside echo during CPR showing RV dilation supports PE diagnosis. |
💊 Code Drug Doses
| Drug | Dose | Indication |
|---|---|---|
| Epinephrine (Adrenalin) | 1 mg IV q3–5 min | All cardiac arrest rhythms. First-line vasopressor. |
| Amiodarone (Cordarone) | 300 mg IV push (1st dose), 150 mg (2nd dose) | Refractory VFib/pVT after 3+ shocks. |
| Lidocaine | 1–1.5 mg/kg IV, then 0.5–0.75 mg/kg | Alternative to amiodarone for VFib/pVT. |
| Atropine | 1 mg IV q3–5 min (max 3 mg) | Symptomatic bradycardia (NOT for asystole or PEA). |
| Adenosine (Adenocard) | 6 mg rapid IV push → if no effect → 12 mg → 12 mg | Stable SVT. Must use rapid push + flush at proximal IV site. |
| Calcium chloride | 1–2 g IV (10–20 mL of 10%) | Hyperkalemia with ECG changes, calcium channel blocker OD, hypocalcemia. |
| Calcium gluconate | 3 g IV (30 mL of 10%) | Same indications. 3× less elemental calcium than CaCl₂. Safer peripherally. |
| Sodium bicarbonate | 1 mEq/kg IV | Severe metabolic acidosis, TCA overdose, hyperkalemia (adjunct). |
| Magnesium | 2 g IV over 15 min | Torsades de pointes. Also hypomagnesemia-related arrhythmias. |
| Vasopressin (Pitressin) | 40 units IV × 1 | Can replace first or second epi dose in cardiac arrest (AHA 2020 removed specific recommendation but still acceptable). |
🏥 Rapid Response Assessment
When You Get the Call — ABCDE
A — Airway
Speaking? Stridor? Secretions? Can they protect their airway? If not → jaw thrust, suction, consider intubation. Call anesthesia early if airway is threatened.
B — Breathing
RR, SpO₂, work of breathing, auscultate. Wheezing → bronchodilator. Crackles → fluid overload vs pneumonia. Absent breath sounds → PTX? Stridor → upper airway obstruction → call ENT/anesthesia. Apply O₂ while assessing.
C — Circulation
HR, BP, rhythm, mental status, cap refill, urine output. If hypotensive → IVF bolus (unless cardiogenic). If no pulse → call code, start CPR. Get 12-lead ECG. Access: 2 large-bore IVs.
D — Disability
GCS, pupils, glucose (stat fingerstick — ALWAYS check). New focal deficit → stroke alert. Seizure → benzos (lorazepam 4 mg IV). AMS → consider naloxone 0.4 mg IV (opioid reversal).
E — Exposure/Environment
Expose the patient — look for rashes (anaphylaxis, meningococcemia), surgical sites, lines, drains, skin findings. Check temperature. Review meds + recent changes. What changed?
Common Rapid Response Triggers
| Trigger | First Steps | Think |
|---|---|---|
| Acute desaturation | O₂, check SpO₂ probe, auscultate, CXR, ABG | PE, mucus plug, PTX, flash pulm edema, pneumonia, aspiration |
| Acute hypotension | Passive leg raise (NOT Trendelenburg — no evidence), IVF bolus, HR check, 12-lead ECG | Sepsis, hemorrhage, PE, cardiogenic, anaphylaxis, adrenal crisis |
| Tachycardia | 12-lead ECG, BP, fluid status, pain assessment | SVT, Afib/RVR, PE, sepsis, hypovolemia, pain, anxiety, withdrawal |
| Acute AMS | Glucose, O₂, vitals, pupils, review meds | Hypoglycemia, opioids, stroke, seizure (postictal), sepsis, hypercarbia |
| Acute chest pain | 12-lead ECG within 10 min, troponin, vitals, O₂ | ACS, PE, dissection, PTX, pericarditis |
Cross-Cover Algorithms
The 6 calls you'll get at 3 AM and the 60-second decision tree for each. Assess, intervene, decide if you need to call your senior.
🌡️ Fever (T ≥ 38.3°C / 101°F)
Assess
Vitals (HR, BP, SpO₂). Is the patient septic? (Tachycardic, hypotensive, altered?) Look at the patient — line sites, surgical wounds, skin, lungs, abdomen, Foley.
Workup
Blood cultures × 2 (before abx). UA + urine culture. CXR. CBC, BMP, lactate. C. diff stool if diarrhea. Line cultures if central line > 48h. Wound culture if surgical site erythema.
Intervene
Acetaminophen 1g PO/IV. If septic → IVF bolus + start empiric antibiotics per source. If neutropenic → cefepime 2g IV within 60 min (oncologic emergency).
Call senior if
Sepsis (HR > 110, SBP < 90, lactate > 2, altered). Neutropenic fever (ANC < 500). New fever on immunosuppression. Unclear source with clinical deterioration.
Common pitfalls: Post-op day 1–2 fever is often atelectasis (encourage incentive spirometry) — but still work it up. Drug fever (eosinophilia, timing with new med). DVT (check legs). C. diff (new diarrhea + recent abx).
📉 Hypotension (SBP < 90 or MAP < 65)
Assess
Go see the patient immediately. Vitals + mental status. Check lines/drains for blood. Recent meds (antihypertensives, opioids, sedatives). Abdomen (GI bleed?). JVD (PE, tamponade, tension PTX)?
Intervene
IVF bolus 500 mL–1L NS or LR. Passive leg raise to assess fluid responsiveness. Hold antihypertensives. If on pressors → uptitrate and notify ICU. If bleeding → type and screen, activate MTP if massive.
Workup
CBC (drop in Hgb?), BMP, lactate, 12-lead ECG. Blood cultures if febrile. Consider: bedside echo (tamponade? RV strain? empty LV?), CXR (PTX? widened mediastinum?).
Call senior if
Not responding to 2L IVF. Active hemorrhage. New arrhythmia. Concern for PE, tamponade, or tension PTX. Need for pressors.
Think SHOCK: Septic (warm, febrile), Hypovolemic (dry, bleeding), Obstructive (PE, tamponade, PTX), Cardiogenic (JVD, crackles, cold), Anaphylactic (rash, wheezing, new med/food).
📉 Desaturation (SpO₂ < 92%)
Assess
Apply O₂ first, assess second. Check probe placement (cold fingers, nail polish give false readings). Confirm with ABG if uncertain. Look at patient: work of breathing, tracheal position, breath sounds, JVD.
Intervene
Nasal cannula 2–6 L → face mask 10–15 L → non-rebreather → high-flow nasal cannula → BiPAP → intubation. If wheezing → albuterol nebulizer. If crackles + JVD → furosemide IV (flash pulm edema). If absent breath sounds unilateral → PTX? (needle decompress if tension).
Workup
CXR (stat portable), ABG, 12-lead ECG. Consider: CTPA if PE suspected (tachycardia + pleuritic pain + risk factors). BNP if heart failure. Troponin if ACS.
Call senior if
Not improving with supplemental O₂. Need for BiPAP or intubation. Concern for PE, PTX, or flash pulm edema. New infiltrate on CXR in the right clinical context.
Top 5 overnight causes: mucus plug (suction + turn), flash pulmonary edema (Lasix), PE, aspiration, pneumothorax (post-procedure or on vent). Also: opioid-induced hypoventilation → check RR, give naloxone if < 8.
🧠 Altered Mental Status
Assess
Stat fingerstick glucose (hypoglycemia is the fastest fixable cause). Vitals. Pupils. GCS. Focal neuro exam (asymmetry → stroke alert). Review med list (opioids, benzos, anticholinergics).
Intervene
Glucose < 70 → D50 1 amp IV. Suspected opioid OD (pinpoint pupils, RR < 8) → naloxone 0.4 mg IV. Benzodiazepine OD → supportive (flumazenil rarely indicated). Seizure → lorazepam 4 mg IV.
Workup
BMP (Na⁺, Ca²⁺, glucose), CBC, ammonia (if liver disease), UA (UTI in elderly?), ABG, lactate. CT head if focal deficit, fall, anticoagulated, or not improving. Consider LP if meningitis suspected (fever + nuchal rigidity).
Call senior if
Focal neuro deficit (stroke alert). Seizure. Meningeal signs. Not correcting with glucose/naloxone. GCS ≤ 8 (airway at risk).
Most common overnight AMS cause: delirium from medications. Review med list first — Benadryl, benzos, opioids, anticholinergics, steroids. Reorient, minimize stimulation, avoid restraints. Haldol 0.5–1 mg IV only if danger to self/others.
💔 Chest Pain
Assess
12-lead ECG within 10 min. Vitals. Character of pain (substernal pressure vs pleuritic vs positional vs reproducible). Cardiac history. Risk factors.
Intervene
ASA 325 mg chew (if ACS suspected and not already on). NTG 0.4 mg SL q5 min × 3 (hold if SBP < 90 or suspected RV infarct). Morphine only if refractory (not routine). O₂ if SpO₂ < 94%.
Workup
ECG (compare to prior). Troponin (serial 0 and 3h if hs-troponin). CXR. BMP. If ECG shows STEMI → activate cath lab immediately. If PE suspected → D-dimer or CTPA based on Wells score.
Call senior if
STEMI or new ST changes. Hemodynamic instability. Concern for dissection (tearing pain + BP differential). Positive troponin. Chest pain not resolving with NTG.
💧 Low Urine Output (< 0.5 mL/kg/hr × 6h)
Assess
Is the Foley kinked, clogged, or draining? Flush 30 mL NS. If no Foley → bladder scan (> 300 mL = retention → straight cath). Check vitals, volume status (dry vs overloaded), recent meds (NSAIDs, ACEi, diuretics).
Intervene
If hypovolemic → IVF 500 mL NS bolus. If retention → straight cath or Foley. Stop nephrotoxins (NSAIDs, aminoglycosides, contrast). Hold ACEi/ARB if Cr rising. If overloaded (JVD, crackles, edema) → do NOT give more fluid — consider diuresis.
Workup
BMP (Cr trend — compare to baseline), UA with sediment, bladder scan. FENa or FEUrea to differentiate pre-renal vs intrinsic (see Calculators). Consider renal US if obstruction suspected.
Call senior if
Cr doubled from baseline. Anuria (< 50 mL/12h). Hyperkalemia (K⁺ > 6 + ECG changes). Volume overloaded + oliguric (may need emergent dialysis).
Electrolyte Replacement
You'll order these 10 times a day. How much, how fast, PO vs IV, and when to recheck.
⚡ Replacement Protocols
| Electrolyte | Level | Replacement | Expected Rise | Recheck | Pearls |
|---|---|---|---|---|---|
| Potassium (Goal: 4.0–5.0) (ICU goal: 4.0–4.5) |
3.5–3.9 | KCl 40 mEq PO × 1 | ~0.3 mEq/L per 10 mEq | Next AM BMP | Always replete Mg first — hypoMg causes renal K⁺ wasting via the ROMK channel. Mg²⁺ normally inhibits ROMK in the collecting duct. When Mg²⁺ is low → ROMK becomes uninhibited → K⁺ pours into the urine → refractory hypokalemia no matter how much K⁺ you give. Fix the Mg²⁺ first, or the K⁺ won't stay. Max IV rate: 10 mEq/hr peripheral, 20 mEq/hr central. PO preferred if tolerating. Recheck K⁺ 2–4h after IV repletion. |
| 3.0–3.4 | KCl 40 mEq PO × 2 doses (1h apart) or KCl 20 mEq IV × 2 | ~0.6–1.0 mEq/L | 2–4h post-IV | ||
| < 3.0 | KCl 40 mEq IV × 2–3 (with continuous telemetry). PO supplement simultaneously. | Variable — recheck frequently | Q2h until > 3.0 | ||
| Magnesium (Goal: ≥ 2.0) (ICU goal: ≥ 2.0) |
1.5–1.9 | MgOxide 400 mg PO BID or MgSO₄ 2g IV × 1 | ~0.1–0.2 per 1g IV | Next AM | Diarrhea is the dose-limiting PO side effect. IV preferred in critically ill. 1g IV MgSO₄ ≈ 8 mEq Mg. Renal excretion — use caution in CKD. For torsades → 2g IV push. Why Mg matters for K⁺ (ROMK channel): Mg²⁺ normally blocks the ROMK channel in the collecting duct, preventing K⁺ secretion. Low Mg²⁺ → ROMK uninhibited → kidney wastes K⁺ → refractory hypokalemia. Also: low Mg²⁺ causes PTH resistance → refractory hypocalcemia. Always check Mg²⁺ when K⁺ or Ca²⁺ won't correct. |
| < 1.5 | MgSO₄ 4g IV over 4h | ~0.3–0.5 | 2–4h post | ||
| Phosphorus (Goal: 2.5–4.5) |
1.5–2.4 | NeutraPhos 2 packets PO (32 mmol) or Na/K-Phos 15 mmol IV over 2h | ~0.5–1.0 mg/dL | Next AM | IV repletion in CKD → risk of hypocalcemia (CaPO₄ precipitation). Check Ca²⁺ concurrently. Oral preferred unless severe or NPO. K-Phos contains potassium — check K⁺ first. |
| < 1.5 | Na/K-Phos 30 mmol IV over 4–6h | ~1.0–1.5 mg/dL | 2–4h post | ||
| Calcium (Ionized goal: 1.1–1.3) |
Mild (iCa 0.9–1.1) | CaCO₃ 1250 mg PO TID (with meals) + vitamin D | Gradual | Next AM | Always check ionized Ca (not total — albumin confounds). Correct Mg first (hypoMg causes PTH resistance). IV CaCl₂ = 3× more elemental Ca than Ca gluconate but vesicant (central line only). Avoid IV Ca if hyperphosphatemic (CaPO₄ precipitation → calciphylaxis). |
| Severe (iCa < 0.9, symptomatic) | Ca gluconate 2g IV over 20 min (peripheral OK) or CaCl₂ 1g IV (central only) | Transient | Q2h + telemetry |
🔗 The Mg²⁺ → K⁺ → Ca²⁺ Connection (ROMK Channel)
Low Mg²⁺ causes THREE problems:
1. Refractory hypokalemia — Mg²⁺ normally blocks the ROMK channel (Renal Outer Medullary K⁺ channel) in the collecting duct. Without Mg²⁺ → ROMK is wide open → kidney wastes K⁺ into urine → no amount of K⁺ repletion will stick until Mg²⁺ is corrected.
2. Refractory hypocalcemia — Mg²⁺ is required for PTH secretion and end-organ response. Low Mg²⁺ → PTH resistance → Ca²⁺ won't correct.
3. Cardiac arrhythmias — Mg²⁺ stabilizes cardiac membranes. Low Mg²⁺ → prolonged QT → Torsades de Pointes, refractory Afib/RVR, digoxin toxicity.
Clinical rule: When K⁺ or Ca²⁺ won't correct despite adequate repletion → check and replete Mg²⁺ first.
Low Mg²⁺ causes THREE problems:
1. Refractory hypokalemia — Mg²⁺ normally blocks the ROMK channel (Renal Outer Medullary K⁺ channel) in the collecting duct. Without Mg²⁺ → ROMK is wide open → kidney wastes K⁺ into urine → no amount of K⁺ repletion will stick until Mg²⁺ is corrected.
2. Refractory hypocalcemia — Mg²⁺ is required for PTH secretion and end-organ response. Low Mg²⁺ → PTH resistance → Ca²⁺ won't correct.
3. Cardiac arrhythmias — Mg²⁺ stabilizes cardiac membranes. Low Mg²⁺ → prolonged QT → Torsades de Pointes, refractory Afib/RVR, digoxin toxicity.
Clinical rule: When K⁺ or Ca²⁺ won't correct despite adequate repletion → check and replete Mg²⁺ first.
Pain Management & Conversions
WHO pain ladder, PCA dosing, multimodal analgesia, equianalgesic conversions, and steroid equivalency. The complete analgesic guide.
📶 WHO Pain Ladder & Analgesic Guide
WHO Analgesic Ladder (Modified)
Start at the step that matches the patient's pain severity. You do NOT have to climb from Step 1 → 2 → 3 sequentially. A patient with severe post-op pain can start at Step 3 immediately. Add adjuvants at EVERY step.
Step 1 — Mild Pain (1–3/10)
Non-opioid analgesics:
• Acetaminophen (Tylenol) 650–1000 mg PO q6h (max 3g/day if liver disease, 4g if healthy)
• Ibuprofen (Advil) 400–600 mg PO q6h with food
• Ketorolac (Toradol) 15–30 mg IV q6h (max 5 days — renal/GI risk)
• Celecoxib (Celebrex) 200 mg PO BID (lower GI bleed risk)
• Acetaminophen (Tylenol) 650–1000 mg PO q6h (max 3g/day if liver disease, 4g if healthy)
• Ibuprofen (Advil) 400–600 mg PO q6h with food
• Ketorolac (Toradol) 15–30 mg IV q6h (max 5 days — renal/GI risk)
• Celecoxib (Celebrex) 200 mg PO BID (lower GI bleed risk)
⚠️ NSAIDs: avoid in CKD (GFR < 30), active GI bleed, HF, post-CABG, concurrent anticoagulation, platelets < 50K
Step 2 — Moderate Pain (4–6/10)
Weak opioids ± non-opioids:
• Tramadol (Ultram) 50–100 mg PO q6h (max 400 mg/day)
• Hydrocodone/APAP (Norco) 5/325 — 1-2 tabs q4-6h
• Oxycodone IR (OxyContin) 5 mg PO q4-6h PRN
• Continue scheduled acetaminophen + NSAIDs if safe
• Tramadol (Ultram) 50–100 mg PO q6h (max 400 mg/day)
• Hydrocodone/APAP (Norco) 5/325 — 1-2 tabs q4-6h
• Oxycodone IR (OxyContin) 5 mg PO q4-6h PRN
• Continue scheduled acetaminophen + NSAIDs if safe
⚠️ Tramadol: seizure risk, serotonin syndrome with SSRIs/SNRIs, avoid in epilepsy
Step 3 — Severe Pain (7–10/10)
Strong opioids ± non-opioids:
• Morphine (MS Contin) 2–4 mg IV q3-4h PRN
• Hydromorphone (Dilaudid) 0.5–1 mg IV q3-4h PRN
• Fentanyl (Sublimaze) 25–50 mcg IV q1-2h (short duration)
• Oxycodone 5–10 mg PO q4h
• Continue non-opioid adjuncts (multimodal)
• Morphine (MS Contin) 2–4 mg IV q3-4h PRN
• Hydromorphone (Dilaudid) 0.5–1 mg IV q3-4h PRN
• Fentanyl (Sublimaze) 25–50 mcg IV q1-2h (short duration)
• Oxycodone 5–10 mg PO q4h
• Continue non-opioid adjuncts (multimodal)
⚠️ Always start bowel regimen with opioids (senna + docusate). No ceiling for opioid dose in cancer/palliative pain.
Adjuvant Analgesics — Add at ANY Step
| Drug | MOA | Dose | Best For | ⚠️ Side Effects |
|---|---|---|---|---|
| Gabapentin (Neurontin) | Calcium channel α2δ ligand — reduces excitatory neurotransmitter release | 100–300 mg PO TID, titrate to 900–3600 mg/day | Neuropathic pain (diabetic neuropathy, post-herpetic neuralgia, radiculopathy) | ⚠️ Sedation, dizziness, peripheral edema. Renally cleared — reduce dose in CKD. |
| Pregabalin (Lyrica) | Same as gabapentin — higher affinity, more predictable absorption | 75 mg PO BID → max 300 mg BID | Neuropathic pain, fibromyalgia | ⚠️ Same as gabapentin. Schedule V controlled substance (abuse potential). |
| Duloxetine (Cymbalta) | SNRI — inhibits serotonin + norepinephrine reuptake in descending pain pathways | 30 mg PO daily × 1 week → 60 mg daily | Diabetic neuropathy, musculoskeletal pain, fibromyalgia | ⚠️ Nausea (take with food), serotonin syndrome risk with tramadol/other serotonergics. Do NOT stop abruptly. |
| Dexamethasone (Decadron) | Glucocorticoid — reduces peritumoral edema and inflammation | 4–8 mg IV/PO daily | Bone metastases, spinal cord compression, bowel obstruction, cerebral edema | ⚠️ Hyperglycemia, insomnia, GI upset, immunosuppression. Short-term use preferred. |
| Lidocaine patch (5%) | Sodium channel blockade — local anesthetic | 1–3 patches to painful area, 12h on / 12h off | Localized neuropathic pain, post-herpetic neuralgia, musculoskeletal | ⚠️ Minimal systemic absorption. Skin irritation at site. |
| Ketamine (low-dose) | NMDA receptor antagonist — blocks central sensitization | 0.1–0.3 mg/kg/hr IV infusion | Opioid-refractory pain, chronic pain crises, sickle cell VOC | ⚠️ Dissociation, hallucinations, nausea, ↑ secretions. Avoid in psychosis, elevated ICP. |
| Muscle relaxants | Various — central acting (tizanidine, cyclobenzaprine, baclofen) | Tizanidine 2–4 mg TID, Cyclobenzaprine 5–10 mg TID, Baclofen 5–10 mg TID | Musculoskeletal spasm, back pain | ⚠️ Sedation (all), hepatotoxicity (tizanidine), anticholinergic (cyclobenzaprine). Baclofen withdrawal can cause seizures. |
PCA (Patient-Controlled Analgesia) Dosing
PCA is for patients who can self-dose — must be alert, understand the button, and have no cognitive impairment. Family members should NEVER press the PCA button (risk of oversedation/respiratory arrest).
| Opioid | Demand Dose | Lockout | Basal Rate (if needed) | 1-hour Limit | Notes |
|---|---|---|---|---|---|
| Morphine PCA | 1–2 mg | 6–10 min | 0–1 mg/hr (avoid in opioid-naive) | 10 mg | Standard first-line PCA. Avoid in renal failure (M6G accumulation). |
| Hydromorphone PCA | 0.2–0.4 mg | 6–10 min | 0–0.2 mg/hr | 2 mg | Preferred in renal impairment. ~5–7× more potent than morphine IV. |
| Fentanyl PCA | 10–25 mcg | 6–10 min | 0–25 mcg/hr | 150 mcg | Short acting. Good for procedure-related pain. Lipophilic — accumulates with prolonged use. |
⚠️ Basal rate + PCA in opioid-naive patients = dangerous. A continuous basal rate removes the safety net of the PCA system (patient stops pressing button when sedated). Use demand-only dosing for opioid-naive patients. Basal rate only for opioid-tolerant patients with established requirements.
IV → PO Opioid Conversion — When to Switch
- Switch IV → PO when: patient tolerating PO intake, pain controlled ≥ 24h on stable IV dose, no nausea/vomiting
- How: Calculate total 24h IV morphine equivalents → convert to PO using equianalgesic table → reduce by 25% for cross-tolerance → split into scheduled + PRN
- Example: Patient on morphine PCA using 30 mg IV/24h → PO equivalent = 30 × 3 = 90 mg PO morphine/day → reduce 25% = ~68 mg → split: oxycodone ER 30 mg PO BID (60 mg/day) + oxycodone IR 5–10 mg q4h PRN for breakthrough
- PRN breakthrough dose: 10–15% of total daily dose given q3-4h PRN
Multimodal Analgesia — The Modern Approach
Multimodal = combine drugs from different classes to target different pain pathways. This reduces opioid requirements by 30–50%, lowers side effects, and improves pain control. Every patient should get scheduled acetaminophen + NSAID (if safe) BEFORE reaching for opioids.
| Pain Type | Recommended Multimodal Regimen |
|---|---|
| Post-surgical | Scheduled APAP 1g q6h + ketorolac 15 mg IV q6h (≤ 5 days) + gabapentin 300 mg preop + opioid PRN. Consider regional/nerve block. |
| Neuropathic | Gabapentin/pregabalin + duloxetine + lidocaine patch. Opioids are second-line (less effective for neuropathic pain). |
| Cancer / bone mets | Scheduled long-acting opioid + APAP + dexamethasone 4–8 mg + radiation therapy referral. Bisphosphonates for widespread bone mets. |
| Sickle cell VOC | IV morphine/hydromorphone PCA + scheduled APAP + ketorolac (≤ 5 days) + low-dose ketamine if refractory. NSAIDs safe short-term if GFR ok. |
| Chronic non-cancer | Maximize non-opioid: APAP, NSAIDs, duloxetine, gabapentin, PT/CBT. Opioids are last resort — risks of dependence, hyperalgesia. |
| Palliative / end-of-life | Scheduled opioid (no ceiling) + PRN breakthrough + adjuvants. Titrate to comfort. Address total pain (physical, emotional, spiritual). |
Tiered PRN Pain Order Set — What to Write on Admission
Write pain orders in 3 tiers so the nurse can choose based on the patient's assessed pain level — without paging you for every dose. The nurse uses NRS (0–10) for alert patients or CPOT (0–8) for intubated/non-verbal patients to select the right tier.
Alert Patients — Numeric Rating Scale (NRS 0–10)
| Pain Level | NRS Score | Medication | Dose | Route | Frequency |
|---|---|---|---|---|---|
| Mild | 1–3 | Acetaminophen (Tylenol) | 650–1000 mg | PO | q6h PRN |
| Moderate | 4–6 | Oxycodone IR (OxyContin) | 5 mg | PO | q4h PRN |
| Moderate | 4–6 | Alternative: Tramadol (Ultram) | 50 mg | PO | q6h PRN |
| Severe | 7–10 | Hydromorphone (Dilaudid) | 0.5–1 mg | IV | q3h PRN |
| Severe | 7–10 | Alternative: Morphine (MS Contin) | 2–4 mg | IV | q3-4h PRN |
⚠️ Adjust for special populations:
• Elderly / CKD / hepatic: Start at lower end of each tier (oxycodone 2.5 mg, hydromorphone 0.25 mg)
• Opioid-tolerant: May need higher doses at each tier
• Post-surgical: Add scheduled APAP 1g q6h + ketorolac 15 mg IV q6h (multimodal reduces opioid need by 30–50%)
• Elderly / CKD / hepatic: Start at lower end of each tier (oxycodone 2.5 mg, hydromorphone 0.25 mg)
• Opioid-tolerant: May need higher doses at each tier
• Post-surgical: Add scheduled APAP 1g q6h + ketorolac 15 mg IV q6h (multimodal reduces opioid need by 30–50%)
Intubated / Non-Verbal Patients — CPOT Score (0–8)
| Domain | 0 Points | 1 Point | 2 Points |
|---|---|---|---|
| Facial expression | Relaxed, neutral | Tense (brow furrowed, orbit tightened) | Grimacing (teeth clenching, deep furrows) |
| Body movements | Absent, normal position | Protection (slow, cautious, touching pain site) | Restlessness (pulling at tubes, attempting to sit up, thrashing) |
| Compliance with ventilator (intubated) or Vocalization (extubated) | Tolerating vent / talking normally | Coughing but tolerating / sighing, moaning | Fighting vent, triggering alarms / crying out, sobbing |
| Muscle tension (passive flexion/extension of upper extremity) | Relaxed, no resistance | Resistance to passive movements | Strong resistance, unable to complete movement |
| Pain Level | CPOT Score | Medication | Dose | Route | Frequency |
|---|---|---|---|---|---|
| Minimal | 0–2 | Acetaminophen (Tylenol) | 1000 mg | IV | q6h PRN |
| Moderate | 3–4 | Fentanyl (Sublimaze) | 25 mcg | IV | q2h PRN |
| Significant | 5–8 | Fentanyl (Sublimaze) | 50–100 mcg | IV | q1-2h PRN |
| Significant | 5–8 | Alternative: Hydromorphone (Dilaudid) | 0.5 mg | IV | q3h PRN |
⚠️ CPOT ≥ 3 = significant pain — treat it. Intubated patients cannot tell you they hurt. Studies show ICU patients experience moderate-to-severe pain during routine care (turning, suctioning, wound care). Undertreated pain increases delirium, prolongs ventilation, and causes PTSD.
⚠️ Always reassess within 30 minutes of giving PRN pain medication. If CPOT or NRS unchanged → escalate to next tier or consider continuous infusion. Document pre- and post-intervention pain scores.
💊 Opioid Equianalgesic Table
When converting between opioids, reduce the calculated equianalgesic dose by 25–50% to account for incomplete cross-tolerance. Conversion ratios are approximate — always titrate to effect.
| Opioid | IV/IM Dose | PO Dose | IV:PO Ratio | Duration | Notes |
|---|---|---|---|---|---|
| Morphine (MS Contin) | 10 mg | 30 mg | 1:3 | 3–4h | Reference standard. Active metabolite (M6G) accumulates in renal failure → ↑ sedation/respiratory depression. |
| Hydromorphone (Dilaudid) | 1.5 mg | 7.5 mg | 1:5 | 3–4h | ~7× more potent than morphine IV. Preferred in renal failure (no active metabolite). Most commonly used IV opioid on wards. |
| Oxycodone (OxyContin) | N/A (PO only) | 20 mg | PO only | 3–4h | ~1.5× morphine PO. Available as IR and ER (OxyContin). |
| Hydrocodone | N/A (PO only) | 30 mg | PO only | 4–6h | Equivalent to PO morphine mg-for-mg. Often combined with acetaminophen (Norco). |
| Fentanyl IV | 100 mcg | N/A | IV only* | 0.5–1h | ~100× morphine potency. Rapid onset (1–2 min IV). Short acting — good for procedures. Lipophilic → accumulates with repeated dosing. |
| Fentanyl patch | 25 mcg/hr ≈ 60–90 mg PO morphine/day | — | 72h | Only for opioid-tolerant patients. Takes 12–24h to reach steady state. Fever increases absorption → overdose risk. | |
| Tramadol (Ultram) | N/A | ~100–150 mg ≈ morphine 10 mg PO | — | 4–6h | Weak opioid + SNRI. Seizure risk. Serotonin syndrome risk. Max 400 mg/day. |
| Methadone | DO NOT use standard equianalgesic ratios. Conversion is non-linear — becomes dramatically more potent at higher morphine equivalents. Always consult pharmacy or pain service for methadone conversions. Long QTc risk. | ||||
Quick Conversion Math
- Morphine IV to PO: multiply by 3 (10 mg IV = 30 mg PO)
- Hydromorphone IV to PO: multiply by 5 (1 mg IV = 5 mg PO)
- Morphine PO to oxycodone PO: multiply by 0.67 (30 mg morphine = 20 mg oxycodone)
- Morphine PO to hydromorphone PO: divide by 4 (30 mg morphine = 7.5 mg hydromorphone)
💊 Steroid Equivalency Table
| Steroid | Equivalent Dose | Relative Anti-inflammatory Potency | Relative Mineralocorticoid | Duration | Notes |
|---|---|---|---|---|---|
| Hydrocortisone (Solu-Cortef) | 20 mg | 1× | 1× (highest) | Short (8–12h) | Physiologic replacement: 15–20 mg AM + 5–10 mg PM. Stress dose: 100 mg IV q8h. Has mineralocorticoid activity → fluid retention at high doses. |
| Prednisone (Deltasone) / Prednisolone (Orapred) | 5 mg | 4× | 0.8× | Intermediate (12–36h) | Most commonly prescribed oral steroid. Prednisone is a prodrug (converted to prednisolone in liver — use prednisolone in liver failure). |
| Methylprednisolone (Solu-Medrol) | 4 mg | 5× | 0.5× | Intermediate (12–36h) | Preferred IV steroid for most indications. Pulse dose: 1g IV daily × 3 days (lupus, vasculitis, MS flare). |
| Dexamethasone (Decadron) | 0.75 mg | 25× | 0 (none) | Long (36–54h) | Most potent. No mineralocorticoid → no fluid retention. Best for cerebral edema, croup, meningitis. Does NOT suppress cortisol assays (use for cosyntropin testing). Long half-life → harder to taper. |
| Fludrocortisone (Florinef) | N/A | 10× | 125× (pure mineralocorticoid) | Long | Used for mineralocorticoid replacement only (Addison disease — 0.1 mg daily). Not used as anti-inflammatory. |
Quick Conversions
- Prednisone 40 mg PO = methylprednisolone 32 mg IV = dexamethasone 6 mg = hydrocortisone 160 mg
- Prednisone 5 mg = the classic "physiologic" equivalent dose
- ≥ 20 mg prednisone/day × ≥ 3 weeks = HPA axis suppression → needs taper
Admission Orders & I-PASS
The admission order framework you use every admit, and the sign-out template that keeps your cross-cover partner safe overnight.
📋 Admission Order Template — ADC VANDALISML
| Letter | Category | What to Order |
|---|---|---|
| A | Admit to | Service (medicine, ICU, telemetry), attending name, resident/intern name |
| D | Diagnosis | Admitting diagnosis (e.g., "acute decompensated heart failure," "community-acquired pneumonia") |
| C | Condition | Stable, guarded, critical |
| V | Vitals | Frequency (q4h floor, q1h ICU). Parameters to notify (HR > 130, SBP < 90, SpO₂ < 92%, T > 38.5, UOP < 30 mL/hr × 2h) |
| A | Allergies | Drug allergies + reaction type (rash vs anaphylaxis — this changes management) |
| N | Nursing | I&Os, daily weights (HF, CKD), fall precautions, aspiration precautions, wound care, restraint orders, fingerstick glucose schedule (AC+HS if diabetic), foley care |
| D | Diet | Regular, cardiac (< 2g Na), renal (low K⁺/PO₄), diabetic (carb-controlled), NPO (pre-procedure), clear liquids, pureed/thickened (dysphagia) |
| A | Activity | Ad lib, bed rest, ambulate TID with assist, PT/OT consult, fall precautions |
| L | Labs | AM labs (BMP, CBC). Admission: BMP, CBC, LFTs, lactate, troponin, BNP, UA, blood cultures, coags — based on diagnosis. Type and screen if anemia/bleeding risk. |
| I | IV fluids | NS at ___mL/hr, or hep-lock (no maintenance fluids). See Fluid Guide. |
| S | Special studies / consults | ECG, CXR, echo, CT. Consults: cardiology, GI, surgery, social work, palliative. |
| M | Medications | Home meds reconciliation (continue, hold, adjust). New treatment meds. VTE prophylaxis (enoxaparin 40 SC daily or heparin 5000 SC q8h — every patient). Bowel regimen (senna + docusate if on opioids). Insulin (basal-bolus, not just sliding scale). PRNs: acetaminophen 1g q6h, ondansetron 4 mg q6h, melatonin 3 mg qHS. |
| L | Lines / tubes / drains | IV access (PIV, central line), Foley (document indication — remove ASAP), NG tube, chest tube, drains |
The 3 most commonly missed admission orders: (1) VTE prophylaxis — #1 preventable cause of inpatient death. (2) Insulin orders in diabetics (not just sliding scale). (3) Code status documentation.
🔄 I-PASS Sign-Out Template
I-PASS Study, 2014: I-PASS handoff reduced medical errors by 23% and preventable adverse events by 30%.
| Letter | Component | Example |
|---|---|---|
| I | Illness severity | "Stable" / "Watcher" / "Unstable." Watcher = most important category — these patients might deteriorate overnight. |
| P | Patient summary | "65M with HFrEF, admitted for ADHF, on IV diuresis, down 3 kg." One sentence. Diagnosis + current treatment trajectory. |
| A | Action list | "Check PM BMP for K⁺ (on Lasix drip). Urology following for Foley, may call to remove. Waiting on blood culture final." What needs to happen overnight. |
| S | Situation awareness / contingency planning | "If SBP drops < 90 → hold Lasix drip, give 250 mL NS bolus, recheck BMP, call me if doesn't improve. If K⁺ < 3.5 → replete 40 mEq IV KCl." If-then statements. |
| S | Synthesis by receiver | Cross-cover reads back key action items and contingencies. Asks questions. Closed-loop communication. |
The "S" (situation awareness) is the most important part. Don't just list problems — tell your cross-cover what might go wrong and what to do about it. "If X happens → do Y" saves lives at 3 AM.
IV Fluid Guide
Which fluid, how much, and when. NS vs LR vs D5 vs albumin — the answer depends on the clinical scenario. Stop giving everyone "NS at 125."
💧 Fluid Selection
Crystalloids
| Fluid | Na⁺ | Cl⁻ | K⁺ | Buffer | Osmolality | Use |
|---|---|---|---|---|---|---|
| NS (0.9% NaCl) | 154 | 154 | 0 | None | 308 | Volume resuscitation (default bolus fluid), hypernatremia correction, metabolic alkalosis (Cl⁻-responsive — NS provides chloride). Caution: large volumes → hyperchloremic metabolic acidosis. |
| LR (Lactated Ringer's) PREFERRED | 130 | 109 | 4 | Lactate 28 | 273 | Preferred resuscitation fluid for most patients. SMART, 2018: balanced crystalloids (LR) reduced death, new renal failure, and persistent renal dysfunction vs NS. Less hyperchloremic acidosis. |
| D5W | 0 | 0 | 0 | None | 252 | Free water replacement (hypernatremia, DI). NOT for volume resuscitation (glucose is metabolized → leaves free water → distributes into all compartments). Correct hypernatremia: D5W or ½NS. |
| ½NS (0.45% NaCl) | 77 | 77 | 0 | None | 154 | Maintenance fluid (with 20 mEq KCl/L = "D5 ½NS + 20 KCl"). Hypernatremia correction. Hypotonic — NOT for boluses. |
| D5NS | 154 | 154 | 0 | None | 560 | Adrenal crisis (dextrose + volume). DKA maintenance (once glucose < 250, switch from NS to D5NS to continue insulin). |
| D5W + NaHCO₃ (Bicarb drip) | Varies | 0 | 0 | NaHCO₃ | Varies | Common recipe: 150 mEq NaHCO₃ (3 amps of 50 mEq) in 1L D5W → run at 150–200 mL/hr. Uses: • Salicylate (aspirin) toxicity — urine alkalinization (goal urine pH 7.5–8.0) enhances renal excretion • TCA overdose — serum alkalinization overcomes sodium channel blockade (wide QRS → give until QRS narrows) • Severe metabolic acidosis (pH < 7.1) — bridge while treating underlying cause • Hyperkalemia (temporizing — shifts K⁺ intracellularly, less reliable than insulin/glucose) • Rhabdomyolysis — urine alkalinization (goal urine pH > 6.5) prevents myoglobin precipitation in tubules • Tumor lysis syndrome — historically used for urine alkalinization (now rasburicase preferred) ⚠️ Do NOT mix with calcium in same line (precipitates). Monitor for hypernatremia, metabolic alkalosis, hypokalemia. |
| 3% Hypertonic saline | 513 | 513 | 0 | None | 1027 | Symptomatic severe hyponatremia (seizures, coma): 100–150 mL bolus over 10–20 min. Also for cerebral edema (herniation). ICU only. Never give peripherally at high rates. |
Fluid Categories — Resuscitation vs Maintenance vs Replacement vs Specialty
| Category | Purpose | Fluids Used | Rate | Key Rules |
|---|---|---|---|---|
| 🔴 Resuscitation (Volume expansion) | Restore intravascular volume in shock, sepsis, hemorrhage, severe dehydration | LR (preferred) SMART, 2018 NS (acceptable) Albumin 5% (if refractory) | Bolus: 500 mL–1L over 15–30 min. Sepsis: 30 mL/kg in first 3h. | • Isotonic fluids ONLY — ~25% stays intravascular (¼ of crystalloid bolus), rest goes interstitial • Colloids (albumin): ~100% stays intravascular in healthy physiology. ⚠️ In sepsis/critical illness, capillary leak allows albumin to extravasate into interstitium → loses its advantage. This is why balanced crystalloids (LR) remain first-line for sepsis resuscitation, NOT albumin SAFE, 2004 ALBIOS, 2014 • NEVER use D5W or ½NS for resuscitation — D5W: only ~8% stays intravascular (distributes as free water across all compartments). ½NS: only ~17% stays intravascular • Reassess after each bolus (JVP, lung exam, MAP, UOP, lactate) • Stop when target MAP ≥ 65 or signs of fluid overload |
| 🟡 Maintenance (Daily needs) | Replace insensible losses + obligatory urine output in NPO patients who are euvolemic | D5 ½NS + 20 KCl/L (standard) D5NS (if Na⁺ low or adrenal crisis) D5 ¼NS (pediatrics) | 4-2-1 rule: First 10 kg: 4 mL/kg/hr Next 10 kg: 2 mL/kg/hr Each additional kg: 1 mL/kg/hr (~75–125 mL/hr for adults) | ⚠️ NOT everyone gets maintenance fluids! • ✅ Give if: NPO + euvolemic • ❌ Do NOT give if: eating/drinking, HF, cirrhosis, SIADH, CKD/ESRD, volume overloaded, post-resuscitation • Hypotonic (½NS) because kidneys retain Na⁺ and excrete free water normally • Dextrose prevents starvation ketosis (~170 kcal/L) • Add KCl 20 mEq/L (daily K⁺ need ~40–60 mEq) • NOT for volume resuscitation — hypotonic fluids don't stay intravascular |
| 🔵 Replacement (Specific deficits) | Replace specific electrolyte or water deficits | D5W — free water (hypernatremia, DI) ½NS — mild hypernatremia 3% Hypertonic — severe hyponatremia NS — Cl⁻-responsive metabolic alkalosis | Depends on deficit calculation and correction rate limits | • Hypernatremia: correct ≤ 10 mEq/L per 24h • Hyponatremia: correct ≤ 8 mEq/L per 24h (risk of ODS if too fast) • Match the fluid to the deficit — don't just give NS for everything |
| 🟣 Specialty (Drug vehicles / specific protocols) | Carry medications or correct specific metabolic derangements | D5W + NaHCO₃ — bicarb drip (salicylate/TCA OD, rhabdo, acidosis) D5NS — DKA (when BG < 250, switch to D5 to continue insulin) D5W — drug carrier (amiodarone, many drips) Albumin 25% — oncotic pull in HF + hypoalbuminemia | Protocol-specific | • Bicarb drip: never mix with calcium in same line • DKA: D5 prevents hypoglycemia while insulin clears ketones • Some drugs are ONLY compatible with D5W (amiodarone, phenytoin) |
⚠️ The #1 mistake: Using D5W or ½NS for volume resuscitation.
1L NS or LR → ~250 mL stays intravascular (25%)
1L ½NS → ~170 mL stays intravascular (17%)
1L D5W → ~83 mL stays intravascular (8%) — basically free water
1L Albumin 5% → ~1000 mL stays intravascular (100%) in healthy capillaries. In sepsis/capillary leak → albumin extravasates and this advantage is lost.
First-line resuscitation = balanced crystalloids (LR). Albumin is reserved for specific indications (SBP, HRS, post-LVP) or refractory shock after crystalloid.
1L NS or LR → ~250 mL stays intravascular (25%)
1L ½NS → ~170 mL stays intravascular (17%)
1L D5W → ~83 mL stays intravascular (8%) — basically free water
1L Albumin 5% → ~1000 mL stays intravascular (100%) in healthy capillaries. In sepsis/capillary leak → albumin extravasates and this advantage is lost.
First-line resuscitation = balanced crystalloids (LR). Albumin is reserved for specific indications (SBP, HRS, post-LVP) or refractory shock after crystalloid.
Colloids
| Fluid | Use | Do NOT Use |
|---|---|---|
| Albumin 5% | SBP (1.5 g/kg day 1, 1 g/kg day 3). HRS (with midodrine + octreotide). Post-LVP > 5L (6–8 g/L removed). Sepsis (if not responding to crystalloid). | Traumatic brain injury SAFE, 2004: increased mortality. |
| Albumin 25% | Volume expansion with minimal fluid volume (useful in HF + hypoalbuminemia → draws fluid from interstitium into intravascular space). | Same as 5%. Expensive. |
Avoid hydroxyethyl starch (HES / Voluven) — increases AKI and mortality in critically ill patients VISEP, 2008 6S, 2012. FDA black box warning. Use crystalloids or albumin instead.
Quick Decision Guide
| Scenario | Best Fluid |
|---|---|
| Sepsis / Shock resuscitation | LR boluses (30 mL/kg). Albumin if refractory. |
| DKA | NS initially (volume-depleted + hyponatremia common). Switch to D5½NS when glucose < 250. |
| Hypernatremia | D5W or ½NS (free water). Correct ≤ 10 mEq/L per 24h. |
| Hyponatremia (symptomatic) | 3% hypertonic saline 100–150 mL bolus. ≤ 8 mEq/L per 24h. |
| Metabolic alkalosis (Cl-responsive) | NS (provides chloride to correct the alkalosis). |
| Maintenance (NPO patient) | D5½NS + 20 KCl at 75–125 mL/hr (or use 4-2-1 rule). |
| Pancreatitis | LR (preferred over NS — less SIRS, less AKI). |
| Salicylate (ASA) toxicity | D5W + NaHCO₃ drip (150 mEq in 1L D5W). Goal urine pH 7.5–8.0. Enhances renal excretion. |
| TCA overdose (wide QRS) | NaHCO₃ bolus (1–2 mEq/kg IV push), then bicarb drip. Give until QRS narrows. |
| Rhabdomyolysis | Aggressive LR + consider bicarb drip (goal urine pH > 6.5 to prevent myoglobin cast nephropathy). |
| Severe metabolic acidosis (pH < 7.1) | NaHCO₃ drip as bridge. Treat underlying cause. Not beneficial in DKA (insulin fixes it). |
| HF / volume overloaded | No fluids. Diurese. If needs meds → use smallest volume (hep-lock, concentrated drips). |
| Cirrhosis + SBP | Albumin (not crystalloid — albumin reduces HRS and mortality). |
📐 Rates & Formulas
Who Actually Needs Maintenance Fluids?
| ✅ Give Maintenance Fluids | ❌ Do NOT Give Maintenance Fluids |
|---|---|
| NPO (nothing by mouth) — surgery, intubated, bowel obstruction, severe vomiting | Eating and drinking normally — just saline-lock the IV |
| Euvolemic — not dehydrated, not overloaded | Heart failure — extra fluid worsens congestion |
| No IV fluid restriction | Cirrhosis with ascites — fluid restricted (1–1.5L/day) |
| Unable to match insensible losses orally | SIADH / hyponatremia — fluid restriction is first-line treatment |
| CKD/ESRD on dialysis — can't excrete the volume | |
| Volume overloaded for any reason — pulmonary edema, anasarca | |
| Post-resuscitation — once volume restored, STOP. Don't leave "NS at 125" running. |
⚠️ The classic intern mistake: Admitting a patient and reflexively ordering "D5½NS at 125 mL/hr" without asking: can this patient eat? Are they fluid-restricted? Three days later they're 5 kg up with new pulmonary edema.
Rule: If the patient can eat → no maintenance fluids. If they can't eat but are volume overloaded → no maintenance fluids. Maintenance fluids are ONLY for the NPO + euvolemic patient.
Rule: If the patient can eat → no maintenance fluids. If they can't eat but are volume overloaded → no maintenance fluids. Maintenance fluids are ONLY for the NPO + euvolemic patient.
Maintenance Rate — 4-2-1 Rule
- First 10 kg: 4 mL/kg/hr
- Next 10 kg: 2 mL/kg/hr
- Each additional kg: 1 mL/kg/hr
- Example: 70 kg patient → (4×10) + (2×10) + (1×50) = 40 + 20 + 50 = 110 mL/hr
Free Water Deficit (for Hypernatremia)
FWD = TBW × (Na/140 − 1)
TBW = weight (kg) × 0.6 (male) or × 0.5 (female). Replace deficit over 48–72h (correct ≤ 10 mEq/L per 24h). Add ongoing losses (insensible + urine).
Which Fluid for Hypernatremia? — Decision Tree
The deficit formula tells you how much. This tells you which fluid:
| Volume Status | Step 1 | Step 2 (Correction) | Free Water per Liter |
|---|---|---|---|
| Hypovolemic (most common — dehydration, vomiting, diarrhea, poor PO intake) | NS bolus first — restore intravascular volume. NS is "hypotonic" relative to the patient's serum Na⁺ (154 vs 160+), so it will still lower Na⁺ slightly. | Once hemodynamically stable → switch to ½NS (provides Na⁺ + free water) | ½NS = 500 mL free water/L NS = 0 mL (but still relatively hypotonic to patient) |
| Euvolemic (pure water loss — diabetes insipidus, insensible losses, inadequate water intake) | D5W — pure free water replacement. No volume deficit to correct first. | D5W = 1000 mL free water/L | |
| Hypervolemic (rare — iatrogenic hypertonic saline, sodium bicarb excess) | D5W + furosemide — diuretic removes excess Na⁺ while D5W replaces free water | D5W = 1000 mL free water/L + furosemide excretes Na⁺-rich urine | |
⚠️ Classic pimp question: "Na⁺ is 158 and the patient is hypotensive — do you start D5W?"
NO. D5W is free water — only ~8% stays intravascular. A hypotensive patient needs volume first (NS bolus), then switch to ½NS or D5W for Na⁺ correction once hemodynamically stable. Fix the volume, then fix the sodium.
NO. D5W is free water — only ~8% stays intravascular. A hypotensive patient needs volume first (NS bolus), then switch to ½NS or D5W for Na⁺ correction once hemodynamically stable. Fix the volume, then fix the sodium.
Free water content of common fluids:
D5W: 1000 mL free water per liter (100%)
¼NS (0.2%): 750 mL free water per liter (75%)
½NS (0.45%): 500 mL free water per liter (50%)
NS (0.9%): 0 mL free water per liter (0% — isotonic)
Oral water / NG flushes: 1000 mL per liter (100%) — best option if patient can tolerate PO
D5W: 1000 mL free water per liter (100%)
¼NS (0.2%): 750 mL free water per liter (75%)
½NS (0.45%): 500 mL free water per liter (50%)
NS (0.9%): 0 mL free water per liter (0% — isotonic)
Oral water / NG flushes: 1000 mL per liter (100%) — best option if patient can tolerate PO
Lab Interpretation
What's actually important in the CBC, BMP, LFTs, and coags — not just the reference ranges, but what the abnormalities mean clinically and what to do about them.
📐 Classic Fishbone Diagrams
BMP Fishbone
AG = Na⁺ − (Cl⁻ + HCO₃⁻) | Normal: 8–12 | BUN:Cr > 20:1 → pre-renal AKI
CBC Fishbone
Transfuse: Hgb < 7 (most) | < 8 (ACS) | Plt < 10K (prophylactic) | < 50K (procedure)
CMP = BMP + Hepatic Panel
BMP (8 values): Na⁺, K⁺, Cl⁻, HCO₃⁻, BUN, Cr, Glucose, Ca²⁺
CMP adds (6 more): Albumin, Total protein, AST, ALT, ALP, Total bilirubin
When to order CMP over BMP: New admission, liver disease, medications with hepatotoxicity, TPN, unexplained AMS, jaundice
CMP adds (6 more): Albumin, Total protein, AST, ALT, ALP, Total bilirubin
When to order CMP over BMP: New admission, liver disease, medications with hepatotoxicity, TPN, unexplained AMS, jaundice
🔬 CBC
| Lab | Normal | High | Low | Clinical Action |
|---|---|---|---|---|
| WBC | 4.5–11 K | Leukocytosis: infection (#1), steroids (demargination), stress, leukemia, medication | Leukopenia: sepsis (bad sign — WBC consumed), chemo, bone marrow failure, SLE, viral | Leukocytosis + fever → blood cultures + workup. Neutropenia (ANC < 500) + fever → cefepime within 60 min. |
| Hgb/Hct | M: 14–17 F: 12–16 | Polycythemia vera, dehydration (hemoconcentration), chronic hypoxia | Anemia: classify by MCV. Microcytic (iron def, thalassemia), normocytic (chronic disease, AKI, bleeding), macrocytic (B12/folate, EtOH, MDS) | Transfuse if Hgb < 7 (most patients) or < 8 (ACS). Reticulocyte count to assess production. |
| Platelets | 150–400 K | Reactive (infection, inflammation, iron deficiency, splenectomy). Essential thrombocythemia if > 450K persistent. | Thrombocytopenia: ↓ production (chemo, EtOH, MDS), ↑ destruction (ITP, TTP, HIT, DIC), sequestration (splenomegaly), dilutional (massive resuscitation) | If new drop → review meds (heparin → 4T score for HIT). < 50K → hold anticoagulation. < 10K → transfuse (unless TTP/HIT). |
🔬 BMP / CMP
| Lab | Normal | Key Abnormalities | Quick Action |
|---|---|---|---|
| Na⁺ | 136–145 | Low: see Hyponatremia. High: free water deficit (dehydration, DI, inadequate access to water). | Correct ≤ 8–10 mEq/L per 24h in either direction. |
| K⁺ | 3.5–5.0 | High: AKI, ACEi/ARB, spironolactone, rhabdo, hemolysis (pseudohyperK), acidosis. Low: diuretics, GI losses, renal wasting. | K⁺ > 6 + ECG changes → calcium first, then insulin/D50. See Hyperkalemia. Always check Mg. |
| HCO₃ / CO₂ | 22–28 | Low: metabolic acidosis (calculate AG). High: metabolic alkalosis or chronic respiratory acidosis compensation. | Low HCO₃ → calculate anion gap → if elevated, calculate delta-delta. See Acid-Base. |
| BUN / Cr | BUN 7–20 Cr 0.7–1.3 | ↑ BUN/Cr > 20:1: pre-renal (dehydration, HF, GI bleed). ↑ BUN + Cr proportionally: intrinsic renal (ATN). Cr trend matters more than absolute value. | Compare to baseline. Rising Cr → hold nephrotoxins (NSAIDs, ACEi, contrast), check volume status, UA, FENa. |
| Glucose | 70–100 (fasting) | High: DM, steroids, stress response, DKA. Low: insulin excess, sulfonylurea, liver failure, sepsis, adrenal insufficiency, alcohol. | < 70 → D50 1 amp IV + recheck in 15 min. > 300 → check ketones + anion gap (DKA?). |
| Calcium | 8.5–10.5 (total) 1.1–1.3 (ionized) | Always correct for albumin or check ionized. See Hypercalcemia. | High Ca → check PTH. Low iCa → check Mg, PO₄, PTH, vitamin D. |
🔬 Liver Function Tests
| Pattern | AST/ALT | Alk Phos / GGT | Bilirubin | Think |
|---|---|---|---|---|
| Hepatocellular | ↑↑↑ (AST/ALT > 10× ULN) | Mildly ↑ | Variable | Viral hepatitis, drug-induced (acetaminophen — check level + NAC), ischemic hepatitis ("shock liver"), autoimmune hepatitis, Wilson disease |
| Cholestatic | Mildly ↑ | ↑↑↑ | ↑↑ | Bile duct obstruction (stone, mass, stricture) → RUQ US first. Intrahepatic: PBC, PSC, drug-induced, infiltrative. GGT confirms hepatic origin of alk phos. |
| Mixed | ↑↑ | ↑↑ | ↑ | Drug-induced, granulomatous hepatitis |
| AST > ALT (> 2:1) | Ratio > 2:1 | Alcoholic hepatitis (classic ratio). Also: cirrhosis, Wilson disease, rhabdomyolysis (AST from muscle — check CK). | ||
"LFTs" is a misnomer. AST, ALT, and alk phos measure liver INJURY, not function. True liver FUNCTION markers: albumin (synthesis), INR (clotting factor synthesis), bilirubin (conjugation/excretion). A patient with normal AST/ALT but INR of 3 and albumin of 2 has severe liver dysfunction.
🔬 Coags, Inflammatory Markers & More
| Lab | Normal | Clinical Meaning |
|---|---|---|
| PT / INR | PT 11–13.5s INR 0.9–1.1 | Extrinsic pathway (factors VII, X, V, II, fibrinogen). Elevated: warfarin, liver disease, DIC, vitamin K deficiency. INR is the standardized version of PT. |
| aPTT | 25–35s | Intrinsic pathway (XII, XI, IX, VIII). Elevated: heparin (therapeutic monitoring), hemophilia (VIII or IX deficiency), lupus anticoagulant (paradoxically prolonged but prothrombotic), DIC. |
| Fibrinogen | 200–400 mg/dL | Low: DIC (consumed), liver failure. High: acute phase reactant (inflammation). Most specific lab for DIC severity. Critical value < 100 → give cryoprecipitate. |
| D-dimer | < 500 ng/mL | Sensitive but NOT specific. Elevated in PE, DVT, DIC, surgery, pregnancy, cancer, infection, trauma — basically any hospitalized patient. Useful to RULE OUT PE/DVT when low pretest probability (Wells ≤ 4). |
| Lactate | < 2.0 mmol/L | ↑: tissue hypoperfusion (sepsis, shock — Type A) or impaired clearance (liver failure, metformin — Type B). Lactate > 4 in sepsis → mortality > 30%. Trend is more important than single value. |
| Procalcitonin | < 0.1 ng/mL | < 0.25: bacterial infection unlikely. > 0.5: likely bacterial. Useful for: antibiotic de-escalation in pneumonia/sepsis (if procal drops > 80% → safe to stop abx). NOT reliable in: immunocompromised, post-surgery, burns, pancreatitis. |
| ESR | M: 0–22 F: 0–29 | Non-specific inflammation. Very high (> 100): infection (endocarditis, osteomyelitis), autoimmune (SLE, PMR/GCA), malignancy (myeloma). Slow to rise and slow to fall. SLE flare: ↑ ESR + normal CRP. |
| CRP | < 3 mg/L | Faster marker of inflammation than ESR. Rises within 6h, peaks 48h. Good for tracking treatment response. CRP elevated in SLE = think infection, not flare. |
| Troponin (hs-TnI) | Varies by assay | Myocardial injury. NOT specific for MI — elevated in: PE, HF, sepsis, CKD (chronic elevation), myocarditis, takotsubo, cardioversion. Trend matters: rise-and-fall pattern = acute injury. Stable low-level = chronic (CKD, HF). |
| BNP / NT-proBNP | BNP < 100 NT-proBNP < 300 | Rule out HF: BNP < 100 or NT-proBNP < 300 makes HF very unlikely. Falsely low: obesity (adipose tissue clears BNP). Falsely high: Afib, PE, CKD, age. |
Drug Interactions
The combinations that actually hurt patients on the wards. QT prolongation, serotonin syndrome, and the high-risk pairs you need to catch before they cause harm.
⚡ QT-Prolonging Drugs
QTc > 500 ms = high risk for torsades de pointes. Risk multiplies when combining QT-prolonging drugs + hypokalemia + hypomagnesemia. Check ECG, K⁺, and Mg²⁺ before and during treatment.
| Category | High-Risk Drugs | Ward Relevance |
|---|---|---|
| Antiarrhythmics | Amiodarone (Cordarone), sotalol (Betapace), dofetilide (Tikosyn), procainamide (Pronestyl) | Amiodarone is the most commonly prescribed. Check QTc before loading. |
| Antibiotics | Fluoroquinolones (levofloxacin, moxifloxacin > cipro), azithromycin, TMP-SMX (rare) | Moxifloxacin has the highest QT risk among FQs. Azithro risk is lower but additive with other drugs. |
| Antifungals | Fluconazole (Diflucan), voriconazole (Vfend) | Fluconazole at higher doses (> 400 mg). Also inhibits CYP2C9/3A4 → increases levels of warfarin, phenytoin. |
| Antiemetics | Ondansetron (Zofran), droperidol | Ondansetron at doses > 16 mg IV. FDA warning. 4 mg IV is generally safe but still additive. Check QTc if combining with other QT drugs. |
| Antipsychotics | Haloperidol (Haldol) (especially IV), ziprasidone, chlorpromazine | IV haloperidol has higher QT risk than IM/PO. Check QTc before and during use. Hold if QTc > 500. |
| Antidepressants | Citalopram, escitalopram (dose-dependent), TCAs | Citalopram max 20 mg in age > 60 (FDA). TCAs: QRS widening + QT prolongation. |
| Other | Methadone, sumatriptan, donepezil | Methadone: always check QTc at baseline and periodically. Dose-dependent. |
Risk Multipliers
- Hypokalemia — replete K⁺ > 4.0 if on QT drugs
- Hypomagnesemia — replete Mg²⁺ > 2.0
- Hypocalcemia
- Bradycardia (more time in repolarization)
- Female sex (baseline longer QT)
- Combining ≥ 2 QT-prolonging drugs — the risk is synergistic, not just additive
🧠 Serotonin Syndrome
Onset within hours of adding/increasing a serotonergic drug. Classic triad: AMS + autonomic instability + neuromuscular excitation (CLONUS is the most specific sign).
Dangerous Combinations
| Drug A | + Drug B | Risk Level |
|---|---|---|
| SSRI / SNRI | MAOI (phenelzine, tranylcypromine, selegiline) | CONTRAINDICATED — 14-day washout required between SSRI and MAOI |
| SSRI / SNRI | Linezolid (Zyvox) (weak MAOI) | HIGH RISK — hold SSRI if linezolid essential. Consult ID + psychiatry. |
| SSRI / SNRI | Tramadol | MODERATE — very common ward combination. Avoid if possible. Use alternative analgesic. |
| SSRI / SNRI | Fentanyl (Sublimaze) (especially IV/patch) | MODERATE — serotonergic at higher doses. Monitor closely. |
| SSRI / SNRI | Triptans (sumatriptan) | LOW-MODERATE — FDA warning but actual risk is very low. Can use with monitoring. |
| SSRI / SNRI | Methylene blue (IV) | HIGH RISK — methylene blue is an MAOI. Hold SSRI ≥ 2 weeks before elective use. |
| SSRI / SNRI | Ondansetron (Zofran) | LOW — 5-HT3 antagonist. Theoretical risk. Clinically rare. Generally safe to use. |
Treatment
- Stop all serotonergic agents
- Cyproheptadine 12 mg PO loading → 4 mg q6h (serotonin antagonist)
- Benzodiazepines for agitation and muscle rigidity
- Cooling if hyperthermic. Avoid paralysis (masks clonus — makes monitoring impossible).
- Most cases resolve within 24–72h after stopping the offending drug
⚠️ Key Drug Combinations to Watch
| Combination | Risk | What to Do |
|---|---|---|
| ACEi/ARB + K⁺-sparing diuretic + NSAID | "Triple whammy" → hyperkalemia + AKI | Avoid triple combination. If unavoidable → check K⁺ and Cr within 1 week. Stop NSAID if possible. |
| Warfarin + TMP-SMX | ↑↑ INR (TMP-SMX inhibits CYP2C9) | INR can double within 3–5 days. Check INR 3 days after starting TMP-SMX. Reduce warfarin dose empirically. |
| Warfarin + fluconazole | ↑↑ INR (fluconazole inhibits CYP2C9) | Same as above. Reduce warfarin dose by ~25–50%. Check INR frequently. |
| Warfarin + amiodarone | ↑ INR (CYP inhibition) — effect persists weeks after stopping amio | Reduce warfarin dose by 30–50% when starting amiodarone. Monitor INR weekly. |
| Statin + clarithromycin/erythromycin | Rhabdomyolysis (CYP3A4 inhibition → statin levels ↑↑) | Hold statin during macrolide course. Or use azithromycin (no CYP3A4 inhibition). |
| Colchicine (Colcrys) + clarithromycin | Fatal toxicity (CYP3A4 + P-gp inhibition → colchicine accumulates) | Do NOT co-administer. Multiple reported deaths. Reduce colchicine dose or hold during macrolide. |
| Metformin + IV contrast | Lactic acidosis (if contrast causes AKI → metformin accumulates) | Hold metformin day of contrast. Resume 48h later if Cr stable. eGFR < 30 → hold regardless. |
| Digoxin + amiodarone | Digoxin toxicity (amio increases dig levels ~70%) | Reduce digoxin dose by 50% when starting amiodarone. Check dig level in 1 week. |
| Carbamazepine (Tegretol) + many drugs | ↓ levels of warfarin, DOACs, OCP, steroids (potent CYP3A4 inducer) | Check for interactions with all co-medications. May need dose increases of affected drugs. |
| Allopurinol (Zyloprim) + azathioprine (Imuran) | Fatal myelosuppression (allopurinol blocks xanthine oxidase → azathioprine accumulates) | Reduce azathioprine dose by 75% if must co-administer. Or use mycophenolate instead. Monitor CBC closely. |
Anticoagulation Reversal
When the patient on blood thinners is bleeding or needs emergency surgery. Know the agent, know the antidote, know the dose. Every minute counts in life-threatening hemorrhage.
🩸 Emergency Reversal
| Anticoagulant | Reversal Agent | Dose | Onset | Key Notes |
|---|---|---|---|---|
| Warfarin | 4-Factor PCC (Kcentra) LIFE-THREATENING | INR 2–4: 25 units/kg INR 4–6: 35 units/kg INR > 6: 50 units/kg | Minutes | First-line for life-threatening bleed. Always give with vitamin K 10 mg IV (slow push over 10 min — anaphylaxis risk if fast). PCC effect is temporary (6–8h); vitamin K provides sustained reversal (6–24h). FFP is second-line (large volume, slow, infection risk). |
| Warfarin | Vitamin K (phytonadione) NON-EMERGENT | INR > 10, no bleed: 2.5–5 mg PO Minor bleed: 5–10 mg IV slow | 6–24h | PO preferred for non-emergent. IV onset faster but anaphylaxis risk. SubQ absorption is erratic — avoid. Recheck INR in 6–12h. |
| Dabigatran (Pradaxa) | Idarucizumab (Praxbind) | 5g IV (given as 2 × 2.5g boluses) | Minutes | Specific monoclonal antibody fragment. Complete reversal within minutes. Single use. If unavailable: 4F-PCC 50 units/kg (partial effect). Hemodialysis removes ~60% of dabigatran (it's dialyzable — unique among DOACs). |
| Rivaroxaban (Xarelto) Apixaban (Eliquis) Edoxaban (Savaysa) | Andexanet alfa (Andexxa) | Low dose: 400 mg bolus → 4 mg/min × 2h High dose: 800 mg bolus → 8 mg/min × 2h | Minutes | Recombinant modified Factor Xa decoy. Very expensive (~$50,000/dose). Low dose if last DOAC dose > 8h ago or low-dose apixaban. High dose if within 8h or rivaroxaban. If unavailable: 4F-PCC 50 units/kg (reasonable alternative, much cheaper). |
| Unfractionated heparin | Protamine sulfate | 1 mg per 100 units heparin given in last 2–3h. Max 50 mg. | 5 min | Full reversal. Risk: hypotension, bradycardia, anaphylaxis (especially in patients with fish allergy, prior protamine, or NPH insulin use — NPH contains protamine). |
| Enoxaparin (LMWH) | Protamine sulfate | 1 mg per 1 mg enoxaparin (if within 8h of dose). 0.5 mg per 1 mg if 8–12h. | 5 min | Only ~60% reversal (protamine neutralizes anti-IIa but not anti-Xa activity of LMWH). If still bleeding → consider 4F-PCC. |
| tPA / fibrinolytics | Cryoprecipitate + TXA | Cryo 10 units (fibrinogen > 200). TXA 1g IV over 10 min. | Minutes | Replenish fibrinogen (consumed by tPA). TXA is antifibrinolytic. Also give platelets if < 100K. Aminocaproic acid is alternative to TXA. |
🔧 Pre-Procedure Hold Times
| Drug | Hold Before Procedure | Resume After | Bridging Needed? |
|---|---|---|---|
| Warfarin (Coumadin) | 5 days (INR < 1.5 for most procedures) | 12–24h post (once hemostasis confirmed) | Only if high thrombotic risk: mechanical mitral valve, recent VTE (< 3 mo), CHA₂DS₂-VASc ≥ 7. Use enoxaparin 1 mg/kg BID. Most patients do NOT need bridging BRIDGE, 2015: bridging increased bleeding without reducing thromboembolism. |
| Apixaban (Eliquis) | 48h (72h if high bleed risk or CrCl < 30) | 24–48h post | No bridging needed (short half-life, rapid onset on resumption). |
| Rivaroxaban (Xarelto) | 48h (72h if CrCl < 30) | 24–48h post | No bridging. |
| Dabigatran (Pradaxa) | 48–72h (CrCl 50–80). 96h+ if CrCl < 50. | 24–48h post | No bridging. Longer hold in renal impairment (renally cleared). |
| Enoxaparin (therapeutic) | 24h | 24–48h post | N/A |
| Heparin drip | 4–6h (check aPTT) | When safe per surgeon | N/A |
| Aspirin (primary prevention) | 7 days | 24h post | N/A |
| Aspirin (cardiac stent) | DO NOT STOP | N/A | Continue through procedure unless life-threatening bleed risk. Stopping ASA within 6 months of DES → stent thrombosis → MI. |
| Clopidogrel (Plavix) | 5 days | 24h post | Consult cardiology before holding if recent stent. |
Insulin Calculator
Convert sliding scale usage into a proper basal-bolus regimen. Enter the patient's 24h sliding scale insulin usage and get a calculated basal-bolus prescription.
🧮 Sliding Scale → Basal-Bolus Converter
Method 1 — From Sliding Scale Usage
Add up all sliding scale insulin given in the past 24h.
Method 2 — Weight-Based (Insulin-Naive)
For patients not previously on insulin or no sliding scale data available.
📋 Quick Reference
| Scenario | Recommendation |
|---|---|
| Patient eating normally | Full basal-bolus-correction: 50% basal (glargine QHS) + 50% nutritional (lispro AC meals) + correction scale |
| NPO | Continue basal (reduce 20–50% if concerned). Hold nutritional. Correction-only sliding scale q6h. Never hold basal completely in Type 1. |
| Tube feeds (continuous) | Basal (glargine) + correction q6h. Or NPH q12h + correction. Or 70/30 insulin q12h. |
| On steroids | ↑ TDD by 20–40%. Steroids cause afternoon/evening hyperglycemia → increase lunch and dinner nutritional doses more than basal. |
| Transitioning from drip | 24h drip total × 80% = TDD. Split 50/50. Give SubQ basal 2–4h BEFORE stopping drip (overlap for glargine onset). |
| Correction factor | 1800 ÷ TDD = how many mg/dL 1 unit drops glucose. Example: TDD 60 → CF = 30 → 1 unit drops BG by 30 mg/dL. |
Radiology Quick Reference
Systematic CXR interpretation, common CT findings, and when to order what. You don't need to be a radiologist — you need to not miss the dangerous stuff.
🩻 Systematic CXR — ABCDE
| Step | What to Check | Key Findings |
|---|---|---|
| A — Airway | Trachea (midline?), carina, mainstem bronchi | Tracheal deviation: TOWARD collapse/atelectasis, AWAY from tension PTX/large effusion. ETT tip: 2–4 cm above carina. |
| B — Bones & soft tissue | Ribs (fractures?), clavicles, spine, subcutaneous emphysema | Rib fractures → PTX? Flail chest (≥3 consecutive ribs, ≥2 places)? Lytic lesions (mets)? SubQ air → esophageal rupture, necrotizing infection. |
| C — Cardiac | Heart size, silhouette, mediastinum width | CTR > 0.5 = cardiomegaly (on PA film). Boot-shaped → RVH. Water-bottle → pericardial effusion. Widened mediastinum > 8 cm → aortic dissection, aortic aneurysm, lymphoma. |
| D — Diaphragm | Costophrenic angles (blunted?), free air under diaphragm, elevated hemidiaphragm | Blunted CP angles: ≥ 200 mL effusion (lateral decubitus more sensitive). Free air under diaphragm → perforated viscus (surgical emergency). Elevated hemidiaphragm → phrenic nerve palsy, hepatomegaly, subpulmonic effusion. |
| E — Everything else (lungs) | Lung fields: compare L vs R, upper vs lower. Infiltrates, masses, pneumothorax, lines/tubes | White-out: large effusion (meniscus), complete atelectasis (shifted structures toward), massive PNA. PTX: visceral pleural line + absent lung markings. Kerley B lines: pulmonary edema. Check all lines: ETT, central line, NG tube, chest tube, pacer wires. |
Before interpreting: check patient name, date, PA vs AP (AP magnifies heart → can't assess cardiomegaly), rotation (spinous processes centered between clavicular heads), inspiration (≥ 9 posterior ribs = adequate), penetration (should barely see spine through cardiac silhouette).
🔍 Common CT Findings
| Finding | Think | Clinical Action |
|---|---|---|
| CT Head — hyperdense (white) | Acute blood (ICH, SDH, EDH, SAH) | SDH: crescent-shaped, crosses suture lines. EDH: lens-shaped, doesn't cross sutures. SAH: blood in sulci/cisterns → CTA for aneurysm. ICH: check INR, reverse anticoag. |
| CT Head — hypodense (dark) | Ischemic stroke (after 6–12h), chronic SDH, edema | Acute stroke may be normal on CT < 6h → loss of gray-white differentiation is earliest sign. MRI DWI is more sensitive early. |
| CTPA — filling defect in PA | Pulmonary embolism | Saddle PE (at bifurcation) → hemodynamically significant. RV/LV ratio > 1 → RV strain. Check troponin, BNP. |
| CT Chest — ground glass opacities (GGO) | PCP pneumonia (HIV), viral PNA (COVID, influenza), pulmonary edema, DAH, early ILD, drug toxicity | Bilateral diffuse GGO + HIV → check CD4, start TMP-SMX for PCP. Bilateral + ICU → ARDS. Peripheral/basal → UIP/IPF pattern. |
| CT Chest — tree-in-bud pattern | TB, atypical mycobacteria, aspiration | Small airway disease. Centrilobular nodules + tree-in-bud = active infectious bronchiolitis. Isolate for TB. Get sputum AFB × 3. |
| CT Abdomen — free air | Perforated viscus | Surgical emergency. Most common: perforated duodenal ulcer, perforated diverticulitis, perforated appendix. Get surgical consult immediately. |
| CT Abdomen — portal venous gas | Mesenteric ischemia, bowel necrosis | Ominous sign. Also pneumatosis intestinalis (air in bowel wall). Lactate elevated. Surgical emergency. CT angiography for mesenteric vessels. |
| CT Abdomen — dilated bowel | SBO vs ileus | SBO: transition point (dilated → decompressed), small bowel > 3 cm. Ileus: diffusely dilated, no transition point. SBO → surgical consult. Toxic megacolon (C. diff): colon > 6 cm. |
📋 What Imaging to Order
| Clinical Question | Best Study | Notes |
|---|---|---|
| Chest pain — ACS ruled out, PE suspected | CTPA | Wells score first. If low probability → D-dimer. If D-dimer positive or high probability → CTPA. V/Q scan if contrast allergy or CKD. |
| Stroke symptoms (< 24h) | CT Head without contrast (rule out hemorrhage) → CTA head/neck (LVO) → MRI DWI (confirm ischemic) | CT to rule out bleed before tPA. CTA for large vessel occlusion (thrombectomy candidate). MRI DWI most sensitive for acute ischemia. |
| Abdominal pain | CT abdomen/pelvis with IV contrast | Most versatile. RLQ pain in young female → consider US first (ovarian pathology, avoid radiation). RUQ pain → RUQ US first (gallstones, cholecystitis). |
| GI bleed — upper vs lower | EGD first. CT angiography if massive/unstable. | CTA abdomen/pelvis if active bleeding (extravasation). Tagged RBC scan if slow intermittent bleed. Colonoscopy within 24h for lower GIB. |
| Renal colic / stones | CT abdomen/pelvis WITHOUT contrast | Non-contrast CT is gold standard for stones (contrast obscures them). US is first-line in pregnancy. |
| Biliary disease | RUQ ultrasound | First-line for gallstones, cholecystitis. MRCP for common bile duct stones if US equivocal. HIDA scan for acalculous cholecystitis (EF < 35%). |
| DVT suspected | Compression ultrasound | Sensitivity > 95% for proximal DVT. If negative but high clinical suspicion → repeat in 5–7 days or whole-leg US. |
| Aortic dissection | CTA chest/abdomen/pelvis | Gold standard. TEE is alternative (especially if too unstable for CT). D-dimer < 500 has high NPV for dissection. |
| Pleural effusion workup | CXR → US-guided thoracentesis | Lateral decubitus CXR to confirm free-flowing. Bedside US for marking. CT chest with contrast if concern for malignancy, empyema, or loculated. |
| Pulmonary nodule found | Follow Fleischner criteria | Size, morphology (solid vs GGO vs part-solid), risk factors determine follow-up interval. Part-solid nodules have highest malignancy risk. PET-CT for solid nodules ≥ 8 mm. |
Contrast contraindications: eGFR < 30 (risk of CIN — but don't withhold if life-threatening indication like PE, dissection, stroke), contrast allergy (premedicate: prednisone 50 mg at 13h, 7h, 1h before + diphenhydramine 50 mg 1h before). Metformin: hold day of contrast, resume 48h later if Cr stable.
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Sepsis · DKA · ARDS · Heart Failure · Antibiotics · ECG · Code Blue · Calculators
Sepsis · DKA · ARDS · Heart Failure · Antibiotics · ECG · Code Blue · Calculators
Massive Transfusion Protocol
Hemorrhagic shock requiring rapid blood product replacement. 1:1:1 ratio (pRBC:FFP:platelets). Activate MTP early — do not wait for labs. Permissive hypotension until surgical control.
🔍 Overview
Definition & Triggers
Massive transfusion = replacement of ≥1 entire blood volume (≈10 units pRBC) in 24h, or ≥4 units pRBC in 1 hour with ongoing hemorrhage. Activate MTP when anticipating need for massive resuscitation.
| MTP Trigger | Details |
|---|---|
| ABC Score ≥ 2 | Assessment of Blood Consumption: penetrating mechanism, SBP ≤ 90, HR ≥ 120, positive FAST |
| Shock Index > 1.0 | HR/SBP ratio — simple bedside predictor of need for transfusion |
| Clinical judgment | Obvious massive hemorrhage (GI bleed, trauma, postpartum, surgical) |
Do NOT wait for labs to activate MTP. By the time Hgb drops, the patient has already lost 30–40% of blood volume.
🚨 Management
1:1:1 Resuscitation
Based on PROPPR, 2015 — balanced ratio resuscitation. Goal: approximate whole blood composition.
| Product | Ratio | Key Notes |
|---|---|---|
| pRBCs | 1 | O-neg until type & screen available (O-pos acceptable for males) |
| FFP | 1 | Replaces clotting factors. Thaw takes 20–30 min — keep thawed plasma available |
| Platelets | 1 | 1 apheresis unit per 6-pack pRBC |
| Cryoprecipitate | Give when fibrinogen < 150 | 10 units = ↑ fibrinogen ~70 mg/dL |
Adjuncts
- Tranexamic Acid (TXA) 1g IV over 10 min → 1g over 8h — give within 3 hours of injury (CRASH-2, 2010)
- Calcium: Replace aggressively — citrate in blood products chelates calcium → hypocalcemia → cardiac arrest. Give Calcium Chloride 1g IV per 4 units pRBC
- Permissive hypotension: Target SBP 80–90 until surgical hemostasis (except TBI — MAP ≥ 80)
- Damage control resuscitation: Limit crystalloid. Avoid hypothermia, acidosis, coagulopathy ("lethal triad")
🧪 Workup
Labs During MTP
- CBC q30–60 min
- PT/INR, PTT, fibrinogen q30–60 min
- BMP (Ca²⁺, K⁺ — hyperkalemia from stored blood)
- ABG/VBG (pH, lactate, base deficit)
- TEG/ROTEM if available (point-of-care coagulation)
- Type & screen / crossmatch
Monitor ionized calcium closely. Hypocalcemia from citrate toxicity is the #1 preventable cause of cardiac arrest during MTP.
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| Tranexamic Acid (TXA) | 1g IV bolus → 1g over 8h | Antifibrinolytic — give within 3h of injury |
| Calcium Chloride | 1g IV per 4 units pRBC | Prevent/treat citrate-induced hypocalcemia |
| Calcium Gluconate | 3g IV (equivalent to 1g CaCl) | Alternative if no central line (less tissue necrosis) |
| Cryoprecipitate | 10 units IV | Fibrinogen < 150 mg/dL |
| Vitamin K (Phytonadione) | 10 mg IV | If on warfarin or INR > 1.5 |
📊 Monitoring
During MTP
- Vitals q5–15 min
- Ionized Ca²⁺ q30 min — replace aggressively
- Temperature — warm all products, forced air warming blanket
- Urine output — Foley, target ≥ 0.5 mL/kg/hr
- ABG/lactate q30–60 min (trend as resuscitation marker)
- CBC, coags, fibrinogen q30–60 min
- K⁺ — hyperkalemia from stored blood lysis
📋 On Rounds
Pimp Questions
What is the "lethal triad" in trauma?
Hypothermia + acidosis + coagulopathy. These three form a vicious cycle: hypothermia impairs coagulation cascade enzymes, acidosis inhibits clotting factor function, and coagulopathy leads to ongoing hemorrhage → more hypothermia and acidosis. Damage control resuscitation targets all three: warm products, limit crystalloid (worsens acidosis/dilutional coagulopathy), balanced 1:1:1 ratio.
Why do we give calcium during MTP?
Stored blood products contain citrate as anticoagulant. Citrate chelates ionized calcium. During rapid transfusion, citrate overwhelms hepatic metabolism → hypocalcemia → prolonged QT, hypotension, decreased cardiac output, cardiac arrest. Give 1g CaCl per 4 units pRBC. Monitor iCa q30 min.
When should TXA be given and what is the evidence?
Within 3 hours of injury onset. CRASH-2 trial (2010): TXA reduced all-cause mortality in bleeding trauma patients (14.5% vs 16%). Given > 3 hours it may increase mortality. Mechanism: inhibits plasminogen → plasmin conversion, reducing fibrinolysis.
⚡ Summary
MTP Trigger
ABC score ≥ 2, Shock Index > 1, or clinical judgment. Do NOT wait for labs.
Ratio
1:1:1 pRBC:FFP:Platelets. Based on PROPPR trial. Goal = approximate whole blood.
TXA
1g IV over 10 min → 1g over 8h. Within 3 hours only (CRASH-2). Antifibrinolytic.
Calcium
1g CaCl per 4 units pRBC. Citrate chelates Ca²⁺ → cardiac arrest if untreated.
Lethal Triad
Hypothermia + acidosis + coagulopathy. Warm products, limit crystalloid, 1:1:1 ratio.
Labs
CBC, coags, fibrinogen, iCa, K⁺, ABG q30-60 min. TEG/ROTEM if available.
Brain Death Evaluation
Irreversible cessation of all brain function including brainstem. Standardized evaluation required. Two clinical exams by qualified physicians separated by observation period. Apnea test is the key confirmatory component.
🔍 Overview
Definition
Brain death = irreversible loss of all functions of the entire brain, including brainstem. Legal death in all US states. Requires systematic evaluation to exclude confounders.
Prerequisites (Must Meet ALL)
| Prerequisite | Details |
|---|---|
| Known cause | Established etiology sufficient to cause brain death (e.g., massive stroke, TBI, anoxic injury) |
| Irreversibility | No possibility of recovery — adequate time for observation |
| No confounders | Core temp ≥ 36°C, SBP ≥ 100, no CNS depressants (check drug levels), no neuromuscular blockade, no severe metabolic derangements |
🚨 Management
Clinical Examination (Two Required)
| Brainstem Reflex | Test | Expected in Brain Death |
|---|---|---|
| Pupillary | Bright light in each eye | Fixed, dilated (4–9 mm), no response |
| Corneal | Cotton wisp or saline drops | No blink |
| Oculocephalic | Doll's eyes (turn head side to side) | No eye movement (eyes stay midline) |
| Oculovestibular | Cold caloric (50 mL ice water in ear canal) | No eye deviation toward cold ear |
| Gag | Stimulate posterior pharynx | No response |
| Cough | Suction catheter to carina | No cough |
Apnea Test
- Pre-oxygenate with 100% FiO₂ × 10 min
- Obtain baseline ABG (PaCO₂ should be 35–45)
- Disconnect ventilator, deliver O₂ via T-piece at 6 L/min
- Observe 8–10 minutes for any respiratory effort
- Repeat ABG — positive test: PaCO₂ ≥ 60 OR ↑ ≥ 20 from baseline with NO respiratory effort
- Abort if SBP < 90, SpO₂ < 85%, or cardiac arrhythmia
🧪 Workup
Required Studies
- CT/MRI showing devastating brain injury
- Core temperature ≥ 36°C
- Drug screen / levels (barbiturates, benzos, opioids, neuromuscular blockers)
- BMP — no severe electrolyte/metabolic derangements
- ABG — before and after apnea test
Ancillary Tests (if clinical exam cannot be completed)
| Test | Finding in Brain Death |
|---|---|
| Cerebral angiography | No intracerebral blood flow (gold standard) |
| EEG | Electrocerebral silence × 30 min |
| Nuclear scan (HMPAO) | "Hollow skull" — no cerebral uptake |
| Transcranial Doppler | Reverberating flow or absent diastolic flow |
💊 Medications
No medications are used for brain death evaluation per se. Key considerations:
- Confirm absence of CNS depressants — must have drug levels below therapeutic range. Wait 5 half-lives for barbiturates, benzodiazepines, paralytics
- Vasopressors — maintain SBP ≥ 100 during evaluation (organ perfusion if donation candidate)
- Desmopressin (DDAVP) 1–4 mcg IV — for diabetes insipidus (common with brain death — loss of ADH from posterior pituitary)
- Levothyroxine (Synthroid) — T4 replacement if organ donation planned
- Methylprednisolone (Solu-Medrol) — stress-dose steroids if organ donation planned
📊 Monitoring
- Core temp — must be ≥ 36°C throughout
- SBP ≥ 100 mmHg during exam
- SpO₂ continuous during apnea test
- Urine output — diabetes insipidus is common (polyuria, low urine osmolality)
- Na⁺ — hypernatremia from DI
- Document exact times of both examinations
📋 On Rounds
Pimp Questions
What confounders must be excluded before brain death testing?
Hypothermia (core temp must be ≥ 36°C), hypotension (SBP must be ≥ 100), CNS depressants (barbiturates, benzos, opioids — check levels), neuromuscular blockade (confirm train-of-four), and severe metabolic derangements (electrolyte abnormalities, hepatic/uremic encephalopathy). Each of these can mimic brain death and must be corrected or excluded.
What defines a positive apnea test?
After disconnecting the ventilator for 8–10 min with O₂ insufflation: PaCO₂ ≥ 60 mmHg OR rise ≥ 20 mmHg from baseline with NO respiratory effort observed. This confirms the brainstem has no CO₂-driven respiratory drive. Abort if hemodynamic instability or desaturation.
Why is diabetes insipidus common in brain death?
The posterior pituitary loses function → no ADH (vasopressin) secretion → massive free water diuresis. Presents as polyuria (> 300 mL/hr), hypernatremia, low urine specific gravity (< 1.005). Treat with DDAVP 1–4 mcg IV. Important for organ preservation.
⚡ Summary
Prerequisites
Known cause, irreversibility, core temp ≥ 36°C, SBP ≥ 100, no CNS depressants, no NMB.
Clinical Exam
Absent brainstem reflexes: pupillary, corneal, oculocephalic, oculovestibular, gag, cough. Two exams required.
Apnea Test
PaCO₂ ≥ 60 or ↑ ≥ 20 with NO respiratory effort. Pre-oxygenate, O₂ insufflation during test.
Ancillary Tests
If clinical exam incomplete: cerebral angiography (gold standard), EEG, nuclear scan, TCD.
Common Complication
Diabetes insipidus — loss of ADH → polyuria, hypernatremia. Treat with DDAVP.
Documentation
Two exams by qualified physicians. Record exact times. Time of death = time of second exam completion.
Targeted Temperature Management
Post-cardiac arrest neuroprotection via controlled hypothermia (32–36°C) for 24h. Prevents secondary neuronal injury from reperfusion. Initiate early after ROSC. Avoid fever aggressively.
🔍 Overview
Indications
| Indication | Target Temperature | Evidence |
|---|---|---|
| Cardiac arrest (shockable rhythm) | 32–36°C × 24h | TTM, 2013; TTM2, 2021 |
| Cardiac arrest (non-shockable) | 32–36°C × 24h | Weaker evidence but still recommended by AHA guidelines. HYPERION, 2019 showed 33°C improved neurologic outcome in non-shockable rhythm arrests. |
| Key principle | Avoid fever (> 37.7°C) | Fever after cardiac arrest strongly associated with worse neurologic outcomes |
TTM2 (2021) found no benefit of 33°C vs normothermia. The key takeaway: aggressive fever prevention is what matters most. Target ≤ 37.5°C at minimum.
🚨 Management
Three Phases of TTM
| Phase | Duration | Details |
|---|---|---|
| Induction | ASAP after ROSC | Cold IV saline 30 mL/kg (NOT during CPR), surface/intravascular cooling device. Reach target temp within 4h. |
| Maintenance | 24 hours | Hold at target ± 0.5°C. Continuous temp monitoring (esophageal or bladder probe). |
| Rewarming | 0.25°C/hour | SLOW — rapid rewarming causes rebound cerebral edema, seizures, hemodynamic instability. Takes 12–16 hours. |
Rewarm SLOWLY — 0.25°C/hour maximum. Rapid rewarming negates all benefit of TTM and causes rebound injury.
🧪 Workup
- Continuous core temperature (esophageal or bladder probe — NOT rectal, NOT axillary)
- Continuous EEG monitoring (seizure detection)
- CBC, BMP, Mg, PO₄ q6h (electrolyte shifts during cooling/rewarming)
- Coagulation studies q12h
- Lactate trending
- CT head — rule out hemorrhagic cause
- ECG — Osborn waves (J waves) at < 32°C
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Propofol (Diprivan) | 5–50 mcg/kg/min IV | Sedation — prevents shivering. First-line. |
| Fentanyl (Sublimaze) | 25–100 mcg/h IV | Analgesia + anti-shivering |
| Cisatracurium (Nimbex) | 1–3 mcg/kg/min IV | NMB — last resort for refractory shivering. Masks seizures — need continuous EEG |
| Meperidine (Demerol) | 25–50 mg IV | Anti-shivering (lowers shivering threshold). Unique among opioids. |
| Buspirone (Buspar) | 30 mg PO/NG | Anti-shivering adjunct |
| Magnesium Sulfate | Target Mg 3–4 mg/dL | Raises shivering threshold, neuroprotective |
📊 Monitoring
- Core temp q15 min during induction, q1h during maintenance
- Continuous EEG — mandatory if paralyzed (NMB masks seizures)
- K⁺, Mg²⁺, PO₄ q4–6h (shift intracellularly during cooling, rebound during rewarming)
- Glucose q1–4h (insulin sensitivity increases with hypothermia)
- Bedside Shivering Assessment Scale (BSAS) q1h
- Hemodynamics — bradycardia is expected at 33°C (do NOT treat unless unstable)
📋 On Rounds
Pimp Questions
What is the current target temperature after cardiac arrest based on TTM2?
TTM2 (2021) found no benefit of 33°C hypothermia vs normothermia (≤37.5°C). The key finding: aggressive fever prevention is what matters. Current practice: target 32–36°C based on institutional protocol, but the most important thing is preventing fever (> 37.7°C), which is strongly associated with worse neurologic outcomes.
Why is shivering a major concern during TTM?
Shivering is the body's thermoregulatory response to cooling. It increases metabolic rate 2–5x, generates heat (counteracting cooling), increases oxygen consumption, raises ICP, and causes patient discomfort. The anti-shivering cascade: surface counter-warming → acetaminophen + buspirone + meperidine → propofol/fentanyl → paralysis (last resort, requires continuous EEG).
What electrolyte abnormalities occur during TTM?
During cooling: K⁺, Mg²⁺, PO₄ shift intracellularly → hypokalemia, hypomagnesemia, hypophosphatemia. Replace cautiously. During rewarming: These ions shift back out → rebound hyperkalemia (can be dangerous). This is why rewarming must be slow (0.25°C/hr) and electrolytes checked frequently.
⚡ Summary
Indication
Comatose post-cardiac arrest (shockable or non-shockable). Start ASAP after ROSC.
Target
32–36°C × 24h. TTM2 suggests ≤37.5°C may suffice. AVOID FEVER — this is the key.
Rewarming
0.25°C/hour. SLOW. Rapid rewarming → rebound cerebral edema, seizures, hyperkalemia.
Shivering
Buspirone + meperidine → propofol/fentanyl → NMB (needs continuous EEG if paralyzed).
Electrolytes
K⁺/Mg/PO₄ shift in during cooling, shift out during rewarming. Monitor q4-6h.
Monitoring
Core temp (esophageal/bladder), continuous EEG, K⁺ q4h, glucose q1-4h, BSAS q1h.
Cardiac Tamponade
Pericardial fluid compresses chambers → impaired filling → obstructive shock. Beck's triad: hypotension, JVD, muffled heart sounds. Echo-guided pericardiocentesis is lifesaving.
🔍 Overview
Pathophysiology
Pericardial effusion → intrapericardial pressure exceeds chamber filling pressure → impaired diastolic filling → ↓ cardiac output → obstructive shock. Rate of accumulation matters more than volume — acute 150 mL can cause tamponade; chronic effusions may accumulate 1–2 L before symptoms.
Etiology
| Category | Causes |
|---|---|
| Malignancy | Lung, breast, lymphoma, melanoma — most common cause of large effusions |
| Infection | Viral (Coxsackie, Echo), TB (especially in endemic areas), bacterial, fungal |
| Uremia | CKD/ESRD — hemorrhagic pericarditis |
| Iatrogenic | Post-cardiac surgery, catheterization, pacemaker insertion |
| Trauma | Penetrating chest injury, aortic dissection |
| Autoimmune | SLE, RA, scleroderma |
Beck's Triad: Hypotension + JVD + muffled heart sounds. Present in only ~30% of cases. Do NOT rely on complete triad — echo is the diagnostic tool.
🚨 Management
Emergent Management
- IV fluids — aggressive volume resuscitation to maintain preload (bridge to pericardiocentesis)
- AVOID diuretics, nitrates, positive pressure ventilation (all reduce preload → cardiovascular collapse)
- Pericardiocentesis — echo-guided, subxiphoid approach. Aspirate even 20–30 mL can dramatically improve hemodynamics
- Pericardial drain — leave catheter if recurrent/malignant effusion
- Pericardial window — surgical option for recurrent tamponade
Do NOT give positive pressure ventilation to tamponade patients if avoidable. PPV ↓ venous return → immediate cardiovascular collapse. Avoid intubation until pericardiocentesis is imminent or underway.
🧪 Workup
Diagnosis
- Echocardiography — gold standard. RA/RV diastolic collapse, IVC plethora, respiratory variation in mitral/tricuspid inflow
- ECG — low voltage, electrical alternans (beat-to-beat QRS amplitude variation = swinging heart)
- CXR — "water bottle" heart silhouette
- Pulsus paradoxus — SBP drop > 10 mmHg with inspiration
💊 Medications
Tamponade is a mechanical problem requiring mechanical solution (drainage). No medications fix tamponade.
| Intervention | Details |
|---|---|
| IV NS bolus | 500–1000 mL — bridge to pericardiocentesis |
| Phenylephrine (Neo-Synephrine) | If hypotensive — maintain SVR as bridge. 100–200 mcg IV boluses |
| AVOID | Diuretics, nitrates, β-blockers, positive pressure ventilation |
📊 Monitoring
- Continuous telemetry and pulse oximetry
- Arterial line — pulsus paradoxus monitoring
- Repeat echo — assess for reaccumulation
- Pericardial drain output — track hourly
- CVP — elevated and non-responsive to fluids
📋 On Rounds
Pimp Questions
Why is positive pressure ventilation dangerous in tamponade?
PPV increases intrathoracic pressure → decreases venous return to the right heart. In tamponade, cardiac output is already critically preload-dependent. Removing venous return → immediate cardiovascular collapse. If intubation is necessary, prepare for hemodynamic crash and have pericardiocentesis ready.
What is pulsus paradoxus and why does it occur?
SBP drop > 10 mmHg with inspiration. Normally, inspiration increases RV filling and slightly decreases LV filling. In tamponade, the rigid pericardium constrains total cardiac volume — inspiratory RV expansion occurs at the expense of LV compression (ventricular interdependence). This exaggerates the normal drop in SBP.
What echo findings suggest tamponade?
(1) RA collapse in systole (most sensitive early sign), (2) RV diastolic collapse (more specific), (3) IVC plethora (dilated, no respiratory variation), (4) > 25% respiratory variation in mitral inflow velocities. A large effusion without these findings = effusion without tamponade.
⚡ Summary
Pathophys
Pericardial fluid → impaired diastolic filling → obstructive shock. Rate > volume.
Beck's Triad
Hypotension + JVD + muffled heart sounds. Only ~30% have all three. Use echo.
Echo Findings
RA systolic collapse, RV diastolic collapse, IVC plethora, respiratory variation.
Treatment
Pericardiocentesis (echo-guided). IV fluids as bridge. AVOID diuretics/PPV.
Avoid
Diuretics, nitrates, β-blockers, PPV — all reduce preload → collapse.
ECG
Low voltage, electrical alternans. Pulsus paradoxus > 10 mmHg.
Pulmonary Hypertension
Mean PAP ≥ 20 mmHg at rest by right heart catheterization. WHO Group 1 (PAH) is the classic form. RV failure is the primary cause of death. Avoid volume overload and systemic vasodilators.
🔍 Overview
WHO Classification
| Group | Category | Examples |
|---|---|---|
| 1 | Pulmonary Arterial HTN (PAH) | Idiopathic, heritable, CTD-associated (scleroderma), HIV, portopulmonary, drugs |
| 2 | Left heart disease | HFrEF, HFpEF, valvular disease — MOST COMMON cause of PH |
| 3 | Lung disease/hypoxia | COPD, ILD, OSA |
| 4 | CTEPH | Chronic thromboembolic PH — potentially curable with pulmonary endarterectomy |
| 5 | Multifactorial | Sarcoidosis, hematologic, metabolic |
Group 2 (left heart disease) is the most common cause of PH. PAH-specific therapies are CONTRAINDICATED in Group 2 — they worsen pulmonary edema.
🚨 Management
General Principles
- Treat underlying cause — Group 2: optimize HF. Group 3: supplemental O₂. Group 4: anticoagulation ± PTE
- PAH-specific therapy — only for Group 1 (and select Group 4/5). Based on vasoreactivity testing
- Avoid: excessive IV fluids (RV cannot handle volume), systemic vasodilators (worsen V/Q mismatch), high-dose diuretics (RV is preload-dependent)
PAH-Specific Drug Classes
| Pathway | Drugs | Notes |
|---|---|---|
| Endothelin receptor antagonists | Bosentan (Tracleer), Ambrisentan (Letairis), Macitentan (Opsumit) | Check LFTs monthly (hepatotoxicity). Teratogenic. |
| PDE-5 inhibitors | Sildenafil (Revatio), Tadalafil (Adcirca) | ↑ cGMP → pulm vasodilation. Avoid with nitrates. |
| Prostacyclin pathway | Epoprostenol (Flolan), Treprostinil (Remodulin), Iloprost (Ventavis) | Epoprostenol = most potent. Continuous IV infusion. Line infection risk. Never abruptly stop — rebound PH crisis. |
| sGC stimulator | Riociguat (Adempas) | For PAH or inoperable CTEPH. Contraindicated with PDE-5i. |
🧪 Workup
- TTE — RV dilation/dysfunction, TR jet velocity, RVSP estimate, RA pressure
- Right heart catheterization — diagnostic gold standard. mPAP ≥ 20 mmHg, PCWP, CO, PVR
- Vasoreactivity testing — inhaled NO or IV epoprostenol during RHC. + response → trial of CCB
- PFTs — exclude Group 3
- V/Q scan — exclude Group 4 (CTEPH)
- CT chest — parenchymal lung disease
- Labs: BNP/NT-proBNP, HIV, ANA, LFTs
- 6-minute walk distance — functional assessment
💊 Medications
| Drug | Dose | Route | Key Notes |
|---|---|---|---|
| Sildenafil (Revatio) | 20 mg TID | PO | First-line oral. Avoid nitrates. |
| Tadalafil (Adcirca) | 40 mg daily | PO | Once daily dosing advantage |
| Ambrisentan (Letairis) | 5–10 mg daily | PO | ERA. Monthly LFTs. |
| Epoprostenol (Flolan) | 2–16 ng/kg/min | Continuous IV | Most potent. Never stop abruptly. Half-life 3–5 min. |
| Riociguat (Adempas) | 0.5–2.5 mg TID | PO | For PAH or CTEPH. Do not combine with PDE-5i. |
📊 Monitoring
- 6-minute walk distance q3–6 months
- BNP/NT-proBNP trending
- RV function on echo q6–12 months
- LFTs monthly if on ERA
- Functional class (WHO FC I–IV)
- Volume status — RV is preload sensitive. Diurese carefully.
📋 On Rounds
Pimp Questions
Why are PAH-specific therapies contraindicated in Group 2 PH?
Group 2 PH is caused by elevated left-sided filling pressures. PAH-specific vasodilators (prostacyclins, ERAs, PDE-5i) dilate the pulmonary vasculature → increased flow into an already congested left heart → worsening pulmonary edema and flash pulmonary edema. Treat the underlying LV dysfunction instead.
What happens if you abruptly stop epoprostenol?
Rebound PH crisis and death. Epoprostenol has a half-life of only 3–5 minutes. Abrupt cessation → acute pulmonary vasoconstriction → acute RV failure → death within minutes to hours. Patients need continuous infusion via dedicated central line. Line complications (infection, occlusion) are medical emergencies.
How do you differentiate pre-capillary from post-capillary PH?
Right heart catheterization. Pre-capillary (Groups 1,3,4,5): mPAP ≥ 20, PCWP ≤ 15, PVR ≥ 3 Wood units. Post-capillary (Group 2): mPAP ≥ 20, PCWP > 15. Combined: PCWP > 15 AND PVR ≥ 3 (out-of-proportion PH).
⚡ Summary
Definition
mPAP ≥ 20 mmHg by RHC. Group 2 (left heart disease) is most common overall.
Diagnosis
RHC is gold standard. TTE screens. V/Q scan for CTEPH. Vasoreactivity testing for CCB trial.
Group 1 Therapy
ERAs + PDE-5i ± prostacyclins. Combination therapy based on risk stratification.
Key Avoid
PAH drugs in Group 2 (worsens edema). Never stop epoprostenol abruptly (rebound crisis).
RV Management
Avoid volume overload. Careful diuresis. Maintain preload. Avoid systemic vasodilators.
Monitoring
6MWD, BNP, echo, WHO functional class. LFTs monthly on ERAs.
Stable Angina & Chronic CAD
Predictable chest pain with exertion, relieved by rest or nitroglycerin. Atherosclerotic plaque causing fixed stenosis. Optimize with GDMT before revascularization. Lifestyle modification is foundation.
🔍 Overview
Definition
Stable angina = predictable, reproducible chest discomfort triggered by exertion or emotional stress, lasting 2–10 min, relieved by rest or sublingual nitroglycerin. Caused by fixed coronary stenosis limiting flow during increased demand.
Risk Stratification
| Feature | Low Risk | High Risk |
|---|---|---|
| Stress test | No ischemia, good exercise capacity | Ischemia at low workload, ↓ EF with exercise, ≥ 2 mm ST depression |
| Anatomy | Single-vessel disease, normal EF | Left main, 3-vessel disease, ↓ EF |
| Symptoms | CCS Class I–II | CCS Class III–IV despite GDMT |
🚨 Management
Medical Therapy (GDMT)
- Anti-anginal: β-blockers (1st line) → CCBs (if β-blocker contraindicated) → long-acting nitrates → ranolazine
- Anti-ischemic risk reduction: Aspirin 81 mg daily, high-intensity statin, ACEi/ARB (especially if DM, HTN, HFrEF)
- Lifestyle: Smoking cessation (#1 modifiable risk factor), exercise, weight loss, Mediterranean diet, BP < 130/80, A1c < 7%
Revascularization
Based on ISCHEMIA, 2020 — no mortality benefit of routine revascularization over GDMT in stable CAD.
- PCI — symptom relief. No mortality benefit in stable CAD (COURAGE, ISCHEMIA).
- CABG — survival benefit in left main disease, 3-vessel disease with ↓ EF, or diabetes with multi-vessel disease
🧪 Workup
- ECG — may be normal at rest. ST depression during pain.
- Stress testing — exercise preferred. Pharmacologic if cannot exercise. Nuclear/echo for added anatomic info.
- Coronary CT angiography — anatomic assessment, calcium scoring
- Cardiac catheterization — if high-risk features on non-invasive testing
- Lipid panel, HbA1c, BMP, TSH
- Echo — baseline LV function
💊 Medications
| Drug | Dose | Role | Key Notes |
|---|---|---|---|
| Metoprolol Succinate (Toprol XL) | 25–200 mg daily | 1st line anti-anginal | ↓ HR → ↓ myocardial O₂ demand. Target HR 55–60. |
| Amlodipine (Norvasc) | 5–10 mg daily | 2nd line / add-on | Long-acting DHP CCB. Use if β-blocker contraindicated or vasospastic angina. |
| Isosorbide Mononitrate (Imdur) | 30–120 mg daily | Add-on anti-anginal | 10–14h nitrate-free interval required to prevent tolerance. |
| Ranolazine (Ranexa) | 500–1000 mg BID | Add-on | Late sodium current inhibitor. No hemodynamic effects. Prolongs QTc. |
| Aspirin | 81 mg daily | Antiplatelet | Lifelong. Reduces MI and CV death. |
| Atorvastatin (Lipitor) | 40–80 mg daily | High-intensity statin | Plaque stabilization + LDL reduction. Target LDL < 70. |
📊 Monitoring
- Symptom frequency and functional capacity (CCS class)
- Lipid panel q3–12 months until at goal, then annually
- BP target < 130/80
- HbA1c q3–6 months if diabetic
- Stress test — repeat if symptoms change
- Echo if new HF symptoms
📋 On Rounds
Pimp Questions
What did the ISCHEMIA trial show about revascularization in stable CAD?
No reduction in death or MI with routine invasive strategy vs conservative management in patients with stable CAD and moderate-severe ischemia. Invasive strategy improved anginal symptoms more. Key takeaway: GDMT is the foundation — revascularization is for symptom control in stable disease, not mortality reduction.
When does CABG provide a survival benefit over PCI?
Left main disease (≥ 50% stenosis), 3-vessel disease with reduced EF, and diabetes with multi-vessel disease (FREEDOM trial). CABG provides more complete revascularization with better long-term outcomes in these high-risk anatomies.
Why is a nitrate-free interval important?
Continuous nitrate exposure → nitrate tolerance within 24–48h via depletion of sulfhydryl groups needed for NO generation. A 10–14 hour nitrate-free interval (usually overnight) restores sensitivity. This is why isosorbide mononitrate is dosed once daily in the morning.
⚡ Summary
Definition
Predictable exertional chest pain, 2–10 min, relieved by rest/NTG. Fixed coronary stenosis.
Anti-Anginals
β-blocker (1st line) → CCB → long-acting nitrate → ranolazine. Layer as needed.
Risk Reduction
ASA 81mg, high-intensity statin (LDL < 70), ACEi/ARB. Lifestyle modification.
ISCHEMIA Trial
No mortality benefit of routine revascularization vs GDMT in stable CAD.
CABG Benefit
Left main, 3-vessel + ↓ EF, diabetes + multi-vessel disease.
Nitrate Tolerance
10–14h nitrate-free interval required. Dose ISMN once daily (AM).
Inflammatory Bowel Disease
Crohn disease (transmural, skip lesions, any GI segment) vs Ulcerative Colitis (mucosal, continuous, colon only). Distinguish from infectious colitis. Biologics have transformed management.
🔍 Overview
Crohn Disease vs Ulcerative Colitis
| Feature | Crohn Disease | Ulcerative Colitis |
|---|---|---|
| Location | Mouth to anus (terminal ileum most common) | Colon only — rectum always involved, extends proximally |
| Depth | Transmural → fistulas, strictures, abscesses | Mucosa/submucosa only |
| Pattern | Skip lesions, cobblestoning | Continuous, no skip lesions |
| Histology | Non-caseating granulomas | Crypt abscesses, pseudopolyps |
| Bloody diarrhea | Less common | Hallmark symptom |
| Smoking | Worsens disease | Protective (but don't recommend!) |
| Surgery | Not curative — disease recurs | Total colectomy is curative |
Toxic megacolon (colon dilation > 6 cm + systemic toxicity) is a life-threatening complication of both CD and UC. Requires surgical consultation, broad-spectrum antibiotics, and possible colectomy.
🚨 Management
Step-Up Therapy
| Severity | UC Treatment | Crohn Treatment |
|---|---|---|
| Mild | Mesalamine (Asacol/Lialda) PO/PR | Mesalamine (limited evidence) or budesonide |
| Moderate | Oral steroids → thiopurines or biologics | Budesonide (Entocort) → thiopurines or biologics |
| Severe | IV steroids → Infliximab (Remicade) or cyclosporine | IV steroids → anti-TNF or vedolizumab |
| Perianal/Fistulizing | N/A | Anti-TNF (infliximab preferred) + antibiotics + surgical drainage |
Extraintestinal Manifestations
- MSK: Peripheral arthritis (follows disease activity), sacroiliitis/ankylosing spondylitis (independent)
- Skin: Erythema nodosum (follows activity), pyoderma gangrenosum (independent)
- Eyes: Uveitis, episcleritis
- Hepatobiliary: Primary sclerosing cholangitis (strong UC association)
🧪 Workup
- Colonoscopy with biopsies — gold standard for diagnosis
- CT enterography/MR enterography — small bowel involvement (Crohn)
- Stool studies — C. diff, cultures, O&P (rule out infectious mimics)
- CRP, ESR — inflammation markers
- Fecal calprotectin — non-invasive marker of intestinal inflammation
- CBC (anemia), albumin, iron studies
- pANCA (UC ~70%) vs ASCA (Crohn ~60%)
💊 Medications
| Drug | Dose | Class | Key Notes |
|---|---|---|---|
| Mesalamine (Asacol) | 2.4–4.8 g/day PO | 5-ASA | UC first-line mild disease. Minimal role in Crohn. |
| Budesonide (Entocort) | 9 mg daily × 8 wk taper | Steroid | Ileal/right colon Crohn. Less systemic effects than prednisone. |
| Azathioprine (Imuran) | 2–2.5 mg/kg/day | Thiopurine | Steroid-sparing. Check TPMT before starting. Risk: lymphoma, pancreatitis. |
| Infliximab (Remicade) | 5 mg/kg IV wk 0,2,6 then q8wk | Anti-TNF | Moderate-severe IBD. Screen for TB/Hep B before starting. |
| Vedolizumab (Entyvio) | 300 mg IV q8wk | Anti-integrin | Gut-selective. Lower infection risk than anti-TNF. |
| Ustekinumab (Stelara) | Induction IV → 90 mg SC q8wk | Anti-IL12/23 | Moderate-severe Crohn. Growing UC evidence. |
📊 Monitoring
- CRP, fecal calprotectin q3–6 months
- Colonoscopy surveillance — ↑ colon cancer risk, start 8 years after diagnosis, then q1–3 years
- CBC, LFTs q3 months on thiopurines
- TB screen before biologics
- Annual skin exam (↑ skin cancer risk on thiopurines)
- DEXA scan — steroid-related osteoporosis
📋 On Rounds
Pimp Questions
How do you distinguish Crohn from UC on colonoscopy?
Crohn: Skip lesions (patchy inflammation), cobblestone mucosa, aphthous ulcers, deep linear ulcers, strictures. Can involve terminal ileum. Histology: non-caseating granulomas (found in ~30%). UC: Continuous inflammation starting at rectum extending proximally, loss of vascular pattern, pseudopolyps, friability. Histology: crypt abscesses, crypt architectural distortion.
What must you screen for before starting anti-TNF therapy?
(1) Tuberculosis — QuantiFERON Gold or PPD (anti-TNF reactivates latent TB). (2) Hepatitis B — HBsAg, anti-HBc, anti-HBs (risk of fulminant reactivation). (3) Hepatitis C. (4) Age-appropriate cancer screening. (5) Vaccination status (give live vaccines BEFORE starting, not after).
What is PSC and which IBD is it associated with?
Primary Sclerosing Cholangitis — progressive fibrosis and stricturing of intra/extrahepatic bile ducts. Strongly associated with UC (~70-80% of PSC patients have UC). Diagnosed by MRCP (beading of bile ducts). Increases risk of cholangiocarcinoma. UC + PSC patients have even higher colorectal cancer risk.
⚡ Summary
Crohn vs UC
Crohn: transmural, skip lesions, granulomas, fistulas. UC: mucosal, continuous from rectum, crypt abscesses.
Mild UC
Mesalamine (5-ASA) PO/PR. Mild Crohn: budesonide.
Moderate-Severe
Steroids bridge → biologics (anti-TNF, vedolizumab, ustekinumab). Thiopurines steroid-sparing.
Before Biologics
Screen TB (QFT), Hep B, vaccinations. Give live vaccines before starting.
Complications
Toxic megacolon, fistulas/abscesses (Crohn), strictures, colon cancer (surveillance at 8yr).
EIMs
Arthritis, erythema nodosum, pyoderma gangrenosum, uveitis, PSC (UC association).
Small Bowel Obstruction & Ileus
SBO: mechanical obstruction (adhesions #1, hernias #2). Ileus: functional without mechanical cause. CT with IV contrast is diagnostic. Most partial SBO resolves with NGT + bowel rest. Surgical emergency if strangulation.
🔍 Overview
SBO vs Ileus
| Feature | SBO (Mechanical) | Ileus (Functional) |
|---|---|---|
| Cause | Adhesions (#1, 60–75%), hernias, tumor, volvulus | Post-operative, electrolyte imbalance, opioids, peritonitis |
| Imaging | Dilated proximal bowel + decompressed distal bowel + transition point | Diffuse dilation of small AND large bowel, no transition point |
| Air-fluid levels | Multiple, differential (step-ladder pattern) | Few, similar height |
| Management | NGT, NPO, IVF. Surgery if complete/strangulated. | Treat underlying cause. Bowel rest. Ambulation. |
Signs of strangulation (surgical emergency): Fever, tachycardia, peritonitis, leukocytosis, elevated lactate, non-reducible hernia, pneumatosis on CT. Do NOT delay surgery.
🚨 Management
Conservative Management (Partial SBO)
- NPO — strict bowel rest
- NGT to low intermittent suction — decompression
- IV fluids — aggressive resuscitation (3rd-spacing)
- Electrolyte repletion — K, Mg, PO₄
- Serial abdominal exams q4–8h
- Water-soluble contrast (Gastrografin) — both diagnostic and therapeutic. If contrast reaches colon by 24h → likely to resolve without surgery
Surgical Indications
- Complete SBO with no improvement in 48–72h
- Signs of strangulation/ischemia
- Closed-loop obstruction
- Free air (perforation)
- Incarcerated/strangulated hernia
🧪 Workup
- CT abdomen/pelvis with IV contrast — gold standard. Shows transition point, dilated vs decompressed bowel, signs of ischemia
- Abdominal X-ray — dilated small bowel (> 3 cm), air-fluid levels, absent distal gas (complete SBO)
- BMP — dehydration, electrolyte derangements
- CBC — leukocytosis (strangulation)
- Lactate — elevated with ischemia/strangulation
- Lipase — rule out pancreatitis
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| IV Normal Saline | Bolus 1–2 L then maintenance | Volume resuscitation — significant 3rd-spacing |
| Ondansetron (Zofran) | 4 mg IV q6h PRN | Anti-emetic |
| Gastrografin | 100 mL via NGT | Water-soluble contrast — diagnostic and therapeutic (osmotic draws fluid into lumen) |
| Piperacillin-Tazobactam (Zosyn) | 3.375 g IV q6h | If strangulation/perforation suspected — broad-spectrum coverage |
| AVOID opioids | — | Worsen ileus. Use non-opioid pain management when possible. |
📊 Monitoring
- NGT output — track volume q shift
- Serial abdominal exams q4–8h (distension, tenderness, peritonitis)
- Vitals q4h — tachycardia/fever = strangulation
- Lactate q6–12h if concern for ischemia
- Daily KUB or CT if no improvement
- I/Os — significant fluid losses via NGT and 3rd-spacing
📋 On Rounds
Pimp Questions
What is the most common cause of SBO in developed countries?
Adhesions from prior abdominal surgery (60–75%). Second most common: hernias (incarcerated inguinal, ventral, internal). Third: malignancy. In patients with NO prior surgery, always examine for hernias carefully — groin, umbilical, incisional sites.
How does Gastrografin help in SBO management?
Dual role: (1) Diagnostic — if contrast reaches the colon on follow-up XR at 24h, the SBO will likely resolve non-operatively (high negative predictive value for need for surgery). (2) Therapeutic — hyperosmolar → draws fluid into bowel lumen → reduces edema at obstruction point → may help resolve partial SBO. Meta-analyses show reduced need for surgery and shorter hospital stay.
What are the signs of strangulated SBO?
Clinical: Fever, tachycardia, localized peritonitis (rebound/guarding), non-reducible hernia. Labs: Leukocytosis, elevated lactate, metabolic acidosis. CT findings: Mesenteric haziness/fluid, bowel wall thickening, decreased/absent wall enhancement, pneumatosis intestinalis (gas in bowel wall). This is a surgical emergency — do not delay for further workup.
⚡ Summary
Causes
Adhesions (#1), hernias (#2), tumor, volvulus. Ileus: post-op, opioids, electrolytes.
Imaging
CT with IV contrast = gold standard. Shows transition point, ischemia signs. XR: air-fluid levels.
Conservative Rx
NPO, NGT suction, IV fluids, electrolyte repletion. Gastrografin trial.
Surgery When
Complete SBO >48-72h, strangulation signs, closed-loop, free air, incarcerated hernia.
Strangulation Signs
Fever, peritonitis, ↑ lactate, ↑ WBC, CT: decreased enhancement, pneumatosis.
Avoid
Opioids (worsen ileus). Replace fluids aggressively (3rd-spacing significant).
Cholangitis & Cholecystitis
Cholangitis: infected bile duct obstruction. Charcot triad (fever, RUQ pain, jaundice). Reynolds pentad adds AMS + shock. Emergent biliary drainage (ERCP). Cholecystitis: gallbladder inflammation — Murphy sign, cholecystectomy within 72h.
🔍 Overview
Cholangitis vs Cholecystitis
| Feature | Acute Cholangitis | Acute Cholecystitis |
|---|---|---|
| Pathophys | Bile duct obstruction + infection → bacteremia | Gallbladder outlet obstruction (stone in cystic duct) → inflammation ± infection |
| Classic signs | Charcot triad: fever + RUQ pain + jaundice | Murphy sign: inspiratory arrest with RUQ palpation |
| Severe | Reynolds pentad: Charcot + AMS + shock | Gangrenous, emphysematous, perforated |
| Key labs | ↑ bili, ↑ ALP/GGT, ↑ WBC, + blood cultures | ↑ WBC, ± mild LFT elevation |
| Imaging | CBD dilation > 8 mm, ± stone visible | GB wall thickening, pericholecystic fluid, + Murphy on US |
| Treatment | ERCP within 24–48h (emergent if septic) | Cholecystectomy within 72h |
Reynolds pentad (Charcot triad + AMS + shock) = toxic cholangitis. This is a medical emergency requiring EMERGENT ERCP and ICU admission. Mortality 50% without drainage.
🚨 Management
Acute Cholangitis
- IV antibiotics — start immediately after blood cultures
- ERCP with sphincterotomy — biliary drainage within 24–48h. Emergent if Reynolds pentad.
- If ERCP fails: percutaneous transhepatic cholangiography (PTC) or surgical drainage
- Fluid resuscitation, vasopressors if septic shock
Acute Cholecystitis
- Laparoscopic cholecystectomy within 72h — early surgery is safe and reduces hospital stay
- NPO, IV fluids, antibiotics, pain control
- Percutaneous cholecystostomy — if too sick for surgery (bridge procedure)
🧪 Workup
- RUQ ultrasound — first-line. GB stones, wall thickening, pericholecystic fluid, CBD dilation
- MRCP — if US inconclusive for CBD stones
- HIDA scan — if cholecystitis diagnosis unclear (non-filling of GB = cystic duct obstruction)
- CBC, CMP (bilirubin, ALP, GGT, AST, ALT), lipase
- Blood cultures × 2 — before antibiotics in cholangitis
- Lactate — if concern for sepsis
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| Piperacillin-Tazobactam (Zosyn) | 3.375–4.5 g IV q6h | First-line for cholangitis and complicated cholecystitis |
| Ciprofloxacin (Cipro) + Metronidazole (Flagyl) | 400 mg IV q12h + 500 mg IV q8h | Alternative if PCN allergy |
| Meropenem (Merrem) | 1g IV q8h | Severe/healthcare-associated cholangitis |
| Ketorolac (Toradol) | 15–30 mg IV q6h | Pain — preferred over opioids initially |
📊 Monitoring
- Vitals q4h — watch for sepsis
- LFTs daily — trending improvement after drainage
- Blood cultures — clearance documentation
- Surgical follow-up — cholecystectomy timing
- I/Os — aggressive fluid resuscitation
📋 On Rounds
Pimp Questions
When is emergent vs urgent ERCP indicated in cholangitis?
Emergent (< 12–24h): Reynolds pentad (Charcot + shock + AMS), failing to respond to antibiotics and fluids, organ failure. Urgent (24–48h): Charcot triad without shock, responding to initial resuscitation but needs definitive drainage. Tokyo Guidelines Grade III (organ dysfunction) → emergent. Grade II (non-responding) → urgent. Grade I (mild) → can be semi-elective.
Why is a HIDA scan useful when ultrasound is inconclusive for cholecystitis?
HIDA scan measures gallbladder filling and function. IV radiotracer is taken up by hepatocytes and excreted into bile. If the gallbladder does not fill (non-visualization at 4h), it confirms cystic duct obstruction = acute cholecystitis. Sensitivity 97%, specificity 94%. Most useful when US shows no stones but clinical suspicion is high (acalculous cholecystitis in ICU patients).
What organisms cause cholangitis?
Gram-negatives dominate: E. coli (most common, ~25-50%), Klebsiella, Enterobacter, Pseudomonas. Anaerobes: Bacteroides, Clostridium. Gram-positives: Enterococcus. Polymicrobial in many cases. This is why empiric coverage needs gram-negative + anaerobic coverage (Zosyn, or FQ + metronidazole).
⚡ Summary
Cholangitis
Infected bile duct obstruction. Charcot triad: fever + RUQ pain + jaundice. ERCP for drainage.
Reynolds Pentad
Charcot triad + AMS + shock = toxic cholangitis. EMERGENT ERCP. 50% mortality without drainage.
Cholecystitis
GB wall inflammation. Murphy sign. US first-line. Lap chole within 72h.
Antibiotics
Zosyn (first-line), cipro + flagyl (PCN allergy), meropenem (severe).
Imaging
RUQ US first. MRCP for CBD stones. HIDA if US inconclusive (sens 97%).
Organisms
E. coli, Klebsiella, Enterococcus, Bacteroides. Polymicrobial. Cover GN + anaerobes.
Acute Alcoholic Hepatitis
Acute hepatic inflammation from heavy alcohol use. AST typically 2–6× ULN with AST:ALT >2:1, jaundice, and recent heavy drinking. Maddrey Discriminant Function (DF) ≥32 defines severe disease — consider steroids. MELD score also predicts mortality. Nutrition may be the most important intervention.
🔍 Overview
Definition & Diagnosis
- AST typically 2–6× ULN (rarely > 500 in pure alcoholic hepatitis)
- AST:ALT ratio > 2:1 — classic pattern (alcohol damages mitochondrial AST, and ALT requires pyridoxal phosphate which is depleted in alcoholics)
- Recent heavy alcohol use (typically > 40g/day women, > 60g/day men for > 6 months)
- Jaundice (bilirubin often markedly elevated)
- Exclude other causes: viral hepatitis, drug-induced, autoimmune
Maddrey Discriminant Function (DF)
- DF = 4.6 × (patient PT − control PT) + total bilirubin
- DF < 32: mild-moderate → supportive care
- DF ≥ 32: severe → consider prednisolone
MELD Score
- MELD also predicts mortality in alcoholic hepatitis
- MELD > 21: significant mortality risk, correlates with DF ≥ 32
🚨 Management
DF < 32 — Mild-Moderate
- Supportive care — these patients are MALNOURISHED
- High-calorie, high-protein nutrition (35–40 kcal/kg/day) — nutrition may be the single most important intervention
- Thiamine (Vitamin B1) 100 mg IV/PO daily
- Folic acid 1 mg PO daily
- Multivitamin daily
- Alcohol cessation — absolute requirement
DF ≥ 32 — Severe
- Prednisolone (Orapred) 40 mg PO daily × 28 days → taper
- Calculate Lille score at day 7 — this is MANDATORY
- Lille > 0.45 = non-responder → STOP steroids (no benefit, only side effects)
- Lille < 0.45 = responder → complete 28-day course
- PLUS all supportive care above (nutrition, thiamine, folate, MVI)
Contraindications to Steroids
- Active GI bleed
- Uncontrolled infection
- HBV/HCV co-infection
- Hepatorenal syndrome
Pentoxifylline for alcoholic hepatitis is DEAD. STOPAH, 2015 showed no benefit. Prednisolone showed modest short-term mortality benefit but no long-term benefit. Nutrition may be the most important intervention.
Updated Practice — Old teaching: pentoxifylline is an alternative to steroids. WRONG — STOPAH definitively showed pentoxifylline doesn't work. Steroids remain the only pharmacologic option for severe AH, but the benefit is modest and short-term.
🧪 Workup
| Test | Purpose |
|---|---|
| AST, ALT | AST:ALT > 2:1 classic. AST rarely > 500. |
| Total/direct bilirubin | Often markedly elevated (used in DF and MELD) |
| INR/PT | Synthetic function, used in DF calculation |
| Albumin | Malnutrition and synthetic function |
| CBC | Leukocytosis common; macrocytic anemia (MCV > 100) |
| BMP | Creatinine (HRS surveillance), electrolytes |
| Hepatitis serologies | Rule out viral hepatitis (HBV, HCV) |
| Lipase | Rule out concurrent pancreatitis |
| RUQ ultrasound + Doppler | Evaluate liver, rule out biliary obstruction, assess portal flow |
| Maddrey DF | Calculate: 4.6 × (PT − control PT) + bilirubin |
| MELD score | Additional prognostic tool |
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| Prednisolone (Orapred) | 40 mg PO daily × 28 days → taper | Severe AH (DF ≥ 32). Stop if Lille > 0.45 at day 7. |
| Thiamine (Vitamin B1) | 100 mg IV/PO daily | All patients — prevent Wernicke encephalopathy |
| Folic acid | 1 mg PO daily | All patients — folate deficiency common in alcoholics |
| Multivitamin | 1 tab PO daily | Nutritional repletion |
| Nutritional supplementation | 35–40 kcal/kg/day | High-calorie, high-protein diet. Consult dietitian. |
| Lactulose | 15–30 mL PO q2–4h titrate to 3–4 BM/day | If hepatic encephalopathy present |
📊 Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| Lille score | Day 7 (MUST calculate) | > 0.45 = stop steroids. < 0.45 = complete course. |
| LFTs | Twice weekly | Trending bilirubin, AST, ALT improvement |
| BMP | Daily | Creatinine (HRS surveillance), electrolytes |
| Infection screening | Ongoing | Steroids mask infection — low threshold to culture |
| Glucose | QID while on steroids | Steroids cause hyperglycemia — sliding scale insulin |
| Mental status | Each assessment | Hepatic encephalopathy monitoring |
📋 On Rounds
Pimp Questions
Why prednisolone and NOT prednisone for alcoholic hepatitis?
Prednisolone is the active form. Prednisone is a prodrug that requires hepatic conversion to prednisolone. In a patient with severe alcoholic hepatitis, the damaged liver cannot reliably convert prednisone → prednisolone. Using prednisolone bypasses this step and ensures the patient receives the active drug.
What is the Lille score cutoff and what does it mean?
Lille score > 0.45 at day 7 = non-responder. These patients derive no benefit from continued steroids and are only exposed to steroid side effects (infection, hyperglycemia). Stop steroids immediately. Lille < 0.45 = responder → complete the 28-day course. The Lille model uses day 0 and day 7 bilirubin, albumin, age, creatinine, and PT to predict response.
What did the STOPAH trial show?
STOPAH, 2015 was the largest RCT in alcoholic hepatitis (n=1103). Pentoxifylline showed NO benefit at any time point — it is definitively dead. Prednisolone showed a trend toward reduced 28-day mortality (OR 0.72, p=0.06) but no significant benefit at 90 days or 1 year. Bottom line: steroids provide modest short-term benefit; pentoxifylline provides none.
📣 Sample Presentation
One-Liner
"Mr. Davis is a 48-year-old man with 20-year history of heavy alcohol use (1 pint vodka daily) presenting with 2 weeks of jaundice, AST 280, ALT 95, bilirubin 18, INR 2.1, Maddrey DF 58 — severe alcoholic hepatitis."
Key Points to Cover on Rounds
Severe alcoholic hepatitis (DF 58). Started prednisolone 40 mg PO daily. Lille score to be calculated on day 7 — if > 0.45 will stop steroids. Hepatitis serologies negative. No active GI bleed, no uncontrolled infection. Nutrition: high-calorie high-protein diet (35 kcal/kg/day), thiamine 100 mg IV, folate 1 mg, MVI. Alcohol cessation counseling initiated. Monitoring: LFTs twice weekly, daily BMP for HRS surveillance, glucose QID on steroids.
⚡ Summary
Diagnosis
AST:ALT > 2:1, AST 2–6× ULN, jaundice, heavy alcohol use. Calculate Maddrey DF.
Maddrey DF
4.6 × (PT − control PT) + bilirubin. DF ≥ 32 = severe → consider prednisolone.
Treatment
Prednisolone 40 mg × 28d if DF ≥ 32. Lille at day 7. Nutrition is paramount.
Lille Score
> 0.45 at day 7 = non-responder → STOP steroids. < 0.45 → complete course.
STOPAH 2015
Pentoxifylline: NO benefit. Prednisolone: modest 28-day benefit, no long-term benefit.
Nutrition
35–40 kcal/kg/day + thiamine + folate + MVI. These patients are malnourished.
Hepatorenal Syndrome
AKI in cirrhosis after excluding other causes. Kidneys are structurally normal but functionally failing due to splanchnic vasodilation → systemic underfilling → renal vasoconstriction. Diagnosis of exclusion. Terlipressin FDA-approved 2022. Liver transplant is the only cure.
🔍 Overview
Definition & Classification
- HRS-AKI (formerly Type 1): Rapid Cr rise > 0.3 mg/dL in 48h or doubling of Cr within 7 days. Median survival 2 weeks without treatment.
- HRS-CKD (formerly Type 2): Gradual, stable Cr elevation. Often associated with refractory ascites.
Pathophysiology
- Portal hypertension → splanchnic vasodilation (nitric oxide, other vasodilators)
- → Effective arterial underfilling → activation of RAAS, sympathetic nervous system, ADH
- → Renal vasoconstriction → decreased GFR
- → Kidneys are structurally normal but functionally failing
- If you transplant these kidneys into a healthy person, they work perfectly
HRS is a diagnosis of EXCLUSION. You MUST rule out: hypovolemia (albumin challenge), ATN (urine Na > 40, muddy brown casts), obstruction (ultrasound), nephrotoxic drugs. If FENa < 1% and bland UA → think HRS.
🚨 Management
Stepwise Approach
Step 1 — Stop nephrotoxins
STOP all nephrotoxic meds, diuretics, beta-blockers, NSAIDs, ACEi/ARBs. These worsen renal perfusion.
Step 2 — Albumin challenge
Albumin 1 g/kg (max 100g) IV × 2 days. Rule out pre-renal AKI. If no Cr improvement → HRS.
Step 3 — Triple therapy (classic)
Midodrine (ProAmatine) 7.5–12.5 mg PO TID + Octreotide (Sandostatin) 100–200 mcg SQ TID + Albumin 25–50g IV daily. Splanchnic vasoconstriction + volume expansion.
Step 4 — Terlipressin (preferred if available)
Terlipressin (Terlivaz) 0.5–1 mg IV q6h + albumin. FDA-approved 2022 based on CONFIRM, 2024. First drug specifically approved for HRS.
Step 5 — TIPS
Transjugular intrahepatic portosystemic shunt — reduces portal pressure. Consider if appropriate candidate.
Definitive — Liver transplant
Liver transplant is the only cure. HRS often resolves after successful transplant because the underlying portal hypertension is corrected.
🧪 Workup
| Test | Expected in HRS | Purpose |
|---|---|---|
| BMP | ↑ Cr, ↑ BUN | Baseline and trending renal function |
| UA with microscopy | Bland (no casts, no cells) | ATN has muddy brown casts; GN has RBC casts |
| Urine Na | < 10 mEq/L | Very low urine Na = avid renal sodium retention |
| FENa | < 1% | Pre-renal physiology (kidneys structurally normal) |
| Renal ultrasound | Normal kidneys | Rule out obstruction |
| Hepatic panel, INR, albumin | Deranged (cirrhosis) | Confirm underlying liver disease severity |
| Diagnostic paracentesis | Rule out SBP | SBP is a common trigger for HRS |
💊 Medications
| Drug | Dose | Mechanism / Notes |
|---|---|---|
| Midodrine (ProAmatine) | 7.5–12.5 mg PO TID | Alpha-1 agonist → splanchnic vasoconstriction |
| Octreotide (Sandostatin) | 100–200 mcg SQ TID | Inhibits splanchnic vasodilation |
| Albumin 25% | 25–50 g IV daily | Volume expansion + oncotic pressure support |
| Terlipressin (Terlivaz) | 0.5–1 mg IV q6h | Vasopressin analog. FDA-approved for HRS 2022. Preferred over triple therapy if available. |
| Norepinephrine | 0.5–3 mcg/kg/min IV drip | ICU alternative to midodrine/octreotide. More potent vasoconstrictor. |
📊 Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| Creatinine | Daily (q12h if ICU) | Trending improvement = therapy working. No response by 48–72h → escalate. |
| Urine output | Strict I&Os | UOP > 0.5 mL/kg/hr. Oliguria common in HRS. |
| MAP | Continuous or q4h | Target MAP > 65–70. Midodrine/terlipressin should improve MAP. |
| Daily weights | Daily | Fluid balance assessment |
| Hepatic panel | Daily | Underlying liver disease trajectory |
📋 On Rounds
Pimp Questions
What is the pathophysiology of hepatorenal syndrome?
Portal hypertension → splanchnic vasodilation (mediated by nitric oxide and other vasodilators) → effective arterial underfilling → baroreceptor-mediated activation of RAAS, sympathetic nervous system, and ADH → intense renal vasoconstriction → decreased GFR. The kidneys are structurally normal — if transplanted into a healthy recipient, they work perfectly. This is why liver transplant cures HRS.
Why do we give an albumin challenge before diagnosing HRS?
To rule out pre-renal AKI (hypovolemia). Cirrhotics are often volume-depleted from diuretics, GI losses, or poor intake. Albumin 1 g/kg (max 100g) × 2 days provides a structured volume challenge. If creatinine improves → it was pre-renal, not HRS. If no improvement despite adequate volume → diagnosis of HRS is supported. This step is required by diagnostic criteria.
What's new about terlipressin?
Terlipressin (Terlivaz) was FDA-approved in 2022 as the first drug specifically approved for HRS. The CONFIRM trial showed terlipressin + albumin improved verified HRS reversal vs placebo + albumin. Key safety concern: respiratory adverse events, especially in patients who are volume overloaded. Must monitor closely for pulmonary edema.
Why stop beta-blockers in HRS?
Beta-blockers (nadolol, propranolol, carvedilol) reduce cardiac output in cirrhotics who are already hemodynamically compromised. In the setting of HRS, the heart needs to maximize output to compensate for splanchnic vasodilation. Beta-blockers blunt this compensatory response → further reduction in effective arterial volume → worsening renal perfusion. Studies show beta-blockers in decompensated cirrhosis with refractory ascites may increase mortality.
⚡ Summary
Definition
AKI in cirrhosis. Diagnosis of exclusion. Bland UA, FENa < 1%, urine Na < 10.
Pathophys
Splanchnic vasodilation → underfilling → renal vasoconstriction. Kidneys structurally normal.
Step 1–2
Stop nephrotoxins/diuretics/BBs. Albumin 1g/kg × 2 days challenge.
Triple Therapy
Midodrine + octreotide + albumin. Classic regimen for HRS.
Terlipressin
FDA-approved 2022 (CONFIRM trial). Preferred if available. Watch for respiratory events.
Definitive
Liver transplant is the only cure. TIPS as bridge in select patients.
Hypernatremia
Na⁺ > 145 mEq/L — almost ALWAYS from free water deficit, not sodium excess. Causes: inadequate water intake (altered mental status, intubated, elderly), diabetes insipidus, osmotic diuresis, GI losses. Correct ≤10 mEq/L per 24 hours for chronic hypernatremia.
🔍 Overview
Definition
- Na > 145 mEq/L — almost always from free water deficit (not sodium excess)
- Serum osmolality is always elevated (> 295 mOsm/kg)
Causes
| Category | Examples |
|---|---|
| Inadequate water intake | Altered mental status, intubated patients without free water, elderly with impaired thirst, NPO without adequate IVF |
| Diabetes insipidus | Central DI: post-neurosurgery, pituitary injury, brain death. Nephrogenic DI: lithium, hypercalcemia, hypokalemia |
| Osmotic diuresis | Hyperglycemia (DKA/HHS), mannitol, urea (high-protein TPN) |
| GI losses | Diarrhea (especially osmotic diarrhea — lactulose), vomiting, NG suction |
| Renal losses | Loop diuretics, post-obstructive diuresis |
🚨 Management
Stepwise Approach
Step 1 — Calculate free water deficit
FWD = TBW × (Na/140 − 1)
TBW = weight (kg) × 0.5 (women) or 0.6 (men)
Example: 70 kg man, Na 160 → TBW = 42 L → FWD = 42 × (160/140 − 1) = 42 × 0.143 = 6 L deficit
TBW = weight (kg) × 0.5 (women) or 0.6 (men)
Example: 70 kg man, Na 160 → TBW = 42 L → FWD = 42 × (160/140 − 1) = 42 × 0.143 = 6 L deficit
Step 2 — Replace free water
D5W IV (250–500 mL/hr) or 0.45% NS or free water via NG/PO if able to take PO. Add ongoing losses to replacement calculation.
Step 3 — Correct at safe rate
≤10 mEq/L per 24 hours for chronic hypernatremia (> 48h). Overcorrection risk: cerebral edema. Acute hypernatremia (< 48h, e.g., ICU patient who missed free water) can be corrected faster.
Step 4 — Treat underlying cause
Desmopressin (DDAVP) for central DI. Stop offending drugs for nephrogenic DI (lithium, etc.). Treat hyperglycemia if osmotic diuresis.
Correct Na ≤10 mEq/L in 24 hours for chronic hypernatremia (> 48h). Rapid correction → cerebral edema → herniation. For acute hypernatremia (< 48h, e.g., ICU patient who missed free water), faster correction is safe.
Do NOT use NS (154 mEq/L Na) to correct hypernatremia if Na is > 154 — NS is hypotonic relative to the patient but still has a lot of sodium. Use D5W or 0.45% NS instead.
🧪 Workup
| Test | Purpose |
|---|---|
| BMP | Na level, Cr (dehydration), glucose (osmotic diuresis) |
| Serum osmolality | Always elevated in true hypernatremia (> 295) |
| Urine osmolality | High (> 600): appropriate ADH response — not getting enough water. Low (< 300): DI — kidneys not concentrating urine |
| Urine Na | Helps differentiate renal vs extrarenal losses |
| Glucose | Rule out osmotic diuresis from hyperglycemia |
| Urine specific gravity | Low in DI, high in appropriate response |
Diabetes Insipidus Workup
- Urine osm < 300 → suspect DI
- Give DDAVP → if urine concentrates (osm > 600) = Central DI (responds to exogenous ADH)
- If no response to DDAVP = Nephrogenic DI (kidneys resistant to ADH)
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| D5W | 250–500 mL/hr IV (adjust to correction rate) | Primary free water replacement — no sodium |
| 0.45% NS (half-normal saline) | Variable rate IV | Alternative to D5W — provides some sodium + free water |
| Desmopressin (DDAVP) | 1–2 mcg IV or SQ | Central DI — replaces deficient ADH |
| Free water flushes | 200–500 mL via NG q4–6h | Enteral free water if NG access available — most physiologic |
📊 Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| Serum Na | q4–6h during correction | Decrease ≤10 mEq/24h for chronic. Faster OK if acute (< 48h). |
| I&Os | Strict | Track free water replacement and ongoing losses |
| Urine output | Hourly | Polyuria in DI (can be > 3–20 L/day) |
| Daily weights | Daily | Fluid balance tracking |
| Serum osmolality | q12–24h | Should normalize with Na correction |
📋 On Rounds
Pimp Questions
How do you calculate the free water deficit?
FWD = TBW × (Na/140 − 1). TBW = weight (kg) × 0.6 (men) or 0.5 (women). Example: 70 kg man, Na 160 → TBW = 42 L → FWD = 42 × (160/140 − 1) = 42 × 0.143 = 6 liters. Important: this estimates the deficit at a single point in time. You must also account for ongoing losses (urine, insensible) and recheck Na frequently. Replace the deficit over 48–72h to avoid overcorrection.
How do you differentiate central vs nephrogenic DI?
Both present with polyuria and dilute urine (urine osm < 300). Give DDAVP (exogenous ADH): if urine concentrates (> 600 mOsm) → Central DI (the pituitary isn't making ADH, but the kidneys can respond). If urine stays dilute → Nephrogenic DI (kidneys are resistant to ADH). Common causes: Central = post-neurosurgery, pituitary tumors, brain death. Nephrogenic = lithium (#1), hypercalcemia, hypokalemia.
Why not use NS to correct severe hypernatremia?
NS contains 154 mEq/L of sodium. If the patient's Na is > 154, NS is actually hypotonic relative to them and will technically lower Na — but very slowly because it still contains a lot of sodium. For efficient free water replacement, use D5W (distributes as pure free water once glucose is metabolized) or 0.45% NS (77 mEq/L Na — provides free water while maintaining some tonicity). D5W is preferred for significant hypernatremia.
What is the maximum correction rate for chronic hypernatremia?
≤10 mEq/L per 24 hours. In chronic hypernatremia (> 48h), brain cells generate idiogenic osmoles (organic osmolytes — taurine, glutamine, etc.) to prevent cellular dehydration. Rapid correction removes these osmoles faster than the brain can adapt → water shifts INTO brain cells → cerebral edema → herniation. For acute hypernatremia (< 48h), the brain hasn't had time to accumulate osmolytes, so faster correction (1–2 mEq/h) is safe.
📣 Sample Presentation
One-Liner
"Mrs. Johnson is an 82-year-old woman from a nursing home, found lethargic with Na 162, BUN 45, Cr 1.8, urine osm 650 — hypernatremia from inadequate free water intake with appropriate ADH response."
Key Points to Cover on Rounds
Hypernatremia (Na 162) from inadequate oral intake. Urine osm 650 = appropriate ADH response (not DI). Free water deficit: ~5.3 L. Replacing with D5W at 250 mL/hr + free water via PO as tolerated. Target correction ≤10 mEq/24h. Na last check 4h ago: 158 (trending appropriately). Strict I&Os. Repeat Na in 4h. Addressing underlying cause: speech therapy for dysphagia evaluation, assisted feeding.
⚡ Summary
Definition
Na > 145. Almost always free water deficit. Serum osm always elevated.
Causes
Inadequate intake (most common), DI (central/nephrogenic), osmotic diuresis, GI losses.
Free Water Deficit
FWD = TBW × (Na/140 − 1). TBW = weight × 0.5 (F) or 0.6 (M).
Treatment
D5W or 0.45% NS or free water PO/NG. DDAVP for central DI.
Correction Rate
≤10 mEq/24h chronic. Faster OK if acute (< 48h). Overcorrection → cerebral edema.
DI Workup
Urine osm < 300 → give DDAVP. Concentrates = central DI. No response = nephrogenic DI.
Gallstone Pancreatitis
Gallstones cause ~40% of acute pancreatitis. Stone impacts at ampulla of Vater → blocked pancreatic duct → autodigestion. Key difference from alcoholic pancreatitis: gallstone pancreatitis needs CHOLECYSTECTOMY during the same admission. ALT > 150 has ~85% PPV for gallstone etiology.
🔍 Overview
Epidemiology & Pathophysiology
- Gallstones cause ~40% of acute pancreatitis (alcohol ~40%, other ~20%)
- Stone impacts at ampulla of Vater → blocked pancreatic duct → premature activation of pancreatic enzymes → autodigestion
- Key difference from alcoholic pancreatitis: gallstone pancreatitis needs CHOLECYSTECTOMY
Diagnosis
- Lipase > 3× ULN — most sensitive and specific single test
- ALT > 150 U/L has ~85% PPV for gallstone etiology — very helpful clue!
- RUQ ultrasound showing gallstones ± CBD dilation
- Clinical: epigastric/RUQ pain radiating to back, nausea/vomiting
🚨 Management
Initial Management (Same as All Pancreatitis)
- Goal-directed IV LR — NOT aggressive fluids. WATERFALL, 2022 showed aggressive fluids ↑ fluid overload without benefit.
- Pain control — hydromorphone/morphine, ondansetron for nausea
- Early feeding — low-fat solid diet as tolerated. No need to wait for lipase to normalize.
- NO prophylactic antibiotics
Cholecystectomy Timing
| Severity | Timing | Rationale |
|---|---|---|
| Mild pancreatitis | Same admission (ideally within 72h) | Delaying to outpatient → 25–30% recurrence rate. PONCHO, 2015 showed same-admission chole is safe and reduces recurrence. |
| Severe/necrotizing | Delay 4–6 weeks | Operating during severe pancreatitis = higher complication rate. Wait for inflammation to resolve. |
ERCP Indications
- Only if concurrent cholangitis (fever + jaundice + RUQ pain = Charcot triad)
- OR persistent CBD obstruction (elevated bilirubin not improving)
- Routine ERCP for all gallstone pancreatitis is NOT recommended — APEC, 2024
Do NOT discharge gallstone pancreatitis without cholecystectomy or a plan for same-admission cholecystectomy. Recurrence rate is 25–30% if you send them home with gallbladder in situ. PONCHO, 2015 showed same-admission cholecystectomy is safe and reduces recurrence.
Updated Practice — Old teaching: get ERCP for all gallstone pancreatitis. WRONG — ERCP is only indicated if there is concurrent cholangitis (Charcot triad) or persistent bile duct obstruction. Routine ERCP in resolving gallstone pancreatitis does not improve outcomes.
🧪 Workup
| Test | Purpose / Key Values |
|---|---|
| Lipase | > 3× ULN diagnostic. Don't need to normalize before feeding/surgery. |
| ALT | > 150 U/L = ~85% PPV for gallstone etiology — very helpful! |
| Total/direct bilirubin | Elevated = stone may still be impacted. Improving = stone likely passed. |
| Alk phos | Elevated in biliary obstruction |
| CBC | Leukocytosis (inflammation), hemoconcentration (dehydration) |
| BMP | Cr (organ failure), glucose, calcium |
| CRP at 48h | Severity marker. CRP > 150 at 48h suggests severe pancreatitis. |
| RUQ ultrasound | Gallstones, CBD dilation (> 6 mm suggests obstruction) |
| MRCP | If diagnostic uncertainty — avoids invasive ERCP. Better for CBD stone detection. |
| CT abdomen/pelvis | Only if not improving by day 3–5 (assess for necrosis, complications) |
💊 Medications
| Drug | Dose | Notes |
|---|---|---|
| Lactated Ringer's | Goal-directed (not aggressive) | WATERFALL 2022: aggressive fluids ↑ overload, no benefit |
| Hydromorphone (Dilaudid) | 0.5–1 mg IV q3–4h PRN | Pain control. Morphine is also acceptable. |
| Ondansetron (Zofran) | 4 mg IV q6h PRN | Nausea/vomiting |
| NO prophylactic antibiotics | — | Antibiotics only if infected necrosis or cholangitis confirmed |
📊 Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| Lipase | Trending (not daily) | Don't need to normalize before feeding or surgery |
| LFTs (bilirubin, ALT) | Daily | Improving bilirubin = stone likely passed. Persistently elevated → ERCP. |
| BMP | Daily | Cr (organ failure), calcium (severity marker) |
| CRP at 48h | Once at 48h | > 150 = likely severe pancreatitis |
| CT abdomen | Only if not improving day 3–5 | Assess for necrosis, pseudocyst, fluid collections |
| Surgical consult | Early (same admission) | Cholecystectomy timing — don't discharge without a plan |
📋 On Rounds
Pimp Questions
When should you get an ERCP in gallstone pancreatitis?
Only two indications: (1) Concurrent cholangitis — Charcot triad (fever + jaundice + RUQ pain). ERCP for biliary decompression. (2) Persistent CBD obstruction — bilirubin not improving, CBD remains dilated. Routine ERCP for all gallstone pancreatitis is NOT recommended. APEC, 2024 showed no benefit of early routine ERCP.
What is the significance of ALT > 150 in pancreatitis?
ALT > 150 U/L has ~85% positive predictive value for gallstone etiology. This is one of the most useful lab clues to distinguish gallstone pancreatitis from alcoholic pancreatitis. It reflects transient biliary obstruction causing hepatocyte injury. A normal ALT does not rule out gallstones, but a markedly elevated ALT strongly supports it. Always get a RUQ ultrasound to confirm.
Same-admission vs delayed cholecystectomy — what does the evidence say?
PONCHO, 2015 showed same-admission cholecystectomy (within 72h) for mild gallstone pancreatitis reduced gallstone-related complications from 17% to 5%. The recurrence rate if you discharge without chole is 25–30%. For severe/necrotizing pancreatitis, delay 4–6 weeks (operating in acute severe inflammation ↑ complications).
Why not routine ERCP for gallstone pancreatitis?
Most gallstones that cause pancreatitis pass spontaneously — the stone transiently impacts the ampulla then dislodges. By the time you do ERCP, the stone is often already gone. APEC, 2024 confirmed that routine ERCP in gallstone pancreatitis (without cholangitis) does not improve outcomes and exposes patients to ERCP risks (post-ERCP pancreatitis 3–5%, bleeding, perforation). Reserve ERCP for cholangitis or persistent obstruction.
📣 Sample Presentation
One-Liner
"Ms. Garcia is a 45-year-old woman with BMI 34, presenting with epigastric pain radiating to the back, lipase 2800, ALT 320, bilirubin 3.2, RUQ US showing gallstones and CBD 8 mm — gallstone pancreatitis."
Key Points to Cover on Rounds
Gallstone pancreatitis (ALT 320 — high PPV for gallstone etiology). Goal-directed LR. Pain controlled with hydromorphone. Tolerating low-fat diet. Bilirubin trending down (3.2 → 2.1) — stone likely passed, no ERCP needed. No cholangitis. Surgery consulted — plan for same-admission laparoscopic cholecystectomy tomorrow (within 72h of admission per PONCHO). No prophylactic antibiotics. CRP at 48h: 80 (mild disease).
⚡ Summary
Etiology
Gallstones ~40% of pancreatitis. ALT > 150 = ~85% PPV for gallstones.
Initial Rx
Goal-directed LR (not aggressive per WATERFALL). Pain control. Early feeding. No prophylactic abx.
Cholecystectomy
Same admission for mild (PONCHO). Delay 4-6 wk for severe. 25-30% recurrence if discharged without.
ERCP
Only for cholangitis or persistent obstruction. NOT routine (APEC 2024).
Key Trials
PONCHO 2015 (same-admission chole), WATERFALL 2022 (no aggressive fluids), APEC 2024 (no routine ERCP).
Monitoring
LFTs daily (improving bili = stone passed). CRP 48h. CT only if not improving day 3-5.
Metabolic Alkalosis
pH > 7.45 with elevated HCO₃⁻. Most common acid-base disorder in hospitalized patients. Classify by urine chloride: saline-responsive (UCl < 20) vs saline-resistant (UCl > 20). Replace chloride, not just volume.
🔍 Overview
Pathophysiology
Two requirements: (1) Generation — something creates the alkalosis (vomiting, diuretics, etc.), (2) Maintenance — something prevents the kidney from excreting the excess HCO₃⁻ (volume depletion, Cl⁻ depletion, hypokalemia, mineralocorticoid excess).
Classification by Urine Chloride
| UCl < 20 (Saline-Responsive) | UCl > 20 (Saline-Resistant) |
|---|---|
| Vomiting / NGT suction (#1 cause) | Primary hyperaldosteronism |
| Post-diuretic (remote use) | Cushing syndrome |
| Post-hypercapnic | Current diuretic use |
| Chloride-losing diarrhea (rare) | Bartter/Gitelman syndrome |
| Treatment: NS + KCl | Treatment: Treat underlying cause |
🚨 Management
Treatment Based on Urine Chloride
- Saline-responsive (UCl < 20): IV NS (provides Cl⁻ for kidney to excrete HCO₃⁻) + KCl repletion. Fix the volume and chloride deficit.
- Saline-resistant (UCl > 20): Treat underlying cause (e.g., spironolactone for hyperaldosteronism, stop diuretics)
- Severe/refractory: Acetazolamide (Diamox) 250–500 mg IV — forces renal HCO₃⁻ wasting
- Life-threatening (pH > 7.55): Consider HCl infusion (0.1–0.2 N) via central line, or dialysis
Hypokalemia perpetuates metabolic alkalosis. When K⁺ is low, the kidney reabsorbs K⁺ in exchange for H⁺ secretion → paradoxical aciduria. Replace K⁺ aggressively.
🧪 Workup
- ABG — confirm primary metabolic alkalosis (↑ pH, ↑ HCO₃⁻, compensatory ↑ PaCO₂)
- Urine chloride — key classification tool. < 20 = saline-responsive, > 20 = saline-resistant
- BMP — K⁺ (usually low), Cl⁻ (usually low)
- Urine electrolytes — Na⁺, K⁺, Cl⁻
- If saline-resistant: renin, aldosterone, cortisol
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| IV Normal Saline | 125–250 mL/h | Saline-responsive alkalosis — provides Cl⁻ |
| Potassium Chloride (KCl) | 10–40 mEq/h IV (max 40 mEq/h via central) | K⁺ repletion — essential for correction |
| Acetazolamide (Diamox) | 250–500 mg IV q6–12h | Refractory alkalosis — carbonic anhydrase inhibitor → renal HCO₃⁻ wasting |
| Spironolactone (Aldactone) | 25–100 mg PO daily | Hyperaldosteronism-related alkalosis |
📊 Monitoring
- ABG/VBG q4–6h until correcting
- BMP q6h — K⁺, Cl⁻, HCO₃⁻ trending
- Urine output — ensure adequate
- Repeat urine Cl⁻ to assess response
- Telemetry — hypokalemia → arrhythmia risk
📋 On Rounds
Pimp Questions
Why is urine chloride more useful than urine sodium in metabolic alkalosis?
In metabolic alkalosis, the kidney may be "obligated" to excrete Na⁺ with HCO₃⁻ (bicarbonuria) even in volume-depleted states, making urine Na⁺ unreliable. Urine Cl⁻ is not affected by this obligatory loss and accurately reflects volume status. UCl < 20 = volume/Cl⁻ depleted → will respond to saline. UCl > 20 = not volume depleted → look for mineralocorticoid excess.
What is "contraction alkalosis" and how does it occur?
When volume contracts (diuretics, vomiting), the same amount of HCO₃⁻ is dissolved in less plasma volume → concentration effect. Additionally, volume depletion activates RAAS → increased proximal tubule Na⁺/HCO₃⁻ reabsorption → maintenance of alkalosis. The kidney "can't let go" of HCO₃⁻ because it's trying to retain Na⁺ and volume. Giving NS provides Na⁺ and Cl⁻, allowing the kidney to excrete HCO₃⁻.
Why does hypokalemia cause paradoxical aciduria?
When K⁺ is depleted, the kidney's principal cells in the collecting duct reabsorb K⁺ instead of secreting it, and intercalated cells secrete more H⁺ to maintain electroneutrality. This produces acidic urine despite systemic alkalosis — "paradoxical aciduria." It also means the kidney is generating NEW HCO₃⁻, perpetuating the alkalosis. K⁺ must be repleted to correct the alkalosis.
⚡ Summary
Classification
UCl < 20 = saline-responsive (vomiting, diuretics). UCl > 20 = saline-resistant (hyperaldo, Cushing).
Saline-Responsive Rx
IV NS + KCl. Provides Cl⁻ for kidney to excrete HCO₃⁻. Fix volume + chloride deficit.
Saline-Resistant Rx
Treat cause: spironolactone for hyperaldo, stop offending diuretics.
Refractory
Acetazolamide (Diamox) — forces renal HCO₃⁻ wasting. Severe: HCl infusion or dialysis.
Hypokalemia
Perpetuates alkalosis via paradoxical aciduria. MUST replace K⁺ to correct alkalosis.
Key Lab
Urine chloride (NOT sodium) — more reliable in alkalosis because of obligatory bicarbonuria.
Intracerebral Hemorrhage
Spontaneous bleeding into brain parenchyma. Hypertension is #1 cause. Rapid BP lowering to SBP < 140. Reverse anticoagulation STAT. Hematoma expansion in first 6h drives mortality. Neurosurgery consult for all ICH.
🔍 Overview
Etiology by Location
| Location | Most Likely Cause |
|---|---|
| Basal ganglia / putamen | Hypertension (#1 cause, #1 location) |
| Thalamus | Hypertension |
| Pons | Hypertension |
| Cerebellum | Hypertension (surgical emergency if > 3 cm) |
| Lobar (cortical) | Cerebral amyloid angiopathy (elderly), AVM (young), tumor |
Hematoma expansion occurs in ~30% of ICH patients within the first 6 hours. This is the main driver of early deterioration. Aggressive BP control and anticoagulation reversal are TIME-CRITICAL.
🚨 Management
Acute Management
- BP control: Target SBP < 140 within 1 hour (INTERACT2, 2013). Use Nicardipine (Cardene) or Clevidipine (Cleviprex) drip.
- Reverse anticoagulation STAT:
- Warfarin → 4-factor PCC (KCentra) + Vitamin K 10 mg IV
- Dabigatran → Idarucizumab (Praxbind) 5g IV
- Rivaroxaban/Apixaban → Andexanet Alfa (Andexxa) or 4F-PCC
- Neurosurgery consult — all ICH. Cerebellar ICH > 3 cm or with hydrocephalus → surgical evacuation
- ICP management: HOB 30°, osmotic therapy (mannitol or hypertonic saline), EVD if hydrocephalus
- Seizure prophylaxis: NOT routine — treat only clinical seizures. Continuous EEG if altered.
- Tranexamic acid (TXA): Consider within 3 hours of injury, especially in mild-to-moderate TBI. CRASH-3, 2019 showed reduced head-injury related death when given early.
🧪 Workup
- Non-contrast CT head — STAT. Shows hyperdense (white) acute blood. First-line.
- CTA head — spot sign (contrast extravasation = active bleeding, predicts expansion)
- CBC, PT/INR, PTT, fibrinogen — coagulation status
- BMP, glucose
- Type and screen
- MRI — can evaluate underlying cause (tumor, AVM, cavernoma) once stable
- CTA/MRA — evaluate for vascular malformation if non-hypertensive location
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Nicardipine (Cardene) | 5–15 mg/h IV drip | BP control — titratable, no ICP effects |
| Clevidipine (Cleviprex) | 1–21 mg/h IV drip | Ultra-short acting alternative |
| 4-factor PCC (KCentra) | 25–50 units/kg IV | Warfarin reversal. Faster than FFP. |
| Idarucizumab (Praxbind) | 5 g IV | Dabigatran reversal. Immediate effect. |
| Mannitol (Osmitrol) | 0.5–1 g/kg IV bolus | ICP reduction — osmotic diuresis |
| Hypertonic Saline (23.4%) | 30 mL IV via central line | ICP crisis — can use via peripheral at lower concentration (3%) |
📊 Monitoring
- Neuro checks q1h — GCS, pupil exam, focal deficits
- Arterial line — continuous BP monitoring, target SBP < 140
- Repeat CT head at 6h and for any clinical change
- ICP monitoring if EVD placed — target ICP < 20, CPP > 60
- Na⁺ q4–6h if using hypertonic saline (target 145–155)
- ICH Score — prognostication tool (GCS, volume, IVH, age, infratentorial)
📋 On Rounds
Pimp Questions
What is the ICH Score and what does it predict?
Prognostic score for 30-day mortality: GCS 3-4 (+2), GCS 5-12 (+1), ICH volume ≥ 30 mL (+1), IVH present (+1), Infratentorial (+1), Age ≥ 80 (+1). Score 0 = 0% mortality, Score 5 = 100% mortality. Do NOT use as sole basis for withdrawal of care — prognostic models are imperfect and self-fulfilling prophecies contribute to poor outcomes.
Why is cerebellar hemorrhage a neurosurgical emergency?
The posterior fossa is a tight space. Cerebellar hemorrhage > 3 cm can cause: (1) Brainstem compression → rapid decline, (2) 4th ventricle obstruction → obstructive hydrocephalus, (3) Tonsillar herniation → death. Surgical evacuation is life-saving. EVD for hydrocephalus. These patients can have excellent outcomes with timely intervention — unlike supratentorial ICH.
How do you reverse DOACs in acute ICH?
Dabigatran: Idarucizumab (Praxbind) 5g IV — monoclonal antibody fragment, immediate full reversal. Rivaroxaban/Apixaban (factor Xa inhibitors): Andexanet alfa (Andexxa) — recombinant modified factor Xa decoy. If unavailable, use 4-factor PCC 50 units/kg IV. Key: Do NOT wait for drug levels. Time is brain — reverse empirically if recent DOAC use and ICH confirmed on CT.
⚡ Summary
Diagnosis
Non-contrast CT head STAT. Hyperdense acute blood. CTA for spot sign (active bleeding).
BP Target
SBP < 140 within 1h (INTERACT2). Nicardipine or clevidipine drip. A-line for monitoring.
Anticoag Reversal
Warfarin → 4F-PCC + Vit K. Dabigatran → idarucizumab. Xa-inhibitors → andexanet or PCC.
Surgery
Cerebellar ICH > 3cm or with hydrocephalus → surgical evacuation. Neurosurgery consult for all.
ICP Management
HOB 30°, mannitol/HTS, EVD if hydrocephalus. Target ICP < 20, CPP > 60.
Prognosis
ICH Score predicts 30-day mortality. Do NOT use as sole basis for withdrawal of care.
Headache & Migraine
Primary (migraine, tension, cluster) vs secondary (SAH, meningitis, mass, temporal arteritis). Red flags: thunderclap onset, worst ever, focal neuro, fever, papilledema, age > 50 new onset. Triptans for acute migraine.
🔍 Overview
Primary Headache Classification
| Type | Features | Duration |
|---|---|---|
| Migraine without aura | Unilateral, pulsating, moderate-severe, nausea/vomiting, photophobia/phonophobia, worse with activity | 4–72 hours |
| Migraine with aura | Visual (scintillating scotoma), sensory, or speech aura preceding headache by 5–60 min | 4–72 hours |
| Tension-type | Bilateral, pressing/tightening ("band-like"), mild-moderate, NO nausea/vomiting | 30 min–7 days |
| Cluster | Unilateral orbital/temporal, severe, with autonomic features (lacrimation, rhinorrhea, ptosis, miosis). Male predominance. | 15–180 min, occurs in clusters |
Red flags (SNOOP): Systemic (fever, weight loss, cancer, HIV), Neurologic (focal deficits, papilledema), Onset sudden (thunderclap → SAH until proven otherwise), Older (new onset > 50 → GCA), Positional/progressive/precipitated by Valsalva.
🚨 Management
Acute Migraine Treatment
| Severity | Treatment |
|---|---|
| Mild-moderate | NSAIDs (Ibuprofen (Advil) 400–800mg, Naproxen (Aleve) 500mg) + Metoclopramide (Reglan) 10mg or antiemetic |
| Moderate-severe | Sumatriptan (Imitrex) 6mg SC or 50–100mg PO. Contraindicated in CAD, uncontrolled HTN, prior stroke. |
| ER/refractory | "Migraine cocktail": Ketorolac (Toradol) 30mg IV + Prochlorperazine (Compazine) 10mg IV + Diphenhydramine (Benadryl) 25mg IV + IV fluids |
| Status migrainosus | Dexamethasone (Decadron) 10mg IV + above cocktail. Dihydroergotamine (DHE) protocol if refractory. |
Migraine Prophylaxis (≥ 4 headache days/month)
- Topiramate (Topamax) 25–100mg BID — weight loss side effect
- Propranolol (Inderal) 40–160mg daily — also treats anxiety, tremor
- Amitriptyline (Elavil) 10–75mg QHS — good for comorbid insomnia/tension-type
- Valproate (Depakote) 500–1500mg daily — teratogenic, weight gain
- CGRP monoclonal antibodies: Erenumab (Aimovig), Fremanezumab (Ajovy), Galcanezumab (Emgality)
🧪 Workup
When to Image
- Thunderclap headache → CT head STAT → if negative, LP for xanthochromia (SAH)
- New neurologic deficits → CT/MRI + consider CTA/MRA
- New headache age > 50 → ESR, CRP (GCA) + imaging
- Positional headache → MRI brain + possible LP (CSF pressure)
- Progressive or worsening pattern → MRI with contrast
- Typical migraine with normal exam → generally NO imaging needed
💊 Medications
| Drug | Dose | Use | Key Notes |
|---|---|---|---|
| Sumatriptan (Imitrex) | 50–100mg PO, 6mg SC | Acute migraine | Triptan class — 5-HT1B/1D agonist. Avoid in CAD, prior stroke. |
| Ketorolac (Toradol) | 15–30mg IV/IM | Acute migraine (ER) | NSAID. Max 5 days. Renal caution. |
| Prochlorperazine (Compazine) | 10mg IV | Anti-emetic + anti-migraine | Dopamine antagonist. Give with diphenhydramine to prevent EPS. |
| Topiramate (Topamax) | 25–100mg BID | Prophylaxis | Weight loss, paresthesias, kidney stones, word-finding difficulty. |
| Erenumab (Aimovig) | 70–140mg SC monthly | Prophylaxis | CGRP antibody. Few side effects. Constipation. |
📊 Monitoring
- Headache diary — frequency, severity, triggers, medication use
- Medication overuse headache — triptans > 10 days/month, NSAIDs > 15 days/month
- BMI and side effects on prophylactics
- Renal function if on NSAIDs chronically
- LFTs if on valproate
📋 On Rounds
Pimp Questions
What is the workup for thunderclap headache?
Thunderclap = maximal intensity within seconds to 1 minute. #1 concern: subarachnoid hemorrhage (SAH). Workup: (1) Non-contrast CT head — sensitivity 98% within 6h, drops to 50% by day 5. (2) If CT negative → LP — look for xanthochromia (yellow CSF from bilirubin, appears 6–12h after bleed) and elevated RBCs that do NOT clear with successive tubes. (3) If LP negative → CTA/MRA — evaluate for reversible cerebral vasoconstriction syndrome (RCVS), cerebral venous thrombosis, dissection.
Why are triptans contraindicated in cardiovascular disease?
Triptans are 5-HT1B/1D agonists. The 5-HT1B receptor is found on cranial blood vessels (causing vasoconstriction — the therapeutic effect) but ALSO on coronary arteries. In patients with CAD, triptans can cause coronary vasospasm → myocardial ischemia → MI. Contraindicated in: known CAD, prior MI/stroke/TIA, Prinzmetal angina, uncontrolled HTN, hemiplegic migraine.
What is medication overuse headache and how do you manage it?
MOH = chronic daily headache caused by regular use of acute headache medications. Triptans > 10 days/month, NSAIDs/acetaminophen > 15 days/month. The medication itself perpetuates the headache cycle. Management: (1) Educate the patient, (2) Withdraw the offending medication (can do abruptly for triptans, taper for opioids), (3) Start preventive therapy, (4) Bridge with a short course of steroids or DHE during withdrawal period.
⚡ Summary
Red Flags
SNOOP: Systemic, Neuro deficits, Onset sudden, Older >50, Positional/Progressive.
Migraine Rx
Mild: NSAIDs. Moderate: triptans (sumatriptan). Severe: IV cocktail (ketorolac + compazine + benadryl).
Prophylaxis
≥ 4 headache days/month. Topiramate, propranolol, amitriptyline, or CGRP antibodies.
Thunderclap
CT head → LP (xanthochromia) → CTA/MRA. SAH until proven otherwise.
Cluster Headache
High-flow O₂ (12-15L NRB) + sumatriptan SC. Prophylaxis: verapamil.
MOH
Triptans > 10d/mo, NSAIDs > 15d/mo. Withdraw offending agent + start preventive.
Spinal Cord Compression
Oncologic emergency. Back pain → radiculopathy → weakness → sensory level → bowel/bladder dysfunction. MRI STAT. Dexamethasone 10mg IV immediately. Neurosurgery + radiation oncology within hours. Time to treatment determines outcome.
🔍 Overview
Etiology
| Cause | Details |
|---|---|
| Metastatic disease | #1 cause. Lung, breast, prostate, RCC, myeloma. Usually epidural (vertebral body mets → posterior extension) |
| Primary spine tumors | Meningioma, schwannoma, ependymoma |
| Epidural abscess | Fever + back pain + risk factors (IVDU, recent spinal procedure). S. aureus #1. |
| Epidural hematoma | Post-procedure or anticoagulation |
| Disc herniation | Most common cause of non-malignant cord compression |
ANY cancer patient with new back pain must have spinal cord compression excluded. Once motor deficits appear, the window for meaningful recovery is hours. Ambulatory status at diagnosis is the #1 predictor of outcome.
🚨 Management
Emergent Management
- Dexamethasone 10 mg IV STAT then 4 mg IV q6h — reduces vasogenic edema around cord
- MRI entire spine with contrast — STAT. Multiple levels in 30% of cases.
- Neurosurgery consult — surgical decompression if: single level, good functional status, life expectancy > 3 months, radioresistant tumor
- Radiation oncology consult — definitive treatment for most metastatic SCC. Start within 24h.
- Pain management — often severe. Opioids appropriate.
Surgery vs Radiation
Patchell trial (2005): Surgery followed by radiation was superior to radiation alone for ambulatory recovery (84% vs 57%) in patients with single-level metastatic SCC and reasonable prognosis.
🧪 Workup
- MRI entire spine with gadolinium — gold standard. Must image ENTIRE spine (multiple lesions in 30%)
- CT myelogram — if MRI contraindicated (pacemaker)
- Plain films — vertebral body collapse, but misses early compression
- Neuro exam — motor level, sensory level, rectal tone (cauda equina), reflexes
- Post-void residual — bladder dysfunction is late sign
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Dexamethasone (Decadron) | 10 mg IV bolus → 4 mg IV q6h | Reduce cord edema. Start immediately on clinical suspicion. |
| Oxycodone (OxyContin) | 5–15 mg PO q4–6h | Pain control. Often severe. |
| Gabapentin (Neurontin) | 300–900 mg TID | Neuropathic pain adjunct |
| Omeprazole (Prilosec) | 20–40 mg daily | GI prophylaxis with high-dose steroids |
📊 Monitoring
- Neuro checks q2–4h — motor strength, sensory level, bladder function
- Blood glucose q6h — steroid-induced hyperglycemia
- Bowel/bladder function — Foley if retention, bowel regimen
- DVT prophylaxis — high risk for VTE
- Skin integrity — if immobilized
📋 On Rounds
Pimp Questions
What is the clinical progression of spinal cord compression?
Back pain (earliest, present in 95%) → radiculopathy (dermatomal pain) → motor weakness (UMN pattern: spasticity, hyperreflexia below level) → sensory level → bowel/bladder dysfunction (latest — if present, prognosis for recovery is poor). Ambulatory status at presentation is the #1 predictor of outcome. Once paraplegia develops, only 10% regain ambulation.
Why must you image the ENTIRE spine in suspected SCC?
30% of patients with metastatic SCC have disease at multiple spinal levels. Imaging only the symptomatic level may miss additional lesions that could cause future compression or be targeted with radiation. Additionally, a symptomatic thoracic lesion may have additional cervical involvement that changes surgical planning. Always order MRI of the entire spine with gadolinium contrast.
What is cauda equina syndrome and how does it differ from cord compression?
Cauda equina syndrome affects the nerve roots below the conus medullaris (L1-L2), producing LMN signs: flaccid weakness, areflexia, saddle anesthesia, and early bowel/bladder dysfunction (urinary retention → overflow incontinence). Cord compression above this level produces UMN signs: spastic weakness, hyperreflexia, Babinski sign. Both are surgical emergencies, but the clinical picture differs. Post-void residual > 200 mL is highly suggestive of cauda equina.
⚡ Summary
Presentation
Back pain (95%) → radiculopathy → weakness → sensory level → bowel/bladder (late, poor prognosis).
Immediate Action
Dexamethasone 10mg IV STAT. MRI entire spine with contrast. Neurosurgery + rad onc consult.
Key Predictor
Ambulatory status at diagnosis. 80% who walk at diagnosis remain ambulatory. 10% regain if paraplegic.
Imaging
MRI entire spine with gadolinium. 30% have multiple levels. CT myelogram if MRI contraindicated.
Causes
Metastatic (#1): lung, breast, prostate, RCC, myeloma. Also: abscess, hematoma, disc herniation.
Treatment
Surgery + radiation (Patchell trial) > radiation alone for single-level disease with good prognosis.
Trauma Primary & Secondary Survey
ATLS framework: ABCDE primary survey identifies life threats in minutes. Adjuncts: FAST, CXR, pelvic XR. Secondary survey is head-to-toe after stabilization. Hemorrhagic shock classification guides resuscitation.
🔍 Overview
Primary Survey (ABCDE)
| Step | Assessment | Interventions |
|---|---|---|
| A — Airway | Patent? Speaking? Stridor? Facial/neck trauma? | Jaw thrust (maintain C-spine), suction, definitive airway if needed |
| B — Breathing | RR, SpO₂, breath sounds bilateral? Tracheal deviation? Chest wall movement? | Needle decompression (tension pneumo), chest tube, seal open pneumo |
| C — Circulation | HR, BP, skin (cool/clammy?), active bleeding? Pelvis stable? | 2 large-bore IVs, tourniquets, pelvic binder, MTP if needed |
| D — Disability | GCS, pupils, gross motor/sensory | Treat ↑ ICP (HOB 30°, mannitol/HTS), identify herniation |
| E — Exposure | Fully undress, log roll, inspect everywhere | Warm blankets, prevent hypothermia |
Hemorrhagic Shock Classification
| Class | Blood Loss | HR | BP | Mental Status |
|---|---|---|---|---|
| I | < 750 mL (15%) | Normal | Normal | Normal |
| II | 750–1500 mL (15–30%) | ↑ (100–120) | Normal | Anxious |
| III | 1500–2000 mL (30–40%) | ↑ (>120) | ↓ | Confused |
| IV | > 2000 mL (>40%) | ↑ (>140) | ↓↓ | Obtunded |
🚨 Management
Adjuncts to Primary Survey
- FAST exam — Focused Assessment with Sonography in Trauma. 4 views: RUQ, LUQ, subxiphoid, suprapubic. Identifies free fluid.
- CXR (AP supine) — pneumothorax, hemothorax, mediastinal widening
- Pelvic XR — pelvic fracture (hemodynamic instability source)
- Foley — urine output monitoring (do NOT place if blood at meatus, high-riding prostate, scrotal hematoma)
- NGT/OGT — decompress stomach. OGT if midface fracture suspected.
Secondary Survey
Head-to-toe exam AFTER primary survey and stabilization. "Fingers and tubes in every orifice." Log roll to examine spine. Complete neuro exam. Document all injuries.
🧪 Workup
- FAST exam — bedside, during primary survey
- CXR, pelvic XR
- CT pan-scan (head, C-spine, chest, abdomen/pelvis with IV contrast) — stable patients
- CBC, BMP, coags, type & crossmatch, lactate, ABG
- Urine drug screen, blood alcohol, pregnancy test
- Tetanus status
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Tranexamic Acid (TXA) | 1g IV over 10 min → 1g over 8h | Antifibrinolytic — within 3h of injury |
| pRBC / FFP / Platelets | 1:1:1 ratio | MTP for hemorrhagic shock Class III–IV |
| Ketamine (Ketalar) | 1–2 mg/kg IV | RSI induction — hemodynamically stable, bronchodilator |
| Rocuronium (Zemuron) | 1.2 mg/kg IV | Paralytic for RSI — longer duration but sugammadex reversible |
| Norepinephrine (Levophed) | 0.1–0.5 mcg/kg/min | Vasopressor — AFTER volume resuscitation, not as substitute |
📊 Monitoring
- Continuous vitals, telemetry, SpO₂
- Repeat FAST if clinical change
- Serial GCS q1h in TBI
- Urine output ≥ 0.5 mL/kg/hr (Foley)
- Serial lactate (clearance as resuscitation marker)
- Repeat labs q4–6h during active resuscitation
📋 On Rounds
Pimp Questions
When is a FAST exam unreliable?
FAST detects free fluid (≥ 200 mL) but cannot identify retroperitoneal bleeding (renal, vascular, pelvic fractures), hollow viscus injury, or diaphragmatic injury. Sensitivity is operator-dependent (~85–96% for hemoperitoneum). A negative FAST does NOT rule out intra-abdominal injury — if clinical suspicion remains high, proceed with CT.
Why do you NOT place a Foley if there is blood at the urethral meatus?
Blood at the meatus, high-riding prostate on DRE, or scrotal/perineal hematoma suggest urethral injury. Blindly inserting a Foley could convert a partial urethral tear into a complete transection. Get a retrograde urethrogram (RUG) first. If positive, urology places a suprapubic catheter instead.
What is the "lethal diamond" in trauma?
Extension of the lethal triad: hypothermia + acidosis + coagulopathy + hypocalcemia (from massive transfusion). Citrate in blood products chelates calcium → cardiac dysfunction. The damage control resuscitation approach addresses all four: warm products, limit crystalloid (worsens acidosis), 1:1:1 ratio, and replace calcium (1g CaCl per 4 units pRBC).
⚡ Summary
Primary Survey
ABCDE: Airway (c-spine), Breathing, Circulation, Disability (GCS), Exposure. Fix life threats as found.
FAST
4 views: RUQ, LUQ, subxiphoid, suprapubic. Detects free fluid ≥ 200mL. Cannot detect retroperitoneal bleed.
Shock Classes
I: <15%, normal. II: 15-30%, tachy. III: 30-40%, ↓BP, confused. IV: >40%, obtunded.
MTP
1:1:1 pRBC:FFP:Platelets. TXA within 3h. Calcium replacement. Permissive hypotension.
Secondary Survey
Head-to-toe after stabilization. Log roll. Complete neuro exam. "Tubes and fingers in every orifice."
Foley Contraindications
Blood at meatus, high-riding prostate, scrotal hematoma → RUG first before Foley.
Acute Abdomen
Sudden onset abdominal pain requiring urgent evaluation. Surgical vs medical cause is the critical distinction. CT is the workhorse imaging. Pain out of proportion to exam = mesenteric ischemia or vascular emergency.
🔍 Overview
Differential by Location
| Location | Key Diagnoses |
|---|---|
| RUQ | Cholecystitis, hepatitis, hepatic abscess, Fitz-Hugh-Curtis, RLL pneumonia |
| Epigastric | Peptic ulcer, pancreatitis, MI (inferior), aortic dissection/aneurysm |
| LUQ | Splenic infarct/rupture, pancreatitis (tail), LLL pneumonia |
| RLQ | Appendicitis, Meckel's, ovarian torsion, ectopic pregnancy, IBD |
| Suprapubic | UTI, urinary retention, ovarian torsion, ectopic pregnancy, cystitis |
| LLQ | Diverticulitis, ovarian pathology, sigmoid volvulus, IBD |
| Periumbilical | Early appendicitis, SBO, mesenteric ischemia, AAA rupture |
| Diffuse | Perforated viscus, peritonitis, mesenteric ischemia, DKA, SBO |
Cannot-miss diagnoses: AAA rupture, mesenteric ischemia (pain out of proportion), ectopic pregnancy (all women of childbearing age get β-hCG), testicular/ovarian torsion, perforated viscus.
🚨 Management
Immediate Steps
- ABCs — stabilize hemodynamics first
- IV access, fluids, labs — CBC, BMP, lipase, LFTs, lactate, UA, β-hCG (all women)
- Pain control — Morphine (MS Contin) or Fentanyl (Sublimaze). Treating pain does NOT mask surgical findings.
- NPO — if surgical cause suspected
- Surgery consult — peritonitis, free air, hemodynamic instability
Surgical Emergencies (Cannot Wait)
- Perforated viscus (free air under diaphragm)
- AAA rupture
- Mesenteric ischemia with infarction
- Strangulated hernia/SBO
- Testicular/ovarian torsion
- Ectopic pregnancy with hemodynamic instability
🧪 Workup
- CT abdomen/pelvis with IV contrast — workhorse imaging for acute abdomen
- Upright CXR — free air under diaphragm (perforated viscus)
- US — RUQ (biliary), pelvic (OB/GYN pathology), bedside FAST
- CBC, BMP, lipase, LFTs, lactate, UA
- β-hCG — ALL women of childbearing age. Ectopic kills.
- Type & screen if surgical candidate
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Morphine (MS Contin) | 2–4 mg IV q2–4h | Pain control — does NOT mask surgical exam |
| Ketorolac (Toradol) | 15–30 mg IV | NSAID — good for renal colic, biliary colic |
| Ondansetron (Zofran) | 4 mg IV | Anti-emetic |
| Piperacillin-Tazobactam (Zosyn) | 3.375 g IV q6h | Broad-spectrum if peritonitis/perforation |
| IV NS/LR | Bolus 1–2 L | Volume resuscitation |
📊 Monitoring
- Serial abdominal exams q2–4h
- Vitals q1–4h depending on severity
- Lactate trending (mesenteric ischemia)
- Urine output if critically ill
- Surgical re-evaluation if worsening
📋 On Rounds
Pimp Questions
Why must every woman of childbearing age get a pregnancy test with abdominal pain?
Ectopic pregnancy can present as abdominal pain with or without vaginal bleeding and can rupture catastrophically → hemorrhagic shock → death in minutes. It is the #1 cause of first-trimester maternal death. A negative β-hCG essentially rules it out. Cost of the test is trivial compared to the consequence of missing it.
Does giving opioids for abdominal pain mask surgical findings?
No. This is a persistent myth. Multiple studies (including a Cochrane review) show that analgesics do not impair diagnostic accuracy and may actually improve exam quality by allowing patients to cooperate. Withholding pain control is unethical. Treat pain while completing the workup.
What is the significance of pain out of proportion to physical exam?
Classic for mesenteric ischemia. Early mesenteric ischemia causes severe visceral pain but the abdomen may appear benign on exam (no peritoneal signs yet — ischemia hasn't progressed to infarction/necrosis). By the time peritonitis develops, bowel is dead. High lactate + pain out of proportion + risk factors (Afib, atherosclerosis, hypercoagulable) → CTA abdomen STAT.
⚡ Summary
RLQ Pain
Appendicitis (#1). Also: Meckel's, ovarian torsion, ectopic, IBD. CT to confirm.
Cannot Miss
AAA rupture, mesenteric ischemia, ectopic pregnancy, torsion, perforated viscus.
β-hCG
ALL women of childbearing age. No exceptions. Ectopic is #1 cause of 1st-trimester death.
Pain Management
Opioids DO NOT mask surgical findings. Treat pain. Ketorolac for colic.
Free Air
Upright CXR or CT. Free air under diaphragm = perforated viscus → emergent surgery.
Mesenteric Ischemia
Pain out of proportion to exam. ↑ Lactate. CTA STAT. Afib is major risk factor.
Superior Vena Cava Syndrome
Obstruction of SVC → facial/upper extremity swelling, JVD, dyspnea. Most common cause: malignancy (lung cancer, lymphoma). CT with contrast is diagnostic. Oncologic emergency if airway compromise. Radiation/chemo for malignant causes.
🔍 Overview
Etiology
| Cause | Frequency | Details |
|---|---|---|
| Lung cancer | ~50% | NSCLC > SCLC. Right-sided tumors compress SVC. |
| Lymphoma | ~15% | Mediastinal mass — NHL > Hodgkin |
| Thrombosis (catheter-related) | ~20% | Central lines, ports, pacemaker leads |
| Other malignancy | ~10% | Thymoma, germ cell tumors, metastatic |
Clinical Features
- Facial/periorbital edema (worse when supine or bending forward)
- Upper extremity swelling (bilateral)
- JVD, prominent chest wall veins (collateral circulation)
- Dyspnea, cough, stridor (airway edema)
- Headache, visual changes (cerebral edema — rare, serious)
True emergency only if: stridor/airway compromise, cerebral edema (altered mental status), or hemodynamic instability. Most SVC syndrome evolves over days-weeks and is NOT an immediate life threat.
🚨 Management
Management
- Elevate head of bed — reduces venous pressure
- Get tissue diagnosis FIRST — treatment depends on histology. Biopsy before empiric treatment unless airway emergency.
- Malignant: Radiation therapy (rapid relief) and/or chemotherapy based on tumor type. SCLC and lymphoma are very chemo-sensitive.
- Thrombotic: Anticoagulation ± catheter-directed thrombolysis ± SVC stent
- Endovascular stenting — rapid symptom relief regardless of cause. Used as bridge to definitive therapy or if refractory.
- Dexamethasone — if concern for airway edema or lymphoma
🧪 Workup
- CT chest with IV contrast — gold standard. Shows mass, thrombus, extent of obstruction, collaterals
- Tissue biopsy — CRITICAL before treatment. Sputum cytology, bronchoscopy, CT-guided biopsy, mediastinoscopy
- CXR — mediastinal widening, right-sided mass
- Upper extremity venous duplex — if catheter-related thrombosis suspected
- CBC, CMP, LDH, coags
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Dexamethasone (Decadron) | 4–10 mg IV q6h | Reduce edema — especially if lymphoma or airway compromise |
| Furosemide (Lasix) | 20–40 mg IV | Diuresis to reduce edema (limited evidence) |
| Enoxaparin (Lovenox) | 1 mg/kg SC q12h | Anticoagulation for thrombotic SVC syndrome |
| Chemotherapy | Regimen-specific | SCLC, lymphoma — chemo-sensitive tumors respond rapidly |
📊 Monitoring
- Airway assessment — stridor, dyspnea, voice changes
- Head/facial edema trending
- SpO₂ continuous
- Response to treatment (edema resolution)
- Avoid upper extremity IV/BP (unreliable with SVC obstruction)
📋 On Rounds
Pimp Questions
Why should you obtain tissue diagnosis before treating SVC syndrome?
Because treatment depends entirely on histology. SCLC gets chemo (cisplatin/etoposide). NSCLC may get radiation, chemo, or targeted therapy. Lymphoma gets chemo (R-CHOP or similar). Empiric radiation can obscure the tissue diagnosis and render the tumor unbiopsyable. Exception: If there is airway compromise or hemodynamic instability, emergent stenting or radiation is appropriate before biopsy.
What are the contraindications for upper extremity procedures in SVC syndrome?
Avoid upper extremity IV access, blood draws, and BP measurements on the affected side. Venous pressures are markedly elevated → (1) IV fluids won't flow properly, (2) BP readings will be inaccurate (falsely elevated venous component), (3) Tourniquets can worsen edema and compartment syndrome risk. Use lower extremity or femoral access instead.
⚡ Summary
Causes
Lung cancer (#1), lymphoma, catheter thrombosis. Right-sided mediastinal masses.
Presentation
Facial/arm edema, JVD, dyspnea, chest wall collaterals. Worse supine/bending forward.
Diagnosis
CT chest with IV contrast. Get tissue biopsy BEFORE treatment (except airway emergency).
Treatment
Radiation/chemo (based on histology). Stenting for rapid relief. Dexamethasone for edema.
True Emergency
Only if: stridor/airway compromise, cerebral edema, hemodynamic instability.
Avoid
Upper extremity IVs, BP, blood draws on affected side. Use femoral/lower extremity.
Septic Arthritis
Joint infection — S. aureus #1 cause. Hot, swollen, painful joint with restricted ROM. Joint aspiration is MANDATORY — WBC > 50,000 with > 75% PMNs is presumptive. IV antibiotics + surgical washout. Delay = joint destruction.
🔍 Overview
Key Features
| Feature | Details |
|---|---|
| Presentation | Acute monoarthritis — hot, swollen, erythematous joint. Severe pain with passive ROM. Fever in ~50%. |
| #1 Organism | S. aureus (all ages). Neisseria gonorrhoeae in young sexually active adults. |
| #1 Joint | Knee (most common). Also hip, shoulder, wrist, ankle. |
| Risk factors | Prior joint disease (RA, OA), prosthetic joint, IVDU, immunosuppression, skin infection, recent procedure |
| Route | Hematogenous spread (#1), direct inoculation (trauma, surgery), contiguous (osteomyelitis) |
Any acute monoarthritis is septic arthritis until proven otherwise. Joint aspiration before antibiotics. Delay in treatment causes irreversible cartilage destruction within 24–48h.
🚨 Management
Treatment
- Joint aspiration — MANDATORY. Send synovial fluid for: cell count + diff, Gram stain, culture, crystal analysis (rule out gout/pseudogout)
- Empiric IV antibiotics — start immediately after aspiration
- Surgical washout/drainage — I&D or arthroscopic lavage. Essential for source control.
- Duration: IV antibiotics × 2–4 weeks (6 weeks if prosthetic joint)
Empiric Antibiotic Selection
| Scenario | Empiric Regimen |
|---|---|
| Standard | Vancomycin (Vancocin) 15–20 mg/kg IV q8–12h (MRSA coverage) |
| GN coverage needed | Add Ceftriaxone (Rocephin) 2g IV daily or Cefepime (Maxipime) |
| Young, sexually active | Ceftriaxone (Rocephin) 1g IV daily (gonococcal arthritis) |
| Prosthetic joint | Vancomycin + cefepime (broad). Infectious disease + orthopedics consulted. |
🧪 Workup
Synovial Fluid Analysis
| Finding | Normal | Inflammatory | Septic |
|---|---|---|---|
| WBC | < 200 | 2,000–50,000 | > 50,000 (often > 100K) |
| PMNs | < 25% | 50–75% | > 75% |
| Gram stain | Negative | Negative | Positive in 50–75% |
| Culture | Negative | Negative | Positive in 70–90% |
| Crystals | None | May have | Absent (but gout + septic can coexist!) |
- Blood cultures × 2 (positive in ~50%)
- CBC, CRP, ESR (elevated)
- GC/CT NAAT if gonococcal suspected
- X-ray of joint (baseline — may be normal early)
💊 Medications
| Drug | Dose | Coverage |
|---|---|---|
| Vancomycin (Vancocin) | 15–20 mg/kg IV q8–12h | MRSA, MSSA, strep |
| Ceftriaxone (Rocephin) | 2g IV daily | GN coverage, gonococcal |
| Nafcillin (Unipen) | 2g IV q4h | MSSA — de-escalate to this once sensitivities known |
| Cefazolin (Ancef) | 2g IV q8h | Alternative for MSSA |
📊 Monitoring
- Repeat aspiration if not improving in 48–72h
- CRP trending (should halve every 3–5 days)
- Joint ROM and swelling assessment daily
- Vancomycin levels (AUC-based dosing)
- Blood cultures — document clearance
📋 On Rounds
Pimp Questions
Can gout and septic arthritis coexist?
Yes! This is a common exam question and real clinical pitfall. Finding crystals does NOT exclude infection. Up to 5% of proven septic joints will also have crystals. If clinical suspicion for infection is high (fever, WBC > 50K, risk factors), treat as septic even if crystals are present. Always send Gram stain and culture regardless of crystal findings.
How does gonococcal arthritis differ from non-gonococcal?
Gonococcal: Young, sexually active. Often migratory polyarthralgia → settles in one joint. Associated with tenosynovitis and skin lesions (painless papules/pustules). Blood cultures often negative. Synovial fluid cultures positive in only 25–50%. Non-gonococcal (S. aureus): Usually monoarticular, higher WBC counts, more destructive, blood cultures positive in ~50%. Treatment differs: GC → ceftriaxone; S. aureus → vancomycin ± surgical drainage.
What is the Kocher criteria and when is it used?
Kocher criteria are used for pediatric hip septic arthritis: (1) Fever > 38.5°C, (2) Non-weight-bearing, (3) ESR > 40, (4) WBC > 12,000. Meeting 4/4 criteria = 99.6% probability of septic arthritis. Meeting 0/4 = 0.2% probability. Developed for children but conceptually similar approach in adults — any acute monoarthritis with fever + elevated inflammatory markers needs aspiration.
⚡ Summary
#1 Rule
Acute monoarthritis = septic until proven otherwise. Aspirate before antibiotics.
#1 Organism
S. aureus (all ages). N. gonorrhoeae in young sexually active adults.
Synovial Fluid
WBC > 50K with > 75% PMNs = septic. Culture + in 70-90%. Gram stain + in 50-75%.
Treatment
Empiric vancomycin (MRSA). Add ceftriaxone for GN coverage. IV × 2-4 weeks.
Surgery
Joint washout/I&D essential. Delay causes irreversible cartilage destruction in 24-48h.
Pitfall
Crystals do NOT exclude infection. Gout + septic coexist in ~5%. Always send cultures.
Code Status & Advance Directives
Goals of care discussions define what treatments align with patient values. POLST/MOLST translates goals into actionable medical orders. DNR/DNI ≠ comfort care. Full code ≠ always appropriate. Document clearly.
🔍 Overview
Key Terminology
| Term | Definition |
|---|---|
| Full Code | All resuscitative measures including CPR, intubation, vasopressors, defibrillation |
| DNR (Do Not Resuscitate) | No chest compressions or defibrillation if pulseless. Does NOT limit other treatments. |
| DNI (Do Not Intubate) | No endotracheal intubation. May still receive BiPAP, medications, other interventions. |
| DNR/DNI | No CPR AND no intubation. All other treatments still available unless specified. |
| Comfort Measures Only (CMO) | Focus entirely on symptom relief. No disease-directed treatments. Hospice-level care. |
| POLST/MOLST | Portable medical order translating goals into specific treatment decisions (antibiotics, fluids, hospitalization, CPR) |
| Advance Directive | Legal document expressing wishes for future care when unable to decide (living will, healthcare proxy) |
DNR ≠ "do not treat." A patient can be DNR and still receive ICU-level care, antibiotics, surgery, and full medical management. DNR ONLY addresses cardiac arrest.
🚨 Management
Framework for Goals of Care Conversation
| Step | What to Say |
|---|---|
| 1. Ask permission | "Would it be okay if we talked about what's most important to you regarding your medical care?" |
| 2. Assess understanding | "What is your understanding of your illness and where things are?" |
| 3. Explore values | "What's most important to you? What are you hoping for? What are you worried about?" |
| 4. Share prognosis | "I wish things were different, but I'm worried that..." (wish-worry framework) |
| 5. Make recommendation | "Based on what you've told me is important, I would recommend..." |
| 6. Document | Document code status, healthcare proxy, POLST. Communicate to all team members. |
Never ask: "Do you want us to do everything?" This question is uninformative — nobody would say no. Instead, explain what interventions entail and ask what outcomes are acceptable.
🧪 Workup
Information to Gather
- Current understanding of illness/prognosis
- Prior advance directives or POLST forms
- Healthcare proxy/POA identification
- Religious/spiritual considerations
- Family dynamics and decision-makers
- Prior experiences with hospitalization, ICU, mechanical ventilation
- What quality of life means to the patient
💊 Medications
No specific medications for code status discussions. For symptom management in comfort care transitions:
| Symptom | Medication | Dose |
|---|---|---|
| Pain | Morphine Sulfate | 2–4 mg IV q2h PRN or 5–10 mg PO q4h |
| Dyspnea | Morphine Sulfate | 2 mg IV q2h PRN (opioids treat air hunger) |
| Anxiety | Lorazepam (Ativan) | 0.5–1 mg IV/SL q4h PRN |
| Secretions | Glycopyrrolate (Robinul) | 0.2 mg IV q4h PRN or Scopolamine (Transderm Scōp) patch |
| Nausea | Ondansetron (Zofran) | 4 mg IV q6h PRN |
| Agitation/delirium | Haloperidol (Haldol) | 0.5–2 mg IV q4h PRN |
📊 Monitoring
- Symptom assessment q4h (pain, dyspnea, agitation scales)
- Document goals of care discussion in medical record
- Ensure code status is accurately reflected in EMR
- Communicate changes to nursing, covering providers, and consultants
- Family meeting documentation
- Reassess code status with clinical changes
📋 On Rounds
Pimp Questions
What is the difference between an advance directive and a POLST?
Advance directive is a LEGAL document completed by anyone (regardless of health status) expressing wishes for future care. It designates a healthcare proxy and/or describes treatment preferences. It is interpreted and must be translated into medical orders. POLST (Physician Orders for Life-Sustaining Treatment) is a MEDICAL ORDER signed by a physician for patients with serious illness. It immediately actionable — paramedics, nurses, and physicians can follow it directly. POLST overrides a general advance directive because it is more specific and recent.
Can you perform CPR on a patient who is DNR if they have a reversible cause of arrest?
No, unless the patient or surrogate specifically requests a "conditional" or "limited" code status. DNR means no CPR regardless of the cause. However, you CAN and SHOULD treat the reversible condition aggressively (e.g., give calcium for hyperkalemia, treat anaphylaxis) — treating the cause is NOT CPR. If a patient or family specifically requests "DNR except in case of X," this should be clearly documented.
How do you handle disagreement between family members about code status?
(1) Identify the legally designated healthcare proxy/POA — their decision has legal authority. (2) If no proxy, follow your state's surrogate hierarchy (spouse → adult children → parents → siblings). (3) Focus the conversation on "what would the patient want?" (substituted judgment) rather than what family members want. (4) Ethics committee consultation if unable to resolve. (5) Never use code status discussions as family therapy — focus on the patient's values and goals.
⚡ Summary
DNR ≠ Do Not Treat
DNR only addresses cardiac arrest. All other care continues unless specifically limited.
Never Ask
"Do you want everything?" Instead: explain interventions, ask what outcomes are acceptable.
Conversation Framework
Ask permission → Assess understanding → Explore values → Share prognosis → Recommend → Document.
POLST vs AD
AD = legal document, any time, interpreted. POLST = medical order, serious illness, immediately actionable.
CMO Symptoms
Morphine (pain + dyspnea), lorazepam (anxiety), glycopyrrolate (secretions), haldol (agitation).
Documentation
Code status in EMR. Healthcare proxy identified. Communicate to ALL team members.
Family Meeting Framework
Structured approach to family meetings for goals of care, bad news delivery, and complex decision-making. Preparation, setting, and communication skills are essential. The SPIKES framework guides difficult conversations.
🔍 Overview
SPIKES Framework for Breaking Bad News
| Step | Component | Example |
|---|---|---|
| S | Setting | Private room, sit down, phone off, tissues available. Ensure right people present. |
| P | Perception | "What is your understanding of what's been happening with your mom's health?" |
| I | Invitation | "Would it be okay if I shared some information about the test results?" |
| K | Knowledge | Use a warning shot: "I'm afraid I have some difficult news..." Then share information clearly. |
| E | Emotions | NURSE: Name, Understand, Respect, Support, Explore. "I can see this is really hard." |
| S | Summary/Strategy | Summarize, outline next steps, provide follow-up plan. "Let me make sure we're on the same page." |
🚨 Management
Before the Meeting
- Pre-meeting huddle — align the medical team on prognosis and recommendations
- Identify decision-maker — who has POA/proxy? Who else should attend?
- Review chart — know the clinical facts, prognosis, treatment options
- Set agenda — what decisions need to be made?
- Book a private room — never deliver bad news in a hallway or shared space
During the Meeting
- Introductions — everyone states their name and role
- Ask before telling — "What is your understanding of what's been going on?"
- Use clear, simple language — avoid jargon. Say "died" not "passed away"
- Allow silence — silence after bad news is therapeutic, not awkward
- Address emotions before information — respond to tears/anger before continuing
- Make a recommendation — families want guidance, not just options
- Summarize and document
🧪 Workup
Common Family Meeting Indications
- New serious diagnosis (cancer, terminal illness)
- Clinical deterioration despite treatment
- Goals of care / code status discussion
- Transition to comfort measures
- Surrogate decision-making (incapacitated patient)
- Family conflict about care plan
- Prolonged ICU stay without improvement
💊 Medications
No medications specific to family meetings. Refer to code status/palliative sedation topics for comfort care medications when goals of care change.
📊 Monitoring
- Document family meeting in EMR (attendees, discussion, decisions)
- Update code status if changed
- Follow-up meeting scheduled if needed (complex decisions often need multiple conversations)
- Communicate outcomes to bedside nurse, overnight team, consultants
- Social work/chaplain follow-up with family as needed
📋 On Rounds
Pimp Questions
What is the most common mistake in family meetings?
Talking too much and not listening enough. The most effective family meetings involve asking open-ended questions and sitting with the answers. Families need to process emotions before they can process information. If you jump straight to medical facts without exploring understanding and emotions, families cannot absorb what you're saying. The "ask-tell-ask" framework works well: Ask what they understand, Tell the information, Ask what questions they have.
How do you handle an angry family member in a meeting?
(1) Do not become defensive — anger is usually about fear, grief, or helplessness. (2) Name the emotion: "I can see you're frustrated, and that makes sense given how difficult this has been." (3) Validate: "Anyone in this situation would feel the same way." (4) Explore: "Can you tell me more about what's been hardest for you?" (5) Do NOT argue facts during emotional escalation — address emotions first, then return to medical information. If safety is a concern, take a break.
⚡ Summary
SPIKES
Setting → Perception → Invitation → Knowledge → Emotions → Summary. Framework for bad news.
Pre-Meeting
Align team on prognosis. Identify decision-maker. Book private room. Set agenda.
Key Phrases
"What is your understanding?" "I wish things were different." "I'm worried that..."
Emotions First
NURSE: Name, Understand, Respect, Support, Explore. Address feelings before giving more info.
Silence
Allow silence after bad news. It is therapeutic and necessary for processing. Do not fill it.
Document
Attendees, discussion, decisions, follow-up plan. Update code status. Communicate to team.
Tuberculosis
Mycobacterium tuberculosis — airborne transmission. Latent TB (positive PPD/IGRA, no symptoms) vs Active TB (cough, fever, night sweats, weight loss, cavitary lesions). Airborne isolation. 4-drug RIPE therapy × 6 months.
🔍 Overview
Latent vs Active TB
| Feature | Latent TB (LTBI) | Active TB |
|---|---|---|
| Symptoms | None | Cough > 2–3 wks, hemoptysis, fever, night sweats, weight loss |
| CXR | Normal | Upper lobe cavitary lesions, infiltrates, hilar LAD, Ghon complex |
| AFB smear | Negative | May be positive (3 sputum samples) |
| Infectious | No | Yes — airborne isolation required |
| PPD/IGRA | Positive | Usually positive (can be negative if immunosuppressed) |
Airborne isolation (negative pressure room, N95 for staff) for ANY suspected active TB until 3 consecutive negative AFB smears collected 8–24h apart.
🚨 Management
Active TB: RIPE Therapy
| Drug | Duration | Major Side Effects |
|---|---|---|
| Rifampin (Rifadin) | 6 months | Orange body fluids, hepatotoxicity, drug interactions (CYP450 inducer) |
| Isoniazid (INH) | 6 months | Hepatotoxicity, peripheral neuropathy (give Pyridoxine (Vitamin B6) 25–50 mg daily) |
| Pyrazinamide | 2 months | Hepatotoxicity, hyperuricemia/gout |
| Ethambutol (Myambutol) | 2 months | Optic neuritis — check visual acuity monthly. Red-green color blindness. |
Latent TB Treatment
- Isoniazid (INH) 300 mg daily × 9 months (classic regimen)
- Rifampin (Rifadin) 600 mg daily × 4 months (shorter, preferred)
- INH + Rifapentine (Priftin) weekly × 12 weeks (3HP regimen — DOT)
🧪 Workup
- PPD (tuberculin skin test) — read at 48–72h. Induration (not redness) matters. Cutoff varies by risk.
- IGRA (QuantiFERON, T-SPOT) — blood test, single visit, not affected by BCG vaccination
- CXR — upper lobe infiltrates, cavitary lesions, Ghon/Ranke complex
- 3 sputum AFB smears and cultures — collected 8–24h apart. Culture is gold standard (takes 2–6 wks).
- NAAT (GeneXpert/Xpert MTB/RIF) — rapid PCR, also detects rifampin resistance
- HIV test — all TB patients (TB-HIV coinfection common)
💊 Medications
| Drug | Dose | Key Monitoring |
|---|---|---|
| Isoniazid (INH) | 5 mg/kg (max 300 mg) daily | LFTs monthly. Give B6 (pyridoxine) to prevent neuropathy. |
| Rifampin (Rifadin) | 10 mg/kg (max 600 mg) daily | LFTs. CYP450 inducer — check all drug interactions. |
| Pyrazinamide | 25 mg/kg daily | LFTs, uric acid (causes hyperuricemia). |
| Ethambutol (Myambutol) | 15–20 mg/kg daily | Visual acuity and color vision monthly. |
| Pyridoxine (Vitamin B6) | 25–50 mg daily | Given with INH to prevent peripheral neuropathy. |
📊 Monitoring
- LFTs at baseline, monthly during treatment
- Visual acuity monthly if on ethambutol
- Sputum AFB monthly until conversion (negative × 2)
- Drug susceptibility results — adjust regimen for MDR-TB
- HIV testing
- DOT (directly observed therapy) recommended for all active TB
📋 On Rounds
Pimp Questions
Why do you give pyridoxine (B6) with isoniazid?
INH inhibits pyridoxal phosphokinase → depletes active vitamin B6 (pyridoxine) → peripheral neuropathy (stocking-glove distribution). Risk factors: malnutrition, pregnancy, HIV, diabetes, alcoholism, renal failure. Give B6 25–50 mg daily to all patients on INH as prophylaxis.
What is the most feared side effect of ethambutol?
Optic neuritis — presents as decreased visual acuity, red-green color blindness, central scotomas. Usually dose-dependent and reversible if caught early. Check baseline visual acuity and color vision, then monthly. Discontinue immediately if visual changes occur.
When can you remove a TB patient from airborne isolation?
Three criteria: (1) 3 consecutive negative AFB smears collected 8–24h apart, (2) Clinical improvement on appropriate therapy, (3) Alternative diagnosis established. In practice, many hospitals require all three. Cultures take weeks but smears can be done same day.
⚡ Summary
Latent vs Active
Latent: + PPD/IGRA, no symptoms, normal CXR, not infectious. Active: symptoms, abnormal CXR, infectious.
RIPE Therapy
Rifampin + INH (6 mo) + Pyrazinamide + Ethambutol (2 mo). Always give B6 with INH.
Isolation
Airborne (negative pressure, N95). Until 3 negative AFB smears 8-24h apart.
Side Effects
INH: hepatotoxicity, neuropathy. Rifampin: orange fluids, CYP inducer. Ethambutol: optic neuritis.
Diagnosis
3 sputum AFB smears/cultures. NAAT (GeneXpert) for rapid detection + rifampin resistance.
Always Test
HIV in all TB patients. LFTs at baseline and monthly. Visual acuity if on ethambutol.
Fungal Infections
Candida (ICU, lines, immunosuppression), Aspergillus (neutropenic, transplant), Cryptococcus (HIV, CD4 < 100), endemic mycoses (Histo, Coccidio, Blasto). Echinocandins for Candida, voriconazole for Aspergillus, amphotericin for severe.
🔍 Overview
Major Fungal Pathogens
| Organism | Risk Factors | Key Features |
|---|---|---|
| Candida | ICU, central lines, TPN, broad-spectrum abx, neutropenia | Candidemia, oral thrush, esophagitis. Remove lines. Echinocandin first-line. |
| Aspergillus | Neutropenia, transplant, chronic steroids, COPD | Invasive pulmonary aspergillosis (IPA). "Halo sign" on CT. Galactomannan antigen. |
| Cryptococcus | HIV (CD4 < 100), transplant | Meningitis — headache, fever. India ink, cryptococcal antigen (CrAg). Elevated opening pressure. |
| Histoplasma | Ohio/Mississippi River Valley, bat/bird guano | Pneumonia ± mediastinal LAD. Urine/serum antigen. Can mimic sarcoidosis. |
| Coccidioides | Southwestern US deserts | "Valley fever." Pneumonia, erythema nodosum, meningitis (if disseminated). |
| PJP (Pneumocystis) | HIV (CD4 < 200), immunosuppression | Bilateral ground-glass opacities. ↑ LDH. TMP-SMX treatment AND prophylaxis. |
🚨 Management
Treatment by Organism
| Infection | First-Line | Duration |
|---|---|---|
| Candidemia | Micafungin (Mycamine) 100 mg IV daily or Caspofungin (Cancidas) 70mg load then 50mg daily | 14 days after first negative blood culture. REMOVE all central lines. |
| Invasive Aspergillus | Voriconazole (Vfend) 6mg/kg IV q12h × 2, then 4mg/kg q12h | 6–12 weeks minimum. Check voriconazole trough levels. |
| Crypto meningitis | Amphotericin B (AmBisome) + Flucytosine (Ancobon) × 2 wk → Fluconazole (Diflucan) | Induction 2 wk → consolidation 8 wk → maintenance 1 yr |
| PJP (moderate-severe) | TMP-SMX (Bactrim) 15–20 mg/kg/day IV (TMP component) + prednisone if PaO₂ < 70 | 21 days. Add steroids if hypoxic. |
| Histoplasmosis (severe) | Amphotericin B (AmBisome) → Itraconazole (Sporanox) | Ampho × 1–2 wk → itra × 12 months |
Candida in blood is NEVER a contaminant. Even a single positive blood culture for Candida = true candidemia. Treat every time. This is different from bacteria, where a single bottle of coag-negative staph may be a contaminant.
📋 Clinical Example — When to Treat Candida
| Site | Significance | Action |
|---|---|---|
| Blood (even 1 bottle) | Always real — never contaminant | Echinocandin + remove ALL lines + ophtho consult + echo + blood cx q48h until clearance. 14 days after first negative cx. |
| Urine (candiduria) | Usually colonization, especially with Foley | Do NOT routinely treat. Treat only if: symptomatic UTI, neutropenic, pre-urologic procedure, or renal transplant. Remove/replace Foley first. |
| Sputum | Almost always colonization | Do NOT treat. Candida pneumonia is exceedingly rare. Sputum Candida does not warrant antifungals. |
| Wound / drain | Often colonization | Treat only if deep tissue/peritoneal culture + clinical signs of infection. Surface swabs are unreliable. |
| Peritoneal fluid | Significant if from surgical sample | Treat — intra-abdominal candidiasis. Echinocandin + source control. |
Key teaching point: Growing Candida from a non-sterile site (sputum, urine with Foley, superficial wound) is NOT the same as invasive candidiasis. Only blood cultures and deep sterile-site cultures warrant antifungal treatment.
🧪 Workup
- Blood cultures — Candida grows in standard cultures. Aspergillus rarely grows from blood.
- Galactomannan antigen — serum test for Aspergillus (sensitivity ~70% in neutropenic)
- Beta-D-glucan (BDG) — pan-fungal marker. Elevated in Candida, Aspergillus, PJP. NOT in Crypto or Mucor.
- Cryptococcal antigen (CrAg) — serum and CSF. Very sensitive and specific.
- India ink stain — CSF for Crypto (encapsulated yeast). Less sensitive than CrAg.
- Histoplasma/Coccidioides urine antigen
- CT chest — halo sign (aspergillus), ground-glass (PJP), cavitary (histo, coccidio)
💊 Medications
| Drug Class | Agents | Key Notes |
|---|---|---|
| Echinocandins | Micafungin (Mycamine), Caspofungin (Cancidas), Anidulafungin (Eraxis) | First-line candidemia. NO activity vs Cryptococcus or Mucor. Well tolerated. |
| Azoles | Fluconazole (Diflucan), Voriconazole (Vfend), Itraconazole (Sporanox), Posaconazole (Noxafil) | Vori = first-line aspergillus. Fluconazole for step-down Candida. Check levels for vori. |
| Polyenes | Amphotericin B Liposomal (AmBisome) | Broadest spectrum. Nephrotoxic (liposomal form less so). Use for severe/refractory infections. |
📊 Monitoring
- Blood cultures q48h until clearance (candidemia)
- Voriconazole trough levels (target 1–5.5 mcg/mL)
- Renal function if on amphotericin (BMP daily)
- LFTs on azoles
- Ophthalmology consult for all candidemia (rule out endophthalmitis)
- Echo for candidemia (rule out endocarditis)
📋 On Rounds
Pimp Questions
Why must you remove central lines in candidemia?
Central venous catheters serve as a biofilm nidus for Candida — antifungals cannot penetrate biofilm effectively. Failure to remove lines is associated with persistent fungemia, metastatic complications (endophthalmitis, endocarditis), and increased mortality. Remove ALL central lines if possible and place new lines at a different site.
Why do you add steroids to PJP treatment?
In moderate-severe PJP (PaO₂ < 70 or A-a gradient > 35), the inflammatory response to dying organisms causes worsening respiratory failure. Prednisone 40 mg BID × 5 days, then 40 mg daily × 5 days, then 20 mg daily × 11 days reduces inflammation and improves survival. Must be started within 72h of treatment initiation.
Why is beta-D-glucan NOT elevated in Cryptococcus or Mucor?
BDG detects (1→3)-β-D-glucan, a cell wall component of most fungi. Cryptococcus has a thick polysaccharide capsule that masks BDG. Mucor/Rhizopus (mucormycosis) produce minimal BDG. Therefore, a negative BDG does NOT rule out these infections. Use CrAg for crypto and tissue biopsy/culture for mucor.
⚡ Summary
Candida
ICU/lines/TPN. Echinocandin first-line. Remove all central lines. 14 days after clearance.
Aspergillus
Neutropenia/transplant. Voriconazole first-line. Halo sign on CT. Galactomannan antigen.
Crypto
HIV CD4 < 100. Meningitis. CrAg (serum/CSF). Ampho B + flucytosine → fluconazole.
PJP
HIV CD4 < 200. Ground-glass, ↑ LDH. TMP-SMX. Add steroids if PaO₂ < 70.
BDG
Pan-fungal marker. NOT elevated in Crypto or Mucor. Elevated in Candida, Aspergillus, PJP.
Candidemia Workup
Blood cultures q48h, ophthalmology (endophthalmitis), echo (endocarditis), remove lines.
Nephrotic vs Nephritic Syndrome
Nephrotic: massive proteinuria (>3.5g/day), hypoalbuminemia, edema, hyperlipidemia. Nephritic: hematuria, RBC casts, HTN, mild proteinuria, ↓ GFR. The distinction guides workup and differential.
🔍 Overview
Key Distinction
| Feature | Nephrotic Syndrome | Nephritic Syndrome |
|---|---|---|
| Proteinuria | > 3.5 g/day (massive) | < 3.5 g/day (mild-moderate) |
| Hematuria | Absent or mild | Present — dysmorphic RBCs, RBC casts |
| Edema | Severe (periorbital, anasarca) | Mild-moderate |
| Albumin | ↓↓ (< 3 g/dL) | Normal or mildly ↓ |
| Lipids | ↑↑ Hyperlipidemia | Normal |
| BP | Variable | Hypertension |
| GFR | Initially preserved | ↓ (acute kidney injury) |
| Mechanism | Podocyte injury → protein leak | GBM inflammation → blood leak |
Common Causes
| Nephrotic | Nephritic |
|---|---|
| Minimal change disease (children #1) | IgA nephropathy (#1 worldwide) |
| FSGS (adults #1, especially AA) | Post-streptococcal GN (children) |
| Membranous nephropathy (PLA2R antibody) | Lupus nephritis (class III/IV) |
| Diabetic nephropathy | ANCA vasculitis (GPA, MPA) |
| Amyloidosis | Anti-GBM (Goodpasture) |
🚨 Management
Nephrotic Syndrome Management
- ACEi/ARB — reduce proteinuria (first-line for ALL proteinuric kidney disease)
- Diuretics — loop diuretics for edema. May need albumin co-infusion if severe hypoalbuminemia.
- Statin — hyperlipidemia management
- Anticoagulation — consider if albumin < 2.5 (loss of antithrombin III → hypercoagulable state → renal vein thrombosis)
- Disease-specific treatment — steroids (MCD), rituximab (MN, FSGS), immunosuppression
Nephritic Syndrome Management
- Treat underlying cause — immunosuppression for lupus nephritis, ANCA vasculitis
- BP control — ACEi/ARB preferred
- Supportive — fluid/salt restriction, diuretics if edema
- Urgent nephrology + renal biopsy — rapidly progressive GN (RPGN) is an emergency
🧪 Workup
- Urinalysis with microscopy — proteinuria, hematuria, RBC casts (nephritic), fatty casts/oval fat bodies (nephrotic)
- Spot urine protein/creatinine ratio (UPCR) — > 3.5 = nephrotic range
- 24-hour urine protein — gold standard quantification
- BMP — creatinine, eGFR
- Albumin, lipid panel
- Serologies: ANA, dsDNA, complement (C3/C4), ANCA, anti-GBM, PLA2R Ab, hepatitis panel, HIV
- Renal biopsy — usually needed for definitive diagnosis
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Lisinopril (Zestril) | 5–40 mg daily | Reduce proteinuria. First-line for ALL proteinuric kidney disease. |
| Furosemide (Lasix) | 20–80 mg IV/PO | Edema management. May need high doses with hypoalbuminemia. |
| Prednisone (Deltasone) | 1 mg/kg daily × 4–8 wk | Minimal change disease (dramatic response). Taper over weeks. |
| Rituximab (Rituxan) | 375 mg/m² IV | Membranous nephropathy, refractory FSGS, lupus nephritis |
| Cyclophosphamide (Cytoxan) | Varies | ANCA vasculitis, severe lupus nephritis |
📊 Monitoring
- UPCR trending — goal: reduce proteinuria > 50%
- Creatinine and eGFR
- Albumin levels
- BP — target < 130/80 with proteinuria
- Edema assessment, daily weights
- DVT surveillance if albumin < 2.5 (hypercoagulable)
📋 On Rounds
Pimp Questions
Why are nephrotic patients hypercoagulable?
The kidney leaks antithrombin III (a key anticoagulant) in the urine along with other proteins. Loss of ATIII → uninhibited thrombin activity → hypercoagulable state. Clinical significance: renal vein thrombosis (especially in membranous nephropathy), DVT, PE. Consider prophylactic anticoagulation when albumin < 2.5 g/dL.
What is the most common cause of nephrotic syndrome in adults vs children?
Adults: FSGS (#1 overall, especially in African Americans) and membranous nephropathy (#1 primary cause in Caucasians). Diabetic nephropathy is the #1 secondary cause. Children: Minimal change disease (#1, ~80%). MCD responds dramatically to steroids — > 90% achieve remission within 4–8 weeks.
What does low C3/C4 complement tell you about glomerulonephritis?
Low complement = complement consumption = immune complex deposition. Low C3 AND C4: SLE (Class III/IV), cryoglobulinemia, endocarditis-associated GN. Low C3 only: post-streptococcal GN, MPGN, C3 glomerulopathy. Normal complement: IgA nephropathy, ANCA vasculitis, anti-GBM disease. This narrows the differential significantly.
⚡ Summary
Nephrotic
Proteinuria > 3.5g/day, hypoalbuminemia, edema, hyperlipidemia. Podocyte injury.
Nephritic
Hematuria, RBC casts, HTN, ↓ GFR. GBM inflammation. RPGN is an emergency.
#1 Causes
Nephrotic: FSGS (adults), MCD (kids). Nephritic: IgA (#1 worldwide), post-strep (kids).
All Get ACEi
ACEi/ARB reduces proteinuria in ALL proteinuric kidney disease. First-line.
Hypercoagulable
Loss of antithrombin III → renal vein thrombosis, DVT, PE. Anticoagulate if albumin < 2.5.
Complement
Low C3+C4: SLE, cryo. Low C3 only: post-strep, MPGN. Normal: IgA, ANCA, anti-GBM.
Renal Tubular Acidosis
Non-anion gap metabolic acidosis (NAGMA) caused by defective renal acid handling. Type 1 (distal): cannot secrete H⁺. Type 2 (proximal): cannot reabsorb HCO₃⁻. Type 4: hypoaldosteronism → hyperkalemia.
🔍 Overview
RTA Classification
| Feature | Type 1 (Distal) | Type 2 (Proximal) | Type 4 (Hypoaldo) |
|---|---|---|---|
| Defect | Cannot secrete H⁺ in collecting duct | Cannot reabsorb HCO₃⁻ in proximal tubule | ↓ Aldosterone effect → ↓ H⁺/K⁺ secretion |
| Serum K⁺ | ↓ Hypokalemia | ↓ Hypokalemia | ↑ Hyperkalemia |
| Urine pH | > 5.5 (cannot acidify) | < 5.5 (can acidify once bicarb threshold exceeded) | < 5.5 |
| Serum HCO₃⁻ | Can be very low (< 10) | Usually 12–20 (self-limited) | Usually > 15 (mild) |
| Associations | Sjögren, SLE, nephrocalcinosis, kidney stones | Fanconi syndrome, multiple myeloma, carbonic anhydrase inhibitors | Diabetes (#1), ACEi/ARBs, K-sparing diuretics, adrenal insufficiency |
| Treatment | Oral NaHCO₃ 1–2 mEq/kg/day | Oral NaHCO₃ (high doses needed) + thiazide | Fludrocortisone (Florinef), low-K diet, loop diuretics |
Type 4 RTA is the most common RTA. Most commonly caused by diabetic nephropathy (hyporeninemic hypoaldosteronism). ACEi/ARBs and K-sparing diuretics also cause it.
🚨 Management
Treatment by Type
- Type 1 (Distal): Oral sodium bicarbonate or sodium citrate 1–2 mEq/kg/day. Potassium supplementation (KCl). Relatively easy to correct — low doses suffice.
- Type 2 (Proximal): Oral sodium bicarbonate — but requires HIGH doses (10–15 mEq/kg/day) because bicarb is wasted in urine. Add thiazide diuretic (induces mild volume contraction → increases proximal reabsorption). K⁺ supplementation often needed.
- Type 4: Treat hyperkalemia first. Fludrocortisone (Florinef) 0.1 mg daily if hypoaldosteronism. Low-potassium diet. Furosemide (Lasix) (increases K⁺ excretion). Discontinue offending drugs (ACEi, K-sparing diuretics, TMP-SMX).
🧪 Workup
- ABG/VBG — non-anion gap metabolic acidosis (NAGMA)
- BMP — serum HCO₃⁻, K⁺, anion gap
- Urine pH — key differentiator (> 5.5 in Type 1)
- Urine anion gap — (Na⁺ + K⁺) - Cl⁻. Positive = RTA (renal cause). Negative = GI HCO₃⁻ loss (diarrhea).
- Serum aldosterone, renin (if Type 4 suspected)
- Urine electrolytes
💊 Medications
| Drug | Dose | Type |
|---|---|---|
| Sodium Bicarbonate | 1–2 mEq/kg/day (Type 1); 10–15 mEq/kg/day (Type 2) | Types 1 & 2 |
| Potassium Citrate | 20–40 mEq BID-TID | Type 1 — corrects acidosis AND prevents stones |
| Fludrocortisone (Florinef) | 0.1 mg PO daily | Type 4 — mineralocorticoid replacement |
| Furosemide (Lasix) | 20–40 mg PO daily | Type 4 — enhances K⁺ excretion |
| Hydrochlorothiazide (Microzide) | 12.5–25 mg daily | Type 2 — volume contraction increases proximal HCO₃⁻ reabsorption |
📊 Monitoring
- BMP q1–4 weeks until stable (K⁺, HCO₃⁻, Cr)
- Urine pH — response to treatment
- Renal imaging — nephrocalcinosis/stones in Type 1
- Growth monitoring in children (chronic acidosis impairs growth)
📋 On Rounds
Pimp Questions
How does urine anion gap help differentiate causes of NAGMA?
Urine anion gap (UAG) = (UNa + UK) - UCl. In NAGMA from GI losses (diarrhea), the kidney compensates by excreting more NH₄⁺ (which carries Cl⁻) → UCl is high → UAG is negative (kidney is working). In RTA, the kidney CANNOT excrete acid properly → less NH₄⁺/Cl⁻ → UAG is positive (kidney is the problem). Mnemonic: "Negative is Normal" (the kidney is doing its job).
Why is Type 2 RTA harder to treat than Type 1?
In Type 2, the proximal tubule has a lowered threshold for HCO₃⁻ reabsorption. Any supplemental bicarb is filtered and immediately wasted in the urine (until serum bicarb falls below the lowered threshold). This means you need massive doses (10–15 mEq/kg/day), which also deliver a large sodium load → volume expansion → even more bicarb wasting. Adding a thiazide causes mild volume contraction, which increases proximal reabsorption efficiency.
⚡ Summary
Type 1 (Distal)
Cannot secrete H⁺. Urine pH > 5.5. Hypokalemia. Stones/nephrocalcinosis. Low-dose bicarb works.
Type 2 (Proximal)
Cannot reabsorb HCO₃⁻. Fanconi, myeloma. Needs HIGH-dose bicarb + thiazide.
Type 4
Most common. ↓ Aldosterone → hyperkalemia. DM, ACEi, K-sparing diuretics. Fludrocortisone.
Urine AG
Positive = RTA (kidney problem). Negative = GI loss (kidney compensating). "Negative is Normal."
K⁺ Pattern
Types 1&2: hypokalemia. Type 4: HYPERkalemia. This is the key clinical differentiator.
All NAGMA
Check anion gap first (must be normal). Then urine AG and urine pH to classify.
PMR & Giant Cell Arteritis
PMR: bilateral shoulder/hip girdle pain and stiffness in elderly. ESR/CRP markedly elevated. Dramatic response to low-dose prednisone. GCA: temporal headache, jaw claudication, vision loss. Emergent steroids — do not wait for biopsy.
🔍 Overview
PMR vs GCA
| Feature | PMR | GCA |
|---|---|---|
| Age | > 50 (mean ~72) | > 50 (mean ~72) |
| Symptoms | Bilateral shoulder/hip girdle pain, morning stiffness > 45 min | New temporal headache, jaw claudication, scalp tenderness, visual changes |
| Feared complication | 15–20% develop GCA | Permanent vision loss (anterior ischemic optic neuropathy) |
| ESR/CRP | ↑↑ (ESR often > 40–50) | ↑↑↑ (ESR often > 50–100) |
| Diagnosis | Clinical + ↑ inflammatory markers + response to steroids | Temporal artery biopsy (gold standard). Temporal artery US. |
| Treatment | Prednisone (Deltasone) 12.5–25 mg daily | Prednisone (Deltasone) 60 mg daily (or 1g IV methylpred × 3 days if vision threatened) |
If GCA is suspected with visual symptoms → start high-dose steroids IMMEDIATELY. Do NOT wait for biopsy. Vision loss is irreversible. Biopsy can be done within 1–2 weeks of starting steroids without affecting results.
🚨 Management
PMR Treatment
- Prednisone (Deltasone) 12.5–25 mg daily — dramatic response within 24–72h (if no response, reconsider diagnosis)
- Taper over 12–18 months (very slow — relapse is common)
- Calcium + Vitamin D + DEXA (steroid-induced osteoporosis prevention)
GCA Treatment
- Prednisone (Deltasone) 60 mg daily — immediate start
- If vision threatened: Methylprednisolone (Solu-Medrol) 1g IV daily × 3 days, then oral prednisone
- Slow taper over 1–2 years
- Tocilizumab (Actemra) — IL-6 inhibitor, steroid-sparing agent (GiACTA trial)
- Low-dose aspirin — reduces ischemic complications (visual, stroke)
🧪 Workup
- ESR, CRP — both markedly elevated
- CBC — normocytic anemia common, ↑ platelets
- Temporal artery biopsy — GCA gold standard. Get ≥ 1 cm sample. Skip lesions mean negative biopsy doesn't exclude GCA.
- Temporal artery US — "halo sign" (hypoechoic wall thickening). Increasingly used as first-line in Europe.
- CK — normal in PMR (elevated CK → consider myositis instead)
- RF, anti-CCP — negative (rule out RA, which can mimic PMR)
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| Prednisone (Deltasone) | 12.5–25 mg (PMR) / 60 mg (GCA) | First-line both conditions |
| Methylprednisolone (Solu-Medrol) | 1g IV × 3 days | GCA with threatened vision loss |
| Tocilizumab (Actemra) | 162 mg SC weekly | GCA steroid-sparing (GiACTA trial) |
| Methotrexate (Trexall) | 7.5–15 mg weekly | Steroid-sparing in relapsing PMR (limited evidence) |
| Aspirin | 81 mg daily | GCA — reduces ischemic events |
📊 Monitoring
- ESR/CRP q2–4 weeks initially — guide steroid taper
- Symptom assessment — relapse common during taper
- Blood glucose (steroid-induced diabetes)
- DEXA scan + calcium/vitamin D (osteoporosis prevention)
- BP monitoring (steroids cause HTN)
- Ophthalmology follow-up in GCA
📋 On Rounds
Pimp Questions
What is the diagnostic significance of a "dramatic response" to low-dose prednisone in PMR?
PMR has such a characteristic response to low-dose steroids (12.5–25 mg) that failure to improve within 24–72 hours should prompt reconsideration of the diagnosis. Consider alternatives: RA (check RF, anti-CCP), polymyositis (check CK), malignancy (age-appropriate screening), infection, or hypothyroidism. The dramatic response is almost pathognomonic and is essentially a therapeutic trial.
Why can temporal artery biopsy be negative in GCA?
GCA causes segmental (skip) inflammation of the vessel wall. The biopsy may sample a non-inflamed segment between skip lesions. This is why: (1) The biopsy should be ≥ 1 cm (ideally 2–3 cm), (2) Bilateral biopsies increase sensitivity to ~95%, (3) A negative biopsy does NOT rule out GCA if clinical suspicion is high — treat anyway. Biopsy remains positive for up to 2 weeks after starting steroids.
⚡ Summary
PMR
Age > 50, bilateral shoulder/hip pain, morning stiffness, ↑ ESR/CRP. Prednisone 12.5-25mg. Dramatic response.
GCA
Temporal headache, jaw claudication, vision loss. Prednisone 60mg. IV methylpred if vision threatened.
Vision Loss
Anterior ischemic optic neuropathy. IRREVERSIBLE. Start steroids BEFORE biopsy. Do not wait.
Biopsy
Temporal artery biopsy is gold standard. Skip lesions → can be negative. Treat empirically if high suspicion.
Tocilizumab
IL-6 inhibitor (Actemra). Steroid-sparing in GCA (GiACTA trial). SC weekly.
PMR → GCA
15-20% of PMR patients develop GCA. Monitor for headache, visual symptoms, jaw claudication.
Hypoparathyroidism
Low PTH → hypocalcemia + hyperphosphatemia. Most common cause: post-thyroidectomy/parathyroidectomy. Chvostek and Trousseau signs. Treat with calcium + calcitriol. Monitor for QTc prolongation and seizures.
🔍 Overview
Pathophysiology
PTH maintains serum calcium by: (1) increasing renal Ca²⁺ reabsorption, (2) stimulating osteoclasts (bone resorption), (3) activating vitamin D (1,25-dihydroxy) in the kidney → ↑ intestinal Ca²⁺ absorption. Loss of PTH → low calcium, high phosphate.
Etiology
| Cause | Details |
|---|---|
| Post-surgical (#1) | After thyroidectomy or parathyroidectomy — parathyroid glands damaged/removed |
| Autoimmune | Autoimmune polyendocrine syndrome type 1 (APS-1) |
| Hypomagnesemia | Mg < 1.0 → impaired PTH secretion AND PTH resistance. Fix Mg first! |
| Infiltrative | Hemochromatosis, Wilson disease, metastatic cancer |
| DiGeorge syndrome | 22q11 deletion — absent parathyroids + thymic aplasia |
Always check magnesium in hypocalcemia. Hypomagnesemia causes functional hypoparathyroidism — PTH cannot be secreted or act properly. Calcium will NOT correct until magnesium is repleted.
🚨 Management
Acute Symptomatic Hypocalcemia
- Calcium gluconate 1–2g IV over 10–20 min (preferred over CaCl for peripheral IV — less tissue necrosis)
- Follow with continuous infusion: 0.5–1.5 mg/kg/hr of elemental calcium
- Correct magnesium if low — MgSO₄ 2g IV
- Continuous telemetry — monitor QTc
Chronic Management
- Calcium Carbonate (Tums) 1–3g elemental calcium daily in divided doses
- Calcitriol (Rocaltrol) 0.25–2 mcg daily — active vitamin D (PTH normally activates vitamin D; without PTH, must give active form)
- Natpara (recombinant PTH) — for refractory cases not controlled with calcium/calcitriol
🧪 Workup
- Serum calcium — low (correct for albumin: add 0.8 per 1g albumin below 4)
- Ionized calcium — most accurate
- PTH — low or inappropriately normal (confirms hypoparathyroidism)
- Phosphate — elevated (PTH normally promotes PO₄ excretion)
- Magnesium — check in ALL hypocalcemia. Low Mg → functional hypoPTH
- 25-OH vitamin D — rule out deficiency (common confounder)
- ECG — prolonged QTc
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Calcium Gluconate | 1–2g IV over 10–20 min | Acute symptomatic hypocalcemia — peripheral IV safe |
| Calcium Chloride | 1g IV | 3× more elemental Ca than gluconate — central line only (tissue necrosis risk) |
| Calcitriol (Rocaltrol) | 0.25–2 mcg daily | Active vitamin D — replaces PTH-dependent activation |
| Calcium Carbonate (Tums) | 500–1500 mg elemental Ca TID | Chronic oral replacement. Take with food (needs acid for absorption). |
| Magnesium Sulfate | 2–4g IV | Correct hypomagnesemia FIRST — calcium won't correct otherwise |
📊 Monitoring
- Ionized calcium q4–6h during IV replacement
- ECG — QTc monitoring (prolonged QTc → torsades risk)
- Serum Ca, PO₄, Mg, creatinine q1–3 months chronic
- 24-hour urine calcium — avoid hypercalciuria (no PTH → impaired renal Ca reabsorption → kidney stones)
- Renal ultrasound annually — nephrocalcinosis risk
📋 On Rounds
Pimp Questions
Why must you correct magnesium before calcium in hypocalcemia?
Magnesium is essential for both PTH secretion and PTH action at target organs. When Mg is < 1.0 mg/dL: (1) PTH secretion is impaired (despite low calcium, PTH remains low), (2) PTH receptors are resistant. Giving calcium without fixing magnesium is futile — the body cannot maintain calcium homeostasis. Always check Mg in any hypocalcemia.
What is the difference between Chvostek and Trousseau signs?
Chvostek sign: Tapping the facial nerve (anterior to ear) → ipsilateral facial muscle twitching. Present in ~10% of normal people — less specific. Trousseau sign: Inflate BP cuff above systolic for 3 min → carpopedal spasm (hand/wrist flexion = "obstetrician's hand"). More specific for hypocalcemia (~94% specific). Both indicate neuromuscular irritability from low ionized calcium.
⚡ Summary
#1 Cause
Post-thyroidectomy/parathyroidectomy. Iatrogenic parathyroid removal/damage.
Lab Pattern
↓ Ca, ↓ PTH, ↑ PO₄. Always check Mg — low Mg causes functional hypoPTH.
Acute Rx
Calcium gluconate 1-2g IV (peripheral safe). CaCl via central only. Telemetry for QTc.
Chronic Rx
Oral calcium carbonate + calcitriol (active vitamin D — bypasses need for PTH activation).
Fix Mg First
Mg < 1.0 → impaired PTH secretion AND resistance. Calcium won't correct without Mg.
Monitoring
Ionized Ca, QTc (torsades risk), 24h urine Ca (nephrocalcinosis), renal US annually.
Burns Management
Rule of 9s for BSA estimation. Parkland formula for fluid resuscitation (4 mL × kg × %BSA burned). Major burns: ≥ 20% BSA, inhalation injury, circumferential, face/hands/genitals. Early intubation if airway concern.
🔍 Overview
Burn Classification
| Depth | Appearance | Sensation | Healing |
|---|---|---|---|
| Superficial (1st) | Red, dry, no blisters (sunburn) | Painful | 3–5 days, no scarring |
| Partial thickness (2nd) | Blisters, moist, pink/red | Very painful | Superficial: 2–3 wks. Deep: 3–8 wks, may need grafting |
| Full thickness (3rd) | White/brown/black, leathery, dry | Painless (nerves destroyed) | Requires excision and grafting |
| 4th degree | Extends to muscle, bone, tendon | Painless | Amputation may be required |
Rule of 9s (Adult BSA)
- Head: 9%
- Each arm: 9%
- Anterior trunk: 18%
- Posterior trunk: 18%
- Each leg: 18%
- Perineum: 1%
- Patient's palm ≈ 1% BSA
Inhalation injury clues: singed nasal/facial hair, carbonaceous sputum, stridor, hoarseness, facial burns. Intubate early — airway edema worsens over hours. Once obstructed, intubation becomes impossible.
🚨 Management
Parkland Formula (First 24h)
4 mL × body weight (kg) × %BSA burned = total LR in 24h. Give half in first 8 hours (from time of burn, not arrival), second half over next 16 hours. Only count 2nd/3rd degree burns. Titrate to urine output 0.5–1 mL/kg/hr (adults).
Key Interventions
- Airway — early intubation if inhalation injury suspected. Do NOT wait for desaturation.
- Escharotomy — circumferential full-thickness burns → compartment syndrome. Limb: loss of pulse. Chest: restricted ventilation. Emergent bedside incision through eschar.
- Tetanus prophylaxis
- Pain control — IV opioids (burns are extremely painful)
- Wound care — gentle debridement, topical antimicrobials
- Transfer to burn center — ≥ 20% BSA, full thickness > 5%, face/hands/feet/genitals, inhalation, electrical/chemical, children
🧪 Workup
- BSA estimation (Rule of 9s or Lund-Browder chart)
- CBC, BMP, lactate, coags
- Carboxyhemoglobin (COHb) — if enclosed-space fire (CO poisoning)
- ABG — metabolic acidosis, CO levels
- CXR — inhalation injury
- Type and screen
- Urine myoglobin — if electrical burn or rhabdomyolysis suspected
💊 Medications
| Drug | Dose | Purpose |
|---|---|---|
| Lactated Ringer's | Parkland formula | Resuscitation fluid of choice (NOT NS — hyperchloremic acidosis risk) |
| Morphine (MS Contin) | 0.1 mg/kg IV q2–4h | Pain — burns are extremely painful. IV only (poor absorption otherwise). |
| Silver Sulfadiazine (Silvadene) | Topical to wounds | Topical antimicrobial. Avoid on face (staining). Sulfa allergy caution. |
| Mafenide (Sulfamylon) | Topical | Penetrates eschar — used for ear burns (prevents chondritis). Painful on application. Can cause metabolic acidosis. |
| Tetanus toxoid | 0.5 mL IM | If not up to date |
📊 Monitoring
- Urine output — primary resuscitation endpoint. Target 0.5–1 mL/kg/hr (adults), 1 mL/kg/hr (children)
- Vitals q1h during resuscitation
- COHb levels if CO exposure
- Daily wound assessment
- Temperature — burn patients are hypothermic (lost skin barrier)
- Caloric needs — burns are the highest metabolic demand of any injury (25–35 kcal/kg/day + 40 kcal/%BSA)
📋 On Rounds
Pimp Questions
Why do you use Lactated Ringer's instead of Normal Saline for burn resuscitation?
Burns require massive fluid volumes (Parkland formula). Large-volume NS causes hyperchloremic metabolic acidosis (dilutional, from supraphysiologic Cl⁻ concentration). LR has a more physiologic electrolyte composition. Additionally, LR contains lactate which is converted to bicarbonate by the liver, providing a mild buffer effect.
When is escharotomy indicated?
Circumferential full-thickness burns that compromise circulation or ventilation. The burned eschar is inelastic — as underlying tissue swells, pressure rises. Limb: loss of distal pulses, paresthesias, pain with passive stretch (compartment syndrome). Chest: inability to ventilate (restricted chest wall expansion). Escharotomy is a bedside procedure — longitudinal incision through eschar to release pressure. No anesthesia needed (full-thickness burns are insensate).
What is the significance of carboxyhemoglobin (COHb) levels?
CO binds hemoglobin with 250× greater affinity than O₂ → left-shifts the oxyhemoglobin curve → tissue hypoxia despite "normal" PaO₂. SpO₂ is UNRELIABLE — pulse ox cannot distinguish COHb from OxyHb. COHb > 15% is significant, > 25% is severe. Treatment: 100% O₂ via NRB (half-life of COHb drops from 5h to 1h). Hyperbaric O₂ for severe cases (COHb > 25%, neurologic symptoms, pregnancy).
⚡ Summary
Rule of 9s
Head 9%, each arm 9%, anterior trunk 18%, posterior 18%, each leg 18%, perineum 1%.
Parkland Formula
4 mL × kg × %BSA. Half in first 8h (from burn time), half over next 16h. LR, not NS.
Urine Output
Primary resuscitation target: 0.5-1 mL/kg/hr adults, 1 mL/kg/hr children.
Airway
Intubate EARLY if inhalation injury suspected. Singed hair, stridor, carbonaceous sputum.
Escharotomy
Circumferential full-thickness burns → compartment syndrome. Bedside incision through eschar.
CO Poisoning
COHb levels (SpO₂ unreliable). 100% O₂ NRB. Hyperbaric if severe.
Hypothermia & Drowning
Core temp < 35°C. Mild (32–35°C): shivering. Moderate (28–32°C): loss of shivering, confusion, Osborn waves. Severe (< 28°C): VF risk, appears dead. Warm before declaring death. Active rewarming for moderate-severe.
🔍 Overview
Classification
| Severity | Core Temp | Features |
|---|---|---|
| Mild | 32–35°C | Shivering, tachycardia, vasoconstriction, altered judgment |
| Moderate | 28–32°C | Shivering stops, confusion→stupor, bradycardia, Osborn (J) waves on ECG, atrial fibrillation |
| Severe | < 28°C | Coma, areflexia, VF risk, fixed dilated pupils, appears dead |
| Profound | < 24°C | Asystole, no vital signs. May still be salvageable with rewarming. |
"No one is dead until they are warm and dead." Do NOT declare death until core temp ≥ 32°C and rewarming efforts have failed. Hypothermia is neuroprotective — full recovery has occurred after prolonged cold-water submersion.
🚨 Management
Rewarming Strategies
| Severity | Method | Details |
|---|---|---|
| Mild (32–35°C) | Passive external rewarming | Remove wet clothes, warm blankets, warm environment. Body generates heat via shivering. |
| Moderate (28–32°C) | Active external rewarming | Forced warm air blankets (Bair Hugger), warm IV fluids (40–42°C), heating pads to trunk |
| Severe (< 28°C) | Active core rewarming | Warm IV fluids, warm humidified O₂, bladder/peritoneal lavage with warm saline, ECMO/cardiopulmonary bypass (gold standard for cardiac arrest) |
Cardiac Arrest in Hypothermia
- ECMO/CPB — gold standard rewarming for VF arrest in hypothermia. Rewarms at 5–10°C/hr.
- Continue CPR — may need prolonged resuscitation
- Defibrillation: May attempt up to 3 shocks if temp < 30°C. If unsuccessful, defer further shocks until core temp ≥ 30°C.
- Medications: Withhold vasopressors and antiarrhythmics until core temp ≥ 30°C (drugs don't work and accumulate in cold circulation)
🧪 Workup
- Core temperature — rectal or esophageal probe (NOT oral/tympanic — inaccurate in hypothermia)
- ECG — Osborn (J) waves, prolonged intervals, atrial fibrillation, VF
- ABG — pH interpretation complex (use temperature-corrected values)
- BMP — hyperkalemia (cell lysis), hypoglycemia
- CBC, coags (hypothermia causes coagulopathy)
- Lactate
- TSH, cortisol — rule out myxedema/adrenal crisis as cause
💊 Medications
| Intervention | Details | Notes |
|---|---|---|
| Warm IV NS/LR (40–42°C) | 250–500 mL boluses | Use fluid warmer. Contributes modestly to rewarming. |
| Warm humidified O₂ | 42–46°C via ETT or NRB | Active core rewarming adjunct |
| Warm bladder lavage | 42°C NS via 3-way Foley | Moderate core rewarming |
| Warm peritoneal lavage | 42°C NS via peritoneal catheter | More effective than bladder lavage |
| ECMO | Venoarterial (VA-ECMO) | Gold standard for severe hypothermic cardiac arrest. Rewarms 5–10°C/hr. |
Withhold IV medications until core temp ≥ 30°C. Drugs are ineffective in cold circulation, don't metabolize, and accumulate → risk of toxicity when patient rewarms.
📊 Monitoring
- Continuous core temperature (esophageal or rectal probe)
- Continuous telemetry — VF/VT risk during rewarming
- K⁺ q1–2h — hyperkalemia from cell lysis; also predicts prognosis (K⁺ > 12 = non-survivable)
- ABG q1–2h during rewarming
- Glucose — hypothermia causes hypoglycemia
- Watch for "afterdrop" — core temp continues to drop after rescue as cold peripheral blood returns to core
📋 On Rounds
Pimp Questions
What are Osborn (J) waves?
Positive deflection at the J point (junction of QRS and ST segment) on ECG, pathognomonic for hypothermia. Appear at core temp < 32°C, increase in amplitude as temperature drops. Also called "J waves" or "hypothermic hump." Resolve with rewarming. Not an indication for anti-arrhythmic therapy.
Why is K⁺ > 12 mEq/L considered non-survivable in hypothermia?
Severe hyperkalemia (> 12) in hypothermia indicates massive cell lysis and tissue death — the cells have been irreversibly damaged by ice crystal formation. This level of intracellular potassium release means the patient likely has extensive organ damage incompatible with survival, even with successful rewarming. It is one of the few criteria used to guide termination of resuscitation in hypothermic arrest.
What is "afterdrop" and why is it dangerous?
After rescue from cold exposure, core temperature continues to DROP for a period even as external rewarming begins. Mechanism: rewarming the periphery causes vasodilation → cold, acidotic peripheral blood returns to the core → further cooling of the heart. This can trigger VF. Prevention: rewarm the core first (trunk, not extremities). Avoid excessive peripheral rubbing or limb rewarming before core temperature begins rising.
⚡ Summary
Classification
Mild 32-35°C (shivering). Moderate 28-32°C (no shivering, J waves). Severe <28°C (VF, coma).
Golden Rule
"No one is dead until warm and dead." Do not declare death until core temp ≥ 32°C.
Rewarming
Mild: passive. Moderate: Bair Hugger, warm IV. Severe: ECMO (gold standard for arrest).
Cardiac Arrest
Continue CPR. Max 3 shocks if <30°C, defer more until ≥30°C. Withhold meds until ≥30°C.
K⁺ Prognostic
K⁺ > 12 mEq/L = non-survivable (massive cell lysis). Serial K⁺ guides resuscitation.
Afterdrop
Core temp drops further after rescue — cold peripheral blood returns to core. Rewarm core first.
Hyperviscosity Syndrome
Elevated serum viscosity from excess immunoglobulins (Waldenström IgM most common) or extreme leukocytosis/polycythemia. Classic triad: bleeding, visual changes, neurologic symptoms. Emergent plasmapheresis.
🔍 Overview
Causes
| Cause | Details |
|---|---|
| Waldenström macroglobulinemia | #1 cause. IgM paraprotein — large pentamer is most viscous. Symptoms at IgM > 3 g/dL. |
| Multiple myeloma | Less common (IgA > IgG — IgA polymerizes). ~2–5% of MM cases. |
| Leukostasis | WBC > 100K (AML) or > 200–300K (CLL/ALL). White cell plugging in microvasculature. |
| Polycythemia vera | Hct > 60–65%. RBC sludging. |
Classic Triad
- Mucosal bleeding — epistaxis, gingival bleeding (paraprotein interferes with platelet function and clotting factors)
- Visual changes — blurred vision, "sausage-link" retinal veins on fundoscopy, retinal hemorrhages
- Neurologic symptoms — headache, confusion, dizziness, stroke, coma
Do NOT transfuse pRBCs before plasmapheresis in paraprotein hyperviscosity — adding RBCs to already viscous blood will worsen sludging and can precipitate stroke or MI.
🚨 Management
Emergent Treatment
- Plasmapheresis (plasma exchange) — first-line for symptomatic hyperviscosity. Removes paraprotein directly. 1–2 sessions typically provide rapid relief.
- Leukostasis: Leukapheresis + hydroxyurea + start definitive chemotherapy. IV fluids for dilution.
- Polycythemia: Phlebotomy to target Hct < 45%.
- IV fluids — aggressive hydration to reduce viscosity
- Avoid diuretics — worsens hemoconcentration
- Avoid pRBC transfusion — until viscosity is reduced (except for life-threatening anemia)
🧪 Workup
- Serum viscosity — normal 1.4–1.8 cP. Symptoms typically at > 4 cP. Emergency at > 5–6 cP.
- SPEP + immunofixation — identify paraprotein
- CBC with diff — WBC count (leukostasis), Hct (polycythemia)
- Quantitative immunoglobulins
- Fundoscopic exam — "sausage-link" veins, papilledema, retinal hemorrhages
- BMP, LDH, uric acid
- Coagulation studies — may be abnormal (paraprotein interference)
💊 Medications
| Intervention | Details | Notes |
|---|---|---|
| Plasmapheresis | 1–1.5 plasma volumes per session | First-line. 1–2 sessions for symptom relief. Bridge to chemotherapy. |
| IV NS | Aggressive hydration | Dilute viscous blood. Avoid dehydration. |
| Hydroxyurea (Hydrea) | 50–100 mg/kg/day | Leukostasis — cytoreduction while awaiting chemo |
| Phlebotomy | Target Hct < 45% | Polycythemia vera |
📊 Monitoring
- Serum viscosity — trend during plasmapheresis
- Fundoscopic exams — resolution of retinal findings
- Neuro checks — improvement in mental status
- CBC — WBC trending (leukostasis), Hct (polycythemia)
- Avoid pRBC transfusion until viscosity controlled
📋 On Rounds
Pimp Questions
Why is IgM the most common cause of hyperviscosity among paraproteins?
IgM exists as a pentamer — 5 immunoglobulin units linked together, making it the largest antibody (~900 kDa vs 150 kDa for IgG). This enormous size dramatically increases serum viscosity even at relatively modest concentrations. IgA can also cause hyperviscosity because it polymerizes, but IgG rarely does. This is why Waldenström (IgM-producing) causes hyperviscosity much more commonly than myeloma (usually IgG).
What is the difference between hyperviscosity from paraproteins vs leukostasis?
Paraprotein hyperviscosity: Increased serum viscosity from immunoglobulin. Treated with plasmapheresis. Leukostasis: NOT truly viscosity — it's mechanical plugging of microvasculature by large, sticky blast cells (AML blasts are stickier than ALL). WBC > 100K in AML is concerning. Treated with leukapheresis + hydroxyurea + emergent chemo. Both present similarly (CNS, pulmonary, bleeding), but treatment is different.
⚡ Summary
#1 Cause
Waldenström (IgM pentamer). Also: myeloma (IgA), leukostasis (WBC >100K), polycythemia.
Classic Triad
Mucosal bleeding + visual changes (sausage-link veins) + neurologic symptoms.
Treatment
Plasmapheresis (paraprotein). Leukapheresis + hydroxyurea (leukostasis). Phlebotomy (PV).
Do NOT Transfuse
No pRBC until viscosity reduced — worsens sludging → stroke/MI risk.
Fundoscopy
"Sausage-link" retinal veins, papilledema, retinal hemorrhages. Pathognomonic.
Viscosity Levels
Normal 1.4-1.8 cP. Symptoms >4 cP. Emergency >5-6 cP.
Dermatomyositis & Polymyositis
Inflammatory myopathies causing proximal muscle weakness. DM has characteristic skin findings (heliotrope rash, Gottron papules). Elevated CK. Associated with malignancy (DM). EMG and muscle biopsy confirm diagnosis. Steroids first-line.
🔍 Overview
Dermatomyositis vs Polymyositis
| Feature | Dermatomyositis | Polymyositis |
|---|---|---|
| Skin findings | Heliotrope rash (purple eyelid discoloration), Gottron papules (papules over MCP/PIP/knuckles), V-sign, shawl sign, mechanic's hands | None |
| Muscle weakness | Proximal, symmetric, progressive | Proximal, symmetric, progressive |
| Histology | Perimysial inflammation, perifascicular atrophy | Endomysial inflammation, CD8+ T cells invading fibers |
| Malignancy | Strong association — screen for ovarian, lung, breast, GI, lymphoma | Weaker association |
| Antibodies | Anti-Mi-2, anti-MDA5, anti-TIF1-γ (malignancy-associated) | Anti-Jo-1 (antisynthetase syndrome: ILD, arthritis, mechanic's hands) |
DM in adults requires age-appropriate malignancy screening. Anti-TIF1-γ antibody is specifically associated with malignancy-associated DM. Screen with CT chest/abdomen/pelvis, mammogram, colonoscopy, and pelvic exam.
🚨 Management
Treatment
- First-line: Prednisone (Deltasone) 1 mg/kg/day × 4–6 weeks, then taper
- Steroid-sparing: Methotrexate (Trexall) or Azathioprine (Imuran)
- Refractory: Rituximab (Rituxan), IVIG, Mycophenolate (CellCept)
- ILD management: If antisynthetase syndrome — mycophenolate, rituximab, or cyclophosphamide
- Physical therapy — maintain function during and after treatment
- Malignancy screening — age-appropriate, especially in DM
🧪 Workup
- CK — elevated (usually > 10× normal). Primary marker of muscle damage.
- Aldolase — elevated (more specific for muscle, also elevated)
- Myositis-specific antibodies — Anti-Jo-1, anti-Mi-2, anti-MDA5, anti-SRP, anti-TIF1-γ
- EMG — myopathic pattern (short, small, polyphasic motor units, fibrillation potentials)
- MRI of thighs — STIR sequences show edema in affected muscles. Can guide biopsy site.
- Muscle biopsy — gold standard for diagnosis and classification
- PFTs — ILD screening (anti-Jo-1)
- Malignancy screening — CT, mammogram, colonoscopy
💊 Medications
| Drug | Dose | Role |
|---|---|---|
| Prednisone (Deltasone) | 1 mg/kg/day | First-line. Taper over months once CK normalizes and strength improves. |
| Methotrexate (Trexall) | 15–25 mg weekly | Steroid-sparing. Give with folic acid. Avoid in ILD (can cause drug-induced ILD). |
| Azathioprine (Imuran) | 2–3 mg/kg/day | Steroid-sparing alternative. Check TPMT. |
| IVIG | 2 g/kg over 2–5 days monthly | Refractory cases, especially DM |
| Rituximab (Rituxan) | 375 mg/m² × 4 weekly | Refractory myositis, antisynthetase-associated ILD |
📊 Monitoring
- CK q2–4 weeks — primary marker of response
- Muscle strength testing (manual muscle testing) — clinical improvement lags behind CK normalization
- PFTs q6–12 months — ILD monitoring
- Steroid side effects — glucose, BMD (DEXA), BP, cataracts
- Malignancy screening annually × 3–5 years in DM
📋 On Rounds
Pimp Questions
How do you distinguish myositis from steroid myopathy during treatment?
This is a critical clinical challenge. Both cause proximal weakness. Myositis flare: CK is elevated/rising, inflammatory markers up. Steroid myopathy: CK is NORMAL, no inflammatory markers. Steroid myopathy is painless. If CK is normal but weakness persists/worsens, consider reducing steroids. If CK is rising, the myositis is active and steroids may need to be increased or a steroid-sparing agent added.
What is antisynthetase syndrome?
A clinical syndrome associated with anti-aminoacyl-tRNA synthetase antibodies (most commonly anti-Jo-1). Features: (1) ILD (interstitial lung disease — often the dominant and most life-threatening feature), (2) Inflammatory myopathy, (3) Mechanic's hands (cracked, rough skin on palms/fingers), (4) Arthritis, (5) Raynaud phenomenon, (6) Fever. ILD drives prognosis — PFTs and CT chest are essential at diagnosis.
⚡ Summary
DM vs PM
DM: heliotrope rash, Gottron papules, malignancy association. PM: no skin findings, endomysial CD8+ cells.
Key Lab
CK elevated (often >10× normal). Aldolase also elevated. Myositis-specific antibodies.
Diagnosis
EMG (myopathic pattern), MRI thighs (edema on STIR), muscle biopsy (gold standard).
Treatment
Prednisone 1mg/kg first-line. Steroid-sparing: MTX or azathioprine. Refractory: rituximab, IVIG.
Malignancy
DM strongly associated. Anti-TIF1-γ = malignancy-associated. Screen: CT, mammogram, colonoscopy.
Antisynthetase
Anti-Jo-1. ILD + myopathy + mechanic's hands + arthritis. ILD drives prognosis.
Prognostication Tools
Evidence-based tools to estimate prognosis and guide goals-of-care discussions. PPI, PPS, and surprise question for cancer. ePrognosis for geriatrics. Prognostication is imperfect — communicate uncertainty honestly.
🔍 Overview
Key Prognostic Tools
| Tool | Population | What It Predicts |
|---|---|---|
| Surprise Question | Any serious illness | "Would I be surprised if this patient died in the next 12 months?" If no → initiate palliative discussion. |
| PPS (Palliative Performance Scale) | Cancer and non-cancer | Functional status 0–100%. PPS ≤ 50% → median survival ~6 months. PPS ≤ 30% → days to weeks. |
| PPI (Palliative Prognostic Index) | Cancer | Predicts survival < 3 weeks vs > 6 weeks based on PPS, oral intake, edema, dyspnea, delirium. |
| APACHE II/IV | ICU patients | ICU mortality prediction. Higher score = higher mortality. |
| MELD score | Liver disease | 3-month mortality in cirrhosis. Transplant prioritization. |
| Seattle Heart Failure Model | Heart failure | 1–5 year survival in chronic HF based on multiple variables. |
Physicians systematically overestimate survival — by a factor of 3–5× on average. Use validated tools to supplement clinical judgment. Communicate in ranges, not precise dates.
🚨 Management
Communicating Prognosis
- Ask before telling: "How much information would you like to know about what to expect?"
- Use ranges: "We're talking about days to weeks" or "weeks to months" rather than specific dates
- Frame honestly: "I hope for the best, but I'm worried we may be looking at weeks rather than months"
- Acknowledge uncertainty: "No one can predict exactly — these are estimates based on what we know"
- Functional decline trajectory: Describe what to expect (increasing sleep, decreasing intake, less interaction)
Common Prognostic Time Frames
| Time Frame | Clinical Indicators |
|---|---|
| Months | Declining functional status, weight loss, increasing symptoms, frequent hospitalizations |
| Weeks | Bed-bound most of day, minimal oral intake, drowsy, dependent for all ADLs |
| Days | Bed-bound, minimal consciousness, mottling, Cheyne-Stokes breathing, no oral intake |
| Hours | Unresponsive, irregular breathing, cool/mottled extremities, mandibular breathing |
🧪 Workup
Assessment Components
- Functional status — PPS, Karnofsky, ECOG performance status
- Nutritional status — weight loss trajectory, albumin, BMI
- Disease-specific markers — tumor markers, MELD, NYHA class, eGFR trajectory
- Hospitalization frequency — readmissions suggest declining trajectory
- Symptom burden — increasing symptom load suggests progression
- Patient/family understanding and wishes
💊 Medications
Prognostication itself does not involve medications. When prognosis guides transition to comfort care, see the Code Status & Advance Directives topic for symptom management medications (morphine for pain/dyspnea, lorazepam for anxiety, glycopyrrolate for secretions, haloperidol for agitation).
📊 Monitoring
- Reassess prognosis with each clinical change
- Serial functional status assessment
- Update goals of care as prognosis changes
- Document prognostic discussions in medical record
- Communicate changes to all team members and family
📋 On Rounds
Pimp Questions
What is the "surprise question" and how accurate is it?
"Would I be surprised if this patient died in the next 12 months?" A negative answer (you would NOT be surprised) identifies patients who would benefit from palliative care discussions. Sensitivity ~70%, specificity ~70%. It performs best as a screening tool — not for precise prognostication, but for triggering earlier goals-of-care conversations. Can be applied to any illness.
Why do physicians consistently overestimate survival?
Multiple cognitive biases: (1) Optimism bias — physicians want patients to do well, (2) Therapeutic optimism — belief that treatment is helping more than it is, (3) Anchoring — to the patient's best functional state rather than current trajectory, (4) Patient expectations — pressure from patients/families who want hope. Studies show physicians overestimate by 3–5× on average. Using validated prognostic tools helps counteract these biases.
⚡ Summary
Surprise Question
"Would I be surprised if they died in 12 months?" If no → palliative discussion. Screening tool.
PPS
Palliative Performance Scale 0-100%. ≤50% → ~6mo median. ≤30% → days to weeks.
Physician Bias
Physicians overestimate survival 3-5×. Use validated tools. Communicate in ranges.
Time Frames
Months: declining function. Weeks: bed-bound, minimal intake. Days: mottling, Cheyne-Stokes.
Communication
Ask permission. Use ranges. "I hope for the best but worry..." Acknowledge uncertainty.
Disease-Specific
MELD (liver), Seattle Model (HF), APACHE (ICU), PPI (cancer). Each has validated data.
Contrast-Induced Nephropathy
AKI within 48–72h of iodinated contrast exposure. Rise in Cr ≥ 0.3 mg/dL or ≥ 50% from baseline. Risk factors: CKD, diabetes, dehydration, high contrast volume. Prevention: IV NS hydration before and after contrast.
🔍 Overview
Definition & Risk Factors
Contrast-induced nephropathy (CIN) or contrast-associated AKI: rise in serum creatinine ≥ 0.3 mg/dL or ≥ 50% from baseline within 48–72 hours of iodinated contrast administration.
| Risk Factor | Details |
|---|---|
| CKD (eGFR < 30) | #1 risk factor. Risk is very low with eGFR > 45. |
| Diabetes + CKD | Combined = highest risk. Diabetes alone (without CKD) is NOT a significant risk factor. |
| Volume depletion | Dehydration concentrates contrast in kidneys → direct tubular toxicity |
| High contrast volume | Risk proportional to volume. Minimize contrast used. |
| Nephrotoxic medications | NSAIDs, aminoglycosides, ACEi/ARBs (hold if possible day of contrast) |
| Heart failure | Reduced renal perfusion |
Risk of CIN has been overestimated. Recent large studies suggest true contrast-induced AKI is much less common than previously thought, especially with IV contrast (vs intra-arterial). Do NOT withhold indicated CT scans for fear of CIN — delayed diagnosis is often more dangerous.
🚨 Management
Prevention Protocol
- IV isotonic saline — 1 mL/kg/hr for 6–12h before AND 6–12h after contrast. #1 proven prevention.
- Minimize contrast volume — use lowest effective dose
- Hold nephrotoxins — NSAIDs, aminoglycosides. Consider holding ACEi/ARB day of contrast.
- Metformin: Hold for 48h AFTER contrast (not before). Risk of lactic acidosis if AKI develops — metformin accumulates.
- Use low-osmolar or iso-osmolar contrast
- N-acetylcysteine — no longer recommended (multiple trials show no benefit)
- Avoid repeat contrast within 48–72h if possible
🧪 Workup
- Baseline creatinine + eGFR — assess risk
- BMP at 48–72h post-contrast — check for Cr rise
- Urinalysis — muddy brown granular casts (ATN pattern)
- Urine sodium — may be elevated (tubular injury)
- Assess volume status — dehydration increases risk
💊 Medications
| Intervention | Details | Evidence |
|---|---|---|
| IV NS | 1 mL/kg/hr × 6–12h pre- and post-contrast | Best evidence for prevention. Only proven intervention. |
| IV NaHCO₃ | 3 mL/kg/hr × 1h pre, then 1 mL/kg/hr × 6h post | PRESERVE trial: NOT superior to NS. Use NS instead. |
| N-Acetylcysteine (Mucomyst) | 600–1200 mg PO BID × 2 days | No longer recommended. ACT and PRESERVE trials showed no benefit. |
| Hold metformin | Hold 48h AFTER contrast | Prevents lactic acidosis if AKI develops. Resume when Cr stable. |
📊 Monitoring
- Creatinine at 48–72h post-contrast
- Urine output — monitor if high-risk
- Resume metformin only after confirming stable creatinine at 48h
- Most CIN is self-limited — Cr peaks at 3–5 days, returns to baseline by 7–14 days
📋 On Rounds
Pimp Questions
Should you hold a contrast CT in a patient with CKD and acute illness?
Generally no — do not withhold indicated imaging. The risk of CIN has been overestimated in observational studies (confounded by other causes of AKI in sick patients). Multiple recent studies suggest true IV contrast-induced AKI is uncommon. Delayed or missed diagnosis from avoiding CT is often more dangerous than the small risk of CIN. Hydrate, minimize contrast volume, and proceed with the study if clinically indicated.
Why was N-acetylcysteine (NAC) removed from CIN prevention protocols?
NAC was widely used for decades based on small, conflicting studies. The ACT trial (2011) and PRESERVE trial (2018) definitively showed that NAC provides no benefit over IV saline alone for preventing CIN. Furthermore, NAC may cause a spurious decrease in creatinine (analytically interferes with the assay), giving a false impression of renal protection. Current guidelines recommend IV hydration only.
⚡ Summary
#1 Risk Factor
CKD (eGFR < 30). Diabetes + CKD = highest risk. DM alone is NOT significant risk.
Prevention
IV NS 1 mL/kg/hr × 6-12h before and after. Only proven intervention.
NAC
No longer recommended. ACT and PRESERVE trials showed no benefit over NS alone.
Metformin
Hold 48h AFTER contrast (not before). Resume when Cr stable. Risk: lactic acidosis if AKI.
Don't Delay
CIN risk is overestimated. Do NOT withhold indicated imaging — missed diagnosis is more dangerous.
Course
Self-limited. Cr peaks day 3-5, returns to baseline 7-14 days. Rarely needs dialysis.
Diabetic Foot Infection
Polymicrobial infection in neuropathic/ischemic diabetic foot. Probe-to-bone test (PPV ~89% for osteomyelitis). Mild: oral antibiotics. Moderate-severe: IV antibiotics + surgery. Vascular assessment critical — ischemia = poor healing.
🔍 Overview
IDSA Classification
| Severity | Features | Setting |
|---|---|---|
| Uninfected | Wound without purulence or inflammation | Wound care only |
| Mild | Erythema < 2 cm, superficial, no systemic signs | Outpatient oral antibiotics |
| Moderate | Erythema > 2 cm, deep tissue involvement (abscess, osteomyelitis), no SIRS | Inpatient IV antibiotics ± surgery |
| Severe | SIRS/sepsis, limb-threatening ischemia, necrotizing | ICU, emergent surgery, broad IV antibiotics |
Probe-to-bone test: Insert sterile blunt probe into wound. If you feel bone → PPV ~89% for osteomyelitis. If negative → NPV ~56% (still need MRI if clinical suspicion high). Simple, bedside, do it on every diabetic foot wound.
🚨 Management
Treatment Approach
| Severity | Antibiotic | Duration |
|---|---|---|
| Mild | Amoxicillin-Clavulanate (Augmentin) 875/125 PO BID or TMP-SMX (Bactrim) DS BID (if MRSA risk) | 1–2 weeks |
| Moderate (no osteo) | Ampicillin-Sulbactam (Unasyn) 3g IV q6h or Piperacillin-Tazobactam (Zosyn) if Pseudomonas risk | 2–3 weeks |
| Moderate + osteo | Same as above → narrow based on bone culture | 6 weeks (4–6 weeks post-debridement) |
| Severe | Vancomycin (Vancocin) + Piperacillin-Tazobactam (Zosyn) or Meropenem (Merrem) | Based on response + cultures |
Additional Interventions
- Surgical debridement — remove necrotic tissue, drain abscesses
- Vascular assessment — ABI, arterial duplex. Ischemia = poor healing → revascularization may be needed before wound can heal
- Offloading — non-weight-bearing or total contact cast. Critical for healing.
- Glycemic control — target glucose < 180 during acute infection
- Bone biopsy — gold standard for osteomyelitis diagnosis + culture-guided therapy
📋 Clinical Example — Diabetic Foot Infection Assessment
Patient: 62M with T2DM (A1c 9.8%), presents with left foot ulcer between 4th and 5th toes, purulent drainage, erythema extending 3cm, no fever, WBC 11.2.
Bedside assessment:
- Probe-to-bone test: Insert sterile blunt probe into wound → contacts hard, gritty surface → POSITIVE (PPV ~89% for osteomyelitis).
- Erythema 3cm → moderate infection (> 2cm from wound edge).
- Pedal pulses: dorsalis pedis faint, posterior tibial absent → order ABI (vascular assessment critical — ischemic foot won't heal regardless of antibiotics).
Imaging: X-ray foot → cortical erosion of 5th metatarsal head. MRI foot → bone marrow edema with rim enhancement → confirms osteomyelitis. ESR: 82 (> 70 → high specificity for osteomyelitis in diabetic foot).
Treatment plan:
- Admit. IV antibiotics: ampicillin-sulbactam (Unasyn) 3g IV q6h + vancomycin (Vancocin) if MRSA risk.
- Surgical consult: debridement of necrotic tissue, obtain DEEP bone biopsy for culture (NOT surface swab — surface swabs grow colonizers, not pathogens).
- Vascular surgery consult: ABI 0.6 → significant PAD → may need revascularization before wound will heal.
- Duration: 6 weeks total antibiotics for osteomyelitis, guided by bone culture sensitivities. IV-to-oral switch is acceptable once clinically improving, adequate source control, and an oral agent with good bone penetration is available (OVIVA, 2019).
- Glucose control: target < 180 during acute infection.
Key: The triad for diabetic foot success = antibiotics + surgical debridement + vascular assessment. Missing any one → treatment failure.
🧪 Workup
- Probe-to-bone test — bedside, every diabetic foot wound
- Wound culture (deep tissue, NOT surface swab)
- X-ray foot — osteomyelitis (takes 10–14 days to appear on plain film)
- MRI foot — gold standard imaging for osteomyelitis (sensitivity ~90%)
- ESR — > 70 mm/hr has high specificity for osteomyelitis
- CBC, BMP, HbA1c
- ABI (ankle-brachial index) — vascular assessment
- Blood cultures — if septic
💊 Medications
| Drug | Dose | Coverage |
|---|---|---|
| Amoxicillin-Clavulanate (Augmentin) | 875/125 mg PO BID | Mild — strep, MSSA, anaerobes |
| Ampicillin-Sulbactam (Unasyn) | 3g IV q6h | Moderate — broad coverage including anaerobes |
| Piperacillin-Tazobactam (Zosyn) | 3.375g IV q6h | Moderate-severe with Pseudomonas risk |
| Vancomycin (Vancocin) | 15-20 mg/kg IV q8-12h | MRSA coverage — add for severe or MRSA risk |
| Ertapenem (Invanz) | 1g IV daily | Once-daily option for moderate (OPAT friendly). No Pseudomonas. |
📊 Monitoring
- Wound assessment — size, depth, appearance q1–3 days
- Inflammatory markers — ESR, CRP trending
- Blood glucose — tight control during infection
- Vascular status — perfusion adequate for healing?
- Repeat imaging if not improving (MRI at 4–6 weeks)
📋 On Rounds
Pimp Questions
Why should you get deep tissue cultures instead of surface swabs?
Surface swabs grow colonizing organisms (every chronic wound is colonized with bacteria), NOT the pathogens causing the deep infection. Deep tissue cultures (obtained during debridement or aspiration of purulence/abscess) provide accurate pathogen identification and antibiotic sensitivities. Surface swabs lead to inappropriate antibiotic choices and treatment failures. Never base antibiotic selection on surface swab cultures.
What is the significance of ESR > 70 in diabetic foot?
An ESR > 70 mm/hr has a high specificity (~90%) for osteomyelitis in the setting of a diabetic foot wound. While not diagnostic alone, it significantly raises the pre-test probability and supports the need for MRI. Combined with a positive probe-to-bone test, the probability of osteomyelitis approaches 95%. ESR is also useful for monitoring treatment response.
⚡ Summary
Probe-to-Bone
PPV ~89% for osteomyelitis. Do on every diabetic foot wound. Simple bedside test.
Mild
Augmentin or Bactrim PO × 1-2 weeks. Outpatient.
Moderate-Severe
Unasyn or Zosyn IV. Add vancomycin if MRSA risk. Surgical debridement.
Osteomyelitis
MRI = gold standard. ESR > 70 specific. Bone biopsy for culture. 6 weeks antibiotics.
Vascular
ABI assessment. Ischemia = won't heal → revascularization needed before wound management.
Cultures
Deep tissue only. NEVER surface swabs — they grow colonizers, not pathogens.
Non-Opioid Symptom Management
Managing nausea, constipation, dyspnea, insomnia, anorexia, and pruritus without opioids. Layer therapies systematically. Anticipate symptoms before they occur. Comfort is always achievable.
🔍 Overview
Common Symptoms & First-Line Approaches
| Symptom | First-Line | Second-Line |
|---|---|---|
| Nausea/Vomiting | Ondansetron (Zofran) 4mg IV/PO q6h | Haloperidol (Haldol) 0.5–2mg, Dexamethasone (Decadron) (for ↑ ICP, bowel obstruction) |
| Constipation | Senna (Senokot) 2 tabs BID + Docusate (Colace) | Lactulose (Kristalose), Polyethylene Glycol (MiraLAX), Methylnaltrexone (Relistor) (opioid-induced) |
| Dyspnea | Fan to face, positioning, oxygen (if hypoxic) | Low-dose morphine 2mg IV q2h (treats air hunger centrally) |
| Insomnia | Sleep hygiene, Melatonin 3–5mg QHS | Trazodone (Desyrel) 25–100mg, Mirtazapine (Remeron) 7.5–15mg |
| Anorexia/Cachexia | Small frequent meals, liberalize diet restrictions | Dexamethasone (Decadron) 2–4mg daily (short-term appetite boost), Megestrol (Megace) |
| Pruritus | Moisturizers, Hydroxyzine (Vistaril) 25mg q6h | Gabapentin (Neurontin) 100–300mg TID (uremic/neuropathic), Naltrexone (ReVia) (cholestatic) |
| Hiccups | Chlorpromazine (Thorazine) 25–50mg PO/IV | Baclofen (Lioresal) 5–10mg TID, Gabapentin (Neurontin) |
| Secretions (death rattle) | Glycopyrrolate (Robinul) 0.2mg IV q4h | Scopolamine (Transderm Scōp) patch, Atropine 1% drops SL |
🚨 Management
Principles of Symptom Management
- Assess systematically — use validated scales (Edmonton Symptom Assessment Scale)
- Treat the underlying cause when appropriate and aligned with goals
- Anticipate — start bowel regimen with opioids, anti-emetics with chemo
- Layer therapies — combine drugs with different mechanisms
- Reassess frequently — symptoms change, adjust accordingly
- Non-pharmacologic — positioning, music therapy, aromatherapy, massage, spiritual care
🧪 Workup
Assessment Tools
- ESAS (Edmonton Symptom Assessment Scale) — 9 symptoms rated 0–10. Quick, validated.
- Visual Analog Scale (VAS) — pain intensity
- Constipation Assessment Scale
- CAM (Confusion Assessment Method) — delirium screening
- Review medication list — many symptoms are drug side effects
- Consider reversible causes — hypercalcemia (confusion, nausea), bowel obstruction (nausea), uremia (pruritus, nausea)
💊 Medications
| Drug | Dose | Symptom | Notes |
|---|---|---|---|
| Ondansetron (Zofran) | 4mg IV/PO q6h | Nausea | 5-HT3 antagonist. Causes constipation. |
| Haloperidol (Haldol) | 0.5–2mg IV/PO q4–6h | Nausea, delirium, agitation | Dopamine antagonist. Versatile in palliative care. |
| Dexamethasone (Decadron) | 2–8mg daily | Nausea, anorexia, pain, ↑ICP | Short-term boost. Many side effects long-term. |
| Methylnaltrexone (Relistor) | 8–12mg SC q48h | Opioid-induced constipation | Peripheral opioid antagonist — doesn't reverse analgesia. |
| Glycopyrrolate (Robinul) | 0.2mg IV q4h | Secretions | Doesn't cross BBB (no sedation/delirium). Preferred over scopolamine. |
| Mirtazapine (Remeron) | 7.5–15mg QHS | Insomnia, anorexia, nausea | Multi-symptom relief. Sedating + appetite stimulant at low dose. |
📊 Monitoring
- ESAS scores trending q shift or daily
- Bowel function chart — BMs tracked
- Pain scores with interventions
- Sleep quality
- Functional status changes
- Family satisfaction — are they comfortable?
📋 On Rounds
Pimp Questions
Why is a fan to the face effective for dyspnea?
Cool air flow across the trigeminal nerve (V2 distribution — face) stimulates mechanoreceptors that suppress the sensation of breathlessness centrally. Multiple RCTs show it reduces dyspnea perception independent of oxygen saturation. It is a simple, free, evidence-based intervention. A small bedside fan directed at the face is often more effective than supplemental O₂ in non-hypoxic patients.
Why is glycopyrrolate preferred over scopolamine for death rattle?
Both are anticholinergics that reduce secretion production. Glycopyrrolate does NOT cross the blood-brain barrier → no central side effects (no sedation, no delirium, no agitation). Scopolamine DOES cross the BBB → can cause or worsen delirium, sedation, and paradoxical agitation. In actively dying patients who may already have delirium, glycopyrrolate is safer. Important: neither drug removes existing secretions — they only prevent NEW secretion production. Repositioning and gentle suctioning help for existing secretions.
⚡ Summary
Nausea
Ondansetron first-line. Haloperidol versatile. Dexamethasone for ↑ICP/obstruction.
Constipation
Senna + docusate. Methylnaltrexone (Relistor) for opioid-induced. Anticipate with opioid starts.
Dyspnea
Fan to face (evidence-based). Low-dose morphine treats air hunger centrally. O₂ only if hypoxic.
Secretions
Glycopyrrolate preferred (no BBB crossing → no delirium). Prevents new secretions only.
Mirtazapine
Multi-symptom agent: insomnia + anorexia + nausea. 7.5mg QHS. Very useful in palliative.
Principle
Anticipate, layer therapies, reassess. Non-pharm too: positioning, fan, music, spiritual care.
VTE Prophylaxis
Every inpatient needs VTE risk assessment. Padua score for medical patients. Caprini score for surgical. Pharmacologic (LMWH preferred) unless contraindicated. Mechanical (SCDs) if bleeding risk. "Did you order the DVT ppx?" — yes, always.
🔍 Overview
Risk Assessment
| Tool | Population | Threshold |
|---|---|---|
| Padua Score | Medical inpatients | ≥ 4 = high risk → pharmacologic prophylaxis |
| Caprini Score | Surgical patients | Score-based: 0 = early ambulation, 1–2 = SCDs, 3–4 = pharmacologic, ≥ 5 = extended prophylaxis |
| IMPROVE Bleed Score | Medical inpatients | Assesses bleeding risk — high score → mechanical prophylaxis instead |
Padua Score Components
- Active cancer (+3)
- Previous VTE (+3)
- Reduced mobility (+3)
- Known thrombophilia (+3)
- Recent trauma/surgery (+2)
- Age ≥ 70 (+1)
- Heart or respiratory failure (+1)
- AMI or stroke (+1)
- Acute infection or rheumatic disorder (+1)
- Obesity BMI ≥ 30 (+1)
- Hormonal therapy (+1)
VTE prophylaxis is one of the most impactful things you order every day. Hospital-acquired VTE is preventable. Not ordering prophylaxis is a patient safety event.
🚨 Management
Prophylaxis Options
| Method | Option | Dose |
|---|---|---|
| Pharmacologic (preferred) | Enoxaparin (Lovenox) | 40 mg SC daily (or 30 mg SC q12h if BMI > 40 or CrCl < 30 → use UFH) |
| Heparin (unfractionated) | 5,000 units SC q8h (preferred if CrCl < 30 or high bleed risk — shorter half-life) | |
| Mechanical | SCDs (sequential compression devices) | Both legs, worn whenever in bed |
| Extended prophylaxis | Rivaroxaban (Xarelto) or Enoxaparin (Lovenox) | Post-discharge for high-risk medical (MARINER) or post-surgical (hip/knee) |
🔄 Updated Practice: Old teaching: sequential compression devices (SCDs) are equivalent to pharmacologic VTE prophylaxis. Current practice: pharmacologic prophylaxis (enoxaparin 40 mg SQ daily or heparin 5000 units SQ q8-12h) is superior to mechanical prophylaxis alone. SCDs should be used only when pharmacologic prophylaxis is contraindicated (active bleeding, severe thrombocytopenia). The combination of both is used in highest-risk patients (trauma, major orthopedic surgery).
Contraindications to Pharmacologic Prophylaxis
- Active bleeding
- Severe thrombocytopenia (platelets < 50K)
- Recent intracranial hemorrhage
- Epidural/spinal anesthesia (hold LMWH around procedure)
- HIT (heparin-induced thrombocytopenia) — use mechanical only or argatroban if treatment-dose needed
🧪 Workup
- Padua Score (medical) or Caprini Score (surgical) — on admission
- IMPROVE Bleed Score — if considering pharmacologic
- Platelet count — < 50K → mechanical only
- Creatinine/CrCl — CrCl < 30 → use UFH instead of LMWH
- Review medications — anticoagulants already on board?
💊 Medications
| Drug | Dose | Key Notes |
|---|---|---|
| Enoxaparin (Lovenox) | 40 mg SC daily | Preferred LMWH. Predictable pharmacokinetics. No monitoring needed. |
| Heparin (UFH) | 5,000 units SC q8h | Use if CrCl < 30, high bleed risk (shorter half-life), or obese patients. |
| Fondaparinux (Arixtra) | 2.5 mg SC daily | Alternative if HIT. Factor Xa inhibitor. Renally cleared. |
📊 Monitoring
- Reassess VTE risk with clinical changes
- Platelet count — HIT screening if on heparin products > 4 days (4Ts score)
- Signs of bleeding (hematuria, melena, hemoglobin drop)
- Ensure SCDs are actually ON the patient and functioning
- At discharge — does the patient need extended prophylaxis?
📋 On Rounds
Pimp Questions
Why is q8h UFH preferred over q12h for VTE prophylaxis?
Multiple meta-analyses show that 5,000 units SC q8h (TID) is superior to q12h (BID) for preventing VTE in medical patients. The difference is particularly significant for DVT prevention. Q8h maintains more consistent anti-Xa levels. The trade-off is slightly higher minor bleeding risk, but the VTE prevention benefit outweighs this.
When should you use UFH instead of LMWH for prophylaxis?
(1) CrCl < 30 mL/min — LMWH is renally cleared and accumulates → bleeding risk. UFH is metabolized by the reticuloendothelial system. (2) High bleeding risk — UFH has a shorter half-life (1–2h vs 4–5h for LMWH), so effects wear off faster if bleeding occurs. (3) Planned procedures — easier to manage perioperatively. (4) Morbid obesity — some guidelines recommend UFH q8h or adjusted LMWH dosing (enoxaparin 40 mg q12h for BMI > 40).
⚡ Summary
Every Patient
VTE risk assessment on admission. Padua ≥ 4 (medical) or Caprini-based (surgical) → prophylax.
First-Line
Enoxaparin 40mg SC daily. Use UFH 5000 SC q8h if CrCl < 30 or high bleed risk.
Mechanical
SCDs if pharmacologic contraindicated (active bleed, plt < 50K, HIT, recent ICH).
Contraindications
Active bleeding, plt < 50K, recent ICH, epidural, HIT.
Obese Patients
Standard enox 40mg may be insufficient. Consider 40mg q12h or UFH q8h for BMI > 40.
Discharge
Assess need for extended prophylaxis (post-hip/knee surgery, high-risk medical → rivaroxaban).
Seronegative Spondyloarthropathies
Group of inflammatory arthritides that are RF-negative, HLA-B27 associated. Includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, IBD-associated arthritis. Axial inflammation + enthesitis are hallmarks. NSAIDs first-line, then biologics.
🔍 Overview
Classification
| Disease | Key Features | Unique Associations |
|---|---|---|
| Ankylosing Spondylitis | Inflammatory back pain (worse at rest, better with exercise), sacroiliitis, kyphosis | "Bamboo spine" on X-ray. Anterior uveitis (#1 EAM). Aortic insufficiency. Apical pulmonary fibrosis. |
| Psoriatic Arthritis | Arthritis + psoriasis. DIP joints, dactylitis ("sausage digits"), enthesitis | "Pencil-in-cup" deformity on X-ray. Nail pitting. Arthritis mutilans (severe). |
| Reactive Arthritis | "Can't see, can't pee, can't climb a tree" — conjunctivitis, urethritis, arthritis | Post-GI (Salmonella, Shigella, Campylobacter) or post-GU (Chlamydia). Keratoderma blennorrhagica. |
| IBD-Associated | Peripheral arthritis (follows IBD activity) or axial arthritis (independent of IBD) | Treat the underlying IBD. Peripheral arthritis improves with IBD control. |
Shared Features (All SpA)
- HLA-B27 positive (AS ~90%, reactive ~70%, PsA ~50%)
- Seronegative — RF negative, anti-CCP negative
- Enthesitis — inflammation at tendon/ligament insertion sites (Achilles, plantar fascia)
- Dactylitis — "sausage digit" diffuse swelling of entire finger/toe
- Inflammatory back pain — onset < 40, insidious, morning stiffness > 30 min, improves with exercise, worse at rest
- Extra-articular: uveitis, psoriasis, IBD
🚨 Management
Treatment Approach
| Line | Axial Disease | Peripheral Disease |
|---|---|---|
| 1st | NSAIDs (full dose, continuous if needed) | NSAIDs, local steroids |
| 2nd | Anti-TNF (Adalimumab (Humira), Etanercept (Enbrel), Infliximab (Remicade)) | DMARDs (Methotrexate (Trexall), Sulfasalazine (Azulfidine)) |
| 3rd | Secukinumab (Cosentyx) (anti-IL-17) | Anti-TNF or anti-IL-17 |
Traditional DMARDs (methotrexate, sulfasalazine) do NOT work for axial disease. They only help peripheral joints. For axial SpA, go directly from NSAIDs → biologics (anti-TNF or anti-IL-17).
🧪 Workup
- HLA-B27 — positive in 90% of AS, 70% reactive, 50% PsA. Not diagnostic alone (8% of general population is positive).
- X-ray pelvis (SI joints) — sacroiliitis (sclerosis, erosions, fusion). May take years to appear.
- MRI SI joints — bone marrow edema = early sacroiliitis. Gold standard for early disease.
- CRP, ESR — may be elevated
- RF, anti-CCP — negative (to confirm seronegative)
- X-ray spine — syndesmophytes, bamboo spine (late AS)
- Skin exam — psoriasis (nails, scalp, intergluteal fold)
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| Naproxen (Aleve) | 500 mg BID | First-line all SpA. Full-dose, continuous for axial disease. |
| Indomethacin (Indocin) | 25–50 mg TID | Traditional NSAID for AS. Very effective but GI side effects. |
| Adalimumab (Humira) | 40 mg SC q2 weeks | Anti-TNF. First biologic for axial or peripheral SpA failing NSAIDs. |
| Secukinumab (Cosentyx) | 150 mg SC monthly | Anti-IL-17. Alternative to anti-TNF. Avoid in IBD (can worsen). |
| Sulfasalazine (Azulfidine) | 1–1.5 g BID | Peripheral joints only. No axial benefit. |
📊 Monitoring
- BASDAI (Bath AS Disease Activity Index) — patient-reported outcome q3–6 months
- CRP trending
- Spinal mobility (Schober test, chest expansion)
- Ophthalmology — uveitis screening annually
- DEXA — AS patients at risk for osteoporosis (spinal fusion + inflammation)
- TB screening before biologics
📋 On Rounds
Pimp Questions
How do you differentiate inflammatory back pain from mechanical back pain?
Inflammatory: Age of onset < 40, insidious onset, morning stiffness > 30 min, improves with exercise, worse with rest, night pain (second half of night), alternating buttock pain. Mechanical: Any age, often acute onset, worse with activity, better with rest, no morning stiffness. Having 4+ inflammatory features has ~95% specificity for SpA. The key differentiator: inflammatory back pain gets BETTER with movement, mechanical gets WORSE.
Why are traditional DMARDs ineffective for axial SpA?
The pathophysiology of axial SpA involves entheseal inflammation and new bone formation at the spine/SI joints driven primarily by IL-17 and TNF pathways, not the same T-cell/B-cell mediated pathways targeted by traditional DMARDs (methotrexate, sulfasalazine). These drugs act on synovial inflammation (peripheral joints) but cannot penetrate or modulate the entheseal/axial inflammatory process. This is why guidelines recommend skipping DMARDs and going directly to biologics (anti-TNF or anti-IL-17) for axial disease.
⚡ Summary
Shared Features
RF-negative, HLA-B27+, enthesitis, dactylitis, inflammatory back pain, uveitis.
AS
Bamboo spine, sacroiliitis, uveitis, aortic insufficiency. MRI SI joints for early diagnosis.
PsA
DIP joints, nail pitting, dactylitis, pencil-in-cup deformity. Treat with DMARDs → biologics.
Reactive
"Can't see, pee, climb a tree." Post-GI/GU infection. Chlamydia testing important.
Axial Rx
NSAIDs → anti-TNF or anti-IL-17 directly. DMARDs DO NOT WORK for axial disease.
Inflammatory Back Pain
Age <40, insidious, AM stiffness >30min, better with exercise, worse with rest.
Essential Skills
🎓 Intern Survival Guide
Everything you wish someone told you on day one. Practical tips for presentations, notes, pages, and cross-cover from residents who've been there.
🗣️
How to Present on Rounds
The One-Liner: "Mr. Smith is a 62-year-old with CHF who presented with acute dyspnea."
Template:
1. One-liner (age, history, presentation)
2. Overnight events
3. Subjective (how patient feels today)
4. Vitals (trend, current)
5. Physical exam (pertinent positives/negatives)
6. Labs/studies (new results)
7. Assessment & Plan (by problem)
Pro tips: Under 3 minutes. Know your patient's hospital day. Have the med list ready. Lead with what changed.
Template:
1. One-liner (age, history, presentation)
2. Overnight events
3. Subjective (how patient feels today)
4. Vitals (trend, current)
5. Physical exam (pertinent positives/negatives)
6. Labs/studies (new results)
7. Assessment & Plan (by problem)
Pro tips: Under 3 minutes. Know your patient's hospital day. Have the med list ready. Lead with what changed.
📝
How to Write Notes
Admission H&P:
CC → HPI → ROS → PMH/PSH/Meds/Allergies/Social/Family → PE → Labs → A&P
Daily Progress Note:
Subjective → Objective (vitals, exam, labs) → Assessment & Plan (by problem)
Pro tips:
• Problem-based A&P is key
• Include disposition plan every day
• Copy-forward is dangerous — always update exam and labs
• DVT ppx, diet, activity, code status — address daily
• Less is more — focused > 10-page novel
CC → HPI → ROS → PMH/PSH/Meds/Allergies/Social/Family → PE → Labs → A&P
Daily Progress Note:
Subjective → Objective (vitals, exam, labs) → Assessment & Plan (by problem)
Pro tips:
• Problem-based A&P is key
• Include disposition plan every day
• Copy-forward is dangerous — always update exam and labs
• DVT ppx, diet, activity, code status — address daily
• Less is more — focused > 10-page novel
📟
Handling Pages & Cross-Cover
When paged: Get patient name, room, nurse, problem. Pull chart. Go see the patient. Document.
Common pages:
• Fever: Cultures (blood/urine), CXR, exam
• Pain: Acetaminophen → NSAID → opioid
• Insomnia: Melatonin → trazodone. Avoid benzos.
• HTN: Symptomatic? Asymptomatic HTN rarely needs emergent Rx
• Hypoglycemia: D50 if < 70 and symptomatic. Recheck 15 min.
• Fall: Neuro exam, CT head if on anticoag
• Chest pain: ECG, troponin, compare to prior
Common pages:
• Fever: Cultures (blood/urine), CXR, exam
• Pain: Acetaminophen → NSAID → opioid
• Insomnia: Melatonin → trazodone. Avoid benzos.
• HTN: Symptomatic? Asymptomatic HTN rarely needs emergent Rx
• Hypoglycemia: D50 if < 70 and symptomatic. Recheck 15 min.
• Fall: Neuro exam, CT head if on anticoag
• Chest pain: ECG, troponin, compare to prior
💡
Day One Survival Tips
Before day one: EMR access, know how to page, bring phone charger
On wards:
• Pre-round early — see patients before rounds
• Write your plan before rounds
• Carry a patient list with key info
• Ask for help — seniors expect and respect it
• "I don't know, but I'll look it up" is always acceptable
• Sign out clearly
For your sanity:
• Eat when you can, sleep when you can
• Imposter syndrome is universal — you belong here
• Your co-interns are your best resource
On wards:
• Pre-round early — see patients before rounds
• Write your plan before rounds
• Carry a patient list with key info
• Ask for help — seniors expect and respect it
• "I don't know, but I'll look it up" is always acceptable
• Sign out clearly
For your sanity:
• Eat when you can, sleep when you can
• Imposter syndrome is universal — you belong here
• Your co-interns are your best resource
🏥
Admission Orders: ADC VANDALISM
Admit to: floor/tele/ICU
Diagnosis
Condition: stable/guarded/critical
Vitals: frequency
Allergies: verify
Nursing: I&Os, weights, precautions
Diet: regular/cardiac/NPO
Activity: bed rest/ambulate
Labs: AM labs, trending
IV fluids: type, rate
Special: DVT ppx, GI ppx, bowel regimen
Medications: home meds + new meds
Diagnosis
Condition: stable/guarded/critical
Vitals: frequency
Allergies: verify
Nursing: I&Os, weights, precautions
Diet: regular/cardiac/NPO
Activity: bed rest/ambulate
Labs: AM labs, trending
IV fluids: type, rate
Special: DVT ppx, GI ppx, bowel regimen
Medications: home meds + new meds
🔑
Key Numbers to Save Day One
• Rapid Response / Code Blue
• Pharmacy
• Blood Bank
• Radiology
• IR (Interventional Radiology)
• Lab
• Social Work / Case Management
• Chaplain / Spiritual Care
• Your senior resident / chief — always your first call when unsure
• Pharmacy
• Blood Bank
• Radiology
• IR (Interventional Radiology)
• Lab
• Social Work / Case Management
• Chaplain / Spiritual Care
• Your senior resident / chief — always your first call when unsure
Clinical Tools
✅ Rounding Checklists
Structured checklists to ensure nothing is missed. Print-friendly. Based on patient safety evidence.
🫁 ICU Daily Checklist
ABCDEF Bundle + Safety Checks
☐ A — Analgesia/Sedation: RASS goal? Pain score?
☐ B — SAT & SBT: Daily awakening + breathing trials
☐ C — Sedation choice: Avoid benzos if possible
☐ D — Delirium: CAM-ICU assessment
☐ E — Early mobility: OOB? PT/OT?
☐ F — Family: Updated? Meeting needed?
☐ Lines — still needed? Date? Dressing?
☐ Tubes — Foley needed? NGT?
☐ DVT ppx ordered
☐ GI ppx (stress ulcer) if indicated
☐ HOB 30° (VAP prevention)
☐ Glucose target < 180
☐ Nutrition — enteral feeds within 48h
☐ Bowel regimen — last BM?
☐ Daily goals — what needs to happen today?
🏥 Floor/Wards Daily Checklist
Pre-rounding + Safety
☐ Overnight events / pages
☐ Patient subjective — how do they feel?
☐ Vitals trend — fever curve, BP, HR
☐ Focused exam
☐ New labs / imaging results
☐ DVT ppx ordered
☐ Diet appropriate
☐ Activity — OOB? PT/OT?
☐ Foley — still needed?
☐ IV → PO conversion possible?
☐ Home meds restarted or held for reason?
☐ Bowel regimen (especially on opioids)
☐ Code status confirmed
☐ Disposition — discharge date? Barriers?
☐ Patient education — understanding?
🚪 Admission Checklist
Every new admission
☐ H&P completed
☐ Admission orders (ADC VANDALISM)
☐ DVT prophylaxis ordered
☐ Home med reconciliation
☐ Allergies verified
☐ Code status discussed
☐ Diet ordered
☐ IV fluids if needed
☐ AM labs ordered
☐ Telemetry if indicated
☐ Fall risk assessed
☐ Isolation precautions if needed
☐ Consults placed
☐ Patient/family updated
☐ Sign-out prepared
🏠 Discharge Checklist
Safe transitions of care
☐ Medication reconciliation
☐ Prescriptions sent to pharmacy
☐ Patient can afford meds
☐ Follow-up appointments scheduled
☐ Discharge summary completed
☐ Patient education (teach-back)
☐ Red flag symptoms explained
☐ Pending results — who follows up?
☐ Home services ordered if needed
☐ DME ordered if needed
☐ Transportation arranged
☐ PCP notified
☐ Post-discharge call scheduled (48-72h)
Hands-On Skills
🩺 Procedure Guides
Step-by-step bedside procedure references. Indications, contraindications, landmarks, technique, and complications. Not a substitute for supervised training.
🔴
Central Venous Catheter (Central Line)
IJ, Subclavian, Femoral — Seldinger technique under ultrasound guidance
Indications
• Vasopressor administration (norepinephrine, vasopressin)
• Inadequate peripheral access
• CVP monitoring
• TPN / hyperosmolar infusions (> 900 mOsm)
• Hemodialysis access
• Rapid volume resuscitation (large-bore catheter)
• Inadequate peripheral access
• CVP monitoring
• TPN / hyperosmolar infusions (> 900 mOsm)
• Hemodialysis access
• Rapid volume resuscitation (large-bore catheter)
Contraindications
• Infection at insertion site
• Thrombus in target vessel
• Subclavian: avoid if coagulopathic (non-compressible)
• IJ: caution with ↑ ICP (Trendelenburg worsens ICP)
• Femoral: higher infection rate — use only if IJ/subclavian not feasible
• Thrombus in target vessel
• Subclavian: avoid if coagulopathic (non-compressible)
• IJ: caution with ↑ ICP (Trendelenburg worsens ICP)
• Femoral: higher infection rate — use only if IJ/subclavian not feasible
Technique (IJ — Most Common)
1. Consent, time-out, full barrier precautions (cap, mask, sterile gown, gloves, full drape)
2. Position: Trendelenburg, head turned away
3. Ultrasound: Identify IJ (compressible) lateral to carotid (pulsatile, non-compressible)
4. Prep & drape — chlorhexidine, wide sterile field
5. Lidocaine — local anesthesia at insertion site
6. Access: 18G needle under US guidance, confirm venous blood (dark, non-pulsatile)
7. Guidewire — advance through needle, watch on US, confirm no arrhythmia on monitor
8. Nick skin with scalpel, dilator over wire
9. Thread catheter over wire — never let go of the wire!
10. Remove wire, flush all ports, suture, dressing
11. CXR — confirm tip at cavoatrial junction, rule out pneumothorax
2. Position: Trendelenburg, head turned away
3. Ultrasound: Identify IJ (compressible) lateral to carotid (pulsatile, non-compressible)
4. Prep & drape — chlorhexidine, wide sterile field
5. Lidocaine — local anesthesia at insertion site
6. Access: 18G needle under US guidance, confirm venous blood (dark, non-pulsatile)
7. Guidewire — advance through needle, watch on US, confirm no arrhythmia on monitor
8. Nick skin with scalpel, dilator over wire
9. Thread catheter over wire — never let go of the wire!
10. Remove wire, flush all ports, suture, dressing
11. CXR — confirm tip at cavoatrial junction, rule out pneumothorax
⚠️ Complications
Pneumothorax (subclavian > IJ), arterial puncture, air embolism, arrhythmia (wire in heart), infection (CLABSI), thrombosis. Never advance against resistance.
🟠
Arterial Line
Radial (preferred), femoral, brachial — continuous BP monitoring and frequent ABGs
Indications
• Continuous BP monitoring (hemodynamic instability, vasopressors)
• Frequent ABG sampling
• Intra-operative monitoring (cardiac surgery, major procedures)
• BP cuff unreliable (morbid obesity, arrhythmia)
• Frequent ABG sampling
• Intra-operative monitoring (cardiac surgery, major procedures)
• BP cuff unreliable (morbid obesity, arrhythmia)
Pre-Procedure
• Modified Allen test — confirm dual blood supply (radial + ulnar) before radial art line
• Compress both radial and ulnar arteries → release ulnar → hand should pink up in < 7 seconds
• If Allen test negative (no collateral flow) → use other wrist or femoral
• Compress both radial and ulnar arteries → release ulnar → hand should pink up in < 7 seconds
• If Allen test negative (no collateral flow) → use other wrist or femoral
Technique (Radial)
1. Position: Wrist dorsiflexed 20–30° over towel roll, tape hand to arm board
2. Prep: Chlorhexidine, sterile drape
3. Lidocaine: Small wheal over radial pulse
4. US-guided (recommended) or palpation
5. 20G catheter-over-needle at 15–30° angle, advance until flash of arterial blood (pulsatile, bright red)
6. Advance catheter off needle into artery, remove needle
7. Connect to transducer, level at phlebostatic axis (4th ICS, mid-axillary)
8. Confirm waveform — arterial waveform with dicrotic notch
2. Prep: Chlorhexidine, sterile drape
3. Lidocaine: Small wheal over radial pulse
4. US-guided (recommended) or palpation
5. 20G catheter-over-needle at 15–30° angle, advance until flash of arterial blood (pulsatile, bright red)
6. Advance catheter off needle into artery, remove needle
7. Connect to transducer, level at phlebostatic axis (4th ICS, mid-axillary)
8. Confirm waveform — arterial waveform with dicrotic notch
⚠️ Complications
Hematoma, thrombosis, distal ischemia (rare with good Allen test), infection, pseudoaneurysm. Never flush forcefully — risk of retrograde embolism to brain.
🟡
Lumbar Puncture (LP)
Diagnostic and therapeutic — meningitis, SAH, idiopathic intracranial hypertension
Indications
• Suspected meningitis/encephalitis
• Rule out SAH (CT-negative thunderclap headache)
• Diagnosis: MS, GBS, carcinomatous meningitis, normal pressure hydrocephalus
• Therapeutic: idiopathic intracranial hypertension (IIH), intrathecal medications
• Rule out SAH (CT-negative thunderclap headache)
• Diagnosis: MS, GBS, carcinomatous meningitis, normal pressure hydrocephalus
• Therapeutic: idiopathic intracranial hypertension (IIH), intrathecal medications
Contraindications
• ↑ ICP with mass lesion — get CT head BEFORE LP if: papilledema, focal neuro deficits, altered consciousness, immunocompromised, age > 60, seizure within 1 week
• Skin infection at puncture site
• Severe coagulopathy (INR > 1.5, platelets < 50K)
• Spinal epidural abscess
• Skin infection at puncture site
• Severe coagulopathy (INR > 1.5, platelets < 50K)
• Spinal epidural abscess
CSF Interpretation
Bacterial: ↑ WBC (>1000, PMN predominant), ↑ protein, ↓ glucose, + Gram stain
Viral: ↑ WBC (10-500, lymphocyte predominant), normal/↑ protein, normal glucose
TB/fungal: ↑ WBC (lymphocytes), ↑ protein, ↓↓ glucose
SAH: RBCs that do NOT clear (tube 1 vs tube 4), xanthochromia
Normal: OP 6-20 cmH₂O, WBC < 5, protein 15-45, glucose 40-70
Viral: ↑ WBC (10-500, lymphocyte predominant), normal/↑ protein, normal glucose
TB/fungal: ↑ WBC (lymphocytes), ↑ protein, ↓↓ glucose
SAH: RBCs that do NOT clear (tube 1 vs tube 4), xanthochromia
Normal: OP 6-20 cmH₂O, WBC < 5, protein 15-45, glucose 40-70
Technique
1. Position: Lateral decubitus (fetal position) or seated, spine flexed. Lateral decubitus preferred for opening pressure measurement.
2. Landmark: L3-L4 or L4-L5 interspace (iliac crest line = L4 spinous process). Always below L2 (conus medullaris ends at L1-L2).
3. Prep: Chlorhexidine, sterile drape
4. Lidocaine: Local anesthesia (subcutaneous + deeper tissues along planned needle path)
5. Spinal needle (20-22G, atraumatic tip preferred — reduces post-LP headache): advance midline with bevel parallel to longitudinal fibers of dura, angled slightly cephalad
6. Feel the "pop" through ligamentum flavum and dura
7. Remove stylet — CSF should flow
8. Opening pressure — measured with manometer in lateral decubitus. Normal: 6-20 cmH₂O
9. Collect tubes: Tube 1 (cell count), Tube 2 (glucose, protein), Tube 3 (Gram stain, culture, extras), Tube 4 (cell count — compare to tube 1 for traumatic tap)
10. Replace stylet before removing needle (reduces post-LP headache risk)
2. Landmark: L3-L4 or L4-L5 interspace (iliac crest line = L4 spinous process). Always below L2 (conus medullaris ends at L1-L2).
3. Prep: Chlorhexidine, sterile drape
4. Lidocaine: Local anesthesia (subcutaneous + deeper tissues along planned needle path)
5. Spinal needle (20-22G, atraumatic tip preferred — reduces post-LP headache): advance midline with bevel parallel to longitudinal fibers of dura, angled slightly cephalad
6. Feel the "pop" through ligamentum flavum and dura
7. Remove stylet — CSF should flow
8. Opening pressure — measured with manometer in lateral decubitus. Normal: 6-20 cmH₂O
9. Collect tubes: Tube 1 (cell count), Tube 2 (glucose, protein), Tube 3 (Gram stain, culture, extras), Tube 4 (cell count — compare to tube 1 for traumatic tap)
10. Replace stylet before removing needle (reduces post-LP headache risk)
⚠️ Post-LP Headache
Positional headache (worse upright, better supine) in ~10-30%. Reduce risk: atraumatic needle, smaller gauge, replace stylet before removal. Treatment: caffeine, analgesics, and if severe → epidural blood patch (definitive).
🟢
Paracentesis
Diagnostic and therapeutic — ascites evaluation, large-volume removal
Indications
• Diagnostic: New-onset ascites, rule out SBP (all cirrhotics admitted with ascites should get diagnostic para)
• Therapeutic: Tense ascites causing respiratory compromise, abdominal discomfort
• Therapeutic: Tense ascites causing respiratory compromise, abdominal discomfort
Key Studies to Send
• Cell count with differential — PMN ≥ 250 = SBP (treat empirically with ceftriaxone)
• Albumin — calculate SAAG (serum albumin - ascites albumin). SAAG ≥ 1.1 = portal hypertension
• Total protein
• Culture — inoculate blood culture bottles at bedside (higher yield)
• Glucose, LDH, amylase, cytology — if secondary peritonitis or malignancy suspected
• Albumin — calculate SAAG (serum albumin - ascites albumin). SAAG ≥ 1.1 = portal hypertension
• Total protein
• Culture — inoculate blood culture bottles at bedside (higher yield)
• Glucose, LDH, amylase, cytology — if secondary peritonitis or malignancy suspected
Technique
1. Position: Supine, slightly tilted to side of puncture
2. Site: LLQ (preferred) — 2 fingerbreadths medial and cephalad to ASIS. Avoid surgical scars, visible vessels, rectus sheath
3. US guidance — confirm fluid pocket ≥ 2 cm, mark site
4. Prep: Chlorhexidine, sterile drape
5. Lidocaine: All layers including peritoneum
6. Z-track technique — pull skin 2 cm caudally before inserting needle (reduces post-procedure leak)
7. Insert needle/catheter while aspirating, advance until fluid returns
8. Collect samples or connect to vacuum bottles for large-volume
9. Large-volume (> 5L): Give albumin 6-8g per liter removed (prevents post-paracentesis circulatory dysfunction)
2. Site: LLQ (preferred) — 2 fingerbreadths medial and cephalad to ASIS. Avoid surgical scars, visible vessels, rectus sheath
3. US guidance — confirm fluid pocket ≥ 2 cm, mark site
4. Prep: Chlorhexidine, sterile drape
5. Lidocaine: All layers including peritoneum
6. Z-track technique — pull skin 2 cm caudally before inserting needle (reduces post-procedure leak)
7. Insert needle/catheter while aspirating, advance until fluid returns
8. Collect samples or connect to vacuum bottles for large-volume
9. Large-volume (> 5L): Give albumin 6-8g per liter removed (prevents post-paracentesis circulatory dysfunction)
⚠️ Key Points
Do NOT correct coagulopathy before paracentesis in cirrhosis. INR/platelets do not predict bleeding risk in liver disease (rebalanced hemostasis). Routine transfusion of FFP/platelets is NOT indicated. SBP: PMN ≥ 250 → start ceftriaxone (Rocephin) 2g IV daily empirically, don't wait for culture.
🔵
Thoracentesis
Diagnostic and therapeutic — pleural effusion evaluation and drainage
Indications
• Diagnostic: Any new or unexplained pleural effusion
• Therapeutic: Symptomatic (dyspnea) effusion
• Exception: bilateral small effusions in known CHF responding to diuretics — can observe without tapping
• Therapeutic: Symptomatic (dyspnea) effusion
• Exception: bilateral small effusions in known CHF responding to diuretics — can observe without tapping
Light's Criteria (Exudate if ANY met)
• Pleural protein / serum protein > 0.5
• Pleural LDH / serum LDH > 0.6
• Pleural LDH > 2/3 upper limit of normal serum LDH
Transudate: CHF, cirrhosis, nephrotic syndrome
Exudate: Infection (parapneumonic/empyema), malignancy, PE, TB, rheumatologic
• Pleural LDH / serum LDH > 0.6
• Pleural LDH > 2/3 upper limit of normal serum LDH
Transudate: CHF, cirrhosis, nephrotic syndrome
Exudate: Infection (parapneumonic/empyema), malignancy, PE, TB, rheumatologic
Technique
1. Position: Seated, leaning forward on bedside table
2. US guidance mandatory — mark fluid pocket, ensure ≥ 1 cm depth
3. Site: 1-2 interspaces below fluid level, posterior axillary or midscapular line. Always go ABOVE the rib (neurovascular bundle runs under each rib)
4. Prep: Chlorhexidine, sterile drape
5. Lidocaine: Subcutaneous → intercostal muscles → OVER the rib → parietal pleura (aspirate as you go — fluid confirms pleural space)
6. Insert catheter-over-needle — advance while aspirating, then thread catheter
7. Collect samples: Cell count, protein, LDH, glucose, pH, culture, cytology
8. Max removal: 1-1.5L per session (prevents re-expansion pulmonary edema). Stop if chest tightness or cough.
9. Post-procedure CXR — only if air aspirated, symptoms, or multiple needle passes
2. US guidance mandatory — mark fluid pocket, ensure ≥ 1 cm depth
3. Site: 1-2 interspaces below fluid level, posterior axillary or midscapular line. Always go ABOVE the rib (neurovascular bundle runs under each rib)
4. Prep: Chlorhexidine, sterile drape
5. Lidocaine: Subcutaneous → intercostal muscles → OVER the rib → parietal pleura (aspirate as you go — fluid confirms pleural space)
6. Insert catheter-over-needle — advance while aspirating, then thread catheter
7. Collect samples: Cell count, protein, LDH, glucose, pH, culture, cytology
8. Max removal: 1-1.5L per session (prevents re-expansion pulmonary edema). Stop if chest tightness or cough.
9. Post-procedure CXR — only if air aspirated, symptoms, or multiple needle passes
⚠️ Complications
Pneumothorax (US guidance reduces risk dramatically), bleeding, re-expansion pulmonary edema (remove ≤ 1.5L), vasovagal, infection. Empyema (pH < 7.2, glucose < 40, pus) → chest tube, NOT repeat thoracentesis.
🟣
Rapid Sequence Intubation (RSI)
Emergent airway management — preparation, pre-oxygenation, induction, paralysis, placement
Indications for Intubation
• Failure to protect airway (GCS ≤ 8)
• Failure to oxygenate (refractory hypoxemia despite NRB/NIPPV)
• Failure to ventilate (rising PaCO₂, respiratory fatigue)
• Anticipated clinical course (burns, angioedema, massive hematemesis)
• Failure to oxygenate (refractory hypoxemia despite NRB/NIPPV)
• Failure to ventilate (rising PaCO₂, respiratory fatigue)
• Anticipated clinical course (burns, angioedema, massive hematemesis)
The 7 P's of RSI
1. Preparation: Equipment check (ETT sizes 7.0-8.0, laryngoscope, suction, BVM, bougie, backup airway — LMA), monitors on, IV access
2. Pre-oxygenation: 100% FiO₂ × 3-5 min (NRB at 15L/min or flush rate). Apneic oxygenation via nasal cannula at 15L during attempt
3. Pre-treatment: Consider fentanyl (Sublimaze) 1-3 mcg/kg for sympathetic response
4. Paralysis with induction: Induction agent + paralytic simultaneously
5. Protection/Positioning: Sniffing position (ear to sternal notch alignment). Cricoid pressure (Sellick) — controversial
6. Placement: Direct/video laryngoscopy. Visualize cords, pass ETT, confirm with ETCO₂
7. Post-intubation: CXR, vent settings, sedation, secure tube
2. Pre-oxygenation: 100% FiO₂ × 3-5 min (NRB at 15L/min or flush rate). Apneic oxygenation via nasal cannula at 15L during attempt
3. Pre-treatment: Consider fentanyl (Sublimaze) 1-3 mcg/kg for sympathetic response
4. Paralysis with induction: Induction agent + paralytic simultaneously
5. Protection/Positioning: Sniffing position (ear to sternal notch alignment). Cricoid pressure (Sellick) — controversial
6. Placement: Direct/video laryngoscopy. Visualize cords, pass ETT, confirm with ETCO₂
7. Post-intubation: CXR, vent settings, sedation, secure tube
RSI Medications
Induction agents:
• Ketamine (Ketalar) 1-2 mg/kg IV — hemodynamically stable, bronchodilator. First choice in asthma/sepsis
• Etomidate (Amidate) 0.3 mg/kg IV — hemodynamically neutral. Adrenal suppression (single dose is safe)
• Propofol (Diprivan) 1-2 mg/kg IV — ↓ BP, ↓ ICP. Avoid in hypotension
Paralytics:
• Succinylcholine (Anectine) 1.5 mg/kg IV — fastest onset (45-60 sec), shortest duration (6-10 min). Avoid in hyperkalemia, burns > 48h, crush injury, neuromuscular disease
• Rocuronium (Zemuron) 1.2 mg/kg IV — onset 60-90 sec, duration 45-60 min. Reversible with sugammadex (Bridion). Preferred if succinylcholine contraindicated
• Ketamine (Ketalar) 1-2 mg/kg IV — hemodynamically stable, bronchodilator. First choice in asthma/sepsis
• Etomidate (Amidate) 0.3 mg/kg IV — hemodynamically neutral. Adrenal suppression (single dose is safe)
• Propofol (Diprivan) 1-2 mg/kg IV — ↓ BP, ↓ ICP. Avoid in hypotension
Paralytics:
• Succinylcholine (Anectine) 1.5 mg/kg IV — fastest onset (45-60 sec), shortest duration (6-10 min). Avoid in hyperkalemia, burns > 48h, crush injury, neuromuscular disease
• Rocuronium (Zemuron) 1.2 mg/kg IV — onset 60-90 sec, duration 45-60 min. Reversible with sugammadex (Bridion). Preferred if succinylcholine contraindicated
⚠️ Confirmation
End-tidal CO₂ (ETCO₂) is the ONLY reliable confirmation of ETT placement. Auscultation alone is NOT sufficient. No ETCO₂ = esophageal intubation until proven otherwise → remove tube and re-attempt. CXR confirms position but NOT placement (takes too long).
Quick Reference
⚡ Electrolyte Replacement
Standard replacement protocols for common electrolyte abnormalities. Adjust for renal function. Recheck levels after repletion.
🟠 Potassium (K⁺)
Goal: 4.0–5.0 mEq/L (≥ 4.0 in cardiac patients)
| K⁺ Level | Replacement | Expected ↑ |
|---|---|---|
| 3.5–3.9 | KCl 40 mEq PO × 1 | ↑ ~0.4 mEq/L |
| 3.0–3.4 | KCl 40 mEq PO × 2 (or 20 mEq IV × 2) | ↑ ~0.8 mEq/L |
| 2.5–2.9 | KCl 20 mEq IV × 3–4 + 40 mEq PO | Variable |
| < 2.5 | KCl 40 mEq IV (10 mEq/hr peripheral, 20 mEq/hr central) + telemetry | Check q2h |
⚠️ Always check Mg²⁺. Hypomagnesemia prevents K⁺ correction. Fix Mg first. Max peripheral IV rate: 10 mEq/hr (burning). Max central: 20 mEq/hr. Telemetry if K⁺ < 3.0.
🟡 Magnesium (Mg²⁺)
Goal: ≥ 2.0 mg/dL (≥ 2.0 in cardiac/ICU)
| Mg²⁺ Level | Replacement |
|---|---|
| 1.5–1.9 | MgO 400 mg PO BID × 2 days (or MgSO₄ 2g IV × 1) |
| 1.0–1.4 | MgSO₄ 2g IV × 2 doses |
| < 1.0 | MgSO₄ 4g IV over 4h + recheck. Telemetry. May need 8–12g total over 24h. |
⚠️ Key facts: IV Mg causes flushing/warmth (warn patient). Oral Mg causes diarrhea (MgO worst, Mg glycinate better tolerated). Renal patients: reduce dose — Mg is renally cleared. 50% of hypoK is from concurrent hypoMg.
🟢 Phosphate (PO₄)
Goal: 2.5–4.5 mg/dL
| PO₄ Level | Replacement |
|---|---|
| 2.0–2.4 | Neutra-Phos 2 packets PO (or K-Phos 2 tabs PO) |
| 1.5–1.9 | Na-Phos or K-Phos 15 mmol IV over 2h |
| < 1.5 | Na-Phos or K-Phos 30 mmol IV over 4–6h (max 7 mmol/hr) |
⚠️ Choose Na-Phos vs K-Phos based on K⁺ level. K-Phos if K is also low (repletes both). Na-Phos if K is normal/high. IV phosphate can cause hypocalcemia — check Ca. Reduce dose in renal failure.
🔵 Calcium (Ca²⁺)
Goal: iCa 1.1–1.3 mmol/L / Total Ca 8.5–10.5 mg/dL (corrected for albumin)
| Scenario | Replacement |
|---|---|
| Mild (asymptomatic) | Calcium carbonate (Tums) 1–2g PO TID with meals + Vitamin D |
| Moderate (symptomatic) | Calcium gluconate 1–2g IV over 10–20 min |
| Severe / symptomatic | Calcium gluconate 1–2g IV bolus → continuous infusion 0.5–1.5 mg/kg/hr |
| Cardiac arrest / severe | Calcium CHLORIDE 1g IV push (central line only — 3× more elemental Ca) |
⚠️ Always check Mg first. HypoMg → impaired PTH → refractory hypoCa. Correct albumin: add 0.8 per 1g albumin below 4.0. CaCl via central line ONLY (tissue necrosis if infiltrates). Ca gluconate safe peripherally.
🔴 Sodium (Na⁺) — Correction Limits
See Hyponatremia topic for full management
≤ 8
mEq/L rise in 24h
(max safe correction rate)
(max safe correction rate)
≤ 10–12
mEq/L rise in 48h
(be even more cautious if chronic)
(be even more cautious if chronic)
ODS
Osmotic demyelination syndrome
if corrected too fast
if corrected too fast
Hyponatremia: NS for hypovolemic, fluid restrict for euvolemic (SIADH), diuretics for hypervolemic. HTS 3% for severe symptoms (seizure, coma) — 100 mL bolus, recheck Na in 2h. Hypernatremia: Free water deficit = 0.6 × wt × ((Na/140) − 1). Replace slowly — max correction 10 mEq/24h to avoid cerebral edema.
Quick Reference
💧 IV Fluids Guide
Which fluid, when, and why. The most common order you'll write — make sure you understand what each fluid does.
| Fluid | Na⁺ | Cl⁻ | K⁺ | Buffer | Osmolarity | When to Use |
|---|---|---|---|---|---|---|
| Normal Saline (0.9% NaCl) | 154 | 154 | 0 | None | 308 | Volume resuscitation, hyponatremia, hyperkalemia. Caution: hyperchloremic metabolic acidosis and increased AKI risk with large volumes (SMART, 2018 — NS increased composite of death, new RRT, or persistent renal dysfunction vs balanced crystalloids). |
| Lactated Ringer's (LR) | 130 | 109 | 4 | Lactate 28 | 273 | Preferred resuscitation fluid. More physiologic. Less acidosis than NS. Contains 4 mEq/L K⁺ but this is clinically insignificant — LR actually lowers serum K⁺ better than NS because NS causes acidosis-driven K⁺ shift (SMART, 2018). Safe in hyperkalemia. |
| D5W (5% Dextrose) | 0 | 0 | 0 | None | 252 | Free water. Hypernatremia correction, medication diluent. NOT for resuscitation (distributes to total body water). |
| D5 1/2 NS | 77 | 77 | 0 | None | 406 | Maintenance fluid. Provides free water + some Na. Common maintenance choice. |
| D5 NS | 154 | 154 | 0 | None | 560 | Maintenance with higher Na. DKA (when glucose < 250, switch from NS to D5NS). |
| 3% Hypertonic Saline | 513 | 513 | 0 | None | 1026 | Severe symptomatic hyponatremia (seizure, coma). 100 mL bolus. Also for ↑ ICP in TBI. Often needs central line. |
| Albumin 5% | 145 | — | — | — | 290 | Volume expansion in cirrhosis (post-LVP, SBP). Sepsis (controversial). Oncotic pressure support. |
| Albumin 25% | 145 | — | — | — | 1500 | Concentrated — pulls fluid intravascularly. Diuretic-resistant edema with hypoalbuminemia. Give with furosemide (Lasix). |
📐 Maintenance Fluid Rate
4-2-1 Rule (Holliday-Segar):
• First 10 kg: 4 mL/kg/hr
• Next 10 kg: 2 mL/kg/hr
• Each kg above 20: 1 mL/kg/hr
Example (70 kg):
(10×4) + (10×2) + (50×1) = 40 + 20 + 50 = 110 mL/hr
Common shortcut: Most adults get 75–125 mL/hr maintenance. Adjust for heart failure (restrict), renal failure, and ongoing losses.
• First 10 kg: 4 mL/kg/hr
• Next 10 kg: 2 mL/kg/hr
• Each kg above 20: 1 mL/kg/hr
Example (70 kg):
(10×4) + (10×2) + (50×1) = 40 + 20 + 50 = 110 mL/hr
Common shortcut: Most adults get 75–125 mL/hr maintenance. Adjust for heart failure (restrict), renal failure, and ongoing losses.
🚫 Common Mistakes
• NS for everything → hyperchloremic acidosis. Use LR when possible.
• D5W for resuscitation → it's free water, not volume expander. Only 1/12 stays intravascular.
• Forgetting K⁺ in maintenance → add 20 mEq KCl/L to maintenance fluids (unless hyperkalemic or renal failure).
• Running maintenance in volume-overloaded CHF → if they're eating, they don't need IV fluids!
• Not adjusting for renal failure → reduce rate. They can't clear the volume.
• LR in hyperkalemia → contains 4 mEq/L K⁺. Use NS instead.
• D5W for resuscitation → it's free water, not volume expander. Only 1/12 stays intravascular.
• Forgetting K⁺ in maintenance → add 20 mEq KCl/L to maintenance fluids (unless hyperkalemic or renal failure).
• Running maintenance in volume-overloaded CHF → if they're eating, they don't need IV fluids!
• Not adjusting for renal failure → reduce rate. They can't clear the volume.
• LR in hyperkalemia → contains 4 mEq/L K⁺. Use NS instead.
Quick Reference
🩸 Transfusion Guide
Blood product thresholds, transfusion reactions, and special considerations. Know when to transfuse and when to hold.
| Product | Threshold | Expected Response | Key Notes |
|---|---|---|---|
| pRBCs | Hgb < 7 (general) Hgb < 8 (ACS, symptomatic cardiac) Hgb < 10 (some surgical/active bleed) | 1 unit ↑ Hgb ~1 g/dL | Restrictive (Hgb < 7) is preferred over liberal in most patients. TRICC, 1999; FOCUS, 2011 |
| Platelets | < 10K (prophylactic) < 20K (fever/infection) < 50K (active bleeding/procedure) < 100K (neurosurgery/CNS procedure) | 1 unit ↑ plt ~30–50K | Do NOT transfuse in TTP/HIT (worsens thrombosis). In ITP, only if active severe bleeding. |
| FFP | Active bleeding + INR > 1.5 Urgent warfarin reversal (with PCC) DIC with bleeding Massive transfusion (1:1:1) | ~10–15 mL/kg | NOT for correcting mildly elevated INR without bleeding. Liver disease INR is NOT an indication for FFP alone. |
| Cryoprecipitate | Fibrinogen < 150 (DIC) Fibrinogen < 200 (MTP) Uremic bleeding (contains vWF) | 10 units ↑ fibrinogen ~70 mg/dL | Contains: fibrinogen, factor VIII, vWF, factor XIII. Use for fibrinogen replacement primarily. |
🚨 Transfusion Reactions
Febrile Non-Hemolytic (most common)
→ Fever, chills. Stop transfusion, acetaminophen (Tylenol). Rule out hemolytic.
Allergic (urticarial)
→ Hives, itching. Stop, diphenhydramine (Benadryl) 25-50mg IV. If mild and resolves, can restart slowly.
Anaphylaxis
→ Hypotension, bronchospasm, angioedema. STOP. Epinephrine (Adrenalin) 0.3mg IM. IgA deficiency is classic risk factor.
Acute Hemolytic (most dangerous)
→ ABO incompatibility. Fever, flank pain, dark urine, DIC. STOP IMMEDIATELY. NS bolus, send type & screen recollection. Can be fatal.
TRALI (Transfusion-Related Acute Lung Injury)
→ Acute respiratory distress within 6h. Bilateral infiltrates. No volume overload. Supportive care. #1 cause of transfusion-related death.
TACO (Transfusion-Associated Circulatory Overload)
→ Dyspnea, HTN, pulmonary edema. Volume overload. Diuretics. Transfuse slowly in CHF/elderly.
→ Fever, chills. Stop transfusion, acetaminophen (Tylenol). Rule out hemolytic.
Allergic (urticarial)
→ Hives, itching. Stop, diphenhydramine (Benadryl) 25-50mg IV. If mild and resolves, can restart slowly.
Anaphylaxis
→ Hypotension, bronchospasm, angioedema. STOP. Epinephrine (Adrenalin) 0.3mg IM. IgA deficiency is classic risk factor.
Acute Hemolytic (most dangerous)
→ ABO incompatibility. Fever, flank pain, dark urine, DIC. STOP IMMEDIATELY. NS bolus, send type & screen recollection. Can be fatal.
TRALI (Transfusion-Related Acute Lung Injury)
→ Acute respiratory distress within 6h. Bilateral infiltrates. No volume overload. Supportive care. #1 cause of transfusion-related death.
TACO (Transfusion-Associated Circulatory Overload)
→ Dyspnea, HTN, pulmonary edema. Volume overload. Diuretics. Transfuse slowly in CHF/elderly.
📋 Practical Tips
Before transfusing:
• Type & screen on file? (valid 72h at most institutions)
• Consent obtained?
• Two-nurse verification at bedside (check patient ID, blood band, product label)
• Pre-medicate with acetaminophen ± diphenhydramine if prior reactions
During transfusion:
• Vitals at: baseline, 15 min, 30 min, 1 hour, completion
• pRBCs: infuse over 1–2 hours (max 4 hours per unit)
• Give furosemide (Lasix) 20mg IV between units if CHF risk
• STOP transfusion for: fever > 1°C, rigors, hypotension, chest pain, dyspnea, dark urine
Special situations:
• Jehovah's Witness: Respect refusal. Document clearly. Cell saver may be acceptable.
• Massive transfusion: 1:1:1 ratio. Calcium with every 4 units. Warm products.
• Irradiated products: Required for immunocompromised (BMT, Hodgkin, intrauterine transfusion) — prevents TA-GVHD
• CMV-negative: For CMV-negative transplant recipients and pregnant women
• Type & screen on file? (valid 72h at most institutions)
• Consent obtained?
• Two-nurse verification at bedside (check patient ID, blood band, product label)
• Pre-medicate with acetaminophen ± diphenhydramine if prior reactions
During transfusion:
• Vitals at: baseline, 15 min, 30 min, 1 hour, completion
• pRBCs: infuse over 1–2 hours (max 4 hours per unit)
• Give furosemide (Lasix) 20mg IV between units if CHF risk
• STOP transfusion for: fever > 1°C, rigors, hypotension, chest pain, dyspnea, dark urine
Special situations:
• Jehovah's Witness: Respect refusal. Document clearly. Cell saver may be acceptable.
• Massive transfusion: 1:1:1 ratio. Calcium with every 4 units. Warm products.
• Irradiated products: Required for immunocompromised (BMT, Hodgkin, intrauterine transfusion) — prevents TA-GVHD
• CMV-negative: For CMV-negative transplant recipients and pregnant women
Quick Reference
💓 ECG Pattern Guide
High-yield ECG patterns every resident must recognize. Organized by clinical urgency. When in doubt, compare to prior ECGs and get a 12-lead.
🚨 Emergent — Act Immediately
STEMI
ST-Elevation Myocardial Infarction
Pattern: ST elevation ≥ 1mm in ≥ 2 contiguous leads (≥ 2mm in V1-V3 for men)
Morphology: Concave-up ("tombstone") or convex-up ST elevation with reciprocal ST depression in opposite leads
Localisation:
• II, III, aVF → Inferior (RCA)
• V1-V4 → Anterior (LAD)
• I, aVL, V5-V6 → Lateral (LCx)
• V1-V2 depression → Posterior (get V7-V9)
• V3R-V4R elevation → RV infarct (avoid nitrates/volume depletion)
Action: Activate cath lab. ASA 325mg chewed. Heparin. Door-to-balloon < 90 min.
Morphology: Concave-up ("tombstone") or convex-up ST elevation with reciprocal ST depression in opposite leads
Localisation:
• II, III, aVF → Inferior (RCA)
• V1-V4 → Anterior (LAD)
• I, aVL, V5-V6 → Lateral (LCx)
• V1-V2 depression → Posterior (get V7-V9)
• V3R-V4R elevation → RV infarct (avoid nitrates/volume depletion)
Action: Activate cath lab. ASA 325mg chewed. Heparin. Door-to-balloon < 90 min.
Ventricular Tachycardia (VT)
Wide complex, regular, ≥ 3 consecutive beats
Pattern: Wide QRS (> 120ms), regular, rate 150-250 bpm
Features favouring VT over SVT with aberrancy:
• AV dissociation (P waves marching independently)
• Capture/fusion beats
• Concordance (all precordial QRS same direction)
• Very wide QRS (> 160ms)
• Northwest axis (extreme right axis deviation)
Rule: Wide complex tachycardia = VT until proven otherwise, especially if age > 50 or structural heart disease.
Action: Stable → amiodarone (Cordarone) 150mg IV. Unstable → synchronized cardioversion. Pulseless → defibrillate.
Features favouring VT over SVT with aberrancy:
• AV dissociation (P waves marching independently)
• Capture/fusion beats
• Concordance (all precordial QRS same direction)
• Very wide QRS (> 160ms)
• Northwest axis (extreme right axis deviation)
Rule: Wide complex tachycardia = VT until proven otherwise, especially if age > 50 or structural heart disease.
Action: Stable → amiodarone (Cordarone) 150mg IV. Unstable → synchronized cardioversion. Pulseless → defibrillate.
Hyperkalemia
Progressive changes as K⁺ rises
Progression:
• K⁺ 5.5-6.5: Peaked T waves (tall, narrow, symmetric — earliest sign)
• K⁺ 6.5-7.5: Prolonged PR → flattened P waves → widened QRS
• K⁺ 7.5-8.0: Sine wave pattern (QRS merges with T wave)
• K⁺ > 8.0: VF → asystole
Action: Calcium gluconate 1g IV immediately (stabilises membrane). Then insulin + D50 to shift K⁺. See Hyperkalemia topic for full protocol.
• K⁺ 5.5-6.5: Peaked T waves (tall, narrow, symmetric — earliest sign)
• K⁺ 6.5-7.5: Prolonged PR → flattened P waves → widened QRS
• K⁺ 7.5-8.0: Sine wave pattern (QRS merges with T wave)
• K⁺ > 8.0: VF → asystole
Action: Calcium gluconate 1g IV immediately (stabilises membrane). Then insulin + D50 to shift K⁺. See Hyperkalemia topic for full protocol.
Complete Heart Block (3rd Degree)
No atrial impulses conduct to ventricles
Pattern: P waves and QRS complexes completely independent (AV dissociation). Regular P-P intervals. Regular R-R intervals. But NO relationship between them.
Escape rhythm:
• Junctional escape (narrow QRS, 40-60 bpm) → more stable
• Ventricular escape (wide QRS, 20-40 bpm) → unstable, high risk of asystole
Action: Atropine 1mg IV (may not work if infranodal). Transcutaneous pacing. Cardiology for transvenous pacer. Dopamine or epinephrine drip as bridge.
Escape rhythm:
• Junctional escape (narrow QRS, 40-60 bpm) → more stable
• Ventricular escape (wide QRS, 20-40 bpm) → unstable, high risk of asystole
Action: Atropine 1mg IV (may not work if infranodal). Transcutaneous pacing. Cardiology for transvenous pacer. Dopamine or epinephrine drip as bridge.
⚠️ Urgent — Requires Prompt Attention
Wellens Syndrome
Critical LAD stenosis — will STEMI if missed
Pattern: Deep symmetric T-wave inversions (Type A, more common) or biphasic T waves (Type B) in V2-V3 (± V1, V4-V6)
Key: Seen during pain-FREE interval (not during active chest pain). During pain, ST may be elevated.
Critical point: Do NOT stress test — will STEMI on the treadmill. Needs cath.
Action: Admit, anticoagulate, cardiology consult for cath. Medical management until intervention.
Key: Seen during pain-FREE interval (not during active chest pain). During pain, ST may be elevated.
Critical point: Do NOT stress test — will STEMI on the treadmill. Needs cath.
Action: Admit, anticoagulate, cardiology consult for cath. Medical management until intervention.
Brugada Syndrome
Risk of sudden cardiac death in structurally normal heart
Type 1 (diagnostic): Coved ST elevation ≥ 2mm in V1-V3 with T-wave inversion. "Shark fin" morphology.
Type 2 (suggestive): Saddleback ST elevation in V1-V3. Not diagnostic alone — needs provocation test (ajmaline/procainamide).
Key features: Young male, Asian descent, family history of sudden death, syncope, nocturnal agonal breathing.
Action: EP consult. ICD is the only proven therapy (no drug prevents VF in Brugada). Avoid fever (unmasks pattern), avoid Class I antiarrhythmics.
Type 2 (suggestive): Saddleback ST elevation in V1-V3. Not diagnostic alone — needs provocation test (ajmaline/procainamide).
Key features: Young male, Asian descent, family history of sudden death, syncope, nocturnal agonal breathing.
Action: EP consult. ICD is the only proven therapy (no drug prevents VF in Brugada). Avoid fever (unmasks pattern), avoid Class I antiarrhythmics.
Prolonged QTc
Risk of Torsades de Pointes
Normal: < 440ms (men), < 460ms (women)
Concerning: > 480ms
Dangerous: > 500ms → high risk for Torsades de Pointes (TdP)
Common offenders: Haloperidol (Haldol), ondansetron (Zofran), fluoroquinolones, azithromycin (Zithromax), methadone, amiodarone (Cordarone), antipsychotics, hypoK, hypoMg
Action: Stop offending drug. Replete K⁺ > 4.0, Mg²⁺ > 2.0. If TdP occurs: IV magnesium 2g bolus + overdrive pacing (↑ HR shortens QT).
Concerning: > 480ms
Dangerous: > 500ms → high risk for Torsades de Pointes (TdP)
Common offenders: Haloperidol (Haldol), ondansetron (Zofran), fluoroquinolones, azithromycin (Zithromax), methadone, amiodarone (Cordarone), antipsychotics, hypoK, hypoMg
Action: Stop offending drug. Replete K⁺ > 4.0, Mg²⁺ > 2.0. If TdP occurs: IV magnesium 2g bolus + overdrive pacing (↑ HR shortens QT).
PE / Right Heart Strain
Acute right ventricular pressure overload
Classic (but uncommon): S1Q3T3 — deep S in lead I, Q wave + T inversion in lead III. Present in only ~20% of PE.
More common findings:
• Sinus tachycardia (#1 finding — most sensitive)
• Right axis deviation
• T-wave inversions in V1-V4 (RV strain pattern)
• New RBBB or incomplete RBBB
• Atrial fibrillation (new onset)
Remember: A normal ECG does NOT rule out PE. ECG is often normal in PE.
Action: If PE suspected → Wells score → D-dimer or CT-PA. See PE topic.
More common findings:
• Sinus tachycardia (#1 finding — most sensitive)
• Right axis deviation
• T-wave inversions in V1-V4 (RV strain pattern)
• New RBBB or incomplete RBBB
• Atrial fibrillation (new onset)
Remember: A normal ECG does NOT rule out PE. ECG is often normal in PE.
Action: If PE suspected → Wells score → D-dimer or CT-PA. See PE topic.
📋 Important Patterns to Recognise
Atrial Fibrillation
Irregularly irregular — most common sustained arrhythmia
Pattern: No P waves (fibrillatory baseline), irregularly irregular R-R intervals, narrow QRS (unless aberrancy/BBB)
Distinguish from:
• Atrial flutter: Regular, sawtooth P waves (especially II, III, aVF), often 150 bpm (2:1 block)
• MAT: ≥ 3 different P-wave morphologies, irregular, associated with COPD/hypoxia
Action: Rate control (metoprolol (Lopressor) or diltiazem (Cardizem)). CHA₂DS₂-VASc for anticoagulation. See Afib topic.
Distinguish from:
• Atrial flutter: Regular, sawtooth P waves (especially II, III, aVF), often 150 bpm (2:1 block)
• MAT: ≥ 3 different P-wave morphologies, irregular, associated with COPD/hypoxia
Action: Rate control (metoprolol (Lopressor) or diltiazem (Cardizem)). CHA₂DS₂-VASc for anticoagulation. See Afib topic.
Pericarditis
Diffuse ST elevation — NOT a STEMI
Pattern: Diffuse concave-up ST elevation in nearly ALL leads + PR depression (especially II) + ST depression in aVR
Distinguish from STEMI:
• Pericarditis: diffuse (many territories), NO reciprocal changes, PR depression, concave-up
• STEMI: localised (one territory), reciprocal changes present, often convex-up
Key: PR depression in lead II is nearly pathognomonic for pericarditis.
Action: NSAIDs + colchicine (Colcrys). Echo to rule out effusion/tamponade. Do NOT give thrombolytics (not a STEMI!).
Distinguish from STEMI:
• Pericarditis: diffuse (many territories), NO reciprocal changes, PR depression, concave-up
• STEMI: localised (one territory), reciprocal changes present, often convex-up
Key: PR depression in lead II is nearly pathognomonic for pericarditis.
Action: NSAIDs + colchicine (Colcrys). Echo to rule out effusion/tamponade. Do NOT give thrombolytics (not a STEMI!).
Heart Blocks (1st, 2nd degree)
AV conduction delays
1st degree: Prolonged PR > 200ms. Every P conducts. Usually benign — no treatment.
2nd degree Type I (Wenckebach): Progressive PR prolongation → dropped beat → cycle repeats. Usually nodal. Often benign.
2nd degree Type II (Mobitz II): Constant PR interval with sudden dropped QRS (no warning). Infranodal. High risk of progressing to complete heart block. Needs pacemaker.
Key rule: Wenckebach = watch. Mobitz II = pacer.
2nd degree Type I (Wenckebach): Progressive PR prolongation → dropped beat → cycle repeats. Usually nodal. Often benign.
2nd degree Type II (Mobitz II): Constant PR interval with sudden dropped QRS (no warning). Infranodal. High risk of progressing to complete heart block. Needs pacemaker.
Key rule: Wenckebach = watch. Mobitz II = pacer.
Bundle Branch Blocks
QRS > 120ms — which bundle is blocked?
RBBB: rsR' ("bunny ears") in V1-V2, wide S in I/V6. Mnemonic: "MaRRoW" — V1 has R (tall R'), V6 has W (wide S).
LBBB: Broad notched R in I/V6, deep QS or rS in V1. Mnemonic: "WiLLiaM" — V1 has W (QS), V6 has M (notched R).
Clinical significance:
• RBBB: Can be normal. New RBBB in ACS/PE → concerning.
• LBBB: Almost always pathological. New LBBB + chest pain → treat as STEMI equivalent (Sgarbossa criteria). Old LBBB makes STEMI diagnosis difficult.
Sgarbossa criteria (STEMI in LBBB): Concordant ST elevation ≥ 1mm (5 pts), concordant ST depression ≥ 1mm in V1-V3 (3 pts), discordant ST elevation ≥ 5mm (2 pts). ≥ 3 pts → STEMI.
LBBB: Broad notched R in I/V6, deep QS or rS in V1. Mnemonic: "WiLLiaM" — V1 has W (QS), V6 has M (notched R).
Clinical significance:
• RBBB: Can be normal. New RBBB in ACS/PE → concerning.
• LBBB: Almost always pathological. New LBBB + chest pain → treat as STEMI equivalent (Sgarbossa criteria). Old LBBB makes STEMI diagnosis difficult.
Sgarbossa criteria (STEMI in LBBB): Concordant ST elevation ≥ 1mm (5 pts), concordant ST depression ≥ 1mm in V1-V3 (3 pts), discordant ST elevation ≥ 5mm (2 pts). ≥ 3 pts → STEMI.
Digoxin Effect vs Toxicity
Know the difference — one is expected, one is dangerous
Digoxin effect (therapeutic): "Salvador Dali moustache" — downsloping ST depression with scooped/sagging morphology. Shortened QT. This is expected and NOT toxic.
Digoxin toxicity:
• Virtually ANY arrhythmia (classic: regularised Afib, bidirectional VT, accelerated junctional rhythm, PAT with block)
• Nausea, vomiting, visual disturbances (yellow halos)
• Risk factors: hypoK, hypoMg, renal failure, advanced age
Action for toxicity: Hold digoxin. Check level + K⁺ + Mg²⁺. Digoxin-specific antibody (Digibind/DigiFab) if haemodynamically unstable, life-threatening arrhythmia, or K⁺ > 5.0.
Digoxin toxicity:
• Virtually ANY arrhythmia (classic: regularised Afib, bidirectional VT, accelerated junctional rhythm, PAT with block)
• Nausea, vomiting, visual disturbances (yellow halos)
• Risk factors: hypoK, hypoMg, renal failure, advanced age
Action for toxicity: Hold digoxin. Check level + K⁺ + Mg²⁺. Digoxin-specific antibody (Digibind/DigiFab) if haemodynamically unstable, life-threatening arrhythmia, or K⁺ > 5.0.
Hypothermia (Osborn/J Waves)
Pathognomonic for hypothermia
Pattern: Positive deflection at the J-point (junction of QRS and ST segment). Amplitude increases as temperature drops.
Other findings: Bradycardia, prolonged intervals (PR, QRS, QT), atrial fibrillation, muscle tremor artifact (shivering)
Key: At core temp < 28°C → high risk of VF. Osborn waves resolve with rewarming. NOT an indication for antiarrhythmics.
Action: Rewarm. See Hypothermia topic. "No one is dead until warm and dead."
Other findings: Bradycardia, prolonged intervals (PR, QRS, QT), atrial fibrillation, muscle tremor artifact (shivering)
Key: At core temp < 28°C → high risk of VF. Osborn waves resolve with rewarming. NOT an indication for antiarrhythmics.
Action: Rewarm. See Hypothermia topic. "No one is dead until warm and dead."
📐 Quick Reference — Intervals & Axes
| Parameter | Normal | Abnormal | Think... |
|---|---|---|---|
| Heart Rate | 60-100 bpm | < 60 = bradycardia, > 100 = tachycardia | 300 / (# large boxes between R-R) |
| PR Interval | 120-200 ms | > 200 = 1st degree AV block. Short PR = WPW or junctional | 3-5 small boxes |
| QRS Duration | < 120 ms | > 120 = BBB, ventricular rhythm, hyperK, or pre-excitation | < 3 small boxes |
| QTc | < 440 (M) / < 460 (F) | > 500 = high Torsades risk | QTc = QT / √RR. Use calc. |
| Axis | -30° to +90° | Left axis: -30° to -90° (LVH, LAFB). Right axis: +90° to +180° (RVH, PE, LPFB) | Lead I and aVF both upright = normal |
ECG Systematic Approach: Rate → Rhythm → Axis → Intervals (PR, QRS, QT) → ST segment/T waves → Compare to prior. Never skip steps — pattern recognition fails when you're tired. Systematic review catches what your eyes miss.
Quick Reference
🧪 Lab Interpretation Guide
Comprehensive quick reference for common lab abnormalities, workup algorithms, and interpretation pearls. Organized by lab category for rapid bedside use.
1. CBC Abnormalities
| Lab | High | Low | Key Differentials |
|---|---|---|---|
| WBC | >11K: infection, steroids, stress, CML, leukemoid reaction | <4K: viral, meds (chemo, immunosuppressants), aplastic anemia, SLE, HIV | Bandemia >10% = left shift → suggests bacterial infection |
| Hemoglobin | >16.5 M / 15 F: polycythemia vera, chronic hypoxia, dehydration | See anemia workup below | MCV guides anemia workup |
| Platelets | >450K: reactive (infection/inflammation/iron deficiency), CML, ET | <150K: ITP*, TTP*/HUS*, DIC*, HIT*, liver disease, meds, pseudothrombocytopenia *ITP = Immune Thrombocytopenic Purpura *TTP = Thrombotic Thrombocytopenic Purpura *HUS = Hemolytic Uremic Syndrome *DIC = Disseminated Intravascular Coagulation *HIT = Heparin-Induced Thrombocytopenia | ALWAYS check smear if <50K. Rule out pseudothrombocytopenia (EDTA clumping) |
2. Anemia Workup (by MCV)
| MCV Category | Differential Diagnosis |
|---|---|
| Microcytic (<80) | Iron deficiency (most common), thalassemia, anemia of chronic disease, sideroblastic, lead poisoning |
| Normocytic (80–100) | Acute blood loss, ACD, CKD, mixed deficiency, bone marrow failure |
| Macrocytic (>100) | B12/folate deficiency, alcohol, liver disease, hypothyroidism, MDS, meds (methotrexate, AZT) |
Iron Studies Interpretation
| Condition | Ferritin | TIBC | Iron | % Sat |
|---|---|---|---|---|
| Iron deficiency | ↓ (<30) | ↑ | ↓ | ↓ (<20%) |
| ACD | ↑ or normal | ↓ | ↓ | Normal or ↓ |
| Thalassemia | Normal | Normal | Normal | Normal |
| Sideroblastic | ↑ | Normal | ↑ | ↑ |
3. Hemolysis Workup
| Finding | Expected in Hemolysis |
|---|---|
| LDH | ↑↑ (released from lysed RBCs) |
| Haptoglobin | ↓↓ (binds free hemoglobin → consumed) |
| Indirect bilirubin | ↑ (from heme breakdown) |
| Reticulocyte count | ↑ (bone marrow compensating) |
| Peripheral smear | Schistocytes (MAHA*), spherocytes (autoimmune), sickle cells *MAHA = Microangiopathic Hemolytic Anemia |
| Direct Coombs (DAT) | + = autoimmune hemolysis, − = non-immune (TTP, DIC, mechanical) |
4. Liver Panel
| Pattern | AST/ALT | Alk Phos | Bilirubin | Interpretation |
|---|---|---|---|---|
| Hepatocellular | ↑↑↑ (>1000) | Normal / mild ↑ | Variable | Viral hepatitis, acetaminophen, ischemic hepatitis, autoimmune |
| Cholestatic | Mild ↑ | ↑↑↑ | ↑ (conjugated) | Biliary obstruction, PBC, PSC, drugs |
| Infiltrative | Normal / mild ↑ | ↑↑ | Normal | Malignancy, granulomatous disease, amyloid |
| Mixed | ↑↑ | ↑↑ | ↑ | Drug-induced, sepsis |
Liver Panel Pearls: AST:ALT >2:1 = alcoholic liver disease (De Ritis ratio). ALT > AST in most other causes. AST/ALT >1000 = “shock liver,” acetaminophen, viral, Wilson’s, autoimmune.
5. Renal Panel
| Lab / Ratio | Significance |
|---|---|
| BUN/Cr ratio >20:1 | Pre-renal azotemia, GI bleed (protein load), high-protein diet |
| BUN/Cr ratio <10:1 | Intrinsic renal, liver disease, malnutrition |
| FENa* <1% *FENa = Fractional Excretion of Sodium | Pre-renal (kidneys retaining Na) |
| FENa >2% | Intrinsic renal (ATN* — kidneys can’t retain Na) *ATN = Acute Tubular Necrosis |
| FEUrea* <35% *FEUrea = Fractional Excretion of Urea | Pre-renal (use if on diuretics — FENa unreliable) |
| Urine Na <20 | Pre-renal |
| Urine Na >40 | Intrinsic renal or SIADH |
6. Coagulation
| Lab | Measures | Causes of Prolongation |
|---|---|---|
| PT/INR | Extrinsic pathway (VII) → common | Warfarin, liver disease, vitamin K deficiency, DIC |
| aPTT | Intrinsic pathway (XII, XI, IX, VIII) | Heparin, hemophilia A/B, lupus anticoagulant, DIC |
| Both ↑ | Common pathway (X, V, II, fibrinogen) | DIC, liver failure, massive transfusion |
| Mixing study corrects | Factor deficiency | Replace the missing factor |
| Mixing study doesn’t correct | Inhibitor present | Lupus anticoagulant, factor inhibitor |
DIC Labs: ↑PT, ↑aPTT, ↓fibrinogen (<200), ↑D-dimer, ↓platelets, schistocytes on smear.
7. Cardiac Biomarkers
| Marker | Elevated In | Interpretation Pearls |
|---|---|---|
| Troponin | MI, PE, myocarditis, HF, renal failure, sepsis, demand ischemia | Rise-fall pattern with delta = acute MI. Chronically elevated = CKD/HF |
| BNP / NT-proBNP | HF, cor pulmonale, PE, AF, sepsis | BNP >400 or NT-proBNP >900 strongly suggests HF. Age-adjusted cutoffs for NT-proBNP. Falsely LOW in obesity |
| CK / CK-MB | MI, rhabdomyolysis, myositis, strenuous exercise | Less specific than troponin for MI. CK >5× ULN in rhabdo |
8. Inflammatory Markers
| Marker | Key Points | High-Yield Values |
|---|---|---|
| ESR | Nonspecific. ↑ in infection, autoimmune, malignancy, anemia, pregnancy | Very high (>100): endocarditis, osteomyelitis, TB, myeloma, temporal arteritis |
| CRP | More specific than ESR. Rises/falls faster | ↑ in infection, inflammation. <10 = mild, >100 = likely bacterial infection |
| Procalcitonin | More specific for BACTERIAL infection | <0.25 = unlikely bacterial, >0.5 = likely bacterial. Guides antibiotic de-escalation. NOT elevated in viral or autoimmune |
| Ferritin | Acute phase reactant — ↑ in inflammation regardless of iron status | Very high (>1000): HLH, adult-onset Still’s, liver disease, iron overload |
| LDH | Nonspecific tissue damage marker | ↑ in hemolysis, lymphoma, liver disease, PE, PJP, TLS |
9. Thyroid Function Tests
| TSH | Free T4 | Diagnosis |
|---|---|---|
| ↑ | ↓ | Primary hypothyroidism |
| ↓ | ↑ | Primary hyperthyroidism (Graves’, toxic nodule, thyroiditis) |
| ↓ | ↓ | Central hypothyroidism (pituitary / hypothalamic) |
| ↓ | Normal | Subclinical hyperthyroidism or sick euthyroid |
| ↑ | Normal | Subclinical hypothyroidism |
10. ABG Interpretation (Step-by-Step)
| Step | Action |
|---|---|
| 1 | pH <7.35 = acidemia, pH >7.45 = alkalemia |
| 2 | Check PaCO2: if same direction as pH → respiratory cause |
| 3 | Check HCO3: if opposite direction as pH → metabolic cause |
| 4 | Check compensation (Winter’s formula for metabolic acidosis: expected PaCO2 = 1.5 × HCO3 + 8 ± 2) |
| 5 | If metabolic acidosis: check anion gap (Na − Cl − HCO3, normal 12 ± 2) |
| 6 | If AG elevated: check delta-delta ratio (ΔAG / ΔHCO3). >2 = concurrent metabolic alkalosis. <1 = concurrent NAGMA* *NAGMA = Non-Anion Gap Metabolic Acidosis |
AG Metabolic Acidosis (MUDPILES): Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates
Non-AG Metabolic Acidosis (HARDUP): Hyperalimentation, Addison’s, RTA, Diarrhea, Ureteral diversion, Pancreatic fistula
Learning Library
🎬 Media Library
Movies, documentaries, TV series, and books for medical professionals. Unwind after a shift or level up your financial literacy.
📚 Medical Finance Books
Why this matters: Medical school doesn't teach personal finance, but the decisions you make during residency — student loan strategy, disability insurance, retirement accounts — can mean hundreds of thousands of dollars over your career.
The White Coat Investor
James Dahle, MD
The bible of physician finance. Student loans, investing, insurance, retirement, and tax strategies. Start here.
Financial Residency
Ryan Inman
Written for residents. Budgeting on a resident salary, PSLF vs refinance, building a foundation early.
The Physician Philosopher's Guide
Jimmy Turner, MD
Finance meets burnout and intentional living. The "why" behind financial independence.
The Psychology of Money
Morgan Housel
Behavior — not knowledge — drives financial outcomes. Short chapters, easy read on call.
I Will Teach You to Be Rich
Ramit Sethi
6-week program to automate your finances. Simple system for people who don't want to think about money.
The Millionaire Next Door
Thomas Stanley
High income doesn't equal wealth — spending habits do. A reality check for future attendings.
Die with Zero
Bill Perkins
Challenges "save everything." Optimize life experiences, not just net worth.
Rich Dad Poor Dad
Robert Kiyosaki
Assets vs liabilities and financial literacy. Simple concepts med school never covers.
🎬 Movies
Patch Adams
1998 · Comedy Drama
Robin Williams as a med student who believes humor and compassion are the best medicine
Awakenings
1990 · Drama
Robin Williams and Robert De Niro — a neurologist discovers L-DOPA's effects on catatonic patients
The Doctor
1991 · Drama
A surgeon becomes a patient and learns empathy. Required viewing for bedside manner
Wit
2001 · Drama
Emma Thompson as a professor with ovarian cancer. Devastating portrayal of the patient experience
Something the Lord Made
2004 · True Story
First blue baby operation — Vivien Thomas and Alfred Blalock at Johns Hopkins
Philadelphia
1993 · Drama
Tom Hanks as a lawyer with AIDS fighting discrimination. Landmark film for HIV awareness
Lorenzo's Oil
1992 · True Story
Parents of a boy with ALD develop an experimental treatment. The power of patient advocacy
Gifted Hands: The Ben Carson Story
2009 · True Story
Cuba Gooding Jr. as neurosurgeon Ben Carson — from struggling student to pioneering the first successful separation of conjoined twins joined at the head
📽️ Documentaries
Extremis
2016 · Netflix
ICU end-of-life decisions filmed in real time. Essential for goals-of-care conversations
Bleeding Edge
2018 · Netflix
Medical device industry and patient safety. Eye-opening
Lenox Hill
2020 · Netflix
Docuseries following 4 physicians at Lenox Hill Hospital in NYC
The Surgeon's Cut
2020 · Netflix
4 pioneering surgeons share their personal stories and groundbreaking procedures
The First Year
2001 · Documentary
Follows 7 interns through their first year of residency. Raw and real
📺 TV Series
Scrubs
2001–2010 · Comedy
The most accurate portrayal of residency culture. Comedy with surprisingly emotional depth
House MD
2004–2012 · Drama
Diagnostic reasoning at its best (and most dramatic). Great for clinical thinking
ER
1994–2009 · Drama
The gold standard for medical drama. More realistic than most modern shows
The Pitt
2025 · Drama
Noah Wyle returns to the ER. Real-time 15-hour shift in a Pittsburgh trauma center. The most realistic medical show since ER
Learning Library
🎙️ Channels & Podcasts
Curated medical education YouTube channels, podcasts, and websites. The best free resources for residents and medical students.
YouTube Channels
| Channel | Focus | Why It's Good |
|---|---|---|
| OnlineMedEd | General IM | High-yield video lectures covering all core clerkship and residency topics |
| Conan Liu MD | General IM | Internal medicine & residency — practical clinical content for residents |
| The ICU Channel | Critical Care | Ventilator management, hemodynamics, and ICU procedures explained clearly |
| Ninja Nerd | Board Review | Detailed pathophysiology lectures with excellent whiteboard diagrams |
Podcasts
| Podcast | Focus | Why It's Good |
|---|---|---|
| The Curbsiders | General IM | Deep dives on clinical topics with expert guests. The go-to IM podcast |
| EMCrit | Critical Care | Scott Weingart — gold standard for resuscitation and ICU education |
| Core IM | General IM | 5-Pearls format — concise clinical pearls. Perfect for commutes |
| Clinical Problem Solvers | General IM | Clinical reasoning podcast — diagnostic thinking step by step |
| Divine Intervention | Board Review | High-yield board review for Step 2/Step 3. Rapid-fire clinical pearls |
🌐 Websites & Blogs
| Website | Focus | Why It's Good |
|---|---|---|
| Life in the Fast Lane (LITFL) | Emergency Med | Massive free library — ECG interpretation, toxicology, critical care |
| UpToDate | General IM | The clinical decision support standard. Usually institutional access |
💡 Tip: Most residency programs provide free access to UpToDate, DynaMed, and AMBOSS. Check with your program coordinator. For everything else on this list — it's all free.
Learning Library
🔗 Resources
Essential medical education resources — guidelines, references, and tools every resident should bookmark.
📚 Recommended Books
Oxford Handbook of Clinical Medicine
Ian B. Wilkinson et al.
The classic pocket reference for medical students and junior doctors. Covers all major clinical topics in a concise, practical format
Guide to the Most Common Internal Medicine Workups and Diseases
Mitchell Edwards, D.O.
Evidence-based guide to common hospital-based workups and diseases seen in internal medicine. Perfect for residents and students on IM rotations
Marino's The ICU Book
Paul L. Marino, MD PhD FCCM
The gold standard ICU reference. Covers ventilators, hemodynamics, sepsis, nutrition, and every critical care topic in a clear, practical style
Harrison's Principles of Internal Medicine
Longo, Fauci, Kasper et al. · 22nd Edition
The definitive internal medicine textbook. Comprehensive pathophysiology, diagnosis, and management across every specialty
Pocket Medicine
Marc S. Sabatine · 9th Edition
The Massachusetts General Hospital handbook of internal medicine. Concise, high-yield reference that fits in your white coat pocket
📋 Clinical Guidelines
| Resource | What It Covers |
|---|---|
| Surviving Sepsis Campaign 2026 | Latest SSC guidelines — replaces qSOFA with NEWS/MEWS, updated fluid resuscitation, vasopressor, and corticosteroid recommendations |
| Surviving Sepsis Campaign 2021 | Prior SSC guidelines — sepsis bundles, 1-hour targets, and initial resuscitation framework |
| AHA/ACC Heart Failure Guidelines | 2022 HF guidelines including GDMT rapid initiation |
| KDIGO Guidelines | CKD, AKI, glomerulonephritis, and electrolyte management |
| IDSA Practice Guidelines | Infectious disease — CAP, HAP, C. diff, UTI, endocarditis, and more |
| ATS Guidelines | Pulmonary — COPD, asthma, ARDS, ILD, pulmonary hypertension |
| ADA Standards of Care | Diabetes management — inpatient, outpatient, DKA, insulin protocols |
🧰 Clinical Tools
| Tool | What It Does |
|---|---|
| MDCalc | Clinical calculators — MELD, Wells, CHA₂DS₂-VASc, CURB-65, and 500+ more |
| Epocrates | Drug reference — interactions, dosing, pill identification. Free version available |
| Micromedex | Comprehensive drug information — usually institutional access |
📚 Reference & Learning
| Resource | What It Is |
|---|---|
| UpToDate | The clinical decision support standard. Usually institutional access |
| PubMed | Search the medical literature. Free access to abstracts and many full-text articles |
💡 Tip: Most residency programs provide free access to UpToDate, DynaMed, Micromedex, and VisualDx. Check with your program coordinator — don't pay for something your institution already covers.
System
About RoundsRx
Free, evidence-based clinical toolkit — built by residents, for residents.
What is RoundsRx?
RoundsRx is a free, offline-capable clinical toolkit designed for the bedside. It covers 175 clinical topics across 15 rotations — from ICU protocols and cardiology to nephrology, heme/onc, and palliative care. Every topic includes a standardized structure: overview, workup, management, medications, monitoring, rounds presentation, and a printable one-pager.
Unlike traditional references, RoundsRx is built around how residents actually work — with pimp questions for rounds prep, clinical case scenarios, drug tables with brand names and dosing, trial citations with hover descriptions, and "updated practice" flags that highlight where old teaching has been overturned by new evidence.
Beyond clinical content, RoundsRx includes a media library with medical movies, documentaries, TV series, and recommended books for residents — plus a curated resources page with clinical guidelines, tools, and textbook recommendations — because residency is more than just medicine.
Latest Build
March 24, 2026
Version 3.2
Build Stats
175
Clinical Topics
1,777
Drug Entries
753
Pimp Questions
15
Rotation Pages
792
Trial Citations
34
Clinical Examples
263
Updated Practice Flags
23
Calculators
Key Features
🔍 Fuzzy Search
Typo-tolerant search across all topics, drugs, and 41 landmark trials. Results scroll directly to the matching content.
📚 Trial Citations
792 trial badges with hover tooltips explaining study design, key findings, and clinical impact.
🧠 Pimp Me Quiz
753 attending-style questions with reveal answers — including SSC 2026 guideline updates. Filter by rotation or topic. Perfect for pre-rounds prep.
🔄 Updated Practice
263 flags highlighting where old teaching has been overturned — so you don't cite outdated evidence on rounds.
📋 Clinical Cases
34 step-by-step bedside scenarios with timelines, drug choices, and teaching points at each decision point.
🌙 Dark Mode + Offline
Full dark mode support. Service worker enables offline access — works in the hospital even without WiFi.
🧮 23 Calculators
Organized by rotation — Nephrology, Cardiology, Pulmonology, ICU, GI, General. CrCl, MELD, CHA₂DS₂-VASc, Wells, NEWS/MEWS, and more.
🖨️ Print-Ready
Every topic has a one-pager designed for printing. QR poster for resident lounges. Optimized print styles.
Standard Tabs (All Topics)
🔍 Overview
🧪 Workup
🚨 Management
💊 Medications
📊 Monitoring
🏥 Rounds
📋 Summary
📄 One-Pager
Architecture
Single-file app — entire site is one HTML file. No build tools, no frameworks, no dependencies. Just open and use.
Offline-first — service worker caches everything. Works in hospital basements, elevators, and airplane mode.
72,800+ DOM nodes — all 175 topics pre-rendered in the HTML. No API calls, no loading spinners, instant tab switching.
Fuzzy search — Damerau-Levenshtein edit distance with sliding window matching. Handles transpositions, insertions, deletions, and substitutions.
CSP protected — Content Security Policy meta tag + escapeHtml() sanitization on all dynamic content. XSS-hardened despite being a static app.
Changelog
v3.2 — March 24, 2026
- SSC 2026 guidelines integrated across sepsis topic — all SSC 2018/2021 references updated
- ACS 2025 guidelines added to What's New
- NEWS/MEWS/NEWS2 calculators added (replacing qSOFA per SSC 2026)
- Clinical calculators organized by rotation — Nephrology, Cardiology, Pulmonology, ICU, GI, General
- Media Library — medical movies, documentaries, TV series, and finance books for residents
- Gifted Hands: The Ben Carson Story added to Movies
- Resources page — recommended books section (Oxford Handbook, Harrison's, Pocket Medicine, ICU Book, Guide to IM Workups)
- Resources page — SSC 2026 guidelines added, cleaned up tools and references
- Channels & Podcasts — YouTube and podcast icons replace emojis
- Recently viewed topics in sidebar
- Offline indicator banner
- Share button (WhatsApp, email, text, copy link)
- Black sidebar redesign with improved contrast
- SSC 2026 pimp questions — 6 new guideline-specific questions in sepsis topic
- 11 new SSC 2026 pearls added to Pearl of the Day rotation
- Pearl of the Day now starts at random position each page load
- SSC 2026 dashboard banner linking to What's New
- Clean URL routing (pushState) — no more # in URLs, SEO-friendly
- Sitemap updated with clean URLs for Google Search Console
- Google Analytics tracks individual page/section views
- RoundsRx logo click returns to dashboard
- Meta description optimized for SSC 2026 search traffic
- Focus outline removed on section navigation
- Diagnostic Dash temporarily removed (under development)
- Google Analytics integration
- Smart back button with navigation history
- Service worker auto-update on deploy
- Deployed live at roundsrx.com via Netlify
v3.1 — March 24, 2026
- Fuzzy search — typo-tolerant search using Damerau-Levenshtein distance
- 41 landmark trials now searchable by name (PARADIGM-HF, DAPA-HF, RALES, etc.)
- Search results scroll directly to matching section and highlight the target
- HFrEF vs HFpEF side-by-side management comparison with 14 trial citations
- STEMI clinical case scenarios with troponin intervals
- Clinical case block styling improvements
v3.0 — March 22, 2026
- 34 clinical worked examples with step-by-step bedside scenarios
- 263 "Updated Practice" callouts flagging old vs new teaching
- 792 trial badges — all with hover descriptions
- 1,775+ drug entries with brand names
- 21 clinical calculators
- New tools: Lab Interpretation Guide, ECG Pattern Guide, Antibiotic Duration Cheat Sheet, IV Fluids Guide, What's New section
- 70+ stub sections replaced with real disease-specific content
- 20+ mislabeled sections corrected (copy-paste errors)
- Fixed corrupted HTML in asthma, HCM topics
- 73 abbreviation definitions added across tables
v2.0 — March 21, 2026
- Expanded to 146 clinical topics across 15 rotations
- 657 pimp questions with reveal answers
- Collapsible sidebar, dark mode, mobile responsive
- SEO optimization, PWA offline support
v1.0 — March 12, 2026
- Initial build: 89 topics across 15 rotations
- Dashboard, search, dark mode
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Last updated: March 24, 2026 at 9:57 PM
Immune Thrombocytopenia (ITP)
Antibody-mediated platelet destruction. Diagnosis of exclusion. Most adults need treatment only if platelets < 30K or bleeding.
🔍 Overview
Overview
ITP is an autoimmune condition where IgG autoantibodies target platelet surface glycoproteins (GPIIb/IIIa, GPIb/IX), leading to splenic phagocytosis and accelerated platelet destruction. It is a diagnosis of exclusion — there is no confirmatory test. Incidence: ~3-4/100,000 adults/year. Primary ITP (80%) has no identifiable cause. Secondary ITP (20%) is associated with SLE, HIV, HCV, H. pylori, CLL, or medications (heparin → HIT, not ITP). Key principle: treat the patient, not the number. Many patients tolerate platelets of 20-30K without significant bleeding.
🧪 Workup
Workup
- CBC with peripheral smear — isolated thrombocytopenia with large platelets (young, reactive). All other cell lines normal. If pancytopenia → think MDS, aplastic anemia, infiltrative process.
- Peripheral smear — must review. Rules out pseudothrombocytopenia (platelet clumping from EDTA — redraw in citrate tube), schistocytes (TTP/HUS), blasts (leukemia), leukoerythroblastic picture (marrow infiltration).
- HIV, HCV — required in all new ITP (secondary causes that change management)
- H. pylori testing — stool antigen or breath test. Eradication can improve platelet count.
- Direct Coombs (DAT) — Evans syndrome = autoimmune hemolytic anemia + ITP. If DAT positive → treat as Evans.
- Immunoglobulins (quantitative Ig) — CVID can present with ITP
- ANA — if SLE suspected (young woman with ITP)
- Coags (PT/INR, aPTT) — should be normal. If abnormal → think DIC, liver disease, factor deficiency.
- Bone marrow biopsy — NOT routine for typical ITP. Indicated if: age > 60 (rule out MDS), atypical features (other cytopenias, splenomegaly, lymphadenopathy), or refractory to first-line therapy.
🚨 Management
Management
- Observation only if platelets ≥ 30K and no bleeding and no upcoming procedures — most patients don't need treatment. [ASH Guidelines, 2019]
- First-line — Corticosteroids:
- Dexamethasone 40 mg PO daily × 4 days — preferred by many experts. Faster response, shorter course. Can repeat q2-4 weeks × 3-4 cycles. [Wei, 2016]
- Prednisone 1 mg/kg daily × 2-4 weeks → taper. Classic approach. Response in 70-80% but relapse rate ~60-80% after taper.
- First-line adjunct — IVIG 1g/kg × 1-2 days: for active bleeding or platelets < 10K or pre-procedure. Fastest response (24-48h) but transient (2-4 weeks). Fc receptor blockade → reduced splenic phagocytosis.
- Anti-D (WinRho) 50-75 mcg/kg IV: only for Rh-positive, non-splenectomized patients. Causes mild extravascular hemolysis that "distracts" the spleen. FDA black box: rare fatal intravascular hemolysis.
- Second-line — TPO receptor agonists: Eltrombopag 50 mg PO daily or Romiplostim 1-10 mcg/kg SQ weekly. Stimulate megakaryopoiesis. ~80% response. Maintenance therapy — platelets drop when stopped. [RAISE, 2011; EXTEND]
- Second-line — Rituximab 375 mg/m² weekly × 4: ~60% initial response but only ~20-30% sustained at 5 years. Best in younger patients with short disease duration.
- Second-line — Fostamatinib (SYK inhibitor): 100-150 mg BID PO. For refractory ITP. [FIT, 2018]
- Third-line — Splenectomy: ~65% long-term remission. Defer at least 12-24 months (spontaneous remission possible). Requires pre-op vaccines (pneumococcal, meningococcal, Hib) ≥ 2 weeks before surgery.
- Emergency bleeding: Platelets + IVIG + methylprednisolone 1g IV + aminocaproic acid (antifibrinolytic). Consider emergent splenectomy if refractory.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Dexamethasone | 40 mg daily × 4 days | PO | Preferred first-line. Can repeat q2-4 wk. Wei, 2016 |
| Prednisone | 1 mg/kg × 2-4 wk → taper | PO | Alternative first-line. 70-80% response. High relapse on taper. |
| IVIG | 1 g/kg × 1-2 days | IV | Fastest response (24-48h). For bleeding or plt < 10K. Transient. Monitor for infusion reactions, aseptic meningitis. |
| Eltrombopag | 50 mg daily (titrate 25-75) | PO | TPO-RA. Response in 1-2 wk. Monitor LFTs. Take on empty stomach (no dairy/Ca). RAISE, 2011 |
| Romiplostim | 1-10 mcg/kg weekly | SQ | TPO-RA. Titrate by platelet response. Risk of marrow reticulin fibrosis (reversible). |
| Rituximab | 375 mg/m² weekly × 4 | IV | Anti-CD20. 60% initial response, ~25% durable at 5y. Check HBV before. Arnold, 2007 |
| Fostamatinib | 100-150 mg BID | PO | SYK inhibitor for refractory ITP. SE: diarrhea, HTN, LFT elevation. FIT, 2018 |
| Aminocaproic acid | 4-5g load → 1g/hr | IV/PO | Antifibrinolytic for emergency bleeding. Adjunct to platelets. |
📊 Monitoring
Monitoring
- Platelet count — q1-2 days during active treatment; weekly during titration; monthly once stable. Goal: ≥ 30K (not "normal").
- Bleeding assessment — skin (petechiae, purpura, ecchymoses), mucosal (oral blood blisters = "wet purpura" = higher bleed risk), menorrhagia, epistaxis, GI, intracranial
- Blood glucose — while on steroids (dexamethasone/prednisone)
- LFTs — q2-4 weeks on eltrombopag (hepatotoxicity risk)
- CBC with differential — monitor for new cytopenias (would suggest secondary cause or MDS)
- Reticulin fibrosis — consider bone marrow biopsy if on TPO-RA > 1 year (rare reversible marrow fibrosis)
- Infection screening — on immunosuppression (rituximab, chronic steroids). HBV reactivation monitoring with rituximab.
🏥 Rounds
Sample Presentation
Mrs. Patel is a 34-year-old woman presenting with 3 days of spontaneous bruising and petechiae on bilateral lower extremities. No mucosal bleeding, no epistaxis, no hemoptysis, no melena. No recent illness or new medications. No joint pains or rash. VS stable. Exam: scattered petechiae on shins, no splenomegaly, no lymphadenopathy. Labs: platelets 8K (previously normal 6 months ago), Hgb 13.2, WBC 6.8, peripheral smear shows large platelets with no schistocytes/blasts. PT/INR normal. HIV negative, HCV negative, H. pylori stool antigen negative. DAT negative.
Key Points: Isolated thrombocytopenia with large platelets and otherwise normal CBC + smear = classic ITP. Plt < 10K with mucosal bleeding risk → start IVIG 1g/kg + dexamethasone 40 mg × 4 days. No need for bone marrow biopsy in a young patient with typical presentation.
Pimp Questions
❓ What is the platelet threshold for treatment in ITP?
Platelets < 30K or any clinically significant bleeding, regardless of count. Treat the patient, not the number. Many patients tolerate 20-30K without bleeding. [ASH Guidelines, 2019]
❓ What must you always check on the peripheral smear before diagnosing ITP?
Rule out pseudothrombocytopenia (EDTA-induced platelet clumping — redraw in citrate tube), schistocytes (TTP/HUS/DIC), blasts (leukemia), and leukoerythroblastic picture (marrow infiltration). ITP should show large platelets and nothing else abnormal.
❓ When do you give IVIG vs steroids alone in ITP?
IVIG 1 g/kg for: active bleeding, platelets < 10K, or pre-procedure urgent platelet rise needed. IVIG works in 24-48 hours (fastest). Steroids alone are adequate for stable patients with plt 10-30K and no active bleeding. IVIG effect is transient (2-4 weeks).
❓ What is Evans syndrome?
Evans syndrome = autoimmune hemolytic anemia (AIHA) + ITP. Positive direct Coombs test + thrombocytopenia. More aggressive course than ITP alone. Often associated with SLE or lymphoproliferative disorders. Treatment: steroids, rituximab. Check DAT in all ITP patients.
❓ What vaccines are required before splenectomy for ITP?
Pneumococcal (PCV20 or PCV15 + PPSV23), meningococcal (MenACWY + MenB), and Haemophilus influenzae type b (Hib). Give ≥ 2 weeks before surgery. Post-splenectomy: lifelong risk of overwhelming post-splenectomy infection (OPSI) from encapsulated organisms.
❓ What are TPO receptor agonists and when do you use them?
Eltrombopag (oral, daily) and romiplostim (SQ, weekly) stimulate megakaryopoiesis via the thrombopoietin receptor. Second-line for chronic ITP failing steroids. ~80% response rate. Maintenance therapy — platelets drop when stopped. Monitor LFTs (eltrombopag) and for reticulin fibrosis (both). [RAISE, 2011]
❓ When do you perform a bone marrow biopsy in ITP?
NOT routine. Indications: (1) age > 60 (rule out MDS), (2) atypical features (other cytopenias, splenomegaly, lymphadenopathy, abnormal smear), (3) refractory to first-line therapy, (4) before splenectomy (some centers). In typical young-adult ITP with isolated thrombocytopenia, diagnosis is clinical.
❓ What is "wet purpura" and why is it important?
Wet purpura = hemorrhagic bullae (blood blisters) in the oral mucosa. It indicates a higher risk of serious hemorrhage compared to dry purpura (skin-only petechiae/ecchymoses). Wet purpura with plt < 10K is an indication for urgent treatment with IVIG + high-dose steroids.
📋 Summary
Summary
Definition
Autoimmune platelet destruction. Diagnosis of exclusion. Isolated thrombocytopenia + large platelets.
Workup
CBC + smear (rule out pseudo, TTP, leukemia). HIV, HCV, H. pylori, DAT, coags. BMBx only if atypical.
Treat If
Plt < 30K OR bleeding. Goal: safe platelet count, not normal. Treat patient not number.
First-Line
Dexamethasone 40 mg × 4d or prednisone 1 mg/kg. IVIG 1g/kg if bleeding or plt < 10K.
Second-Line
TPO-RA (eltrombopag, romiplostim), rituximab, fostamatinib. Splenectomy = third-line.
Pearl
Wet purpura = high bleed risk. Evans = ITP + AIHA. Always check smear. Don't BMBx young typical ITP.
📄 One Pager
One-Pager
ITP
Immune Thrombocytopenia
Diagnosis
Isolated thrombocytopenia + large platelets on smear. Normal WBC/Hgb. Rule out: pseudothrombocytopenia (EDTA clumping), TTP (schistocytes), DIC (fibrinogen), HIT (heparin exposure), drug-induced. Check HIV, HCV, H. pylori, DAT.
Treatment Algorithm
Plt ≥ 30K no bleeding → observe. Plt < 30K or bleeding → dexamethasone 40 mg × 4d ± IVIG if severe. Refractory → TPO-RA (eltrombopag/romiplostim) or rituximab. Last resort → splenectomy (vaccinate first).
Key Drugs
IVIG 1g/kg (fastest, 24-48h, transient). Dexamethasone 40 mg × 4d. Eltrombopag 50 mg PO daily. Romiplostim 1-10 mcg/kg SQ weekly. Rituximab 375 mg/m² × 4. Aminocaproic acid for emergency bleeding.
Oncologic Emergencies
Life-threatening complications of malignancy requiring immediate recognition: SVC syndrome, cord compression, brain mets, hyperviscosity, and tumor lysis.
🔍 Overview
Overview
Oncologic emergencies are complications of cancer or its treatment that require immediate intervention to prevent death or irreversible organ damage. The key emergencies: (1) Superior vena cava (SVC) syndrome — obstruction of SVC, usually by lung cancer or lymphoma. (2) Malignant spinal cord compression (MSCC) — epidural metastasis compressing the cord. (3) Brain metastases with herniation — elevated ICP. (4) Hyperviscosity syndrome — Waldenström macroglobulinemia or multiple myeloma. (5) Tumor lysis syndrome — covered separately. (6) Febrile neutropenia — covered separately. (7) Malignant pericardial effusion/tamponade. The intern's role: recognize the pattern, start dexamethasone, and call oncology/radiation/surgery.
🧪 Workup
Workup
- SVC syndrome: CT chest with contrast (confirms obstruction + identifies cause). CXR may show widened mediastinum. Tissue diagnosis before radiation if patient is stable.
- Cord compression: MRI entire spine with contrast — gold standard. Order STAT. Must image ENTIRE spine (multiple levels in 10-38%). Check post-void residual (early bladder dysfunction).
- Brain mets: MRI brain with contrast. CT if MRI unavailable. Fundoscopy for papilledema. Assess for midline shift and herniation signs.
- Hyperviscosity: Serum viscosity (> 4-5 cP = symptomatic). Fundoscopy ("sausage-link" retinal veins). SPEP + serum free light chains. Peripheral smear (rouleaux).
- Malignant tamponade: Echocardiography (pericardial effusion + RA/RV diastolic collapse). Pulsus paradoxus > 10 mmHg. ECG: low voltage, electrical alternans.
🚨 Management
Management
- SVC syndrome: Elevate HOB. Dexamethasone 10 mg IV (if lymphoma suspected — exquisitely steroid-sensitive). Radiation therapy for NSCLC. Endovascular stenting for rapid relief. Anticoagulation if thrombus. Do NOT delay treatment for tissue diagnosis if severely symptomatic.
- Cord compression: Dexamethasone 10 mg IV STAT → 4 mg IV q6h. Must give within 24h of symptom onset — neurologic outcome correlates with pre-treatment function. Radiation (most common treatment). Surgery if: unknown primary (need tissue), radioresistant tumor, mechanical instability, or single-level disease with good prognosis. Patchell, Lancet 2005
- Brain mets: Dexamethasone 10 mg IV → 4 mg q6h (reduce edema). Anticonvulsants only if seizure has occurred (not prophylactic). Surgery for single resectable met with controlled primary. SRS (stereotactic radiosurgery) for ≤ 4 mets. WBRT for diffuse mets or poor prognosis.
- Hyperviscosity: Emergent plasmapheresis. Avoid pRBC transfusion before pheresis (increases viscosity further). Start definitive chemotherapy after pheresis.
- Tamponade: Pericardiocentesis (echo-guided). Pericardial window if recurrent. Intrapericardial chemotherapy or sclerotherapy for malignant effusions.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Dexamethasone | 10 mg IV bolus → 4 mg q6h | IV | For cord compression, brain mets, SVC (lymphoma). Reduces vasogenic edema. Start immediately — do not wait for imaging. |
| Levetiracetam | 500-1000 mg BID | IV/PO | If seizure with brain mets. NOT for prophylaxis in brain mets without seizure. |
| Mannitol | 0.5-1 g/kg IV | IV | Impending herniation from brain mets. Osmotic diuresis reduces ICP. Bridge to dexamethasone effect. |
| Hypertonic saline 3% | 150-250 mL bolus | IV | Alternative to mannitol for acute ICP crisis. |
| Radiation therapy | Per radiation oncology | — | Mainstay for cord compression, SVC (solid tumors), brain mets (WBRT/SRS). |
| Heparin | Weight-based | IV | SVC syndrome with associated thrombus. |
📊 Monitoring
Monitoring
- Neuro exam q4h — for cord compression and brain mets. Motor strength, sensory level, rectal tone, post-void residual. Deterioration = urgent re-imaging.
- Serum viscosity — before and after plasmapheresis. Target < 4 cP.
- Blood glucose — high-dose dexamethasone causes significant hyperglycemia. Sliding scale insulin + glucose checks q6h.
- Pericardial effusion reaccumulation — repeat echo at 24-48h post-pericardiocentesis. 40-70% recurrence rate with malignant effusions.
- Respiratory status — SVC syndrome patients at risk for airway compromise. Keep intubation equipment at bedside.
🏥 Rounds
Sample Presentation
Mr. Johnson is a 62-year-old man with known Stage IV NSCLC (right upper lobe, 3 cycles of pembrolizumab) presenting with 2 days of progressive lower extremity weakness and urinary retention. Exam: 4/5 hip flexors bilateral, absent ankle reflexes, T10 sensory level, post-void residual 400 mL. No saddle anesthesia. VS stable. MRI spine: T9-T10 epidural mass with cord compression.
Key Points: This is MSCC — give dexamethasone 10 mg IV STAT, consult radiation oncology AND spine surgery. Motor function at presentation is the strongest predictor of outcome. Ambulatory at diagnosis → 80% remain ambulatory. Non-ambulatory → only 10-20% regain walking.
Pimp Questions
❓ What is the most important prognostic factor in malignant cord compression?
Pre-treatment neurologic status. Patients who are ambulatory at diagnosis have ~80% chance of remaining ambulatory. Patients who are paraplegic at diagnosis have < 10% chance of regaining ambulation. This is why immediate dexamethasone and urgent imaging matter — every hour counts. [Patchell, 2005]
❓ Why do you NOT give prophylactic anticonvulsants for brain metastases?
Multiple RCTs show no benefit from prophylactic AEDs in brain mets without prior seizure, AND significant side effects (rash, drug interactions with chemo, sedation). AAN guidelines explicitly recommend against prophylaxis. Treat only if seizure has occurred. Levetiracetam preferred (fewer drug interactions than phenytoin).
❓ Why should you avoid pRBC transfusion before plasmapheresis in hyperviscosity?
Transfusing pRBCs increases blood viscosity further by raising hematocrit. In a patient already symptomatic from hyperviscosity (IgM paraprotein causing sludging), this can precipitate stroke, retinal vein occlusion, or cardiac failure. Do plasmapheresis FIRST, then transfuse if needed afterward.
❓ Name the classic triad of SVC syndrome.
Facial/upper extremity edema + dyspnea + distended neck/chest wall veins. Worse when leaning forward or lying flat. Pemberton sign: facial plethora + cyanosis when arms raised above head. Most common cause: lung cancer (especially right-sided). Second: lymphoma (more steroid-responsive).
❓ What imaging do you order for suspected cord compression and why must you image the entire spine?
MRI entire spine with gadolinium contrast — gold standard. Must image the ENTIRE spine because 10-38% of patients have multiple levels of compression. Treating only the symptomatic level while missing another will lead to treatment failure. CT myelography is an alternative if MRI contraindicated.
❓ When is surgery preferred over radiation for cord compression?
Surgery (decompressive laminectomy ± stabilization) is preferred when: (1) unknown primary (need tissue for diagnosis), (2) radioresistant tumor (renal cell, melanoma), (3) mechanical spinal instability, (4) single level of disease with good overall prognosis, (5) progression during or after radiation. [Patchell, 2005] showed surgery + RT was superior to RT alone for single-level compression.
📋 Summary
Summary
SVC Syndrome
CT chest w/ contrast. Dex if lymphoma. Radiation or stent. Don't delay for biopsy if severe.
Cord Compression
Dex 10mg IV STAT. MRI entire spine. Radiation ± surgery. Neuro function at dx = prognosis.
Brain Mets
Dex 10mg IV. MRI brain. SRS if ≤4 mets. WBRT if diffuse. No prophylactic AEDs.
Hyperviscosity
Emergent plasmapheresis. No pRBC before pheresis. Fundoscopy. Serum viscosity >4-5.
Tamponade
Echo → pericardiocentesis. Pericardial window if recurrent. 40-70% recurrence rate.
Key Pearl
Dexamethasone first, ask questions later. Most onc emergencies benefit from immediate steroids.
📄 One Pager
One-Pager
Oncologic Emergencies
Recognize, stabilize, consult
The Big Five
SVC syndrome (facial edema + dyspnea + neck veins). Cord compression (back pain + weakness + bladder dysfunction). Brain mets (headache + focal deficit + seizure). Hyperviscosity (visual changes + bleeding + confusion). Tamponade (Beck triad: hypotension + JVD + muffled heart sounds).
Universal First Step
Dexamethasone 10 mg IV for cord compression, brain mets, SVC (lymphoma). Addresses vasogenic edema in all three. Start before imaging returns. Call oncology + appropriate surgical service.
Source Trials
Patchell 2005 (surgery + RT vs RT for cord compression) · AAN Brain Mets Guidelines (no prophylactic AEDs)
Pancytopenia
Simultaneous reduction of all three cell lines. Systematic approach: peripheral smear first, then bone marrow biopsy. Think production vs destruction.
🔍 Overview
Overview
Pancytopenia = anemia + leukopenia + thrombocytopenia. Not a diagnosis but a lab finding requiring systematic workup. Framework: decreased production (marrow failure: aplastic anemia, MDS, leukemia, myelofibrosis, infiltration by solid tumor, infection, medication) vs increased destruction/sequestration (hypersplenism, autoimmune, HLH, DIC). The peripheral smear is the single most important initial test — it guides the entire workup.
🧪 Workup
Workup
- Peripheral smear — the MOST important test. Blasts → leukemia. Teardrop cells + leukoerythroblastic picture → myelofibrosis/marrow infiltration. Dysplastic cells → MDS. Schistocytes → TTP/DIC. Megaloblastic → B12/folate deficiency. Normal morphology → aplastic anemia, drug-induced, viral.
- Reticulocyte count — low = production problem. High (unexpected in pancytopenia) = peripheral destruction + splenic sequestration.
- B12 + folate — megaloblastic anemia can cause pancytopenia (ineffective hematopoiesis)
- LDH, haptoglobin, indirect bilirubin — hemolysis markers
- HIV, HBV, HCV, EBV, CMV, parvovirus B19 — viral marrow suppression
- ANA, RF — autoimmune causes (Felty syndrome = RA + splenomegaly + neutropenia)
- Copper level — copper deficiency mimics MDS (sideroblastic anemia + neutropenia)
- Flow cytometry — if blasts or abnormal lymphocytes on smear
- Bone marrow biopsy + aspirate — definitive test. Hypercellular = MDS, leukemia, megaloblastic. Hypocellular = aplastic anemia. Dry tap = myelofibrosis. Granulomas = infection (TB, fungal). Send: morphology, cytogenetics, flow, iron stain, reticulin stain.
🚨 Management
Management
- Treat the underlying cause:
- B12 deficiency: IM cyanocobalamin 1000 mcg daily × 7 → weekly × 4 → monthly. Pancytopenia resolves within weeks.
- Drug-induced: Stop offending agent (methotrexate, chemotherapy, TMP-SMX, linezolid, valproate). Recovery in 1-3 weeks typically.
- Aplastic anemia: Age < 40 + matched sibling donor → allogeneic stem cell transplant. Older patients → immunosuppressive therapy: horse ATG + cyclosporine + eltrombopag. [RACE, 2022]
- MDS: Risk stratify (IPSS-R). Low-risk → ESA, lenalidomide (del5q). High-risk → azacitidine [AZA-001] or transplant if eligible.
- Leukemia: Induction chemotherapy per subtype. APL = ATRA + arsenic trioxide (curative in > 90%).
- HLH: Etoposide-based protocol (HLH-2004). Dexamethasone. Cyclosporine. Treat trigger.
- Supportive care: pRBC for Hgb < 7 (or < 8 symptomatic). Platelets if < 10K or bleeding. Neutropenic precautions if ANC < 500. G-CSF if severe neutropenia with infection.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Cyanocobalamin | 1000 mcg IM daily × 7d | IM | B12 deficiency. Expect retic crisis at day 5-7. Monitor K⁺ (drops with new cell production). |
| Horse ATG (ATGAM) | 40 mg/kg/day × 4 days | IV | Aplastic anemia immunosuppression. Give with steroids (serum sickness prophylaxis). Scheinberg, 2011 |
| Cyclosporine | 5-6 mg/kg/day divided BID | PO | With ATG for aplastic anemia. Target trough 200-400. Nephrotoxicity, HTN, tremor. |
| Eltrombopag | 150 mg daily | PO | Added to ATG+CsA in aplastic anemia improves response. RACE, 2022 |
| Azacitidine | 75 mg/m² SQ × 7 days q28d | SQ | High-risk MDS. Delays AML transformation. AZA-001, 2009 |
| Lenalidomide | 10 mg daily × 21/28 days | PO | MDS with del(5q). 67% transfusion independence. VTE prophylaxis required. |
| Filgrastim (G-CSF) | 5 mcg/kg SQ daily | SQ | Severe neutropenia with infection. Not for chronic use in MDS (may accelerate AML). |
📊 Monitoring
Monitoring
- CBC with differential — q1-2 days during active treatment, weekly during recovery
- Reticulocyte count — expect retic crisis at day 5-7 after B12 repletion (confirms response)
- K⁺, PO₄, Mg — can drop rapidly with new hematopoiesis ("refeeding" of the marrow). Monitor and replete.
- Cyclosporine trough — if on immunosuppression for aplastic anemia. Target 200-400. Check Cr (nephrotoxic).
- Ferritin — chronic transfusion → iron overload. Consider chelation if ferritin > 1000.
- Bone marrow repeat — at 3-6 months to assess response to therapy. Earlier if clinical deterioration.
- Cytogenetics monitoring — MDS can evolve. New cytogenetic abnormalities may change management.
🏥 Rounds
Sample Presentation
Mrs. Chen is a 72-year-old woman referred for pancytopenia found on routine labs: Hgb 8.1, WBC 2.8 (ANC 900), platelets 78K. No B symptoms. No bleeding. No infections. Medications: metformin, lisinopril. Peripheral smear: macrocytosis, hypersegmented neutrophils, oval macrocytes. B12 level: 89 pg/mL (low). MMA elevated. Folate normal. Retic count 0.5%.
Key Points: Classic megaloblastic pancytopenia from B12 deficiency. Smear is diagnostic — hypersegmented neutrophils + oval macrocytes. Start IM B12 immediately. Expect reticulocyte crisis at day 5-7 and monitor K⁺ (drops with new hematopoiesis). No bone marrow biopsy needed if smear + B12 level confirm the diagnosis.
Pimp Questions
❓ What is the single most important initial test in pancytopenia?
Peripheral blood smear. It guides the entire workup: blasts (leukemia), teardrops (myelofibrosis), schistocytes (TTP/DIC), megaloblastic changes (B12/folate), dysplastic cells (MDS), normal morphology (aplastic anemia, viral, drug-induced).
❓ How can B12 deficiency cause pancytopenia?
B12 is required for DNA synthesis. Deficiency causes ineffective hematopoiesis — cells are produced but destroyed before release (intramedullary hemolysis). All three cell lines affected. The marrow is actually hypercellular (not empty) — megaloblastic precursors are dying before maturation. This can mimic MDS.
❓ What is a "dry tap" on bone marrow aspiration and what does it suggest?
A dry tap = inability to aspirate marrow despite proper needle placement. Classic for myelofibrosis (marrow replaced by reticulin/collagen fibrosis). Also seen in hairy cell leukemia, metastatic carcinoma (packed marrow), and some cases of aplastic anemia. Core biopsy is essential when aspirate fails.
❓ What electrolyte must you monitor when starting B12 repletion?
Potassium. As new red blood cells are rapidly produced (reticulocyte crisis), potassium shifts intracellularly. This can cause severe hypokalemia — potentially fatal if not monitored and repleted. Also monitor phosphate and magnesium for the same reason.
❓ Name a non-hematologic cause of pancytopenia that is commonly missed.
Copper deficiency. Causes sideroblastic anemia + neutropenia ± thrombocytopenia. Mimics MDS on smear and marrow. Risk factors: gastric bypass surgery, zinc supplementation (zinc competes with copper absorption), malnutrition, TPN without copper. Serum copper and ceruloplasmin are low. Responds to copper supplementation.
❓ What is HLH and how does it present?
Hemophagocytic lymphohistiocytosis (HLH) — uncontrolled immune activation with macrophage phagocytosis of blood cells. Presents with: persistent fever, splenomegaly, pancytopenia, hyperferritinemia (> 500, often > 10,000), hypertriglyceridemia, hypofibrinogenemia, elevated soluble IL-2 receptor. Triggers: infection (EBV), malignancy (lymphoma), autoimmune. Fatal without treatment — etoposide-based protocol. [HLH-2004]
📋 Summary
Summary
Definition
Anemia + leukopenia + thrombocytopenia. A lab finding, not a diagnosis.
First Test
Peripheral smear. Blasts=leukemia. Teardrops=fibrosis. Megaloblastic=B12. Dysplastic=MDS.
Key Labs
Retic count, B12/folate, LDH, HIV/HBV/HCV, copper, ANA. Then bone marrow biopsy.
Production ↓
Aplastic anemia, MDS, leukemia, myelofibrosis, B12/folate, drugs, viral, infiltration
Destruction ↑
Hypersplenism, DIC, TTP, HLH, autoimmune
Pearl
Check copper. Hypersegmented neutrophils = B12 (not MDS). Dry tap = myelofibrosis.
📄 One Pager
One-Pager
Pancytopenia
Systematic Approach
Workup Algorithm
Step 1: Peripheral smear (most important). Step 2: Retic count (production vs destruction). Step 3: B12, folate, HIV, HCV, copper. Step 4: Bone marrow biopsy if not explained by above.
Common Causes by Smear
Blasts → leukemia. Teardrops → myelofibrosis. Megaloblastic → B12/folate. Dysplastic → MDS. Schistocytes → TTP. Normal → aplastic anemia, drug, viral.
Trials
RACE 2022 (ATG+CsA+eltrombopag for AA) · AZA-001 2009 (azacitidine for MDS) · HLH-2004 (etoposide protocol) · Scheinberg 2011 (horse vs rabbit ATG)
Chemotherapy Toxicities
Recognition and management of life-threatening chemo side effects: cardiotoxicity, mucositis, typhlitis, hemorrhagic cystitis, immune checkpoint toxicities, and infusion reactions.
🔍 Overview
Overview
Chemotherapy toxicities are a leading cause of treatment discontinuation, ICU admission, and death in cancer patients. The intern must recognize organ-specific toxicities by drug class: anthracyclines (cardiotoxicity), bleomycin (pulmonary fibrosis), cisplatin (nephro/oto/neurotoxicity), vinca alkaloids (neuropathy), cyclophosphamide (hemorrhagic cystitis), checkpoint inhibitors (immune-related adverse events in any organ). Key principle: know which chemo the patient received and its expected toxicity profile.
🧪 Workup
Workup
- Know the regimen — review the chemo protocol. Each drug has specific toxicities.
- CBC with differential — nadir timing varies: 7-14 days for most agents, 4-6 weeks for nitrosoureas
- BMP, LFTs, LDH — organ toxicity screening
- Troponin + BNP + echo — if anthracycline cardiotoxicity suspected
- CT chest — bleomycin/checkpoint pneumonitis
- UA — hemorrhagic cystitis (cyclophosphamide/ifosfamide)
- TSH — checkpoint inhibitor thyroiditis (most common irAE)
- AM cortisol — checkpoint hypophysitis
- Lipase — checkpoint pancreatitis
🚨 Management
Management
- Anthracycline cardiotoxicity: Echo (EF decline > 10% to below 50% = hold). Dexrazoxane for cardioprotection if cumulative dose high. Standard HF therapy if cardiomyopathy develops. Lifetime dose limits: doxorubicin 450-550 mg/m².
- Bleomycin lung toxicity: Stop bleomycin. Steroids (prednisone 1 mg/kg). Avoid high FiO₂ — oxygen worsens bleomycin lung injury (free radical mechanism). Keep SpO₂ 88-92% target.
- Typhlitis (neutropenic enterocolitis): CT abdomen (bowel wall thickening, pneumatosis). Broad-spectrum abx (pip-tazo + vanc). NPO + IV fluids. Surgery if perforation/peritonitis.
- Hemorrhagic cystitis: Aggressive IVF hydration. Continuous bladder irrigation (CBI). MESNA prophylaxis with cyclophosphamide/ifosfamide (binds acrolein metabolite). Urology if severe clot retention.
- Checkpoint inhibitor irAEs: Grade 1 → continue + monitor. Grade 2 → hold checkpoint, prednisone 0.5-1 mg/kg. Grade 3 → hold checkpoint, methylprednisolone 1-2 mg/kg. Grade 4 → permanently discontinue, methylprednisolone 1-2 mg/kg ± infliximab (colitis) or mycophenolate (hepatitis). [NCCN irAE Guidelines]
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| MESNA | 60-100% of cyclophosphamide dose | IV | Prevents hemorrhagic cystitis. Binds acrolein (toxic metabolite) in bladder. Give with cyclo/ifosfamide. |
| Dexrazoxane | 10:1 ratio to doxorubicin | IV | Iron chelator. Cardioprotection for cumulative anthracycline doses ≥ 300 mg/m². |
| Amifostine | 910 mg/m² IV pre-cisplatin | IV | Nephroprotection for cisplatin. Free radical scavenger. Causes hypotension. |
| Prednisone | 1-2 mg/kg daily | PO | irAEs Grade 2+. Taper over 4-6 weeks minimum. Too-rapid taper → flare. |
| Infliximab | 5 mg/kg IV | IV | Steroid-refractory checkpoint colitis. NCCN irAE, 2024 |
| Ondansetron | 8 mg IV pre-chemo | IV | Acute emesis. Add dexamethasone + NK1 antagonist for high emetogenic regimens. |
| Palonosetron | 0.25 mg IV | IV | Longer-acting 5-HT3 for delayed emesis prevention. |
📊 Monitoring
Monitoring
- CBC nadir — typically day 7-14 (day 21-28 for nitrosoureas). Check CBC before each cycle.
- Echo/MUGA q3 months on anthracyclines — stop if EF drops > 10% below baseline to < 50%
- PFTs before and during bleomycin — stop if DLCO drops > 20%
- Cr + Mg with cisplatin (nephrotoxicity + magnesium wasting)
- Audiometry with cisplatin (ototoxicity — irreversible high-frequency hearing loss)
- TSH q4-6 weeks on checkpoint inhibitors (thyroiditis → hypothyroidism)
- LFTs q2-4 weeks on checkpoint inhibitors (hepatitis)
- Urine output + UA with cyclophosphamide (hemorrhagic cystitis)
🏥 Rounds
Sample Presentation
Mr. Davis is a 58-year-old man with metastatic melanoma on pembrolizumab (cycle 8) presenting with 5 days of watery diarrhea (8-10 episodes/day), crampy abdominal pain, no blood. Afebrile. Exam: diffuse abdominal tenderness, no peritoneal signs. Labs: WBC 11K, Cr 1.4 (baseline 0.9). C. diff negative. CT: diffuse colonic wall thickening. TSH 12 (baseline 2.5).
Key Points: Checkpoint inhibitor colitis (Grade 3 — ≥ 7 stools/day over baseline) + new hypothyroidism. Hold pembrolizumab. Start methylprednisolone 1 mg/kg IV. If no improvement in 3 days → infliximab 5 mg/kg. Start levothyroxine for hypothyroidism. GI consult for possible colonoscopy with biopsy.
Pimp Questions
❓ What is the most common immune-related adverse event from checkpoint inhibitors?
Thyroiditis/hypothyroidism (up to 10-20% with anti-PD-1). Often painless thyroiditis → transient hyperthyroidism → permanent hypothyroidism requiring levothyroxine. Check TSH q4-6 weeks. Unlike most irAEs, hypothyroidism does NOT require holding checkpoint therapy.
❓ Why should you avoid high FiO₂ in bleomycin lung toxicity?
Bleomycin causes pulmonary injury via free radical generation. High concentrations of oxygen provide more substrate for free radical production, worsening the lung injury. Target SpO₂ 88-92%. This is critical during surgery in patients with bleomycin history — anesthesia must avoid high FiO₂ even years later.
❓ What is MESNA and how does it work?
MESNA (2-mercaptoethane sulfonate sodium) binds acrolein, the toxic metabolite of cyclophosphamide and ifosfamide that causes hemorrhagic cystitis. MESNA is renally excreted and acts directly in the bladder lumen to neutralize acrolein. Always give with cyclophosphamide (especially high-dose) and ifosfamide.
❓ What is the cumulative dose limit for doxorubicin and why?
450-550 mg/m² lifetime. Above this threshold, risk of irreversible dilated cardiomyopathy increases sharply. Doxorubicin causes cardiotoxicity via free radical damage to cardiomyocytes + topoisomerase IIβ inhibition. Can occur during treatment (acute) or years later (late-onset). Monitor with serial echocardiography. Dexrazoxane is cardioprotective at high cumulative doses.
❓ How do you grade and manage checkpoint inhibitor hepatitis?
Grade 1 (AST/ALT 1-3× ULN): continue checkpoint, monitor LFTs weekly. Grade 2 (3-5× ULN): hold checkpoint, prednisone 0.5-1 mg/kg. Grade 3 (5-20× ULN): hold, methylprednisolone 1-2 mg/kg. Grade 4 (> 20× ULN): permanently discontinue, methylprednisolone 2 mg/kg, add mycophenolate (NOT infliximab — hepatotoxic). Rule out viral hepatitis and autoimmune hepatitis first.
❓ What is typhlitis and which patients get it?
Typhlitis (neutropenic enterocolitis) = inflammation/necrosis of the cecum in severely neutropenic patients (ANC < 500), usually during chemo nadir. Presents with RLQ pain, fever, diarrhea (often bloody). CT: cecal wall thickening > 4mm, pericecal fat stranding, ± pneumatosis. Treatment: broad-spectrum antibiotics, NPO, IVF. Surgery only if perforation/peritonitis. Mortality 20-50%.
📋 Summary
Summary
Cardiotoxicity
Anthracyclines (doxorubicin). Echo q3mo. Lifetime limit 450-550 mg/m². Dexrazoxane if high dose.
Pulmonary
Bleomycin → fibrosis. Stop drug. Steroids. Avoid high FiO₂ (even years later).
Hemorrhagic Cystitis
Cyclophosphamide/ifosfamide. Prevent with MESNA. Treat with CBI + hydration.
Checkpoint irAEs
Grade 1→monitor. Grade 2→hold+steroids. Grade 3-4→high-dose steroids ± infliximab/MMF.
Typhlitis
Neutropenic cecal inflammation. RLQ pain + fever + ANC<500. CT: cecal wall thickening. Abx + NPO.
Key Rule
Always know the regimen. Each drug has predictable toxicities. Ask: "What chemo did they get?"
📄 One Pager
One-Pager
Chemo Toxicities
Know the drug, predict the toxicity
Drug → Toxicity Map
Anthracyclines → heart. Bleomycin → lungs. Cisplatin → kidneys + ears + nerves. Vincristine → peripheral neuropathy. Cyclophosphamide → bladder. Checkpoint inhibitors → any organ (thyroid most common).
Antidotes/Prevention
MESNA (hemorrhagic cystitis). Dexrazoxane (anthracycline cardiotoxicity). Amifostine (cisplatin nephrotoxicity). Leucovorin (methotrexate rescue). Aggressive hydration (cisplatin, ifosfamide, TLS prevention).
Lymphoma
Hodgkin vs Non-Hodgkin lymphoma: when to suspect, how to work up, what the intern needs to know for inpatient management, and oncologic emergencies to watch for.
🔍 Overview
Overview
Lymphoma = malignancy of lymphocytes. Two major categories: Hodgkin lymphoma (HL) — bimodal peak (20s and 60s), Reed-Sternberg cells, excellent prognosis (cure rate > 80%), contiguous nodal spread. Non-Hodgkin lymphoma (NHL) — much more common (90% of lymphomas), heterogeneous group from indolent (follicular) to aggressive (DLBCL, Burkitt). Key teaching point for interns: you are not expected to manage the chemo — you are expected to recognize lymphoma, complete the staging workup, manage inpatient complications (tumor lysis, febrile neutropenia, cord compression, SVC syndrome), and ensure tissue gets to pathology properly.
🧪 Workup
Workup
- Excisional lymph node biopsy — gold standard. NOT fine needle aspiration (FNA). FNA disrupts architecture needed for subtyping. Core needle biopsy acceptable if excisional not feasible.
- Pathology: hematoxylin/eosin, immunohistochemistry (CD20, CD3, CD15, CD30, Ki-67), flow cytometry, cytogenetics/FISH
- PET/CT — staging (Ann Arbor). PET-avid = aggressive. PET-negative nodes in follicular lymphoma may still be involved.
- CT chest/abdomen/pelvis — if PET not available
- Bone marrow biopsy — required for NHL staging. Optional for HL with PET/CT (PET replaced BMBx in many centers).
- Labs: CBC, CMP, LDH (prognostic, correlates with tumor burden), uric acid (TLS risk), hepatitis B (reactivation risk with rituximab), HIV (lymphoma association), ESR (HL prognostic factor), β2-microglobulin (NHL prognostic)
- Echocardiography — baseline EF before anthracycline-containing regimens
- Fertility counseling — before starting chemo (especially alkylating agents). Sperm banking / oocyte cryopreservation.
🚨 Management
Management
- Hodgkin Lymphoma:
- Early stage (I-II) favorable: ABVD × 2-4 cycles ± involved-site radiation. Cure rate > 90%.
- Advanced stage (III-IV): ABVD × 6 cycles or BV-AVD (brentuximab-AVD). [ECHELON-1, 2018]
- PET-adapted: interim PET after 2 cycles guides therapy intensity.
- DLBCL (most common aggressive NHL): R-CHOP × 6 cycles (rituximab + cyclophosphamide/doxorubicin/vincristine/prednisone). Cure rate 60-70%. CNS prophylaxis with intrathecal methotrexate for high-risk (testicular, breast, kidney, adrenal involvement). [GELA, 2002]
- Follicular lymphoma (indolent): Watch-and-wait for asymptomatic low tumor burden. Treat when symptomatic: rituximab ± bendamustine or CHOP. Not curable with standard therapy — median survival > 15 years with serial treatments.
- Burkitt lymphoma: Medical emergency — fastest growing human tumor. Hyper-CVAD or similar intensive regimen. TLS prophylaxis critical (aggressive IVF + rasburicase).
- Intern responsibilities: TLS prevention, infection prophylaxis, transfusion support, recognize treatment complications, ensure adequate IV access (port placement), fertility counseling documentation.
💊 Medications
Medications
| Drug | Dose/Regimen | Route | Notes |
|---|---|---|---|
| R-CHOP | Rituximab + Cyclo/Doxo/Vincristine/Pred | IV | Standard for DLBCL. q21 days × 6 cycles. GELA, 2002 |
| ABVD | Doxorubicin/Bleomycin/Vinblastine/Dacarbazine | IV | Standard for Hodgkin. q28 days. Monitor PFTs (bleomycin). |
| Rituximab | 375 mg/m² | IV | Anti-CD20. Infusion reactions common (premedicate). Screen HBV (reactivation risk — give entecavir prophylaxis if HBsAg+ or anti-HBc+). |
| Brentuximab vedotin | 1.2 mg/kg q2wk | IV | Anti-CD30 ADC. HL + some NHL. Peripheral neuropathy. ECHELON-1, 2018 |
| TMP-SMX | 1 DS tab Mon/Wed/Fri | PO | PCP prophylaxis during and 6 months after R-CHOP/ABVD. |
| Acyclovir | 400 mg BID | PO | VZV prophylaxis during chemo. |
| Entecavir | 0.5 mg daily | PO | HBV prophylaxis if anti-HBc positive + receiving rituximab. |
📊 Monitoring
Monitoring
- CBC before each cycle — delay if ANC < 1000 or platelets < 100K
- Interim PET/CT — after 2 cycles (HL) or 3-4 cycles (NHL). Complete metabolic response = Deauville 1-3.
- Echo q3 months during anthracycline therapy (doxorubicin cardiotoxicity)
- PFTs during bleomycin therapy — stop if DLCO drops > 20% from baseline
- HBV DNA monthly if on rituximab with HBV risk (reactivation can be fatal)
- LDH + uric acid before each cycle — rising LDH suggests progression; high uric acid = TLS risk
- Post-treatment surveillance: CT q6 months × 2 years, then annually × 5 years. PET only if suspected relapse (not for routine surveillance).
🏥 Rounds
Sample Presentation
Mr. Rodriguez is a 28-year-old man presenting with 6 weeks of painless left cervical lymphadenopathy (3 cm), night sweats, 10 lb weight loss, and pruritus. No fevers. No cough. Exam: firm, rubbery, non-tender left cervical and left supraclavicular nodes. No hepatosplenomegaly. Labs: WBC 9K, Hgb 11.8, LDH 320 (elevated), ESR 45. CXR: mediastinal widening.
Key Points: Young male with B symptoms (weight loss > 10%, night sweats) + painless lymphadenopathy + mediastinal mass = classic Hodgkin lymphoma until proven otherwise. Next step: excisional lymph node biopsy (NOT FNA). Expect Reed-Sternberg cells (CD15+/CD30+). Staging with PET/CT. ABVD × 2-6 cycles based on stage. Cure rate > 80%.
Pimp Questions
❓ Why should you NOT do FNA for suspected lymphoma?
FNA provides individual cells but destroys the lymph node architecture needed for subtyping. Lymphoma diagnosis requires: architecture assessment (follicular vs diffuse), immunohistochemistry panel (CD20, CD3, CD15, CD30, Ki-67), and often FISH/cytogenetics. An excisional biopsy (or at minimum core needle biopsy) provides all of this. FNA can suggest lymphoma but cannot subtype it.
❓ What are B symptoms and why do they matter?
B symptoms: (1) Fever > 38°C, (2) drenching night sweats, (3) weight loss > 10% in 6 months. They indicate higher disease burden and worse prognosis. In Hodgkin lymphoma, B symptoms upstage the disease (Stage IIB is treated like advanced stage). Pruritus and alcohol-induced pain are associated symptoms but not technically B symptoms.
❓ Why must you screen for hepatitis B before starting rituximab?
Rituximab (anti-CD20) depletes B cells → HBV reactivation risk. Even patients with resolved infection (HBsAg−, anti-HBc+) can reactivate. Reactivation can cause fulminant hepatic failure. Screen ALL patients with HBsAg, anti-HBs, anti-HBc. If anti-HBc positive → start entecavir prophylaxis and monitor HBV DNA monthly. Continue prophylaxis 12 months after last rituximab dose.
❓ What is the difference between Hodgkin and Non-Hodgkin lymphoma?
Hodgkin: Reed-Sternberg cells (CD15+/CD30+), bimodal age (20s, 60s), contiguous spread (node to adjacent node), excellent prognosis (> 80% cure), mediastinal mass common. NHL: much more common (90%), diverse subtypes, non-contiguous spread, prognosis varies (follicular = indolent/incurable vs DLBCL = aggressive/curable vs Burkitt = ultra-aggressive).
❓ When do you "watch and wait" vs treat lymphoma?
Watch and wait is appropriate for asymptomatic follicular lymphoma with low tumor burden. Criteria for treatment: B symptoms, cytopenias from marrow involvement, bulky disease (> 7 cm), organ compression, rapid growth, or patient preference. Treating asymptomatic follicular lymphoma does not improve survival. For ALL aggressive lymphomas (DLBCL, Burkitt, HL with B symptoms), treatment should start promptly.
❓ What fertility counseling is needed before starting lymphoma chemotherapy?
Alkylating agents (cyclophosphamide, procarbazine) and radiation cause gonadal toxicity. Men: sperm banking before first cycle. Women: oocyte/embryo cryopreservation (requires 2 weeks for ovarian stimulation — discuss urgency with oncology). ABVD has lower gonadal toxicity than BEACOPP. Document the fertility discussion — it is a quality measure and medicolegal requirement.
📋 Summary
Summary
Hodgkin
Reed-Sternberg cells. Bimodal. ABVD. Cure > 80%. B symptoms upstage.
DLBCL
Most common aggressive NHL. R-CHOP × 6. Cure 60-70%. CNS prophylaxis if high-risk.
Follicular
Indolent. Watch-and-wait if asymptomatic. Not curable but median survival > 15y.
Workup
Excisional biopsy (never FNA). PET/CT staging. BMBx. LDH, HBV, HIV, echo, PFTs.
Intern Job
TLS prevention. Infection prophylaxis. Transfusion. Recognize complications. Fertility counseling.
Pearl
Screen HBV before rituximab. Don't FNA a node. B symptoms matter. Fertility talk before chemo.
📄 One Pager
One-Pager
Lymphoma
Hodgkin vs Non-Hodgkin
Key Regimens
HL: ABVD (or BV-AVD). DLBCL: R-CHOP. Follicular: rituximab ± bendamustine. Burkitt: intensive regimen + TLS prophylaxis (rasburicase).
Before Starting Chemo
Echo (baseline EF). PFTs (if bleomycin). HBV screen (rituximab reactivation risk). HIV. Fertility counseling. Port placement. TLS risk assessment.
Trials
GELA 2002 (R-CHOP for DLBCL) · ECHELON-1 2018 (BV-AVD for HL) · RELEVANCE (rituximab + lenalidomide for follicular)
Hyperosmolar Hyperglycemic State (HHS)
Life-threatening diabetic emergency with extreme hyperglycemia (> 600), hyperosmolality (> 320), and profound dehydration. Mortality 5-20% — much higher than DKA.
🔍 Overview
Overview
HHS is a diabetic emergency characterized by severe hyperglycemia (> 600 mg/dL), hyperosmolality (> 320 mOsm/kg), and profound dehydration (average 8-10L deficit) without significant ketoacidosis (pH > 7.30, bicarb > 18, minimal ketonemia). [ADA Consensus, Kitabchi 2009 Occurs almost exclusively in Type 2 diabetes, typically in elderly patients with limited water access (nursing home, dementia, post-CVA). Mortality is 5-20% — much higher than DKA — because patients are older with more comorbidities and the degree of dehydration is more severe. Triggers: infection (#1, especially UTI/pneumonia), medication non-compliance, new diabetes diagnosis, MI, stroke, medications (steroids, thiazides). Key difference from DKA: HHS patients have enough insulin to prevent lipolysis/ketogenesis, but not enough for glucose uptake. Treatment priority: fluids first, insulin second.
🧪 Workup
Workup
- Fingerstick glucose — often > 600 mg/dL (can exceed 1000). Some glucometers read "HIGH" above 500 → send serum glucose.
- BMP — Na⁺ (correct for hyperglycemia: add 1.6 mEq per 100 mg/dL glucose above 100), K⁺ (total body depleted even if serum normal/elevated), Cr (pre-renal AKI from dehydration), bicarb (should be > 18 in pure HHS)
- Serum osmolality (measured) — > 320 mOsm/kg diagnostic. Calculate: 2×Na + glucose/18 + BUN/2.8. Effective osmolality (excludes BUN): 2×Na + glucose/18 > 320.
- ABG/VBG — pH > 7.30 in pure HHS. If pH < 7.30 → mixed HHS/DKA (treat as DKA).
- Serum ketones/BHB — should be minimal. If significantly elevated → DKA component.
- CBC — leukocytosis (common even without infection due to stress demargination). Left shift or bandemia more suggestive of infection.
- Blood cultures, UA/urine culture, CXR — infection workup (trigger in > 50% of cases)
- Lactate — hypoperfusion from dehydration
- ECG — rule out MI as trigger. Check for hyperkalemia/hypokalemia changes.
- Lipase — pancreatitis can trigger HHS
🚨 Management
Management
- Step 1 — AGGRESSIVE IV FLUIDS (priority #1):
- NS 1-1.5 L/hr × first 1-2 hours (15-20 mL/kg/hr). These patients are 8-10L depleted.
- After initial bolus: NS 250-500 mL/hr if corrected Na low or normal. 0.45% NS if corrected Na elevated.
- When glucose < 300 → add D5 0.45% NS (not D5W — need to continue volume repletion).
- Step 2 — POTASSIUM REPLETION: Check K⁺ before insulin. If K⁺ < 3.3 → replete BEFORE insulin. If 3.3-5.3 → add 20-40 mEq K⁺ per liter of IVF. If > 5.3 → hold K⁺, recheck in 2h.
- Step 3 — INSULIN (lower priority than fluids): Regular insulin 0.1 U/kg/hr IV drip (no bolus in HHS). Start AFTER 1-2L fluids and confirmed K⁺ ≥ 3.3. Target glucose decline: 50-70 mg/dL per hour. Reduce rate to 0.02-0.05 U/kg/hr when glucose < 300. ADA Hyperglycemic Crises Protocol, Kitabchi 2009
- Step 4 — TREAT THE TRIGGER: Antibiotics for infection. Hold offending medications. Manage MI/stroke if present.
- Step 5 — DVT PROPHYLAXIS: Enoxaparin 40 mg SQ daily. HHS is a hypercoagulable state (hemoconcentration + immobility).
⚠ Do NOT drop osmolality > 3 mOsm/kg/hr — risk of cerebral edema (especially in elderly). Fluids alone will drop glucose significantly before insulin is even started. Fluids first, insulin second.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| NS (0.9% NaCl) | 1-1.5 L/hr × 1-2h → 250-500 mL/hr | IV | First-line. Priority #1. Average deficit 8-10L. Switch to 0.45% if corrected Na high. |
| Regular insulin | 0.1 U/kg/hr (no bolus) | IV drip | Start AFTER fluids + K⁺ ≥ 3.3. Target BG drop 50-70/hr. Reduce when < 300. |
| KCl | 20-40 mEq per liter IVF | IV | Total body K⁺ depleted. Replete before insulin. K⁺ < 3.3 → hold insulin until repleted. |
| D5 + 0.45% NS | 150-250 mL/hr | IV | When glucose < 300. Continue volume repletion while preventing hypoglycemia. |
| Enoxaparin | 40 mg SQ daily | SQ | DVT prophylaxis — HHS is hypercoagulable. |
| Glargine | 0.2-0.3 U/kg SQ | SQ | Give 2-4h BEFORE stopping insulin drip for transition. Do NOT stop drip without basal overlap. |
📊 Monitoring
Monitoring
- Fingerstick glucose q1h — target decline 50-70 mg/dL per hour. Faster correction risks cerebral edema.
- BMP q2-4h — K⁺ (shifts dramatically with insulin), Na⁺ (corrected Na should rise as glucose falls — if not, you're giving too much free water), Cr (improving = adequate hydration)
- Serum osmolality q2-4h — target decline ≤ 3 mOsm/kg/hr. If dropping faster → slow IVF rate.
- Urine output q1h — target ≥ 0.5 mL/kg/hr (sign of adequate resuscitation). Foley catheter in ICU.
- Mental status — should improve as osmolality normalizes. If AMS worsens despite improving labs → CT head (stroke may have been the trigger).
- Fluid balance (I&Os) — track meticulously. Goal: replace deficit over 24-48h.
- Resolution criteria: glucose < 300, osmolality < 315, patient alert/eating → transition to SQ insulin. ADA/AACE Consensus, 2009
🏥 Rounds
Sample Presentation
Mrs. Williams is an 78-year-old woman with T2DM, dementia, and HTN, brought from nursing home with 3 days of altered mental status, decreased PO intake, and new incontinence. VS: T 100.4°F, HR 112, BP 92/58, RR 20. Exam: dry mucous membranes, tenting, somnolent but arousable. Labs: glucose 923, Na 149 (corrected 163), K 4.8, Cr 2.8 (baseline 1.1), pH 7.34, bicarb 20, BHB 0.8, serum osm 384. UA: pyuria. CXR: clear.
Key Points: Classic HHS — glucose > 600, osm > 320, no significant ketoacidosis. Trigger: UTI (pyuria + fever). Start NS 1.5L/hr. K⁺ is adequate → can start insulin at 0.1 U/kg/hr after first 1-2L fluids. Treat UTI empirically. DVT prophylaxis. ICU for monitoring. This patient has ~10L fluid deficit.
Pimp Questions
❓ What is the key pathophysiologic difference between HHS and DKA?
In HHS, patients have enough circulating insulin to prevent lipolysis and ketogenesis, but not enough for peripheral glucose uptake. So they develop extreme hyperglycemia without significant ketoacidosis. In DKA, there is absolute insulin deficiency → uninhibited lipolysis → ketone body production → metabolic acidosis. This is why HHS is nearly exclusive to Type 2 DM (some residual insulin production).
❓ Why are fluids more important than insulin in HHS?
HHS patients have an average 8-10L fluid deficit (vs 3-5L in DKA). Aggressive IV fluids alone will drop glucose by 75-100 mg/dL per hour through dilution + improved renal perfusion → glycosuria. Starting insulin before adequate hydration risks cardiovascular collapse (glucose drops → water moves intracellularly → further intravascular depletion) and cerebral edema (too-rapid osmolality correction).
❓ How do you calculate corrected sodium in hyperglycemia?
Corrected Na = measured Na + 1.6 × [(glucose − 100) / 100]. Hyperglycemia causes osmotic water shift from ICF to ECF → dilutional hyponatremia. The corrected Na tells you the true sodium status. If corrected Na is elevated → the patient is even more hyperosmolar and dehydrated than the measured Na suggests. Use corrected Na to guide IVF choice (0.9% vs 0.45% NS).
❓ Why is mortality in HHS so much higher than DKA?
HHS mortality is 5-20% (vs 1-5% for DKA) because: (1) patients are older with more comorbidities, (2) the trigger is often a serious acute illness (MI, stroke, sepsis), (3) degree of dehydration is much more severe (8-10L), (4) hyperosmolality itself causes end-organ damage, (5) HHS is a hypercoagulable state → arterial and venous thrombosis.
❓ What is the risk of correcting osmolality too quickly?
Cerebral edema. The brain adapts to chronic hyperosmolality by generating idiogenic osmoles (intracellular solutes). Rapid correction of serum osmolality causes water to shift into brain cells → edema. Target osmolality decline ≤ 3 mOsm/kg/hr. This is analogous to osmotic demyelination in too-rapid sodium correction.
❓ When do you transition from IV insulin drip to subcutaneous insulin?
When the patient meets ALL of: (1) glucose < 300, (2) osmolality < 315, (3) alert and eating. Give basal insulin (glargine 0.2-0.3 U/kg) 2-4 hours BEFORE stopping the drip — the drip has a half-life of only 5-10 minutes, so any gap in coverage → rebound hyperglycemia.
📋 Summary
Summary
Criteria
Glucose > 600, Osm > 320, pH > 7.30, bicarb > 18, minimal ketones
Fluid Deficit
8-10 L average. NS 1-1.5 L/hr × 1-2h → 250-500 mL/hr. Fluids BEFORE insulin.
Insulin
0.1 U/kg/hr IV (no bolus). Start AFTER fluids + K⁺ ≥ 3.3. Target 50-70 drop/hr.
Trigger
Infection #1 (UTI, PNA). Also: MI, stroke, meds (steroids), non-compliance.
Mortality
5-20% (much higher than DKA). Older patients, worse dehydration, hypercoagulable.
Pearl
Fluids alone drop glucose 75-100/hr. Don't overcorrect osm (< 3/hr). DVT prophylaxis always.
📄 One Pager
One-Pager
HHS
Hyperosmolar Hyperglycemic State
Protocol
Step 1: NS 1-1.5 L/hr × 1-2h (FLUIDS FIRST). Step 2: Check K⁺ — replete if < 3.3 BEFORE insulin. Step 3: Insulin 0.1 U/kg/hr IV (no bolus). Step 4: Treat trigger (infection, MI). Step 5: DVT prophylaxis.
HHS vs DKA
HHS: glucose > 600, osm > 320, no ketoacidosis, T2DM, elderly, 8-10L deficit, mortality 5-20%. DKA: glucose > 250, AG acidosis, ketones, T1DM (or T2), younger, 3-5L deficit, mortality 1-5%.
Danger Zone
Osm correction > 3/hr → cerebral edema. Insulin before fluids → cardiovascular collapse. Insulin before K⁺ → fatal hypokalemia. Stop drip without basal overlap → rebound hyperglycemia.
Myxedema Coma
Life-threatening decompensated hypothyroidism. Mortality 25-60%. Classic: hypothermia + AMS + precipitating event in a patient with untreated hypothyroidism.
🔍 Overview
Overview
Myxedema coma is the most severe form of hypothyroidism, representing decompensation of long-standing untreated or undertreated disease. Despite the name, actual coma is present in only ~20% — most present with AMS, obtundation, or extreme lethargy. Mortality is 25-60% even with treatment. Classic triad: (1) altered mental status, (2) hypothermia (often < 95°F/35°C), (3) precipitating event. Triggers: infection (#1), cold exposure, sedatives/opioids, surgery, MI, stroke, medication non-compliance. Almost exclusively affects elderly women in winter. Think of it as multi-organ failure from severe thyroid hormone deficiency: decreased cardiac output, hypoventilation (CO₂ retention), hypothermia, hyponatremia (impaired free water excretion), hypoglycemia, and ileus.
🧪 Workup
Workup
- TSH — markedly elevated in primary hypothyroidism (most cases). Low/normal TSH = central (pituitary) hypothyroidism.
- Free T4 — very low. Free T3 also low but less reliable.
- AM cortisol — MUST check before giving levothyroxine. Concomitant adrenal insufficiency is common (either autoimmune polyendocrine syndrome or central hypothyroidism with secondary AI). Giving T4 without cortisol replacement → adrenal crisis.
- BMP — hyponatremia (impaired free water excretion → dilutional), hypoglycemia, elevated Cr (decreased renal perfusion)
- ABG/VBG — respiratory acidosis (CO₂ retention from hypoventilation). May need intubation.
- CBC — anemia (chronic disease), possible leukocytosis if infection triggered
- CK — rhabdomyolysis from hypothyroid myopathy
- Lipase — ileus/pancreatitis
- Blood cultures, UA, CXR — infection workup (most common trigger)
- ECG — bradycardia, low voltage, prolonged QTc, J (Osborn) waves from hypothermia
- Core temperature — use low-reading thermometer. Standard thermometers may not register below 94°F.
🚨 Management
Management
- Step 1 — Stress-dose steroids FIRST: Hydrocortisone 100 mg IV before or simultaneously with T4. Never give T4 alone — may precipitate adrenal crisis if concomitant AI (which you won't know until cortisol results return). [Endocrine Society]
- Step 2 — IV levothyroxine (T4): Loading dose 200-400 mcg IV × 1, then 50-100 mcg IV daily. Must be IV — GI absorption is unreliable in myxedema (ileus, edema). Some experts add IV T3 (liothyronine) 5-20 mcg IV q8h for faster onset (T4 takes days to convert to active T3).
- Step 3 — Supportive care:
- Passive rewarming — warm blankets, warming to room temperature. Do NOT actively rewarm aggressively (causes vasodilation → cardiovascular collapse).
- Mechanical ventilation if hypercapnic respiratory failure (CO₂ narcosis)
- Fluid resuscitation — cautious (impaired cardiac function). Avoid free water (worsens hyponatremia).
- Vasopressors if hypotension refractory to fluids + steroids
- Glucose — D50 for hypoglycemia
- Step 4 — Treat the trigger: Broad-spectrum antibiotics if infection suspected (low threshold — hypothermia masks fever).
⚠ The most dangerous mistake: giving levothyroxine without cortisol coverage. T4 increases metabolic rate → increases cortisol demand → if adrenals can't respond → adrenal crisis → death.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Hydrocortisone | 100 mg IV bolus → 50 mg IV q8h | IV | GIVE BEFORE OR WITH T4. Stress-dose steroids until AI is ruled out. Endocrine Society, 2014 |
| Levothyroxine (Synthroid/T4) | 200-400 mcg IV load → 50-100 mcg IV daily | IV | Must be IV (GI absorption unreliable). Onset: days. T4→T3 conversion impaired in critical illness. |
| Liothyronine (T3) | 5-20 mcg IV q8h | IV | Optional — faster onset than T4. Use cautiously in elderly/cardiac patients (arrhythmia risk). Stop once clinically improving. |
| D50W | 25g (50 mL) IV PRN | IV | For hypoglycemia (common in myxedema due to decreased gluconeogenesis). |
| Broad-spectrum antibiotics | Per clinical suspicion | IV | Low threshold — infection is #1 trigger and hypothermia masks fever. Empiric coverage until cultures return. |
📊 Monitoring
Monitoring
- Core temperature q2-4h — low-reading thermometer. Warming should be gradual. Target: rise of 0.5°C per hour maximum.
- Cardiac telemetry — continuous. Watch for bradycardia, heart block, QTc prolongation, torsades. T3 replacement can cause tachycardia/arrhythmia.
- TSH + Free T4 — recheck at 24-48h (T4 should be rising). TSH takes weeks to normalize — don't chase it.
- AM cortisol result — if < 18 mcg/dL → confirmed AI → continue hydrocortisone. If normal → can taper steroids.
- BMP q6-12h — Na⁺ (should improve with T4), glucose (hypoglycemia risk), K⁺
- ABG — CO₂ trending (hypercapnia should improve). Intubate if pCO₂ rising or AMS worsening.
- Mental status — should improve over 24-72h with treatment. If not → re-evaluate for missed trigger (sepsis, stroke).
- CK trending — rhabdomyolysis from myxedema myopathy (aggressive IVF + monitor renal function)
🏥 Rounds
Sample Presentation
Mrs. Thompson is a 82-year-old woman with known hypothyroidism (ran out of levothyroxine 2 months ago) brought from home by family for progressive lethargy × 5 days, now barely arousable. VS: T 93.6°F (34.2°C), HR 48, BP 88/52, RR 10. Exam: periorbital edema, macroglossia, dry skin, delayed DTRs, non-pitting edema of extremities. Labs: TSH > 100, Free T4 < 0.1, Na 118, glucose 52, cortisol pending, pCO₂ 68.
Key Points: Classic myxedema coma — hypothermia + AMS + bradycardia + hyponatremia + hypoglycemia + CO₂ retention in untreated hypothyroid. IMMEDIATE: hydrocortisone 100 mg IV → then T4 200-400 mcg IV. D50 for glucose. Passive rewarming. Consider intubation for hypercapnic respiratory failure (pCO₂ 68). ICU. Treat infection empirically.
Pimp Questions
❓ Why must you give steroids BEFORE levothyroxine in myxedema coma?
Many myxedema patients have concomitant adrenal insufficiency — either autoimmune polyendocrine syndrome (Hashimoto's + Addison's) or central hypothyroidism with secondary AI. Giving T4 increases metabolic rate → increases cortisol demand. If the adrenals can't respond → acute adrenal crisis → cardiovascular collapse → death. Always give hydrocortisone 100 mg IV first or simultaneously. [Endocrine Society]
❓ Why must levothyroxine be given IV in myxedema coma?
Myxedema causes impaired GI absorption from: (1) intestinal mucosal edema, (2) ileus/decreased motility, (3) decreased blood flow to the gut. Oral bioavailability of T4, which is already ~70% in normal patients, drops further. IV levothyroxine bypasses all of these issues and provides 100% bioavailability.
❓ Why is aggressive rewarming dangerous in myxedema coma?
Active rewarming causes peripheral vasodilation → drops preload → cardiovascular collapse in a patient who already has decreased cardiac output and contractility from hypothyroidism. Passive rewarming (warm blankets, raising room temperature) is safer. Target warming rate: 0.5°C per hour maximum.
❓ Why does myxedema coma cause hyponatremia?
Hypothyroidism causes hyponatremia through impaired free water excretion: (1) decreased cardiac output → decreased renal perfusion → increased ADH secretion, (2) decreased GFR → decreased free water delivery to collecting duct, (3) direct effect of thyroid hormone deficiency on aquaporin channels. The hyponatremia improves with T4 replacement — do NOT fluid restrict or give hypertonic saline (risks cerebral edema from too-rapid correction).
❓ What is the role of IV T3 (liothyronine) in myxedema coma?
T3 is the active thyroid hormone (T4 is a prohormone that must be converted to T3). In critical illness, peripheral T4→T3 conversion is impaired (sick euthyroid/non-thyroidal illness). IV T3 provides the active hormone directly, with onset in hours (vs days for T4). However, T3 is more likely to cause arrhythmia — use cautiously in elderly patients with cardiac disease. Most experts use combination T4 + low-dose T3.
❓ How do you differentiate myxedema coma from other causes of hypothermia + AMS?
Key clues for myxedema: (1) history of hypothyroidism or thyroidectomy scar, (2) periorbital/non-pitting edema, (3) macroglossia, (4) delayed relaxation phase of DTRs (pathognomonic), (5) hyponatremia + hypoglycemia + hypercapnia triad, (6) bradycardia disproportionate to hemodynamics. TSH and Free T4 confirm, but treatment should NOT wait for lab results if clinical suspicion is high.
📋 Summary
Summary
Triad
AMS + hypothermia + precipitant in untreated hypothyroidism
Step 1
Hydrocortisone 100 mg IV FIRST — rule out concomitant AI before T4
Step 2
T4 200-400 mcg IV load → 50-100 daily. ± T3 5-20 mcg IV q8h.
Labs
TSH sky-high, Free T4 undetectable, Na low, glucose low, pCO₂ high
Mortality
25-60% even with treatment. Elderly women in winter.
Danger
T4 without steroids → adrenal crisis. Active rewarming → cardiovascular collapse.
📄 One Pager
One-Pager
Myxedema Coma
Decompensated Hypothyroidism
Protocol
Step 1: Hydrocortisone 100 mg IV (BEFORE T4). Step 2: T4 200-400 mcg IV load ± T3 5-20 mcg IV q8h. Step 3: Passive rewarming. Step 4: Treat trigger. Step 5: ICU monitoring.
Classic Features
Hypothermia (< 95°F). Bradycardia. AMS → obtundation. Hyponatremia. Hypoglycemia. Hypercapnia. Non-pitting edema. Macroglossia. Delayed DTRs. Periorbital puffiness.
Pheochromocytoma
Catecholamine-secreting tumor of the adrenal medulla. Rule of 10s: 10% bilateral, 10% extra-adrenal (paraganglioma), 10% malignant, 10% familial. Alpha-block BEFORE beta-block.
🔍 Overview
Overview
Pheochromocytoma is a catecholamine-secreting neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. Extra-adrenal tumors = paragangliomas (arise from sympathetic ganglia — organ of Zuckerkandl most common). Classic presentation: paroxysmal triad of headache + sweating + palpitations with hypertension. Accounts for < 1% of hypertension but must be considered in: resistant HTN, hypertensive crisis with paroxysms, adrenal incidentaloma, familial syndromes (MEN2A/2B, VHL, NF1, SDH mutations). "Rule of 10s": 10% bilateral, 10% extra-adrenal, 10% malignant, 10% pediatric, ~40% familial (higher than classically taught). The critical teaching point: Alpha-blockade MUST precede beta-blockade — unopposed alpha stimulation during beta-blockade → hypertensive crisis.
🧪 Workup
Workup
- Plasma free metanephrines — best initial screening test. Sensitivity > 97%. Elevated metanephrine (from epinephrine) or normetanephrine (from norepinephrine). Draw with patient supine × 30 min. Lenders et al., Endocrine Society 2014
- 24-hour urine metanephrines + catecholamines — confirmatory if plasma equivocal. Also useful for monitoring post-resection.
- CT abdomen/pelvis with contrast — localize adrenal mass. Pheos are typically > 3 cm, heterogeneous, > 10 HU on non-contrast CT (lipid-poor), enhance avidly.
- MRI abdomen — alternative. Classic "light bulb" bright signal on T2-weighted images. Preferred in pregnancy, children, and known SDH mutations.
- MIBG scan (I-123) — functional imaging for metastatic disease, extra-adrenal paragangliomas, or recurrence. If MIBG negative → FDG-PET or Ga-68 DOTATATE PET.
- Genetic testing — recommended for ALL pheos/paragangliomas. Up to 40% have germline mutations: SDHx (most common), RET (MEN2), VHL, NF1, MAX, TMEM127.
- Do NOT biopsy adrenal mass if pheo is suspected — risk of catecholamine crisis during needle insertion.
🚨 Management
Management
- Step 1 — Alpha-blockade (start 10-14 days before surgery):
- Phenoxybenzamine 10 mg BID → titrate to 20-30 mg BID (non-competitive, irreversible alpha-blocker — gold standard pre-op). Target: seated BP < 130/80 with standing SBP > 90. [Lenders et al., Endocrine Society 2014
- Alternative: doxazosin 2-8 mg daily (competitive alpha-1 blocker — shorter acting, less reflex tachycardia).
- Step 2 — Beta-blockade (ONLY after adequate alpha-blockade): Start 2-3 days before surgery or once HR > 100 on alpha-blocker. Propranolol 20-40 mg TID or atenolol 25-50 mg daily. Controls reflex tachycardia from alpha-blockade.
- Step 3 — Volume expansion: High-sodium diet + liberal fluids in the 1-2 weeks pre-op. Chronic catecholamine excess → vasoconstriction → intravascular volume depletion. Volume resuscitation prevents post-resection hypotension.
- Step 4 — Surgery: Laparoscopic adrenalectomy is definitive treatment. Intraoperative: expect BP swings during tumor manipulation → have nitroprusside (for hypertensive surges) and phenylephrine (for hypotension post-ligation) ready.
- Hypertensive crisis management: Phentolamine 2-5 mg IV q5min (competitive alpha-blocker) or nicardipine drip. NEVER give beta-blocker alone — unopposed alpha → worse hypertension.
⚠ ALPHA BEFORE BETA — always. Beta-blockade alone removes beta-2 vasodilation → unopposed alpha-1 vasoconstriction → lethal hypertensive crisis. This is one of the most tested principles in endocrinology. Goldstein et al., 1999
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Phenoxybenzamine | 10 mg BID → titrate to 20-30 mg BID | PO | Non-competitive alpha-blocker. Start 10-14 days pre-op. Irreversible — long duration. Orthostatic hypotension, nasal congestion, reflex tachycardia. |
| Doxazosin | 2-8 mg daily | PO | Competitive alpha-1 blocker. Shorter acting than phenoxybenzamine. Less tachycardia. Some centers prefer. |
| Propranolol | 20-40 mg TID | PO | ONLY after alpha-blockade established. Controls reflex tachycardia. Start 2-3 days before surgery. |
| Metyrosine | 250 mg QID (max 4g/day) | PO | Tyrosine hydroxylase inhibitor — blocks catecholamine synthesis. For refractory hypertension or inoperable tumors. Sedation, EPS side effects. |
| Phentolamine | 2-5 mg IV q5min PRN | IV | Hypertensive crisis. Competitive alpha-blocker. Fast onset. Have ready in OR during tumor manipulation. |
| Nicardipine | 5-15 mg/hr IV | IV drip | Alternative for intraoperative/crisis BP control. Smooth, titratable. |
📊 Monitoring
Monitoring
- BP (standing + seated) daily during alpha-blockade titration — target: seated < 130/80, standing SBP > 90 mmHg (orthostatic tolerance confirms adequate blockade)
- HR — if > 100 on alpha-blocker → start beta-blocker (after adequate alpha-blockade confirmed)
- Pre-op checklist: BP controlled × 7-14 days, mild orthostatic hypotension present, HR 60-80, no ECG ischemia, no new ST changes × 2 weeks
- Intraoperative: arterial line mandatory. Expect BP surges during tumor manipulation → phentolamine/nitroprusside ready. Expect hypotension after tumor ligation → volume + phenylephrine/vasopressin ready.
- Post-op glucose — hypoglycemia is common after tumor removal (catecholamines were suppressing insulin → insulin rebound). Monitor glucose q1-2h × 24h.
- Post-op plasma metanephrines — at 2-4 weeks. Should normalize. If persistently elevated → residual/metastatic disease.
- Annual biochemical screening — lifelong (recurrence risk ~5-10%). More frequent if genetic syndrome.
- Genetic counseling — all patients. Screen first-degree relatives if mutation found.
🏥 Rounds
Sample Presentation
Mr. Park is a 42-year-old man presenting with episodic headaches, diaphoresis, and palpitations × 6 months. Episodes last 15-30 min, occur 2-3 times per week, associated with severe hypertension (240/130 during episodes, 155/95 baseline). Home medications: amlodipine 10 mg, lisinopril 40 mg, HCTZ 25 mg (resistant HTN). Labs: plasma normetanephrine 1850 pg/mL (> 4× ULN). CT abdomen: 4.2 cm right adrenal mass, heterogeneous enhancement, 38 HU on non-contrast.
Key Points: Classic pheo — paroxysmal triad + resistant HTN + markedly elevated normetanephrine + lipid-poor adrenal mass. Start phenoxybenzamine 10 mg BID immediately. Titrate over 10-14 days. High-sodium diet for volume expansion. Add propranolol ONLY after adequate alpha-blockade. Genetic testing. Laparoscopic adrenalectomy after medical optimization.
Pimp Questions
❓ Why must you alpha-block BEFORE beta-blocking in pheochromocytoma?
Beta-2 receptors cause vasodilation. If you block them with a beta-blocker while catecholamines are still high, you remove the vasodilatory counterbalance → unopposed alpha-1 vasoconstriction → severe hypertensive crisis. Alpha-blockade first reduces the vasoconstriction, then beta-blockade safely controls the reflex tachycardia. This is one of the most tested principles in endocrinology.
❓ What is the best initial screening test for pheochromocytoma?
Plasma free metanephrines. Sensitivity > 97% — best rule-out test. Metanephrine (from epinephrine) and normetanephrine (from norepinephrine) are continuously produced by tumor metabolism (not just during paroxysms), making them more reliable than catecholamine levels. Draw with patient supine × 30 min to avoid false positives from sympathetic activation. [Lenders, 2014]
❓ Why should you NOT biopsy a suspected pheochromocytoma?
Needle insertion into the tumor causes massive catecholamine release → hypertensive crisis, arrhythmia, MI, stroke, death. Diagnosis is made by biochemistry (metanephrines) + imaging. If you see an adrenal mass and pheo is in the differential, rule out pheo biochemically BEFORE any invasive procedure.
❓ What percentage of pheochromocytomas are hereditary and what syndromes should you screen for?
Up to 40% have a germline mutation (much higher than the historical "10%"). Key syndromes: MEN2A/2B (RET mutation — pheo + medullary thyroid carcinoma ± hyperparathyroidism), VHL (hemangioblastomas + renal cell + pheo), NF1 (neurofibromas + pheo), SDHx mutations (paraganglioma-pheochromocytoma syndrome — most common hereditary cause). Genetic testing recommended for ALL patients.
❓ What happens to blood glucose immediately after pheochromocytoma resection?
Hypoglycemia. Catecholamines suppress insulin secretion and stimulate gluconeogenesis/glycogenolysis. After tumor removal, the catecholamine-mediated insulin suppression is abruptly removed → rebound hyperinsulinemia → hypoglycemia. Monitor glucose q1-2h for 24h post-op. Have D50 ready.
❓ What blood pressure pattern on ambulatory monitoring suggests pheochromocytoma?
Paroxysmal hypertension with intervening normotension or hypotension. Also: loss of nocturnal dipping (BP stays elevated at night instead of the normal 10-20% drop). Some patients present with orthostatic hypotension — paradoxically, chronic catecholamine excess → receptor downregulation + volume depletion → orthostasis between paroxysms.
📋 Summary
Summary
Triad
Headache + sweating + palpitations with paroxysmal hypertension
Screen
Plasma free metanephrines (sensitivity > 97%). 24h urine for confirmation.
Imaging
CT/MRI adrenal → MIBG or DOTATATE PET for extra-adrenal/metastatic
Treatment
Alpha-block × 10-14d → beta-block → volume expand → surgery.
Never Do
Beta-block alone. Biopsy the mass. Skip genetic testing.
Post-Op
Monitor glucose (hypoglycemia). Metanephrines at 2-4 wk. Annual screening lifelong.
📄 One Pager
One-Pager
Pheochromocytoma
Alpha before Beta. Always.
Pre-Op Protocol
Day 1-14: Phenoxybenzamine 10 mg BID → titrate. Day 10+: Add propranolol ONLY after alpha adequate. Diet: high sodium + fluids. Goal: BP < 130/80 seated, SBP > 90 standing. OR ready: phentolamine + nitroprusside + phenylephrine.
Red Flags
Do NOT biopsy (catecholamine crisis). Do NOT beta-block first (unopposed alpha → crisis). 40% hereditary → always genetic test. Post-op hypoglycemia — monitor glucose q1-2h × 24h.
Trials
Lenders 2014 (plasma metanephrines screening) · Endocrine Society Pheo Guidelines 2014
Inpatient Hypoglycemia
The most common inpatient endocrine emergency. Every episode of glucose < 70 requires intervention. Recurrent hypoglycemia increases mortality independent of the cause.
🔍 Overview
Overview
Inpatient hypoglycemia (glucose < 70 mg/dL) affects up to 10-30% of hospitalized diabetic patients and is independently associated with increased mortality, longer LOS, and ICU transfer. NICE-SUGAR, NEJM 2009 Classified as: Level 1 (54-70 mg/dL, alert), Level 2 (< 54, clinically significant), Level 3 (severe, requiring assistance from another person). Most common causes: (1) insulin-food mismatch (holding meals while continuing insulin), (2) renal insufficiency (reduced insulin clearance), (3) reduced PO intake (NPO, nausea, surgery), (4) medication errors. Key principle: every hypoglycemic event is preventable and deserves root cause analysis. The attending will ask "why did this happen and what did you change?"
🧪 Workup
Workup
- Confirm with venous glucose — point-of-care glucometers are less accurate at low ranges. Whipple's triad: symptoms + low glucose + symptom resolution with glucose correction.
- Review insulin/secretagogue doses — #1 cause. Check timing of last insulin dose vs last meal. Basal insulin too high? Sliding scale overlapping with scheduled dose?
- BMP — Cr (AKI/CKD reduces insulin clearance → prolonged insulin effect), hepatic function (reduced gluconeogenesis)
- Medication reconciliation — sulfonylureas (long-acting, especially in CKD), insulin dose errors, fluoroquinolones (rare), pentamidine, beta-blockers (mask symptoms)
- NPO status — was patient made NPO for procedure while basal insulin continued?
- Nutrition assessment — decreased PO intake, skipped meals, vomiting, new tube feed interruption
- If non-diabetic unexplained hypoglycemia: insulin level + C-peptide + proinsulin + sulfonylurea screen (draw DURING hypoglycemia). High insulin + high C-peptide = endogenous hyperinsulinism (insulinoma). High insulin + low C-peptide = exogenous insulin. High C-peptide + positive SU screen = sulfonylurea use.
- Cortisol — if adrenal insufficiency suspected (especially if recurrent hypoglycemia with hypotension)
🚨 Management
Management
- Immediate treatment (Glucose < 70):
- Alert + able to eat: 15-20g fast-acting carbs (4 oz juice, 3-4 glucose tabs, 1 tbsp honey) → recheck in 15 min → repeat if still < 70 → follow with complex carb snack (crackers + peanut butter)
- Unable to eat / AMS / NPO: D50W 25g (50 mL) IV push → recheck in 15 min → repeat PRN → start D10W drip at 50-100 mL/hr if recurrent
- No IV access: Glucagon 1 mg IM/SQ. Causes nausea — position on side.
- Prevent recurrence (most important step):
- Reduce basal insulin by 20-40% if the episode occurred overnight or fasting ADA Standards of Care, 2023
- Hold or reduce prandial insulin if patient is eating less than usual or NPO
- Discontinue sulfonylurea in CKD/AKI (long half-life → recurrent hypoglycemia for 24-72h)
- Adjust sliding scale — reduce correction factor if consistently hypoglycemic
- Ensure meal delivery before prandial insulin — coordinate with nursing
- Hold prandial insulin if patient is NPO — only continue basal (and reduce by 20-50%)
- Document root cause analysis in the note — attendings expect it.
Sulfonylurea-induced hypoglycemia (especially glipizide/glyburide in CKD) can recur for 24-72 hours even after initial correction. These patients need D10 drip + hourly glucose checks + admission for observation. Octreotide 50 mcg SQ q6h can reduce insulin secretion in refractory cases.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| D50W (Dextrose 50%) | 25g (50 mL) IV push | IV | First-line for severe/unable to eat. Repeat q15min PRN. Causes phlebitis — use large bore IV. |
| D10W drip | 50-100 mL/hr | IV | For recurrent hypoglycemia (especially sulfonylurea-induced). Prevents repeated D50 pushes. |
| Glucagon | 1 mg IM/SQ | IM/SQ | If no IV access. Mobilizes hepatic glycogen. Ineffective if glycogen-depleted (alcoholics, liver failure). Causes nausea. |
| Octreotide (Sandostatin) | 50 mcg SQ q6h | SQ | For sulfonylurea-induced hypoglycemia refractory to D10. Suppresses insulin release from pancreatic beta cells. [McLaughlin, 2000] |
| Oral glucose (juice/tabs) | 15-20g fast-acting carbs | PO | First-line if alert + able to swallow. Follow with complex carbs. Recheck at 15 min. |
📊 Monitoring
Monitoring
- Fingerstick glucose q15 min until glucose > 100 and stable
- Then q1h × 4h to ensure no recurrence (especially with long-acting insulin or sulfonylureas)
- Resume regular glucose monitoring (AC/HS or q6h) once stable
- Review all insulin orders after ANY hypoglycemic event — this is the intern's most important action
- Notify attending of any Level 2 (< 54) or Level 3 (severe) hypoglycemia
- Hypoglycemia event report — many hospitals require formal incident reporting
- Pre-prandial glucose + post-meal check if adjusting regimen — verify effectiveness of changes
- A1c — helps guide discharge insulin regimen (A1c < 7% on insulin = possibly over-basal'd)
🏥 Rounds
Sample Presentation
Mr. Garcia is a 68-year-old man with T2DM on glargine 40 units + glipizide 10 mg BID, admitted for pneumonia, found to have fingerstick glucose of 38 at 3 AM. Diaphoretic, confused. Last meal was dinner at 5 PM (ate 50% of tray). Cr 2.4 (baseline 1.2). Received full sliding scale correction of 6 units at 9 PM for glucose of 220.
Key Points: Three contributors: (1) Glipizide in AKI (reduced clearance → prolonged hypoglycemic effect), (2) reduced PO intake, (3) sliding scale correction on top of basal + sulfonylurea. Immediate: D50 25g IV → start D10 drip. Prevent: STOP glipizide (always in AKI). Reduce glargine by 40% (24 units). Reduce sliding scale. This patient needs q1h glucose checks × 24h because glipizide will continue to cause hypoglycemia.
Pimp Questions
❓ Why is sulfonylurea-induced hypoglycemia more dangerous than insulin-induced?
Sulfonylureas (especially glyburide and glipizide) have long half-lives (12-24h+) that are prolonged further in CKD. Unlike insulin which has a predictable duration, sulfonylureas can cause recurrent hypoglycemia for 24-72 hours even after initial correction. This is why patients need D10 drip + observation, not just a D50 push and discharge. Octreotide can help by suppressing insulin release.
❓ How do you differentiate insulinoma from exogenous insulin administration?
Draw labs during hypoglycemia: Insulinoma: high insulin + high C-peptide + high proinsulin (endogenous production). Exogenous insulin: high insulin + LOW C-peptide (exogenous insulin suppresses endogenous production). Sulfonylurea use: high insulin + high C-peptide + positive sulfonylurea screen. C-peptide is the key differentiator because commercial insulin preparations do not contain C-peptide.
❓ When should you use octreotide for hypoglycemia?
Sulfonylurea-induced hypoglycemia refractory to D10 drip. Octreotide (somatostatin analog) suppresses insulin secretion from pancreatic beta cells. Dose: 50 mcg SQ q6h. It is NOT useful for insulin-induced hypoglycemia (the problem is exogenous insulin, not endogenous secretion). Consider in: recurrent hypoglycemia despite D10, glipizide/glyburide with CKD, intentional sulfonylurea ingestion. [McLaughlin, 2000]
❓ What insulin adjustments should you make after an inpatient hypoglycemic event?
Root cause analysis + immediate order changes: (1) If overnight/fasting hypo → reduce basal insulin by 20-40%. (2) If post-prandial hypo → reduce prandial/correction dose. (3) If NPO → hold prandial, reduce basal by 20-50%. (4) If on sulfonylurea + AKI/CKD → STOP sulfonylurea. (5) If multiple sliding scale corrections overlapping → simplify regimen. Document the analysis and changes in your note — this is expected by attendings.
❓ Why does glucagon not work in alcoholic or liver failure patients?
Glucagon works by mobilizing hepatic glycogen stores (glycogenolysis). In chronic alcoholics and liver failure patients, glycogen stores are depleted (alcohol inhibits gluconeogenesis + poor nutritional intake). Without glycogen to break down, glucagon is ineffective. These patients need IV dextrose (D50 or D10 drip) — there is no alternative.
❓ What is the "rule of 15" for hypoglycemia?
For alert patients who can eat: give 15 grams of fast-acting carbohydrate (4 oz juice, 3-4 glucose tabs) → recheck glucose in 15 minutes → repeat if still < 70. Once glucose > 70, follow with a complex carbohydrate snack to prevent recurrence. Simple and effective — but only works if the patient can protect their airway and swallow safely.
📋 Summary
Summary
Definition
Glucose < 70. Level 1: 54-70. Level 2: < 54. Level 3: needs help.
Treat
Alert: 15g carbs PO. Unable to eat: D50 25g IV. No IV: glucagon 1 mg IM. Recurrent: D10 drip.
Prevent
Reduce basal 20-40%. Stop SU in CKD. Hold prandial if NPO. Review all insulin orders.
SU Danger
Recurs × 24-72h (long half-life + CKD). D10 drip + octreotide 50 mcg q6h.
Root Cause
Document: insulin-food mismatch, NPO status, AKI, med error, reduced PO intake.
Pearl
Every hypo event is preventable. The attending will ask what you changed.
📄 One Pager
One-Pager
Inpatient Hypoglycemia
Treat, prevent, document
Immediate
Alert: 15g PO carbs → recheck 15 min. AMS/NPO: D50 25g IV → repeat PRN → D10 drip. No IV: glucagon 1 mg IM.
Prevent Recurrence
Reduce basal 20-40%. STOP sulfonylurea in AKI. Hold prandial if NPO. Ensure meal before prandial insulin. SU hypo: D10 drip + octreotide + observe 24-72h.
Workup If Non-Diabetic
Draw DURING hypo: insulin, C-peptide, proinsulin, sulfonylurea screen. High insulin + low C-peptide = exogenous. High insulin + high C-peptide = insulinoma or SU.
Hypocalcemia
Ionized calcium < 4.4 mg/dL or corrected total Ca < 8.5. Emergent when symptomatic (tetany, seizures, QTc prolongation). Most common causes: hypoparathyroidism (post-surgical), vitamin D deficiency, CKD.
🔍 Overview
Overview
Hypocalcemia = ionized Ca < 4.4 mg/dL or corrected total Ca < 8.5 mg/dL. Correct total calcium for albumin: corrected Ca = total Ca + 0.8 × (4 − albumin). Always check ionized calcium in critically ill patients (more accurate with hypoalbuminemia, acid-base disturbances). Most common causes: (1) Post-surgical hypoparathyroidism (after thyroidectomy/parathyroidectomy — most common inpatient cause), (2) Vitamin D deficiency (most common overall), (3) CKD (decreased 1,25-OH vitamin D production), (4) Hypomagnesemia (impairs PTH secretion AND causes PTH resistance — MUST correct Mg first), (5) Acute pancreatitis (calcium saponification), (6) Massive transfusion (citrate chelates calcium). Symptoms correlate with rate of decline more than absolute level.
🧪 Workup
Workup
- Ionized calcium — most accurate, especially in ICU (not affected by albumin or pH). < 4.4 mg/dL = hypocalcemia.
- Corrected total calcium — if ionized not available. Corrected = total + 0.8 × (4 − albumin).
- Albumin — for correction. Low albumin → falsely low total Ca (but ionized is normal).
- PTH (intact) — the diagnostic branch point. Low PTH = hypoparathyroidism (post-surgical, autoimmune, infiltrative). High PTH = secondary hyperparathyroidism (vitamin D deficiency, CKD, PTH resistance).
- Magnesium — MUST check. Mg < 1.5 → impairs PTH secretion AND causes end-organ PTH resistance. Hypocalcemia will NOT correct until Mg is repleted.
- 25-OH vitamin D — < 20 ng/mL = deficiency. Most common cause of hypocalcemia worldwide.
- 1,25-dihydroxy vitamin D — low in CKD (can't hydroxylate 25-OH to active form). Also low in hypoparathyroidism (PTH stimulates 1-alpha-hydroxylase).
- Phosphate — high PO₄ + low Ca = hypoparathyroidism or CKD. Low PO₄ + low Ca = vitamin D deficiency.
- ECG — prolonged QTc (risk of torsades de pointes). Also: ST changes mimicking ischemia.
- BMP, Cr — CKD assessment
🚨 Management
Management
- EMERGENT (symptomatic or iCa < 3.2):
- Calcium gluconate 1-2g IV over 10-20 min (10-20 mL of 10% solution). Can repeat. Preferred over calcium chloride (less tissue necrosis if infiltrates, can go through peripheral IV). Endocrine Society Guidelines, Brandi 2016
- Calcium chloride 1g IV — 3× more elemental calcium than gluconate. Requires central line (severe tissue necrosis if peripheral infiltration). Use for cardiac arrest or severe tetany.
- Follow bolus with calcium gluconate drip: 5-10g in 500 mL D5W over 12-24h (0.5-1.5 mg/kg/hr elemental Ca).
- Correct MAGNESIUM FIRST: Hypocalcemia will NOT respond to calcium supplementation if Mg is depleted. MgSO₄ 2-4g IV over 20-60 min.
- Chronic management:
- Vitamin D deficiency: Ergocalciferol 50,000 IU PO weekly × 8-12 wk → maintenance 1000-2000 IU daily
- Hypoparathyroidism: Calcitriol 0.25-2 mcg PO BID + calcium carbonate 1-3g TID with meals. Target: low-normal Ca (8-8.5) to avoid hypercalciuria.
- CKD: Calcitriol (active vitamin D) + phosphate binders. Correct 25-OH vitamin D if deficient. Manage per CKD-MBD guidelines.
Post-thyroidectomy "hungry bone syndrome": After parathyroidectomy for hyperparathyroidism, bones rapidly take up calcium → severe, prolonged hypocalcemia. May need IV calcium drip × days + high-dose oral calcium + calcitriol. Check Ca q6h post-op. Witteveen et al., 2013
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Calcium gluconate 10% | 1-2g (10-20 mL) IV over 10-20 min | IV | First-line IV. Can use peripheral IV. 93 mg elemental Ca per gram. Repeat PRN. Follow with drip. |
| Calcium chloride 10% | 1g (10 mL) IV over 5-10 min | IV (central) | 3× more elemental Ca than gluconate (272 mg/g). Central line ONLY — tissue necrosis risk. For arrest/severe tetany. |
| Ca gluconate drip | 5-10g in 500 mL D5W over 12-24h | IV | Continuous infusion for sustained correction. Do NOT mix with bicarb (precipitates). |
| MgSO₄ | 2-4g IV over 20-60 min | IV | Correct Mg BEFORE Ca. Hypomagnesemia causes PTH resistance → Ca won't correct. |
| Calcitriol | 0.25-2 mcg PO BID | PO | Active vitamin D. For hypoparathyroidism + CKD. Fast onset (1-2 days). Monitor Ca closely (narrow window). |
| Ergocalciferol (D2) | 50,000 IU weekly × 8-12 wk | PO | Vitamin D deficiency repletion. Then maintenance 1000-2000 IU daily. |
| Calcium carbonate | 500-1500 mg elemental TID with meals | PO | Chronic replacement. Requires gastric acid for absorption (take with food, not with PPI). |
📊 Monitoring
Monitoring
- Ionized calcium q4-6h during IV replacement (q2h if critically symptomatic)
- ECG — QTc monitoring. QTc should shorten as Ca normalizes. Torsades risk if QTc > 500 ms.
- Mg level — recheck after repletion. Must remain > 1.5 for Ca correction to work.
- Post-thyroidectomy: ionized Ca q6h × 24-48h. Albumin-corrected Ca unreliable post-surgery (fluid shifts). ATA Thyroidectomy Guidelines, 2020
- Phosphate — trending helps differentiate causes. Falling PO₄ + rising Ca on treatment = responding to vitamin D/PTH replacement.
- Chvostek and Trousseau signs — clinical bedside assessment. Chvostek: tap facial nerve → ipsilateral facial twitch. Trousseau: BP cuff inflated above systolic × 3 min → carpal spasm (more specific).
- 24h urine calcium — for chronic hypoparathyroidism. Target: avoid hypercalciuria (> 300 mg/24h) → nephrolithiasis risk.
- Cr — calcium + vitamin D therapy can worsen renal function. Monitor in CKD patients.
🏥 Rounds
Sample Presentation
Mrs. Liu is a 55-year-old woman, post-op day 1 from total thyroidectomy for papillary thyroid carcinoma. Nurse calls for perioral tingling and hand cramping. VS: HR 92, BP 128/78. Exam: positive Trousseau sign, positive Chvostek sign. Labs: iCa 3.6 mg/dL (low), Mg 1.8, PO₄ 5.2 (high), PTH < 5 (low). ECG: QTc 510 ms.
Key Points: Post-surgical hypoparathyroidism (most common cause of acute hypocalcemia in hospital). Low PTH + low Ca + high PO₄ = classic. QTc prolonged → emergent. Give calcium gluconate 2g IV over 20 min → start drip. Start calcitriol 0.5 mcg BID + calcium carbonate 1g TID. Check iCa q6h. This may be transient (parathyroids stunned) or permanent.
Pimp Questions
❓ Why must you correct magnesium before calcium?
Hypomagnesemia causes hypocalcemia through TWO mechanisms: (1) Impaired PTH secretion — Mg is required for PTH release from the parathyroid gland. (2) End-organ PTH resistance — Mg is needed for PTH to activate its receptor in bone and kidney. The result: giving calcium without correcting Mg is futile — the Ca will continue to drop because PTH is dysfunctional. Always check and correct Mg first.
❓ What is the difference between calcium gluconate and calcium chloride?
Calcium gluconate: 93 mg elemental Ca per gram. Can go through peripheral IV. Lower tissue necrosis risk. First-line for most situations. Calcium chloride: 272 mg elemental Ca per gram (3× more). Requires central line — causes severe tissue necrosis if peripheral IV infiltrates. Reserved for cardiac arrest, severe tetany, or when rapid correction needed via central access.
❓ What is Trousseau sign and why is it more specific than Chvostek sign?
Trousseau sign: inflate BP cuff above systolic × 3 min → carpal spasm (metacarpophalangeal flexion + interphalangeal extension + thumb adduction = "obstetrician's hand"). Specificity ~94% for hypocalcemia. Chvostek sign: tap facial nerve → ipsilateral facial muscle twitch. Specificity only ~30% — present in ~10% of normocalcemic individuals. Trousseau is far more reliable clinically.
❓ What is "hungry bone syndrome"?
After parathyroidectomy for severe hyperparathyroidism, the chronically suppressed bones suddenly have normal PTH levels → rapid uptake of calcium, phosphate, and magnesium into demineralized bone → severe, prolonged hypocalcemia (can last days to weeks). Risk factors: high pre-op PTH, high pre-op ALP, vitamin D deficiency, high pre-op Ca. Treatment: aggressive IV calcium drip + high-dose oral calcium + calcitriol. May need 10+ grams of elemental calcium per day initially.
❓ How does the phosphate level help differentiate causes of hypocalcemia?
High PO₄ + low Ca: hypoparathyroidism (PTH normally causes renal phosphate wasting — without PTH, PO₄ rises) or CKD (can't excrete PO₄). Low PO₄ + low Ca: vitamin D deficiency (both Ca and PO₄ are low due to impaired gut absorption) — PTH is appropriately elevated (secondary hyperparathyroidism), which causes phosphaturia. Phosphate is a crucial clue that most people forget to check.
❓ Why should you NOT mix IV calcium with bicarbonate?
Calcium and bicarbonate form calcium carbonate precipitate (insoluble chalk) in the IV tubing. This can cause tubing occlusion and — more dangerously — if the precipitate enters the bloodstream, it can cause embolic tissue damage. Always flush lines between calcium and bicarb. Same applies to calcium + phosphate-containing solutions.
📋 Summary
Summary
Confirm
Ionized Ca (most accurate) or corrected total Ca. Check Mg + PTH + PO₄ + vitamin D.
Emergent
Ca gluconate 1-2g IV/20min → drip. Ca chloride via central only. Correct Mg FIRST.
Low PTH
Hypoparathyroid (post-surgical #1). Rx: calcitriol + oral calcium.
High PTH
Secondary: vitamin D deficiency, CKD. Rx: ergocalciferol or calcitriol.
Post-Surg
Check iCa q6h × 48h after thyroidectomy. Hungry bone = severe prolonged hypoCa.
Pearl
PO₄ high + Ca low = hypopara. PO₄ low + Ca low = vitamin D. Always check Mg.
📄 One Pager
One-Pager
Hypocalcemia
Correct Mg first. Always.
Emergent Treatment
Ca gluconate 1-2g IV over 10-20 min (peripheral OK). Follow with drip 5-10g/24h. Ca chloride via central only (3× more elemental Ca). MgSO₄ 2-4g IV if Mg < 1.5.
Diagnostic Branch
PTH low → hypoparathyroidism (post-surgical, autoimmune). PTH high → secondary (vitamin D deficiency, CKD). PO₄ helps: high PO₄ = hypopara/CKD. Low PO₄ = vitamin D deficiency.
Bedside Tests
Chvostek (tap facial nerve → twitch, 30% specific). Trousseau (BP cuff → carpal spasm, 94% specific). ECG: QTc prolongation → torsades risk.
Diabetes Insipidus
Massive free water loss from ADH deficiency (central) or resistance (nephrogenic). Classic: polyuria (> 3L/day), polydipsia, dilute urine (osm < 300), rising serum Na⁺.
🔍 Overview
Overview
Diabetes insipidus (DI) is the inability to concentrate urine, causing massive free water loss. Two types: Central DI — deficient ADH production from posterior pituitary (post-pituitary surgery #1, head trauma, tumors, idiopathic, Sheehan syndrome). Nephrogenic DI — kidneys resistant to ADH (lithium #1 cause, hypercalcemia, hypokalemia, tubulointerstitial disease, medications). Key features: polyuria > 3L/day (can exceed 15-20L), dilute urine (osm < 300), hypernatremia if free water access is restricted. Triphasic response post-pituitary surgery: DI (days 1-5) → SIADH (days 5-10, transient ADH release from dying neurons) → permanent DI (if > 80% of ADH neurons destroyed). This is a dangerous pattern — the SIADH phase can cause fatal hyponatremia if you're giving DDAVP for the initial DI phase.
🧪 Workup
Workup
- Serum Na⁺ + serum osmolality — Na usually > 145, osm > 295. If patient has free water access, Na may be normal (compensated by polydipsia).
- Urine osmolality + urine specific gravity — Uosm < 300 mOsm/kg (often < 100) in the presence of elevated serum osm = inappropriately dilute = DI. Sp. gravity < 1.005.
- 24-hour urine volume — > 3L/day (often 5-15L). UOP > 250 mL/hr should prompt immediate evaluation.
- Water deprivation test — gold standard for diagnosis (rarely needed in obvious cases). [Miller et al., 1970 Withhold fluids, monitor urine osm and body weight. In DI, urine remains dilute despite rising serum osm. Then give DDAVP 2 mcg IV: if Uosm rises > 50% → central DI (responds to exogenous ADH). If no response → nephrogenic DI.
- Copeptin level — newer test, co-secreted with ADH. Low copeptin + hyperosmolality = central DI. Fenske et al., 2018
- MRI pituitary — if central DI suspected. Look for absent posterior pituitary bright spot (normal T1 hyperintensity from ADH-containing vesicles).
- Calcium + potassium — hypercalcemia and hypokalemia cause nephrogenic DI
- Lithium level — most common drug cause of nephrogenic DI (40% of chronic lithium users develop some concentrating defect)
- Medication review — lithium, amphotericin B, foscarnet, demeclocycline, cidofovir
🚨 Management
Management
- Central DI:
- DDAVP (desmopressin) — synthetic ADH analog. [DDAVP Trial Response, Miller 1970 Intranasal: 10-40 mcg daily (divided BID). PO: 0.1-0.4 mg BID-TID. IV/SQ: 1-4 mcg q12h (ICU). Titrate to urine output and serum Na⁺.
- Free water replacement — calculate free water deficit: FWD = TBW × [(Na/140) − 1]. Replace 50% in first 24h, remainder over next 24-48h. Limit Na correction to ≤ 10-12 mEq/24h (risk of cerebral edema if corrected too fast in chronic hypernatremia).
- Nephrogenic DI:
- Remove cause — stop lithium (if possible), correct hypercalcemia, correct hypokalemia
- Thiazide diuretics (paradoxical effect) — hydrochlorothiazide 25 mg daily. Causes mild volume depletion → increased proximal Na⁺/H₂O reabsorption → less water delivered to collecting duct → reduced urine volume. Counterintuitive but effective.
- Amiloride 5-10 mg daily — specifically for lithium-induced NDI. Blocks lithium entry through ENaC in collecting duct.
- Low-sodium, low-protein diet — reduces solute load → reduces obligatory urine volume
- NSAIDs (indomethacin) — reduce prostaglandin-mediated antagonism of ADH. Adjunct, not first-line.
- ICU management of acute DI: D5W or free water via NG tube. Match UOP with replacement (mL for mL replacement initially). DDAVP 1-2 mcg IV q12h. BMP q4-6h.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| DDAVP (desmopressin) | 10-40 mcg daily (nasal); 0.1-0.4 mg BID (PO); 1-4 mcg q12h (IV) | IN/PO/IV | Central DI treatment. V2 receptor agonist. No vasopressor effect (unlike native ADH). Risk: hyponatremia from overcorrection. |
| Hydrochlorothiazide (Microzide) | 25 mg daily | PO | Nephrogenic DI. Paradoxical antidiuresis via proximal volume depletion. Monitor K⁺. |
| Amiloride | 5-10 mg daily | PO | Lithium-induced NDI specifically. Blocks ENaC → blocks lithium entry into principal cells. |
| Indomethacin | 25-50 mg TID | PO | Adjunct for NDI. Reduces prostaglandin antagonism of ADH. GI/renal side effects. |
| D5W | Per free water deficit | IV | Free water replacement. Replace 50% of deficit in first 24h. Limit Na correction ≤ 10-12 mEq/24h. |
📊 Monitoring
Monitoring
- Urine output hourly — in ICU/acute DI. UOP > 250 mL/hr = uncontrolled DI → needs DDAVP or more free water.
- Serum Na⁺ q4-6h — target decline ≤ 10-12 mEq/24h in chronic hypernatremia. Faster correction → cerebral edema.
- Urine osmolality — rising Uosm on DDAVP confirms central DI and response to therapy.
- Daily weights + strict I&Os — fluid balance critical
- Post-pituitary surgery: UOP + Na q4-6h × 72h minimum. Watch for triphasic response — DI phase (days 1-5) may transition to SIADH (days 5-10). Stop DDAVP if UOP drops and Na falls.
- Lithium level — if continuing lithium with amiloride, monitor both
🏥 Rounds
Sample Presentation
Mr. Ahmed is a 45-year-old man, post-op day 2 from transsphenoidal resection of pituitary macroadenoma. Overnight UOP 4.2L in 8 hours (525 mL/hr). Clear, dilute urine. Na 152 (was 139 pre-op), serum osm 312, urine osm 89, urine SG 1.002. Patient reports extreme thirst.
Key Points: Post-surgical central DI — massive polyuria with dilute urine and rising Na. Start DDAVP 1 mcg IV q12h. Replace free water deficit with D5W. Monitor Na q4h. Watch for triphasic response — stop DDAVP immediately if UOP drops and Na starts falling (SIADH phase).
Pimp Questions
❓ How do you distinguish central from nephrogenic DI?
DDAVP challenge: give DDAVP 2 mcg IV and measure urine osm. Central DI: Uosm rises > 50% (kidneys respond to exogenous ADH because the problem is lack of production). Nephrogenic DI: Uosm does NOT rise (< 10% increase — kidneys are resistant to ADH). Clinical clues: post-pituitary surgery → central. On lithium → nephrogenic.
❓ What is the triphasic response after pituitary surgery?
Phase 1 (days 1-5): DI — surgical damage → decreased ADH release → polyuria. Phase 2 (days 5-10): SIADH — dying posterior pituitary neurons release stored ADH → water retention → hyponatremia. Phase 3 (day 10+): Permanent DI if > 80% of ADH neurons destroyed. The SIADH phase is dangerous — if you're giving DDAVP from phase 1, continuing it into phase 2 → severe hyponatremia. Must stop DDAVP when UOP drops.
❓ Why do thiazides help nephrogenic DI? Isn't that paradoxical?
Thiazides block NaCl reabsorption in the distal tubule → mild volume depletion → activates proximal tubule Na⁺/H₂O reabsorption → less water delivered to the collecting duct → reduced total urine volume. The collecting duct (where ADH acts) receives less filtrate to work with. It's a volume-depletion-mediated effect, not a direct ADH effect. Reduces UOP by 30-50%.
❓ Why is amiloride specifically useful in lithium-induced nephrogenic DI?
Lithium enters principal cells of the collecting duct via the epithelial sodium channel (ENaC). Once inside, lithium interferes with aquaporin-2 insertion (the water channel that ADH activates). Amiloride blocks ENaC → blocks lithium entry → prevents lithium from impairing the ADH signaling cascade. This is specific to lithium-induced NDI — amiloride does not help other causes of NDI.
❓ What is the free water deficit formula?
FWD = TBW × [(Na/140) − 1]. TBW = 0.6 × weight (kg) for men, 0.5 × weight for women. Example: 70 kg man, Na 160 → FWD = 42 × [(160/140) − 1] = 42 × 0.14 = 6 liters. Replace 50% in first 24h, rest over next 24-48h. Limit Na correction ≤ 10-12 mEq/24h to avoid cerebral edema (brain adapted to hyperosmolality with idiogenic osmoles).
📋 Summary
Summary
Diagnosis
Polyuria > 3L/day + dilute urine (Uosm < 300) + high serum osm. DDAVP challenge differentiates central vs nephrogenic.
Central DI
DDAVP (intranasal/PO/IV). Post-surgical #1. Responds to exogenous ADH.
Nephrogenic DI
Remove cause (lithium, hypercalcemia). Thiazide + amiloride (lithium). Low-Na diet.
Triphasic
DI → SIADH → permanent DI post-pituitary surgery. Stop DDAVP if UOP drops.
Replacement
FWD = TBW × [(Na/140)−1]. Replace 50% in 24h. Na correction ≤ 10-12 mEq/24h.
Pearl
Absent bright spot on MRI T1 = central DI. Thiazides are paradoxically helpful in NDI.
📄 One Pager
One-Pager
Diabetes Insipidus
Central vs Nephrogenic
DDAVP Challenge
Give DDAVP 2 mcg IV → measure Uosm. Rises > 50% = central (responds). No change = nephrogenic (resistant). Copeptin: low = central DI.
Treatment
Central: DDAVP + free water. Nephrogenic: remove cause + thiazide + amiloride (lithium) + low-Na diet. ICU: match UOP with D5W mL-for-mL.
Cushing's Syndrome
Chronic cortisol excess. Most common cause: exogenous steroids. Most common endogenous cause: pituitary adenoma (Cushing's disease). Systematic biochemical → localization approach.
🔍 Overview
Overview
Cushing's syndrome = clinical manifestations of chronic cortisol excess. Exogenous (iatrogenic steroids) is by far the most common cause overall. Among endogenous causes: Cushing's disease (ACTH-secreting pituitary adenoma, ~70%), ectopic ACTH (small cell lung cancer, carcinoid, ~15%), adrenal adenoma/carcinoma (~15%). Classic features: central obesity, moon facies, dorsal fat pad (buffalo hump), violaceous striae (> 1 cm wide), proximal muscle weakness, easy bruising, hyperglycemia, HTN, osteoporosis, hirsutism, menstrual irregularity, depression/psychosis. Key teaching point: the workup is a 3-step process — (1) confirm hypercortisolism, (2) determine ACTH dependence, (3) localize the source.
🧪 Workup
Workup
- Step 1 — Confirm hypercortisolism (need 2 of 3 tests positive):
- 24-hour urine free cortisol (× 2) — elevated > 3× ULN is virtually diagnostic. Mild elevations can be false positive (pseudo-Cushing: alcoholism, depression, obesity).
- Late-night salivary cortisol (× 2) — loss of diurnal cortisol rhythm. Cortisol should nadir at 11 PM. Elevated = abnormal. Convenient outpatient test.
- 1 mg overnight dexamethasone suppression test (DST) — give dex 1 mg PO at 11 PM → check 8 AM cortisol. Normal: cortisol < 1.8 mcg/dL (suppressed). Cushing's: cortisol fails to suppress (> 1.8). [Nieman, 2008]
- Step 2 — ACTH level (determine dependence):
- ACTH elevated (> 20 pg/mL) → ACTH-dependent: pituitary (Cushing's disease) vs ectopic ACTH
- ACTH suppressed (< 5 pg/mL) → ACTH-independent: adrenal source (adenoma, carcinoma, bilateral hyperplasia)
- Step 3 — Localize:
- ACTH-dependent: MRI pituitary (60% show adenoma). If MRI negative or equivocal → inferior petrosal sinus sampling (IPSS) with CRH stimulation (gold standard to confirm pituitary vs ectopic).
- ACTH-independent: CT adrenals (adenoma vs carcinoma vs bilateral hyperplasia)
- Ectopic ACTH: CT chest/abdomen (small cell, carcinoid, thymic tumors). Octreotide scan. PET/CT.
🚨 Management
Management
- Exogenous Cushing's: Taper steroids as disease allows. Never stop abruptly (adrenal suppression → adrenal crisis). Taper over weeks-months depending on duration.
- Cushing's disease (pituitary): Transsphenoidal surgery (TSS) — first-line. Cure rate 65-90% for microadenomas. Post-op: patients develop adrenal insufficiency (need hydrocortisone replacement until HPA axis recovers — months to years). If surgery fails: repeat TSS, radiation, bilateral adrenalectomy, or medical therapy.
- Adrenal adenoma: Laparoscopic adrenalectomy — curative. Post-op AI (contralateral adrenal suppressed).
- Adrenal carcinoma: Surgical resection + mitotane (adrenolytic agent). Poor prognosis.
- Ectopic ACTH: Treat underlying tumor. Medical cortisol reduction while awaiting definitive therapy.
- Medical therapy (cortisol-lowering agents): ketoconazole (steroidogenesis inhibitor), metyrapone (11β-hydroxylase inhibitor), osilodrostat [LINC-3, 2022], mifepristone (glucocorticoid receptor antagonist — for hyperglycemia), pasireotide (somatostatin analog for Cushing's disease). [SEISMIC, 2012]
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Ketoconazole | 200-400 mg BID-TID | PO | Steroidogenesis inhibitor. Most commonly used medical therapy. Monitor LFTs (hepatotoxicity). QTc prolongation. Drug interactions (CYP3A4). |
| Metyrapone | 250-750 mg TID-QID | PO | 11β-hydroxylase inhibitor. Blocks cortisol synthesis. Can cause hyperandrogenism (hirsutism, acne). Monitor cortisol + ACTH. |
| Osilodrostat | 2-7 mg BID | PO | 11β-hydroxylase inhibitor. Newer. LINC-3, 2022. QTc monitoring. Adrenal insufficiency risk. |
| Mifepristone | 300-1200 mg daily | PO | GR antagonist. FDA-approved for Cushing's-associated hyperglycemia. Cannot monitor cortisol (blocked receptor). Monitor clinically. SEISMIC, 2012 |
| Pasireotide | 0.6-0.9 mg SQ BID | SQ | Somatostatin analog for Cushing's disease. Hyperglycemia is major side effect (up to 70%). |
| Mitotane | 2-6 g/day (titrate) | PO | Adrenolytic — for adrenal carcinoma. Causes AI (needs replacement). Monitor levels (target 14-20 mcg/mL). Teratogenic. |
📊 Monitoring
Monitoring
- 24h urine free cortisol — to monitor treatment response. Target: normalization.
- AM cortisol + ACTH — post-TSS: check day 1-3. Undetectable cortisol (< 2) = successful surgery. Patient needs hydrocortisone replacement.
- Morning cortisol off replacement — periodically to assess HPA axis recovery (may take 6-18 months post-surgery). Cosyntropin stim test when cortisol approaches normal.
- LFTs q2-4 weeks on ketoconazole
- ECG (QTc) on ketoconazole, osilodrostat
- Blood glucose — Cushing's causes insulin resistance. May need insulin during active disease. Hyperglycemia also a major side effect of pasireotide.
- DEXA scan — osteoporosis screening (cortisol excess → bone loss)
- MRI pituitary annually × 5 years post-TSS (recurrence monitoring)
🏥 Rounds
Sample Presentation
Ms. Rivera is a 38-year-old woman with new-onset diabetes, HTN, 30 lb weight gain (central), wide purple striae on abdomen, and proximal weakness × 8 months. No exogenous steroid use. Labs: 24h UFC 380 mcg (3× ULN), late-night salivary cortisol 0.85 mcg/dL (elevated), 1 mg DST cortisol 12.4 (failed suppression). ACTH 68 pg/mL (elevated). MRI pituitary: 8 mm left-sided adenoma.
Key Points: Classic Cushing's disease — confirmed hypercortisolism (2/3 tests positive), ACTH-dependent, pituitary adenoma on MRI. Refer for TSS. Pre-op: control hyperglycemia (insulin), VTE prophylaxis (hypercoagulable), PCP prophylaxis if severely Cushingoid, address osteoporosis. Post-op: expect AI (start hydrocortisone replacement).
Pimp Questions
❓ What are the 3 steps in the Cushing's workup?
Step 1: Confirm hypercortisolism — 2 of 3 positive: 24h UFC, late-night salivary cortisol, 1 mg DST. Step 2: ACTH level — high = ACTH-dependent (pituitary or ectopic), low = ACTH-independent (adrenal). Step 3: Localize — MRI pituitary (if ACTH-dependent) or CT adrenals (if ACTH-independent). IPSS if pituitary MRI equivocal. [Nieman, 2008]
❓ What is inferior petrosal sinus sampling (IPSS)?
Gold standard to differentiate pituitary vs ectopic ACTH. Catheters placed in bilateral inferior petrosal sinuses (drain the pituitary). Compare petrosal ACTH to peripheral ACTH before and after CRH stimulation. Central-to-peripheral ACTH ratio ≥ 2 (basal) or ≥ 3 (post-CRH) = pituitary source. If ratio < 2 → ectopic ACTH. Indicated when MRI is negative or equivocal.
❓ Why do patients develop adrenal insufficiency after successful pituitary surgery?
Chronic ACTH excess from the pituitary adenoma → chronic cortisol excess → suppresses CRH and the normal corticotrophs (negative feedback). When the adenoma is removed, the remaining normal pituitary tissue is atrophied and cannot produce adequate ACTH → secondary adrenal insufficiency. HPA axis recovery takes 6-18 months. Patients need hydrocortisone replacement until the axis recovers.
❓ What features help distinguish Cushing's from simple obesity?
Cushing's-specific features: (1) Proximal muscle weakness (can't rise from chair without arms — obesity alone doesn't cause this), (2) wide (> 1 cm) violaceous striae (obesity has narrow, pink striae), (3) easy bruising + skin thinning, (4) new-onset diabetes + HTN + osteoporosis in a young person, (5) facial plethora. Weight gain in Cushing's is classically central with thin extremities (muscle wasting). Obese patients have more generalized fat distribution.
❓ Why can't you monitor cortisol levels on mifepristone?
Mifepristone is a glucocorticoid receptor antagonist — it blocks the receptor, not cortisol production. In fact, cortisol levels rise on mifepristone (loss of negative feedback → ACTH increases → cortisol increases). You must monitor clinical response (glucose, weight, striae, weakness) and urinary cortisol will be misleadingly HIGH. This makes dose titration challenging.
📋 Summary
Summary
Step 1
Confirm: 24h UFC + salivary cortisol + 1mg DST (need 2/3 positive)
Step 2
ACTH: High → pituitary or ectopic. Low → adrenal.
Step 3
Localize: MRI pituitary (high ACTH) or CT adrenals (low ACTH). IPSS if equivocal.
Treatment
TSS for Cushing's disease (cure 65-90%). Adrenalectomy for adrenal tumors. Medical if inoperable.
Post-Op
Expect AI → hydrocortisone until HPA recovery (6-18 months). Check AM cortisol periodically.
Pearl
Wide purple striae + proximal weakness = Cushing's, not obesity. #1 cause overall = exogenous steroids.
📄 One Pager
One-Pager
Cushing's Syndrome
Confirm → ACTH → Localize
3-Step Workup
1. Confirm: 24h UFC, late-night salivary cortisol, 1mg DST (2/3 positive). 2. ACTH: high = pituitary/ectopic, low = adrenal. 3. Localize: MRI pituitary or CT adrenals. IPSS if MRI equivocal.
Trials
Nieman 2008 (Endocrine Society Guidelines) · LINC-3 2022 (osilodrostat) · SEISMIC 2012 (mifepristone)
Hyperthyroidism / Graves' Disease
Graves' = most common cause of hyperthyroidism. TSI-mediated thyroid stimulation. Treatment: thionamides, RAI, or surgery. Know when each is preferred.
🔍 Overview
Overview
Hyperthyroidism = excessive thyroid hormone production/release. Causes: Graves' disease (70-80% — autoimmune, TSI stimulates TSH receptor), toxic multinodular goiter (elderly, autonomous nodules), toxic adenoma (single hot nodule), thyroiditis (subacute/painless — transient release of preformed hormone, NOT overproduction), exogenous thyroid hormone, iodine-induced (Jod-Basedow). Graves' has unique extra-thyroidal features: Graves' ophthalmopathy (proptosis, lid lag, diplopia — 25-50%), pretibial myxedema (localized dermopathy), thyroid acropachy (digital clubbing). Symptoms: anxiety, tremor, weight loss, heat intolerance, palpitations (AF in 10-15%), diarrhea, menstrual irregularity, hyperreflexia.
🧪 Workup
Workup
- TSH — suppressed (< 0.1 mIU/L). Most sensitive initial test.
- Free T4 + Free T3 — both elevated in overt hyperthyroidism. T3 thyrotoxicosis: suppressed TSH + normal FT4 + elevated FT3 (early Graves' or toxic nodule).
- TSI (thyroid-stimulating immunoglobulins) or TRAb (TSH receptor antibodies) — positive in Graves'. Specific. Can be used to confirm diagnosis without RAIU in pregnancy or when RAIU unavailable.
- Radioactive iodine uptake (RAIU) — differentiates causes:
- Diffusely elevated = Graves'
- Focal hot nodule (suppressed rest) = toxic adenoma
- Patchy = toxic multinodular goiter
- Low/absent uptake = thyroiditis (preformed hormone release, not production), exogenous, or iodine excess
- ESR/CRP — elevated in subacute (de Quervain) thyroiditis (painful + elevated inflammatory markers)
- CBC — baseline before starting thionamides (agranulocytosis risk)
- LFTs — baseline before thionamides (PTU → hepatotoxicity)
- ECG — atrial fibrillation (10-15% of hyperthyroid patients). Often rate-controlled with beta-blockers alone.
- Thyroid ultrasound — if nodule palpated or RAIU shows focal uptake. Evaluate for suspicious features.
🚨 Management
Management
- Beta-blocker (ALL patients, symptom control): Propranolol 20-40 mg TID-QID (preferred — also blocks T4→T3 conversion) or atenolol 50-100 mg daily. Continue until euthyroid.
- Graves' disease — 3 treatment options:
- Thionamides (methimazole preferred): Methimazole 10-30 mg daily → titrate to euthyroid → trial of 12-18 months. Remission rate ~40-50%. PTU only for: first trimester pregnancy (methimazole is teratogenic: aplasia cutis, choanal atresia), thyroid storm, methimazole allergy. [ATA Guidelines, 2016]
- Radioactive iodine (RAI, I-131): Ablates thyroid. Preferred in US for definitive treatment. Results in permanent hypothyroidism (which is easier to manage). Contraindications: pregnancy, breastfeeding, moderate-severe Graves' ophthalmopathy (can worsen — give prednisone cover).
- Thyroidectomy: Preferred for: large goiter with compressive symptoms, coexisting suspicious nodule, moderate-severe ophthalmopathy, patient preference, children who fail thionamides. Requires pre-op euthyroid state.
- Thyroiditis: Self-limited (4-8 weeks). Beta-blockers only. NSAIDs or prednisone for pain (subacute). Thionamides are USELESS (no new hormone being made — just release of preformed).
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Methimazole (Tapazole) | 10-30 mg daily → titrate | PO | First-line thionamide. Once daily dosing. Agranulocytosis (0.2-0.5%) — check CBC if fever/sore throat. Teratogenic in 1st trimester. ATA, 2016 |
| PTU (propylthiouracil) | 100-200 mg TID | PO | ONLY for: 1st trimester pregnancy, thyroid storm, methimazole allergy. TID dosing. FDA black box: severe hepatotoxicity (fulminant liver failure). Also blocks T4→T3. |
| Propranolol | 20-40 mg TID-QID | PO | Symptom control. Also blocks peripheral T4→T3 conversion. Use in ALL hyperthyroid patients. |
| Radioactive iodine (I-131) | Per nuclear medicine calculation | PO | Definitive. Causes permanent hypothyroidism (expected outcome). Avoid pregnancy × 6 months after. Worsen ophthalmopathy → prednisone cover. |
| SSKI (saturated KI) | 1-2 drops TID | PO | Wolff-Chaikoff effect — acute iodine load transiently blocks thyroid hormone release. Pre-op preparation for thyroidectomy. Give AFTER thionamide established. |
| Cholestyramine | 4g TID | PO | Adjunct — binds thyroid hormone in gut, reduces enterohepatic recirculation. Used in severe thyrotoxicosis. |
📊 Monitoring
Monitoring
- TFTs (TSH + FT4) q4-6 weeks during thionamide titration. TSH may remain suppressed for months — use FT4 to guide dose adjustments initially.
- CBC — if fever or sore throat on thionamides (agranulocytosis: ANC < 500). Get STAT CBC. Incidence 0.2-0.5%, usually within first 90 days.
- LFTs — baseline + periodic on PTU. Discontinue if transaminases > 3× ULN. PTU hepatotoxicity can be fulminant.
- TSI/TRAb — if monitoring for remission after thionamide trial. Persistently elevated = high relapse risk. Check before stopping thionamide at 12-18 months.
- Post-RAI: TFTs q4-6 weeks × 6 months. Hypothyroidism typically develops by 6-12 weeks. Start levothyroxine when TSH rises.
- Post-thyroidectomy: Check calcium q6h × 48h (hypoparathyroidism risk). Start levothyroxine. Check TSH at 6 weeks.
- Ophthalmopathy assessment — active inflammation = orbital CT/MRI, refer ophthalmology. IV methylprednisolone for moderate-severe active orbitopathy [EUGOGO].
🏥 Rounds
Sample Presentation
Ms. Patel is a 32-year-old woman with 3 months of 15 lb weight loss despite increased appetite, palpitations, tremor, anxiety, and heat intolerance. Exam: HR 108, diffusely enlarged thyroid with bruit, lid lag, mild proptosis bilateral, fine tremor. Labs: TSH < 0.01, FT4 4.8 (elevated), FT3 12 (elevated), TSI positive. RAIU: diffusely elevated at 65% (normal 10-30%).
Key Points: Classic Graves' disease — suppressed TSH, elevated FT4/FT3, positive TSI, diffusely elevated RAIU. Start propranolol for symptoms. Discuss 3 treatment options. Methimazole 20 mg daily for 12-18 month trial is reasonable first-line (32-year-old who may want pregnancy). Check CBC + LFTs baseline. Ophthalmology referral for proptosis.
Pimp Questions
❓ Why is methimazole preferred over PTU?
Methimazole advantages: once-daily dosing (vs TID for PTU), lower hepatotoxicity risk, more consistent pharmacokinetics, no FDA black box warning. PTU is preferred ONLY in: (1) first trimester pregnancy (methimazole causes aplasia cutis + choanal atresia), (2) thyroid storm (PTU also blocks T4→T3 conversion), (3) methimazole allergy/intolerance. After first trimester, switch back to methimazole. [ATA, 2016]
❓ How does RAIU differentiate causes of thyrotoxicosis?
High uptake (diffuse) = Graves'. High uptake (focal) = toxic adenoma or toxic MNG. Low/absent uptake = thyroiditis (preformed hormone leaking from damaged gland — no new synthesis), exogenous thyroid hormone, or iodine excess. This is the key test because treatment differs fundamentally: thionamides work for Graves'/toxic nodules (blocking new synthesis) but are useless in thyroiditis (nothing being synthesized).
❓ Why can RAI worsen Graves' ophthalmopathy?
RAI-induced thyroid destruction releases thyroid antigens that cross-react with orbital tissue (TSH receptor is expressed in orbital fibroblasts). This triggers an immune flare targeting the orbits → worsening inflammation, proptosis, diplopia. Risk is highest in smokers and those with pre-existing active ophthalmopathy. Prevention: prednisone 0.3-0.5 mg/kg starting the day of RAI × 4-6 weeks taper in moderate-risk patients. Avoid RAI entirely in moderate-severe active ophthalmopathy.
❓ What is the most feared side effect of thionamides and how do you screen for it?
Agranulocytosis (ANC < 500) — incidence 0.2-0.5%, usually within first 90 days. Can be fatal if not recognized. DO NOT do routine CBC monitoring (too insensitive, can develop rapidly between checks). Instead: educate the patient to present immediately for fever, sore throat, or mouth sores → get STAT CBC. If ANC < 500 → stop thionamide permanently, admit, broad-spectrum antibiotics, G-CSF, switch to non-thionamide therapy (RAI or surgery).
❓ How do you manage hyperthyroidism in pregnancy?
First trimester: PTU (methimazole is teratogenic). Second/third trimester: switch to methimazole (PTU hepatotoxicity risk). Use the lowest effective dose — aim for FT4 at upper limit of normal (mild maternal hyperthyroidism is safer than fetal hypothyroidism from overtreatment). RAI is absolutely contraindicated in pregnancy (ablates fetal thyroid). Check TSI/TRAb in third trimester — if elevated, neonatal hyperthyroidism possible. [ATA, 2016]
📋 Summary
Summary
Diagnosis
TSH suppressed + FT4/FT3 high. TSI/TRAb for Graves'. RAIU differentiates all causes.
Graves' Rx
Methimazole 12-18 mo trial (40% remission), RAI (definitive), or surgery.
Thyroiditis
Low RAIU. Self-limited. Beta-blockers only. Thionamides are useless.
Pregnancy
PTU in 1st trimester → methimazole after. Lowest dose. No RAI ever.
Emergency
Agranulocytosis: fever + sore throat → STAT CBC → stop thionamide → admit.
Pearl
RAI worsens ophthalmopathy (give prednisone cover). Propranolol also blocks T4→T3.
📄 One Pager
One-Pager
Hyperthyroidism
Graves', Toxic Nodule, Thyroiditis
RAIU Pattern
Diffuse high = Graves'. Focal hot = toxic adenoma. Patchy = MNG. Low = thyroiditis/exogenous/iodine.
Treatment Choice
Methimazole first-line (12-18 mo). RAI if definitive needed (causes hypothyroidism). Surgery for large goiter/nodule/ophthalmopathy. Thyroiditis: beta-blockers only.
Trials
ATA Hyperthyroidism Guidelines 2016 · EUGOGO (ophthalmopathy management)
Primary Aldosteronism
Most common cause of secondary hypertension. Screen: ARR (aldosterone-to-renin ratio). Confirm: salt loading. Localize: adrenal CT + adrenal vein sampling. Cause: adenoma (Conn's) vs bilateral hyperplasia.
🔍 Overview
Overview
Primary aldosteronism (PA) is autonomous aldosterone production independent of the renin-angiotensin system. It is the most common cause of secondary hypertension, affecting 5-13% of all hypertensive patients and up to 20% of resistant HTN. Two main subtypes: bilateral adrenal hyperplasia (BAH, ~60%) and aldosterone-producing adenoma (APA / Conn's syndrome, ~35%). The distinction matters because APA is surgically curable while BAH is treated medically. Classic lab triad: hypertension + hypokalemia + metabolic alkalosis, but most patients are normokalemic (hypokalemia is present in only 30-50%). PA causes cardiovascular damage disproportionate to BP — higher rates of stroke, MI, AF, and HF than essential HTN at the same BP level. PASO, 2017
🧪 Workup
Workup
- Step 1 — Screening (ARR): Plasma aldosterone concentration (PAC) / plasma renin activity (PRA) = aldosterone-to-renin ratio. ARR > 30 with PAC ≥ 10-15 ng/dL = positive screen. Draw morning, seated, K⁺-repleted. Hold interfering medications: spironolactone × 6 weeks, eplerenone × 6 weeks, ACEi/ARB acceptable (may cause false negatives). [Endocrine Society, 2016]
- Who to screen: Resistant HTN (≥ 3 drugs), HTN + hypokalemia, HTN + adrenal incidentaloma, HTN onset < 40, severe HTN (≥ 160/100), HTN + family history of early stroke or PA
- Step 2 — Confirmatory test (suppress aldosterone):
- IV saline infusion test: 2L NS over 4h → measure PAC. If PAC > 10 ng/dL post-infusion = confirmed (aldosterone should suppress but doesn't).
- Oral salt loading: High-sodium diet × 3 days → 24h urine aldosterone. > 12 mcg/24h = confirmed.
- Fludrocortisone suppression test: Fludrocortisone 0.1 mg q6h × 4 days → PAC remains > 6. Most specific but rarely used (cumbersome, risk of hypokalemia).
- Step 3 — Subtype differentiation + localization:
- CT adrenals — look for unilateral adenoma (> 1 cm). BUT: CT is wrong 38% of the time (nonfunctioning incidentaloma mimics APA, or microadenoma is missed).
- Adrenal vein sampling (AVS) — gold standard to lateralize aldosterone production. Lateralization ratio ≥ 4:1 = unilateral source → surgery. Essential for ALL surgical candidates unless: age < 35 with clear > 1 cm unilateral adenoma + normal contralateral.
🚨 Management
Management
- Unilateral APA (Conn's): Laparoscopic adrenalectomy — cures hypokalemia in nearly all, cures or improves HTN in 50-80%. Pre-op: control BP and K⁺ with MRA (spironolactone or eplerenone). Post-op: monitor K⁺ (contralateral zona glomerulosa may be suppressed → transient hypoaldosteronism).
- Bilateral adrenal hyperplasia: Medical therapy with mineralocorticoid receptor antagonists (MRA):
- Spironolactone 25-100 mg daily — most effective MRA. Anti-androgenic side effects: gynecomastia (up to 50% in men), menstrual irregularity, decreased libido. PATHWAY-2, 2015
- Eplerenone 50-100 mg BID — selective MRA. Fewer anti-androgenic side effects. More expensive. May need higher doses.
- Target: BP < 130/80, normalize K⁺, reduce cardiovascular risk
- Adjunct: Sodium restriction (< 2g/day), additional antihypertensives as needed (CCB, thiazide)
- Monitoring K⁺ on MRA: Hyperkalemia risk, especially with CKD or ACEi/ARB combo. Check K⁺ + Cr at 1 week, 4 weeks, then q3-6 months.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Spironolactone (Aldactone) | 25-100 mg daily | PO | First-line MRA. Most effective for PA. Anti-androgenic SE (gynecomastia 50%, sexual dysfunction). Monitor K⁺. PATHWAY-2, 2015 |
| Eplerenone (Inspra) | 50-100 mg BID | PO | Selective MRA. Fewer hormonal SE. More expensive. May need higher doses than spironolactone. |
| Amiloride | 5-10 mg daily | PO | Alternative for K⁺-sparing if MRA intolerance. Less effective for BP lowering than spironolactone. |
| Nifedipine (Procardia) | 30-60 mg daily | PO | Add-on antihypertensive. Does not interfere with ARR screening. |
📊 Monitoring
Monitoring
- K⁺ + Cr at 1 week, 4 weeks, then q3-6 months on MRA — hyperkalemia risk (especially with CKD, ACEi/ARB)
- BP — target < 130/80. Most patients need additional antihypertensives besides MRA.
- ARR is NOT useful for monitoring — it's only a screening test. Follow clinical endpoints (BP, K⁺).
- Post-adrenalectomy: Check K⁺ and aldosterone at 1 month. Expect transient hyperkalemia (suppressed contralateral adrenal). Hold MRA. Resume antihypertensives only if BP remains elevated.
- Annual cardiovascular risk assessment — PA causes disproportionate end-organ damage. Screen for AF, LVH (echo), proteinuria.
🏥 Rounds
Sample Presentation
Mr. Kim is a 48-year-old man with resistant hypertension (amlodipine 10, lisinopril 40, HCTZ 25 — BP 158/96) and persistent hypokalemia (K⁺ 3.0 despite supplementation). BMI 28. No secondary HTN features on exam. Labs: PAC 28 ng/dL, PRA 0.3 ng/mL/hr, ARR 93. Confirmatory: saline infusion PAC 18 ng/dL (failed suppression). CT adrenals: 1.4 cm left adrenal adenoma.
Key Points: Confirmed primary aldosteronism — positive ARR, failed saline suppression. CT shows left adenoma, BUT must do adrenal vein sampling before committing to surgery (CT is wrong 38% of the time). Start spironolactone 50 mg while awaiting AVS. Replace K⁺. If AVS lateralizes left → laparoscopic left adrenalectomy.
Pimp Questions
❓ Why can't you rely on CT alone to decide on surgery for primary aldosteronism?
CT is wrong in up to 38% of cases. Reasons: (1) Nonfunctioning adrenal incidentalomas are common (5-10% of adults have them) — a visible nodule may NOT be the aldosterone source. (2) Microadenomas (< 1 cm) may be the true source but invisible on CT. (3) Bilateral hyperplasia can have an asymmetric appearance mimicking a unilateral adenoma. Adrenal vein sampling (AVS) is the gold standard — it directly measures aldosterone from each adrenal vein. [Endocrine Society, 2016]
❓ What medications must you hold before ARR screening and for how long?
Spironolactone and eplerenone: hold × 6 weeks (major interference). Diuretics: hold × 4 weeks (cause hypokalemia → suppress aldosterone; stimulate renin). Beta-blockers: suppress renin → false positive ARR. ACEi/ARBs: may cause false negatives (stimulate renin) but are ACCEPTABLE to continue if needed for BP control. Safe alternatives: verapamil, hydralazine, doxazosin (alpha-blocker). Always ensure K⁺ is repleted before testing.
❓ Why does primary aldosteronism cause hypokalemia and metabolic alkalosis?
Aldosterone acts on the principal cells of the collecting duct → activates ENaC → Na⁺ reabsorption creates a negative lumen potential → drives K⁺ and H⁺ secretion. Result: (1) Na⁺ retention → volume expansion → HTN, (2) K⁺ secretion → hypokalemia, (3) H⁺ secretion → metabolic alkalosis. However, only 30-50% of PA patients are hypokalemic at diagnosis — most are normokalemic.
❓ Why does PA cause more cardiovascular damage than essential HTN at the same BP?
Aldosterone has direct mineralocorticoid receptor-mediated effects on the heart, vasculature, and kidneys independent of BP: (1) myocardial fibrosis → LVH and diastolic dysfunction, (2) vascular inflammation and stiffness, (3) glomerular damage → proteinuria, (4) increased AF risk. PA patients have 2-4× higher rates of stroke, MI, and AF compared to BP-matched essential HTN. This is why MRA therapy improves outcomes beyond BP lowering alone. PASO, 2017
📋 Summary
Summary
Screen
ARR > 30 + PAC ≥ 10-15. Morning, seated, K⁺-repleted. Hold spironolactone × 6 wk.
Confirm
Saline infusion (PAC > 10 post), oral salt loading (urine aldo > 12), or fludrocortisone.
Localize
CT adrenals + AVS (gold standard). CT alone is wrong 38%.
APA (Conn's)
Laparoscopic adrenalectomy. Cures K⁺. Cures/improves HTN 50-80%.
BAH
Spironolactone 25-100 mg or eplerenone 50-100 BID. Low-Na diet. Monitor K⁺.
Pearl
Most PA patients are normokalemic. CV damage exceeds BP-matched essential HTN.
📄 One Pager
One-Pager
Primary Aldosteronism
Screen → Confirm → Localize
3-Step Workup
Screen: ARR > 30 + PAC ≥ 10. Confirm: saline infusion (PAC > 10 post). Localize: CT adrenals + AVS (gold standard, CT wrong 38%). Lateralization ≥ 4:1 → surgery.
Trials
Endocrine Society PA Guidelines 2016 · PATHWAY-2 2015 (spironolactone best add-on for resistant HTN) · PASO 2017 (PA cardiovascular outcomes)
Hypothyroidism
Most common endocrine disorder. Hashimoto's thyroiditis is the #1 cause in iodine-sufficient areas. Levothyroxine replacement — simple in concept, nuanced in practice.
🔍 Overview
Overview
Hypothyroidism = insufficient thyroid hormone production. Primary (> 95%): thyroid gland failure — TSH high, FT4 low. Central (< 5%): pituitary or hypothalamic disease — TSH low/normal, FT4 low. Hashimoto's thyroiditis (chronic autoimmune) is the #1 cause in iodine-sufficient countries. Other causes: post-RAI, post-thyroidectomy, post-radiation, medications (amiodarone, lithium, checkpoint inhibitors), iodine deficiency (worldwide), infiltrative (sarcoidosis, hemochromatosis). Prevalence: 5-10% (overt + subclinical). Subclinical hypothyroidism: TSH elevated (4.5-10), FT4 normal. Treatment controversial — treat if: TSH > 10, symptoms, pregnancy/planning pregnancy, positive TPO antibodies with TSH > 7. Symptoms: fatigue, cold intolerance, weight gain, constipation, dry skin, hair loss, menorrhagia, depression, myalgias, delayed DTRs.
🧪 Workup
Workup
- TSH — most sensitive test. Elevated in primary hypothyroidism. Normal/low in central hypothyroidism (misleading — always check FT4 if clinical suspicion).
- Free T4 — low confirms hypothyroidism. TSH high + FT4 low = primary overt hypothyroidism. TSH high + FT4 normal = subclinical.
- TPO antibodies (anti-thyroid peroxidase) — positive in Hashimoto's (~95%). Useful for: (1) confirming etiology, (2) predicting progression from subclinical → overt, (3) informs treatment decisions in subclinical hypothyroidism.
- Anti-thyroglobulin antibodies — positive in ~60% of Hashimoto's. Less specific than TPO.
- Lipid panel — hypothyroidism causes hyperlipidemia (elevated LDL). May normalize with treatment. Don't start statins until euthyroid.
- CBC — normocytic or macrocytic anemia is common
- BMP — hyponatremia (impaired free water excretion), elevated Cr (decreased renal perfusion)
- CK — elevated from hypothyroid myopathy (can be markedly elevated, mimicking rhabdomyolysis)
- If central hypothyroidism suspected: check FT4 (not just TSH), pituitary MRI, assess other pituitary axes (ACTH/cortisol, FSH/LH, GH, prolactin). Must rule out adrenal insufficiency before starting T4 (same principle as myxedema coma).
🚨 Management
Management
- Levothyroxine (T4): Standard replacement. Full dose: 1.6 mcg/kg/day. Start lower in elderly or cardiac patients: 12.5-25 mcg daily → increase by 12.5-25 mcg q6-8 weeks.
- How to take: On empty stomach, 30-60 min before breakfast (or at bedtime, ≥ 3h after last meal). Separate from calcium, iron, PPIs, soy, coffee by ≥ 4 hours (all impair absorption).
- Dose adjustments:
- Check TSH at 6-8 weeks (TSH has a long half-life — don't recheck sooner).
- Target TSH 0.5-2.5 mIU/L for most adults. Elderly (> 70): target 3-6 (higher TSH is protective, over-replacement → AF + osteoporosis).
- Pregnancy: target TSH < 2.5 in 1st trimester. Levothyroxine dose typically increases 25-50% during pregnancy. [ATA, 2017]
- Subclinical hypothyroidism: Treat if: TSH > 10, pregnant/planning pregnancy, symptoms + TPO positive, goiter, TSH 7-10 with positive TPO (high progression risk).
- T3 supplementation: NOT recommended routinely. Some patients feel better on T4+T3 combination, but no RCT shows superiority. Consider only if persistent symptoms despite normalized TSH on adequate T4.
- Common pitfalls: Non-compliance (#1 cause of persistently elevated TSH on "adequate" dose). Drug interactions (calcium, iron, PPI). Celiac disease (malabsorption). Weight-based recalculation after significant weight change.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Levothyroxine (T4) | 1.6 mcg/kg/day (full dose); start 25-50 mcg in elderly | PO | Standard of care. Empty stomach, 30-60 min before breakfast. Separate from Ca, Fe, PPI by 4h. Half-life 7 days → steady state in 6 wk. ATA, 2014 |
| Liothyronine (T3) | 5-25 mcg daily (divided BID-TID) | PO | NOT routine. Short half-life → TID dosing. Consider only if persistent symptoms on adequate T4 with normal TSH. Variable absorption. |
| IV levothyroxine | 50-100% of oral dose | IV | For patients who cannot take PO (ICU, post-surgical). 100% bioavailable vs ~70% PO. For myxedema coma: loading dose 200-400 mcg. |
📊 Monitoring
Monitoring
- TSH at 6-8 weeks after any dose change — do NOT recheck sooner (TSH equilibration takes 4-6 weeks). Adjust by 12.5-25 mcg increments.
- Annual TSH once stable on appropriate dose
- Pregnancy: TSH monthly through first trimester, then q4-6 weeks. Increase dose 25-50% as early as 4-6 weeks gestation. ATA, 2017
- Central hypothyroidism: Monitor Free T4 (NOT TSH — TSH is unreliable when the pituitary is the problem). Target FT4 in upper half of reference range.
- Elderly (> 70): Target TSH 3-6. Do NOT over-replace — subclinical hyperthyroidism from excess T4 → AF, osteoporosis, fractures.
- Drug interactions: Reassess dose when starting/stopping calcium, iron, PPIs, estrogen (increases TBG → need more T4), phenytoin/carbamazepine (increase T4 metabolism).
- Lipid panel — recheck 3-6 months after achieving euthyroidism (hyperlipidemia often normalizes).
🏥 Rounds
Sample Presentation
Mrs. Johnson is a 45-year-old woman with 6 months of fatigue, 10 lb weight gain, constipation, cold intolerance, and hair thinning. PMH: nothing. No medications. Exam: dry skin, periorbital puffiness, bradycardia (HR 56), delayed DTR relaxation. No goiter. Labs: TSH 48 mIU/L (elevated), Free T4 0.4 ng/dL (low), TPO Ab 420 IU/mL (strongly positive).
Key Points: Classic overt primary hypothyroidism from Hashimoto's thyroiditis (positive TPO antibodies). Start levothyroxine ~100 mcg daily (estimated 1.6 × 65 kg). Fasting, 30-60 min before breakfast. Recheck TSH in 6-8 weeks. Target TSH 0.5-2.5. Also check lipids (likely elevated — will improve with treatment).
Pimp Questions
❓ Why must you wait 6-8 weeks to recheck TSH after a levothyroxine dose change?
Levothyroxine has a half-life of 7 days. It takes approximately 5 half-lives (35 days) to reach steady state. Checking TSH sooner gives a misleading result because the new dose hasn't equilibrated yet. If you increase dose and recheck at 2 weeks, the TSH may still appear elevated → you increase again → overcorrection → iatrogenic hyperthyroidism.
❓ What medications interfere with levothyroxine absorption?
Must separate by ≥ 4 hours: (1) Calcium (supplements and antacids), (2) Iron, (3) PPIs/H2 blockers (need gastric acid for T4 absorption), (4) Soy products, (5) Cholestyramine (binds T4 in gut), (6) Sucralfate, (7) Coffee (reduces absorption by ~30%). Practical advice: take levothyroxine first thing in morning with water only, eat/take other meds ≥ 30-60 min later.
❓ When do you treat subclinical hypothyroidism?
Always treat: TSH > 10, pregnant or planning pregnancy, goiter. Strongly consider treating: TSH 7-10 with positive TPO antibodies (high progression rate to overt hypothyroidism, ~5% per year), symptoms suggestive of hypothyroidism, hyperlipidemia that may improve with treatment. Observe: TSH 4.5-7 without symptoms or risk factors. Elderly > 70: higher TSH may be physiologically normal — treating can cause harm (AF, fractures).
❓ Why should levothyroxine dose be increased in pregnancy?
Pregnancy increases T4 demand by 25-50% due to: (1) increased TBG (estrogen-mediated → more T4 bound, less free), (2) increased plasma volume (dilution), (3) placental deiodinase (degrades T4), (4) fetal thyroid doesn't function until week 12 — fetus depends entirely on maternal T4 for neurodevelopment. Maternal hypothyroidism → lower fetal IQ, neurodevelopmental delay. Increase dose empirically by 2 extra tablets per week when pregnancy confirmed. [ATA, 2017]
❓ What is the #1 cause of persistently elevated TSH in a patient on levothyroxine?
Non-compliance. Before increasing the dose, always ask: (1) Are you taking it daily? (2) On empty stomach, 30-60 min before eating? (3) Are you taking calcium, iron, or PPIs near the dose? (4) Any new medications? A common pattern: patient takes T4 intermittently, TSH remains elevated → dose is increased → patient takes it consistently for a few days before the lab → TSH normalizes temporarily → cycle repeats.
📋 Summary
Summary
Diagnosis
TSH high + FT4 low = primary overt. TSH high + FT4 normal = subclinical. Check TPO Ab.
Treatment
Levothyroxine 1.6 mcg/kg/day. Empty stomach, 30-60 min before food. Separate Ca, Fe, PPI by 4h.
Monitoring
TSH at 6-8 weeks after dose change. Target 0.5-2.5 (elderly: 3-6). Annual once stable.
Subclinical
Treat if: TSH > 10, pregnant, goiter, symptoms + TPO positive, TSH 7-10 + TPO positive.
Pregnancy
Increase dose 25-50% early. Target TSH < 2.5 first trimester. Monthly TFTs.
Pearl
#1 cause of refractory elevated TSH = non-compliance. Central hypothyroidism: monitor FT4, not TSH.
📄 One Pager
One-Pager
Hypothyroidism
Simple drug, nuanced dosing
Levothyroxine Rules
1.6 mcg/kg/day. Empty stomach, 30-60 min before food. Separate Ca/Fe/PPI by 4h. Start low in elderly/cardiac (25 mcg). Recheck TSH at 6-8 weeks. Target 0.5-2.5.
Subclinical Decision
TSH > 10 → treat. TSH 7-10 + TPO+ → treat. Pregnant → treat (target < 2.5). Elderly → often observe (higher TSH may be normal).
Trials
ATA Hypothyroidism Guidelines 2014 · ATA Thyroid in Pregnancy 2017
Multiple Myeloma
Malignant plasma cell neoplasm producing monoclonal immunoglobulin. CRAB criteria define end-organ damage. Intern role: recognize, manage complications, support through chemo.
🔍 Overview
Overview
Multiple myeloma (MM) is a clonal plasma cell neoplasm in the bone marrow producing a monoclonal immunoglobulin (M-protein). Median age at diagnosis: 69 years, more common in African Americans (2×). The disease spectrum: MGUS → smoldering myeloma → active myeloma. Active myeloma requires CRAB criteria (end-organ damage): Calcium elevated (> 11), Renal insufficiency (Cr > 2), Anemia (Hgb < 10), Bone lesions (lytic on skeletal survey or PET/CT). SLiM criteria added in 2014: Sixty percent bone marrow plasma cells, Light chain ratio ≥ 100, MRI with > 1 focal lesion ≥ 5mm — these define myeloma even without CRAB. IMWG, 2014
🧪 Workup
Workup
- SPEP + UPEP with immunofixation — detects M-protein. SPEP identifies the spike; immunofixation types it (IgG most common, then IgA). UPEP detects Bence Jones proteinuria (free light chains).
- Serum free light chains (sFLC) — kappa:lambda ratio. Abnormal ratio with elevated involved chain supports monoclonal process. Essential for light-chain-only myeloma (15%).
- CBC — anemia (normocytic, rouleaux on smear), may have leukopenia/thrombocytopenia with advanced marrow infiltration
- BMP — hypercalcemia, renal insufficiency (light chain cast nephropathy — "myeloma kidney")
- Albumin + β2-microglobulin — ISS staging: Stage I (β2M < 3.5, alb ≥ 3.5), Stage III (β2M ≥ 5.5). R-ISS, 2015
- LDH — elevated = high tumor burden/aggressive biology
- Bone marrow biopsy + aspirate — ≥ 10% clonal plasma cells = myeloma. Send cytogenetics/FISH: high-risk features: del(17p), t(4;14), t(14;16), gain(1q), del(1p).
- Skeletal survey (whole-body low-dose CT or PET/CT) — lytic lesions (punched-out). Do NOT use DEXA or conventional XR for screening. PET/CT preferred (more sensitive).
- Quantitative immunoglobulins — immune paresis (suppression of uninvolved Ig classes → infection risk)
- Viscosity — if IgM or very high M-protein (hyperviscosity rare in IgG myeloma, more common in Waldenström)
🚨 Management
Management
- Transplant-eligible (< 70, good performance): Induction → stem cell collection → autologous stem cell transplant (ASCT) → maintenance. Standard induction: VRd (bortezomib/lenalidomide/dexamethasone) × 3-4 cycles. [SWOG S0777, 2017]. Post-ASCT maintenance: lenalidomide until progression. DETERMINATION, 2022
- Transplant-ineligible: VRd (dose-adjusted) or DRd (daratumumab/lenalidomide/dex) until progression. MAIA, 2019
- Supportive care (intern-critical):
- Bone disease: Zoledronic acid 4 mg IV q4 weeks (or denosumab if CrCl < 30). Reduces skeletal events. Check dental clearance first (ONJ risk).
- Infection prophylaxis: Acyclovir (VZV on bortezomib), TMP-SMX or levofloxacin first 3 months, IVIG if recurrent infections with hypogammaglobulinemia
- VTE prophylaxis: Lenalidomide + dex → aspirin (low risk) or LMWH/DOAC (high risk: prior VTE, obesity, immobility)
- Renal protection: Aggressive hydration, avoid NSAIDs and contrast if possible, treat hypercalcemia
- Pain: Radiation for focal bone pain, vertebroplasty/kyphoplasty for compression fractures
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Bortezomib | 1.3 mg/m² SQ weekly | SQ | Proteasome inhibitor. Peripheral neuropathy (dose-limiting). VZV reactivation → acyclovir prophylaxis. SWOG S0777, 2017 |
| Lenalidomide | 25 mg PO days 1-21/28 | PO | IMiD. VTE risk → thromboprophylaxis. Teratogenic. Dose-reduce for CrCl < 30. Maintenance post-ASCT: 10-15 mg. |
| Daratumumab | 16 mg/kg IV weekly → q2w → q4w | IV/SQ | Anti-CD38 mAb. Infusion reactions (pre-medicate). Interferes with blood bank crossmatch (anti-CD38 on reagent RBCs). MAIA, 2019 |
| Dexamethasone | 40 mg weekly (20 mg if > 75y) | PO | Backbone of all myeloma regimens. Hyperglycemia, insomnia, mood changes, infection risk. |
| Zoledronic acid | 4 mg IV over 15 min q4w | IV | Bone-modifying agent. Reduces SREs. Dental exam before starting (ONJ risk). Dose-adjust for CrCl. MRC Myeloma IX, 2012 |
| Carfilzomib | 20-56 mg/m² IV | IV | 2nd-gen proteasome inhibitor for relapsed MM. Cardiac toxicity (HF, HTN) — check echo baseline. Less neuropathy than bortezomib. |
📊 Monitoring
Monitoring
- SPEP + sFLC q1-2 cycles — track M-protein decline (response criteria: CR, VGPR, PR per IMWG)
- CBC + BMP before each cycle — cytopenias, renal function
- Ca²⁺ — trending (hypercalcemia is a myeloma emergency)
- Peripheral neuropathy assessment — on bortezomib. Grade ≥ 2 → dose-reduce or switch to carfilzomib.
- Echo — baseline + periodic on carfilzomib (cardiotoxicity)
- Dental exam q6 months on bisphosphonates (ONJ monitoring)
- Cr + urine protein — myeloma kidney monitoring. Improving Cr on treatment = good prognostic sign.
- Quantitative Ig — immune paresis monitoring. IVIG if recurrent serious infections.
🏥 Rounds
Sample Presentation
Mr. Wallace is a 71-year-old man presenting with progressive low back pain × 3 months, fatigue, and 15 lb weight loss. Found to have: Hgb 8.4, Ca 12.8, Cr 2.6, total protein 11.2. SPEP: IgG kappa M-spike 4.2 g/dL. sFLC: kappa 890, lambda 12, ratio 74. Skeletal survey: multiple lytic lesions in spine, pelvis, skull. BMBx: 65% clonal plasma cells, FISH: standard risk.
Key Points: Active myeloma with full CRAB: Ca 12.8, Cr 2.6, Anemia (Hgb 8.4), Bone lesions. Also meets SLiM (60% plasma cells). ISS Stage III (β2M likely elevated with that Cr). Immediate: IV hydration + zoledronic acid for hypercalcemia, transfuse for Hgb < 7, renal protection. Start VRd induction. Transplant-ineligible at 71 → consider DRd.
Pimp Questions
❓ What are the CRAB criteria?
Calcium > 11 mg/dL. Renal insufficiency (Cr > 2 or CrCl < 40). Anemia (Hgb < 10 or 2 g below normal). Bone disease (lytic lesions, pathologic fractures, osteoporosis with compression fracture). Any one of these in the setting of a clonal plasma cell disorder = active myeloma requiring treatment. [IMWG, 2014]
❓ Why does daratumumab interfere with blood bank crossmatching?
Daratumumab (anti-CD38) binds to CD38 expressed on reagent red blood cells used in the blood bank, causing a panreactive indirect Coombs test. This makes antibody identification impossible. Solutions: (1) notify blood bank before starting daratumumab, (2) use DTT-treated RBCs (denatures CD38), (3) phenotype/genotype patient RBCs before first dose. Critical for transfusion safety.
❓ What is the mechanism of myeloma kidney (cast nephropathy)?
Free light chains (especially lambda) are filtered by glomeruli and form obstructive casts in distal tubules by binding with Tamm-Horsfall protein. This causes tubular obstruction, inflammation, and fibrosis → AKI/CKD. Aggravated by: dehydration, NSAIDs, IV contrast, loop diuretics (increase Tamm-Horsfall), hypercalcemia. Treatment: aggressive hydration, treat myeloma (reduce light chain production), consider plasmapheresis if very high FLC.
❓ What is the difference between MGUS, smoldering myeloma, and active myeloma?
MGUS: M-protein < 3 g/dL + < 10% marrow plasma cells + no CRAB. Risk of progression: ~1%/year. No treatment — observe. Smoldering myeloma: M-protein ≥ 3 OR 10-59% marrow plasma cells + no CRAB/SLiM. Higher risk (~10%/year first 5 years). Observation vs early treatment (emerging data). Active myeloma: CRAB or SLiM criteria met → treat. [IMWG, 2014]
❓ Why do myeloma patients need VZV prophylaxis on bortezomib?
Bortezomib (proteasome inhibitor) causes profound T-cell immunosuppression by inhibiting NF-κB signaling in T lymphocytes. This predisposes to VZV reactivation (shingles) in up to 13% without prophylaxis. Acyclovir 400 mg BID (or valacyclovir 500 mg daily) reduces risk to < 2%. Continue throughout bortezomib therapy + 3 months after.
❓ What high-risk cytogenetic features change myeloma prognosis?
High-risk FISH: del(17p) (loss of TP53 — worst prognosis), t(4;14) (FGFR3/MMSET), t(14;16) (MAF), t(14;20), gain(1q21), del(1p). Standard risk: t(11;14) (cyclin D1), t(6;14), hyperdiploidy. High-risk patients have median OS ~3-4 years vs > 7 years for standard risk. Treatment intensification (quadruplet induction, tandem ASCT) for high-risk.
📋 Summary
Summary
Diagnosis
SPEP + sFLC + BMBx. ≥ 10% clonal plasma cells + CRAB or SLiM criteria.
CRAB
Calcium > 11. Renal Cr > 2. Anemia Hgb < 10. Bone lytic lesions.
Treatment
VRd induction ± ASCT (if eligible) → lenalidomide maintenance. DRd if transplant-ineligible.
Supportive
Zoledronic acid, acyclovir (bortezomib), VTE prophylaxis (lenalidomide), IVIG if recurrent infections.
High Risk
del(17p), t(4;14), t(14;16), gain(1q). Worse prognosis → intensify therapy.
Pearl
Notify blood bank before daratumumab. Myeloma kidney = light chain casts. Avoid NSAIDs + contrast.
📄 One Pager
One-Pager
Multiple Myeloma
CRAB + SLiM
Workup
SPEP/UPEP + immunofixation + sFLC + BMBx (cytogenetics/FISH) + skeletal survey (PET/CT preferred) + β2M/albumin (ISS staging) + quantitative Ig.
Treatment
Eligible: VRd × 3-4 → ASCT → lenalidomide maintenance. Ineligible: DRd or VRd continuous. Supportive: zoledronic acid, acyclovir, VTE prophylaxis, hydration.
Trials
SWOG S0777 (VRd) · MAIA 2019 (DRd) · DETERMINATION 2022 (ASCT role) · IMWG 2014 (diagnostic criteria)
Acute Leukemia (AML / ALL)
Malignant proliferation of immature myeloid (AML) or lymphoid (ALL) blasts. The intern manages complications: TLS, DIC, leukostasis, infections, and transfusion support.
🔍 Overview
Overview
Acute leukemia = rapid clonal expansion of immature hematopoietic cells (blasts) in the bone marrow, spilling into blood. AML (acute myeloid): median age 68, most common adult acute leukemia. ALL (acute lymphoblastic): bimodal — peak in children 2-5y + second peak > 60y. Diagnosis: ≥ 20% blasts in marrow or blood (WHO). Exception: AML with recurrent genetic abnormalities (e.g. t(8;21), inv(16)) can be diagnosed at any blast %. APL (acute promyelocytic leukemia, M3): medical emergency — presents with severe DIC. Treat with ATRA immediately on suspicion, before confirmation. The intern's role: you will not choose chemo regimens — you WILL manage TLS prevention, febrile neutropenia, DIC, transfusion, electrolytes, and pain.
🧪 Workup
Workup
- CBC with differential + peripheral smear — blasts (≥ 20%), may see Auer rods (AML, especially APL). WBC can be markedly elevated (leukostasis risk if > 100K) or low (aleukemic leukemia).
- Bone marrow biopsy + aspirate — definitive. Send: morphology, flow cytometry (lineage: myeloid vs lymphoid), cytogenetics (karyotype), FISH (specific translocations), molecular testing (FLT3, NPM1, IDH1/2, TP53 for AML; BCR-ABL for ALL).
- Coags + fibrinogen — DIC screen (especially APL). If DIC + blasts → start ATRA immediately.
- BMP + uric acid + LDH + phosphate — TLS risk assessment
- G6PD — before rasburicase
- Type & screen — will need multiple transfusions
- HLA typing — early if transplant candidate (start sibling/unrelated donor search)
- Lumbar puncture — ALL requires CNS staging (LP with intrathecal chemotherapy). AML: LP only if CNS symptoms.
- Echo — baseline EF before anthracycline-containing induction
- Infectious workup — blood/urine cultures, CXR, consider fungal markers if prolonged neutropenia expected
🚨 Management
Management
- APL (M3 AML) — EMERGENCY: Start ATRA (all-trans retinoic acid) immediately if APL suspected (Auer rods, DIC, promyelocytic morphology). Do NOT wait for FISH confirmation. ATRA + arsenic trioxide (ATO) cures > 90% of APL. [Lo-Coco, 2013]
- AML induction: "7+3" — cytarabine 7 days + daunorubicin 3 days. Targeted: add midostaurin if FLT3+ [RATIFY, 2017], gemtuzumab ozogamicin if CD33+ favorable risk. Unfit elderly: azacitidine + venetoclax [VIALE-A, 2020].
- ALL induction: Multi-agent (vincristine, prednisone, daunorubicin, asparaginase ± cyclophosphamide). Ph+ ALL: add dasatinib or ponatinib (TKI) [GRAAPH-2005]. CNS prophylaxis with intrathecal methotrexate.
- Consolidation → Transplant: Intermediate/high-risk AML and high-risk ALL → allogeneic stem cell transplant in CR1.
- Intern-managed complications:
- TLS prevention: Aggressive IVF + allopurinol (prophylaxis) or rasburicase (treatment/high-risk). Check TLS labs q6-8h.
- Leukostasis (WBC > 100K): Emergent leukapheresis + hydroxyurea 50-100 mg/kg. Symptoms: dyspnea, confusion, visual changes (WBC plugging microvasculature).
- DIC: Aggressive blood product support (cryoprecipitate for fibrinogen < 100-150, platelets for < 50K with bleeding). Treat the leukemia (definitive DIC treatment).
- Febrile neutropenia: Cefepime or meropenem within 1 hour. See neutropenic fever protocol.
- Transfusion: pRBC for Hgb < 7-8. Platelets for < 10K (prophylactic) or < 50K with bleeding. Irradiated + leukoreduced products.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| ATRA (tretinoin) | 45 mg/m²/day divided BID | PO | APL — start immediately on suspicion. Differentiates promyelocytes. Risk: differentiation syndrome (fever, dyspnea, edema, pleural effusion) → dexamethasone 10 mg BID. Lo-Coco, 2013 |
| Arsenic trioxide | 0.15 mg/kg IV daily | IV | APL (with ATRA). Cure rate > 90%. QTc monitoring (arrhythmia risk). Hepatotoxicity. |
| Cytarabine (Ara-C) | 100-200 mg/m²/day × 7d (induction) | IV | Backbone of AML "7+3." High-dose for consolidation. Cerebellar toxicity at high dose (check cerebellar function daily). |
| Venetoclax | 400 mg daily (after ramp-up) | PO | BCL-2 inhibitor. With azacitidine for unfit AML. High TLS risk — ramp-up dosing + rasburicase. VIALE-A, 2020 |
| Midostaurin | 50 mg BID days 8-21 | PO | FLT3 inhibitor added to 7+3 for FLT3-mutated AML. RATIFY, 2017 |
| Hydroxyurea | 50-100 mg/kg/day | PO | Cytoreduction for leukostasis (WBC > 100K). Bridge until definitive chemo. Also for SCD maintenance. |
📊 Monitoring
Monitoring
- CBC daily during induction — track nadir (typically days 10-21 for AML). Expect 2-4 weeks of pancytopenia.
- TLS labs q6-8h — K⁺, PO₄, Ca²⁺, uric acid, Cr, LDH during first 72h of treatment
- Coags + fibrinogen daily — especially APL. Keep fibrinogen > 100-150 with cryoprecipitate.
- Daily assessment: fever curve, exam (skin for leukemia cutis, gums for infiltration, fundoscopy for leukostasis, neuro for CNS leukemia)
- Day 14 bone marrow (AML) — assess for residual disease. If persistent blasts → may need re-induction.
- QTc — on arsenic trioxide. Hold if QTc > 500 ms. Correct K⁺ and Mg²⁺ aggressively.
- Cerebellar function — on high-dose cytarabine. Dysarthria, ataxia, nystagmus → stop immediately (irreversible).
- MRD (measurable residual disease) — flow cytometry or molecular testing post-induction. Guides consolidation/transplant decision.
🏥 Rounds
Sample Presentation
Ms. Chen is a 58-year-old woman presenting with 2 weeks of fatigue, easy bruising, and gum bleeding. Exam: pallor, petechiae, gingival hyperplasia. Labs: WBC 68K with 78% blasts, Hgb 6.8, platelets 12K, LDH 1200, uric acid 9.2. Smear: large blasts with Auer rods. PT 18, fibrinogen 95.
Key Points: AML with Auer rods + DIC (fibrinogen 95, prolonged PT) → high suspicion for APL. Start ATRA immediately. Aggressive product support: cryoprecipitate for fibrinogen > 150 (higher target in APL), platelets for > 30-50K (APL bleeding threshold). TLS prevention: IVF + rasburicase (uric acid 9.2 + high WBC). Confirm with FISH for PML-RARA t(15;17).
Pimp Questions
❓ Why must you start ATRA immediately when APL is suspected?
APL (M3 AML) presents with severe DIC that is rapidly fatal without treatment. ATRA differentiates the malignant promyelocytes, which resolves the DIC within days. Mortality from APL-related hemorrhage is highest in the first 48-72 hours. Waiting for FISH confirmation of t(15;17) PML-RARA can take 2-5 days — too long. Start ATRA on clinical/morphologic suspicion (Auer rods + DIC + promyelocytic morphology). If wrong, ATRA has minimal toxicity.
❓ What is differentiation syndrome and how do you manage it?
Differentiation syndrome (formerly "ATRA syndrome") occurs when ATRA/ATO causes rapid maturation of leukemic promyelocytes → release of cytokines → capillary leak. Features: fever, dyspnea, weight gain, pulmonary infiltrates, pleural/pericardial effusions, hypotension. Can be fatal. Treatment: dexamethasone 10 mg IV BID + continue ATRA (unless life-threatening). Hold ATRA only if severe. Occurs in ~25% of APL patients, typically within first 1-2 weeks.
❓ What is leukostasis and at what WBC does it occur?
Leukostasis = symptomatic hyperviscosity from WBC plugging microvasculature. Typically when WBC > 100K (lower threshold for AML blasts — larger and stickier than ALL blasts). Symptoms: dyspnea, hypoxia, confusion, visual changes, headache. Treatment: emergent leukapheresis + hydroxyurea. Do NOT transfuse pRBCs before reducing WBC (increases viscosity). AML leukostasis is more dangerous than ALL at the same WBC.
❓ What molecular markers are most important in AML and why?
FLT3-ITD: present in ~30% AML. Worse prognosis. Add midostaurin to 7+3 [RATIFY, 2017]. NPM1: favorable if FLT3-negative — may not need transplant in CR1. IDH1/IDH2: targetable with ivosidenib/enasidenib. TP53: very poor prognosis — poor response to standard chemo. t(8;21), inv(16): core-binding factor AML — favorable, respond well to high-dose cytarabine consolidation.
❓ Why are blood products in leukemia patients irradiated and leukoreduced?
Irradiated: prevents transfusion-associated graft-versus-host disease (TA-GVHD) — donor lymphocytes in the blood product attack the immunocompromised recipient's tissues. TA-GVHD is > 90% fatal. Irradiation inactivates donor lymphocytes. Leukoreduced: removes WBCs → prevents febrile non-hemolytic transfusion reactions, CMV transmission, and HLA alloimmunization (important for future transplant candidates).
📋 Summary
Summary
Diagnosis
≥ 20% blasts in marrow/blood. Flow + cytogenetics + FISH + molecular testing.
APL
ATRA + ATO immediately. Auer rods + DIC. Cure > 90%. Do NOT wait for FISH.
AML
7+3 (cytarabine + daunorubicin). Add midostaurin if FLT3+. Unfit: aza + venetoclax.
ALL
Multi-agent induction + CNS prophylaxis. Add TKI if Ph+. Transplant for high-risk.
Intern Role
TLS prevention, febrile neutropenia, DIC management, transfusion support, electrolytes.
Pearl
WBC > 100K = leukostasis risk → leukapheresis + hydroxyurea. Don't transfuse pRBC first.
📄 One Pager
One-Pager
Acute Leukemia
AML / ALL / APL
APL Emergency
Auer rods + DIC → start ATRA now. Don't wait for FISH. Cryoprecipitate for fibrinogen > 150. ATRA + arsenic trioxide cures > 90%.
Trials
Lo-Coco 2013 (ATRA+ATO for APL) · RATIFY 2017 (midostaurin for FLT3+ AML) · VIALE-A 2020 (aza+venetoclax)
Anticoagulation Management
Warfarin vs DOACs vs heparin: choosing, dosing, monitoring, bridging, and reversal. The most commonly consulted hematology topic on wards.
🔍 Overview
Overview
Anticoagulation management is one of the most common daily tasks on inpatient medicine. Key decisions: (1) Which agent? Heparin (UFH for acute, can titrate, dialyzable) vs LMWH (predictable, SQ, no monitoring) vs warfarin (outpatient, INR monitoring, cheap) vs DOAC (outpatient, no monitoring, fewer interactions, not all indications). (2) When to bridge? Only high-risk patients (mechanical valve, recent VTE < 3 months, prior thrombosis on interruption). (3) How to reverse? Warfarin: vitamin K ± 4-factor PCC. DOACs: idarucizumab (dabigatran), andexanet alfa (Xa inhibitors), or 4F-PCC. Heparin: protamine. Key intern skill: recognizing bleeding vs thrombotic risk and adjusting therapy accordingly.
🧪 Workup
Workup
- Before starting anticoagulation: CBC, PT/INR, aPTT, Cr + CrCl (DOAC dosing), LFTs (hepatic clearance), HAS-BLED score (bleeding risk)
- Warfarin monitoring: INR (target 2-3 for most indications; 2.5-3.5 for mechanical mitral valve). Check INR daily inpatient until stable, then q1-4 weeks outpatient.
- Heparin monitoring: aPTT q6h after initiation or dose change (anti-Xa levels if aPTT unreliable — lupus anticoagulant, elevated baseline). Target aPTT per institutional protocol (usually 1.5-2.5× control).
- LMWH: No routine monitoring. Check anti-Xa level (peak, 4h post-dose) if: obesity (> 150 kg), CKD (CrCl < 30 → use UFH instead), pregnancy.
- DOACs: No routine monitoring. Check Cr + CrCl (dose-adjust apixaban/rivaroxaban at CrCl 15-30; dabigatran CI if CrCl < 30). Drug-specific anti-Xa (rivaroxaban, apixaban) or dTT (dabigatran) for special situations (overdose, pre-surgery, bleeding).
- Indication verification: AF (CHA₂DS₂-VASc ≥ 2 men, ≥ 3 women), VTE treatment, mechanical valve (warfarin only), antiphospholipid syndrome (warfarin preferred over DOACs [TRAPS, 2018])
🚨 Management
Management
- VTE treatment: DOAC preferred (rivaroxaban or apixaban). Duration: provoked DVT = 3 months; unprovoked = extended (reassess annually). Cancer-associated VTE: LMWH or DOAC (edoxaban, rivaroxaban) [HOKUSAI VTE Cancer, 2018; SELECT-D, 2018]. Exception: GI/GU cancer with high bleed risk → LMWH preferred.
- AF anticoagulation: DOAC preferred over warfarin for nonvalvular AF [RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48]. Exception: moderate-severe mitral stenosis or mechanical valve → warfarin only.
- Perioperative bridging:
- Most patients: do NOT bridge. [BRIDGE, 2015] — bridging with LMWH in AF patients on warfarin increased bleeding without reducing thrombosis.
- Bridge ONLY if: mechanical mitral valve, mechanical aortic valve + additional risk factor, VTE within 3 months, prior thrombosis during anticoagulation interruption.
- Stop warfarin 5 days before. Stop DOAC 2-3 days before (longer if CKD). Resume 24-72h post-procedure depending on bleeding risk.
- Reversal:
- Warfarin: Vitamin K 10 mg IV (takes 6-24h). For urgent: 4-factor PCC (Kcentra) 25-50 units/kg (immediate). FFP only if PCC unavailable.
- Dabigatran: Idarucizumab (Praxbind) 5g IV — immediate, complete reversal. RE-VERSE AD, 2017
- Xa inhibitors (rivaroxaban/apixaban/edoxaban): Andexanet alfa (Andexxa) — expensive, limited availability. Alternative: 4-factor PCC 50 units/kg. ANNEXA-4, 2019
- Heparin: Protamine 1 mg per 100 units UFH given in last 2-3h (max 50 mg). Only 60% effective for LMWH.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Apixaban (Eliquis) | 5 mg BID (2.5 if ≥ 2 of: age ≥ 80, wt ≤ 60, Cr ≥ 1.5) | PO | Preferred DOAC for AF (lowest bleeding). No CrCl cutoff but avoid < 15. VTE: 10 mg BID × 7d → 5 mg BID. ARISTOTLE, 2011 |
| Rivaroxaban (Xarelto) | 20 mg daily with food (15 if CrCl 15-50) | PO | Once daily dosing. VTE: 15 mg BID × 21d → 20 mg daily. Take with food (improves absorption). ROCKET AF, 2011 |
| Dabigatran (Pradaxa) | 150 mg BID (110 if age ≥ 80 or high bleed risk) | PO | Direct thrombin inhibitor. CI if CrCl < 30. Has specific reversal (idarucizumab). Dyspepsia common. RE-LY, 2009 |
| Warfarin (Coumadin) | Individualized (typically 2-10 mg daily) | PO | Required for mechanical valves + APS. INR monitoring. Drug/food interactions. Vitamin K dependent factors (II, VII, IX, X, protein C/S). |
| Heparin (UFH) | 80 U/kg bolus → 18 U/kg/hr | IV | Titratable, short half-life, dialyzable. Monitor aPTT q6h. Protamine for reversal. HIT risk. |
| Enoxaparin (Lovenox) | 1 mg/kg BID or 1.5 mg/kg daily | SQ | Predictable pharmacokinetics. Avoid if CrCl < 30 (accumulates). Anti-Xa for monitoring in special populations. |
| 4-Factor PCC (Kcentra) | 25-50 U/kg IV | IV | Warfarin reversal (immediate). Also used off-label for Xa inhibitor reversal. Contains factors II, VII, IX, X + protein C/S. |
📊 Monitoring
Monitoring
- Warfarin INR: daily inpatient → weekly → q2-4 weeks when stable. Time in therapeutic range (TTR) target > 65%.
- Heparin aPTT: q6h after initiation or dose change until 2 consecutive values in range, then q12-24h.
- DOACs: Cr annually (more frequent if CKD). No routine drug levels. CBC at baseline + annually.
- Bleeding assessment: signs (hemoglobin drop, melena, hematuria, bruising), drug interactions (NSAIDs, antiplatelets, CYP3A4 inhibitors)
- HIT screening: platelet count q2-3 days on UFH × first 14 days. 4T score if platelet drop.
- CHA₂DS₂-VASc reassessment: annually for AF patients — score can change (new DM, HF, age threshold).
🏥 Rounds
Sample Presentation
Mr. Davis is a 74-year-old man on warfarin for mechanical aortic valve (INR target 2.5-3.5) admitted for cholecystectomy. Current INR 3.1. Surgery planned in 3 days. Question: how do you manage his anticoagulation perioperatively?
Key Points: Mechanical valve = high thromboembolic risk → bridge with therapeutic LMWH. Stop warfarin now (5 days pre-op). Start enoxaparin 1 mg/kg BID when INR < 2. Hold LMWH 24h pre-surgery. Restart heparin drip post-op when hemostasis confirmed (12-24h). Resume warfarin evening of surgery. Stop heparin when INR therapeutic.
Pimp Questions
❓ When should you bridge anticoagulation perioperatively and when should you not?
Do NOT bridge most patients. [BRIDGE, 2015] showed that bridging AF patients on warfarin with LMWH increased major bleeding 3-fold without reducing stroke. Bridge ONLY: mechanical mitral valve, mechanical aortic valve + additional risk factor (AF, prior stroke, EF < 35%), VTE within 3 months, prior thromboembolism during anticoagulation interruption.
❓ Why are DOACs preferred over warfarin for nonvalvular AF?
Four landmark trials showed DOACs are non-inferior or superior to warfarin for stroke prevention with lower rates of intracranial hemorrhage: RE-LY (dabigatran), ROCKET AF (rivaroxaban), ARISTOTLE (apixaban — also reduced mortality), ENGAGE AF (edoxaban). Additional advantages: no INR monitoring, fewer food/drug interactions, predictable pharmacokinetics, rapid onset.
❓ How do you reverse each anticoagulant?
Warfarin: Vitamin K 10 mg IV (slow, 6-24h) + 4-factor PCC 25-50 U/kg (immediate). Dabigatran: Idarucizumab 5g IV (immediate, complete). Xa inhibitors: Andexanet alfa (expensive) or 4F-PCC 50 U/kg (off-label). Heparin: Protamine 1 mg/100 U UFH. LMWH: Protamine partially effective (~60%). For all: hold drug, apply pressure, transfuse if needed.
❓ Why is warfarin preferred over DOACs in antiphospholipid syndrome?
[TRAPS, 2018] — trial of rivaroxaban vs warfarin in triple-positive APS was stopped early for excess thrombotic events in the rivaroxaban arm (arterial events). DOACs may be acceptable for single/double-positive APS with venous-only events, but triple-positive APS must be on warfarin. Warfarin is also required for mechanical heart valves (DOACs showed excess valve thrombosis in RE-ALIGN).
❓ What is the CHA₂DS₂-VASc score and when do you anticoagulate?
CHF (1), HTN (1), Age ≥ 75 (2), DM (1), Stroke/TIA (2), Vascular disease (1), Age 65-74 (1), Sex female (1). Score 0 (men) or 1 (women): no anticoagulation. Score 1 (men) or 2 (women): consider. Score ≥ 2 (men) or ≥ 3 (women): anticoagulate. DOAC preferred unless valvular AF or APS.
📋 Summary
Summary
AF
DOAC preferred. CHA₂DS₂-VASc ≥ 2M/≥3F → anticoagulate. Warfarin only for mechanical valve or APS.
VTE
DOAC preferred. 3 mo (provoked) vs extended (unprovoked). Cancer: LMWH or DOAC.
Bridging
Most: do NOT bridge [BRIDGE, 2015]. Bridge only: mechanical valve, VTE < 3 mo.
Reversal
Warfarin: 4F-PCC + vit K. Dabigatran: idarucizumab. Xa: andexanet or 4F-PCC. Heparin: protamine.
Monitoring
Warfarin: INR. Heparin: aPTT q6h. LMWH: anti-Xa (special). DOACs: Cr annually.
Pearl
DOACs contraindicated in APS [TRAPS] + mechanical valves [RE-ALIGN]. Rivaroxaban with food.
📄 One Pager
One-Pager
Anticoagulation
Choose, dose, reverse
Agent Selection
AF/VTE: DOAC first-line. Mechanical valve: warfarin only. APS (triple-positive): warfarin only. Cancer VTE: LMWH or DOAC. Acute inpatient: UFH (titratable) or LMWH.
Reversal Agents
Warfarin → 4F-PCC + vit K. Dabigatran → idarucizumab 5g IV. Xa inhibitors → andexanet alfa or 4F-PCC 50 U/kg. UFH → protamine. LMWH → protamine (partial).
Trials
BRIDGE 2015 · RE-LY · ROCKET AF · ARISTOTLE · TRAPS 2018 · RE-VERSE AD · ANNEXA-4 · HOKUSAI VTE Cancer
Anemia Workup
Systematic MCV-based approach: microcytic (iron deficiency #1), normocytic (chronic disease, hemolysis, bleeding), macrocytic (B12/folate, MDS, alcohol). Every anemia deserves a reticulocyte count.
🔍 Overview
Overview
Anemia = Hgb < 13 (men) or < 12 (women). Affects ~25% of hospitalized patients. The approach is MCV-driven: Microcytic (MCV < 80): iron deficiency (#1 worldwide), thalassemia, anemia of chronic disease (can be micro or normo), sideroblastic, lead poisoning. Normocytic (MCV 80-100): anemia of chronic disease/inflammation (#1 inpatient), acute blood loss, hemolysis, CKD (EPO deficiency), mixed deficiency. Macrocytic (MCV > 100): B12/folate deficiency, MDS, alcohol/liver disease, hypothyroidism, medications (methotrexate, hydroxyurea, AZT). The reticulocyte count is the most underordered and most important second test — it tells you whether the marrow is responding appropriately (high retic = destruction/loss) or failing (low retic = production problem).
🧪 Workup
Workup
- Step 1 — CBC + reticulocyte count + peripheral smear
- Reticulocyte index > 2%: marrow is responding → blood LOSS or DESTRUCTION (hemolysis)
- Reticulocyte index < 2%: marrow failure → production problem
- Step 2 — MCV-based workup:
- Microcytic: Iron studies (ferritin, TIBC, serum iron, transferrin sat). Ferritin < 30 = iron deficiency (in inflammation: ferritin < 100 is likely iron deficient). Thalassemia: Mentzer index (MCV/RBC < 13 = thalassemia trait), Hgb electrophoresis.
- Normocytic: BMP (CKD), CRP/ESR (chronic disease), hemolysis labs (LDH, haptoglobin, indirect bili, DAT), reticulocyte count. If hemolysis: Coombs positive = autoimmune (AIHA). Coombs negative = mechanical (TTP, DIC, valve), PNH, G6PD, sickle cell.
- Macrocytic: B12 + folate (if equivocal: methylmalonic acid for B12, homocysteine for both). TSH. LFTs. Peripheral smear (hypersegmented neutrophils = megaloblastic). Consider bone marrow biopsy if unexplained (MDS).
- Iron studies interpretation:
- Iron deficiency: ferritin ↓, TIBC ↑, iron ↓, TfSat < 20%
- Chronic disease: ferritin ↑ (or normal), TIBC ↓, iron ↓, TfSat 15-20%
- Iron deficiency + chronic disease: ferritin 30-100 (unreliably elevated by inflammation), TIBC variable. Check soluble transferrin receptor (sTfR) — elevated = true iron deficiency even with inflammation.
🚨 Management
Management
- Iron deficiency anemia:
- Oral: ferrous sulfate 325 mg (65 mg elemental Fe) every other day on empty stomach with vitamin C [IRON-MIDE, 2020]. Every-other-day dosing is as effective as daily (hepcidin rebound). Avoid with PPIs, calcium, coffee.
- IV iron: if oral intolerant, CKD, inflammatory bowel disease, Hgb < 7, or pre-surgical. Iron sucrose 200 mg × 5 doses or ferric carboxymaltose 750 mg × 2 or low-molecular-weight iron dextran 1000 mg × 1 (single dose, monitor for anaphylaxis × 1h).
- Always find the source: premenopausal women → menstrual loss. Men or postmenopausal → GI source until proven otherwise (EGD + colonoscopy). Celiac screening if no GI source found.
- B12 deficiency: IM cyanocobalamin 1000 mcg daily × 7d → weekly × 4wk → monthly lifelong. High-dose oral (1000-2000 mcg/day) is an alternative for compliant patients without malabsorption.
- Anemia of chronic disease: Treat underlying condition. EPO-stimulating agents (epoetin alfa, darbepoetin) for CKD (target Hgb 10-11, not higher [TREAT, CREATE]). IV iron if concurrent iron deficiency (TfSat < 20%, ferritin < 100).
- Transfusion: Hgb < 7 (restrictive threshold [TRICC, 1999]). < 8 if ACS or symptomatic. 1 unit at a time → recheck.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Ferrous sulfate | 325 mg (65 mg elemental) every other day | PO | Empty stomach + vitamin C for absorption. Every-other-day = daily efficacy with fewer GI SEs. Avoid PPIs, Ca, coffee. IRON-MIDE, 2020 |
| Iron sucrose (Venofer) | 200 mg IV × 5 doses | IV | Safe. No test dose needed. For CKD, oral intolerance, IBD. |
| Ferric carboxymaltose (Injectafer) | 750 mg IV × 2 (1 week apart) | IV | Higher single dose. Risk: hypophosphatemia (can be severe, chronic). Monitor PO₄. |
| LMW iron dextran (INFeD) | 1000 mg IV × 1 dose | IV | Total dose infusion. Anaphylaxis risk (0.6%) → monitor 1h. Test dose optional. |
| Cyanocobalamin (B12) | 1000 mcg IM daily × 7d → weekly × 4 → monthly | IM | Lifelong for pernicious anemia. Expect retic crisis day 5-7. Monitor K⁺. |
| Epoetin alfa | 50-300 IU/kg TIW | SQ | CKD anemia (target Hgb 10-11). VTE risk if Hgb > 11. Iron replete first (TfSat > 20%, ferritin > 100). TREAT, 2009 |
📊 Monitoring
Monitoring
- Reticulocyte count at day 5-7 — after starting B12 or iron. Expected "retic crisis" = brisk reticulocytosis confirming marrow response.
- CBC + reticulocyte at 2-4 weeks — Hgb should begin rising. If not → reassess diagnosis, compliance, concurrent iron deficiency.
- Ferritin at 8-12 weeks — on oral iron. Target ferritin > 100 (or > 200 in CKD). Continue oral iron 3-6 months after Hgb normalizes to replete stores.
- K⁺, PO₄ — drop during rapid erythropoiesis (B12 repletion, EPO therapy). Monitor and replace.
- Iron studies before EPO — functional iron deficiency is #1 cause of EPO resistance. TfSat < 20% or ferritin < 100 → give IV iron.
- Hemolysis markers — if autoimmune: DAT, LDH, haptoglobin, reticulocyte count. Trending LDH is the simplest way to monitor hemolytic activity.
🏥 Rounds
Sample Presentation
Mrs. Martinez is a 52-year-old postmenopausal woman presenting with fatigue × 3 months. No bleeding, no melena. PMH: GERD on omeprazole. Labs: Hgb 8.2, MCV 72, ferritin 8, TIBC 450, TfSat 8%, reticulocyte index 0.5%.
Key Points: Classic iron deficiency anemia — microcytic, low ferritin, high TIBC, low TfSat, low retic (production problem). Postmenopausal woman = GI source until proven otherwise. Needs EGD + colonoscopy. Start oral iron (every other day with vitamin C). Consider IV iron if oral intolerant or Hgb < 7. Celiac screen (anti-TTG) if GI workup negative. PPI may impair iron absorption.
Pimp Questions
❓ What is the most important second test after CBC in anemia workup?
Reticulocyte count. It differentiates production problems (low retic: marrow failure, nutrient deficiency) from destruction/loss (high retic: hemolysis, bleeding). Calculate the reticulocyte index (RI) = retic % × (patient Hgb / normal Hgb) ÷ maturation factor. RI > 2 = appropriate marrow response. RI < 2 = inadequate. Most underordered test in anemia workup.
❓ How do you diagnose iron deficiency in a patient with concurrent inflammation?
Ferritin is an acute phase reactant — inflammation falsely elevates it. A "normal" ferritin of 60 in a patient with CRP of 80 may actually represent iron deficiency. Rules: (1) ferritin < 30 = iron deficient regardless of inflammation. (2) Ferritin 30-100 with inflammation = likely iron deficient. (3) Best additional test: soluble transferrin receptor (sTfR) — elevated in true iron deficiency, NOT affected by inflammation. TfSat < 20% also supports iron deficiency.
❓ Why should oral iron be taken every other day rather than daily?
[IRON-MIDE, 2020] demonstrated that every-other-day dosing is as effective as daily for iron repletion. The mechanism: an oral iron dose triggers hepcidin release (iron-regulatory hormone) that peaks at 24h and blocks iron absorption for ~48h. A second daily dose is largely not absorbed and only causes GI side effects (nausea, constipation). Every-other-day dosing allows hepcidin to fall between doses → better absorption per dose with fewer side effects.
❓ When must you find the source of iron deficiency anemia?
Always in men and postmenopausal women — GI malignancy (colon cancer) until proven otherwise. Get EGD + colonoscopy. In premenopausal women, menstrual loss is the most common cause, but if heavy menstruation doesn't explain the severity, or if there are GI symptoms → scope. Also consider: celiac disease (anti-TTG), gastric bypass (iron absorption site bypassed), chronic NSAID use (GI erosions).
❓ What peripheral smear findings help differentiate causes of anemia?
Target cells: thalassemia, iron deficiency, liver disease. Schistocytes: TTP, DIC, mechanical valve hemolysis. Spherocytes: autoimmune hemolysis (AIHA), hereditary spherocytosis. Hypersegmented neutrophils: B12/folate deficiency (megaloblastic). Teardrop cells + leukoerythroblastic: myelofibrosis/marrow infiltration. Sickle cells: SCD. Rouleaux: myeloma, inflammation. Bite cells/Heinz bodies: G6PD deficiency.
📋 Summary
Summary
Step 1
CBC + reticulocyte count + peripheral smear. Retic high = loss/destruction. Low = production.
Microcytic
Iron studies. Ferritin < 30 = iron deficient. Ferritin 30-100 with inflammation = likely iron deficient. Mentzer < 13 = thalassemia.
Normocytic
CKD (EPO), chronic disease (CRP), hemolysis (LDH, hapto, DAT), bleeding (retic + guaiac).
Macrocytic
B12 + folate + TSH + LFTs. Hypersegmented neutrophils = megaloblastic. MDS if unexplained.
Iron Rx
Oral: every other day + vitamin C. IV if intolerant/CKD/severe. Always find the source.
Pearl
Reticulocyte count is the most underordered test. Ferritin is an acute phase reactant. Smear is free and diagnostic.
📄 One Pager
One-Pager
Anemia Workup
MCV → Retic → Smear
Algorithm
Step 1: CBC + retic + smear. Step 2: MCV-based labs (micro → iron studies; normo → hemolysis labs + CKD; macro → B12/folate). Step 3: Bone marrow if unexplained.
Iron Studies Cheat Sheet
IDA: ferritin ↓, TIBC ↑, TfSat ↓. ACD: ferritin ↑, TIBC ↓, TfSat low-normal. IDA+ACD: ferritin 30-100, check sTfR. Hemolysis: LDH ↑, haptoglobin ↓, retic ↑, DAT±.
Trials
TRICC 1999 (restrictive transfusion) · IRON-MIDE 2020 (every-other-day iron) · TREAT 2009 (EPO in CKD)
Hemolytic Anemia
Accelerated RBC destruction. Coombs test is the branch point: positive = immune (autoimmune, drug, transfusion). Negative = non-immune (mechanical, intrinsic RBC defect). Always check the smear.
🔍 Overview
Overview
Hemolytic anemia = shortened RBC lifespan (< 120 days) causing anemia with compensatory reticulocytosis. Hallmark labs: elevated LDH, elevated indirect bilirubin, low/undetectable haptoglobin, elevated reticulocyte count. Two categories by mechanism: Intravascular hemolysis (RBCs destroyed in circulation — hemoglobinuria, hemoglobinemia, very low haptoglobin — PNH, TTP, mechanical valve, transfusion reaction, DIC). Extravascular hemolysis (RBCs destroyed by splenic macrophages — splenomegaly, jaundice, no hemoglobinuria — AIHA, hereditary spherocytosis, sickle cell, hypersplenism). The direct Coombs test (DAT) is the critical branch point: positive = antibody on RBCs → immune hemolysis. Negative = non-immune → check smear for mechanistic clues.
🧪 Workup
Workup
- Hemolysis labs: LDH (↑), haptoglobin (↓ or undetectable), indirect bilirubin (↑), reticulocyte count (↑). All four should be checked together.
- Direct Coombs test (DAT) — the branch point.
- DAT positive: warm AIHA (IgG — most common, responds to steroids), cold agglutinin disease (IgM + complement — associated with Mycoplasma, lymphoma), drug-induced (cephalosporins, piperacillin, methyldopa), transfusion reaction
- DAT negative: microangiopathic (TTP, DIC, HUS — schistocytes on smear), mechanical (prosthetic valve), PNH (flow cytometry for GPI-anchored proteins), intrinsic RBC defects (G6PD, hereditary spherocytosis, sickle cell, thalassemia). If TTP suspected → calculate PLASMIC score (predicts ADAMTS13 deficiency) PLASMIC Score, Bendapudi 2017
- Peripheral smear — essential. Schistocytes (TMA), spherocytes (AIHA, HS), sickle cells, bite cells (G6PD), target cells (thalassemia, liver)
- Flow cytometry — if PNH suspected (dark urine, pancytopenia, abdominal vein thrombosis). Tests for CD55/CD59 (GPI-anchored proteins absent in PNH).
- G6PD level — check BETWEEN episodes (level is falsely normal during acute hemolysis because young RBCs have more G6PD). Common triggers: sulfa drugs, dapsone, fava beans, infections.
- Cold agglutinin titer — if DAT positive for complement only (C3d) with IgG negative. Associated with Mycoplasma pneumonia, EBV, lymphoma.
- Osmotic fragility — hereditary spherocytosis (spherocytes lyse more easily in hypotonic solution)
🚨 Management
Management
- Warm AIHA (DAT positive, IgG):
- First-line: Prednisone 1 mg/kg daily → taper when Hgb stabilizing. Response in 70-85% within 1-3 weeks.
- Second-line: Rituximab 375 mg/m² × 4 (steroid-refractory or relapsing). Also consider: mycophenolate, azathioprine. Lechner & Jäger, 2015
- Third-line: Splenectomy (if failing medical therapy). Vaccinate before surgery.
- Transfuse if life-threatening anemia — DO transfuse despite positive DAT making crossmatch difficult. Use "least incompatible" units. The blood bank will work with you.
- Cold agglutinin disease (DAT positive, C3d): Keep patient warm (avoid cold exposure, warm IV fluids). Steroids less effective than in warm AIHA. Rituximab first-line. Sutimlimab (anti-C1s complement inhibitor) for chronic CAD [CARDINAL, 2022]. Avoid RBC transfusion if possible (complement activates on transfused cells).
- TTP/HUS: See TTP topic (PLEX, steroids, caplacizumab). HERCULES, Scully 2019
- PNH: Eculizumab (anti-C5 complement inhibitor) [TRIUMPH, 2006]. Meningococcal vaccine required before starting. Ravulizumab (longer-acting) available.
- G6PD: Remove trigger (stop offending drug, treat infection). Supportive care. Avoid oxidant drugs lifelong.
- Mechanical valve hemolysis: Usually mild. If severe → evaluate for paravalvular leak (echo). Iron/folate supplementation for chronic hemolysis.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Prednisone | 1 mg/kg daily → taper | PO | First-line for warm AIHA. 70-85% respond. Taper slowly (relapse if too fast). Chronic steroid toxicity limits duration. |
| Rituximab | 375 mg/m² weekly × 4 | IV | Second-line for warm AIHA, first-line for CAD. Anti-CD20. Screen HBV. Response in 1-3 weeks. |
| Eculizumab | 600 mg IV q7d × 4 → 900 mg q14d | IV | PNH — anti-C5 complement inhibitor. Meningococcal vaccine ≥ 2 weeks before. Lifelong therapy. TRIUMPH, 2006 |
| Sutimlimab | Weight-based IV q2w | IV | CAD — anti-C1s. First targeted therapy for cold agglutinin disease. CARDINAL, 2022 |
| Folic acid | 1 mg daily | PO | All chronic hemolytic anemias — supports increased RBC turnover. Deficiency accelerates anemia. |
📊 Monitoring
Monitoring
- Hemolysis markers q1-2 days during acute episode: LDH (simplest trending marker), haptoglobin, reticulocyte count
- Hgb daily during active hemolysis — transfuse if < 7 (or < 8 if symptomatic/cardiac)
- DAT — recheck if clinical picture changes or treatment response unexpected
- On steroids: blood glucose, BP, mood assessment, bone protection (calcium + vitamin D)
- On eculizumab/ravulizumab: meningococcal vaccination status, breakthrough hemolysis (LDH spike), Cr, CBC
- Cold agglutinin: titer levels, avoid cold triggers, monitor for worsening during winter
- Folate level — chronic hemolysis depletes folate → megaloblastic crisis if not supplemented
🏥 Rounds
Sample Presentation
Mrs. Okafor is a 48-year-old woman with SLE presenting with fatigue, jaundice, and dark urine × 5 days. Exam: pallor, scleral icterus, mild splenomegaly. Labs: Hgb 6.2 (baseline 11), retic 12%, LDH 580, haptoglobin < 10, indirect bili 4.2. DAT strongly positive (IgG + C3d). Smear: spherocytes.
Key Points: Warm AIHA (DAT positive IgG, spherocytes on smear) in the setting of SLE (classic association). Start prednisone 1 mg/kg. Transfuse — Hgb 6.2 is dangerously low, even though crossmatch will be difficult (blood bank uses "least incompatible" units). Folic acid 1 mg daily. Check for Evans syndrome (concurrent thrombocytopenia).
Pimp Questions
❓ What is the difference between intravascular and extravascular hemolysis?
Intravascular: RBCs destroyed IN the circulation → free hemoglobin released → hemoglobinuria (dark/red urine), hemoglobinemia, very low haptoglobin (consumed binding free Hgb), hemosiderinuria. Causes: TTP, DIC, PNH, transfusion reaction, mechanical valve. Extravascular: RBCs destroyed by splenic macrophages → splenomegaly, jaundice (indirect bili), no hemoglobinuria. Causes: AIHA, hereditary spherocytosis, sickle cell, hypersplenism.
❓ Should you withhold transfusion in AIHA because the crossmatch is incompatible?
NO — transfuse if clinically indicated. In warm AIHA, autoantibodies react with virtually ALL donor RBCs, making all crossmatches "incompatible." The blood bank performs extended testing to identify any underlying alloantibodies (from prior transfusions). They provide "least incompatible" units. Transfused RBCs will be destroyed faster than normal, but they provide critical oxygen delivery. Life-threatening anemia always trumps crossmatch difficulty.
❓ Why should you check G6PD levels BETWEEN episodes, not during?
During acute hemolysis, the oldest RBCs (with the LOWEST G6PD activity) are selectively destroyed first. The remaining RBCs + reticulocytes have higher G6PD levels because they're younger → the G6PD level can be falsely normal during the attack. Wait 2-3 months after the episode for the RBC population to normalize, then check. If you must diagnose acutely, a level that is low DURING hemolysis is definitely diagnostic — but a normal level doesn't exclude G6PD deficiency.
❓ What is Evans syndrome?
Evans syndrome = AIHA + immune thrombocytopenia (ITP) (positive DAT + low platelets from antiplatelet antibodies). May also include autoimmune neutropenia. Commonly associated with SLE and lymphoproliferative disorders. More refractory than isolated AIHA or ITP. Treatment: steroids, rituximab, mycophenolate. Splenectomy less effective than in isolated ITP. Always check platelets in new AIHA.
❓ What is the most sensitive lab marker for hemolysis?
Haptoglobin. It binds free hemoglobin and is rapidly cleared by the liver during hemolysis → levels become undetectable. It is the first lab to become abnormal and the last to normalize. Sensitivity ~96%. However, it is also an acute phase reactant — can be falsely "normal" during concurrent inflammation. The combination of undetectable haptoglobin + elevated LDH has the highest sensitivity/specificity for hemolysis.
📋 Summary
Summary
Hemolysis Labs
LDH ↑, haptoglobin ↓, indirect bili ↑, reticulocyte ↑. Check all four.
DAT Positive
Warm AIHA (IgG → steroids), cold agglutinin (C3d → keep warm + rituximab), drug-induced, transfusion reaction
DAT Negative
TTP/DIC (schistocytes), PNH (flow cytometry), G6PD (bite cells), mechanical valve, hereditary spherocytosis
Warm AIHA Rx
Prednisone 1 mg/kg → rituximab → splenectomy. DO transfuse if life-threatening (least incompatible).
PNH
Eculizumab (anti-C5). Meningococcal vaccine first. Lifelong therapy.
Pearl
Haptoglobin = most sensitive marker. G6PD level falsely normal during hemolysis. Always check the smear.
📄 One Pager
One-Pager
Hemolytic Anemia
DAT is the branch point
Algorithm
Confirm hemolysis (LDH ↑ + haptoglobin ↓ + retic ↑ + indirect bili ↑) → DAT. Positive: warm AIHA vs cold vs drug. Negative: check smear — schistocytes (TMA), spherocytes (HS), bite cells (G6PD). PNH: flow cytometry.
Smear Clues
Schistocytes → TTP/DIC/valve. Spherocytes → AIHA or HS. Bite cells/Heinz bodies → G6PD. Sickle cells → SCD. Target cells → thalassemia/liver.
Trials
TRIUMPH 2006 (eculizumab for PNH) · CARDINAL 2022 (sutimlimab for CAD)
Stay Current
📰 What's New
Practice-changing updates in internal medicine. Each entry links to the relevant topic on this site. Bookmark this page and check back regularly.
🔥 2026 Updates
March 2026 · JUST RELEASED
Surviving Sepsis Campaign 2026 — Adult & Pediatric Guidelines
First major update since 2021. Published March 23, 2026 by SCCM/ESICM. 129 statements including 46 entirely new recommendations. Key changes:
Screening: NEWS/NEWS2/MEWS/SIRS now recommended over qSOFA for sepsis screening. qSOFA has poor sensitivity and should not be used as a sole screening tool. Sepsis remains a clinical diagnosis — no single biomarker can rule it in or out.
Fluids: Balanced crystalloids suggested over 0.9% saline. Initial bolus of at least 30 mL/kg IV crystalloid in first 3 hours for sepsis-induced hypoperfusion. Albumin not recommended as supplement to crystalloids. New guidance on fluid removal after resuscitation — a topic not previously addressed.
Vasopressors: Peripheral vasopressors OK to start — don't delay for central access. Norepinephrine remains first-line, then vasopressin, then epinephrine. MAP target 65 mmHg (higher targets showed no mortality benefit). New guidance on BP targets in older adults.
Corticosteroids: IV hydrocortisone 200 mg/day suggested for septic shock with ongoing vasopressor requirement ≥ 4 hours. Shortens shock duration but unclear mortality benefit. This reverses the 2016 recommendation against routine steroids.
Antibiotics: Broad-spectrum within 1 hour for septic shock, within 3 hours for sepsis without shock. Blood cultures before antibiotics when possible. New section on antibiotic optimization beyond just timing.
New topics: "Code sepsis" / sepsis huddle protocols suggested. Performance improvement programs recommended at institutional level. Post-sepsis discharge care including psychological and physical rehabilitation. Prehospital antibiotics may reduce mortality (OR 0.58, very low certainty).
Pediatric: 68-expert panel, 20 new topics. POCUS conditionally recommended to guide resuscitation. 30–40% of children surviving ICU-level sepsis face lasting health issues — long-term follow-up now addressed.
Screening: NEWS/NEWS2/MEWS/SIRS now recommended over qSOFA for sepsis screening. qSOFA has poor sensitivity and should not be used as a sole screening tool. Sepsis remains a clinical diagnosis — no single biomarker can rule it in or out.
Fluids: Balanced crystalloids suggested over 0.9% saline. Initial bolus of at least 30 mL/kg IV crystalloid in first 3 hours for sepsis-induced hypoperfusion. Albumin not recommended as supplement to crystalloids. New guidance on fluid removal after resuscitation — a topic not previously addressed.
Vasopressors: Peripheral vasopressors OK to start — don't delay for central access. Norepinephrine remains first-line, then vasopressin, then epinephrine. MAP target 65 mmHg (higher targets showed no mortality benefit). New guidance on BP targets in older adults.
Corticosteroids: IV hydrocortisone 200 mg/day suggested for septic shock with ongoing vasopressor requirement ≥ 4 hours. Shortens shock duration but unclear mortality benefit. This reverses the 2016 recommendation against routine steroids.
Antibiotics: Broad-spectrum within 1 hour for septic shock, within 3 hours for sepsis without shock. Blood cultures before antibiotics when possible. New section on antibiotic optimization beyond just timing.
New topics: "Code sepsis" / sepsis huddle protocols suggested. Performance improvement programs recommended at institutional level. Post-sepsis discharge care including psychological and physical rehabilitation. Prehospital antibiotics may reduce mortality (OR 0.58, very low certainty).
Pediatric: 68-expert panel, 20 new topics. POCUS conditionally recommended to guide resuscitation. 30–40% of children surviving ICU-level sepsis face lasting health issues — long-term follow-up now addressed.
🔥 2024–2025 Updates
2025
2025 AHA/ACC Acute Coronary Syndromes Guidelines
First unified ACS guideline combining STEMI and NSTEMI into a single framework. Key changes: high-sensitivity troponin now standard for diagnosis with 0/1-hour or 0/2-hour rapid rule-out algorithms. Clopidogrel now preferred over ticagrelor as default P2Y12 inhibitor (based on cost-effectiveness and bleeding data). Pre-treatment with P2Y12 inhibitors before angiography is no longer recommended for NSTEMI. De-escalation from potent P2Y12 to clopidogrel after 1–3 months is endorsed. DAPT duration shortened to 1–3 months followed by P2Y12 monotherapy for high bleeding risk. Routine pre-hospital ECG and direct-to-cath-lab activation reaffirmed for STEMI. Colchicine considered for secondary prevention (post-MI anti-inflammatory). Prasugrel preferred over ticagrelor when PCI is planned and anatomy is known. → STEMI Topic • → NSTEMI Topic
2025
KDIGO 2024 CKD Guidelines Updated
Updated GFR categories and albuminuria staging. SGLT2 inhibitors now first-line for CKD with albuminuria regardless of diabetes status. Finerenone added for diabetic kidney disease. → CKD Topic
2025
2025 AHA/ACC Hypertension Guidelines
First major update since 2017. Replaces the prior hypertension guideline with updated evidence through 2025. Key changes include earlier risk stratification, expanded screening for secondary causes including primary aldosteronism, updated lifestyle and psychosocial intervention recommendations, and more individualized BP targets across the lifespan. Addresses tailored strategies for older adults, CKD, and resistant hypertension. → HTN Emergency Topic
2025
IDSA 2025: First Complicated UTI Guidelines
First-ever IDSA guidelines for complicated UTIs. Provides a clinically relevant classification system for cUTI, stepwise approach to empiric antibiotic selection based on local resistance patterns, guidance on IV-to-oral antibiotic switch timing, and evidence-based duration of therapy. Addresses catheter-associated UTI, pyelonephritis with complicating factors, and urosepsis. → UTI Topic
2025
ATS CAP Guidelines Update — IDSA Declines to Endorse
ATS released updated community-acquired pneumonia guidelines. IDSA agreed with 8 of 10 recommendations but declined endorsement over antibiotic use in viral pneumonia. IDSA argues that nondiscriminatory antibiotic use in patients with positive respiratory virus tests (flu, RSV, COVID) confers more harm than benefit, since most do not have bacterial coinfection. Practice impact: think twice before reflexively adding antibiotics to confirmed viral CAP. → Pneumonia Topic
2024
NCCN irAE Guidelines Updated
Updated management of immune-related adverse events from checkpoint inhibitors. Expanded guidance on steroid dosing, when to hold immunotherapy, and specialty referral triggers. → irAE Topic
2024
SURMOUNT-OSA: Tirzepatide for Sleep Apnea
Tirzepatide (Mounjaro) significantly reduced AHI in obese patients with OSA. Weight loss of ~20% with improvement in sleep apnea severity. May change first-line management of obesity-related OSA. → Obesity Topic
📋 2022–2023 Practice Changes
2023
CLOVERS Trial: Restrictive vs Liberal Fluids in Sepsis
No difference between restrictive and liberal fluid strategies in early septic shock. Supports individualized fluid resuscitation over mandatory 30 mL/kg. → Sepsis Topic
2023
SELECT Trial: Semaglutide Reduces Cardiovascular Events
Semaglutide reduced MACE by 20% in overweight/obese adults with CVD, regardless of diabetes status. First GLP-1 RA with cardiovascular benefit independent of diabetes. → Obesity Topic
2023
STEP-HFpEF: Semaglutide in HFpEF with Obesity
Semaglutide improved symptoms, exercise function, and reduced body weight in obese HFpEF patients. New treatment paradigm — treating the obesity driving HFpEF. → HFpEF Topic
2022
STRONG-HF: Rapid GDMT Initiation Before Discharge
Rapid uptitration of all 4 GDMT pillars before discharge improved 180-day outcomes. Changed practice from slow sequential titration to rapid parallel initiation. → Heart Failure Topic
2022
WATERFALL Trial: No Aggressive Fluids in Pancreatitis
Aggressive LR resuscitation did not improve outcomes in acute pancreatitis and increased fluid overload. Goal-directed fluid therapy is now preferred. → Pancreatitis Topic
2022
DELIVER Trial: Dapagliflozin for HFpEF
SGLT2 inhibitors now benefit ALL heart failure regardless of ejection fraction. Dapagliflozin reduced worsening HF and cardiovascular death in HFpEF. → HFpEF Topic
2022
EMPA-KIDNEY: Empagliflozin for CKD
Empagliflozin reduced CKD progression and cardiovascular death regardless of diabetes status. SGLT2i now standard for CKD with albuminuria. → CKD Topic
⚡ Major Paradigm Shifts (2019–2021)
2021
SSC 2021: Surviving Sepsis Campaign Updated
30 mL/kg fluid bolus downgraded to weak recommendation. Balanced crystalloids suggested over NS. Hour-1 bundle replaces 3-hour and 6-hour bundles. Norepinephrine confirmed first-line vasopressor. → Sepsis Topic
2021
TTM2: Hypothermia After Cardiac Arrest Debunked
33°C hypothermia showed no benefit over normothermia (36°C) after cardiac arrest. Aggressive fever prevention is what matters, not active cooling. Changed post-arrest temperature management. → Post-Cardiac Arrest Topic
2021
IDSA/SHEA 2021: C. difficile — Fidaxomicin First-Line
Fidaxomicin (Dificid) now preferred over oral vancomycin for initial C. diff episodes — lower recurrence rate. Oral metronidazole is NO LONGER recommended for initial episodes. → C. difficile Topic
2020
Vancomycin AUC-Based Dosing (ASHP/IDSA 2020)
Trough-based monitoring (target 15-20 mcg/mL) replaced by AUC/MIC-guided dosing (target 400-600). AUC monitoring reduces nephrotoxicity by ~30% with equivalent efficacy. → Sepsis Topic
2020
EAST-AFNET 4: Early Rhythm Control in AF
Early rhythm control (within 1 year of AF diagnosis) reduced cardiovascular death, stroke, and HF hospitalization vs rate control alone. Shifted the rate vs rhythm debate for newly diagnosed AF. → Atrial Fibrillation Topic
2020
STARRT-AKI & AKIKI: Don't Rush to Dialysis
Early RRT initiation in AKI showed no benefit over a watchful waiting strategy. Delayed approach avoided unnecessary dialysis in ~50% of patients. Only start for absolute indications. → AKI Topic
2019
ATS/IDSA 2019: HCAP Eliminated
Healthcare-Associated Pneumonia (HCAP) removed as a category. Led to massive overtreatment with unnecessarily broad antibiotics. Instead, assess individual MDR risk factors and use nasal MRSA PCR to guide de-escalation. → Pneumonia Topic
2019
OVIVA Trial: Oral Antibiotics for Bone Infections
Oral antibiotics non-inferior to IV for bone and joint infections after initial IV therapy. Changed the dogma of "6 weeks IV only" for osteomyelitis. IV-to-oral step-down is now standard practice. → Osteomyelitis Topic
📚 How to Stay Updated
| Source | What It Is | Cost |
|---|---|---|
| NEJM Journal Watch | Daily summaries of practice-changing studies across all journals | Often free through residency programs |
| The Curbsiders | Internal medicine podcast — deep dives with experts | Free |
| Core IM | Podcast + 5-Pearls — concise clinical pearls | Free |
| REBEL EM / EMCrit | Critical care & EM focused evidence updates | Free |
| UpToDate "What's New" | Real-time guideline updates with practice recommendations | Institutional access |
| Society Guidelines | AHA/ACC, ATS/IDSA, KDIGO, SSC — subscribe to email alerts | Free |
Rhabdomyolysis
Skeletal muscle breakdown releasing myoglobin, CK, potassium, and phosphate into the circulation. Myoglobin causes direct renal tubular obstruction and toxicity → AKI. The three killers: hyperkalemia, AKI, and compartment syndrome. Treatment is aggressive IV hydration — dilute the myoglobin before it destroys the kidneys.
🔍 Overview
Definition
Rhabdomyolysis: Skeletal muscle necrosis with release of intracellular contents (myoglobin, CK, potassium, phosphate, uric acid, LDH) into the circulation. Defined as CK > 5× upper limit of normal (typically > 1,000 U/L, often > 5,000–10,000 in clinically significant cases). CK levels > 10,000 carry a high risk of AKI.
Pathophysiology
Myocyte necrosis (any cause) → release of myoglobin into bloodstream → myoglobin filtered by glomerulus → in acidic urine, myoglobin precipitates as ferrihemate casts → direct renal tubular obstruction + oxidative injury to tubular epithelium + renal vasoconstriction → acute tubular necrosis (ATN) → AKI. Simultaneously, massive release of intracellular K⁺ → life-threatening hyperkalemia, and PO₄ release → hypocalcemia (calcium binds to damaged muscle and phosphate).
Common Causes
- Trauma/crush injury — earthquakes, prolonged immobilization, surgery
- Immobilization — found down (overdose, stroke, fall), prolonged surgery
- Drugs of abuse — cocaine, amphetamines, MDMA, PCP, synthetic cannabinoids
- Medications — statins (especially + fibrates or CYP3A4 inhibitors), daptomycin, colchicine, antipsychotics (NMS)
- Seizures — prolonged/status epilepticus
- Extreme exertion — marathon, military training, CrossFit (especially in heat)
- NMS / Serotonin syndrome — see NMS vs Serotonin Syndrome
- Heat stroke — see Heat Stroke
- Metabolic — hypokalemia, hypophosphatemia, hypothyroidism, DKA
- Infections — influenza, HIV, Legionella, group A strep
Clinical Example
Case
22M found down after a party (likely substance use + prolonged immobilization). Presenting with diffuse myalgias, dark brown urine, and oliguria. Labs: CK 45,000, K⁺ 6.2, Cr 3.4, Ca²⁺ 7.1, PO₄ 6.8, uric acid 12. UA: positive for blood on dipstick but 0 RBCs on microscopy (= myoglobinuria). ECG shows peaked T-waves.
🚨 Management
Treatment Protocol
The THREE killers in rhabdo: (1) Hyperkalemia — can be rapid and fatal, check K⁺ q4–6h. (2) AKI — from myoglobin-induced tubular necrosis. (3) Compartment syndrome — if a limb is involved, check compartment pressures.
| Priority | Intervention | Details |
|---|---|---|
| 1. Aggressive IV fluids | NS or LR at 200–300 mL/hr | Target UOP 200–300 mL/hr (much higher than standard resuscitation). Goal: dilute myoglobin and prevent tubular precipitation. Most patients need 6–10 L in first 24h. Foley catheter mandatory for strict I&Os. |
| 2. Treat hyperkalemia | Calcium gluconate, insulin + D50, kayexalate/patiromer | Check K⁺ q4–6h. If K⁺ > 6.0 or ECG changes → calcium gluconate 1g IV for cardiac membrane stabilization → insulin 10 units + D50 for K⁺ shift → kayexalate or patiromer for removal. See Hyperkalemia. |
| 3. Bicarb (controversial) | Sodium bicarbonate 150 mEq in 1L D5W | Goal: urine pH > 6.5 to keep myoglobin soluble. Controversial — theoretical benefit but no strong RCT evidence. May worsen hypocalcemia (alkalosis binds ionized Ca). Consider if urine pH < 6.5. |
| 4. Compartment check | Measure compartment pressures | If limb injury involved or tense/swollen extremity. Pressure > 30 mmHg or within 30 mmHg of diastolic → emergent fasciotomy. Ortho/surgery consult. |
| 5. Dialysis (if needed) | Continuous RRT (CRRT) preferred | Indications: refractory hyperkalemia, volume overload, severe acidosis, uremia. Standard HD does NOT clear myoglobin (too large). CRRT may have theoretical benefit. |
Do NOT give calcium for hypocalcemia in rhabdo (unless symptomatic with tetany or ECG changes) — calcium deposits in damaged muscle and worsens injury. The calcium will correct on its own as muscles heal.
🧪 Workup
Laboratory Workup
- CK (creatine kinase) — diagnostic. Serial q6–12h until trending down. Peak usually at 24–72h. CK > 5,000 = significant rhabdo risk for AKI.
- BMP — K⁺ (hyperK!), Ca²⁺ (hypoCa), PO₄ (hyperPhos), Cr/BUN (AKI), bicarb (metabolic acidosis)
- Urinalysis — dipstick positive for blood but NO RBCs on microscopy = myoglobinuria. This is a classic boards question. The heme pigment on the dipstick cross-reacts with myoglobin.
- LDH — elevated (nonspecific muscle injury marker)
- Uric acid — often elevated (cell lysis)
- Coags (PT/INR, aPTT, fibrinogen) — DIC risk with severe rhabdo
- Lactate — tissue hypoperfusion marker
- Urine myoglobin — can confirm but not widely available and clears quickly. UA dipstick is adequate.
- Toxicology screen — if etiology unclear (cocaine, amphetamines)
- ECG — hyperkalemia changes (peaked T-waves, wide QRS)
💊 Medications
Rhabdomyolysis Medications
| Drug | Dose | Route | Role |
|---|---|---|---|
| Normal Saline or LR | 200–300 mL/hr | IV | FIRST-LINE — aggressive volume resuscitation to target UOP 200–300 mL/hr. LR may be preferred (less hyperchloremic acidosis) but avoid if K⁺ > 6.0 (contains 4 mEq/L K⁺). |
| Sodium bicarbonate | 150 mEq in 1L D5W | IV infusion | Urine alkalinization (target pH > 6.5). Controversial — no RCT evidence of benefit. Consider if urine pH < 6.5. |
| Calcium gluconate | 1–2 g IV over 10 min | IV | ONLY for hyperkalemia with ECG changes. Do NOT give for asymptomatic hypocalcemia. |
| Insulin (regular) + D50 | 10 units IV + 25g D50 | IV | K⁺ shifting for hyperkalemia. Onset 15–30 min, lasts 4–6h. |
| Kayexalate / Patiromer | Kayexalate 30g PO; Patiromer 8.4g PO | PO | K⁺ removal (delayed onset). Patiromer preferred (fewer GI side effects). |
📈 Monitoring
Monitoring Parameters
| Parameter | Frequency | Target / Action |
|---|---|---|
| Urine output | Hourly (Foley required) | Target 200–300 mL/hr. If not meeting target, increase IV rate. If oliguric despite adequate fluids → nephrology consult. |
| CK (creatine kinase) | q6–12h | Trend to peak and decline. Stop aggressive IVF when CK trending down and < 5,000. |
| BMP (K⁺, Ca, PO₄, Cr) | q6h initially | K⁺ is the most dangerous — check frequently. Cr trend for AKI progression. |
| Urine pH | q6h if giving bicarb | Target > 6.5 if alkalinizing urine. |
| Compartment checks | q2–4h if limb involved | Tense, painful, swollen limb → measure pressures → fasciotomy if > 30 mmHg. |
| Vitals | q4h floor, q1–2h ICU | Watch for fluid overload with aggressive resuscitation. |
📋 On Rounds
Why is the UA positive for blood but shows no RBCs on microscopy?
The urine dipstick detects the heme pigment (peroxidase activity) — it cannot distinguish between hemoglobin and myoglobin. In rhabdomyolysis, myoglobin is filtered by the glomerulus and appears in the urine. The dipstick reads this as "blood positive," but when you spin the urine and look under the microscope, there are no red blood cells. This combination — dipstick + for blood, no RBCs on micro — is the classic finding of myoglobinuria. The same pattern can be seen with intravascular hemolysis (hemoglobinuria). The clinical context (elevated CK, myalgias, dark urine) distinguishes rhabdo from hemolysis.
When should you start dialysis in rhabdomyolysis?
Standard indications for dialysis (AEIOU): Acidosis (severe, refractory to bicarb), Electrolytes (refractory hyperkalemia despite medical management), Ingestion (toxic), Overload (volume overload not responding to diuretics), Uremia (encephalopathy, pericarditis, bleeding). In rhabdo specifically, the most common indication is refractory hyperkalemia. Note: conventional hemodialysis does NOT efficiently clear myoglobin (molecular weight ~17 kDa) — CRRT may have theoretical advantages with a high-cutoff membrane, but the primary goal is managing the metabolic complications (hyperK, acidosis, volume) rather than removing myoglobin itself.
Why should you avoid giving calcium for hypocalcemia in rhabdomyolysis?
In rhabdomyolysis, calcium is sequestered in damaged muscle tissue (binds to necrotic myocytes) and is also bound by elevated phosphate. This causes a transient hypocalcemia that is expected and self-limited — it will correct on its own as muscles heal and release the sequestered calcium (often causing rebound hypercalcemia in the recovery phase). Giving exogenous calcium worsens muscle damage by increasing calcium deposition in already-injured tissue. The only indication for IV calcium in rhabdo is: (1) symptomatic hypocalcemia (tetany, Chvostek/Trousseau signs) or (2) hyperkalemia with ECG changes (peaked T waves, widened QRS) — in which case calcium gluconate is given for cardiac membrane stabilization, not to correct the calcium level.
⚡ Summary
Rhabdomyolysis — Key Points
Diagnosis
CK > 5× ULN (typically > 5,000). UA: dipstick + blood, no RBCs on micro = myoglobinuria. Dark brown "tea-colored" urine.
Treatment
Aggressive IVF (NS/LR 200–300 mL/hr) targeting UOP 200–300 mL/hr. Bicarb for urine alkalinization is controversial.
Three Killers
Hyperkalemia (check K⁺ q4–6h), AKI (myoglobin tubular necrosis), Compartment syndrome (check pressures if limb involved).
Calcium Rule
Do NOT give calcium for asymptomatic hypocalcemia — deposits in damaged muscle. Only give for hyperK with ECG changes or symptomatic tetany.
Common Causes
Crush injury, immobilization ("found down"), drugs of abuse, statins, seizures, extreme exertion, NMS, heat stroke.
Dialysis
Indicated for refractory hyperK, severe acidosis, volume overload, uremia. CRRT preferred. Standard HD does not clear myoglobin.
NMS vs Serotonin Syndrome
Two life-threatening drug-induced hyperthermic syndromes that look similar but have different causes, key findings, and treatments. NMS = dopamine blockade (antipsychotics) with RIGIDITY. Serotonin syndrome = serotonin excess (SSRIs, MAOIs) with CLONUS. Getting the diagnosis right determines the treatment.
🔍 Overview
Side-by-Side Comparison
The #1 distinguishing feature: NMS = RIGIDITY (lead-pipe), SS = CLONUS (hyperreflexia). If the patient is stiff everywhere → think NMS. If they're twitching/jerking → think SS.
| Feature | NMS | Serotonin Syndrome |
|---|---|---|
| Mechanism | Dopamine ANTAGONISM (decreased dopamine) | Serotonin EXCESS (increased serotonin) |
| Causative drugs | Haloperidol, olanzapine, risperidone, metoclopramide, prochlorperazine. Also sudden withdrawal of dopamine agonists (levodopa). | SSRIs, SNRIs, MAOIs, tramadol, linezolid (weak MAOI!), fentanyl, ondansetron, triptans, St. John's Wort, MDMA, dextromethorphan |
| Onset | SLOW — days to weeks after starting/increasing dose | FAST — hours after starting, dose change, or drug interaction |
| Key finding | LEAD-PIPE RIGIDITY (diffuse, not clonus) | CLONUS (especially lower extremity) + hyperreflexia |
| Temperature | Very high (> 40°C common) | Variable (mild to very high) |
| Mental status | Altered (encephalopathy, obtundation) | Agitation, confusion, restlessness |
| Autonomic | Tachycardia, labile BP, diaphoresis | Tachycardia, hypertension, diaphoresis, mydriasis |
| GI symptoms | Usually absent | Diarrhea (serotonin stimulates gut motility) |
| Labs | CK markedly elevated (often > 1,000), leukocytosis, metabolic acidosis | CK may be mildly elevated, otherwise normal |
| Treatment | STOP offending agent, dantrolene + bromocriptine, cooling, ICU | STOP offending agent, benzodiazepines (first-line), cyproheptadine, cooling |
| Duration | Days to weeks to resolve | Usually resolves within 24 hours of stopping drug |
NMS — Neuroleptic Malignant Syndrome
NMS results from acute dopamine D2 receptor blockade in the hypothalamus (thermoregulation failure) and basal ganglia (rigidity). Most common with high-potency antipsychotics (haloperidol) but can occur with ANY dopamine antagonist — including metoclopramide (Reglan) and prochlorperazine (Compazine). Can also occur with abrupt withdrawal of dopaminergic agents (levodopa in Parkinson's patients). Mortality: 10–20% if untreated.
Serotonin Syndrome — Hunter Criteria
Diagnosed using the Hunter Serotonin Toxicity Criteria (most accurate) in a patient on a serotonergic drug: (1) Spontaneous clonus, OR (2) Inducible clonus + agitation or diaphoresis, OR (3) Ocular clonus + agitation or diaphoresis, OR (4) Tremor + hyperreflexia, OR (5) Hypertonia + temperature > 38°C + ocular or inducible clonus. Key drug interaction to know: linezolid is a reversible MAOI — can precipitate SS when combined with SSRIs/SNRIs. This is a classic boards trap.
🚨 Management
NMS Treatment Algorithm
| Step | Intervention | Details |
|---|---|---|
| 1. STOP offending agent | Discontinue ALL antipsychotics/dopamine antagonists | This is the most important step. If NMS from levodopa withdrawal → restart levodopa immediately. |
| 2. Aggressive cooling | Ice packs, cooling blankets, cold IV fluids | Target temp < 39°C. Antipyretics (acetaminophen) do NOT work — this is not cytokine-mediated fever, it's muscle-generated heat. |
| 3. Dantrolene | Dantrolene (Dantrium) 1–2.5 mg/kg IV | Direct-acting muscle relaxant (blocks ryanodine receptor → reduces Ca²⁺ release from SR → reduces muscle contraction and heat generation). May repeat q5–10 min to max 10 mg/kg/day. |
| 4. Bromocriptine | Bromocriptine (Parlodel) 2.5 mg PO/NG q8h | Dopamine agonist — directly counteracts the dopamine blockade causing NMS. Continue for 10 days after NMS resolves (prevent relapse). |
| 5. Supportive | ICU admission, IVF, monitoring | Watch for rhabdomyolysis (check CK), AKI, DIC, aspiration, respiratory failure. Intubation may be needed. |
Serotonin Syndrome Treatment Algorithm
| Step | Intervention | Details |
|---|---|---|
| 1. STOP offending agent | Discontinue ALL serotonergic drugs | Most cases resolve within 24h of stopping the offending drug(s). Review full medication list carefully. |
| 2. Benzodiazepines | Lorazepam 1–2 mg IV or diazepam 5–10 mg IV | FIRST-LINE — controls agitation, reduces muscle activity and heat generation, lowers seizure threshold. Repeat as needed. |
| 3. Cyproheptadine | Cyproheptadine (Periactin) 12 mg PO/NG load, then 2 mg q2h | Serotonin 5-HT2A antagonist — directly blocks excess serotonin. Only available PO/NG (no IV form). Max 32 mg/day. |
| 4. Cooling | External cooling measures | For temperature > 41°C. Avoid antipyretics (ineffective). |
| 5. Avoid | Do NOT give antipsychotics for agitation | Some antipsychotics have serotonergic activity and could worsen SS. Do NOT give dantrolene (ineffective — muscle activity in SS is from neural excitation, not peripheral). |
🧪 Workup
Laboratory Workup (Both NMS and SS)
- CK (creatine kinase) — markedly elevated in NMS (often > 1,000, can be > 10,000). Mildly elevated or normal in SS.
- BMP — Cr (AKI from rhabdo in NMS), K⁺ (hyperK from muscle breakdown), glucose
- CBC — leukocytosis common in NMS (not from infection — stress response)
- LFTs — may be elevated in NMS (hepatic injury)
- Coags (PT/INR, aPTT, fibrinogen) — DIC screening in severe NMS
- UA — myoglobinuria in NMS (dipstick + blood, no RBCs)
- TSH — rule out thyroid storm (hyperthermia + tachycardia differential)
- Toxicology screen — rule out sympathomimetic toxicity, anticholinergic syndrome
- Medication reconciliation — CRITICAL. Identify the offending drug(s). Review ALL medications, supplements, and OTC drugs for serotonergic or dopamine-blocking activity.
💊 Medications
Key Medications
| Drug | Dose | Indication | Key Notes |
|---|---|---|---|
| Dantrolene (Dantrium) | 1–2.5 mg/kg IV, repeat q5–10 min | NMS only | Direct muscle relaxant (ryanodine receptor blocker). Max 10 mg/kg/day. Monitor for hepatotoxicity. NOT for SS. |
| Bromocriptine (Parlodel) | 2.5 mg PO/NG q8h | NMS only | Dopamine agonist — directly counteracts D2 blockade. Continue 10 days after resolution. Can also use amantadine 100 mg PO q12h. |
| Cyproheptadine (Periactin) | 12 mg PO/NG load, then 2 mg q2h | SS only | 5-HT2A antagonist. PO only (no IV form). Max 32 mg/day. Sedating (antihistamine). NOT for NMS. |
| Lorazepam | 1–2 mg IV PRN | SS first-line; adjunct in NMS | Controls agitation, reduces muscle hyperactivity, prevents seizures. Can use diazepam 5–10 mg IV as alternative. |
📈 Monitoring
Monitoring Parameters
| Parameter | Frequency | Target / Action |
|---|---|---|
| Temperature | q1–2h | Target < 39°C. Active cooling if > 40°C. Antipyretics ineffective. |
| CK | q6–12h (NMS) | Trend for rhabdomyolysis severity. If rising → aggressive IVF for renal protection. |
| BMP (K⁺, Cr) | q6–12h | Watch for hyperK (NMS) and AKI. |
| Neurological exam | q2–4h | Rigidity assessment (NMS), clonus assessment (SS), mental status. |
| Vitals | q1–2h ICU | HR, BP (labile in both), SpO₂, RR. |
| Coags | Daily if NMS severe | DIC screening (PT, fibrinogen, D-dimer). |
📋 On Rounds
What is the key distinguishing physical exam finding between NMS and Serotonin Syndrome?
NMS = Lead-pipe RIGIDITY. The patient is stiff, with diffuse muscle rigidity that resists passive movement uniformly throughout the range of motion (like bending a lead pipe). Reflexes may be normal or diminished. SS = CLONUS + hyperreflexia. The patient has rhythmic, involuntary muscular contractions (especially in lower extremities — ankle clonus), plus brisk/exaggerated deep tendon reflexes. Tremor is also common. Think: NMS = stiff, SS = twitchy.
Can linezolid cause serotonin syndrome?
Yes! Linezolid (Zyvox) is a reversible, nonselective monoamine oxidase inhibitor (MAOI) in addition to being an oxazolidinone antibiotic. When given to patients already on SSRIs, SNRIs, or other serotonergic drugs, it can precipitate serotonin syndrome. This is a classic boards question and a real clinical trap — always check the medication list before starting linezolid. If a patient on an SSRI needs linezolid, either hold the SSRI (consider washout period) or choose a different antibiotic. Other unexpected serotonergic drugs: tramadol, fentanyl, ondansetron, dextromethorphan.
Why is bromocriptine used in NMS?
Bromocriptine (Parlodel) is a dopamine D2 receptor agonist. NMS is caused by dopamine D2 blockade (from antipsychotics or other dopamine antagonists), leading to loss of thermoregulation (hypothalamus), rigidity (basal ganglia), and autonomic instability. Bromocriptine directly counteracts the dopamine blockade by stimulating D2 receptors. It restores dopaminergic tone in the hypothalamus and basal ganglia. Dose: 2.5 mg PO/NG q8h (can titrate to 45 mg/day). Important: continue for at least 10 days after NMS resolves — premature discontinuation can cause relapse. Alternative: amantadine 100 mg PO q12h (also increases dopaminergic activity).
What are the Hunter Criteria for Serotonin Syndrome?
The Hunter Serotonin Toxicity Criteria are the most sensitive (84%) and specific (97%) diagnostic criteria for SS. In a patient taking a serotonergic agent, ANY ONE of the following: (1) Spontaneous clonus. (2) Inducible clonus + agitation OR diaphoresis. (3) Ocular clonus + agitation OR diaphoresis. (4) Tremor + hyperreflexia. (5) Hypertonia + temperature > 38°C + (ocular clonus OR inducible clonus). The key theme: clonus is central to almost every criterion. The older Sternbach criteria are less specific. Hunter Criteria replaced them as the preferred diagnostic standard.
⚡ Summary
NMS vs Serotonin Syndrome — Key Points
NMS Cause
Dopamine ANTAGONISTS: haloperidol, olanzapine, metoclopramide. Also levodopa withdrawal. Onset: days–weeks.
SS Cause
Serotonergic drugs: SSRIs, SNRIs, MAOIs, tramadol, linezolid, MDMA. Usually drug interaction. Onset: hours.
Key Finding
NMS = RIGIDITY (lead-pipe). SS = CLONUS (hyperreflexia, especially lower extremity). This is the #1 distinguishing feature.
NMS Treatment
Stop drug. Dantrolene 1–2.5 mg/kg IV. Bromocriptine 2.5 mg PO q8h (continue 10 days). Cooling. ICU.
SS Treatment
Stop drug. Benzodiazepines (first-line). Cyproheptadine 12 mg load then 2 mg q2h. Cooling. Usually resolves in 24h.
Pearl
Linezolid is a weak MAOI → can cause SS with SSRIs. Do NOT give dantrolene for SS. Do NOT give cyproheptadine for NMS.
Hypercalcemia of Malignancy
The most common cause of hypercalcemia in hospitalized patients. "Stones, bones, groans, psychiatric moans." PTH will be SUPPRESSED (unlike primary hyperparathyroidism). Treatment is stepwise: fluids → calcitonin (hours) → bisphosphonate (days). Furosemide for hypercalcemia is outdated.
🔍 Overview
Mechanisms of Malignancy-Related Hypercalcemia
| Mechanism | Frequency | Associated Cancers | Key Lab Finding |
|---|---|---|---|
| PTHrP (Humoral) | ~80% | Squamous cell carcinomas (lung, H&N), renal cell, breast, bladder | PTHrP elevated, PTH suppressed, PO₄ low |
| Osteolytic metastases | ~20% | Breast cancer, multiple myeloma | PTHrP normal, local cytokine release (RANKL, IL-6) |
| 1,25-dihydroxyvitamin D | < 1% | Lymphoma (Hodgkin and non-Hodgkin) | 1,25-vit D elevated (tumor-produced 1-alpha hydroxylase) |
| Ectopic PTH | Very rare | Ovarian, lung small cell (rare) | PTH elevated (from tumor) |
Symptoms — "Stones, Bones, Groans, Psychiatric Moans"
- Stones: Nephrolithiasis, nephrocalcinosis, polyuria (nephrogenic DI from Ca²⁺ → impaired ADH response)
- Bones: Bone pain, pathologic fractures, osteoporosis
- Groans: Abdominal pain, constipation, nausea, vomiting, pancreatitis (rare)
- Psychiatric moans: Confusion, lethargy, depression, psychosis, coma
- Cardiac: Shortened QT interval, bradycardia, AV block (severe)
- Renal: Polyuria → dehydration → worsening hypercalcemia (vicious cycle)
Severity Classification
| Severity | Corrected Ca²⁺ | Approach |
|---|---|---|
| Mild | 10.5–12.0 mg/dL | Oral hydration, monitor, treat underlying malignancy |
| Moderate | 12.0–14.0 mg/dL | IV fluids ± calcitonin + bisphosphonate |
| Severe / Symptomatic | > 14.0 mg/dL or symptomatic | Aggressive IV fluids + calcitonin + bisphosphonate. May need ICU. |
🚨 Management
Stepwise Treatment Protocol
| Step | Intervention | Onset | Details |
|---|---|---|---|
| Step 1: IV NS | Normal Saline 200–300 mL/hr | Immediate | Most patients are severely volume-depleted from hypercalcemia-induced nephrogenic DI (polyuria + poor PO intake). This alone drops Ca by 1–2 mg/dL. Goal: restore euvolemia and enhance renal calcium excretion. |
| Step 2: Calcitonin | Calcitonin (Miacalcin) 4 IU/kg SQ/IM q12h | 4–6 hours | Bridge therapy — works FAST but tachyphylaxis by 48h (receptors downregulate). Drops Ca by ~1–2 mg/dL. Mild side effect: flushing, nausea. Used while waiting for bisphosphonate to kick in. |
| Step 3: Bisphosphonate | Zoledronic acid (Zometa) 4 mg IV over 15 min | 2–4 DAYS | Definitive treatment. Inhibits osteoclast-mediated bone resorption. Effect lasts weeks. Check Cr first — reduce dose if CrCl < 60. Alternative: pamidronate 60–90 mg IV over 2–4h (slower infusion, may be better in renal impairment). |
| Step 4 (Refractory) | Denosumab (Xgeva) 120 mg SQ | Days | For bisphosphonate-refractory hypercalcemia. RANKL inhibitor. Works even in renal failure (not renally cleared, unlike bisphosphonates). Dose on days 1, 8, 15, 29, then monthly. |
Furosemide (Lasix) for hypercalcemia is OUTDATED. Old teaching was "saline + Lasix." Current evidence: Lasix only if volume overloaded. It does not meaningfully lower calcium and risks further dehydration and electrolyte derangements.
Special Situations
- Lymphoma (1,25-vit D mediated): Glucocorticoids (dexamethasone 4 mg IV q6h or equivalent) are effective — they inhibit 1-alpha hydroxylase in tumor cells and decrease 1,25-vit D production.
- Multiple myeloma: Bisphosphonates are standard (both for hypercalcemia and skeletal events). Zoledronic acid or pamidronate.
- Dialysis: If refractory or anuric, hemodialysis with low-calcium dialysate can rapidly lower calcium.
🧪 Workup
Laboratory Workup
- Corrected calcium = measured Ca + 0.8 × (4.0 − albumin). Or check ionized calcium (more accurate, not affected by albumin).
- PTH — should be SUPPRESSED (< 20 pg/mL) in malignancy. If PTH is elevated → think primary hyperparathyroidism (even in cancer patients — can coexist).
- PTHrP — elevated in humoral hypercalcemia of malignancy (80% of cases). Order if PTH suppressed.
- 1,25-dihydroxyvitamin D — elevated in lymphoma. Order if PTHrP is normal and PTH is suppressed.
- 25-hydroxyvitamin D — to rule out exogenous vitamin D toxicity.
- Phosphate — low in PTHrP-mediated (PTHrP causes renal phosphate wasting, same as PTH).
- BMP — Cr (renal function), K⁺, Mg²⁺.
- ECG — shortened QT interval is the classic finding. Also watch for bradycardia, AV block.
- SPEP/UPEP — if myeloma suspected.
💊 Medications
Hypercalcemia Medications
| Drug | Dose | Onset | Duration | Key Notes |
|---|---|---|---|---|
| Normal Saline | 200–300 mL/hr | Immediate | During infusion | First-line. Volume expansion + calciuresis. Drops Ca ~1–2 mg/dL. Watch for volume overload. |
| Calcitonin (Miacalcin) | 4 IU/kg SQ/IM q12h | 4–6 hours | 48h (tachyphylaxis) | Bridge only. Drops Ca ~1–2 mg/dL. Safe but temporary. Tachyphylaxis limits use beyond 48h. |
| Zoledronic acid (Zometa) | 4 mg IV over 15 min | 2–4 days | Weeks | Definitive treatment. Check CrCl — reduce dose if < 60. Risk: osteonecrosis of jaw (rare), renal toxicity. |
| Pamidronate | 60–90 mg IV over 2–4h | 2–4 days | Weeks | Alternative to zoledronic acid. Longer infusion but may be better tolerated in renal impairment. |
| Denosumab (Xgeva) | 120 mg SQ | Days | Weeks | Bisphosphonate-refractory cases. RANKL inhibitor. Works in renal failure. Risk: hypocalcemia, ONJ. |
| Glucocorticoids | Dexa 4 mg IV q6h | Days | During treatment | Effective for lymphoma and granulomatous disease (1,25-vit D mediated). Not effective for PTHrP-mediated. |
📈 Monitoring
Monitoring Parameters
| Parameter | Frequency | Target / Action |
|---|---|---|
| Ionized calcium or corrected Ca | q6–8h until stable | Trend toward normalization. Recheck 2–4 days after bisphosphonate. |
| BMP (Cr, K⁺, Mg²⁺, PO₄) | q12h initially | Cr for AKI/renal recovery. Watch for hypokalemia, hypomagnesemia, hypophosphatemia with fluids. |
| Fluid balance / I&Os | Strict | Maintain euvolemia. Aggressive IVF but watch for volume overload (especially if cardiac history). |
| ECG | Admission + PRN | Shortened QT, bradycardia, AV block. |
| Mental status | q shift | Improvement in confusion/lethargy as calcium normalizes. |
📋 On Rounds
Why is PTH suppressed in hypercalcemia of malignancy?
In malignancy-related hypercalcemia, the elevated calcium provides negative feedback to the parathyroid glands via the calcium-sensing receptor (CaSR). Since the hypercalcemia is driven by PTHrP, osteolytic metastases, or tumor-produced 1,25-vit D — NOT by the parathyroid glands — the glands appropriately suppress PTH secretion. This is the key lab distinction: Malignancy → PTH LOW, PTHrP HIGH. Primary hyperparathyroidism → PTH HIGH (inappropriately), PTHrP normal. If you see hypercalcemia with an elevated PTH in a cancer patient, the patient may have coexistent primary hyperparathyroidism (which is not uncommon).
What is tachyphylaxis with calcitonin, and how does it affect your treatment plan?
Tachyphylaxis = diminishing response to a drug after repeated doses. Calcitonin works by inhibiting osteoclast activity and promoting renal calcium excretion. However, calcitonin receptors downregulate within 48 hours of continuous exposure, and the calcium-lowering effect is lost. This is why calcitonin is a bridge therapy only — it buys you 24–48h of calcium lowering while you wait for the bisphosphonate (zoledronic acid) to take effect, which takes 2–4 days. The treatment timeline: IVF (immediate) → calcitonin (works in hours, lost by 48h) → zoledronic acid (takes 2–4 days, lasts weeks). The calcitonin bridges the gap.
When would you use denosumab instead of zoledronic acid?
Denosumab (Xgeva) is a RANKL inhibitor (monoclonal antibody) used for hypercalcemia refractory to bisphosphonates. Key advantages: (1) Not renally cleared — safe in renal failure (CrCl < 30), whereas bisphosphonates require dose adjustment or are contraindicated. (2) Bisphosphonate-refractory — if Ca remains elevated after adequate bisphosphonate trial. Disadvantages: (1) Risk of rebound hypercalcemia if discontinued abruptly. (2) Severe hypocalcemia can occur — must supplement calcium and vitamin D. (3) Osteonecrosis of the jaw (similar to bisphosphonates). Dosing: 120 mg SQ on days 1, 8, 15, 29, then monthly.
⚡ Summary
Hypercalcemia of Malignancy — Key Points
Mechanisms
PTHrP (80% — squamous, renal, breast), osteolytic mets (20% — breast, myeloma), 1,25-vit D (<1% — lymphoma).
Key Lab
PTH SUPPRESSED (unlike primary hyperparathyroidism). PTHrP elevated. Corrected Ca or ionized Ca. Shortened QT on ECG.
Step 1
Aggressive IV NS 200–300 mL/hr. Most patients are severely volume-depleted. Drops Ca 1–2 mg/dL alone.
Step 2
Calcitonin 4 IU/kg SQ q12h — works in HOURS but tachyphylaxis by 48h. Bridge therapy only.
Step 3
Zoledronic acid 4 mg IV — definitive treatment. Takes 2–4 DAYS. Lasts weeks. Check Cr first.
Outdated
Furosemide for hypercalcemia is OUTDATED. Only use if volume overloaded. Does not meaningfully lower calcium.
Perioperative Medicine
Preoperative risk assessment, medication management around surgery, and co-management of medical issues in surgical patients. Know when to bridge anticoagulation (hint: usually don't), when to order a stress test (hint: rarely), and which medications to hold or continue.
🔍 Overview
Cardiac Risk Assessment
Revised Cardiac Risk Index (RCRI / Lee Index) — 6 independent predictors of major cardiac events after non-cardiac surgery Lee, Circulation 1999:
- High-risk surgery (intraperitoneal, intrathoracic, suprainguinal vascular)
- History of ischemic heart disease
- History of heart failure
- History of cerebrovascular disease (stroke/TIA)
- Diabetes on insulin
- Creatinine > 2.0 mg/dL
| RCRI Score | Risk of Major Cardiac Event | Approach |
|---|---|---|
| 0 | ~3.9% | Low risk — proceed to surgery |
| 1 | ~6.0% | Low-intermediate — proceed if good functional capacity (≥ 4 METs) |
| 2 | ~10.1% | Intermediate — consider stress testing if poor functional capacity AND will change management |
| ≥ 3 | ~15% | High risk — stress testing if will change management, cardiology consult |
Functional Capacity
≥ 4 METs = adequate functional capacity (low cardiac risk regardless of RCRI). 4 METs ≈ climbing one flight of stairs, walking on level ground at 4 mph, doing heavy housework (scrubbing floors, moving furniture). If a patient can do these activities without chest pain or dyspnea, they can likely tolerate surgery without further cardiac testing.
🚨 Management
Cardiac Medication Management
NEVER start a new beta-blocker within 24h of surgery. The POISE trial showed that starting metoprolol perioperatively increased stroke and death despite reducing MI. Only continue beta-blockers if the patient is already on one. POISE, NEJM 2008
- Beta-blockers: CONTINUE if already on one (withdrawal can cause rebound tachycardia and ischemia). Do NOT start new ones perioperatively.
- Statins: CONTINUE perioperatively — associated with reduced cardiac events and mortality.
- ACE inhibitors/ARBs: Generally HOLD morning of surgery (risk of refractory hypotension with anesthesia). Resume postop when tolerating PO.
Anticoagulation Management
| Agent | When to Stop | Bridge? | Key Notes |
|---|---|---|---|
| Warfarin | 5 days before | Bridge with LMWH ONLY if HIGH thrombotic risk: mechanical mitral valve, recent VTE (< 3 months), CHA₂DS₂-VASc ≥ 7 | BRIDGE Trial, NEJM 2015 — most AF patients do NOT need bridging. Bridging increases bleeding without reducing thrombosis. |
| DOACs (apixaban, rivaroxaban) | 2–3 days before (longer if CrCl < 50 for dabigatran) | No bridging needed | Short half-lives. If urgent reversal needed: idarucizumab (dabigatran), andexanet alfa (Xa inhibitors), or PCC. |
| Aspirin | Continue for most surgeries | N/A | Exception: intracranial surgery — hold 7 days before. For most non-cardiac surgery, continuing aspirin is safe. |
| P2Y12 inhibitors (clopidogrel, ticagrelor) | Clopidogrel: 5 days. Ticagrelor: 3–5 days. | No | If patient has recent coronary stent (< 6 weeks BMS, < 6 months DES), surgery should be delayed if possible. Cardiology consult. |
🔄 Updated Practice: Old teaching: stop anticoagulation and bridge all AF patients with heparin before surgery. Current practice: the BRIDGE trial (NEJM 2015) showed that most AF patients do NOT need bridging — no-bridging was non-inferior for thromboembolism and caused significantly less major bleeding. Bridge only for the highest-risk patients: mechanical mitral valve, recent VTE (<3 months), or very high CHA₂DS₂-VASc (≥7). When in doubt, don't bridge.
Diabetes Management
- Metformin: HOLD day of surgery (risk of lactic acidosis with contrast or hypoperfusion). Resume when eating and renal function stable.
- SGLT2 inhibitors: HOLD 3–4 days before surgery (risk of euglycemic DKA — normal glucose but elevated ketones + anion gap). FDA Safety Communication, 2020
- Basal insulin: Reduce to 50–80% of usual dose the night before surgery. Do NOT hold completely (risk of DKA in type 1).
- Bolus/prandial insulin: HOLD the morning of surgery (patient is NPO).
- Oral agents (sulfonylureas, TZDs): HOLD morning of surgery.
- GLP-1 agonists (semaglutide, liraglutide): May hold — risk of delayed gastric emptying and aspiration. ASA recommends holding day of surgery for daily formulations, 1 week for weekly formulations.
Pulmonary Risk Reduction
Updated Practice: Old teaching — get preop PFTs on everyone. WRONG — routine preop PFTs do NOT predict postoperative pulmonary complications and are NOT recommended. Clinical assessment (history, exam, functional capacity) is sufficient.
- Incentive spirometry: Start preop and continue postop — reduces atelectasis and pneumonia.
- Smoking cessation: Ideally ≥ 8 weeks before surgery if possible. Even 24–48h of cessation reduces CO levels and improves O₂ delivery.
- Avoid NG tube if possible (increases aspiration risk).
- Early mobilization postop — most important intervention for preventing pulmonary complications.
🧪 Workup
Preoperative Testing
Only order tests that will change management. Routine "preop labs" without indication increase cost and false positives without improving outcomes.
- ECG: If RCRI ≥ 1, known cardiac disease, or symptoms. Not needed for low-risk patients undergoing low-risk surgery.
- CBC: If anticipated blood loss, anemia symptoms, or liver/renal disease.
- BMP: If renal disease, diabetes, diuretic use, or major surgery with expected fluid shifts.
- Coags (PT/INR): If on anticoagulants, liver disease, or bleeding history.
- Type & screen: If blood loss anticipated.
- Glucose: If diabetic — day-of-surgery glucose management.
- Pregnancy test: All women of childbearing age (many institutions mandate this).
- Stress test: Only if it will change management AND the patient has poor functional capacity (< 4 METs) AND elevated RCRI (≥ 2). Do NOT get routine preop stress tests.
- PFTs: NOT routinely indicated. Only if new/unexplained dyspnea or for lung resection surgery.
- CXR: NOT routinely indicated. Only if acute pulmonary symptoms or significant cardiopulmonary disease.
💊 Medications
Perioperative Medication Management
| Drug Class | Action | Rationale |
|---|---|---|
| Beta-blockers | CONTINUE (do NOT start new) | Withdrawal → rebound tachycardia/ischemia. POISE trial: starting new BB → ↑ stroke + death. |
| Statins | CONTINUE | Pleiotropic anti-inflammatory effects reduce periop cardiac events. |
| ACEi/ARBs | HOLD morning of surgery | Risk of refractory intraop hypotension. Resume when tolerating PO and hemodynamically stable. |
| Warfarin | STOP 5 days before | Bridge only for HIGH thrombotic risk (mechanical mitral valve, recent VTE <3mo). |
| DOACs | STOP 2–3 days before | No bridging needed. Extend to 4–5 days for dabigatran if CrCl < 50. |
| Aspirin | CONTINUE (most cases) | Hold for intracranial surgery. Otherwise, continue. |
| Metformin | HOLD day of surgery | Lactic acidosis risk with hypoperfusion/contrast. |
| SGLT2 inhibitors | HOLD 3–4 days before | Euglycemic DKA risk perioperatively. |
| Basal insulin | Reduce to 50–80% night before | Prevent hypoglycemia while NPO. Do NOT hold entirely in type 1. |
| Sulfonylureas | HOLD morning of surgery | Hypoglycemia risk while NPO. |
| GLP-1 agonists | HOLD (daily: day of; weekly: 1 wk) | Delayed gastric emptying → aspiration risk with anesthesia. |
📈 Monitoring
Postoperative Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| Vitals | q4h floor, q1–2h PACU | Watch for hypotension (bleeding, sepsis), tachycardia (pain, PE, bleeding), fever. |
| Glucose | q6h if diabetic (AC + HS) | Target 140–180 mg/dL inpatient. Avoid hypoglycemia. Sliding scale + reduced basal. |
| DVT prophylaxis | Assess daily | SQ heparin 5,000 units q8h or enoxaparin 40 mg SQ daily. SCDs if anticoag contraindicated. |
| I&Os | Strict if major surgery | UOP ≥ 0.5 mL/kg/hr. Monitor for fluid overload or hypovolemia. |
| Pain management | Each assessment | Multimodal: acetaminophen + NSAIDs (if no contraindication) + opioids PRN. Minimize opioids. |
| Incentive spirometry | q1h while awake | 10 breaths q1h. Prevents atelectasis and postop pneumonia. |
📋 On Rounds
When do you bridge anticoagulation for a patient on warfarin undergoing elective surgery?
Bridge with LMWH ONLY for patients at HIGH thrombotic risk: (1) Mechanical mitral valve (or any mechanical valve with additional risk factors), (2) Recent VTE within 3 months, (3) Very high CHA₂DS₂-VASc (≥ 7). For the vast majority of AF patients, do NOT bridge. The landmark BRIDGE trial (NEJM 2015) showed that bridging in AF patients did not reduce thromboembolism but significantly increased major bleeding. The default should be: stop warfarin 5 days before, check INR day before, proceed if INR ≤ 1.5, resume warfarin postop when eating.
What is the RCRI (Revised Cardiac Risk Index)?
The RCRI (Lee Index) is the most widely used tool for preoperative cardiac risk stratification. It has 6 independent predictors (1 point each): (1) High-risk surgery (intraperitoneal, intrathoracic, suprainguinal vascular), (2) Ischemic heart disease, (3) Heart failure, (4) Cerebrovascular disease, (5) Diabetes on insulin, (6) Cr > 2.0. Score interpretation: 0 = ~3.9% risk of major cardiac event, 1 = ~6%, 2 = ~10%, ≥3 = ~15%. A score of 0 with good functional capacity (≥ 4 METs) means the patient can proceed to surgery without further cardiac workup. Higher scores with poor functional capacity may warrant stress testing — but ONLY if the result would change surgical planning.
Why should you NOT start new beta-blockers perioperatively?
The POISE trial (NEJM 2008) randomized patients to extended-release metoprolol vs placebo started within 2–4h before surgery. Results: metoprolol reduced MI (4.2% vs 5.7%) BUT doubled the rate of stroke (1.0% vs 0.5%) and increased overall mortality (3.1% vs 2.3%). The mechanism: beta-blockers cause perioperative hypotension and bradycardia → cerebral hypoperfusion → stroke. Bottom line: continue beta-blockers if already on them (withdrawal is dangerous) but never start new ones within 24h of surgery.
When should you get a preoperative stress test?
Preop stress tests are indicated only when ALL THREE conditions are met: (1) The result will change management (i.e., you would cancel or modify the surgery based on the result). (2) The patient has poor functional capacity (< 4 METs — cannot climb one flight of stairs). (3) The patient has elevated cardiac risk (RCRI ≥ 2 or known significant cardiac disease). If any of these is missing, a stress test is NOT indicated. Example: If the surgery is an emergency and will proceed regardless → no stress test. If the patient can climb stairs without symptoms → no stress test (good functional capacity = low risk). If RCRI is 0 → no stress test (low risk). Unnecessary stress tests delay surgery and lead to false positives → unnecessary catheterizations → further delays and risks.
⚡ Summary
Perioperative Medicine — Key Points
Cardiac Risk
RCRI: 6 predictors. ≥4 METs = low risk regardless. Stress test only if poor functional capacity + elevated RCRI + will change management.
Beta-blockers
CONTINUE if on them. NEVER start new within 24h of surgery (POISE — ↑ stroke + death). Withdrawal is also dangerous.
Anticoagulation
Warfarin: stop 5 days. Bridge ONLY for mechanical mitral valve, VTE <3mo, very high CHA₂DS₂-VASc. BRIDGE trial: most AF patients do NOT need bridging.
Diabetes
Hold metformin day of surgery. Hold SGLT2i 3–4 days before (euglycemic DKA). Reduce basal insulin to 50–80%. Hold orals AM of surgery.
Pulmonary
Routine preop PFTs NOT recommended. Incentive spirometry, smoking cessation ≥8wk, early postop mobilization. No routine CXR.
SGLT2i Pearl
Hold empagliflozin/dapagliflozin 3–4 days preop. Risk of euglycemic DKA — normal glucose but elevated ketones + anion gap acidosis.
Sarcoidosis
Non-caseating granulomatous disease affecting multiple organs. Lungs involved in 90%. Bilateral hilar lymphadenopathy on CXR is the hallmark. Young adults, especially African Americans. Lofgren syndrome = excellent prognosis.
🔍 Overview
Overview
Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by non-caseating granulomas in affected organs. The lungs are involved in ~90% of cases. Other commonly affected organs: skin (erythema nodosum, lupus pernio), eyes (anterior uveitis), liver (granulomatous hepatitis), heart (conduction abnormalities, cardiomyopathy), and nervous system (cranial nerve palsies, especially CN VII). Epidemiology: peaks at age 25-35, higher incidence and more severe disease in African Americans and Scandinavians.
Lofgren Syndrome
A specific acute presentation with an excellent prognosis (>90% spontaneous resolution): bilateral hilar lymphadenopathy + erythema nodosum + polyarthralgia + fever. So characteristic that biopsy is often NOT required for diagnosis. More common in young women.
Scadding CXR Staging
- Stage 0 — Normal CXR
- Stage I — Bilateral hilar lymphadenopathy (BHL) alone. ~60-80% spontaneous remission.
- Stage II — BHL + pulmonary infiltrates. ~50-60% remission.
- Stage III — Pulmonary infiltrates WITHOUT lymphadenopathy. ~30% remission.
- Stage IV — Pulmonary fibrosis. Irreversible. Poor prognosis.
🚨 Management
Treatment Approach
Many patients need NO treatment — sarcoidosis is self-resolving in a large proportion of cases, especially Stage I and Lofgren syndrome. Observation alone is appropriate for asymptomatic patients with stable disease.
Indications for Treatment
- Progressive pulmonary disease — worsening PFTs, increasing infiltrates
- Cardiac involvement — heart block, cardiomyopathy, ventricular arrhythmias
- Neurological involvement — cranial nerve palsies, CNS mass lesions, seizures
- Hypercalcemia — from granulomatous production of 1,25-dihydroxyvitamin D
- Disfiguring skin disease — lupus pernio
- Significant eye disease — posterior uveitis, optic neuritis refractory to topical therapy
- Renal involvement — nephrocalcinosis, nephrolithiasis from hypercalciuria
First-Line Therapy
Prednisone 20-40 mg daily x 4-6 weeks, then slow taper over 6-12 months. Total treatment duration typically 12+ months. Relapse rate is high (~30-50%) when steroids are tapered. NSAIDs can be used for mild arthralgia and erythema nodosum.
Steroid-Sparing Agents
Consider when: unable to taper below prednisone 10 mg/day, steroid side effects, or relapse on taper.
- Methotrexate (Trexall) — most commonly used steroid-sparing agent. 10-15 mg weekly. Supplement with folic acid.
- Azathioprine (Imuran) — alternative to MTX. 50-200 mg daily. Check TPMT before starting.
- Mycophenolate (CellCept) — 500-1500 mg BID. Used for refractory disease.
Refractory Disease
Infliximab (Remicade) — anti-TNF-alpha. Reserved for severe disease failing conventional therapy. Evidence strongest for lupus pernio and neurosarcoidosis.
🧪 Workup
Diagnostic Workup
- CXR — Scadding staging (I-IV). Bilateral hilar lymphadenopathy is classic.
- CT chest — better characterization of parenchymal disease, lymphadenopathy pattern
- PFTs — restrictive pattern (decreased FVC, decreased DLCO). Obstructive pattern also possible with endobronchial involvement.
- ACE level — elevated in ~60% but NOT diagnostic. Neither sensitive nor specific (see alert below).
- Calcium — check serum calcium (hypercalcemia from granulomatous 1,25-vitamin D production)
- 24-hour urine calcium — hypercalciuria may be present even with normal serum calcium
- CBC, BMP, LFTs — baseline; elevated alk phos suggests hepatic granulomas
- ECG — screen for heart block (PR prolongation, bundle branch block). If abnormal, consider cardiac MRI or PET.
- Ophthalmology exam — screen for uveitis (anterior > posterior), even if asymptomatic
- Biopsy of accessible tissue — lung (transbronchial), skin, lymph node. REQUIRED for definitive diagnosis.
ACE level is NOT a good diagnostic test for sarcoidosis. Sensitivity ~60%, specificity poor. Many false positives and false negatives. ACE inhibitors lower it (false negative), diabetes can raise it (false positive). Diagnosis requires tissue biopsy showing non-caseating granulomas PLUS exclusion of other causes (TB, fungal infection, lymphoma, berylliosis).
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Prednisone 1ST LINE | 20-40 mg daily x 4-6 wk, then taper over 6-12 months | PO | Start at higher dose for severe organ involvement (cardiac, neuro). Monitor glucose, BP, bone density. |
| Methotrexate (Trexall) | 10-15 mg weekly | PO/SQ | Most common steroid-sparing agent. Add folic acid 1 mg daily. Monitor LFTs, CBC q4-8 weeks. Avoid in pregnancy (teratogenic). Vorselaars, Chest 2013 |
| Azathioprine (Imuran) | 50-200 mg daily | PO | Check TPMT before starting (homozygous deficiency = fatal myelosuppression). Monitor CBC regularly. |
| Mycophenolate (CellCept) | 500-1500 mg BID | PO | Alternative steroid-sparing. GI side effects common. Monitor CBC. |
| Infliximab (Remicade) | 3-5 mg/kg IV at weeks 0, 2, 6, then q4-8 weeks | IV | For refractory disease. Screen for TB before starting (anti-TNF reactivates latent TB). Baughman, AJRCCM 2006 |
| Hydroxychloroquine | 200-400 mg daily | PO | Useful for skin sarcoidosis, hypercalcemia, and fatigue. Annual eye exams for retinal toxicity. |
📊 Monitoring
Monitoring
- PFTs — repeat every 3-6 months while on treatment. FVC and DLCO most useful for tracking disease activity.
- CXR or CT chest — every 6-12 months depending on disease severity.
- Serum calcium and 24h urine calcium — monitor for hypercalcemia/hypercalciuria, especially when tapering steroids.
- Ophthalmology — annual screening even if asymptomatic. More frequent if active uveitis.
- ECG — annual. Low threshold for cardiac MRI or PET if new symptoms (palpitations, syncope, dyspnea).
- LFTs — monitor for hepatic sarcoidosis and drug toxicity (MTX, azathioprine).
- CBC — for steroid-sparing drug monitoring (MTX, azathioprine, mycophenolate).
- Bone density (DEXA) — if on prolonged steroids (>3 months prednisone >= 5 mg/day).
- ACE level — some clinicians follow trends, but NOT useful for diagnosis or as sole marker of disease activity.
🏥 Rounds
Sample Presentation
Ms. Davis is a 34-year-old African American woman presenting with 3 months of dry cough, progressive dyspnea on exertion, and bilateral ankle swelling. She also notes painful red bumps on her shins and bilateral ankle pain. CXR shows bilateral hilar lymphadenopathy with diffuse reticular opacities (Stage II). PFTs: FVC 65% predicted, DLCO 58% predicted. Labs: calcium 11.2, ACE level 85 (elevated), LFTs mildly elevated. Ophtho exam: anterior uveitis OS. Transbronchial biopsy: non-caseating granulomas. AFB and fungal stains negative.
Key Points: Classic Stage II sarcoidosis with multisystem involvement (lungs, skin — erythema nodosum, eyes — uveitis, liver, hypercalcemia). Treatment indicated given progressive pulmonary disease and hypercalcemia. Start prednisone 40 mg daily. Plan for steroid-sparing agent (MTX) given likely need for prolonged therapy.
Pimp Questions
❓ Why is ACE level a poor diagnostic test for sarcoidosis?
ACE is produced by epithelioid cells in granulomas. However, it has sensitivity of only ~60% and poor specificity. ACE inhibitors lower the level (false negative), while diabetes, hyperthyroidism, and other granulomatous diseases can raise it (false positive). It should NEVER be used as a sole diagnostic criterion. Diagnosis requires tissue biopsy + exclusion of other causes.
❓ What is Lofgren syndrome and why is it important?
Lofgren syndrome is an acute presentation of sarcoidosis with the triad of: (1) bilateral hilar lymphadenopathy, (2) erythema nodosum, (3) polyarthralgia, often with fever. It has an excellent prognosis (>90% spontaneous resolution) and is so characteristic that biopsy is often not required for diagnosis. Treatment is usually supportive (NSAIDs for symptoms).
❓ How does sarcoidosis cause hypercalcemia?
Activated macrophages within sarcoid granulomas express 1-alpha-hydroxylase, which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol). This extra-renal production is NOT regulated by PTH, leading to increased intestinal calcium absorption and hypercalcemia. Treatment: corticosteroids suppress macrophage activity. PTH is appropriately suppressed (unlike primary hyperparathyroidism).
❓ What cardiac manifestations should you screen for in sarcoidosis?
Cardiac sarcoidosis can cause: (1) conduction abnormalities — AV block (most common), bundle branch block, (2) ventricular arrhythmias — VT, sudden cardiac death, (3) cardiomyopathy — dilated or restrictive. Screen all patients with an ECG. If abnormal or symptomatic, pursue cardiac MRI (late gadolinium enhancement) or FDG-PET. Cardiac involvement is a leading cause of death in sarcoidosis.
❓ When do you NOT need a biopsy for sarcoidosis diagnosis?
Biopsy may be deferred in two scenarios: (1) Lofgren syndrome — the classic triad of bilateral hilar LAD + erythema nodosum + polyarthralgia is so specific that it is considered virtually diagnostic, (2) Asymptomatic bilateral hilar lymphadenopathy in a young patient with a classic CXR pattern and no concerning features for lymphoma or infection — though many clinicians still prefer biopsy confirmation.
📋 Summary
Summary
Pathology
Non-caseating granulomas. Must exclude TB, fungal, lymphoma.
Classic CXR
Bilateral hilar lymphadenopathy. Scadding staging I-IV.
Treatment
Many DON'T need treatment. First-line: prednisone 20-40 mg. Steroid-sparing: MTX, AZA.
ACE Level
NOT diagnostic. Sensitivity 60%, specificity poor. Biopsy is required.
Lofgren
BHL + erythema nodosum + polyarthralgia + fever. Excellent prognosis. Biopsy often NOT needed.
Hypercalcemia
Granulomatous 1,25-vit D production. PTH suppressed. Treat with steroids.
Autoimmune Hepatitis
Chronic liver inflammation from immune-mediated destruction. Predominantly young women. Type 1 (ANA/ASMA+) is most common. AST/ALT can exceed 1000 in acute flares. High relapse rate if treatment stopped. Elevated IgG is the hallmark serologic finding.
🔍 Overview
Overview
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease caused by loss of immune tolerance to hepatocytes. It predominantly affects young women (female:male ratio 4:1) but can occur at any age. Can present as acute hepatitis (AST/ALT often >1000) or chronic liver disease with insidious progression to cirrhosis. Associated with other autoimmune conditions (thyroiditis, UC, RA, celiac).
Types
- Type 1 (80%) — ANA and/or anti-smooth muscle antibody (ASMA) positive. Adults predominantly. Most common worldwide.
- Type 2 — Anti-liver-kidney microsomal antibody (anti-LKM1) positive. More common in children. Tends to be more severe.
🚨 Management
Induction
- Standard induction: Prednisone 40-60 mg daily, tapering over 4-8 weeks to 5-10 mg daily, PLUS Azathioprine (Imuran) 50 mg daily at week 2, uptitrated to 1-2 mg/kg.
- Alternative: Budesonide (Entocort) 9 mg daily — first-pass hepatic metabolism means fewer systemic side effects. BUT: do NOT use in cirrhotic patients (portosystemic shunts bypass first-pass metabolism, negating the benefit). Manns, Gastroenterology 2010
Maintenance
Azathioprine monotherapy (1-2 mg/kg daily) once steroids are tapered. Aim to maintain on the lowest effective azathioprine dose. Relapse rate is 80-90% if treatment is stopped — most patients need lifelong therapy.
TPMT Testing
Check TPMT before starting azathioprine — homozygous TPMT deficiency causes fatal myelosuppression. Heterozygous patients need dose reduction. Also monitor CBC regularly on azathioprine (q2 weeks for first 2 months, then q3 months).
🧪 Workup
Diagnostic Workup
- AST/ALT — often markedly elevated (>1000 in acute flares). Hepatocellular pattern.
- IgG levels — elevated IgG is the hallmark. Polyclonal hypergammaglobulinemia.
- ANA — positive in Type 1 (not specific for AIH)
- ASMA (anti-smooth muscle antibody) — more specific for Type 1 AIH
- Anti-LKM1 — diagnostic of Type 2 AIH
- Liver biopsy — interface hepatitis (lymphoplasmacytic infiltrate at the portal-parenchymal junction) is classic. May show bridging necrosis in severe cases.
- Rule out other causes:
- Viral hepatitis — Hep A IgM, HBsAg, anti-HBc, anti-HCV, Hep E IgM
- Drug-induced liver injury — thorough medication history
- Wilson disease — ceruloplasmin (especially in patients <40)
- Simplified AIH Scoring System — uses ANA/SMA titers, IgG levels, liver histology, and exclusion of viral hepatitis. Score >=7 = definite AIH.
💊 Medications
Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Prednisone INDUCTION | 40-60 mg daily, taper to 5-10 mg over 4-8 weeks | PO | Standard induction. Monitor glucose, BP, bone density on prolonged use. |
| Azathioprine (Imuran) MAINTENANCE | 50 mg daily initially, uptitrate to 1-2 mg/kg | PO | Check TPMT BEFORE starting. Fatal myelosuppression if homozygous deficient. Monitor CBC q2 weeks x 2 months, then q3 months. AASLD 2020 |
| Budesonide (Entocort) | 9 mg daily (3 mg TID) | PO | Alternative to prednisone. First-pass metabolism = fewer systemic effects. Do NOT use in cirrhosis. |
| Mycophenolate (CellCept) | 1-2 g daily | PO | Second-line for azathioprine-intolerant patients. Teratogenic — avoid in pregnancy. |
| Tacrolimus (Prograf) | 1-6 mg daily (target trough 3-5 ng/mL) | PO | Salvage therapy for refractory AIH. Monitor trough levels and renal function. |
📊 Monitoring
Monitoring
- LFTs (AST/ALT) — q2-4 weeks during induction, then q3 months on maintenance. Goal: normalization of transaminases.
- IgG level — normalize with successful treatment. Useful marker of disease activity.
- CBC — monitor for azathioprine myelosuppression. q2 weeks for first 2 months, then q3 months.
- TPMT result — must have before starting azathioprine.
- Liver biopsy — consider repeat biopsy before treatment withdrawal to confirm histologic remission (biochemical remission does NOT guarantee histologic remission).
- Hepatocellular carcinoma screening — if cirrhosis present, standard HCC screening (ultrasound + AFP q6 months).
- Bone density — DEXA if prolonged steroid use.
🏥 Rounds
Sample Presentation
Ms. Patel is a 28-year-old woman with no significant past medical history presenting with 2 weeks of fatigue, jaundice, and RUQ discomfort. Labs: AST 1,240, ALT 1,580, total bilirubin 8.4, INR 1.3, albumin 3.2. IgG markedly elevated at 3,200 (normal <1600). ANA 1:320, ASMA 1:160. Hepatitis A, B, C, E serologies negative. Ceruloplasmin normal. Liver biopsy: interface hepatitis with lymphoplasmacytic infiltrate. Simplified AIH score: 8 (definite AIH).
Key Points: Classic Type 1 AIH in a young woman — markedly elevated transaminases, elevated IgG, positive ANA/ASMA, interface hepatitis on biopsy. Check TPMT, start prednisone 60 mg daily, add azathioprine 50 mg at week 2. Monitor for steroid side effects. Counsel that lifelong therapy is likely needed (80-90% relapse rate if stopped).
Pimp Questions
❓ Why can't you use budesonide in cirrhotic patients with AIH?
Budesonide has high first-pass hepatic metabolism — normally 90% is cleared by the liver, so systemic exposure is minimal. In cirrhosis, portosystemic shunts bypass the liver, so budesonide enters systemic circulation at high levels — losing its advantage over prednisone and causing full systemic steroid side effects. Use prednisone instead.
❓ What is the most important lab to distinguish AIH from other causes of hepatitis?
IgG level. Elevated IgG (polyclonal hypergammaglobulinemia) is the hallmark of AIH and is part of the simplified diagnostic criteria. While ANA and ASMA are useful, they are not specific — ANA can be positive in many conditions. IgG elevation combined with autoantibodies and interface hepatitis on biopsy is the diagnostic triad.
❓ Why must you check TPMT before starting azathioprine?
Azathioprine is metabolized by thiopurine methyltransferase (TPMT). Patients with homozygous TPMT deficiency (~0.3% of population) accumulate toxic metabolites causing fatal myelosuppression — severe pancytopenia. Heterozygous patients (~10%) need dose reduction. Testing prevents a completely preventable catastrophic drug reaction.
❓ What happens when you try to stop AIH treatment?
The relapse rate is 80-90% when treatment is withdrawn, even after achieving biochemical remission. Most patients require lifelong immunosuppression with low-dose azathioprine. Consider attempting withdrawal only after: (1) sustained biochemical remission for >2 years, (2) confirmed histologic remission on repeat biopsy, and (3) very close follow-up with labs q2-4 weeks after stopping.
📋 Summary
Summary
Hallmark
Elevated IgG + autoantibodies (ANA, ASMA, anti-LKM1) + interface hepatitis on biopsy
Types
Type 1: ANA/ASMA+ (80%, adults). Type 2: anti-LKM1+ (children, more severe).
Treatment
Prednisone 40-60 mg + azathioprine 1-2 mg/kg. Check TPMT first!
Maintenance
Azathioprine monotherapy. Lifelong in most. 80-90% relapse if stopped.
Budesonide
Alternative to prednisone. Do NOT use in cirrhosis (portosystemic shunts).
Danger
TPMT deficiency + azathioprine = fatal myelosuppression. Always test first.
PBC / PSC
Two distinct cholestatic liver diseases. PBC: anti-mitochondrial antibody positive, middle-aged women, responds to ursodiol. PSC: associated with UC, beading on MRCP, young men, NO proven medical therapy. Both can progress to cirrhosis.
🔍 Overview
PBC vs PSC Comparison
| Feature | PBC (Primary Biliary Cholangitis) | PSC (Primary Sclerosing Cholangitis) |
|---|---|---|
| Gender | 90% female | ~70% male |
| Age | Middle-aged (40-60) | Young adults (30-40) |
| Key Antibody | Anti-mitochondrial antibody (AMA) — 95% sensitive | p-ANCA (nonspecific) |
| Imaging | Normal bile ducts on MRCP | Beading on MRCP (multifocal strictures + dilations) |
| Pathology | Destruction of small intrahepatic bile ducts | Inflammation and fibrosis of intra- and extrahepatic bile ducts |
| Symptoms | Pruritus, fatigue | Pruritus, jaundice, RUQ pain, cholangitis episodes |
| Associated Conditions | Sjogren, thyroiditis, celiac, RA | Ulcerative colitis (70%), cholangiocarcinoma |
| Cancer Risk | Hepatocellular carcinoma (if cirrhosis) | Cholangiocarcinoma (lifetime risk 10-15%), gallbladder cancer, colon cancer (if UC) |
| Treatment | Ursodiol (UDCA) works | NO proven medical therapy |
🚨 Management
PBC Management
- First-line: Ursodiol (UDCA) 13-15 mg/kg/day (split BID). Improves LFTs, delays histologic progression, improves transplant-free survival. Poupon, NEJM 1991
- Incomplete response to UDCA: Obeticholic acid (Ocaliva) — FXR agonist. Add if ALP >1.67x ULN or bilirubin elevated after 12 months of UDCA. Caution: worsens pruritus significantly. Contraindicated in decompensated cirrhosis (FDA black box). POISE, NEJM 2016
- Pruritus management: Cholestyramine (first-line for itch), rifampin, naltrexone, sertraline
- Liver transplant for decompensated cirrhosis. PBC can recur post-transplant but rarely clinically significant.
PSC Management
- NO proven medical therapy — this is the critical teaching point.
- Ursodiol is commonly prescribed but does NOT improve transplant-free survival in PSC. High-dose ursodiol (28-30 mg/kg) was actually HARMFUL — increased mortality, need for transplant, and serious adverse events. Lindor, Hepatology 2009
- ERCP with balloon dilation for dominant strictures causing cholangitis or progressive jaundice.
- Liver transplant — definitive treatment. PSC can recur post-transplant (~20%).
- Cancer screening: CA 19-9 + MRCP annually for cholangiocarcinoma. Colonoscopy annually if concomitant UC (elevated colon cancer risk).
Updated Practice: Ursodiol works for PBC but NOT for PSC. Despite widespread use, ursodiol has not been shown to improve transplant-free survival in PSC. High-dose ursodiol (28-30 mg/kg) was actually HARMFUL in PSC (Lindor, Hepatology 2009). Standard-dose ursodiol may improve LFTs but without clinical outcomes benefit.
🧪 Workup
PBC Workup
- AMA (anti-mitochondrial antibody) — 95% sensitive and highly specific for PBC. AMA-positive + cholestatic LFTs often sufficient for diagnosis without biopsy.
- LFTs — cholestatic pattern: elevated ALP, GGT. ALT/AST may be mildly elevated.
- IgM — typically elevated in PBC (vs. IgG in AIH)
- Liver biopsy — may not be needed if AMA+ with typical cholestatic LFTs. Shows granulomatous destruction of small bile ducts ("florid duct lesion").
PSC Workup
- MRCP — diagnostic study of choice. Shows multifocal strictures and dilations of intra- and/or extrahepatic bile ducts ("beading" or "string of pearls").
- LFTs — cholestatic pattern (elevated ALP, GGT).
- p-ANCA — positive in ~80% but not specific.
- Colonoscopy — screen for UC even if asymptomatic (70% of PSC patients have UC).
- CA 19-9 — baseline and annually for cholangiocarcinoma screening.
- Liver biopsy — "onion skin" periductal fibrosis is classic but often not needed if MRCP is diagnostic.
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Ursodiol (UDCA) PBC 1ST LINE | PBC | 13-15 mg/kg/day PO | Improves LFTs and transplant-free survival in PBC. Split BID. Take with food. NOT effective for PSC. |
| Obeticholic Acid (Ocaliva) | PBC (UDCA-incomplete) | 5 mg daily, may increase to 10 mg | FXR agonist. Worsens pruritus. Black box: contraindicated in decompensated cirrhosis. POISE, NEJM 2016 |
| Cholestyramine | Pruritus (PBC/PSC) | 4 g BID-QID | First-line for cholestatic pruritus. Separate from other medications by 2-4 hours (bile acid sequestrant binds drugs). |
| Rifampin | Pruritus (refractory) | 150-300 mg BID | Second-line for pruritus. Monitor LFTs (hepatotoxic). Effective in PBC/PSC-related itch. |
| Naltrexone | Pruritus (refractory) | 25-50 mg daily | Opioid antagonist for cholestatic pruritus. Can precipitate opioid withdrawal — start low dose. |
📊 Monitoring
PBC Monitoring
- LFTs — q3-6 months. Track ALP response to UDCA. Incomplete response: ALP >1.67x ULN after 12 months.
- Bilirubin — rising bilirubin is the strongest predictor of poor prognosis in PBC.
- Thyroid function — screen for hypothyroidism (frequently associated).
- DEXA — osteoporosis risk is elevated in cholestatic liver disease.
- Fat-soluble vitamins — A, D, E, K. Malabsorption from cholestasis.
PSC Monitoring
- CA 19-9 + MRCP — annually for cholangiocarcinoma screening.
- Colonoscopy — annually if concomitant UC (elevated colon cancer risk). Even after liver transplant.
- LFTs — q3-6 months. New cholangitis episodes may indicate dominant stricture.
- Gallbladder ultrasound — annually. Increased gallbladder cancer risk. Low threshold for cholecystectomy if polyps found.
🏥 Rounds
Sample Presentation
Mr. Olsen is a 32-year-old man with ulcerative colitis on mesalamine, presenting with progressive jaundice, pruritus, and fatigue over 3 months. Labs: ALP 480, GGT 320, ALT 85, bilirubin 4.2. p-ANCA positive. MRCP shows multifocal intrahepatic and extrahepatic bile duct strictures with beading pattern. Dominant stricture at the common hepatic duct with upstream dilation.
Key Points: Classic PSC — young man with UC, cholestatic LFTs, beading on MRCP. NO medical therapy improves outcomes. Dominant stricture causing jaundice — refer for ERCP with balloon dilation. Start cholangiocarcinoma screening (CA 19-9 + MRCP annually). Ensure annual colonoscopy for UC-associated colon cancer. Discuss liver transplant referral given progressive disease.
Pimp Questions
❓ Why does ursodiol work for PBC but not PSC?
In PBC, toxic bile acids cause destruction of small bile ducts. Ursodiol replaces toxic bile acids with a hydrophilic, non-toxic bile acid, reducing cholangiocyte injury. In PSC, the pathology is fibrosis and stricturing of large bile ducts — a different mechanism not addressed by changing bile acid composition. The high-dose UDCA trial in PSC actually showed HARM — possibly because retained ursodiol above strictures caused hepatotoxicity.
❓ What cancer are you most worried about in PSC?
Cholangiocarcinoma — lifetime risk 10-15%. Can be very difficult to detect because it arises in the setting of already-abnormal bile ducts. Screen with CA 19-9 + MRCP annually. Any new dominant stricture should raise suspicion — brush cytology via ERCP with FISH analysis. Also at risk for gallbladder cancer and colon cancer (if UC).
❓ How do you distinguish PBC from PSC on labs and imaging?
Both are cholestatic (elevated ALP, GGT). PBC: AMA positive (95%), normal bile ducts on MRCP, typically middle-aged woman. PSC: AMA negative, beading/strictures on MRCP, typically young man with UC. The bile ducts on MRCP are the key differentiator — if MRCP is normal but cholestasis persists, think PBC (small duct disease not visible on imaging).
📋 Summary
Summary
PBC Key
AMA+, middle-aged women, pruritus. Ursodiol 13-15 mg/kg WORKS.
PSC Key
Beading on MRCP, young men, 70% have UC. NO proven medical therapy.
PSC Cancer
Cholangiocarcinoma risk 10-15%. Screen CA 19-9 + MRCP annually.
UDCA in PSC
Does NOT improve survival. High-dose was HARMFUL. Common but unproven use.
PBC Incomplete
Obeticholic acid (Ocaliva) if ALP >1.67x after 12 months UDCA. Worsens pruritus.
Definitive Tx
Liver transplant for both if decompensated. PSC recurs ~20% post-transplant.
PRES
Posterior Reversible Encephalopathy Syndrome. Vasogenic edema predominantly in the posterior circulation. Classic presentation: seizures + headache + visual changes + hypertension. MRI is the diagnostic study of choice. Usually reversible if treated promptly.
🔍 Overview
Overview
Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiographic syndrome characterized by vasogenic edema predominantly in the posterior (occipital/parietal) white matter. Pathophysiology: failure of cerebral autoregulation leads to blood-brain barrier breakdown and vasogenic edema.
Common Causes
- Severe hypertension — most common trigger. Exceeds upper limit of autoregulation.
- Eclampsia / pre-eclampsia — one of the most important causes in young women
- Immunosuppressants — tacrolimus, cyclosporine (calcineurin inhibitors) — common in transplant patients
- Chemotherapy — especially VEGF inhibitors (bevacizumab)
- Autoimmune disease — SLE, TTP, thrombotic microangiopathy
- Renal failure — especially with fluid overload and hypertension
Clinical Presentation
Classic features: seizures (most common presenting symptom, 60-75%), headache (50%), visual disturbances (cortical blindness, blurry vision, visual field defects — 33%), altered mental status (28%), and hypertension (often severe). Typically acute/subacute onset over hours to days.
🚨 Management
Management Principles
- TREAT THE CAUSE — this is the most important step:
- Hypertensive emergency: lower BP gradually (IV antihypertensives — nicardipine, labetalol)
- Eclampsia: magnesium sulfate + delivery
- Drug-induced: discontinue offending agent (tacrolimus, cyclosporine, chemotherapy)
- Seizure management: Benzodiazepines for acute seizures. Levetiracetam (Keppra) for prophylaxis/maintenance (fewer drug interactions than phenytoin in transplant patients).
- BP control: Target 25% reduction in MAP over first few hours. Avoid precipitous drops (risk of ischemia). IV nicardipine or labetalol preferred.
- Usually REVERSIBLE if treated promptly — clinical and radiographic improvement typically within days to weeks. Delayed treatment can lead to permanent infarction, hemorrhage, and death.
PRES is a clinical-radiographic diagnosis. MRI is key — CT may miss early changes. Despite the name, PRES is not always posterior (can involve frontal lobes, brainstem, cerebellum) and not always reversible (delayed treatment can cause permanent ischemic injury, hemorrhage, or death).
🧪 Workup
Diagnostic Workup
- MRI brain (with FLAIR) — study of choice. Shows bilateral, symmetric white matter edema in posterior regions (occipital/parietal lobes). FLAIR and T2 sequences show hyperintense signal. DWI helps distinguish vasogenic (PRES) from cytotoxic (stroke) edema.
- CT head — less sensitive, may appear normal early. Can show low-density areas in posterior regions. Rule out hemorrhage.
- BP — often severely elevated (but PRES can occur at normal BPs, especially drug-induced)
- BMP — renal function, electrolytes
- CBC, LDH, peripheral smear, haptoglobin — rule out TTP/HUS if thrombocytopenia present
- Urine protein/Cr ratio — if pregnant or postpartum (pre-eclampsia workup)
- Drug levels — tacrolimus, cyclosporine trough levels if applicable
- LP — typically not needed. CSF may show mild protein elevation. Mainly to rule out meningitis/encephalitis if diagnosis uncertain.
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Nicardipine BP CONTROL | Hypertensive PRES | 5 mg/hr IV, titrate by 2.5 mg/hr q5-15 min (max 15 mg/hr) | Preferred — titratable, consistent effect. No cerebral vasoconstriction. |
| Labetalol | Hypertensive PRES | 10-20 mg IV bolus, double q10 min (max 300 mg) or 1-2 mg/min drip | Alternative to nicardipine. Avoid in severe bradycardia, asthma, heart block. |
| Levetiracetam (Keppra) | Seizure prophylaxis | 500-1000 mg IV/PO BID | Preferred in transplant patients (no CYP interactions — does not affect tacrolimus/cyclosporine levels). |
| Lorazepam (Ativan) | Acute seizures | 2-4 mg IV PRN | First-line for acute seizure control. |
| Magnesium sulfate | Eclampsia-related PRES | 4-6 g IV load, then 1-2 g/hr | Standard of care for eclamptic seizures. Also has antihypertensive effect. |
📊 Monitoring
Monitoring
- Blood pressure — continuous arterial line or frequent NIBP. Target 25% MAP reduction over first hours, then gradually normalize.
- Neurologic exam — serial neuro checks q1-2h. Document mental status, vision, motor function.
- Repeat MRI — in 1-2 weeks to confirm radiographic resolution. If not improving, reconsider diagnosis.
- Seizure monitoring — consider continuous EEG if altered mental status persists or recurrent seizures.
- Drug levels — if calcineurin inhibitor-related, check trough levels and hold/reduce dose until resolution.
- Urine output and renal function — especially if pre-eclampsia or renal failure is the trigger.
🏥 Rounds
Sample Presentation
Mrs. Kim is a 45-year-old woman who is 6 months post-renal transplant on tacrolimus, presenting with sudden-onset severe headache, blurry vision, and a witnessed generalized tonic-clonic seizure. BP on arrival: 210/115. Neuro exam: confused, bilateral visual field deficits. Tacrolimus trough elevated at 18 (target 5-8). MRI brain: bilateral symmetric T2/FLAIR hyperintensity in the occipital and parietal white matter consistent with vasogenic edema. No restricted diffusion. No hemorrhage.
Key Points: Classic PRES — transplant patient on tacrolimus with HTN emergency + seizure + visual changes + posterior white matter edema on MRI. Management: (1) nicardipine drip for BP control, (2) levetiracetam for seizure management (no CYP interactions with tacrolimus), (3) HOLD tacrolimus (supratherapeutic level likely contributing). Expect clinical improvement within days if treated promptly.
Pimp Questions
❓ Why is the posterior circulation preferentially affected in PRES?
The posterior (vertebrobasilar) circulation has less sympathetic innervation than the anterior (carotid) circulation. Sympathetic innervation helps maintain cerebral autoregulation during acute hypertension. Because the posterior circulation lacks this protective mechanism, it is more susceptible to breakthrough hyperperfusion and blood-brain barrier breakdown when BP exceeds the autoregulatory threshold.
❓ How do you differentiate PRES from ischemic stroke on MRI?
Key is DWI (diffusion-weighted imaging). PRES shows vasogenic edema — T2/FLAIR bright, but DWI normal or dark (no restricted diffusion). Ischemic stroke shows cytotoxic edema — DWI bright with corresponding ADC dark (restricted diffusion). If PRES shows restricted diffusion, it suggests progression to infarction (poor prognostic sign).
❓ Why use levetiracetam over phenytoin in transplant patients with PRES?
Phenytoin is metabolized via CYP3A4 and also induces CYP3A4, which metabolizes tacrolimus and cyclosporine. Using phenytoin in transplant patients would dramatically lower immunosuppressant levels, risking acute rejection. Levetiracetam is renally cleared with no CYP interactions, making it the preferred anticonvulsant in this population.
📋 Summary
Summary
Triad
Seizures + headache + visual changes with hypertension. Posterior white matter edema on MRI.
Causes
Severe HTN, eclampsia, tacrolimus/cyclosporine, chemotherapy, autoimmune disease.
Diagnosis
MRI with FLAIR. T2/FLAIR bright in posterior regions. DWI normal (vasogenic, not cytotoxic).
Treatment
Treat the CAUSE. Lower BP. Remove offending drug. Seizure control (levetiracetam).
Prognosis
Usually REVERSIBLE if treated promptly. Delayed Tx = infarction, hemorrhage, death.
Misnomer
Not always posterior. Not always reversible. CT can miss it — MRI is essential.
Amyloidosis
Misfolded protein deposition causing organ dysfunction. AL (light chain) is most common systemic type. Cardiac involvement = very poor prognosis. Classic clue: low voltage ECG + thick walls on echo. Diagnosis: Congo red stain with apple-green birefringence.
🔍 Overview
Overview
Amyloidosis is a group of diseases caused by extracellular deposition of misfolded proteins (amyloid fibrils) in tissues, leading to organ dysfunction. The protein type determines the disease subtype and treatment.
Major Types
- AL Amyloidosis (Light Chain) — from plasma cell dyscrasia. Most common systemic amyloidosis. Light chains (usually lambda) misfold and deposit. Related to multiple myeloma but most patients do NOT have overt myeloma.
- AA Amyloidosis — from serum amyloid A (SAA) protein, produced in chronic inflammation. Causes: RA, Crohn disease, familial Mediterranean fever (FMF), chronic infections. Predominantly affects kidneys.
- ATTR Amyloidosis (Transthyretin) — hereditary (mutant TTR) or wild-type (senile cardiac amyloidosis). Increasingly recognized as a cause of HFpEF in elderly patients.
Organ Involvement
- Heart — restrictive cardiomyopathy. Low voltage on ECG despite thick walls on echo (classic discordance). Diastolic dysfunction. Elevated troponin and BNP.
- Kidney — nephrotic syndrome (proteinuria, edema, hypoalbuminemia)
- Liver — hepatomegaly, elevated ALP
- Nerves — peripheral neuropathy (pain, numbness), autonomic neuropathy (orthostatic hypotension)
- GI — malabsorption, weight loss, GI bleeding
- Tongue — macroglossia (pathognomonic for AL amyloidosis)
Low voltage on ECG + thick walls on echo = think amyloidosis. In HCM, thick walls produce HIGH voltage. This voltage-mass discordance is a classic board question. The amyloid infiltrates the myocardium, increasing wall thickness but reducing electrical signal.
🚨 Management
AL Amyloidosis
- Treat the underlying plasma cell clone — goal is to eliminate the source of amyloidogenic light chains.
- First-line: Daratumumab + CyBorD (cyclophosphamide, bortezomib, dexamethasone). ANDROMEDA, NEJM 2021 — showed significantly higher hematologic complete response rate.
- Autologous stem cell transplant (SCT) — for eligible patients (typically younger, no significant cardiac involvement). Best long-term outcomes.
- Cardiac AL prognosis: Very poor — median survival 6 months untreated. With modern treatment, outcomes improving but cardiac involvement remains the dominant prognostic factor.
AA Amyloidosis
Treat the underlying inflammatory disease. Control RA, Crohn, FMF (colchicine for FMF). Reducing SAA levels can halt progression and even allow regression of amyloid deposits.
Supportive Care
- Heart failure: Diuretics — use cautiously, these patients are preload-dependent (restrictive physiology). Small changes in volume cause dramatic hemodynamic effects. Avoid digoxin (binds amyloid fibrils, causing toxicity at therapeutic levels).
- Orthostatic hypotension: Midodrine 5-10 mg TID, compression stockings, increased salt intake.
- Nephrotic syndrome: ACEi/ARB for proteinuria. Diuretics for edema.
🧪 Workup
Diagnosis
- Tissue biopsy with Congo red stain — apple-green birefringence under polarized light is diagnostic of amyloid.
- Fat pad aspirate — least invasive biopsy site. Sensitivity ~70-80% for AL. If negative but suspicion high, biopsy the affected organ.
- Bone marrow biopsy — to assess plasma cell clone in AL amyloidosis.
Typing the Amyloid
- SPEP / UPEP / serum free light chains — for AL amyloidosis. Free light chain ratio is abnormal in >95% of AL patients.
- SAA levels — for AA amyloidosis. Elevated in chronic inflammatory states.
- Mass spectrometry — gold standard for amyloid subtyping (laser microdissection + mass spec on biopsy tissue).
Cardiac Assessment
- Troponin and BNP/NT-proBNP — markedly elevated in cardiac amyloidosis. Used for staging (Mayo staging system).
- ECG — low voltage (limb leads <5mm) + pseudo-infarct pattern (Q waves without MI) are classic.
- Echocardiogram — thick walls + diastolic dysfunction. "Sparkling" or "granular" myocardium (sometimes described on older machines). Small LV cavity, biatrial enlargement.
- Cardiac MRI — characteristic diffuse subendocardial or transmural late gadolinium enhancement pattern. Global T1 elevation.
- Technetium pyrophosphate (PYP) scan — highly sensitive and specific for ATTR cardiac amyloidosis. Grade 2-3 uptake = diagnostic without biopsy.
💊 Medications
Medications
| Drug | Type | Dose | Notes |
|---|---|---|---|
| Daratumumab (Darzalex) AL 1ST LINE | AL | 16 mg/kg IV weekly x 8, then q2 weeks, then monthly | Anti-CD38 monoclonal antibody. Combined with CyBorD. ANDROMEDA, NEJM 2021 |
| Bortezomib (Velcade) | AL | 1.3 mg/m2 SQ weekly (part of CyBorD) | Proteasome inhibitor. Targets plasma cells. Peripheral neuropathy is dose-limiting toxicity. |
| Cyclophosphamide | AL | 300 mg/m2 PO weekly (part of CyBorD) | Alkylating agent. Dose adjust for renal function. |
| Dexamethasone | AL | 20-40 mg PO weekly (part of CyBorD) | Steroid component. Monitor glucose, infections. |
| Tafamidis (Vyndamax) | ATTR | 80 mg PO daily | TTR stabilizer for ATTR cardiac amyloidosis. Reduced mortality and CV hospitalization. ATTR-ACT, NEJM 2018 |
| Midodrine | Supportive | 5-10 mg PO TID | For orthostatic hypotension from autonomic neuropathy. Hold if supine BP >180. |
📊 Monitoring
Monitoring
- Serum free light chains — q1-3 months during treatment. Hematologic response: normalization of free light chain ratio.
- NT-proBNP and troponin — cardiac biomarkers used for staging and monitoring organ response. Reduction indicates cardiac response.
- 24h urine protein — for renal involvement. Renal response: >50% reduction in proteinuria.
- Echocardiogram — q6-12 months. Monitor wall thickness, diastolic function, strain patterns.
- ALP — for hepatic involvement. Hepatic response: >50% decrease in ALP.
- Orthostatic vitals — for autonomic neuropathy monitoring.
- CBC, BMP — monitor for treatment toxicity (myelosuppression from chemo, renal function).
🏥 Rounds
Sample Presentation
Mr. Franklin is a 62-year-old man presenting with 6 months of progressive dyspnea on exertion, lower extremity edema, and 15-lb weight loss. He also reports numbness/tingling in both feet and lightheadedness when standing. Exam: macroglossia, periorbital purpura, elevated JVP, bilateral pitting edema. Labs: troponin 0.15 (elevated), NT-proBNP 8,400 (markedly elevated), creatinine 1.8, albumin 2.1, 24h urine protein 5.2 g/day. ECG: low voltage + pseudo-infarct pattern. Echo: thick walls (IVS 16mm) + diastolic dysfunction + small LV cavity. Free kappa/lambda ratio markedly abnormal (lambda predominant). Fat pad biopsy: Congo red positive, apple-green birefringence under polarized light.
Key Points: Classic AL amyloidosis with multiorgan involvement — cardiac (restrictive CMP, low voltage + thick walls), renal (nephrotic syndrome), neurologic (peripheral and autonomic neuropathy), macroglossia (pathognomonic). Staging: elevated troponin + NT-proBNP = advanced cardiac involvement (Mayo Stage III). Start Dara-CyBorD. Diuretics for volume overload but use cautiously (preload-dependent). Midodrine for orthostatic hypotension. Avoid digoxin.
Pimp Questions
❓ Why does amyloidosis cause low voltage on ECG despite thick walls on echo?
In HCM, the thick walls are due to myocyte hypertrophy, which increases electrical mass and produces high voltage. In amyloidosis, the thick walls are due to amyloid infiltration between myocytes — the amyloid protein is electrically inert and actually insulates the myocardium, reducing the electrical signal. This creates the classic voltage-mass discordance: thick walls + low voltage = amyloid (not HCM).
❓ Why is digoxin dangerous in cardiac amyloidosis?
Digoxin binds to amyloid fibrils in the myocardium, leading to tissue accumulation and toxicity even at "therapeutic" serum levels. Patients with cardiac amyloidosis are exquisitely sensitive to digoxin and can develop fatal arrhythmias. This is a classic pharmacology teaching point — always avoid digoxin in amyloid cardiomyopathy.
❓ What is the significance of macroglossia in amyloidosis?
Macroglossia is pathognomonic for AL amyloidosis — it does not occur in AA or ATTR types. Present in ~10-15% of AL patients. It is virtually diagnostic when seen in the right clinical context. Look for tooth indentations on the lateral tongue edges. Can also cause dysphagia and obstructive sleep apnea.
❓ How does the ANDROMEDA trial change AL amyloidosis treatment?
ANDROMEDA (NEJM 2021) showed that adding daratumumab (anti-CD38) to CyBorD (bortezomib, cyclophosphamide, dexamethasone) significantly improved hematologic complete response (53% vs 18%) and cardiac and renal organ response rates. Dara-CyBorD is now the standard first-line regimen for newly diagnosed AL amyloidosis.
📋 Summary
Summary
Diagnosis
Congo red stain: apple-green birefringence. Fat pad aspirate is least invasive.
Classic Clue
Low voltage ECG + thick walls echo = amyloid (HCM = thick walls + HIGH voltage).
AL Treatment
Dara-CyBorD (ANDROMEDA). Auto-SCT if eligible. Cardiac = poor prognosis.
AA Treatment
Treat underlying inflammation (RA, Crohn, FMF). Reduce SAA levels.
Avoid
Digoxin (binds amyloid = toxicity). Aggressive diuresis (preload-dependent).
Pathognomonic
Macroglossia = AL amyloidosis. Does not occur in AA or ATTR.
Fat Embolism Syndrome
Classic triad: hypoxemia + neurological changes + petechial rash, occurring 24-72h after long bone fractures. Clinical diagnosis with no definitive lab test. Treatment is supportive. The petechial rash is the most specific finding but appears in only ~50% of cases.
🔍 Overview
Overview
Fat embolism syndrome (FES) occurs when fat globules enter the venous system, leading to pulmonary and systemic embolization with an inflammatory cascade. Classic triad: (1) hypoxemia/respiratory distress, (2) neurological changes (confusion, AMS), (3) petechial rash. Onset is typically 24-72 hours after the inciting event. Incidence: up to 10% of long bone fractures, but clinically significant FES is less common (~1-3%).
Causes
- Long bone fractures — most common cause, especially femur and tibia
- Orthopedic surgery — intramedullary nailing, joint arthroplasty
- Multiple fractures / polytrauma — risk increases with number of fractures
- Liposuction
- Burns, pancreatitis, sickle cell fat marrow necrosis (rare causes)
Pathophysiology
Fat globules from bone marrow enter the venous system through disrupted medullary vessels. In the lungs, fat is hydrolyzed by lipase into free fatty acids, which cause endothelial damage, inflammation, and increased capillary permeability (chemical pneumonitis). Fat also passes through the pulmonary vasculature or a PFO into systemic circulation, causing CNS and skin manifestations.
🚨 Management
Treatment
SUPPORTIVE — there is no specific treatment for fat embolism syndrome.
- Supplemental oxygen — high-flow nasal cannula, NIPPV, or mechanical ventilation as needed
- Mechanical ventilation — lung-protective ventilation if ARDS develops (low tidal volume 6 mL/kg IBW, PEEP, plateau pressure <30 cmH2O)
- Fluid resuscitation — maintain intravascular volume. Avoid hypovolemia (worsens tissue hypoperfusion).
- Early fracture fixation — reduces ongoing fat embolization. Definitive surgical fixation within 24h when possible.
- Supportive ICU care — vasopressors if hemodynamically unstable, seizure management if needed.
Prevention
- Early fracture stabilization — most important preventive measure. External fixation or definitive internal fixation within 24h reduces FES incidence.
- Corticosteroids for PREVENTION: Methylprednisolone 1.5 mg/kg IV q8h x 3 doses before surgery — some evidence of benefit in high-risk patients (bilateral femur fractures, polytrauma). Not universally adopted due to mixed trial results. Schonfeld, Ann Intern Med 1983
Fat embolism syndrome is a CLINICAL diagnosis — there is no definitive lab test. The triad of hypoxemia + neurological changes + petechial rash 24-72h after a long bone fracture is classic. The petechial rash (non-palpable, typically on chest, axillae, and conjunctivae) is the most specific finding but appears in only ~50% of cases. Gurd criteria are commonly referenced.
🧪 Workup
Diagnostic Workup
FES is a clinical diagnosis. No single test is diagnostic. The following support the diagnosis:
- ABG — hypoxemia (PaO2 <60 mmHg). Often the earliest finding.
- CXR — bilateral diffuse infiltrates, "snowstorm" pattern. May take 12-24h to develop. Non-specific.
- CBC — thrombocytopenia (platelet consumption), anemia (from hemolysis by free fatty acids)
- Lipase — may be elevated (fat hydrolysis)
- CT-PA — primarily to rule out pulmonary embolism (PE and FES can both occur after fractures/surgery). FES does NOT show filling defects.
- Retinal exam — cotton-wool spots, petechiae, fat emboli visible in retinal vessels (Purtscher-like retinopathy)
- Bronchoalveolar lavage (BAL) — may show fat-laden macrophages (oil red O stain), but this finding is NOT specific for FES (can occur in other conditions).
- MRI brain — if neurological symptoms prominent. May show "starfield" pattern of punctate T2/FLAIR bright lesions (microembolic infarcts).
Gurd Criteria (Clinical Diagnosis)
Requires at least 1 major + 4 minor criteria, OR 2 major criteria:
- Major: Axillary/subconjunctival petechiae, hypoxemia (PaO2 <60), CNS depression, pulmonary edema
- Minor: Tachycardia, fever, retinal changes, fat in urine, thrombocytopenia, elevated ESR, fat globules in sputum
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Methylprednisolone | Prevention (high-risk) | 1.5 mg/kg IV q8h x 3 doses preop | Some evidence for prophylaxis in high-risk long bone fractures. Not universally adopted. Start before surgical fixation. Schonfeld, Ann Intern Med 1983 |
| Heparin | VTE prophylaxis | 5000 units SQ q8h or enoxaparin 40 mg SQ daily | Standard VTE prophylaxis in trauma patients. Does NOT treat FES specifically, but prevents concomitant VTE. |
| Norepinephrine | Hemodynamic support | 0.1-2 mcg/kg/min IV | If hypotension from RV failure or distributive shock component. Titrate to MAP >65. |
| Levetiracetam (Keppra) | Seizure management | 500-1000 mg IV BID | If seizures from cerebral fat embolism. No specific seizure prophylaxis indicated without seizure activity. |
Note: Treatment is predominantly supportive. No specific pharmacotherapy has proven benefit for established FES.
📊 Monitoring
Monitoring
- Continuous pulse oximetry — hypoxemia is often the earliest sign. O2 sat drop in a trauma patient 24-72h post-fracture should raise suspicion.
- ABG — q6-12h if developing respiratory failure. Monitor for worsening hypoxemia and need for escalation.
- CBC q12h — trending platelets (thrombocytopenia) and hemoglobin (hemolysis). Nadir typically at 48-72h.
- Neurologic exam — serial assessments. AMS can range from confusion to coma. GCS trending.
- CXR daily — track bilateral infiltrates. Monitor for progression to ARDS.
- Skin exam — check chest, axillae, conjunctivae for petechiae q shift. Often transient (may last only 24-48h).
- Urine output — monitor for renal dysfunction. Fat emboli can cause AKI.
🏥 Rounds
Sample Presentation
Mr. Rodriguez is a 24-year-old man admitted 48 hours ago after a motor vehicle collision with bilateral femoral shaft fractures, now s/p external fixation. Overnight he developed acute respiratory distress, confusion, and tachycardia. VS: T 38.5, HR 122, RR 28, BP 110/70, SpO2 82% on RA. Exam: confused, GCS 13 (E3V4M6), petechial rash across the chest and bilateral axillae, bilateral crackles on lung exam. Labs: PaO2 52 on ABG, platelets dropped from 210 to 98, Hgb from 11 to 8.5. CXR: bilateral diffuse infiltrates. CT-PA negative for PE.
Key Points: Classic fat embolism syndrome — classic triad of hypoxemia + AMS + petechial rash, onset 48h after bilateral femur fractures. CT-PA negative rules out PE. Treatment is SUPPORTIVE: high-flow O2 or intubation if worsening (PaO2 52), IVF resuscitation, trending platelets and neurologic status. Plan for definitive fracture fixation (intramedullary nailing) once stabilized. Most cases self-resolve within 72h with supportive care.
Pimp Questions
❓ What is the classic timing and distribution of the petechial rash in FES?
The rash appears 24-72 hours after the fracture and is characteristically found on the chest, axillae, and conjunctivae — areas with high capillary density. The petechiae are non-palpable (unlike vasculitis) and often transient (may disappear within 24-48h). While the most specific finding, petechiae appear in only ~50% of FES cases and can be easily missed if not specifically examined for.
❓ How do you distinguish fat embolism from PE in a trauma patient?
Both can cause hypoxemia post-fracture. Key differences: (1) Timing — PE usually >3-5 days; FES 24-72h, (2) CT-PA — PE shows filling defects; FES shows NO filling defects, (3) Rash — petechial rash is specific to FES, (4) Thrombocytopenia and anemia — more characteristic of FES, (5) AMS — more prominent in FES (cerebral fat emboli). CT-PA should be obtained to rule out PE, as treatments differ dramatically.
❓ Why does early fracture fixation reduce fat embolism risk?
Unstabilized fractures allow ongoing release of fat and marrow contents from the disrupted bone into the venous system with every movement. Early fixation stabilizes the fracture site, reducing mechanical disruption and ongoing fat release. The ETC (Early Total Care) concept — definitive fixation within 24h — has been shown to reduce FES incidence, ARDS, and multiorgan failure in trauma patients.
❓ Why are bilateral femur fractures the highest risk for FES?
The femur has a large medullary cavity with abundant fat and marrow. Bilateral femur fractures double the amount of exposed marrow and fat available for embolization. The volume of fat released correlates with FES severity. Risk increases further with intramedullary reaming during nailing (pressurizes the canal, forcing fat into the venous system). Some surgeons use reamed nailing with venting to reduce this risk.
📋 Summary
Summary
Classic Triad
Hypoxemia + AMS + petechial rash, 24-72h after long bone fracture.
Diagnosis
Clinical diagnosis. No definitive test. CT-PA to rule out PE. Gurd criteria.
Treatment
SUPPORTIVE. O2, ventilation (lung-protective if ARDS), fluids, early fracture fixation.
Rash
Petechiae on chest/axillae/conjunctivae. Most specific finding but only ~50% of cases.
Prevention
Early fracture fixation. ?Methylprednisolone prophylaxis in high-risk cases.
Prognosis
Most cases self-resolve with supportive care. Mortality ~5-15% in severe cases (ARDS).
Malignant Hyperthermia
Rare but lethal pharmacogenetic disorder triggered by volatile anesthetics or succinylcholine. Rising ETCO2 is the earliest sign. Dantrolene is the ONLY specific treatment. Mortality exceeds 70% without treatment, but drops below 5% with early dantrolene.
🔍 Overview
Overview
Malignant hyperthermia (MH) is a rare, life-threatening pharmacogenetic disorder caused by mutations in the RYR1 gene (ryanodine receptor on sarcoplasmic reticulum). Triggered by volatile anesthetics (sevoflurane, desflurane, isoflurane) or succinylcholine. The mutation causes uncontrolled calcium release from the sarcoplasmic reticulum into the myoplasm, leading to sustained muscle contraction, hypermetabolism, and multi-organ failure.
Triggers
- Volatile anesthetics: sevoflurane, desflurane, isoflurane, halothane (most potent trigger)
- Succinylcholine (depolarizing neuromuscular blocker)
- NOT triggered by: non-depolarizing agents (rocuronium, vecuronium), propofol, benzodiazepines, nitrous oxide, opioids, stress alone, exercise alone
Pathophysiology
RYR1 mutation causes defective ryanodine receptor on skeletal muscle sarcoplasmic reticulum. Triggering agent causes uncontrolled calcium release into myoplasm, leading to sustained muscle contraction, exponentially increased oxygen consumption and CO2 production, massive ATP hydrolysis, and heat generation. This cascade produces hypercarbia, metabolic acidosis, rhabdomyolysis, hyperkalemia, and eventually cardiac arrest if untreated.
Presentation
- Earliest sign: Rising ETCO2 (unexpectedly, often >60 mmHg despite adequate ventilation)
- Masseter spasm (trismus after succinylcholine) — may be the first clinical sign
- Rapidly rising temperature — can reach >40°C in minutes (1-2°C every 5 min). Temperature rise is often a LATE sign.
- Muscle rigidity — generalized ("board-like")
- Tachycardia, tachypnea — if spontaneously breathing
- Metabolic acidosis — severe mixed respiratory and metabolic
- Hyperkalemia — from rhabdomyolysis and cellular lysis
- Rhabdomyolysis — CK >20,000 IU/L, dark urine (myoglobinuria)
- DIC — late complication
- Cardiac arrhythmias — from hyperkalemia, acidosis, and hyperthermia
🚨 Management
Immediate Management
STOP all triggering agents IMMEDIATELY. Discontinue volatile anesthetic. Turn off vaporizer. Disconnect circuit from anesthesia machine. Hyperventilate with 100% O2 at high fresh gas flows (>10 L/min). Do NOT waste time changing the circuit — just flush with high-flow O2.
- Dantrolene (Dantrium) 2.5 mg/kg IV push, repeat every 5 minutes until symptoms resolve. No maximum dose in an emergency (typically up to 10 mg/kg total, but more may be needed).
- Call for HELP — you need multiple people to mix dantrolene.
- Active cooling: ice packs to groin/axillae/neck, cold IV normal saline, cooling blankets, iced gastric/bladder lavage if refractory. Target temp <38.5°C, then STOP active cooling (risk of overshoot hypothermia).
- Treat hyperkalemia: calcium gluconate 30 mL of 10% IV (or calcium chloride 10 mL), insulin 10 units + D50 50 mL IV, sodium bicarbonate 1-2 mEq/kg. Do NOT use succinylcholine for intubation.
- Treat acidosis: sodium bicarbonate 1-2 mEq/kg IV for pH <7.2.
- Treat arrhythmias: amiodarone for VT. Do NOT use calcium channel blockers (fatal interaction with dantrolene causing hyperkalemia and cardiovascular collapse).
Dantrolene is the ONLY specific treatment. Every OR must have it stocked. Know where it is BEFORE you need it. Each vial is 20 mg — a 70 kg patient needs ~9 vials for the first dose. It takes time to reconstitute (each vial requires 60 mL sterile water) — call for help immediately. Newer formulations (Ryanodex) come as 250 mg/vial requiring only 5 mL to reconstitute.
Clinical Example: A 25-year-old male undergoing appendectomy under general anesthesia with sevoflurane. 30 minutes into the case, the anesthesiologist notices ETCO2 climbing from 38 to 72 despite increasing minute ventilation. HR jumps to 130. Jaw is rigid. Temperature probe shows 39.2°C and rising. This is MH until proven otherwise — STOP sevoflurane, call for dantrolene, hyperventilate with 100% O2, and begin active cooling.
🧪 Workup
Diagnostic Workup
MH is a clinical diagnosis in the acute setting. Do not delay treatment for labs.
- ETCO2 — earliest sign in the OR. Rising unexpectedly despite adequate ventilation.
- ABG — severe mixed metabolic and respiratory acidosis (pH <7.2, pCO2 >60, base deficit >-8, lactate elevated)
- CK (creatine kinase) — massively elevated (>20,000 IU/L). Peaks at 12-24h. Serial CK q6h.
- BMP — hyperkalemia (from rhabdomyolysis), initially hypercalcemia then hypocalcemia, renal function (AKI from myoglobinuria)
- Myoglobin — serum and urine. Dark/cola-colored urine = myoglobinuria.
- Coagulation panel — PT, PTT, fibrinogen, D-dimer (DIC screen)
- Lactate — markedly elevated (hypermetabolic state)
- Core temperature — continuous monitoring (esophageal or rectal preferred)
Post-Crisis — Confirmatory Testing
- Caffeine-halothane contracture test (CHCT) — gold standard for MH susceptibility. Requires a muscle biopsy (usually vastus lateralis). Performed at specialized MH centers. Sensitivity ~97%, specificity ~78%.
- Genetic testing — RYR1 mutation analysis. If positive, confirms susceptibility. But a negative result does NOT rule it out (only ~50-70% of MH families have identifiable mutations).
- Screen first-degree relatives — autosomal dominant inheritance with variable penetrance.
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Dantrolene (Dantrium) | SPECIFIC treatment for MH | 2.5 mg/kg IV push, repeat q5min PRN | No max dose in crisis. Each 20 mg vial needs 60 mL sterile water to reconstitute. Typical total 10 mg/kg. Continue 1 mg/kg IV q6h x 24-48h after crisis to prevent recrudescence. |
| Dantrolene (Ryanodex) | Newer formulation | 2.5 mg/kg IV push | 250 mg/vial, reconstitutes in only 5 mL. Much faster preparation. Single vial may cover initial dose for most patients. |
| Calcium gluconate 10% | Hyperkalemia cardioprotection | 30 mL (3 amps) IV over 5-10 min | Stabilizes cardiac membrane. Does not lower K+. |
| Regular insulin + D50 | Hyperkalemia treatment | 10 units insulin IV + 50 mL D50 | Drives K+ intracellularly. Check glucose q1h. |
| Sodium bicarbonate | Severe acidosis / hyperK | 1-2 mEq/kg IV | For pH <7.2. Also helps drive K+ intracellularly. |
| Amiodarone | Ventricular arrhythmias | 150 mg IV over 10 min, then 1 mg/min | For VT/VF. Do NOT use calcium channel blockers (lethal interaction with dantrolene). |
NEVER use calcium channel blockers (verapamil, diltiazem) with dantrolene — combination causes fatal hyperkalemia and cardiovascular collapse. Use amiodarone or lidocaine for arrhythmias instead.
📊 Monitoring
Monitoring
- Continuous ETCO2 — most sensitive early indicator. Target normalization (<40 mmHg).
- Core temperature — continuous (esophageal or rectal). Target <38.5°C. Stop active cooling at 38°C to prevent overshoot.
- ABG q30-60 min during acute crisis — trend pH, pCO2, lactate, K+.
- CK q6h x 24h — peak at 12-24h. If >10,000, aggressive IV hydration for renal protection.
- Urine output — target >2 mL/kg/h to prevent myoglobin-induced AKI. Consider mannitol or bicarb drip if myoglobinuria.
- BMP q4-6h — potassium, calcium, creatinine trending.
- Coags q6-12h — DIC surveillance (falling fibrinogen, rising D-dimer, dropping platelets).
- Monitor for recrudescence — MH can recur in 25% of cases within 24-36h. Continue dantrolene 1 mg/kg q6h x 24-48h. Keep in monitored bed (ICU).
🏥 Rounds
Sample Presentation
Mr. Thompson is a 32-year-old male undergoing laparoscopic cholecystectomy under general anesthesia with sevoflurane. 45 minutes into the case, ETCO2 rose from 36 to 78 mmHg despite increasing minute ventilation. HR 142, BP 90/60. Jaw rigidity noted. Temperature probe: 39.8°C and rising rapidly. Volatile anesthetic was immediately discontinued, hyperventilation with 100% O2 initiated, and dantrolene 2.5 mg/kg IV push was given. After 3 doses (total 7.5 mg/kg), ETCO2 began trending down. Active cooling with ice packs and cold NS achieved temp <38.5°C. Labs: CK 45,000, K+ 6.8, pH 7.12, lactate 14. Treated hyperK with calcium, insulin/glucose, and bicarb. Now in ICU on dantrolene 1 mg/kg q6h.
Key Points: Classic MH presentation triggered by sevoflurane. Rising ETCO2 was the earliest sign. Immediate dantrolene was life-saving. Now monitoring for recrudescence (25% risk within 24-36h), renal injury from rhabdomyolysis (CK 45,000 — targeting UOP >2 mL/kg/h), and DIC. Will need genetic counseling and screening of first-degree relatives.
Pimp Questions
❓ What is the earliest sign of malignant hyperthermia in the OR?
Rising ETCO2 (end-tidal CO2). This is often the earliest and most sensitive sign, reflecting the massive hypermetabolic state and increased CO2 production. Temperature elevation is often a LATE sign. The ETCO2 may rise to >60-80 mmHg despite adequate ventilation.
❓ What is the underlying mechanism of malignant hyperthermia?
Uncontrolled calcium release from the sarcoplasmic reticulum via defective ryanodine receptors (RYR1 mutation). The massive intracellular calcium causes sustained muscle contraction, ATP depletion, heat generation, and a hypermetabolic state with exponentially increased O2 consumption and CO2 production.
❓ Can you use succinylcholine for intubation in a patient with known MH susceptibility?
NO. Succinylcholine is a known trigger for MH. Use rocuronium (non-depolarizing agent) instead. Rocuronium can be reversed with sugammadex. All non-depolarizing neuromuscular blockers are safe in MH-susceptible patients.
📋 Summary
Summary
Trigger
Volatile anesthetics (sevoflurane, desflurane, isoflurane) and succinylcholine. RYR1 mutation.
Earliest Sign
Rising ETCO2 despite adequate ventilation. Temperature rise is a LATE sign.
Treatment
STOP trigger + Dantrolene 2.5 mg/kg IV push q5min. No max dose. Active cooling. Treat hyperK.
Key Pearl
Each dantrolene vial = 20 mg. A 70 kg patient needs ~9 vials for first dose. Call for help early.
Avoid
Calcium channel blockers (fatal interaction with dantrolene). Use amiodarone for arrhythmias.
Recrudescence
25% recurrence within 24-36h. Continue dantrolene 1 mg/kg q6h x 24-48h. ICU monitoring.
Acute Liver Failure
Coagulopathy (INR ≥1.5) + hepatic encephalopathy + no prior liver disease + illness <26 weeks. NAC improves transplant-free survival even in non-acetaminophen ALF. Contact transplant center EARLY. Do NOT correct INR prophylactically.
🔍 Overview
Definition
Acute liver failure (ALF) is defined by the triad: (1) Coagulopathy (INR ≥1.5), (2) Hepatic encephalopathy (any grade), and (3) No prior liver disease, with illness duration <26 weeks. It is a medical emergency with mortality >50% without transplant in many etiologies.
Causes
- Acetaminophen (paracetamol) — #1 cause in US/UK. Best prognosis of all causes. Often unintentional (supratherapeutic dosing).
- Viral hepatitis — HAV, HBV (most common worldwide), HEV (especially in pregnancy)
- Autoimmune hepatitis — can present fulminantly
- Wilson disease — suspect in young patients with Coombs-negative hemolytic anemia + ALF
- Budd-Chiari syndrome — hepatic vein thrombosis
- Drug-induced — isoniazid, phenytoin, statins, herbal supplements, anti-TB drugs
- Pregnancy-related — HELLP syndrome, acute fatty liver of pregnancy (AFLP)
- Ischemic hepatitis — "shock liver" from hypoperfusion
- Mushroom poisoning — Amanita phalloides (death cap)
- Indeterminate — ~20% remain without identified cause
Classification by Onset
- Hyperacute: 0-7 days (acetaminophen, ischemic). Often better prognosis with higher chance of spontaneous recovery.
- Acute: 8-28 days
- Subacute: 29 days to 26 weeks (worst prognosis, less cerebral edema but more portal hypertension)
🚨 Management
Immediate Management
Give NAC to ALL acute liver failure — not just acetaminophen. Lee, Gastroenterology 2009 showed improved transplant-free survival in non-acetaminophen ALF (Grades I-II HE).
- N-acetylcysteine (NAC) — IV protocol: 150 mg/kg over 1h, then 50 mg/kg over 4h, then 100 mg/kg over 16h. Continue until INR <1.5 or transplant.
- ICU admission — all ALF patients need ICU-level monitoring.
- Contact transplant center EARLY — do not wait for deterioration. Transfer may become impossible once cerebral edema develops.
- Intubate for Grade III-IV encephalopathy — airway protection. Avoid propofol if hemodynamically unstable.
🔄 Updated Practice: Old teaching: N-acetylcysteine (NAC) only for acetaminophen overdose. Current practice: NAC improves transplant-free survival in ALL causes of acute liver failure, not just acetaminophen (Lee, Gastroenterology 2009). The benefit is greatest in early hepatic encephalopathy (grades I-II). Give NAC to every ALF patient regardless of etiology — there is no reason to withhold it.
Do NOT correct INR prophylactically. INR is your prognostic marker. Only give FFP/PCC if actively bleeding. Correcting INR blinds you to the trajectory and removes your ability to assess for improvement or need for transplant.
King's College Criteria (Transplant Listing)
Acetaminophen ALF
- pH <7.3 after resuscitation, OR
- All three: INR >6.5 + Creatinine >3.4 mg/dL + Grade III-IV HE
Non-Acetaminophen ALF
- INR >6.5 alone, OR
- Any 3 of: age <10 or >40, non-A/non-B hepatitis or drug etiology, jaundice >7 days before HE onset, INR >3.5, bilirubin >17.5 mg/dL
Complications Management
- Cerebral edema: Elevate HOB to 30°. Mannitol 0.5-1 g/kg IV (if serum osm <320) or hypertonic saline (23.4%) for acute herniation. Avoid hyperthermia. Target Na 145-155 mEq/L with hypertonic saline prophylaxis.
- Hypoglycemia: D10 continuous drip. Check glucose q1-2h. Common and life-threatening (failed hepatic gluconeogenesis).
- Coagulopathy: Only treat if actively bleeding. Paradoxically balanced hemostasis (low pro- and anti-coagulant factors). Routine FFP is harmful.
- Infection: Low threshold for empiric antibiotics. Surveillance cultures daily. Up to 80% develop bacterial infection, 30% fungal.
- AKI: Common (50-70%). Avoid nephrotoxins. CRRT preferred over intermittent HD (less hemodynamic instability, better ICP control).
🧪 Workup
Diagnostic Workup — Find the Cause
Etiology-specific workup should be sent simultaneously on arrival:
- Acetaminophen level — check even if not suspected (unintentional overdose is common)
- Viral serologies: HAV IgM, HBsAg, HBc IgM, HCV RNA (not just anti-HCV), HEV IgM (if pregnant or endemic area)
- Autoimmune: ANA, anti-smooth muscle antibody (ASMA), IgG levels
- Wilson disease: Ceruloplasmin (low), 24h urine copper, slit-lamp exam (Kayser-Fleischer rings). Alkaline phosphatase:bilirubin ratio <4 + AST:ALT ratio >2.2 suggests Wilson.
- Budd-Chiari: Doppler ultrasound of hepatic veins
- Pregnancy test — HELLP, AFLP
- Drug screen / toxicology — urine drug screen, medication reconciliation
- HSV — HSV PCR if immunocompromised or unexplained (consider empiric acyclovir)
Baseline Labs
- CBC, CMP (LFTs, BMP), coags (INR, PT, fibrinogen), lactate, ammonia level, lipase
- ABG (acid-base status), phosphate (prognostic — rising phosphate in acetaminophen ALF = failure to regenerate)
- Blood type and screen (anticipate possible transplant)
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| N-acetylcysteine (NAC) | ALL ALF — first-line | 150 mg/kg IV over 1h → 50 mg/kg over 4h → 100 mg/kg over 16h | Continue until INR <1.5 or transplant. Improves transplant-free survival even in NON-acetaminophen ALF. Lee, Gastroenterology 2009 |
| Mannitol 20% | Cerebral edema / herniation | 0.5-1 g/kg IV bolus | Use if serum osm <320. Can repeat x1. Monitor serum osmolality. |
| Hypertonic saline (3% or 23.4%) | Cerebral edema prophylaxis | 3% NaCl infusion targeting Na 145-155 | Prophylactic hypernatremia reduces cerebral edema incidence. 23.4% (30 mL) for acute herniation. |
| Dextrose 10% (D10) | Hypoglycemia prevention | Continuous drip at 75-100 mL/h | Check glucose q1-2h. Hepatic gluconeogenesis fails — hypoglycemia is common and dangerous. |
| Lactulose | Hepatic encephalopathy | 30 mL PO/NG q2h titrated to 3-4 BMs/day | Role in ALF is less established than in cirrhotic HE, but often given. Avoid excessive diarrhea (volume depletion). |
| Piperacillin-tazobactam | Empiric antibiotics | 4.5 g IV q6h | Low threshold. Infection in up to 80%. Fungal prophylaxis (fluconazole) may be warranted. |
📊 Monitoring
Monitoring
- INR, LFTs q6-12h — trending INR is your prognostic window. Rising INR despite NAC = worsening. Falling INR = recovery.
- Glucose q1-2h — hypoglycemia is life-threatening and common. D10 drip.
- Ammonia level q12-24h — levels >150-200 mcmol/L associated with cerebral herniation.
- Neuro checks q1-2h — grade encephalopathy (West Haven criteria). Grade III-IV requires intubation.
- Lactate q6-12h — rising lactate in acetaminophen ALF is a poor prognostic sign.
- BMP q6h — K+, Na+, creatinine, phosphate trending.
- Urine output — target >0.5 mL/kg/h. AKI develops in 50-70%.
- King's College Criteria — reassess at least daily for transplant listing urgency.
- ICP monitoring — controversial. Consider in Grade III-IV HE if transplant candidate. Target CPP >60 mmHg, ICP <20 mmHg.
🏥 Rounds
Sample Presentation
Mrs. Patel is a 28-year-old woman presenting with 5 days of nausea, vomiting, and jaundice, now with confusion and asterixis. She reports taking "extra-strength Tylenol" for back pain, approximately 4-6 g/day for the past week. VS: T 37.2, HR 110, BP 95/60, RR 22. Labs: ALT 8,400, AST 10,200, total bilirubin 8.5, INR 4.8, Cr 2.1, acetaminophen level 45 mcg/mL, pH 7.28, lactate 6.2, ammonia 98. Hepatitis serologies pending. NAC drip started immediately. Transplant hepatology notified.
Key Points: ALF from supratherapeutic acetaminophen (unintentional). Meets ALF criteria: INR ≥1.5 + encephalopathy + no prior liver disease. NAC is the priority. Do NOT correct INR unless actively bleeding. Apply King's criteria serially: pH 7.28 (close to 7.3 cutoff) — if pH drops below 7.3 after resuscitation, meets criteria for transplant listing. Monitor glucose, ammonia, and neuro status closely. Acetaminophen ALF has the best prognosis of all causes if treated promptly.
Pimp Questions
❓ Why do we give NAC in non-acetaminophen acute liver failure?
The Lee 2009 study showed that IV NAC improved transplant-free survival in non-acetaminophen ALF, specifically in patients with Grade I-II encephalopathy (52% vs 30% survival). Mechanism likely relates to antioxidant properties and improved hepatic microcirculation.
❓ Why should you NOT correct INR prophylactically in ALF?
INR is your single best prognostic marker in ALF. Giving FFP/PCC masks the trajectory — you cannot tell if the liver is recovering or worsening. Paradoxically, ALF patients have balanced hemostasis (both pro- and anti-coagulant factors are reduced). They are NOT at increased bleeding risk despite high INR. Only give blood products if actively bleeding or before an invasive procedure.
❓ How do you suspect Wilson disease in ALF?
Young patient (<40) + ALF + Coombs-negative hemolytic anemia + very low alkaline phosphatase (AP:bilirubin ratio <4) + AST:ALT ratio >2.2 + low ceruloplasmin. Wilson ALF has a near-100% mortality without transplant — list immediately.
📋 Summary
Summary
Definition
INR ≥1.5 + encephalopathy + no prior liver disease + <26 weeks.
#1 Cause
Acetaminophen (US/UK). Best prognosis. Often unintentional supratherapeutic dosing.
First-Line
NAC for ALL ALF (not just acetaminophen). 150/50/100 mg/kg IV protocol.
Do NOT
Correct INR prophylactically. It is your prognostic marker. Only give FFP if actively bleeding.
Transplant
Apply King's College Criteria serially. Contact transplant center EARLY.
Complications
Cerebral edema, hypoglycemia (D10 drip), coagulopathy, infection (80%), AKI (50-70%).
Renal Transplant Medicine
Immunosuppression regimens, rejection types, infection timelines, and the critical rule: any transplant patient with rising creatinine is rejection until proven otherwise.
🔍 Overview
Immunosuppression
Standard regimen has three components:
- Induction: Basiliximab (IL-2 receptor antagonist, low immunologic risk) or Anti-thymocyte globulin (ATG) (high immunologic risk, repeat transplant, sensitized patients)
- Maintenance (triple therapy):
- Tacrolimus (Prograf) — calcineurin inhibitor. Target trough varies by time post-transplant: 8-12 ng/mL (month 0-3), 6-10 ng/mL (month 3-12), 4-8 ng/mL (after year 1).
- Mycophenolate (CellCept) — 1000 mg PO BID (or mycophenolic acid 720 mg BID). Antiproliferative agent.
- Prednisone — high dose post-op, taper to 5 mg/day by month 3-6. Some centers do steroid-free protocols.
Types of Rejection
- Hyperacute rejection: Minutes to hours. Preformed antibodies against donor ABO/HLA. Immediate graft thrombosis and loss. Prevented by crossmatch testing. Essentially eliminated by modern crossmatching.
- Acute cellular rejection (ACR): Weeks to months. T-cell mediated. Most common type. Responds well to pulse steroids (methylprednisolone 500 mg IV x 3 days) or ATG for steroid-resistant cases.
- Acute antibody-mediated rejection (AMR): B-cell/antibody mediated. Donor-specific antibodies (DSA). Treat with plasmapheresis + IVIG + rituximab. Harder to treat than ACR.
- Chronic rejection: Months to years. Progressive interstitial fibrosis and tubular atrophy (IF/TA). No effective treatment. Leads to slow graft loss.
Infection Timeline
- Month 0-1: Surgical site infections, UTI, donor-derived infections, CMV (especially D+/R-)
- Month 1-6: Opportunistic infections — CMV (most common), BK virus (nephropathy), PJP (all on prophylaxis during this window)
- Month 6+: Community-acquired infections, late CMV (after prophylaxis stopped), BK nephropathy, Listeria, Nocardia
🚨 Management
Rising Creatinine in a Transplant Patient
Any transplant patient with rising creatinine = rejection until proven otherwise. Get tacrolimus level STAT, UA, donor-specific antibodies, and call transplant nephrology. Do NOT just "watch the creatinine."
Differential for Rising Creatinine
- Rejection (cellular or antibody-mediated)
- Tacrolimus toxicity (check trough level — supratherapeutic)
- BK virus nephropathy (check BK PCR)
- Obstruction (ureteral stricture, lymphocele — renal US)
- Pre-renal (dehydration, NSAID use, ACE/ARB)
- Recurrent disease (FSGS, IgA, diabetic nephropathy)
- CNI nephrotoxicity (chronic tacrolimus injury)
Rejection Treatment
- Acute cellular rejection: Methylprednisolone 500 mg IV daily x 3 days. If steroid-resistant, ATG.
- Antibody-mediated rejection: Plasmapheresis (5-7 sessions) + IVIG 100 mg/kg after each session + Rituximab 375 mg/m2. Consider bortezomib (Velcade) for refractory cases.
- BK nephropathy: Reduce immunosuppression (lower tacrolimus target, decrease mycophenolate). No specific antiviral. Cidofovir and leflunomide have been tried.
Clinical Example: A 55-year-old man 6 months post-renal transplant presents with Cr rising from 1.4 to 2.3 over 2 weeks. He feels well. Tacrolimus trough 4.2 (subtherapeutic). BK PCR negative. UA bland. DSA panel shows new anti-HLA antibodies. Renal biopsy: C4d positive peritubular capillaritis. Diagnosis: acute antibody-mediated rejection. Initiate plasmapheresis + IVIG + rituximab.
🧪 Workup
Workup for Rising Creatinine
- Tacrolimus trough — STAT. Supratherapeutic = CNI toxicity. Subtherapeutic = possible rejection.
- UA + urine culture — UTI is common post-transplant
- BK virus PCR — screen monthly for first 6 months, then q3 months. >10,000 copies = BK viremia requiring immunosuppression reduction.
- CMV PCR — if symptomatic or at high-risk period
- Donor-specific antibodies (DSA) — if AMR suspected
- Renal transplant ultrasound with Doppler — evaluate for hydronephrosis, perinephric collections (lymphocele, hematoma), vascular stenosis
- Transplant renal biopsy — gold standard for diagnosis. Banff classification. Indicated if creatinine rises >25% from baseline without clear cause.
Routine Surveillance Labs
- BMP, CBC, tacrolimus trough, LFTs, fasting glucose, lipid panel
- BK PCR monthly x 6 months, then q3 months x 2 years
- CMV PCR monthly if D+/R- (highest risk)
💊 Medications
Medications
| Drug | Class/Indication | Dose | Notes |
|---|---|---|---|
| Tacrolimus (Prograf) | CNI — maintenance | Varies; target trough 8-12 early, 4-8 late | Nephrotoxic, diabetogenic, tremor, hyperkalemia, hypomagnesemia. Many drug interactions (azoles increase levels, rifampin decreases). Check trough levels. |
| Mycophenolate (CellCept) | Antiproliferative — maintenance | 1000 mg PO BID | GI side effects (diarrhea, nausea). Bone marrow suppression (monitor CBC). Teratogenic. Reduce dose if BK viremia. |
| Prednisone | Corticosteroid — maintenance | Taper to 5 mg daily | Metabolic effects (hyperglycemia, osteoporosis, weight gain). Some centers do steroid withdrawal. |
| TMP-SMX (Bactrim) | PJP prophylaxis | 1 SS tab daily x 6-12 months | Also provides UTI prophylaxis and Toxoplasma, Nocardia, Listeria coverage. |
| Valganciclovir (Valcyte) | CMV prophylaxis | 900 mg PO daily x 3-6 months | For CMV D+/R- (highest risk) or D+/R+. Monitor CMV PCR. Can cause leukopenia. |
| Nystatin | Oral candida prophylaxis | 5 mL swish and swallow QID x 1-3 months | Prevent oral/esophageal candidiasis while on high-dose immunosuppression. |
📊 Monitoring
Monitoring
- Tacrolimus trough — check 2-3x/week early, then weekly, then monthly. Target varies by time post-transplant.
- BMP weekly initially — creatinine trending, electrolytes (hyperK from tacrolimus, hypoMg)
- CBC weekly — leukopenia (mycophenolate, valganciclovir), anemia, thrombocytopenia
- BK virus PCR monthly x 6 months, then q3 months x 2 years
- CMV PCR monthly for high-risk (D+/R-) during and after prophylaxis
- Fasting glucose — post-transplant diabetes (tacrolimus + steroids)
- Lipid panel — dyslipidemia common (tacrolimus, sirolimus)
- Cancer screening — skin checks annually (SCC risk 65-250x increased), cervical screening, colon cancer per guidelines. PTLD surveillance (EBV PCR if EBV D+/R-).
🏥 Rounds
Sample Presentation
Mr. Johnson is a 48-year-old man, 3 months post-deceased donor renal transplant for ESRD from IgA nephropathy. Presenting with creatinine rising from baseline 1.2 to 1.9 over 1 week. No symptoms. Tacrolimus trough: 5.1 (target 6-10, slightly low). BK PCR: negative. CMV PCR: negative. UA: bland. Renal US: no hydronephrosis, normal Doppler flows. DSA: negative. Given rising Cr without clear etiology and subtherapeutic tacrolimus, transplant nephrology recommended renal biopsy. Biopsy showed Banff 1A acute cellular rejection (tubulitis, interstitial inflammation). Started methylprednisolone 500 mg IV x 3 days. Tacrolimus dose increased to target trough 8-10.
Key Points: Rising creatinine in a transplant patient is rejection until proven otherwise. Subtherapeutic tacrolimus was the likely contributing factor. Biopsy is the gold standard. ACR responds well to pulse steroids. Increase maintenance immunosuppression and recheck creatinine in 48-72h.
Pimp Questions
❓ What are the types of rejection and their timelines?
Hyperacute: minutes (preformed antibodies, graft loss). Acute cellular: weeks-months (T-cell mediated, responds to steroids). Acute antibody-mediated: weeks-months (B-cell/DSA, treat with plasmapheresis/IVIG/rituximab). Chronic: months-years (IF/TA, no effective treatment).
❓ What infections occur in each post-transplant time period?
Month 0-1: Surgical site, UTI, donor-derived, early CMV. Month 1-6: CMV (most common), BK virus, PJP — all on prophylaxis. After month 6: Community-acquired, late CMV, BK nephropathy, PTLD.
❓ What is the most important first step when a transplant patient has a rising creatinine?
Check tacrolimus trough level STAT. Supratherapeutic = CNI nephrotoxicity (reduce dose). Subtherapeutic = risk factor for rejection. Then: UA, BK PCR, DSA, renal US. If no clear cause, biopsy. Call transplant nephrology early.
📋 Summary
Summary
Maintenance
Tacrolimus + Mycophenolate + Prednisone. Check tacrolimus trough regularly.
Rising Cr
Rejection until proven otherwise. Tac level STAT, BK PCR, DSA, US, biopsy if unclear.
ACR Treatment
Pulse methylprednisolone 500 mg IV x 3 days. ATG if steroid-resistant.
AMR Treatment
Plasmapheresis + IVIG + Rituximab. Harder to treat than ACR.
Prophylaxis
TMP-SMX (PJP), Valganciclovir (CMV), Nystatin (candida). Duration varies by risk.
Infections
0-1mo: surgical/UTI. 1-6mo: CMV, BK, PJP. 6mo+: community, late CMV, PTLD.
Palliative Extubation
Compassionate withdrawal of mechanical ventilation when goals of care shift to comfort. NOT euthanasia — removing a treatment that is no longer beneficial. Death may occur minutes to days after extubation. Titrate to comfort, not to death.
🔍 Overview
Overview
Palliative extubation (compassionate extubation, terminal wean) is the planned withdrawal of mechanical ventilation when the goals of care have shifted to comfort-focused measures. This is NOT euthanasia and is NOT physician-assisted death — it is the removal of a life-sustaining treatment that is no longer consistent with the patient's wishes or best interests. It is ethically and legally supported by every major medical society.
Death may occur minutes to days after extubation. Families need to understand this range. Some patients (especially those with intact respiratory drive on minimal settings) may survive for days or even be discharged to hospice.
Indications
- Patient/surrogate decision to transition to comfort care
- Terminal illness with no further curative options
- Goals of care no longer consistent with mechanical ventilation
- Advance directive specifying no prolonged mechanical ventilation
Ethical Framework
- There is no ethical or legal distinction between withholding and withdrawing treatment
- The intent is to relieve suffering, not to hasten death (principle of double effect)
- Patient autonomy: competent patients (or surrogates) have the right to refuse any medical treatment
🚨 Management
Pre-Extubation Preparation
- Family meeting: Ensure ALL key decision-makers are present (or via phone). Set clear expectations about the process and timeline. Death may occur in minutes or days.
- Discontinue monitors and alarms. The family should NOT hear alarms going off. Turn off telemetry, SpO2 monitor, ventilator alarms. Remove unnecessary lines (arterial line, etc.).
- Ensure comfort medications are at the bedside BEFORE extubation. Do not start the process until you have drawn up morphine, glycopyrrolate, and midazolam.
- Suction the oropharynx gently before extubation to minimize secretions.
- Wean ventilator settings: Reduce FiO2 to 21% and PEEP to 0 (or 5). This allows a more gradual transition rather than abrupt cessation.
- Pre-medicate: Give morphine 2-4 mg IV 10-15 minutes before extubation to prevent air hunger.
- Notify chaplain, social work if family desires.
The Process
- Remove restraints (patient should be free)
- Disconnect monitors (turn off all alarms)
- Suction oropharynx
- Reduce vent support gradually OR extubate directly (either approach is acceptable)
- Extubate: deflate cuff, remove ETT
- Apply oxygen via nasal cannula at 2-4 L (for COMFORT, not saturation monitoring)
- Assess comfort immediately — give morphine if any signs of distress
- Stay with the family (or have nursing present continuously)
- Pronounce when appropriate (no specific time requirement)
Titrate medications to COMFORT, not to respiratory rate or death. The goal is to relieve suffering. If the patient appears distressed (grimacing, accessory muscle use, tachypnea), give more medication. This is NOT hastening death — it is treating dyspnea. The principle of double effect applies: the intent is comfort, even if a foreseeable side effect is respiratory depression.
🧪 Workup
Pre-Extubation Checklist
There is no diagnostic "workup" per se, but a structured checklist is essential:
- Goals of care documented? — Written consent from surrogate or documented patient wishes (advance directive).
- Ethics consult needed? — If there is disagreement among family members or between team and family.
- Legal requirements met? — State-specific requirements for withdrawal of life-sustaining treatment. Two-physician concurrence in some jurisdictions.
- DNR/DNAR order written? — Essential before extubation. Prevents Code Blue being called.
- Unnecessary interventions discontinued? — Vasopressors, antibiotics, labs, blood draws, nutrition, scheduled medications not contributing to comfort.
- Comfort medications ordered and at bedside? — Morphine, glycopyrrolate, lorazepam, haloperidol, scopolamine patch.
- Family ready and present? — Ask if they want clergy, specific family members, or rituals before proceeding.
- Organ donation discussed? — OPO should be notified per hospital protocol (may have been already).
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Morphine | Dyspnea, pain | 2-5 mg IV q15min PRN | First-line for air hunger and pain. Titrate to comfort. No ceiling dose for comfort care. Start infusion at 2-5 mg/h if frequent boluses needed. Hydromorphone (Dilaudid) 0.5-1 mg IV is an alternative. |
| Glycopyrrolate (Robinul) | Secretions ("death rattle") | 0.2 mg IV q4h PRN | Anticholinergic — reduces new secretion production. Does NOT clear existing secretions (suction for that). Start early — prevention is easier than treatment. |
| Lorazepam (Ativan) | Agitation, air hunger, anxiety | 1-2 mg IV PRN q2-4h | Adjunct for anxiety and terminal restlessness. Can also help with air hunger refractory to opioids. |
| Haloperidol (Haldol) | Terminal delirium | 0.5-1 mg IV q4-6h PRN | For terminal agitation/delirium not controlled by benzodiazepines. Avoid in QTc prolongation. |
| Scopolamine patch | Secretions (long-acting) | 1-3 patches behind ear q72h | Takes 6-12h to take effect. Apply early if death rattle anticipated. Alternative to glycopyrrolate for sustained effect. |
Clinical Example: After extubation, the patient develops tachypnea to 28 and accessory muscle use. The family asks "Is he suffering?" You give morphine 4 mg IV. Within 5 minutes, RR decreases to 18, accessory muscle use resolves, and the patient appears comfortable. This is appropriate symptom management — you treated dyspnea, not the respiratory rate itself.
📊 Monitoring
Monitoring
- Comfort assessment — the ONLY vital sign that matters now. Observe for grimacing, accessory muscle use, restlessness, tachypnea as signs of distress.
- Do NOT monitor: SpO2, blood pressure, heart rate on monitors. These are turned off to avoid distressing the family with alarms and numbers.
- Secretion assessment: Listen for "death rattle" (gurgling with respirations). Treat with glycopyrrolate or scopolamine. Reassure family this is not choking or suffering.
- Medication effectiveness: After each dose, reassess in 10-15 minutes. If still distressed, redose or titrate up.
- Bedside nursing — continuous or very frequent (q15-30 min) presence. The patient and family should never be alone during this process.
- Time of death: Pronounce when breathing has ceased and no pulse is palpable. There is no specific observation period required (institutional policies vary, typically 2-5 minutes of apnea).
🏥 Rounds
Sample Presentation
Mrs. Williams is an 82-year-old woman with metastatic pancreatic cancer, intubated 5 days ago for respiratory failure from bilateral pleural effusions and pneumonia. Despite maximum medical therapy, she has not improved. Family meeting held yesterday with oncology, ICU, and palliative care present. Family reports her advance directive states she would not want prolonged mechanical ventilation. Surrogate (daughter) has elected to transition to comfort-focused care. Plan: discontinue vasopressors, antibiotics, and monitoring. Pre-medicate with morphine 4 mg IV. Extubate at family's readiness. Comfort medications at bedside: morphine drip, glycopyrrolate, lorazepam, haloperidol. Chaplain notified. DNR order in place.
Key Points: Clear goals of care discussion documented. Advance directive supports decision. All comfort medications ready at bedside BEFORE extubation. Monitors will be turned off. Family has been counseled that death may occur in minutes to days. Palliative care team is co-managing. This is ethically and legally supported withdrawal of non-beneficial treatment.
Pimp Questions
❓ Is there an ethical difference between withholding and withdrawing life-sustaining treatment?
No. Every major medical ethics body (AMA, AACN, SCCM) holds that there is no ethical or legal distinction between withholding and withdrawing treatment. Both are acceptable when the treatment is no longer consistent with the patient's goals. In practice, withdrawing can feel harder emotionally, but the ethical framework is identical.
❓ What is the principle of double effect and how does it apply here?
The principle of double effect states that an action with both a good effect (relieving suffering) and a foreseeable bad effect (potential respiratory depression) is ethically permissible if: (1) the action itself is not inherently wrong, (2) the intent is the good effect, (3) the bad effect is not the means to the good effect, and (4) there is proportionate reason. Giving morphine for dyspnea during extubation is ethical even if it may hasten death, because the intent is comfort.
❓ What medications should be at the bedside BEFORE palliative extubation?
At minimum: Morphine (for dyspnea/pain), glycopyrrolate (for secretions), lorazepam (for agitation/air hunger), and haloperidol (for terminal delirium). These should be drawn up and ready to administer immediately. Do NOT begin extubation without these available.
📋 Summary
Summary
What It Is
Withdrawal of non-beneficial mechanical ventilation. NOT euthanasia. Ethically and legally supported.
Before
Family meeting, DNR order, discontinue monitors/alarms, comfort meds at bedside, pre-medicate with morphine.
Process
Remove restraints → disconnect monitors → suction → wean/extubate → nasal cannula for comfort → stay with family.
Key Meds
Morphine (dyspnea), Glycopyrrolate (secretions), Lorazepam (agitation), Haloperidol (delirium).
Guiding Principle
Titrate to COMFORT, not to respiratory rate or death. Principle of double effect.
Timeline
Death may occur minutes to days after extubation. Prepare families for this range.
Inpatient Diabetes Management
Basal-bolus insulin is SUPERIOR to sliding scale alone. Target 140-180 mg/dL in ICU, 100-180 on wards. NEVER hold basal insulin just because a patient is NPO. Sliding scale alone is outdated and reactive — basal-bolus is proactive.
🔍 Overview
Overview
Inpatient hyperglycemia is extremely common and associated with increased mortality, infections, and length of stay. The landmark NICE-SUGAR, 2009 trial showed that targeting 140-180 mg/dL in ICU patients reduces mortality compared to tight glucose control (81-108). For non-ICU patients, the ADA recommends 100-180 mg/dL.
Updated Practice: Sliding scale alone is OUTDATED and inferior. RABBIT 2, 2007 showed basal-bolus achieves better glycemic control with LESS hypoglycemia. Sliding scale = reactive (chasing highs). Basal-bolus = proactive (preventing highs).
Glycemic Targets
- ICU patients: 140-180 mg/dL (NICE-SUGAR)
- Non-ICU patients: 100-180 mg/dL (pre-meal <140, random <180)
- Avoid hypoglycemia: <70 mg/dL is harmful. <54 = clinically significant. <40 = severe.
🚨 Management
Basal-Bolus Protocol
- Total daily dose (TDD): 0.4-0.5 units/kg/day. Reduce to 0.2-0.3 units/kg/day if elderly, CKD (eGFR <30), eating poorly, or high hypoglycemia risk.
- 50% as basal: Glargine (Lantus) or Detemir (Levemir) once daily (usually at bedtime or in the morning).
- 50% as bolus: Divided into 3 equal doses before each meal — Lispro (Humalog) or Aspart (NovoLog) before meals.
- Correction factor: 1700 / TDD = how many mg/dL 1 unit of insulin will drop glucose. Add correction to mealtime dose.
NEVER hold basal insulin just because a patient is NPO. Basal insulin controls hepatic glucose output, not meal glucose. Hold or reduce MEALTIME doses only. Holding basal leads to DKA in type 1 and dangerous hyperglycemia in type 2. If NPO, reduce basal by 20-50% but never hold it entirely.
Special Situations
Steroid-Induced Hyperglycemia
Prednisone causes AFTERNOON/EVENING hyperglycemia (peaks 4-8h after morning dose). The key is to match insulin to the glycemic pattern:
- Add NPH insulin with the morning prednisone dose — NPH peak matches prednisone glycemic peak.
- Starting dose: 0.1-0.2 units/kg. Uptitrate daily based on afternoon/evening glucose readings.
- When steroids are tapered, taper the NPH proportionally (or hyperglycemia will resolve and you risk hypoglycemia).
TPN (Total Parenteral Nutrition)
- Start with regular insulin IN the TPN bag at 1 unit per 10 g dextrose.
- Adjust daily based on glucose readings.
- Supplement with correction scale insulin SQ for persistent hyperglycemia.
- Roll 80% of previous day's correction insulin into the next TPN bag.
Hypoglycemia Protocol
- Glucose <70 mg/dL: If able to eat — 15 g oral glucose (juice box, glucose tabs). If NPO or unable — D50 25 mL (12.5 g) IV push.
- Recheck glucose in 15 minutes. Repeat if still <70.
- If recurrent hypoglycemia: reduce insulin dose by 20%, investigate cause (missed meals, renal clearance, adrenal insufficiency).
Clinical Example: A 65-year-old man with T2DM (A1c 9.2, weight 80 kg) is admitted for cellulitis. He was on metformin + glipizide at home. TDD = 0.4 x 80 = 32 units. Basal: glargine 16 units at bedtime. Bolus: lispro 5 units before each meal (~16 units total divided by 3). Correction factor: 1700/32 = ~53 — so 1 unit drops glucose by ~53 mg/dL. Hold home metformin and glipizide while inpatient.
🧪 Workup
Assessment on Admission
- A1c — if not checked in past 3 months. Reflects 3-month average. Guides discharge planning.
- Home insulin regimen — detailed medication reconciliation. What type, how much, when?
- Type 1 vs Type 2 — critical distinction. Type 1 patients MUST have basal insulin at all times (DKA risk). Check C-peptide if unclear.
- Point-of-care glucose (POC) — AC (before meals) and HS (bedtime) = 4x/day for eating patients. Q6h if NPO.
- Renal function — CKD increases hypoglycemia risk (reduced insulin clearance). Reduce TDD by 25-50% if eGFR <30.
- Nutritional status — is the patient eating? NPO? On TPN? On tube feeds? This drives your insulin strategy.
Daily Glucose Review
- Review all 4 POC glucose values from the past 24h
- Identify patterns: fasting highs = increase basal. Pre-dinner highs = increase lunch bolus. Overnight lows = reduce basal.
- Adjust insulin doses by 10-20% increments daily
💊 Medications
Medications
| Drug | Type | Onset / Peak / Duration | Notes |
|---|---|---|---|
| Glargine (Lantus) | Basal (long-acting) | 2-4h / peakless / 20-24h | Once daily. Provides baseline insulin coverage. Do NOT hold when NPO (reduce by 20-50%). |
| Detemir (Levemir) | Basal (long-acting) | 1-2h / 6-8h / 18-24h | May need BID dosing. Slight peak compared to glargine. |
| NPH | Intermediate-acting | 1-3h / 4-12h / 12-18h | Key for steroid-induced hyperglycemia. Give with morning prednisone. Peak matches steroid glycemic peak. |
| Lispro (Humalog) | Rapid-acting (bolus) | 15 min / 1-2h / 3-5h | Give 0-15 min before meals. Hold if NPO. Correction scale uses this. |
| Aspart (NovoLog) | Rapid-acting (bolus) | 15 min / 1-2h / 3-5h | Equivalent to lispro. Interchangeable. |
| Regular insulin | Short-acting | 30-60 min / 2-4h / 6-8h | Used in IV insulin drips (ICU) and added to TPN bags. Give 30 min before meals if used SQ. |
| D50 (Dextrose 50%) | Hypoglycemia rescue | 25 mL (12.5g) IV push | For glucose <70 when patient cannot eat. Recheck in 15 min. |
📊 Monitoring
Monitoring
- POC glucose AC + HS (before meals and bedtime) = 4 checks/day for eating patients
- POC glucose q6h for NPO patients
- Q1h glucose for patients on IV insulin drip (ICU)
- Hypoglycemia alerts: <70 requires intervention. <54 = clinically significant. <40 = severe — consider dose reduction and workup.
- Daily insulin adjustment: review all 4 values, identify patterns, adjust by 10-20% per day.
- BMP daily — monitor K+ (insulin shifts K+ intracellularly), renal function (affects insulin clearance).
- A1c on admission — guides discharge insulin planning (A1c >9 likely needs insulin at discharge, A1c <8 may resume oral agents).
🏥 Rounds
Sample Presentation
Mr. Garcia is a 58-year-old man with T2DM (A1c 8.7) admitted for community-acquired pneumonia. He is on prednisone 40 mg daily for severe COPD exacerbation. Home regimen: metformin 1000 mg BID + glipizide 10 mg BID. Weight 90 kg. Admission glucose 280. We transitioned to basal-bolus: TDD 0.4 x 90 = 36 units. Glargine 18 units QHS, lispro 6 units AC meals, correction scale. For steroid-induced hyperglycemia: added NPH 10 units (0.1 u/kg) with morning prednisone. Yesterday's glucoses: AM 145, pre-lunch 168, pre-dinner 242, HS 198. The pre-dinner spike confirms steroid effect — increasing NPH to 14 units. Metformin and glipizide held inpatient.
Key Points: Basal-bolus is superior to sliding scale. Added NPH to match prednisone glycemic peak (afternoon). Adjust NPH daily based on afternoon/evening glucoses. When prednisone is tapered, taper NPH proportionally. Will need discharge diabetes plan based on A1c and response to therapy.
Pimp Questions
❓ Why should you NOT hold basal insulin in NPO patients?
Basal insulin controls hepatic glucose output (gluconeogenesis and glycogenolysis), NOT meal-related glucose. Even when fasting, the liver continuously produces glucose. Without basal insulin, Type 1 patients will develop DKA and Type 2 patients will have dangerous hyperglycemia. The correct approach: reduce basal by 20-50% but never hold it. Hold MEALTIME insulin only.
❓ How do you dose NPH for steroid-induced hyperglycemia?
Give NPH with the morning prednisone dose — NPH has a peak at 4-12h that matches the glycemic peak from prednisone (4-8h after dose). Start at 0.1-0.2 units/kg. Uptitrate daily based on afternoon and evening glucose values. When steroids are tapered, taper NPH proportionally to prevent hypoglycemia.
❓ What is the correction factor formula?
1700 / TDD = correction factor (also called insulin sensitivity factor). This tells you how many mg/dL 1 unit of rapid-acting insulin will lower the blood glucose. Example: TDD 40 units → 1700/40 = 42.5 — so 1 unit drops glucose by ~43 mg/dL. For a glucose of 280 with target 150: (280-150)/43 = ~3 units of correction insulin added to mealtime dose.
📋 Summary
Summary
Target
140-180 mg/dL (ICU). 100-180 (non-ICU). NICE-SUGAR
Protocol
Basal-bolus: TDD 0.4-0.5 u/kg. 50% basal (glargine) + 50% bolus (lispro AC meals). RABBIT 2
NPO Rule
NEVER hold basal. Reduce by 20-50%. Hold mealtime doses only.
Steroids
NPH with morning prednisone. Start 0.1-0.2 u/kg. Peak matches steroid glycemic peak.
Correction
1700 / TDD = how much 1 unit drops glucose (mg/dL).
Hypoglycemia
<70: D50 25 mL IV if NPO, or 15 g PO glucose. Recheck in 15 min.
Transfusion Reactions
Recognize, classify, and manage the full spectrum of transfusion reactions. TRALI vs TACO is a board favorite. Stop the transfusion first, ask questions later.
Overview
Transfusion Reaction Types
| Type | Timing | Key Features | Treatment |
|---|---|---|---|
| Acute Hemolytic | Minutes | Fever, flank pain, dark urine, hypotension, DIC | STOP transfusion, NS bolus, send blood bank sample |
| Febrile Non-Hemolytic (FNHTR) | 1–6h | Fever, chills, NO hemolysis | Acetaminophen, slow rate. Most common reaction |
| Allergic (mild) | Min–hours | Urticaria, pruritus, NO hemodynamic instability | Diphenhydramine, can restart slowly |
| Anaphylactic | Minutes | Hypotension, bronchospasm, angioedema (often IgA deficient) | STOP, IM epinephrine |
| TRALI | 2–6h | Acute hypoxemia, bilateral infiltrates, NO volume overload | Supportive (lung-protective vent), resolves 48–72h. Leading cause of transfusion death |
| TACO | 1–6h | Dyspnea, HTN, JVD, pulmonary edema, elevated BNP | Diuresis (furosemide), O2, slow future transfusions |
| Delayed Hemolytic | 3–14 days | Falling Hgb, jaundice, positive DAT | Usually mild, supportive |
TRALI vs TACO (Board Favorite)
| Feature | TRALI | TACO |
|---|---|---|
| BNP | Low / normal | Elevated |
| CVP / JVD | Normal | Elevated |
| BP | Hypotension | Hypertension |
| CXR | Bilateral infiltrates (like ARDS) | Pulmonary edema, effusions |
| Diuretics | No response | Responds |
STOP the transfusion for ANY suspected reaction. Send the bag and a new blood sample to blood bank. Clerical error (wrong blood to wrong patient) is the #1 cause of fatal acute hemolytic reactions.
Workup
Workup
- STOP transfusion — keep IV access
- Send blood bank sample: repeat type & screen, DAT, visual hemolysis check
- CBC, BMP, LDH, haptoglobin, bilirubin, UA (hemoglobinuria)
- Coags if hemolytic/DIC suspected
- BNP + CXR for TRALI vs TACO
- Blood cultures if febrile (bacterial contamination)
Management
Management by Type
| Reaction | Immediate | Ongoing |
|---|---|---|
| Acute Hemolytic | STOP, NS bolus | UOP >1 mL/kg/hr, monitor for DIC |
| FNHTR | Acetaminophen | Can restart slowly. Pre-medicate future |
| Allergic | Diphenhydramine 25–50mg IV | Restart after urticaria resolves. Washed products for recurrence |
| Anaphylactic | Epinephrine 0.3–0.5mg IM | IgA level, future: washed/IgA-deficient products |
| TRALI | O2, intubation PRN | Lung-protective vent, resolves 48–72h. NO diuretics |
| TACO | Furosemide 20–40mg IV | O2, slow future transfusions (1 mL/kg/hr) |
🔄 Updated Practice: Old teaching: premedicate ALL transfusions with acetaminophen + diphenhydramine. Current practice: only premedicate if prior febrile or allergic reaction history. Routine premedication does not prevent serious reactions (TRALI, hemolytic) and delays recognition of early symptoms. Leukoreduction is more effective than premedication at preventing FNHTR.
Medications
Key Medications
| Drug | Indication | Dose |
|---|---|---|
| Acetaminophen | FNHTR, pre-med | 650mg PO/PR |
| Diphenhydramine | Allergic reactions | 25–50mg IV/PO |
| Epinephrine | Anaphylaxis | 0.3–0.5mg IM (1:1000) |
| Furosemide | TACO | 20–40mg IV |
Monitoring
Monitoring
| Parameter | Frequency | Target |
|---|---|---|
| Vital signs | q15min during transfusion | Fever, hypotension, desaturation |
| SpO2 | Continuous | Drop = TRALI/TACO/anaphylaxis |
| UOP | Hourly if hemolytic | >1 mL/kg/hr |
| Hemolysis labs | Post-reaction | Hgb, LDH, haptoglobin, DAT |
On Rounds
How do you differentiate TRALI from TACO?
TRALI = non-cardiogenic (low BNP, bilateral infiltrates, normal CVP, hypotension, no diuretic response). TACO = cardiogenic (high BNP, JVD, HTN, responds to diuretics). TRALI is the leading cause of transfusion death.
What is the #1 cause of fatal acute hemolytic reactions?
Clerical error — wrong blood to wrong patient (ABO mismatch). Bedside verification is mandatory.
Which patients are at risk for anaphylactic transfusion reactions?
IgA-deficient patients with anti-IgA antibodies. Need washed blood products or IgA-deficient donors.
Summary
Summary
Most Common
FNHTR — fever + chills, no hemolysis. Acetaminophen.
Most Deadly
Acute hemolytic (ABO mismatch) and TRALI (#1 cause of transfusion death).
TRALI vs TACO
BNP is key. TRALI = low BNP. TACO = high BNP, responds to diuretics.
First Step
STOP transfusion. Send bag + sample to blood bank.
Acid-Base Disorders
Systematic ABG interpretation: pH, primary disorder, compensation, anion gap, delta-delta, osmolar gap. MUDPILES, HARDUP, Winter’s formula, RTA types. Every ICU admission needs this.
Overview
Step-by-Step ABG Interpretation
- Step 1 — pH: <7.35 = acidemia, >7.45 = alkalemia
- Step 2 — Primary disorder: PaCO2 same direction as pH = metabolic. HCO3 opposite = respiratory
- Step 3 — Compensation: Winter’s formula: Expected PaCO2 = 1.5 × HCO3 + 8 ± 2
- Step 4 — Anion Gap: AG = Na − Cl − HCO3 (normal 12±2). Corrected: add 2.5 per 1g albumin below 4
- Step 5 — Delta-Delta: ΔAG/ΔHCO3. >2 = concurrent met alkalosis. <1 = concurrent NAGMA
- Step 6 — AGMA (MUDPILES): Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates
- Step 7 — NAGMA (HARDUP): Hyperalimentation, Addison, RTA, Diarrhea, Ureteral diversion, Pancreatic fistula
- Step 8 — Osmolar Gap: Measured − (2Na + Glu/18 + BUN/2.8). Gap >10 = toxic alcohol
RTA Types
| Type | Location | Urine pH | Serum K+ | Key Feature |
|---|---|---|---|---|
| Type 1 (Distal) | Distal tubule | >5.5 | Low | Cannot excrete H+. Kidney stones. Batlle 2001 |
| Type 2 (Proximal) | Proximal tubule | <5.5 | Low | Cannot reabsorb HCO3. Fanconi syndrome |
| Type 4 | Collecting duct | <5.5 | HIGH | Hypoaldosteronism (diabetes, ACEi). Most common RTA |
Workup
Labs
- ABG/VBG, BMP (calculate AG), albumin (correct AG), lactate, ketones
- Serum osmolality + calculated osm → osmolar gap
- Urine electrolytes + pH for NAGMA (urine AG = Na+K−Cl; positive = RTA)
- Toxic alcohol levels if osmolar gap elevated
Practice Cases
Case 1: pH 7.28, PaCO2 24, HCO3 11, Na 140, Cl 100, Alb 4.0
Acidemia. Met acidosis. Winter’s: expected PaCO2 = 24.5 (matches). AG = 29 (elevated). Delta-delta = 1.3 (pure AGMA). Simple AGMA. Check lactate, ketones, osmolar gap.
Case 2: pH 7.36, PaCO2 22, HCO3 12, Na 138, Cl 100, Alb 2.0
Normal pH but corrected AG = 31 (add 5 for low albumin). Delta-delta 1.6. Triple disorder: AGMA + met alkalosis + resp alkalosis. Albumin correction was essential.
Case 3: pH 7.52, PaCO2 48, HCO3 38, Na 140, Cl 92, K 2.8
Alkalemia. Met alkalosis with appropriate respiratory compensation. AG = 10 (normal). HypoK + met alkalosis = vomiting, diuretics, or hyperaldosteronism. Check urine Cl.
Management
Treatment by Disorder
| Disorder | Treatment |
|---|---|
| AGMA — DKA | Insulin drip + IVF + K repletion |
| AGMA — Lactic acidosis | Treat cause (sepsis, shock). Optimize perfusion |
| AGMA — Toxic alcohol | Fomepizole 15mg/kg + emergent dialysis |
| NAGMA — RTA Type 1/2 | Oral sodium bicarbonate |
| NAGMA — RTA Type 4 | Treat hyperK, fludrocortisone |
| Met alkalosis | Saline-responsive: NS + KCl. Saline-resistant: treat cause |
🔄 Updated Practice: Old teaching: give sodium bicarbonate for metabolic acidosis. Current practice: bicarb rarely helps and can worsen intracellular acidosis. In DKA, bicarb is only indicated if pH <6.9 (ADA guidelines). In lactic acidosis, treat the underlying cause (fluids, antibiotics, source control) — bicarb does not improve outcomes. Exception: bicarb IS indicated for TCA overdose (sodium channel blockade) and severe hyperkalemia.
Medications
Key Medications
| Drug | Indication | Dose |
|---|---|---|
| Sodium Bicarbonate | Severe acidosis (pH <7.1), TCA OD, RTA | 1–2 mEq/kg IV bolus or 150mEq in D5W drip |
| Fomepizole | Toxic alcohol ingestion | 15mg/kg IV load, then 10mg/kg q12h |
| Fludrocortisone | Type 4 RTA | 0.1mg PO daily |
| Acetazolamide | Resistant met alkalosis | 250–500mg IV/PO |
Monitoring
Monitoring
| Parameter | Frequency | Target |
|---|---|---|
| ABG/VBG | q2–4h acute | Trend pH, PaCO2, HCO3 |
| BMP (AG) | q4–6h | Closing AG = resolving AGMA |
| Lactate | q2–4h if elevated | Trending down = improving |
| Osmolar gap | Serial if toxic alcohol | Closing gap + rising AG = metabolite formation → dialysis |
On Rounds
What is the delta-delta and when does it matter?
ΔAG/ΔHCO3. Detects hidden disorders. >2 = concurrent met alkalosis. <1 = concurrent NAGMA. 1–2 = pure AGMA.
Why correct the AG for albumin?
Albumin is the major unmeasured anion. In hypoalbuminemia, baseline AG is lower — you may miss an AGMA. Add 2.5 per 1g/dL below 4.
Summary
Summary
AGMA
MUDPILES: Methanol, Uremia, DKA, Propylene glycol, Isoniazid, Lactic acid, Ethylene glycol, Salicylates
NAGMA
HARDUP: Hyperalimentation, Addison, RTA, Diarrhea, Ureteral diversion, Pancreatic fistula
Key Formulas
AG = Na-Cl-HCO3. Winter’s: 1.5(HCO3)+8±2. Osm gap = Measured − (2Na + Glu/18 + BUN/2.8)
Delta-Delta
>2 = hidden met alkalosis. <1 = concurrent NAGMA. Always calculate when AG elevated.
Toxicology / Drug Overdose
Specific antidote protocols for highest-yield overdoses: acetaminophen, salicylate, TCA, opioid, BB/CCB. NEVER intubate a salicylate-toxic patient unless absolutely necessary.
Overview
Acetaminophen
- Rumack-Matthew nomogram — APAP level vs time to determine NAC need
- NAC: N-acetylcysteine 150mg/kg/1h → 50mg/kg/4h → 100mg/kg/16h Prescott 1979
- AST/ALT may be normal initially (peaks 72–96h). King’s College for transplant referral
Salicylate
- Tinnitus, tachypnea (resp alkalosis + AG met acidosis). Alkalinize urine: bicarb drip, target urine pH 7.5–8
- Dialysis if level >90 or severe symptoms
NEVER intubate a salicylate-toxic patient unless absolutely necessary. They hyperventilate to compensate for metabolic acidosis. Losing that compensation during intubation → sudden severe acidosis → cardiac arrest.
TCA
- Wide QRS (>100ms), sodium channel blockade, seizures
- Sodium bicarbonate 1–2 mEq/kg IV bolus (narrows QRS)
- NEVER flumazenil in TCA/benzo co-ingestion (lowers seizure threshold)
🔄 Updated Practice: Old teaching: flumazenil (Romazicon) for all benzodiazepine overdoses. Current practice: AVOID flumazenil in chronic benzo users (precipitates withdrawal seizures) and in mixed overdose with TCAs (removes seizure protection). Flumazenil is only safe for iatrogenic oversedation in benzo-naive patients (e.g., post-procedure). When in doubt, don't give it.
Opioid
- Naloxone 0.04–0.4mg IV titrate (start low). Drip for long-acting opioids
BB / CCB
- BB: Glucagon 3–5mg IV
- CCB: High-dose insulin 1u/kg/hr + D10W
Activated charcoal: Only within 1–2h, alert patient, protected airway. NOT for caustics, hydrocarbons, metals, alcohols.
🔄 Updated Practice: Old teaching: gastric lavage ('stomach pumping') for overdose. Current practice: gastric lavage is rarely performed — risk of aspiration, esophageal perforation, and no proven mortality benefit. Activated charcoal within 1-2 hours of ingestion (alert patient, protected airway) is the only recommended GI decontamination in most cases.
Workup
Workup
- APAP level (4h post-ingestion), salicylate level, ethanol
- BMP, ABG, AG, osmolar gap, lactate, LFTs, coags
- ECG (QRS width, QTc)
- Urine drug screen (limited utility)
Management
Antidote Reference
| Toxin | Antidote | Dose |
|---|---|---|
| Acetaminophen | NAC | 150/50/100 mg/kg over 21h IV |
| Opioids | Naloxone | 0.04–0.4mg IV titrate |
| TCA | Sodium bicarbonate | 1–2 mEq/kg IV bolus |
| Beta-blockers | Glucagon | 3–5mg IV |
| CCB | High-dose insulin | 1u/kg/hr + D10W |
| Methanol/EG | Fomepizole | 15mg/kg IV load |
| Organophosphates | Atropine + Pralidoxime | Atropine 2mg IV q5min |
| Digoxin | DigiFab | Based on level |
Medications
Detailed Dosing
| Drug | Dose | Notes |
|---|---|---|
| NAC IV | 150mg/kg in D5W/1h, 50mg/kg/4h, 100mg/kg/16h | Anaphylactoid reactions common first bag |
| Naloxone | 0.04mg → 0.4mg → 2mg titrate. Drip: 2/3 bolus/hr | Short t1/2; re-dosing needed for long-acting opioids |
| Glucagon | 3–5mg IV bolus, infusion 2–5mg/hr | BB OD. Causes vomiting (aspiration risk) |
| Insulin HIE | 1u/kg bolus then 1u/kg/hr + D10W | CCB OD. Monitor glucose q15min, K q1h |
Monitoring
Monitoring by Toxin
| Toxin | Key Monitoring |
|---|---|
| APAP | AST/ALT q6–12h, INR, APAP level, lactate |
| Salicylate | Serial levels q2h, ABG, urine pH hourly |
| TCA | Continuous telemetry, serial ECG QRS width |
| BB/CCB | HR, BP, glucose q15min, K q1h, lactate |
On Rounds
Why is intubating a salicylate patient so dangerous?
They hyperventilate to compensate for metabolic acidosis. During intubation, apnea → CO2 rises → sudden acidemia → salicylate moves into CNS → cardiac arrest. If you must intubate, pre-push bicarb and set vent RR 20–24.
Why is flumazenil contraindicated in TCA overdose?
TCAs lower seizure threshold. Benzos raise it (protective). Flumazenil reverses benzo protection → refractory seizures → worsening acidosis → death.
Summary
Summary
APAP
NAC 150/50/100. Nomogram at 4h. LFTs may be normal early.
Salicylate
Alkalinize urine. NEVER intubate unless necessary. Dialysis if >90.
TCA
Wide QRS → bicarb. No flumazenil.
BB/CCB
BB: Glucagon. CCB: High-dose insulin + D10W.
Intubation / RSI
Rapid Sequence Intubation. Pre-oxygenate, push induction + paralytic, confirm with ETCO2 waveform. Know your agents, contraindications, and difficult airway algorithm.
Overview
Indications
- Failure to protect airway (GCS ≤8), respiratory failure despite NIV, expected deterioration
RSI Sequence
- Pre-oxygenate 3–5min 100% O2, HFNC apneic oxygenation, HOB 20–30°
- Push induction + paralytic simultaneously → wait 45–60s → laryngoscopy
- Confirm with continuous waveform ETCO2
ETCO2 waveform is the GOLD STANDARD. Auscultation alone is NOT sufficient. No waveform = esophageal until proven otherwise.
Induction Agents
| Agent | Dose | Pros | Cons |
|---|---|---|---|
| Etomidate | 0.3mg/kg | Hemodynamically neutral | Adrenal suppression |
| Ketamine | 1–2mg/kg | Bronchodilator, maintains BP. Best for asthma/sepsis | Emergence reactions |
| Propofol | 1–2mg/kg | Fast onset | Drops BP — avoid in hypotension |
Paralytics
| Agent | Dose | Onset | Contraindications |
|---|---|---|---|
| Succinylcholine | 1–1.5mg/kg | 45s (fastest) | HyperK, burns >48h, crush, NMD, malignant hyperthermia |
| Rocuronium | 1.2mg/kg | 60s | Reversible with sugammadex |
🔄 Updated Practice: Old teaching: succinylcholine is the default paralytic for RSI due to fastest onset. Current practice: rocuronium (Zemuron) 1.2 mg/kg has equivalent onset (~60 seconds at this dose), is reversible with sugammadex (Bridion), and has fewer contraindications (no hyperkalemia risk in burns/crush/renal failure/neuromuscular disease). Many centers now use rocuronium as the default paralytic for RSI.
Difficult Airway
- Bougie (first adjunct), video laryngoscopy, LMA rescue, cricothyrotomy last resort
Pre-Assessment
Checklist
- LEMON airway assessment, equipment ready (ETT, laryngoscope, bougie, LMA, suction)
- Hemodynamics: optimize BEFORE intubation, push-dose vasopressors ready
- Pre-oxygenation: 3–5min NRB or HFNC, HOB elevated
Post-Intubation
Initial Vent Settings
| Parameter | Setting |
|---|---|
| TV | 6–8 mL/kg IBW (6 if ARDS) |
| RR | 14–16 (higher if met acidosis) |
| FiO2 | 100% → wean to SpO2 92–96% |
| PEEP | 5 cmH2O (higher if ARDS) |
- CXR for tube position (3–5cm above carina)
- Sedation: propofol or midazolam + fentanyl, target RASS -2 to 0
- HOB 30–45°, oral care q4h, DVT ppx, stress ulcer ppx
Medications
RSI Meds
| Drug | Class | Dose | Pearl |
|---|---|---|---|
| Etomidate | Induction | 0.3mg/kg | Hemodynamically neutral |
| Ketamine | Induction | 1–2mg/kg | Best for asthma/sepsis |
| Propofol | Induction | 1–2mg/kg | Drops BP. Avoid in shock |
| Succinylcholine | Depolarizing NMB | 1–1.5mg/kg | Fastest (45s). CI in hyperK/burns/NMD |
| Rocuronium | Non-depolarizing NMB | 1.2mg/kg | Reversible with sugammadex 16mg/kg |
Monitoring
Monitoring
| Parameter | Target |
|---|---|
| ETCO2 | Continuous. 35–45 mmHg. Loss = dislodged tube |
| SpO2 | 92–96% (88–92% COPD) |
| Plateau pressure | <30 cmH2O |
| ABG | 30min post-intubation |
| CXR | Immediately post-intubation |
On Rounds
Why is succinylcholine contraindicated in burns/crush injuries?
Extrajunctional ACh receptor upregulation after denervation/injury → massive K+ efflux → fatal hyperkalemia. Risk starts ~48h post-injury. Use rocuronium instead.
When choose ketamine over etomidate?
Ketamine for: asthma (bronchodilator), sepsis/hypotension (sympathomimetic, maintains BP). Increasingly the default ED induction agent.
Summary
Summary
Gold Standard
Waveform ETCO2. No waveform = esophageal.
Induction
Etomidate (neutral), Ketamine (asthma/sepsis), Propofol (avoid in hypotension).
Paralytic
Sux 1.5mg/kg (45s, fastest) or Roc 1.2mg/kg (sugammadex reversible).
Post-Intubation
TV 6–8mL/kg IBW, RR 14–16, FiO2 wean, PEEP 5. Sedation + CXR.
ACS Overview
The unifying approach BEFORE you know STEMI vs NSTEMI. ECG within 10 minutes, aspirin 325mg chew, troponin. HEART score for risk stratification. Time is myocardium.
Overview
Approach
- Chest pain → ECG within 10 min → Troponin
- ST elevation in 2 contiguous leads = STEMI → cath lab NOW
- No ST elevation + troponin rising = NSTEMI
- Normal ECG + normal troponin = unstable angina or non-cardiac
HEART Score
| Component | 0 | 1 | 2 |
|---|---|---|---|
| History | Slightly suspicious | Moderately | Highly suspicious |
| ECG | Normal | Non-specific | ST deviation |
| Age | <45 | 45–64 | ≥65 |
| Risk Factors | None | 1–2 | ≥3 or known CAD |
| Troponin | Normal | 1–3×ULN | >3×ULN |
0–3 = Low risk (consider discharge). 4–6 = Moderate (admit). 7–10 = High (early invasive).
Workup
Workup
- 12-lead ECG within 10 min. Repeat q15–30min if normal + symptoms persist
- Serial troponins (hs-trop 0h, 3h). Right-sided ECG (V4R) for inferior STEMI
- CBC, BMP, coags, BNP, CXR
Management
Initial Management (ALL ACS)
| Intervention | Details |
|---|---|
| Aspirin | 325mg chewed immediately |
| O2 | Only if SpO2 <90% DETO2X-AMI |
| Nitroglycerin | 0.4mg SL q5min ×3. AVOID: RV infarct, SBP <90, PDE5i use |
| Heparin | UFH 60u/kg bolus → 12u/kg/hr (or enoxaparin 1mg/kg q12h) |
| Beta-blocker | Within 24h if stable. Avoid in HF, bradycardia, cocaine |
| Atorvastatin | 80mg immediately (high-intensity) |
🔄 Updated Practice: Old teaching: MONA (Morphine, Oxygen, Nitro, Aspirin) as the standard ACS protocol. Current practice: MONA is dead. Morphine may increase mortality in ACS (observational data — use only for refractory pain). Oxygen only if SpO2 <90% (DETO2X-AMI, AVOID trials — hyperoxia may increase infarct size). Focus on: Aspirin + anticoagulation + P2Y12 inhibitor + high-intensity statin + early risk stratification.
Medications
Key Meds
| Drug | Dose | Notes |
|---|---|---|
| Aspirin | 325mg chew, then 81mg daily | ALL ACS unless true allergy |
| Ticagrelor | 180mg load, 90mg BID | Preferred P2Y12 (PLATO trial). Use aspirin 81mg only |
| Clopidogrel | 600mg load, 75mg daily | Alternative. CYP2C19 polymorphisms |
| Heparin | 60u/kg, 12u/kg/hr | aPTT 1.5–2.5× control |
Monitoring
Monitoring
| Parameter | Frequency |
|---|---|
| Telemetry | Continuous. VT/VF risk highest 24–48h |
| Troponins | 0h, 3h (hs-trop) |
| ECGs | q15–30min if symptoms persist |
On Rounds
Why avoid nitroglycerin in RV infarct?
RV is preload-dependent. NTG causes venodilation → drops preload → profound hypotension. Give IVF instead. Check V4R before nitrates in inferior STEMI.
STEMI vs NSTEMI vs UA?
STEMI: Complete occlusion, ST elevation, troponin up. Emergent PCI. NSTEMI: Partial occlusion, no ST elevation, troponin elevated. UA: Same mechanism but troponin normal.
Summary
Summary
First 10 Min
ECG + ASA 325 chewed + IV + troponin. STEMI = cath NOW.
HEART Score
0–3 low (discharge), 4–6 moderate (admit), 7–10 high (invasive).
All ACS
ASA + P2Y12 + anticoag + statin + BB if stable.
Avoid NTG In
RV infarct, SBP <90, PDE5i within 24–48h.
Aortic Stenosis
Most common valvular disease. Classic triad: syncope, angina, heart failure. Once symptoms develop, prognosis is poor without valve replacement. Medical therapy does NOT change outcomes.
Overview
Etiology & Presentation
- Causes: Degenerative/calcific (elderly), bicuspid aortic valve (younger)
- Triad (SAD): Syncope, Angina, Dyspnea (HF)
- Murmur: Crescendo-decrescendo systolic, radiates to carotids. Pulsus parvus et tardus
Severity
| Parameter | Mild | Moderate | Severe |
|---|---|---|---|
| AVA (cm²) | >1.5 | 1.0–1.5 | <1.0 |
| Mean Gradient | <25 | 25–40 | >40 |
| Vmax (m/s) | <3.0 | 3.0–4.0 | >4.0 |
Do NOT give vasodilators aggressively in severe AS. These patients are preload-dependent. Vasodilation → syncope → death.
Workup
Workup
- TTE — gold standard for diagnosis and severity
- ECG: LVH, LAE
- BNP if HF symptoms
- Cardiac cath: pre-op coronary assessment
Management
Management
| Scenario | Management |
|---|---|
| Asymptomatic severe | Serial echo q6–12mo. Exercise testing if questionable |
| Symptomatic severe | VALVE REPLACEMENT (TAVR or SAVR) |
| High surgical risk | TAVR PARTNER Trials |
| Low risk / young | SAVR |
No medical substitute for valve replacement. Diuretics may help symptoms but do not change natural history.
🔄 Updated Practice: Old teaching: balloon aortic valvuloplasty (BAV) as treatment for severe AS. Current practice: BAV is a temporary bridge only — restenosis occurs within 6-12 months in nearly all patients. TAVR (transcatheter aortic valve replacement) has revolutionized AS management (PARTNER trials). TAVR is now approved for all surgical risk categories and is the standard for high/intermediate-risk patients.
Medications
Temporizing
| Drug | Role | Caution |
|---|---|---|
| Furosemide | Symptom relief | Low doses. Aggressive diuresis → hypotension |
| ACEi/ARB | If concurrent HTN | Start very low. Dangerous hypotension in severe AS |
Monitoring
Monitoring
| Parameter | Frequency |
|---|---|
| Echo | q6–12mo severe; q1–2y moderate |
| Symptoms | Every visit. New symptoms = refer for valve replacement |
On Rounds
Classic murmur of AS?
Crescendo-decrescendo systolic at RUSB, radiates to carotids. Late peaking = more severe. Pulsus parvus et tardus. Diminished A2.
Survival estimates once symptoms develop?
Without valve replacement: Angina ~5y, Syncope ~3y, HF ~2y. Steep mortality curve once any symptom appears.
Summary
Summary
Severe AS
AVA <1.0, gradient >40, Vmax >4.0.
Symptoms
SAD: Syncope, Angina, Dyspnea. Once present = valve replacement.
Treatment
Symptomatic = TAVR or SAVR. No medical therapy changes outcomes.
Danger
Avoid vasodilators. Preload-dependent.
Mitral Regurgitation
Acute MR (papillary rupture, endocarditis) = surgical emergency with flash pulmonary edema. Chronic MR is insidious — EF is misleadingly preserved. EF 60% in severe MR = significant dysfunction.
Overview
Acute vs Chronic
| Feature | Acute MR | Chronic MR |
|---|---|---|
| Causes | Papillary rupture (post-MI), endocarditis, chordae rupture | Myxomatous (MVP), rheumatic, functional (LV dilation) |
| Presentation | Flash pulmonary edema, cardiogenic shock | Asymptomatic years → dyspnea |
| Treatment | EMERGENCY SURGERY | Surgery when criteria met |
EF in MR is misleading. LV ejects into low-pressure LA → EF artificially preserved. EF 60% in severe MR = significant dysfunction. Don’t wait for 40%.
Workup
Workup
- TTE (severity, LV size/function), TEE for surgical planning
- ECG: Afib common
- CXR, BNP
- Cardiac cath pre-op
Management
Surgery Indications (Chronic Primary MR)
| Indication | Action |
|---|---|
| Symptomatic severe MR | Surgery (repair > replacement) |
| Asymptomatic + EF ≤60% | Surgery |
| Asymptomatic + LVESD ≥40mm | Surgery |
| Secondary MR + HFrEF | MitraClip if on optimal GDMT COAPT 2018 |
Medications
Medical Therapy
| Drug | Role |
|---|---|
| ACEi/ARB | Afterload reduction. Reduces regurgitant fraction |
| Diuretics | Volume management |
| GDMT (HF pillars) | For secondary MR with HF |
| Nitroprusside | Acute severe MR bridge to surgery (ICU only) |
Monitoring
Monitoring
| Parameter | Frequency |
|---|---|
| Echo | q6–12mo severe; q1–2y moderate |
| AF surveillance | ECG at visits |
On Rounds
Why is EF misleading in MR?
LV ejects into both aorta AND low-pressure LA → inflated EF. EF 60% with severe MR = significant dysfunction (normal heart would be >70%). Surgery threshold is EF ≤60%, not 40%.
What is the COAPT trial?
MitraClip (transcatheter repair) reduced HF hospitalization and mortality in secondary MR with persistent symptoms despite optimal GDMT. Must optimize HF meds first.
Summary
Summary
Acute MR
Flash pulm edema, papillary rupture. EMERGENCY surgery.
Surgery Triggers
Symptomatic, EF ≤60%, LVESD ≥40mm.
EF Trap
EF falsely preserved. 60% = significant dysfunction.
Secondary MR
Optimize GDMT first. MitraClip (COAPT) if persistent.
Acute Limb Ischemia
Surgical emergency. “Time is tissue.” The 6 P’s: Pain, Pallor, Pulselessness, Poikilothermia, Paresthesia, Paralysis. Start heparin IMMEDIATELY, call vascular surgery.
Overview
6 P’s
- Pain — sudden, severe
- Pallor
- Pulselessness
- Poikilothermia (cold)
- Paresthesia
- Paralysis (late = bad)
Rutherford Classification
| Category | Status | Sensory | Motor |
|---|---|---|---|
| I | Viable | None | None |
| IIa | Marginally threatened | Minimal | None |
| IIb | Immediately threatened | Rest pain | Mild-moderate |
| III | Irreversible → amputation | Anesthetic | Paralysis |
SURGICAL EMERGENCY. Start heparin IMMEDIATELY. Do NOT wait for imaging to anticoagulate.
Workup
Workup
- ABI, CTA (if stable). Labs: CBC, BMP (K+), lactate, CK, coags
- ECG for AF (common embolic source)
- Do NOT delay heparin for imaging
Management
Management
| Step | Action |
|---|---|
| 1 | Heparin 80u/kg bolus → 18u/kg/hr IMMEDIATELY |
| 2 | Vascular surgery consult STAT |
| 3 | Catheter-directed thrombolysis, embolectomy, or bypass |
| 4 | Post-reperfusion: watch compartment syndrome → fasciotomy |
Medications
Medications
| Drug | Dose | Notes |
|---|---|---|
| Heparin UFH | 80u/kg bolus, 18u/kg/hr | aPTT 60–80s. Prevents clot propagation |
| tPA (catheter-directed) | 0.5–1mg/hr intra-arterial | Rutherford I–IIa. Takes 12–24h |
Monitoring
Monitoring
| Parameter | Frequency |
|---|---|
| Pulse checks | q1h |
| Compartment pressures | Post-reperfusion. >30mmHg → fasciotomy |
| K+, CK, Cr | q4–6h post-reperfusion |
| aPTT | q6h |
On Rounds
Most common cause of ALI?
Embolism (AF most common source) and in-situ thrombosis (on atherosclerotic disease). Embolic = sudden, no prior claudication. Thrombotic = PAD history, more insidious.
Summary
Summary
6 P’s
Pain, Pallor, Pulselessness, Poikilothermia, Paresthesia, Paralysis.
First Step
Heparin 80u/kg NOW + vascular surgery STAT.
Treatment
Thrombolysis, embolectomy, or bypass by Rutherford class.
Post-Reperfusion
Compartment syndrome, hyperK, rhabdo, acidosis.
Bowel Obstruction
SBO (#1 cause: adhesions) vs LBO (#1 cause: colorectal cancer). Know when to manage conservatively vs when strangulation signs mandate the OR. Sigmoid volvulus = scope first. Cecal volvulus = surgery.
Overview
SBO vs LBO
| Feature | SBO | LBO |
|---|---|---|
| #1 Cause | Adhesions | Colorectal cancer |
| Other | Hernias, malignancy, Crohn | Volvulus (sigmoid > cecal) |
| Conservative | NGT, NPO, IVF ×48–72h | Depends on cause |
| Surgery | Complete, strangulation, failure to resolve | Cancer → resection. Cecal volvulus → surgery |
Volvulus
| Type | First-Line | Definitive |
|---|---|---|
| Sigmoid | Endoscopic decompression | Interval resection |
| Cecal | Surgery (scope does NOT work) | Right hemicolectomy |
Strangulation signs = SURGICAL EMERGENCY: fever, peritoneal signs, free air, leukocytosis, lactate elevation, non-reducible hernia.
Workup
Workup
- CT abdomen/pelvis with IV contrast — gold standard
- CBC, BMP, lactate, lipase
- Upright CXR if free air suspected
Management
Conservative (Partial SBO)
- NGT decompression, NPO, IVF, serial exams q4–8h
- Gastrografin (diagnostic + therapeutic: reaches colon on 24h film = resolving)
Surgery Indications
- Complete obstruction, strangulation, closed-loop, failure to resolve 48–72h, incarcerated hernia
🔄 Updated Practice: Old teaching: mandatory nasogastric tube (NGT) decompression for all small bowel obstruction. Current practice: NGT is indicated for patients with significant vomiting, distension, or complete obstruction. Mild partial SBO with minimal symptoms can be managed with bowel rest, IV fluids, and observation without NGT. Water-soluble contrast (Gastrografin) challenge at 24-48h can be both diagnostic and therapeutic — appearance of contrast in the colon predicts resolution without surgery.
Medications
Medications
| Drug | Role |
|---|---|
| NS / LR | Aggressive volume resuscitation |
| Gastrografin | 100mL via NGT (diagnostic + therapeutic) |
| Ondansetron | Antiemetic 4mg IV q6h |
| Pip-tazo / Cefepime + Metro | If strangulation/perforation suspected |
Monitoring
Monitoring
| Parameter | Frequency |
|---|---|
| Abdominal exam | q4–8h |
| NGT output | q shift |
| CBC, lactate | q8–12h |
On Rounds
SBO vs ileus?
SBO = mechanical (transition point on CT, dilated proximal, decompressed distal). Ileus = functional (diffuse dilation, no transition point). Ileus: post-op, opioids, hypoK, peritonitis.
Why does scope work for sigmoid but not cecal volvulus?
Sigmoid twists at accessible location → sigmoidoscopy can pass tube past twist. Cecal volvulus = cecum twists on mesentery, too proximal for scope. Cecal = surgery (cecopexy or right hemicolectomy).
Summary
Summary
SBO
#1 adhesions. NGT + NPO + IVF. Surgery if strangulation/failure 48–72h.
LBO
#1 CRC. Sigmoid volvulus: scope. Cecal volvulus: surgery.
Strangulation
Fever, peritonitis, free air, WBC, lactate = OR NOW.
SBO vs Ileus
Mechanical (transition point) vs functional (diffuse, no cutoff).
Necrotizing Fasciitis / Gas Gangrene
Rapidly progressive soft tissue infection. Mortality increases ~25% per hour of surgical delay. Pain OUT OF PROPORTION to exam is the hallmark. Surgical debridement IS the treatment. CT can miss early cases.
Overview
Classification
| Type | Organisms | Risk Factors |
|---|---|---|
| Type 1 (Polymicrobial) | Mixed aerobic + anaerobic | Diabetes, post-surgical, immunocompromised |
| Type 2 (Monomicrobial) | Group A Strep | Young, healthy, minor trauma |
| Gas Gangrene | C. perfringens | Trauma, surgical wounds |
Clinical Features
- Pain OUT OF PROPORTION to exam — hallmark
- Rapidly spreading erythema, crepitus, bullae, dusky/necrotic skin
- Systemic toxicity: sepsis, shock. LRINEC ≥6 suggestive
If you suspect nec fasc, go to the OR. Do NOT wait for imaging. CT can MISS early disease. The “finger test” (bedside incision, tissue planes dissect easily) is diagnostic. Every hour of delay increases mortality ~25%.
Workup
Workup
- Clinical diagnosis — do NOT delay for imaging
- Labs: CBC, BMP (Na often low), CRP, lactate, CK, coags, blood cultures
- LRINEC score ≥6 suspicious, ≥8 highly suggestive
- Finger test: bedside incision, easy tissue dissection = nec fasc
Management
Management
- SURGICAL DEBRIDEMENT IS THE TREATMENT — antibiotics are adjunct
- Second-look operation 24–48h. Often serial debridements needed
- ICU for sepsis management
- IVIG for streptococcal toxic shock (1–2 g/kg, controversial but used)
🔄 Updated Practice: Old teaching: obtain CT or MRI to confirm necrotizing fasciitis before consulting surgery. Current practice: if you suspect nec fasc clinically (pain out of proportion, rapidly spreading, systemic toxicity, crepitus), take the patient to the OR immediately. CT can MISS early disease — sensitivity is only ~80%. Every hour of delay in surgical debridement increases mortality by approximately 25%. The 'finger test' (bedside wound exploration — if tissue planes dissect easily with blunt finger) is faster and more reliable than imaging.
Medications
Antibiotic Regimen
| Drug | Dose | Role |
|---|---|---|
| Vancomycin | 25–30mg/kg load, 15–20mg/kg q8–12h | MRSA coverage |
| Piperacillin-Tazobactam | 4.5g IV q6h | Broad GN + anaerobe coverage |
| Clindamycin | 900mg IV q8h | TOXIN SUPPRESSION |
Clindamycin for TOXIN SUPPRESSION, not just coverage. GAS and Clostridium produce exotoxins driving shock. Clindamycin (protein synthesis inhibitor) stops toxin production. Beta-lactams do NOT suppress toxins.
Monitoring
Monitoring
| Parameter | Frequency |
|---|---|
| Wound | q4–6h. Advancing necrosis = return to OR |
| Hemodynamics | Continuous ICU. MAP >65 |
| CBC, CRP, lactate | q6–12h |
On Rounds
Why add clindamycin?
Toxin suppression. GAS and Clostridium make exotoxins (superantigens) driving shock. Clindamycin inhibits protein synthesis → stops toxin production. Beta-lactams target cell wall, not protein synthesis.
Can CT rule out nec fasc?
No. CT can miss early disease. Gas/fascial thickening are late findings. If clinical suspicion high, go to OR. Finger test or intraop exploration is diagnostic.
Summary
Summary
Hallmark
Pain OUT OF PROPORTION + rapid progression + systemic toxicity.
Treatment
SURGICAL DEBRIDEMENT. Vanc + pip-tazo + clindamycin.
Clindamycin
TOXIN SUPPRESSION (protein synthesis inhibitor stops exotoxin production).
Mortality
~25% increase per hour of surgical delay. CT can miss early. Operate if suspected.
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