Clinical Pearls

Never give CCBs or beta-blockers in Afib with WPW -forces conduction down the accessory pathway → VF → death. Use procainamide.

In aortic dissection, control HR BEFORE BP. Dropping BP without slowing HR increases dP/dt (wall shear stress) and propagates the dissection.

Type A dissection involving the RCA mimics inferior STEMI. If you give tPA → tamponade → death. Always consider dissection before treating STEMI.

In HCM with hypotension: IV fluids + phenylephrine. NEVER nitrates, diuretics, dobutamine, or digoxin -all worsen LVOT obstruction.

Irregular wide-QRS tachycardia with beat-to-beat QRS variation and rates often > 200 (up to 300) is pre-excited AF (accessory pathway); a uniform wide QRS is usually AF with bundle branch block. In pre-excited AF, AV nodal blockers, IV amiodarone and adenosine are contraindicated: they push conduction down the pathway to VF. Stable: IV procainamide or ibutilide; unstable: synchronized cardioversion.

Digoxin toxicity: hyperkalemia is the best predictor of mortality (not digoxin level). Give digoxin-specific Fab fragments if K > 5.0, serious arrhythmia, or end-organ damage.

Avoid diltiazem and verapamil in systolic heart failure, they worsen HF exacerbations (negative inotropy). Amlodipine and felodipine are the only CCBs considered safe in HFrEF.

Colchicine 0.5 mg daily (Lodoco, FDA 2023) adds to aspirin plus statin in ASCVD: LoDoCo2 2020 (chronic CAD) cut MACE 31%, COLCOT 2019 (within 30 d of MI) 23%, but CLEAR SYNERGY 2025 (7,062, started early in acute MI) was neutral, so do not start it routinely in acute MI. Contraindicated (fatal toxicity) with strong CYP3A4 or P-gp inhibitors, CrCl < 15 or severe liver disease; caution: diltiazem, CKD, myopathy.

Why is fenofibrate OK with a statin but gemfibrozil isn't? Gemfibrozil inhibits statin glucuronidation → markedly higher rhabdomyolysis risk. Cerivastatin was pulled from the market in 2001 after fatal rhabdo cases driven mainly by gemfibrozil co-administration. Fenofibrate doesn't share this interaction. If gemfibrozil is unavoidable, use it as monotherapy, never with a statin.

Patient with ASCVD on atorva 80, LDL 95, goal <70 -next move? Not 'atorva 160' (no such dose). Add ezetimibe 10 mg → ~20% more LDL drop (IMPROVE-IT 2015). If still not at goal, add a PCSK9i (FOURIER / ODYSSEY OUTCOMES, ~50-60% more drop) or inclisiran q6mo. Atorva 40 → 80 only adds ~6% more reduction but doubles myalgia, so escalating to a second drug beats pushing the statin.

Patient says her statin causes muscle pain -what do you do? Don't accept 'intolerance' on face value. SAMSON (NEJM 2020) showed about 90% of the symptom burden was reproduced by placebo capsules rather than by the statin, and half of participants successfully restarted a statin. Stop the drug, confirm symptoms resolve, rechallenge -same statin or switch to pravastatin / rosuvastatin every-other-day / low-dose atorva. Baseline 1-yr statin adherence is already only ~50%; don't lose patients to nocebo.

Vascepa is not Costco fish oil. Icosapent ethyl is pure EPA and cut MACE 25% in REDUCE-IT 2019, though its mineral oil placebo raised hsCRP and LDL, which may inflate it. Mixed EPA+DHA (Epanova) did nothing vs corn oil in STRENGTH 2020; Lovaza (omega-3-acid ethyl esters) and OTC fish oil lack outcome benefit. CV benefit is specific to Rx EPA on a statin, TG 150-499, with ASCVD or diabetes plus 2+ risk factors.

55F, LDL 220, dad MI at 48 -dx and why does it change your week? Heterozygous familial hypercholesterolemia (HeFH) until proven otherwise (~1 in 200-500, far more common than residents think). Confirm with LDLR / APOB / PCSK9 genetic testing. Cascade-screen all first-degree relatives -50% are affected. The 2026 ACC/AHA Dyslipidemia Guideline recommends a statin in FH children from age 8 when LDL stays ≥ 160 after 3-6 months of lifestyle; don't delay to adulthood.

When do you order Lp(a) and how does it change management? ONCE per lifetime in adults -it's genetically determined and doesn't budge with statin or lifestyle. Lp(a) ≥ 50 mg/dL (or ≥ 125 nmol/L) is a major risk enhancer. Lp(a) ≥ 50 + established ASCVD with goals unmet on a maximal statin → add a PCSK9 antibody (Class 1, 2026); it does not redefine very high risk. Statins don't lower it; PCSK9i and inclisiran lower it ~20-25%. Apheresis for refractory.

Why is the ferritin cutoff for iron deficiency in HF different from a healthy adult? In HF, iron deficiency is defined as ferritin < 100 ng/mL (absolute) OR ferritin 100-299 + TSAT < 20% (functional). The general-population cutoff is ferritin < 30. Reason: HF is a chronic inflammatory state, ferritin is an acute-phase reactant, and a 'normal' ferritin can mask depleted stores. TSAT < 20% is the more reliable functional marker. Affects ~50% of HF patients with or without anemia.

HFrEF patient, ferritin 80, TSAT 14%, NYHA III. Oral iron? No: HF raises hepcidin, which blocks gut absorption, and in IRONOUT-HF 2017 oral iron did not improve peak VO2. Give IV ferric carboxymaltose (Injectafer, US-labeled for HF) or ferric derisomaltose for better exercise capacity and QoL (FAIR-HF, CONFIRM-HF). AFFIRM-AHF 2020 and IRONMAN 2022 cut HF admissions but missed their primary endpoints.

Amlodipine caps simvastatin at 20 mg/day. Amlodipine inhibits intestinal and hepatic CYP3A4, pushing simvastatin exposure up about 1.8x and raising myopathy and rhabdomyolysis risk. Both are cheap generics on every formulary, so simvastatin 40 mg alongside amlodipine 10 mg reads as unremarkable on a med list. One of the most commonly missed interactions in primary care.

The CCB statin caps are not interchangeable: diltiazem and verapamil cap simvastatin at 10 mg, amlodipine at 20 mg. The non-DHPs are the stronger CYP3A4 inhibitors, so they get the tighter limit. Amiodarone and ranolazine sit in the 20 mg tier with amlodipine; dronedarone sits in the 10 mg tier. Applying the wrong tier is the easy error.

A statin dose cap is not a treatment plan. Simvastatin 20 mg is only moderate-intensity (~30% LDL reduction), so capping a patient who has a high-intensity indication quietly leaves them undertreated. If ASCVD or high-risk primary prevention demands high-intensity therapy, switch the statin rather than sit at the cap.

PREVENT gives several risks, and each guideline uses a different one. Statin decisions use 10-year PREVENT-ASCVD (bands 3/5/10%). Stage 1 hypertension and SGLT2i or GLP-1 in type 2 diabetes use 10-year total CVD at 7.5%, which includes heart failure and therefore runs higher. Pre-HF biomarker testing uses PREVENT-HF at 5%. There is no separate CAD output: coronary events sit inside ASCVD.

Hypomagnesemia is the #1 missed cause of refractory Afib with RVR. Always replete Mg²⁺ > 2.0 before escalating rate control.

Early rhythm control within 1 year of AF diagnosis reduces cardiovascular death, stroke, and HF hospitalization.

Apixaban is the preferred DOAC for Afib -lowest bleeding risk of all DOACs with superior stroke prevention vs warfarin.

The four pillars of HFrEF (ARNI + beta-blocker + MRA + SGLT2i) cut all-cause mortality by about half vs ACEi/ARB plus beta-blocker (cross-trial HR 0.53; 0.38 for CV death or HF hospitalization; 1.4 to 6.3 extra years of life; Vaduganathan, Lancet 2020) and by about 61% vs no therapy (Tromp, JACC HF 2022). Start all four early, not one at a time.

Only 3 beta-blockers are evidence-based in HFrEF: carvedilol, metoprolol succinate, and bisoprolol. Others have NO mortality data.

Sacubitril/valsartan (Entresto) reduced CV death by 20% vs enalapril -hold ACEi 36h before switching to avoid angioedema.

Door-to-balloon target is < 90 minutes. Every 30 minutes of delay increases 1-year mortality by 7.5%.

Modified Valsalva (strain + immediate leg raise) converts SVT in 43% of cases vs 17% for standard Valsalva. Try before adenosine.

Colchicine roughly halves recurrent pericarditis: incessant or recurrent disease fell from 37.5% to 16.7% in ICAP (NEJM 2013) and recurrence from 32.3% to 10.7% in COPE (Circulation 2005). Add it to every acute pericarditis regimen; NSAIDs alone are not enough.

HCM is the #1 cause of sudden cardiac death in young athletes. Risk stratify ALL patients: family SCD, wall ≥ 30 mm, unexplained syncope, NSVT.

ECG within 10 minutes for ALL chest pain. The 5 deadly causes: ACS, aortic dissection, PE, tension pneumothorax, esophageal rupture.

Wellens syndrome (biphasic or deep T inversions V2–V3) = critical LAD stenosis. Patient may be pain-free. Do NOT stress test → cath lab.

New LBBB is NOT automatically a STEMI. Use Sgarbossa criteria: concordant STE ≥ 1 mm (5 pts) is the most specific finding.

Defibrillation is the definitive treatment for VFib. Every minute of delay reduces survival by 7–10%. Shock first, then CPR + epi.

Amiodarone 300 mg IV push after 3rd shock for refractory VFib. Second dose 150 mg. Alternative: lidocaine 1–1.5 mg/kg.

High-sensitivity troponin allows a 0/1-hour rule-out pathway -saves hours in the ED without missing MI. Use the ESC algorithm.

Torsemide has better bioavailability (80-100%) than furosemide (~50%) in decompensated HF with gut edema -switch if oral furosemide isn't working.

DOSE 2011: IV furosemide at 2.5x the home oral dose vs 1x showed no significant difference in the coprimary endpoints (symptom relief P=0.06, creatinine change P=0.21), but high dose produced greater diuresis and better secondary decongestion measures with only transient creatinine rise. So dose boldly: start IV at 1 to 2.5x the home oral dose and uptitrate fast; timid dosing under-diureses.

Finerenone (nonsteroidal MRA) in T2D with CKD: FIDELIO-DKD 2020 cut the primary kidney composite (HR 0.82) with fewer CV events as a key secondary, and FIGARO-DKD 2021 made CV benefit the primary result (HR 0.87). Hyperkalemia stops it more often than placebo (2.3% vs 0.9%) but occurs less than with spironolactone (ARTS). FINEARTS-HF 2024 extended benefit to HF with EF 40% or above.

Losartan is the only US ARB with a clinically meaningful uricosuric effect (the parent drug inhibits URAT1; irbesartan did not lower urate head to head). The drop is modest, about 0.3-0.8 mg/dL (roughly 5-10%), so it does not replace urate-lowering therapy. ACR 2020 conditionally recommends choosing losartan preferentially and switching off hydrochlorothiazide when feasible in gout.

Always get a V4R lead in any inferior MI to detect RV involvement. RV infarct = preload-dependent, withhold nitrates and give fluids instead.

Pericarditis first-line: NSAIDs + colchicine. Post-MI pericarditis: ASA + colchicine (avoid NSAIDs). Steroids only if contraindications to NSAIDs.

Inpatient BP over 180/120 without acute target-organ damage: do not order PRN IV labetalol or hydralazine for a number. The 2025 AHA/ACC guideline rates acute IV or oral lowering in noncardiac admissions Class 3: Harm (hypotension, AKI, stroke, MI, mortality in observational data). Recheck the reading, treat pain, anxiety, urinary retention and withdrawal, resume home meds, and titrate oral therapy over days.

Ivabradine is for symptomatic HFrEF (EF 35% or less, sinus rhythm) with resting HR of 70 or more despite a maximally tolerated beta-blocker, or when beta-blockers are contraindicated (Corlanor label, SHIFT). It blocks the sinus node I-funny current, so it is useless in AF and raises AF risk; it cut HF hospitalizations, not CV or all-cause death, and never replaces titrating the beta-blocker first.

ASPREE (2018) showed aspirin for primary CVD prevention in patients > 70 didn't reduce death, dementia, or disability, but DID increase major bleeding. Generally stop ASA for primary prevention in this age group.

Cheyne-Stokes in heart failure = central sleep apnea from volume overload. First-line treatment is DIURESIS. Acetazolamide (mild metabolic acidosis stimulates respiration) is an adjunct if unresponsive.

COMET trial: carvedilol outperformed metoprolol tartrate in HFrEF mortality, but the metoprolol dose wasn't truly equivalent. Still, carvedilol has metabolic advantages (raises insulin sensitivity) and is often preferred.

Febuxostat has higher cardiovascular mortality than allopurinol (4.3% vs 3.2%). Use it only in young patients without CV risk who can't tolerate allopurinol; otherwise try a uricosuric agent.

Loop diuretic not working? Loops are threshold drugs: a sub-threshold dose gives no natriuresis however often it is given (IV furosemide threshold ~10 mg with normal GFR; in moderate CKD the effective dose rises to ~80–160 mg). Double the dose until it works or the ceiling is reached; only then shorten the interval (BID-TID or infusion) to beat post-diuretic sodium retention.

Chlorthalidone and indapamide are favored over HCTZ for potency and longer action, and chlorthalidone carries the ALLHAT outcome data. But in the Diuretic Comparison Project (NEJM 2022, N = 13,523 adults 65+ on HCTZ), switching to chlorthalidone did not reduce CV events (HR 1.04) and caused more hypokalemia (6.0% vs 4.4%); only prior MI or stroke showed benefit (secondary analysis). Check K+ in 1–2 weeks.

SGLT2 inhibitors reduce HFrEF mortality even in non-diabetics, theorized mechanism is metabolic shift to ketone bodies (cardioprotective, anti-inflammatory). Also raises hematocrit and improves remodeling. Reduce diuretic dose when starting.

Bifascicular block (RBBB + LAFB or LPFB) with 1st-degree AV block is often called trifascicular block, but the PR delay may be AV nodal, so it is not itself a pacing indication. Pace (Class I) for alternating bundle branch block, Mobitz II, high-grade or 3rd-degree AV block, or syncope with HV ≥ 70 ms at EP study. Asymptomatic bifascicular block with 1st-degree AV block: no pacemaker; work up any syncope urgently.

Sick sinus syndrome = SA node dysfunction → bradycardia, syncope, sometimes tachy-brady alternation. Definitive treatment is a pacemaker. Only then can you safely rate-control the tachy component with beta-blockers.

Naproxen has the least CV signal of NSAIDs: CNT meta-analysis (Lancet 2013, high-dose vs placebo) major vascular events RR 0.93 vs 1.37 coxibs, 1.41 diclofenac; ibuprofen doubled major coronary events (RR 2.22). All NSAIDs about doubled heart failure. PRECISION 2016: celecoxib non-inferior to naproxen (HR 0.93). Post-MI, acetaminophen first; NSAID only if unavoidable, lowest dose, shortest course.

Reversible NSAIDs can block aspirin from acetylating platelet COX-1. FDA 2006: one ibuprofen 400 mg dose 8 h before or 30 min after IR (non-enteric) aspirin. Naproxen is worse: even 220 mg BID interferes (Anzellotti 2011), the label expects Rx doses to as well, and its 12-17 h half-life means dosing 2 h after aspirin lessens but does not remove the loss. On daily ASA prefer acetaminophen or a non-interfering NSAID.

The way out of a statin CYP3A4 cap is a statin that is not a 3A4 substrate: rosuvastatin, pravastatin, or pitavastatin. Atorvastatin is a 3A4 substrate but carries no labeled CCB dose cap, so it is usually the practical high-intensity swap. Rhabdomyolysis has still been reported with atorvastatin plus amlodipine, so counsel on myalgias either way.

PREVENT gets no vote in four groups. Diabetes, CKD stage 3 or 4 (not dialysis: no benefit in 4D or AURORA) and HIV at ages 40-75, plus LDL-C ≥ 190, are Class 1 statin indications (2026 ACC/AHA): a 44-year-old with diabetes at PREVENT-ASCVD 2% still gets one. In diabetes, ≥ 10% adds ezetimibe or a PCSK9 antibody; it does not set intensity. Run the score to set goals, not to decide whether to treat.

After ROSC, the question that decides temperature control is 'do they follow commands?', not 'what was the rhythm?'. Every adult who does not, including the in-hospital PEA arrest, gets a device holding one constant target between 32 and 37.5°C (89.6 to 99.5°F) for at least 36 hours (2025 AHA; 2020 said 24). Cooling to 33°C (91.4°F) has not beaten normothermia (TTM2), but every trial arm actively prevented fever, so doing nothing is the one untested option. Rewarm no faster than 0.5°C/h (0.9°F/h), and do not prognosticate until 72 h after normothermia and off sedation.

Myoclonus after cardiac arrest is a reason to get an EEG, not a reason to reach for propofol. It follows 18-34% of arrests and up to half of those patients are seizing, which the exam cannot tell you. Jerks time-locked to an EEG correlate are a seizure: treat them. Jerks with no EEG correlate should not be treated (2025 AHA, Class 3): nothing shows they injure the brain, and the sedatives it takes to stop them drop the pressure and cloud the exam you are waiting 72 hours to do. As a lone finding its prognostic value is uncertain, even on day 1.

New dyspnea on ticagrelor is common (13.8% vs 7.8% on clopidogrel in PLATO), but after ACS rule out heart failure, ischemia, PE and bleeding first. Drug dyspnea is usually mild, early and fades: reassure and continue. Caffeine, though an adenosine antagonist, did not lower dyspnea rates in PEGASUS-TIMI 54. If intolerable, switch with a 600 mg clopidogrel load so platelet inhibition does not lapse.

In inferior STEMI, always check V4R -40% have RV involvement. Nitrates and diuretics can cause fatal hypotension in RV infarct.

ACS 2025: Dual antiplatelet therapy duration is now personalized based on bleeding vs ischemic risk -no more blanket 12 months.

Anticoagulate AF regardless of CHA₂DS₂-VASc in: HCM, cardiac amyloidosis, moderate-severe (rheumatic) MS, mechanical valve, LA/LAA thrombus, or peri-cardioversion. The score doesn't apply -stroke risk is already prohibitive.

In AMI shock, early revascularization and Impella CP both cut mortality. SHOCK 1999 (N=302): PCI or CABG missed its 30-day endpoint but cut 6-month mortality (50.3% vs 63.1%). DanGer Shock 2024 (N=360, STEMI shock): Impella CP cut 180-day death (45.8% vs 58.5%) but raised complications (24% vs 6%), so it is Class 2a only in selected patients (ACC/AHA 2025). AMI now causes only about 30% of cardiogenic shock (CCCTN).

IABP has no mortality benefit in MI shock (IABP-SHOCK II 2012, N=600; 39.7% vs 41.3%), nor does routine VA-ECMO (ECLS-SHOCK 2023, N=420; 47.8% vs 49.0%, more bleeding). Impella CP cut 180-day death in selected STEMI shock (DanGer Shock 2024; 45.8% vs 58.5%) but raised complications (24.0% vs 6.2%) and RRT (41.9% vs 26.7%). 2025 ACS guideline: Impella 2a; routine IABP and VA-ECMO Class 3.

SGLT2 inhibitors are the first drug class to show benefit in HFpEF -use in all HF regardless of EF.

Milrinone works when beta-receptors are downregulated (chronic HF on BB) -it bypasses the β-receptor via the PDE3 pathway.

In hypertensive emergency, lower MAP by no more than 25% in the first hour. Dropping too fast causes watershed infarcts.

De Winter T waves (ST depression at J-point + tall symmetric T waves in precordial leads) = STEMI equivalent. Activate the cath lab.

Mechanical complications (free wall rupture, VSD, papillary muscle rupture) peak at days 3–7 post-MI. Sudden decompensation = think mechanical.

HEART score 0–3 = < 2% MACE at 6 weeks. These patients can safely be discharged from the ED with outpatient follow-up.

Delay P2Y12 loading until cath in NSTEMI -10–15% need CABG, and elective CABG means holding ticagrelor 3–5 days, clopidogrel 5 and prasugrel 7 (2025 ACC/AHA).

Adenosine half-life is 6 seconds. Push it fast (antecubital vein), follow with 20 mL NS flush, and elevate the arm.

Ventricular rate of exactly ~150 bpm? Think atrial flutter with 2:1 block until proven otherwise.

Steroids increase pericarditis recurrence. Use only as last resort when NSAIDs + colchicine fail or are contraindicated.

Pericarditis ECG: diffuse concave-up ST elevation + PR depression. STEMI ECG: territorial convex-up ST elevation + reciprocal changes.

Stanford A = any ascending aorta involvement = emergent surgery. Stanford B = descending only = medical management unless complicated.

Symptomatic severe aortic stenosis (SAD triad) = urgent AVR. Without surgery, 50% mortality at 2 years once HF symptoms develop.

IABP is contraindicated in aortic regurgitation -balloon inflation in diastole worsens regurgitant flow back into the LV.

TAVR is now approved for all surgical risk categories for aortic stenosis, not just high-risk or inoperable patients.

Exertional syncope is cardiac until proven otherwise -think AS, HCM, arrhythmia. These patients get admitted with telemetry.

Routine head CT in syncope has a low yield: a 2019 systematic review (Viau, Acad Emerg Med; 17 studies, 3,361 patients) found acute hemorrhage, mass or infarct in 1.1 to 3.8% (3.8% in ED series), mostly in patients with focal deficits, head trauma, age 65 or older, anticoagulation, or seizure or stroke history. Scan for those or SAH concern (sudden severe headache), not every faint.

Mobitz I (Wenckebach) = benign, AV nodal, often transient. Mobitz II = dangerous, infranodal, needs pacemaker even if asymptomatic.

Atropine doesn't work in infranodal block (Mobitz II, 3rd degree with wide QRS) -there's no parasympathetic innervation below the AV node.

Young patient with unexplained heart block → think Lyme disease. Fully reversible with IV ceftriaxone. Always check Lyme serologies.

Cardiac MRI distinguishes myocarditis from MI: mid-wall/epicardial LGE (myocarditis) vs subendocardial/transmural LGE (MI).

Fulminant myocarditis is not benign: the old teaching of a paradoxically better prognosis has been overturned. In Ammirati 2017 (Circulation) in-hospital death or transplant was 25.5% vs 0% for non-fulminant disease, and 9-year transplant-free survival 64.5% vs 100%. Recognize shock early, start MCS before multiorgan failure, and biopsy: giant cell and eosinophilic forms respond to immunosuppression (AHA 2020).

Checkpoint inhibitor myocarditis: rare (~1%) but mortality > 40%. Stop the drug. High-dose IV methylprednisolone immediately.

HCM murmur gets LOUDER with Valsalva (↓ preload → smaller LV → more obstruction). This is the opposite of almost every other murmur.

Mavacamten (cardiac myosin inhibitor) cut the post-exercise LVOT gradient by 47 vs 10 mmHg with placebo in symptomatic obstructive HCM (EXPLORER-HCM, Lancet 2020, n=251); 37% vs 17% met the pVO2/NYHA primary endpoint. It targets sarcomere hypercontractility, HCM's root cause, but can drop LVEF: echo monitoring is mandatory (REMS) and the drug is held if LVEF falls below 50%.

NTG response does NOT distinguish cardiac from non-cardiac chest pain. Esophageal spasm also responds to NTG. Use ECG + troponin instead.

De Winter T waves (upsloping ST depression + peaked T waves V1–V6) = LAD STEMI-equivalent. No ST elevation. Activate cath lab.

In every code: check glucose, check potassium, think H's and T's. The most fixable causes: hypovolemia, hypoxia, hyperkalemia, tension PTX.

Statin indications (2026 ACC/AHA): #1 clinical ASCVD (high-intensity). #2 LDL-C ≥ 190. #3 diabetes age 40-75. #4 CKD stage 3+ or HIV age 40-75. #5 10-yr PREVENT-ASCVD ≥ 5% (moderate; high-intensity at ≥ 10%). Groups 1-4 are treated without a score. The 2018 Pooled Cohort cutoff of 7.5% is retired: PREVENT runs 40-50% lower in the same patient.

SGLT2 inhibitors reduce HF hospitalization even in patients WITHOUT diabetes. They're now foundational HF therapy.

Dobutamine is an inotrope (β1 agonist) -it increases contractility but can cause hypotension through β2-mediated vasodilation. Not a vasopressor.

In cardiogenic shock, milrinone (PDE3 inhibitor) provides inotropy + vasodilation -useful for RV failure and pulmonary HTN.

In hypertensive emergency, lower BP by ≤ 25% in the first hour. Too rapid a drop causes watershed infarcts.

NSTE-ACS (2025 ACC/AHA): intermediate- or high-risk patients get an invasive strategy during hospitalization (Class 1) to cut MACE. GRACE mainly sets timing: > 140 (high risk) makes cath within 24 h reasonable (Class 2a; TIMACS benefit was in GRACE > 140). Refractory angina or hemodynamic or electrical instability = immediate cath regardless of score. Low risk: routine or selective invasive approach.

Syncope during exertion is cardiac until proven otherwise: aortic stenosis, HCM, ARVC, long QT (especially LQT1), CPVT and anomalous coronary artery. Brugada does not belong on the exertional list: its VF clusters at rest and during sleep (Matsuo 1999: 87% of ICD-detected VF episodes during sleep), with fever and vagal states as triggers, so think Brugada (or LQT3) for syncope at rest or in sleep.

Negative troponin at 0h and 3h with low-risk HEART score (0–3) = < 2% chance of MACE at 30 days → safe for discharge.

Statin benefit is greatest in secondary prevention (ASCVD). For primary prevention use the PREVENT-ASCVD calculator: ≥ 10% = high-intensity statin (goal LDL-C < 70), 5 to < 10% = at least moderate-intensity (goal < 100), 3 to < 5% = decide with risk enhancers. Never read a PREVENT score against the old 7.5% Pooled Cohort cutoff.

In Afib with RVR + hypotension, don't chase rate with more diltiazem -you'll drop MAP further. Use amiodarone IV or cardiovert if truly unstable.

Diltiazem often controls rate faster than metoprolol in stable AF with EF > 40%: in the Fromm 2015 ED RCT (N=52), 95.8% vs 46.4% reached HR < 100 by 30 min, with no difference in hypotension or bradycardia. Both are negative inotropes; the 2023 ACC/AHA AF guideline gives either Class 1 but rates IV diltiazem 3: Harm in moderate-severe LV dysfunction, so use a beta blocker, or digoxin or amiodarone if decompensated.

LAA closure (Watchman) is reasonable (Class 2a, 2023 ACC/AHA/ACCP/HRS AF guideline) for AF with CHA2DS2-VASc ≥ 2 and a contraindication to long-term anticoagulation from a nonreversible cause, and may be reasonable (2b) when bleeding risk on OAC is high. The RCT evidence (PROTECT AF, JAMA 2014, 3.8-year follow-up) was in warfarin-eligible patients, where closure was noninferior to warfarin.

Complete revascularization (treat non-culprit lesions) during index admission reduces MACE vs culprit-only PCI in STEMI with multivessel disease.

In severe MR, afterload reduction (nitroprusside, ACEi) reduces regurgitant fraction by favoring forward flow -a temporizing bridge to surgery.

RV infarct (often with inferior MI): clear lungs + hypotension + JVD. Give IV fluids; AVOID nitrates and morphine -RV is preload-dependent and even small drops in preload cause cardiovascular collapse.

New LBBB is no longer a STEMI equivalent on its own -use Sgarbossa criteria (concordant ST elevation ≥ 1 mm, concordant ST depression V1-V3, or excessive discordance) to identify true STEMI in LBBB.

Nitrates are NOT absolutely contraindicated in inferior MI, only when RV is involved. Check V4R first; if no RV infarct, treat symptomatically.

R > S in V1 is posterior ischemia until proven otherwise. RVH can also do this (with RAD), but posterior MI is the can't-miss diagnosis.

Mechanical aortic valves bridge less often than mitral valves, AV has high flow and less stasis. MVR patients need peri-op bridging.

Mechanical AVR: lifelong warfarin, INR 2.5 for a bileaflet or current-generation valve with no thromboembolic risk factors, 3.0 with risk factors or an older-generation valve (ACC/AHA 2020). DOACs are contraindicated. Routine aspirin was dropped: adding 75-100 mg is only Class 2b, for a separate antiplatelet indication with low bleeding risk (Class I in 2014). Bioprosthetic valve anticoagulation is less clear-cut.

HTN emergency: lower SBP no more than 25% in hour 1, then < 160/100 by 2 to 6 h, then 130 to 140 over 24 to 48 h, as faster drops cause watershed ischemia (AHA/ACC 2025). Exceptions: dissection, SBP < 120 and HR < 60 in hour 1; eclampsia or pheo crisis, SBP < 140 in hour 1; ischemic stroke, permissive only if no reperfusion planned, as thrombolysis needs < 185/110 before, < 180/105 for 24 h.

Before diagnostic stress MPI, hold caffeine 12 h (an adenosine-receptor blocker that blunts adenosine, regadenoson and dipyridamole) and, if the referring physician agrees, beta-blockers, CCBs and nitrates, which mask ischemia and lower accuracy (ASNC). Coronary CTA is the opposite: beta-blockers are GIVEN for HR 60 or less, plus SL nitroglycerin to dilate the coronaries (not after a PDE5 inhibitor).

Wide-complex tachycardia in a young, healthy person is MORE likely SVT with aberrancy than VT, but still treat as VT until proven otherwise. Stability ≠ diagnosis.

Paradoxical low-flow low-gradient aortic stenosis: low gradient + preserved EF in a small, underfilled LV (often older women). Looks mild on echo but carries same mortality as classic severe AS.

Obesity paradox in ACS: smokers and obese patients have LOWER ACS mortality. Likely confounded by younger age at presentation and more aggressive workup, don't under-treat these patients.

TEER (MitraClip) is Class 2a for severe secondary MR still NYHA II-IV on optimized GDMT with suitable anatomy, LVEF 20-50%, LVESD ≤ 70 mm and PASP ≤ 70 mmHg (2020 ACC/AHA; COAPT: HF hospitalization 36% vs 68% per patient-year, 2-yr death 29% vs 46%). Optimize GDMT first: MR proportionate to LV dilation often improves with it. Primary MR: Class 2a only if NYHA III-IV at high surgical risk.

Hyperthyroid-induced atrial fibrillation: rate control with beta-blockers is harder, receptor density is upregulated. Often needs higher doses or addition of digoxin until thyroid is controlled.

Torsemide has a longer half-life (3.5 h vs 2 h) and better, more predictable oral bioavailability (80–90% vs 10–80%) than furosemide, consider switching for outpatient HF management.

Nitroprusside rapidly reduces afterload in cardiogenic shock, quick-onset, quick-offset, target MAP 60–70. Transition to oral ACEi/hydralazine once stabilized; limit to 24–48 h with renal dysfunction (thiocyanate toxicity).

In CKD patients with ACE/ARB-induced hyperkalemia, try a K-binder (patiromer, sodium zirconium) BEFORE stopping the RAAS blocker, the drug is providing mortality benefit.

Ischemic cardiomyopathy carries higher sudden-cardiac-death risk than nonischemic, lower ICD threshold. Nonischemic CM may be drug-related (reversible) and infection/nonadherence risks can weigh against device.

CAC does not rule out ACS: it misses non-calcified plaque, including the thin-cap fibroatheromas that rupture, so CAC 0 never replaces ECG and serial troponin. Not useless, though: in 12,376 acute chest pain patients CAC 0 had a 98% NPV for obstructive CAD and 0.8% MACE, yet 9% had non-obstructive plaque (Agha 2022). The 2021 AHA/ACC guideline's CAC role (Class 2a) is low-risk stable, not acute, chest pain.

In ACLS if amiodarone is unavailable, use lidocaine. It depresses Purkinje fiber automaticity and raises the ventricular fibrillation threshold. Either drug works in pulseless VT/VF.

Paradoxical splitting of S2 (splitting disappears on inspiration) suggests delayed aortic closure, think LBBB, severe AS, or HCM. Normal S2 splitting = A2 before P2, widens on inspiration.

Dental prophylaxis is NOT needed for uncomplicated VSDs without a history of endocarditis. Indications: unrepaired cyanotic CHD, prosthetic material within 6 months, or repaired CHD with residual defects at/near the patch.

Pre-cardioversion sedation: in a 2018 meta-analysis of 9 RCTs, etomidate (0.1 to 0.15 mg/kg, usually with fentanyl) caused far less hypotension than propofol (RR 0.11) and less respiratory depression, with similar recovery time and shock success, but more myoclonus (RR 8.9) and nausea. Favor etomidate when BP or EF is low, propofol when hemodynamics are robust; midazolam pretreatment reduces etomidate myoclonus.

In SOAP II (NEJM 2010, N=1,679) dopamine caused twice the arrhythmias of norepinephrine (24.1% vs 12.4%) with no significant 28-day mortality difference overall (52.5% vs 48.5%, p=0.10) or in the septic shock subgroup; mortality was higher only in cardiogenic shock. Norepinephrine is first-line in septic shock (SSC 2026, strong recommendation); avoid dopamine.

Always give thiamine BEFORE glucose in alcoholic patients -glucose depletes remaining thiamine → precipitates Wernicke's.

Rasburicase is contraindicated in G6PD deficiency -generates H₂O₂ → massive hemolysis. Screen before giving.

Epinephrine IM is the ONLY first-line treatment for anaphylaxis. There is NO contraindication -not age, pregnancy, or cardiac disease.

Up to 20% of anaphylaxis has NO skin findings. Don't wait for hives. Isolated hypotension or bronchospasm after allergen = anaphylaxis → give epi.

Neurogenic shock (SCI above T6): BRADYCARDIC hypotension from lost sympathetic tone (unlike hemorrhagic or septic shock). Atropine for bradycardia, norepinephrine for pressure. The 2024 AO Spine/Praxis guideline loosened the old 85–90 mmHg x 7 day rule: keep MAP at least 75–80 and do not push above 90–95 mmHg, for 3–7 days, because the evidence tying a strict 85 target to neurologic recovery is weak.

Naltrexone for OUD: warn patients their opioid tolerance is LOST while on therapy. Relapse with 'usual dose' can be fatal. Counsel on this before every prescription, harm reduction, not moralizing.

Cytokine release syndrome (fever, hypotension, hypoxia) starts a median 2-3 days after axi-cel CAR-T, about 7 days (up to 3 weeks) after cilta-cel, and 1-2 days after a bispecific dose. Tocilizumab (IL-6R blocker) is first-line from grade 2; add dexamethasone for refractory grade 2 (upfront per the axi-cel label) and grade 3-4. ICANS without CRS gets steroids, not tocilizumab.

In hypothermia, warm all IV fluid to 38 to 42°C; cold fluid deepens hypothermia. WMS prefers normal saline over lactated Ringer's because a cold liver clears lactate slowly, but that is expert opinion now contested (LR's lactate is a buffer, not an acid); do not delay volume over fluid choice. Check glucose and give dextrose empirically for altered mental status if no glucometer; shivering depletes glycogen.

D-lactic acidosis (the trap): short bowel and SIBO patients let gut bacteria (Lactobacillus, Strep bovis, Bifidobacterium) ferment unabsorbed carbs into D-lactate, which humans cannot clear (we metabolize L-lactate efficiently but not D-). Presents as episodic post-meal encephalopathy (slurred speech, ataxia, looks intoxicated) with wide anion gap. The standard lactate assay measures L-lactate only and reads normal. Order D-lactate level specifically. Treat: low-carb diet, oral non-absorbable antibiotics (metronidazole, neomycin, rifaximin). Cohen-Woods Type B1.

Lactate elevated, BP normal, patient looks well-perfused → think Type B, not more pressors. Differential: drugs (metformin, linezolid > 2 wks, propofol infusion syndrome, NRTIs, β2 agonists), liver failure (impaired clearance), malignancy (Warburg effect, classic in leukemia/lymphoma), thiamine deficiency, D-lactic in short bowel. Sepsis can also produce Type B physiology before overt hypotension.

Preoxygenate with NIV or high-flow nasal cannula, not a non-rebreather. A non-rebreather cannot deliver FiO2 much above 0.6-0.7 and fails in shunt. In PREOXI, NIV halved hypoxemia during emergency intubation (9.1% vs 18.5%), and the 2026 ATS guideline makes HFNC or NIV a strong recommendation. Keep nasal cannula or HFNC on for apneic oxygenation.

Start vasopressin 0.03 units/min (fixed dose) once norepinephrine reaches ~0.25–0.5 mcg/kg/min -spares catecholamine exposure without titration.

SSC 2026: Peripheral vasopressors are OK to start -don't delay pressors waiting for central line access.

SSC 2026: antibiotics immediately, ideally within 1 hour, for possible, probable or definite septic shock and for probable or definite sepsis without shock (strong). Only possible sepsis without shock allows a rapid time-limited workup, then antibiotics within 3 hours if infection is still suspected. Blood cultures first, ideally before the dose.

Low tidal volume (6 mL/kg PBW) in ARDS reduced mortality by 22% -this is THE most important ventilator intervention.

Driving pressure (Pplat − PEEP) < 15 cmH₂O is the best predictor of survival in ARDS -better than tidal volume alone.

Winter's formula: expected PCO₂ = 1.5 × [HCO₃] + 8 ± 2. If actual PCO₂ doesn't match → there's a second respiratory disorder.

Always correct the anion gap for albumin. For every 1 g/dL albumin below 4, add 2.5 to the AG. A 'normal' AG in a hypoalbuminemic patient may be hiding an AG acidosis.

Glucagon 1–5 mg IV for anaphylaxis in patients on beta-blockers -bypasses blocked β-receptors when epi alone fails.

LR is preferred over NS for resuscitation -SMART trial showed balanced crystalloids reduced major adverse kidney events (MAKE30 composite). Mortality alone trended lower (10.3% vs 11.1%) but was not statistically significant (P = 0.06).

Girard 2008 (ABC trial, N = 336): adding a daily spontaneous awakening trial (sedative interruption) to the daily SBT, vs usual sedation plus SBT, gave 3 more ventilator-free days (14.7 vs 11.6), shorter ICU and hospital stays, and lower 1-year mortality (HR 0.68, NNT 7). Self-extubation rose (16 vs 6) without more reintubation. This is the B (Both SAT and SBT) of the ABCDEF bundle: pair RN and RT each morning.

Neuromuscular blockade in ARDS is targeted, not routine: ROSE 2019 found no benefit of routine early paralysis over light sedation, but SCCM 2026 suggests NMBAs when P/F stays < 150 with persistent hypoxemia or unmet vent targets after ventilator and sedation optimization, for no more than 48 h.

Stress-dose steroids (hydrocortisone 200 mg/day) in community-acquired pneumonia requiring ICU admission reduced mortality in CAPE COD.

Post-hypercapnic alkalosis occurs when chronic CO₂ retention is corrected faster than the kidneys can excrete retained HCO₃⁻. Classic scenario: intubating a chronic CO₂ retainer and ventilating to a 'normal' PaCO₂ of 40 mmHg -the persistent metabolic alkalosis can cause arrhythmias, seizures, and impaired O₂ delivery.

Preventing post-hypercapnic alkalosis: when mechanically ventilating a patient with chronic hypercapnia (e.g., severe COPD, OHS), target their BASELINE PaCO₂, not 40. Wean the ventilator slowly -dropping PaCO₂ too fast leaves behind a large HCO₃⁻ excess the kidneys can't clear quickly.

Treating post-hypercapnic alkalosis: correct chloride depletion with NS (Cl⁻ allows the kidney to excrete HCO₃⁻). Acetazolamide 250-500 mg IV/PO promotes renal HCO₃⁻ wasting. Also replete K⁺ -hypokalemia perpetuates alkalosis by increasing proximal HCO₃⁻ reabsorption.

Hypokalemia causes metabolic alkalosis via two mechanisms: (1) transcellular shift -K⁺ leaves cells, H⁺ moves IN to maintain electroneutrality, raising plasma pH; (2) renal H⁺ wasting -the distal nephron secretes H⁺ instead of K⁺, and intracellular acidosis in tubular cells boosts HCO₃⁻ reabsorption and ammoniagenesis.

Ventilator flow curve showing air trapping? Increase expiratory time: drop RR first, then drop I:E ratio. Avoid changing TV (alters minute ventilation).

Ketamine is the sedative of choice for awake intubation, maintains airway tone, protective reflexes, and respiratory drive while providing dissociation and analgesia.

Fever in sepsis: routine antipyresis neither helps nor clearly harms (HEAT 2015, N = 700: IV acetaminophen did not change ICU-free days or 90-day mortality, 15.9% vs 16.6%); the harm signal was one small, stopped-early trauma-ICU trial. Treat for comfort, to prevent fever after cardiac arrest, in acute brain injury, or in pressor-dependent septic shock (cooling cut pressor needs at 12 h, not 48 h; Schortgen 2012).

Chlorhexidine is superior to povidone for central line insertion, antimicrobial activity lasts ≥ 6 hours on skin. Let it dry fully before draping.

Norepinephrine is first-line pressor in cardiogenic shock, not dopamine (arrhythmias). Add dobutamine for low CO or 'cold-dry' picture. Milrinone over dobutamine for bad RV or pulmHTN (lusitropy + pulmonary vasodilation).

Methadone in acute pain: switch from daily to TID dosing. α-elimination (analgesia) is 8–12 h; β-elimination (withdrawal suppression) is 30–60 h. Once supplemental opioids aren't needed, convert back to daily.

PE shock (Category D-E): norepinephrine is the first-line vasopressor (restores MAP and RV coronary perfusion); add vasopressin second and dobutamine for low output (2026 AHA/ACC PE guideline). Avoid phenylephrine (raises PVR) and fluid loading (dilated RV worsens septal shift; 250 mL boluses only if hypovolemic). Tamponade needs drainage and tension PTX decompression; pressors only bridge.

Ventilator cycle has 3 variables: TRIGGER (what starts inspiration, time, pressure, flow), TARGET (what's sustained, pressure or volume), and CYCLE (what ends inspiration, time, volume, or flow).

Brain death: confirm coma and absent brainstem reflexes, then do the apnea test. If it cannot be completed safely or read (chronic CO₂ retainer, unknown baseline PaCO₂), add a cerebral blood flow test: radionuclide perfusion scan, 4-vessel catheter angiography, or TCD (adults only). The 2023 AAN/AAP/CNS/SCCM guideline retired EEG (does not test the brainstem) and CT angiography (unvalidated, false positives).

Toxic megacolon: colon diameter > 6 cm + systemic toxicity (fever, tachycardia, leukocytosis, electrolyte abnormalities). Stop anti-diarrheals and opioids, decompress with NG, broad-spectrum abx, surgery if no improvement in 24–48 h.

Hypothermia rewarming: start with passive external (blankets) → active external (forced-air, Bair Hugger) → active internal (warm IVF, bladder/peritoneal/thoracic lavage, ECMO for severe). Continue CPR until core temp > 32°C before declaring death ('not dead until warm and dead').

Dexmedetomidine has NO respiratory depression, continue it through extubation and after. Minimal amnesia, may reduce delirium vs benzos/propofol in ICU sedation.

Methadone and buprenorphine save lives in opioid use disorder: all-cause mortality falls roughly 40-50% (Larochelle 2018, post-overdose cohort: methadone aHR 0.47, buprenorphine 0.63; Sordo 2017 meta-analysis). Naltrexone has not shown this benefit. Death risk spikes in the weeks after stopping, so prioritize retention. Frame MOUD as treatment, not 'trading one addiction for another.'

Don't titrate methadone daily: it accumulates (steady state takes 3 to 5 days; half-life 8 to 59 h), and its peak respiratory depressant effect comes later and lasts longer than its relief of pain or withdrawal. Space increases at least 3 to 5 days apart; some patients need up to 12 days. Deaths in early treatment have come from these cumulative effects, so monitor closely after every increase.

Daily sedation holidays + spontaneous breathing trials reduce ventilator days, ICU LOS, and mortality (Kress 2000, Girard 2008). Make SAT/SBT a daily inpatient ICU ritual, not an optional protocol.

Severe alcohol withdrawal load: phenobarbital 10 mg/kg IV (or 130 mg q30 min until effect, cumulative 10–20 mg/kg). Watch for oversedation and respiratory depression, be ready to intubate.

Hold tube feeds in patients on high-dose vasopressors, bowel vasoconstriction + increased metabolic demand = mesenteric ischemia risk. Trophic feeds may be acceptable at low doses; reassess daily.

O₂ dissociation rule of thumb (40-50-60 / 70-80-90): SpO₂ 70 ≈ PaO₂ 40, SpO₂ 80 ≈ PaO₂ 50, SpO₂ 90 ≈ PaO₂ 60. Quick mental shortcut on the steep part of the curve: SpO₂ minus 30 ≈ PaO₂. SpO₂ 90 / PaO₂ 60 is the 'knee': above it you're on the flat plateau (small SpO₂ changes hide big PaO₂ swings); below it you're on a cliff (small PaO₂ drops crash the SpO₂ fast). Targets: ≥ 92% general, 88-92% in COPD CO₂ retainers, 88-92% permissive in ARDS. Pulse ox lies in CO poisoning (reads ~100% despite hypoxia, need co-oximetry) and methemoglobinemia (stuck ~85% regardless of true sat; treat with methylene blue). Curve right-shifts (releases O₂ easier) with fever, acidosis, ↑ CO₂, ↑ 2,3-BPG; left-shifts (holds O₂ tighter) with hypothermia, alkalosis, CO, MetHb, fetal Hb.

Cohen-Woods classifies lactic acidosis as just two types: Type A (tissue hypoperfusion or hypoxia: shock, ischemia, severe hypoxemia, anemia, CO poisoning) and Type B (everything else). Type B has 3 subtypes: B1 underlying disease (liver failure, malignancy, sepsis, thiamine deficiency, short bowel/SIBO), B2 drugs/toxins (metformin, linezolid, propofol, NRTIs, β2 agonists), B3 inborn errors. Every named cause sits inside one bucket. There is no Type C or D.

Refractory lactic acidosis in alcoholics, malnourished, or post-bariatric patients: think thiamine deficiency. Without thiamine, pyruvate cannot enter the TCA cycle and shunts to lactate. Empiric thiamine 200–500 mg IV q8h × 3 days before glucose is both diagnostic and therapeutic, and prevents Wernicke's. Lactate often clears dramatically within hours of repletion.

Respiratory versus metabolic: the pH and the PaCO₂ move in OPPOSITE directions in a respiratory disorder, while the pH and the HCO₃ move in the SAME direction in a metabolic one. CO₂ is an acid, so retaining it drives the pH down; bicarbonate is a base, so losing it drives the pH down. Getting this backwards labels a tiring COPD patient as metabolic and sends you hunting for an anion gap that was never there.

Alkali therapy makes sense in a non-gap acidosis and usually not in a gap acidosis, and the delta ratio is what tells you which one you are looking at. Chloride is not metabolizable, so bicarbonate lost to diarrhea, saline or an RTA is gone and has to be replaced. Lactate and ketones ARE metabolized back to bicarbonate once the process stops, so a gap acidosis self-corrects and bicarb buys only overshoot alkalosis, ionized hypocalcemia and a sodium load.

Prone positioning reduces mortality in severe ARDS (P/F < 150) by nearly 50% when done early and for >16 hours/day.

Post-hypercapnic alkalosis is a chloride-responsive alkalosis (urine Cl⁻ < 25 mEq/L). The triad to fix: give Cl⁻ (NS), give K⁺, and slow down the ventilator. If the patient can't be weaned off the vent, acetazolamide is your best pharmacologic tool.

Balanced crystalloids (LR/PlasmaLyte) reduce major adverse kidney events vs normal saline in critically ill patients.

Passive leg raise predicts fluid responsiveness better than CVP -a 10% stroke volume increase predicts a positive bolus response without giving fluid first.

Lactate clearance ≥ 10% per 2 hours is a reasonable resuscitation target in septic shock (Jones 2010 / EGDT era). ANDROMEDA-SHOCK (2019) separately showed capillary refill–guided resuscitation trended better than lactate-guided for 28-day mortality.

Hydrocortisone speeds shock reversal; a fludrocortisone survival edge is unproven. ADRENAL 2018 (N=3,800, hydrocortisone alone): shock resolved in 3 vs 4 days, 90-day mortality 27.9% vs 28.8%. APROCCHSS 2018 (N=1,241, plus fludrocortisone): 43.0% vs 49.1%, in a sicker cohort (placebo mortality 49% vs 29%). No trial compares the two regimens head to head, so fludrocortisone is optional.

SSC 2026: qSOFA alone misses too many patients. For acutely ill hospitalized patients, use NEWS/NEWS2, MEWS or SIRS rather than qSOFA as the single screening tool (strong recommendation, moderate certainty). SSC sets no numeric cutoff, so follow your institution's trigger; in the RCP NEWS2 scheme a score of 5 or more prompts urgent review and 'think sepsis'.

SSC 2026 suggests IV corticosteroids for adults with septic shock (conditional, low certainty), dropping the 2021 qualifier of an ongoing vasopressor requirement; no wait time is mandated. Typical regimen: hydrocortisone 200 mg/day (50 mg IV q6h or infusion). SSC 2016 suggested against them unless fluids and pressors failed. Expect faster shock reversal; the mortality effect is uncertain.

SSC 2026: Balanced crystalloids (LR/PlasmaLyte) suggested over 0.9% saline. 30 mL/kg is a starting benchmark -titrate to dynamic responsiveness (passive leg raise, stroke volume variation, PPV) rather than a fixed volume.

SSC 2026: New recommendation on fluid removal after resuscitation -a topic not previously addressed. Don't leave patients fluid-overloaded.

SSC 2026: MAP ≥ 65 mmHg remains standard; 60–65 mmHg is acceptable in patients ≥ 65 yo to reduce vasopressor exposure. Higher targets (80) showed no mortality benefit but more arrhythmias.

SSC 2026: 'Code sepsis' huddle protocols are now suggested at institutional level. Performance improvement programs recommended.

SSC 2026 suggests prehospital antibiotics only for definite or probable sepsis with hypotension (septic shock) when in-hospital evaluation is more than 60 min away (conditional, very low certainty). The largest RCT, PHANTASi 2018 (N=2,672, ambulance ceftriaxone), showed no 28-day mortality benefit (8% vs 8%); the benefit signal comes mainly from observational cohorts.

SSC 2026: Post-sepsis care now addressed -survivors need psychological and physical rehabilitation follow-up after discharge.

Phenytoin does NOT work for alcohol withdrawal seizures. The mechanism is GABA-related -only benzos and phenobarbital work.

DTs have 15–20% mortality if untreated. The key feature distinguishing DTs from alcoholic hallucinosis is altered sensorium.

Phenobarbital earns its place in severe AWS. Gold 2007 (retrospective pre/post): an escalating diazepam plus phenobarbital ICU protocol cut intubation from 47% to 22%. Rosenson 2013 (RCT): one 10 mg/kg IV dose added to ED lorazepam cut ICU admission from 25% to 8%, with no more adverse events. Its 53 to 118 h half-life (mean 79 h) gives a built-in self-taper.

Epinephrine falsely elevates lactate via β₂-mediated aerobic glycolysis -you cannot use lactate to guide resuscitation on epi.

Avoid hyperoxia post-ROSC -target SpO₂ 90–98% (2025 AHA), NOT 100%. Free radical injury worsens neurological outcomes.

TTM2 2021 (N=1,900): 33°C gave no benefit over normothermia with early fever treatment (trigger 37.8°C): 6-month death 50% vs 48%, with more arrhythmia causing hemodynamic compromise (24% vs 17%). AHA 2025: protocolized temperature control for every adult not following commands after ROSC (Class 1), kept at 32 to 37.5°C (Class 1) for at least 36 h (2a). Prevent fever; hypothermia is optional.

In TLS, do NOT aggressively replete calcium -it worsens calcium-phosphate deposition in kidneys. Only treat symptomatic hypocalcemia.

Delta-delta > 2 = AG metabolic acidosis + hidden metabolic alkalosis. Delta-delta < 1 = AG acidosis + additional non-AG acidosis.

Type 4 RTA is the most common RTA -non-AG acidosis + hyperkalemia in a diabetic on ACEi. Low aldosterone is the mechanism.

Norepinephrine is the first-line vasopressor in septic shock. Vasopressin is added as a second agent, not dopamine [SSC, 2021].

Never give D5W as a resuscitation fluid -only ~8% stays intravascular (the rest distributes into total body water). Use crystalloids.

Post-arrest (AHA 2025): adults not following commands after ROSC get protocolized temperature control at 32 to 37.5 °C (Class 1) for at least 36 h (2a); rewarm no faster than 0.5 °C/h. TTM2: 33 °C vs normothermia treating fever ≥ 37.8 °C gave similar 6-month mortality (50% vs 48%), so either is acceptable. Prognosticate multimodally no earlier than 72 h after normothermia, off sedation; don't withdraw early.

Tumor lysis: rasburicase is treatment (converts uric acid to allantoin). Allopurinol is prophylaxis only -don't confuse them.

Cuff leak test before extubation in patients intubated > 6 days or with traumatic intubation -absent leak predicts post-extubation stridor.

Higher PEEP may help moderate-severe ARDS (P/F ≤ 200): in the Briel 2010 meta-analysis hospital mortality was 34.1% vs 39.1%, with a trend to harm in mild ARDS, and ATS 2024 suggests higher PEEP without recruitment maneuvers. Compliance-guided titration is unproven: in ART 2017, recruitment plus best-compliance PEEP raised 28-day mortality (55.3% vs 49.3%) and barotrauma, so avoid prolonged recruitment maneuvers.

Delirium screening (CAM-ICU) should be done every shift. Untreated ICU delirium is associated with 3x mortality and long-term cognitive impairment.

Vasopressin in septic shock reduces norepinephrine requirements and may lower dialysis rates (25% vs 35%) but does NOT improve mortality.

Standard fentanyl bolus: 50 mcg IV (0.5–1 mcg/kg q 2 min; max ~250 mcg). Onset < 2 min, duration 30–60 min. 75–125× more potent than morphine, titrate to effect.

Alcohol use disorder non-pharm care: SBIRT (Screening, Brief Intervention, Referral to Treatment). Brief intervention alone has modest efficacy, pair with pharmacotherapy (naltrexone, acamprosate).

CRS (CAR-T, bispecifics): tocilizumab (IL-6R antagonist) is first-line from grade 2: 8 mg/kg IV (max 800 mg), may repeat q8h, max 3 doses in 24 h. Add dexamethasone for grade 3, or grade 2 hypotension refractory to tocilizumab and fluids. ICANS is the reverse: steroids first-line; tocilizumab is not recommended for isolated ICANS, since it raises serum IL-6 without crossing the blood-brain barrier (ASCO 2021).

Meth withdrawal adjuncts: trazodone 50 mg qhs (sleep), diphenhydramine 50 mg q6h PRN (first-line agitation), olanzapine 5 mg q6h PRN (second-line / paranoia), lorazepam reserved for refractory agitation.

Low threshold to involve MICU from the ED: severe DKA with low pH, severe alcohol withdrawal, HFNC on the floor, large PE, hypotension. Early escalation prevents crashes on the floor.

Warn patients about 5–10 lb weight gain with smoking cessation, nicotine suppresses appetite and boosts metabolism. Short-acting NRT (lozenges, gum) helps blunt the gain.

SOAP II (2010, N = 1,679) made norepinephrine first-line for shock: dopamine doubled arrhythmias (24% vs 12%) and raised mortality in the cardiogenic shock subgroup, though overall 28-day mortality did not differ significantly (52.5% vs 48.5%, P = 0.10). SSC 2021/2026 suggest adding vasopressin rather than escalating norepinephrine; SSC 2021 notes it is usually started at NE 0.25–0.5 mcg/kg/min.

Silent chest in acute asthma = the patient is too tight to wheeze. This is NOT improvement -it means imminent respiratory arrest.

Tension pneumothorax is a CLINICAL diagnosis: hypotension + JVD + absent breath sounds. Needle decompress -do NOT wait for CXR.

Massive hemoptysis kills by asphyxiation, not exsanguination. 150 mL of blood can flood the tracheobronchial tree. Protect the airway first.

A negative home sleep apnea test does not rule out OSA, because the denominator is wrong. HSAT has no EEG, so it cannot separate sleep from quiet wakefulness and divides events by total recording time instead of total sleep time. Awake hours dilute the index, which can drop a patient a full severity band. High suspicion plus a negative HSAT means in-lab polysomnography.

When the sleep diary says 2 hours and the patient looks well, think paradoxical insomnia and get actigraphy. Sleep-state misperception is common and is not lying. Actigraphy over 72 hours to 14 days gives an objective total sleep time that reframes the conversation, and it is the AASM-suggested move for non-response to CBT-I or a patient pushing for a higher hypnotic dose.

5 days of prednisone 40 mg is noninferior to 14 days for AECOPD (REDUCE, JAMA 2013, N=314): re-exacerbation within 6 months 37.2% vs 38.4%, with half the cumulative steroid dose (379 vs 793 mg). No need for prolonged courses.

NIV in AECOPD (Brochard, NEJM 1995, N=85) cut intubation from 74% to 26% and in-hospital mortality from 29% to 9%, with shorter stays (35 vs 23 days). Start early when pH is 7.25 to 7.35 with PaCO2 above 45 mmHg; the benefit comes from preventing intubation, so do not wait for the pH to fall further.

Intubation in Category E PE (formerly massive) can cause cardiac arrest -positive pressure drops preload to a failing RV. Use ketamine, low PEEP.

tPA for Category E PE (formerly massive): 100 mg IV over 2 hours. In cardiac arrest: 50 mg IV bolus push. Resume heparin once aPTT < 2× baseline (usually same day) -unlike ischemic stroke, there is no mandatory 24h hold.

Home O₂ in COPD only benefits severe hypoxemia (PaO₂ ≤ 55 or SpO₂ ≤ 88%). LOTT 2016 showed NO benefit for moderate desaturation (89–93%).

SABA-only rescue is no longer recommended in asthma -even mild asthma. All patients need ICS-containing therapy, a position unchanged through GINA 2026.

Post-intubation PEA arrest in asthma = dynamic hyperinflation. Disconnect from vent × 30–60 sec, compress chest to release trapped air.

Complicated parapneumonic effusion (pH < 7.2, glucose < 60, positive Gram stain) requires chest tube drainage -antibiotics alone won't work.

Azithromycin 250 mg daily or 500 mg 3x weekly reduces COPD exacerbations by ~30% in frequent exacerbators -check QTc and exclude NTM first.

In severe asthma, magnesium sulfate 2 g IV over 20 min is underutilized adjunct -reduces admissions in patients not responding to standard bronchodilators.

Age-adjusted D-dimer (age x 10 ng/mL in patients > 50) safely increases specificity without missing clinically significant PE.

MOPETT tested half-dose tPA (50 mg) against anticoagulation ALONE, not against full-dose lysis, so it says nothing about bleeding versus full dose. It reduced pulmonary hypertension at 2.3 years (16% vs 57%) with no bleeding in either arm, but no mortality benefit. Single-center, 121 patients: hypothesis-generating.

YEARS criteria (clinical signs of DVT, hemoptysis, PE most likely) tier D-dimer cutoffs and can safely reduce CTPA use by ~14%.

HFNC reduces CO₂ by washing out anatomic dead space, flow, not FiO₂, drives CO₂ clearance. Turn up the flow, not the oxygen, for hypercapnia.

Home nocturnal NIV in COPD with persistent daytime PaCO2 ≥ 52 mmHg improves outcomes (Köhnlein 2014: 1-year mortality 12% vs 33%; HOT-HMV 2017: readmission or death, HR 0.49). ATS 2020 suggests not starting it during the admission: recheck the gas 2 to 4 weeks after recovery, since many patients clear their CO2. Start in hospital only if the patient cannot be weaned off NIV.

All patients with systemic sclerosis need baseline PFTs, screens for interstitial lung disease and pulmonary hypertension (the leading causes of SSc-related death). Repeat yearly.

Acute chest syndrome in SCD: exchange transfusion if Hb drops or hypoxemia worsens, simple transfusion for mild cases. Pain control without over-sedation (splinting worsens atelectasis). Incentive spirometry every 2 hours.

Steroids reduce mortality in severe CAP needing ICU care (CAPE COD 2023: 28-day mortality 6.2% vs 11.9%; intubation 18% vs 30% in those not ventilated at baseline). Regimen: hydrocortisone 200 mg/day IV for 4 or 7 days by clinical response, then tapered, for 8 or 14 days total. The trial excluded influenza and septic shock on vasopressors, where this benefit is unproven.

β2 agonists (albuterol, IV epinephrine, terbutaline) drive a Type B lactic acidosis. In status asthmaticus or anaphylaxis with high SABA exposure, do not reflexively work this up as sepsis. Lactate trends down once the β2 agonist is dialed back. Same goes for continuous nebs and IV terbutaline drips: check a BMP and lactate, but the rise is expected, not a perfusion problem.

ICS is NOT first-line in COPD (unlike asthma). COPD inflammation is neutrophilic and steroid-resistant. Use eos ≥ 300 to guide ICS addition.

Never give a LABA without ICS in asthma. SMART (Chest 2006, N=26,355) added salmeterol or placebo to usual care, ICS not required. Its primary endpoint (respiratory death or life-threatening event) missed significance (RR 1.40), but asthma deaths, a secondary outcome, were 13 vs 3 (RR 4.37). FDA-mandated 2016 NEJM trials of ICS/LABA vs ICS alone found no excess serious asthma events, so always pair LABA with ICS.

Non-severe CAP antibiotics can stop after as few as 3 days once the patient is clinically stable (ATS 2025: under 5 days, 3-day minimum); severe CAP still gets at least 5 days. Longer courses don't improve outcomes and increase C. diff risk.

In AECOPD, oxygen-induced hypercapnia is mostly V/Q mismatch (hyperoxia releases hypoxic vasoconstriction and raises dead space) plus the Haldane effect (~25%); blunted hypoxic drive is a minor contributor (Aubier 1980). Titrate O2 to SpO2 88 to 92%: in Austin 2010 (BMJ, N=405) prehospital titrated oxygen cut mortality from 9% to 4% vs high-flow.

Avoid aggressive fluids in Category E PE (formerly massive) -the RV is already failing. Overloading worsens septal bowing and drops LV output.

McConnell's sign (RV free wall akinesis with apical sparing) is ~95% specific for acute PE on bedside echo.

Smoking cessation has the largest effect on FEV1 decline (Lung Health Study 1994) and is what changes the disease trajectory. Inhalers are not purely symptomatic: a 2021 review of 9 RCTs (Celli, AJRCCM; 33,051 patients) found FEV1 fell 5 mL/yr more slowly than with placebo, and GOLD 2023 onward says pharmacotherapy may reduce lung function decline. Quit first; inhalers add a modest effect.

GOLD 2023 simplified ABCD to ABE: A = low symptoms/low exacerbations, B = high symptoms, E = exacerbator (≥ 2 moderate or ≥ 1 hospitalized).

Light's criteria misclassify 25% of transudates as exudates (especially CHF on diuretics). Check serum-pleural albumin gradient > 1.2 → transudate.

Pleural fluid pH < 7.2 in parapneumonic effusion = complicated → needs chest tube drainage, not just antibiotics alone.

Aspiration pneumonitis (chemical) does NOT need antibiotics. Only treat if infection develops (fever + leukocytosis + infiltrate persisting at 48h).

Part-solid nodules carry the highest malignancy rate of any morphology: 63% vs 18% for pure ground-glass and 7% for solid in the ELCAP screening series (Henschke 2002, small numbers). Many subsolid nodules are transient, so Fleischner 2017 repeats CT at 3-6 months first; a persistent part-solid nodule with a solid component of 6 mm or more is highly suspicious (consider PET-CT, biopsy or resection).

LDCT screening reduces lung cancer mortality by 20%. Criteria: age 50–80, ≥ 20 pack-years, current smoker or quit within 15 years.

Asthma has normal DLCO. Emphysema has low DLCO. This is the key PFT distinction between the two most common obstructive diseases.

Low DLCO with normal spirometry = pulmonary vascular disease until proven otherwise (pulm HTN, chronic PE, early ILD).

High-flow O₂ speeds pneumothorax reabsorption 4× by creating a nitrogen gradient -even if the patient isn't hypoxic.

OSA is the most common condition found with true resistant hypertension (60-84%, AHA 2018), so screen anyone uncontrolled on ≥ 3 agents with STOP-BANG and refer for a sleep study. But first exclude pseudoresistance (non-adherence, white-coat effect, no thiazide-like diuretic), and the 2025 AHA/ACC guideline says screen ALL resistant hypertension for primary aldosteronism (~20%) even with a normal potassium.

Steroids are HARMFUL in IPF. PANTHER-IPF 2012 showed prednisone + azathioprine + NAC increased mortality. Use antifibrotics instead.

UIP pattern on HRCT (basal honeycombing + traction bronchiectasis) in the right clinical context = IPF. Biopsy often unnecessary.

In massive hemoptysis, position bleeding side DOWN to protect the good lung. Then intubate, bronchoscope, and call IR for embolization.

Procalcitonin cannot rule out bacterial CAP: no cutoff separates viral from bacterial (Self 2017: PCT < 0.1 ng/mL missed about 1 in 5 bacterial pathogens), so ATS/IDSA says treat clinically and radiographically confirmed CAP regardless of PCT. ProACT 2018: PCT guidance did not cut antibiotic days. Its role is stopping: PCT < 0.25 ng/mL or ≥ 80% below peak plus clinical stability supports shortening the course.

Two-year stability means benign only for a SOLID nodule (Fleischner 2017: no further CT once stable at 18–24 months). Subsolid nodules grow slowly yet carry higher malignancy risk (indolent adenocarcinoma), so follow out to 5 years: pure ground-glass ≥ 6 mm, CT at 6–12 months then every 2 years; part-solid ≥ 6 mm, CT at 3–6 months then annually if the solid part stays < 6 mm.

STOP-Bang 5 to 8 means a high probability of moderate-to-severe OSA (about 50 to 60% in Chung 2012 surgical patients). Confirm with sleep testing: AHI 5-14 mild, 15-29 moderate, 30 or more severe. PAP is first-line treatment, especially with daytime sleepiness.

In ILD, UIP pattern on HRCT (basal honeycombing) = IPF → antifibrotics only. Steroids are HARMFUL. NSIP = steroids work.

Massive hemoptysis (> 500 mL/24h): position bleeding side DOWN. Intubate if needed. Bronchial artery embolization is definitive.

PFT patterns (ATS/ERS since 2005; ERS/ATS 2022): obstruction = FEV1/FVC below the lower limit of normal (LLN, z-score < -1.645, 5th percentile); restriction = TLC below LLN with a normal FEV1/FVC; both low = mixed. Fixed 0.70 and 80% predicted cutoffs are not ATS/ERS criteria: they over-call obstruction in older adults and miss it in the young. GOLD 2026 still diagnoses COPD by post-bronchodilator FEV1/FVC < 0.7.

Tension pneumothorax is a clinical diagnosis: do not wait for CXR. Needle decompression first, then chest tube. ATLS 10th edition moved the adult site to the 4th-5th intercostal space just anterior to the midaxillary line (chest wall ~1 cm thinner than at 2nd ICS MCL, where a 5 cm needle failed in ~40% of cadavers); use a 5-8 cm 14G catheter. 2nd ICS MCL remains the pediatric site.

PERC rule only applies when pretest probability is already low (< 15%). Don't PERC-out a patient you think has PE -you're stacking negatives inappropriately.

CURB-65 >= 2 = admit, >= 3 = consider ICU. But it underestimates severity in young patients -clinical judgment still trumps the score.

Legionella urinary antigen only detects serogroup 1 (~80% of cases). Negative test in high-suspicion patient does not rule it out -add sputum PCR.

In COPD on home O₂, target SpO₂ 88-92%, NOT ≥ 95% -hyperoxia worsens hypercapnia via the Haldane effect and V/Q mismatch, not 'lost hypoxic drive'.

Spontaneous pneumothorax in a tall, thin young man -think apical bleb rupture. ~30% recurrence after the first episode; pleurodesis or bleb resection considered after recurrence.

FVC is the first number to read on PFTs. FVC ≥ 80% → check FEV₁/FVC for obstruction. FVC < 80% → check TLC to distinguish restriction from air-trapping obstruction.

Post-pneumothorax counseling: no flying until a chest film confirms full resolution, then wait at least 1 more week (2 weeks if traumatic) per BTS. Scuba diving is off permanently unless bilateral surgical pleurectomy: trapped gas expands on ascent and can turn a recurrence into tension pneumothorax. No heavy lifting or forced expiration for about 2 weeks. Recurrence after a first episode is roughly 30%.

Dyspnea is driven primarily by pCO₂ and pH, NOT oxygen. Carotid body and central chemoreceptors monitor CO₂/pH. J-receptor stretch in pulmonary vasculature also contributes in heart failure.

Heliox requires FiO₂ ≤ 30% to be effective, higher FiO₂ displaces the helium, losing the density advantage that lets it flow past narrow airways. It's a bridging therapy, not definitive.

Awake bronchoscopy is difficult once supplemental O₂ exceeds 6–10 L. Beyond that, intubate for the procedure, trying to push through risks desaturation and loss of airway control.

Roflumilast: warn about diarrhea (9.5% vs 2.7% on placebo), nausea, headache and weight loss (about 2 kg more than placebo over a year; 20% lose 5 to 10% of body weight). Use caution in underweight patients and monitor weight. GI effects come early and usually lessen with continued use, so warning up front protects adherence.

Asthma biologic candidacy: eosinophils > 300 → mepolizumab/benralizumab (anti-IL-5). Omalizumab requires IgE 30–700 IU/mL AND documented perennial aeroallergen sensitization -not just IgE > 30. Dupilumab (anti-IL-4/13) when eos + atopy overlap. Order CBC + IgE + allergen panel before pulm referral.

Any new unexplained pleural effusion warrants diagnostic thoracentesis, unless clearly HF-related. Don't anchor on the easiest explanation; malignant and parapneumonic effusions are often missed this way.

Tree-in-bud opacities on CT = mucus, pus or fluid impacting the smallest airways. First described in endobronchial TB but now nonspecific: infectious bronchiolitis (bacterial, viral, TB, NTM, fungal), aspiration, CF and other bronchiectasis, ABPA, diffuse panbronchiolitis, RA/Sjögren; rarely tumor emboli in small arteries. Hypersensitivity pneumonitis gives ill-defined centrilobular ground-glass nodules instead.

Bicarbonate in DKA is not routine; consider it only for pH < 7.0 (2024 ADA/EASD/JBDS/AACE/DTS consensus; the 2009 ADA cutoff was 6.9): 100 mmol NaHCO3 (8.4%) in 400 mL sterile water, repeated every 2 h until pH > 7.0. Otherwise it gives no outcome benefit and risks hypokalemia (recheck K, as it shifts K into cells), paradoxical CNS acidosis and cerebral edema.

In thyroid storm: PTU first (blocks synthesis), then iodine ≥ 1h later (blocks release). If you give iodine first, you feed the storm.

In myxedema coma: give hydrocortisone BEFORE thyroid hormone. T4 increases cortisol metabolism → unmasking adrenal insufficiency → crisis.

Refractory hypotension + hyponatremia + hyperkalemia + eosinophilia = think adrenal crisis. Give hydrocortisone 100 mg IV -don't wait for labs.

Any patient on ≥ 20 mg prednisone/day × ≥ 3 weeks needs stress-dose steroids during acute illness. Missing this kills patients.

In DKA, don't start insulin until K⁺ is confirmed ≥ 3.5 -insulin drives K⁺ intracellularly and can cause fatal hypokalemia.

Alpha-block BEFORE beta-block in pheochromocytoma. Beta-block alone → unopposed alpha → lethal hypertensive crisis.

Do NOT biopsy a suspected pheochromocytoma -needle insertion → massive catecholamine release → hypertensive crisis → death.

Pheochromocytoma management: ALPHA-blockade first (phenoxybenzamine or doxazosin) for 10–14 days, then beta-blockade. Beta-blockade alone causes unopposed alpha stimulation → hypertensive crisis.

Ask about biotin before trusting a normal troponin or a suppressed TSH. Hair, skin and nail supplements (5–10 mg) saturate the streptavidin in many immunoassays. Sandwich assays read falsely LOW (troponin, TSH), so an MI can be missed; competitive assays read falsely HIGH (free T4, free T3, TRAb), which fakes Graves' disease in a euthyroid patient. For thyroid labs, repeat after holding biotin at least 48 h.

Rybelsus now comes in two formulations that are not interchangeable mg for mg: the original R1 tablets (3, 7, 14 mg) and the better-absorbed R2 tablets (1.5, 4, 9 mg), where R2 4 mg equals R1 7 mg and R2 9 mg equals R1 14 mg. So an R2 9 mg tablet is the top dose, not a step below 14. Wegovy tablets (25 mg, for obesity) titrate through the same 1.5, 4 and 9 mg strengths: check the med list for a second semaglutide product before adding one.

Euglycemic DKA occurs with SGLT2 inhibitors -glucose may be < 200 mg/dL. Always check ketones in SGLT2i users with nausea.

NICE-SUGAR 2009: tight glucose control (81–108) in ICU increased mortality. Target 140–180. Do NOT chase normoglycemia in critically ill patients.

Sliding scale alone is reactive medicine. In RABBIT 2 (2007), basal-bolus glargine plus glulisine got 66% of non-ICU T2DM patients below 140 mg/dL vs 38% on sliding scale, with no more hypoglycemia; length of stay was unchanged. RABBIT 2 Surgery (2011) cut postoperative complications from 24% to 9% but raised glucose below 70 (23% vs 5%). Use basal-bolus-correction, and reduce doses for poor intake or CKD.

PTU is preferred over methimazole in thyroid storm because it also blocks peripheral T4→T3 conversion -methimazole does not.

Avoid aspirin in thyrotoxicosis -it displaces T4 from thyroid-binding globulin → increases free T4 levels. Use acetaminophen for fever.

In HHS, fluids first, insulin second: IV fluids alone lower glucose ~50-70 mg/dL/h (often more in HHS). Start insulin at 0.05 units/kg/h once glucose stops falling (start at once, 0.1 units/kg/h, if significant ketonemia; K must be > 3.5), and keep the rate of fall under 90-120 mg/dL/h to avoid cerebral edema. Fluid deficit ~100-220 mL/kg (7-15 L at 70 kg), replaced over 24-48 h.

RAIU differentiates thyrotoxicosis: high diffuse = Graves', focal hot = toxic adenoma, low = thyroiditis (thionamides useless in thyroiditis).

Levothyroxine half-life is 7 days. Wait 6-8 weeks to recheck TSH after any dose change -sooner gives a misleading result.

Primary aldosteronism is the most common cause of secondary hypertension: 5.9% of unselected primary care hypertensives, rising to 11.8% in stage 3 (Monticone, JACC 2017). Most are normokalemic (hypokalemia in only 9-37% of series), so a normal K+ never excludes it. That is why the 2025 Endocrine Society guideline suggests screening everyone with hypertension with an aldosterone-renin ratio.

Random cortisol < 3 in an acutely ill patient strongly suggests adrenal insufficiency. > 18 essentially rules it out. Middle values need cosyntropin stim.

Hold SGLT2 inhibitors 3-4 days before major surgery to prevent euglycemic DKA perioperatively -a frequently missed med rec step.

Hydrocortisone is preferred over prednisone in adrenal insufficiency, 1:1 glucocorticoid:mineralocorticoid potency. Dexamethasone and methylprednisolone have essentially no mineralocorticoid activity and won't replace aldosterone.

Lamotrigine and levetiracetam are the bone-safe antiepileptics. Carbamazepine, phenytoin, phenobarbital induce CYP450 → accelerate vitamin D breakdown → osteoporosis. Valproate also causes bone loss.

Alendronate (70 mg weekly) is first-line oral osteoporosis therapy. Fracture benefit persists after 5-year courses. Use IV zoledronic acid if GI intolerance or absorption issues.

Hypercalcemia in renal failure: denosumab (RANKL antibody) is preferred when zoledronic acid is unsafe or fails; renal impairment does not alter its clearance (Endocrine Society 2023). Trade-off: severe, sometimes fatal hypocalcemia, most common with CrCl under 30 or dialysis (Xgeva label; Prolia boxed warning 2024). Recheck calcium within days; correct vitamin D deficiency once calcium normalizes.

Thyroid nodule FNA (ATA 2015; the 2025 ATA guideline covers DTC only): high suspicion (solid hypoechoic plus irregular margins, microcalcifications, taller-than-wide or ETE; 70-90% malignant) or intermediate (smooth solid hypoechoic; 10-20%) → FNA ≥ 1 cm; low (iso/hyperechoic solid; 5-10%) → ≥ 1.5 cm; very low (spongiform; < 3%) → FNA ≥ 2 cm or observe; purely cystic (< 1%) → no biopsy, drain only if symptomatic.

MALA almost always needs a trigger: AKI, shock, sepsis or hypoxia; hold metformin in those states, and eGFR < 30 is a contraindication. Iodinated contrast: the FDA label holds it if eGFR 30-60, liver disease, alcoholism, HF or intra-arterial contrast, rechecking eGFR at 48 h; radiology guidance (ESUR 2018, ACR) holds only for eGFR < 30 or AKI. Metformin MALA is rare (unlike phenformin) but can be fatal.

In treated DKA the anion gap closes BEFORE the ketones are gone, which is the opposite of how it feels. Large-volume saline converts the high-gap acidosis into a hyperchloremic one: once GFR improves the ketoacid anions are excreted as sodium salts rather than metabolized back to bicarbonate, and chloride fills the space. The gap normalizes while the bicarb and pH stay low. Follow BHB < 0.6, not the gap.

Natpara is gone (discontinued worldwide at the end of 2024); PTH replacement for hypoparathyroidism is now palopegteriparatide (Yorvipath). Unlike calcium and calcitriol, it lowers urinary calcium. On the day it starts, calcitriol is cut by at least half or stopped per the label, and calcium is rechecked in 7-10 days, because PTH added to unchanged conventional therapy causes hypercalcemia.

Inpatient glucose has two goals, not one: 100&ndash;180 mg/dL on the wards (a separate ward goal since ADA 2025) and 140&ndash;180 in the ICU, each only if reached without significant hypoglycemia. A fasting glucose below 100 on basal insulin predicts hypoglycemia within 24 hours, so lower that day's basal dose instead of waiting for the low.

In pregnancy, recheck a mildly raised TSH before starting levothyroxine. Below 6 mU/L, about half normalize within weeks, and levothyroxine started after the first trimester has not improved pregnancy or child outcomes (CATS, NIH trial). Overt hypothyroidism with TSH 6 or more is treated at once, and the target is a TSH below 2.5.

Basal insulin should never be held entirely in T1DM -even NPO patients need 50-80% of basal dose to prevent DKA. Holding 'because NPO' is dangerous.

Nonpregnant subclinical hypothyroidism (TSH 4.5 to 10) rarely needs treatment; treat TSH > 10. Overtreatment causes AF and bone loss. Pregnancy is no longer a blanket exception (ATA 2026): subclinical hypothyroidism found in the first trimester is treated or rechecked by shared decision; found later, levothyroxine has not improved outcomes (CATS, NIH trial), so it is not started unless it becomes overt.

When transitioning from insulin drip to SubQ, give basal insulin at least 2 h (commonly 2 to 4 h) before stopping the drip (ADA Standards, Section 16). IV insulin's half-life is only minutes, while subcutaneous glargine has a slow, peakless onset, so the overlap prevents rebound hyperglycemia and DKA. Glargine does not reach true steady state until 2 to 4 days of daily dosing.

Central DI responds to DDAVP (urine concentrates). Nephrogenic DI does not (kidneys are resistant). This distinguishes the two.

Lithium is the #1 drug cause of nephrogenic DI. Treat with amiloride (blocks lithium entry into collecting duct) + low-Na diet + thiazide.

DM drug selection is now driven by comorbidities (ASCVD → GLP-1, HF → SGLT2i, CKD → SGLT2i), not just A1c. ADA 2026: GLP-1 RA + SGLT2i combo when A1c ≥1.5% above goal or high CVD risk.

Tirzepatide (Zepbound), a dual GIP/GLP-1 agonist, gave 15.0%, 19.5% and 20.9% mean weight loss at 5, 10 and 15 mg over 72 weeks vs 3.1% with placebo (SURMOUNT-1, N=2,539). Head to head it beat semaglutide 2.4 mg, 20.2% vs 13.7% (SURMOUNT-5, 2025). GI effects are the most common adverse events, mostly during escalation, which is why doses rise by 2.5 mg every 4 weeks.

Semaglutide 2.4 mg reduces MACE by 20% in overweight/obese patients with pre-existing CVD but without diabetes (secondary prevention) -CV benefit independent of glucose.

Myxedema coma: give IV levothyroxine AND hydrocortisone -must treat possible concomitant adrenal insufficiency before giving T4 alone.

Central DI: responds to desmopressin (urine concentrates). Nephrogenic DI: does NOT respond (treat with thiazides + low-Na diet paradoxically).

SGLT2 inhibitors are organ-protective, not just glucose-lowering. EMPA-REG (2015) cut HF hospitalization 35% but enrolled only type 2 diabetes. DAPA-HF (2019) in HFrEF (EF ≤ 40%) and DAPA-CKD (2020) in albuminuric CKD enrolled patients with and without diabetes, with similar benefit in both: HR 0.74 for worsening HF or CV death; HR 0.61 for eGFR decline ≥ 50%, ESKD, or renal/CV death.

Metformin is safe in CKD down to eGFR 30. Reduce dose at eGFR 30–45. Stop below 30.

Semaglutide 2.4 mg weekly achieves ~15% body weight loss. Most weight regains within 1 year of stopping -obesity requires chronic treatment.

In myxedema coma, give stress-dose IV hydrocortisone BEFORE levothyroxine: thyroid hormone accelerates cortisol metabolism and can unmask coexisting adrenal insufficiency, precipitating adrenal crisis. Draw a random serum cortisol first, but do not delay either drug for cosyntropin testing; continue steroids until adrenal insufficiency is excluded.

Sulfonylurea-induced hypoglycemia can recur for 24-72 hours. D10 drip + octreotide 50 mcg SQ q6h for refractory cases.

Hypocalcemia will NOT correct until magnesium is repleted -Mg is required for both PTH secretion and PTH receptor function.

Corrected Ca = total Ca + 0.8 × (4 − albumin). But in ICU patients, always use ionized calcium.

Post-thyroidectomy: check ionized calcium q6h × 48h. Hungry bone syndrome after parathyroidectomy can cause severe prolonged hypocalcemia requiring IV calcium drip × days.

Post-pituitary surgery triphasic response: DI (days 1-5) → SIADH (days 5-10) → permanent DI. Stop DDAVP when UOP drops.

Cushing's workup is 3 steps: (1) confirm hypercortisolism, (2) check ACTH dependence, (3) localize the source.

CT adrenals is wrong 38% of the time in primary aldosteronism -adrenal vein sampling is the gold standard before committing to surgery.

Thiazides paradoxically REDUCE urine output in nephrogenic DI -mild volume depletion increases proximal reabsorption, leaving less water for the collecting duct.

Amiloride specifically treats lithium-induced nephrogenic DI by blocking ENaC, preventing lithium entry into principal cells.

Stress-dose steroids for major surgery: hydrocortisone 100 mg IV pre-op then 50 mg q8h x 24h. Minor procedures usually need no supplementation.

Hypoglycemia unawareness in long-standing T1DM: 2-3 weeks of strict avoidance of lows can restore autonomic symptoms. Relax A1c goal temporarily.

Continuous glucose monitoring reduces A1c and hypoglycemia in T1DM and insulin-treated T2DM -ADA now recommends CGM for anyone on basal+bolus.

Thyroid storm: propranolol + PTU given concurrently (propranolol for adrenergic storm, PTU for synthesis + peripheral T4→T3 conversion), then iodine ≥ 1 hour AFTER PTU. Iodine before thionamide fuels hormone synthesis (Jod-Basedow).

Levothyroxine full-replacement dose = 1.6 mcg/kg lean body weight. Start 25–50 mcg/day in older adults or CV disease. Recheck TSH at 6 weeks, don't chase it sooner.

Transdermal testosterone gel (AndroGel 1.62%, start 40.5 mg daily) is a common first choice: continuous 24 h delivery with steady physiologic levels, unlike the peaks and troughs of injections. Hepatotoxicity applies to 17-alpha-alkylated oral androgens (methyltestosterone), not to FDA-approved oral testosterone undecanoate (Jatenzo). Choose by preference, cost and pharmacokinetics.

ACTH stim test: high ACTH + low AM cortisol + blunted response = primary adrenal insufficiency. Low ACTH + low cortisol + normal response = secondary/tertiary (pituitary/hypothalamic), may need longer-term to atrophy the adrenals.

Prolactinomas are treated with dopamine agonists (cabergoline preferred), not surgery, even with visual field defects. Tumor size often drops within days of starting therapy.

Proliferative or severe non-proliferative diabetic retinopathy: avoid intense exercise or Valsalva-heavy activity, risk of vitreous hemorrhage and retinal detachment.

Bicarbonate in DKA: not routine; consider only if pH < 7.0 (2024 ADA/EASD/JBDS consensus; the old 6.9 cutoff is retired). It does not speed recovery and can cause hypokalemia, reduced tissue O2 uptake and paradoxical CNS acidosis (CO2 crosses the blood-brain barrier faster than HCO3), with cerebral edema risk in children. If used: 100 mmol (8.4%) in 400 mL sterile water every 2 h until pH > 7.0; watch K closely.

DKA in pregnancy can present with near-normal glucose (about 30% euglycemic, < 200 mg/dL), so start dextrose early and never stop the insulin drip because glucose fell. Switch to subQ only when ketoacidosis resolves (ketones < 0.6 mmol/L plus pH ≥ 7.3 or bicarbonate ≥ 18), giving basal insulin 1-2 h before the drip stops. Maternal ketones and acidosis cross the placenta and cause fetal hypoxemia and acidosis.

HRT for vasomotor symptoms: estrogen plus a progestogen if the uterus is present (prevents endometrial hyperplasia); estrogen alone post-hysterectomy. Start under age 60 or within 10 years of menopause, absent contraindications; starting later adds CHD, stroke, VTE and dementia risk (NAMS 2022). Past 60, continue for persistent symptoms with shared decision-making and periodic reevaluation; no automatic stop.

Antiresorptives reduce fractures even when BMD barely rises on DEXA, so a stable scan is not failure. Societies differ: ACP (2017, weak recommendation) advised against BMD monitoring during the 5-year course in women; the Endocrine Society (2019/2020) suggests spine and hip DEXA every 1 to 3 years to detect nonresponse. A significant BMD fall on therapy means check adherence, then secondary causes and absorption.

Gestational diabetes: first-line insulin if lifestyle fails. Metformin and glyburide cross the placenta, data is mixed on long-term effects, so insulin remains preferred for tight glucose control in pregnancy.

PA screen (Endocrine Society 2025): morning aldosterone and renin in every hypertensive, on current meds if stopping is unsafe; MRAs, diuretics and ACEi/ARBs raise renin and mask PA. If negative but suspicion persists, correct K and repeat after holding MRAs/diuretics 4 wk, ACEi/ARBs 2 wk. Suppression testing only if equivocal and surgery is sought; skip if hypokalemic, renin suppressed, aldosterone > 15-20 ng/dL.

Fluid-responsive hypercalcemia is less likely to be malignancy-driven. PTHrP and lytic bone disease often don't correct quickly with volume. Rapid normalization → think primary hyperparathyroidism.

Chloride:phosphorus ratio > 33 suggests PTH-mediated hypercalcemia. PTH promotes renal phosphate wasting AND chloride reabsorption, the ratio captures both at once.

Metformin was traditionally stopped in hospitalized patients because of its predecessor phenformin, which caused fatal lactic acidosis. Modern metformin's risk is much lower; continue unless eGFR < 30, shock, or contrast imaging.

Calcium gluconate does NOT lower potassium -it stabilizes the cardiac membrane. Always follow with insulin + glucose.

SGLT2 inhibitors slow CKD progression regardless of diabetes status -a paradigm shift in nephrology.

Central pontine myelinolysis (osmotic demyelination): correct hyponatremia ≤ 8 mEq/L in 24 hours (≤ 6 in high-risk patients: chronic hypoNa, alcoholism, malnutrition, K-depletion, liver disease). Overcorrection → give D5W or DDAVP to relower sodium.

Mannitol causes HYPERTONIC hyponatremia, so hypertonic saline is the wrong direction. As an effective osmole it stays extracellular and pulls water out of cells, diluting the Na while measured osmolality is HIGH. The tell is an osmolal gap (measured minus calculated osm). Stop the drug and let the kidney clear it. Expect the flip to hypernatremia once the osmotic diuresis phase begins.

Correcting hypovolemic hyponatremia with NS is the #1 cause of accidental overcorrection -once volume is restored, ADH shuts off and kidneys dump water.

Every mEq of K⁺ repleted raises serum Na by ~1 mEq/L. Count K⁺ correction toward the safe Na correction limit to avoid ODS.

Contrast-induced nephropathy risk is substantially lower than previously believed. Do not withhold emergent contrast imaging for borderline creatinine.

Bland urine sediment in AKI points to pre-renal or post-renal. Muddy brown casts = ATN. RBC casts = GN. WBC casts = AIN/pyelo. Always look yourself.

PPIs are an underrecognized cause of chronic AIN and CKD progression -review the indication at every admission and deprescribe when possible.

In suspected diabetic kidney disease, absent retinopathy raises the odds of a non-diabetic cause (OR 0.15 for non-diabetic disease when retinopathy is present) and, with short diabetes duration or active sediment, favors biopsy. It does not exclude DKD: in type 2 diabetes about a quarter of biopsy-proven diabetic nephropathy has no retinopathy. The near-constant retinopathy-nephropathy link holds in type 1 diabetes.

Hypokalemia PERPETUATES metabolic alkalosis -you cannot correct the alkalosis without repleting K⁺. This is why vomiting, diuretic, and hyperaldosteronism-induced alkalosis persist long after the trigger stops. Remember the 3 C's of chloride-responsive alkalosis repletion: Chloride, K⁺, and volume.

Peritoneal dialysis patients on antibiotics > a few days need nystatin (or fluconazole) prophylaxis. Fungal peritonitis often permanently ends PD eligibility.

GFR is a calculated value, it's inaccurate when creatinine is moving. In AKI, eGFR lags reality: rising Cr → eGFR overestimates; falling Cr → eGFR underestimates. Don't dose-adjust off it in flux.

Albumin + furosemide 'sandwich': use when BOTH (1) diuretic-resistant edema AND (2) serum albumin < 2.5 g/dL. Classic settings: nephrotic syndrome with anasarca, cirrhotic refractory edema, ICU third-spacing / capillary leak, post-op volume overload with low albumin. Give 25 g of 25% albumin IV over 30 min, then furosemide 40-80 mg IV push at the end of the infusion. Mechanism: (1) oncotic pull mobilizes interstitial fluid into the vascular space so the loop has volume to work on, and (2) because furosemide is ~95% albumin-bound, supplementing albumin improves drug delivery to the thick ascending limb. Effect is transient (hours), so it's a bridge, not a fix. Don't use if albumin is normal (expensive placebo). Watch for flash pulmonary edema if the heart can't handle the mobilized volume.

Sequential nephron blockade (metolazone + loop): when IV loop diuretic alone isn't producing adequate UOP despite dose escalation in decompensated HF. Give metolazone 2.5-10 mg PO 30-60 min BEFORE the IV loop, so peak tubular effect coincides with the loop hitting the thick ascending limb. Mechanism: chronic loop use upregulates the distal Na-Cl cotransporter (NCC) as a compensatory response ('distal nephron remodeling' or 'braking'), so more of the Na the loop dumps downstream gets reclaimed, blunting further response. Metolazone blocks NCC and shuts down that escape. Preferred over HCTZ because metolazone still works at eGFR < 30 (HCTZ loses efficacy). Warnings: synergy is potent, watch for severe hypokalemia, hypomagnesemia, hypovolemia, and AKI. Check BMP within 24h and daily thereafter. Short-term rescue only, not maintenance; stop once diuresis is adequate.

Transient blindness after a TURP is the glycine, not a stroke. Glycine 1.5% irrigant is an inhibitory retinal neurotransmitter, and it also metabolizes to ammonia, so the patient can stay encephalopathic after the sodium is corrected. Absorbed hypotonic irrigant gives hyponatremia with hypertension and bradycardia, the reverse of the usual intraoperative crash.

FENa is unreliable on diuretics -use FEUrea instead. FEUrea < 35% = pre-renal even if FENa is falsely elevated.

Never combine ACEi + ARB in CKD -no added benefit, but significantly more hyperkalemia and AKI.

AEIOU: Acidosis, Electrolytes (refractory hyperK), Ingestion (toxic alcohols, lithium), Overload (volume), Uremia. These are the emergent dialysis indications.

Nebulized albuterol for hyperkalemia requires 10–20 mg -that's 4–8× the standard asthma dose. Most commonly underdosed.

Hypoglycemia occurs in 10–75% of patients treated with insulin for hyperkalemia. Check glucose at 1h and 2h minimum.

Kayexalate has questionable efficacy and risk of intestinal necrosis. Patiromer and Lokelma have replaced it.

Expect an early, hemodynamic eGFR dip when starting an SGLT2i (small and reversible) or an ACEi/ARB; it is not kidney injury, so do not stop the drug. KDIGO 2024: continue the ACEi/ARB unless creatinine rises more than 30% within 4 weeks; the SGLT2i dip is generally not a reason to discontinue; a drop over 30% with either class warrants a search for volume depletion, NSAIDs or renal artery stenosis.

ESA target in CKD anemia is Hgb 10–11.5 only. Targeting Hgb > 13 doubles stroke risk.

Do NOT start dialysis based on GFR alone. Early initiation (GFR 10–14) showed no survival benefit over late (GFR 5–7).

Morphine is NOT an ICU drug -M6G accumulates in renal failure → prolonged sedation. Use fentanyl or hydromorphone.

Renally cleared beta-blockers accumulate in CKD (reduce dose, watch for bradycardia): atenolol, nadolol and sotalol (accumulation also prolongs QT) are the classic trio, but bisoprolol is about 50% excreted unchanged (half-life triples at CrCl < 40) and acebutolol's active metabolite diacetolol is renal (cut dose 50% at CrCl < 50, 75% at < 25). Metoprolol, carvedilol, propranolol and labetalol are hepatic.

PTH is the first lab after finding hypercalcemia. High PTH = hyperparathyroidism. Low PTH = malignancy. This drives the entire workup.

Calcitonin works fast (4–6h) but tachyphylaxis in 48h. Use as a bridge while waiting for zoledronic acid to kick in (2–4 days).

Furosemide for hypercalcemia is largely obsolete. Hydrate aggressively first. Lasix only if volume-overloaded from the fluids.

Hyponatremia workup: (1) serum osm, (2) volume status, (3) urine Na + urine osm. This 3-step approach classifies every case.

Urine osm < 100 with hyponatremia = kidneys are diluting appropriately → the problem is excessive water intake (polydipsia, beer potomania).

Uremic pericarditis is an ABSOLUTE dialysis indication -it can progress to hemorrhagic tamponade. Does NOT respond to NSAIDs/colchicine.

CRRT over HD in hemodynamically unstable patients -gentler fluid/solute removal over 24h vs rapid shifts in 3–4h. Less hypotension on pressors.

There is no specific BUN or creatinine threshold for starting dialysis. IDEAL 2010: early initiation showed no survival benefit. Treat symptoms, not numbers.

Eosinophils in the urine are neither sensitive nor specific for AIN -stop relying on them. Biopsy if you really need the diagnosis.

In symptomatic hypercalcemia, IV fluids are first-line. Calcitonin works in hours; zoledronic acid works in 2-4 days. Denosumab is an option in CKD.

Severe hypophosphatemia is < 1.0 mg/dL (< 0.32 mmol/L): give IV phosphate at that level, if symptomatic (rhabdomyolysis, hemolysis, CNS symptoms) or if oral intake is not feasible; most asymptomatic patients at 1-2 mg/dL do well with oral repletion. IV phosphate binds calcium and can cause hypocalcemia, hyperphosphatemia and arrhythmia, so dose in mmol/kg, infuse over hours and recheck Ca and PO4 at 6 hours.

Dialysis patients get the standard ACS workup -troponin is still interpretable. Don't dismiss chest pain as 'just uremic'.

IV calcium gluconate in hyperkalemia stabilizes the cardiac membrane within minutes but does NOT lower potassium. Still need insulin + D50, beta-agonist, and definitive removal (kayexalate, dialysis, diuresis).

AV fistulas are generally not used for CRRT, but not because a needle cannot stay in beyond 4 hours (nocturnal HD runs about 8 hours per session). The concern is days of continuous cannulation in a sedated, repositioned ICU patient: needle dislodgement means rapid exsanguination, and infiltration or thrombosis can cost the access. Default to a tunneled or temporary dialysis catheter.

Extreme leukocytosis/thrombocytosis causes pseudohyperkalemia from in vitro cell lysis. Redraw as plasma K⁺ (lithium heparin) before treating.

Urine protein/creatinine ratio is unreliable in AKI, falsely high when Cr is rising, falsely low when recovering. Wait for Cr to stabilize before evaluating proteinuria.

ESRD + anemia: rule out other causes and replete iron first. KDIGO 2026, hemodialysis: give IV iron (PIVOTAL-style proactive dosing) when ferritin ≤ 500 ng/mL and TSAT ≤ 30%; hold it if ferritin > 700, TSAT ≥ 40% or active infection. Start an ESA at Hgb ≤ 9–10 g/dL, target 10–11.5, and never use it to keep Hgb ≥ 11.5 (hypertension; stroke and access thrombosis at higher targets).

Hypercalcemia with polyuria + constipation is a classic combo, calcium directly inhibits renal concentration (nephrogenic DI) and smooth muscle motility. Bones, stones, groans, and psychiatric overtones.

No routine NPO in acute pancreatitis: eating keeps the gut barrier intact and limits bacterial translocation. ACG 2024: in mild AP start a low-fat solid diet within 24 to 48 h as tolerated, no clear-liquid ladder, even if lipase is up. PADI 2021 (N=131, mild-moderate AP): immediate solids cut LOS 8.8 to 3.4 days, complications 26% to 8%. Cannot eat? Tube feed NG over NJ, not TPN.

Pain out of proportion to exam = think mesenteric ischemia. By the time peritoneal signs develop, the bowel is already dead.

INR is NOT a contraindication to paracentesis in cirrhosis. Bleeding risk < 1% even with INR > 2 and platelets < 50K. Just tap them.

Acute mesenteric ischemia: pain out of proportion to exam is the classic tip-off. Lactate and leukocytosis are late. CT angiogram is first-line imaging, don't wait for peritoneal signs, which indicate transmural infarction.

Any cirrhotic admitted with ascites gets a diagnostic paracentesis, per AASLD and EASL. Missed SBP at admission has 20% mortality. Don't defer just because they 'look stable.'

Bloody diarrhea? Don't reflexively give antibiotics. Shiga toxin-producing E. coli (STEC, O157:H7) plus antibiotics raises HUS risk (toxin release, microangiopathy, AKI, thrombocytopenia, worst in kids). Send Shiga toxin PCR BEFORE antibiotics. HUS care is supportive: eculizumab is for atypical HUS; both STEC-HUS RCTs (ECULISHU 2023, ECUSTEC 2024) missed their primary endpoints. Botulism: antitoxin, not antibiotics.

3-6-9 rule for bowel diameter: small bowel 3 cm, colon 6 cm, cecum 9 cm. Wider than that is dilated. The cecum is allowed to be widest but perforates first: by Laplace's law, wall tension = pressure × radius, so the widest segment carries the most tension. Nine is the upper limit of normal, not the danger line: perforation risk climbs above 12 cm and with distension lasting beyond ~6 days.

Rome V (May 2026) lowered the bar for IBS: abdominal pain OR discomfort at least 3 days a month for 3 months, tied to defecation or to a change in stool frequency or form, and the pain cannot be continuous. Rome IV demanded pain at least weekly, which halved prevalence estimates and selected a sicker minority. Constant pain unrelated to bowel habit points to centrally mediated abdominal pain syndrome instead.

Fecal calprotectin 40 µg/g or below, or CRP 0.5 mg/dL or below, leaves a 1% or lower probability of IBD in a patient with IBS-D symptoms and no alarm features (Menees 2015). That number is what lets you diagnose IBS positively at the first visit instead of scoping a 29-year-old: the ACG recommends against routine colonoscopy under 45 without warning signs.

Immune-tolerant hepatitis B is no longer an automatic 'just monitor': AASLD/IDSA 2026 suggests treating HBeAg-positive patients with HBV DNA above 10 million IU/mL and a normal ALT if they are over 40 or have F2+ fibrosis, because liver damage and HCC risk accumulate while the ALT still looks normal. Judge normal ALT by 35 U/L in men and 25 U/L in women, not the lab range.

No prophylactic antibiotics in acute pancreatitis, even with necrosis: in Dellinger 2007 (N=100) meropenem did not reduce pancreatic infection vs placebo (18% vs 12%), mortality or surgery. Start antibiotics on clinical suspicion of infected necrosis; routine FNA is not needed (ACG 2024), and gas in the necrosis or positive cultures proves it. Choose an agent that penetrates necrosis (e.g., a carbapenem).

Ascitic fluid PMN ≥ 250 = SBP. Start ceftriaxone immediately -do NOT wait for culture. Give albumin 1.5 g/kg day 1 + 1 g/kg day 3 in high-risk patients (Cr > 1, BUN > 30, or bilirubin > 4) per AASLD -reduces hepatorenal syndrome and mortality.

Every cirrhotic admitted with GI bleeding gets antibiotic prophylaxis from admission for up to 7 days: it cuts infections, rebleeding and mortality (Cochrane 2010, mortality RR 0.79). Ceftriaxone 1 g IV daily is first choice in advanced cirrhosis, prior quinolone use or high resistance, and the usual US default (no US norfloxacin); Fernández 2006 beat norfloxacin on infections (11% vs 33%), not mortality.

Terlipressin is FDA-approved for HRS-AKI (2022) -shown to reverse HRS in ~30% vs placebo. Watch for respiratory and ischemic complications.

Rifaximin added to lactulose reduces HE recurrence and hospitalizations -don't stop at lactulose alone for patients who've had a prior episode.

Pre-endoscopic erythromycin 250 mg IV 30-90 min before EGD for acute upper GIB improves gastric visualization and reduces repeat endoscopy.

Large-volume paracentesis → replace with 25% albumin (~8g per liter removed). Concentrated albumin raises oncotic pressure without re-expanding total volume; 5% is for volume resuscitation.

Cirrhotic patients still need DVT prophylaxis despite high INR, they lack both procoagulants and anticoagulants, so they can bleed AND clot. INR doesn't reflect real risk.

Eosinophilic esophagitis: first-line is swallowed aerosolized steroids (fluticasone MDI or budesonide slurry), NOT systemic prednisone. Dilate strictures carefully, high mucosal tear risk.

IBD patients are hypercoagulable despite GI bleed risk, systemic inflammation drives a prothrombotic state, especially during flares. Don't withhold DVT prophylaxis.

Vedolizumab blocks only α4β7, the gut-homing integrin for MAdCAM-1. Natalizumab blocks the shared α4 chain, so it also blocks α4β1-VCAM-1 lymphocyte entry into the CNS; lost CNS immune surveillance lets JC virus reactivate as PML. Vedolizumab spares α4β1, so CNS surveillance is preserved; the label cites one postmarketing PML case (HIV, prior immunosuppression), so still watch for new neuro signs.

Suspected appendicitis in pregnancy: graded-compression ultrasound first. If nondiagnostic, MRI (no contrast) next. CT only if MRI is unavailable and clinical suspicion is high.

HCC surveillance: abdominal ultrasound ± AFP every 6 months in cirrhosis of any cause, chronic HBV (even without cirrhosis) at certain ethnicity/age thresholds. Rising AFP without mass → repeat imaging sooner.

Don't protein-restrict in hepatic encephalopathy, old teaching is debunked. Cirrhotic patients are protein-calorie malnourished; restriction worsens outcomes. Treat with lactulose, rifaximin, and adequate protein.

Hemosuccus pancreaticus: bleeding from the ampulla of Vater via the pancreatic duct, rare cause of upper GI bleed. Think of it in chronic pancreatitis, pseudocysts, or pancreatic tumors with unexplained melena and normal upper endoscopy.

HRS-AKI (was type 1 HRS; ADQI-ICA 2024): AKI in cirrhosis with ascites, not improved 24 h after indicated volume resuscitation, no other cause (shock, nephrotoxins, structural injury). The 48-h albumin challenge is retired, so start terlipressin plus albumin promptly. Terlivaz can cause fatal respiratory failure: do not start if SpO2 < 90% or active ischemia. Norepinephrine is the ICU option; cure is transplant.

Today's Kaopectate is bismuth subsalicylate, the same drug as Pepto-Bismol, not kaolin-pectin. Treat it as a salicylate: it carries the aspirin-allergy and Reye's syndrome warnings, stacks with aspirin, and matters on anticoagulants. It also turns stool black, which can be mistaken for melena.

Dicyclomine for IBS cramping is the one place the US guidelines point in opposite directions: ACG 2021 recommends against the US-available antispasmodics (old, small trials, mostly of drugs not sold here), AGA 2022 gives them a conditional yes. If you use it: 20 mg four times daily, up to 40 mg after a week, stop at 2 weeks if it has not helped, never IV, and never stacked on other anticholinergics in older adults (Beers list).

Eluxadoline is contraindicated in anyone without a gallbladder. It is a mu-opioid agonist, and sphincter of Oddi spasm with no gallbladder to buffer the pressure causes pancreatitis, with fatal cases reported in the first week of treatment. The same logic excludes biliary obstruction, any history of pancreatitis, and more than 3 drinks a day. Ask about the cholecystectomy before the prescription, not after the lipase.

Low albumin changes the infliximab dose in acute severe UC. Below 2.5 g/dL, much of the drug is lost through the inflamed colon, so ACG 2025 advises considering a higher or accelerated infliximab dose for rescue. The same guideline advises against routine broad-spectrum antibiotics and TPN for bowel rest.

Restrictive transfusion (Hgb trigger 7) beat liberal (trigger 9) in acute upper GI bleeding (Villanueva 2013, n = 921): 6-week survival 95% vs 91% (HR 0.55), rebleeding 10% vs 16%. Benefit was significant in Child-Pugh A/B cirrhosis (HR 0.30), not Child C. Portal pressure rose only with liberal transfusion, the likely reason overtransfusion promotes variceal rebleeding. Excluded massive bleeding and recent ACS.

MELD 3.0 (includes sex and albumin) now replaces MELD-Na for liver transplant allocation as of 2023 -more accurate mortality prediction.

Opioids worsen IBD outcomes -associated with higher mortality and toxic megacolon risk. Use acetaminophen, avoid NSAIDs, and treat the disease.

Morphine is fine in pancreatitis -the 'sphincter of Oddi spasm' concern is not clinically significant.

Mild gallstone pancreatitis: same-admission cholecystectomy. PONCHO 2015 (N=266, mild disease only) cut readmission for recurrent gallstone complications or death within 6 months from 17% to 5% without more operative complications; ACG 2024 says operate before discharge. In necrotizing biliary pancreatitis, defer cholecystectomy until the necrosis is managed and collections have settled.

LR is preferred over NS for pancreatitis resuscitation -NS causes hyperchloremic acidosis that may worsen inflammation.

Afib is the #1 risk factor for SMA embolism -the most common cause of acute mesenteric ischemia (~50%).

Normal lactate does NOT rule out early mesenteric ischemia. If you're thinking about it, get the CTA now.

SAAG ≥ 1.1 = portal hypertension (cirrhosis, HF). SAAG < 1.1 = non-portal (malignancy, TB, nephrotic). The SAAG tells you WHY there's ascites.

Albumin 6–8 g per liter removed after large volume paracentesis > 5L prevents post-paracentesis circulatory dysfunction and HRS.

Carvedilol is the preferred NSBB in compensated cirrhosis with CSPH (Baveno VII 2022, AASLD 2024): its alpha-1 blockade lowers intrahepatic resistance, so it drops HVPG more than propranolol. Target 12.5 mg/day. PREDESCI 2019: NSBB (propranolol; carvedilol if non-responder) cut decompensation or death vs placebo, 16% vs 27%, mainly less ascites. With ascites either NSBB works; reduce or stop if SBP < 90 or HRS-AKI.

Albumin with antibiotics in SBP reduces HRS from 33% to 10% and mortality from 29% to 10%. Never skip the albumin.

15% of patients with hematochezia have an UPPER GI source. If hemodynamically unstable with bright red blood per rectum → rule out upper source first.

Diverticular bleed is the #1 cause of LGIB in adults > 60. 80% stop spontaneously. Right-sided diverticula bleed more often than left.

Heyde syndrome: aortic stenosis + GI bleeding from angiodysplasia. High shear stress destroys vWF multimers → acquired von Willebrand disease.

Glasgow-Blatchford score of 0-1 in upper GIB identifies patients who can be managed outpatient -a validated ED disposition tool.

In IBD flare, C. diff superinfection is common and changes management -test every flare, even without classic diarrhea pattern change.

SBP diagnosis: ascitic fluid PMN ≥ 250/mm³. Start empiric ceftriaxone immediately -don't wait for culture. Repeat tap not routinely needed unless atypical organisms or no clinical improvement at 48h.

Albumin in SBP (1.5 g/kg on day 1, 1 g/kg on day 3) reduces hepatorenal syndrome and mortality -especially when Cr > 1, BUN > 30, or bilirubin > 4. Don't skip the albumin.

Cirrhotic patients with MAP < 82 have 20% survival at 24 months (vs 70% if MAP > 82). Avoid ACEi/ARB even in CKD; consider stopping beta-blockers once BP drops.

Inoculate ascites fluid directly into blood culture bottles at the bedside (new needle, alcohol-wiped top), yield jumps from 76% to 100% vs delayed lab inoculation.

Terlipressin (Terlivaz) for HRS-AKI: do not start if SpO2 < 90%, respiratory symptoms are worsening, or coronary, limb or mesenteric ischemia is ongoing; stop if SpO2 falls below 90% (boxed warning: fatal respiratory failure, highest with volume overload or ACLF grade 3). May cause fetal harm. If MELD ≥ 35, risk may outweigh benefit: respiratory failure or ischemia can make a listed patient transplant-ineligible.

Take PPIs 30 to 60 min before breakfast (ACG 2022, strong recommendation). They bind only actively secreting proton pumps, so dosing ahead of the meal-stimulated acid surge maximizes irreversible inhibition. Bedtime dosing is discouraged; it controls acid less well than a pre-dinner dose.

Ileus = ALL bowel distended, usually non-tender. Ogilvie's (acute colonic pseudo-obstruction) = COLON only, in a sicker patient, different workup, different decompression.

Asymptomatic Giardia shedders don't need treatment, they clear spontaneously. Symptomatic patients should avoid recreational water for 2 weeks after resolution.

Avoid BOTH opioids AND NSAIDs in IBD. Opioids worsen morbidity/mortality; NSAIDs (including IV ketorolac) can trigger flares. Celecoxib is the one NSAID considered safer.

NG tubes are safe in active variceal bleeding, part of the workup for hematemesis. Theoretical clot disruption risk is not borne out in meta-analyses.

Hyperdynamic circulation in cirrhosis: splanchnic vasodilation drops SVR → low MAP, but CO is high as the body compensates. This physiology drives varices, refractory ascites, and HRS.

Worsening abdominal distention despite a 'nonobstructive' CT read? Escalate anyway, call surgery, place NGT, reimage. A single CT read doesn't override clinical trajectory.

Liver tumor embolization: TACE (transarterial chemoembolization) is standard of care, but contraindicated in portal vein thrombosis. SIRT (selective internal radiation with Y-90) is an alternative when TACE isn't feasible.

TNF-α inhibitor dosing: etanercept (Enbrel) qweek (avoid if uveitis), adalimumab (Humira) q2 weeks, infliximab (Remicade) q4–8 weeks IV, certolizumab (Cimzia) pegylated with longer half-life. IV Remicade is best if adherence is uncertain.

First-time PPI for classic heartburn without alarm features: ACG 2022 recommends an 8-week trial once daily, 30–60 min before breakfast, then an attempt to stop or step down to on-demand use. Avoid open-ended refills; rebound acid hypersecretion can briefly flare symptoms after stopping. No response, or relapse off PPI, earns endoscopy (ideally 2–4 weeks off PPI). PRN calcium carbonate covers breakthrough.

Ascites, even large-volume or refractory, is not by itself a reason to stop beta-blocker variceal prophylaxis (Baveno VII). Dose-reduce or hold the NSBB or carvedilol only for persistent hypotension (SBP < 90 or MAP < 65) or HRS-AKI, when the patient needs the cardiac output to perfuse the kidneys; restart or re-titrate once BP recovers or the AKI resolves, and band the varices if the drug cannot be tolerated.

Post-C. diff transient lactose intolerance is common. Counsel patients to avoid dairy for a few weeks after treatment to prevent persistent diarrhea misread as recurrence. Also discontinue PPIs when possible.

Primary sclerosing cholangitis: no medical therapy, including UDCA, improves transplant-free survival; liver transplant is the only definitive treatment, though PSC recurs in a minority of grafts. Median time to transplant or PSC-related death is ~21 years in a population-based cohort (Boonstra 2013) vs ~13 years in referral centers (sicker patients). ERCP treats dominant strictures and stones, not the disease.

Ascites: SAAG ≥ 1.1 = portal hypertension (cirrhosis, HF, Budd-Chiari). SAAG < 1.1 = non-portal (malignancy, TB, pancreatitis, nephrotic). Protein > 2.5 with high SAAG = cardiac ascites; < 2.5 = cirrhotic.

Spontaneous fungal peritonitis is a cirrhosis diagnosis, distinct from catheter-related fungal peritonitis in peritoneal dialysis. Suspect it with prior SBP prophylaxis or antibiotics, CKD, ICU stay, or SBP failing antibiotics; mortality far exceeds SBP. Candida albicans leads. Start an echinocandin, step down to fluconazole if susceptible; echinocandins miss Cryptococcus, which needs amphotericin-based therapy.

Neutropenic fever: antibiotics within 60 minutes. Every hour of delay increases mortality. Cefepime 2g IV q8h is standard.

Fidaxomicin is now preferred over oral vancomycin for initial C. diff -lower recurrence rate (13% vs 27%) because it preserves normal gut flora.

Bacterial meningitis: antibiotics within 30–60 minutes. Every hour of delay worsens outcome, and door-to-antibiotic beyond 6 hours carries roughly an 8-fold higher mortality. Do NOT wait for LP or CT.

Cefepime at high dose (2 g q8h) in renal impairment causes neurotoxicity (encephalopathy, non-convulsive status). Adjust for CrCl or switch agents.

Neonatal sepsis (< 28 days): ampicillin plus gentamicin is first-line (covers GBS, E. coli and Listeria, which cephalosporins miss). US cefotaxime supply has been unreliable since 2015, so if a 3rd-generation cephalosporin is needed (gram-negative meningitis) use ceftazidime. Avoid ceftriaxone and sulfonamides: both displace bilirubin from albumin (kernicterus), and ceftriaxone precipitates with calcium IV fluids.

Linezolid can cause serotonin syndrome with SSRIs/SNRIs/MAOIs, it's a weak MAOI. Risk is low but counsel to hold SSRIs when feasible. Also causes cytopenias with courses > 2 weeks; monitor CBC.

Severe toxin-mediated infection (nec fasc, STSS, TSS, gas gangrene): add a 50S inhibitor to the beta-lactam. Clindamycin (GAS, MSSA, C. perfringens) or linezolid (MRSA, clinda-resistant GAS) halts toxin synthesis in any growth phase. Eagle effect: at high inoculum, stationary-phase GAS make fewer PBPs, so beta-lactams fail. Rifampin: no benefit in S. aureus bacteremia (ARREST 2018); keep it for hardware biofilm.

Moxifloxacin is the one fluoroquinolone that cannot treat a UTI. Only about 20% is excreted unchanged in urine, because it is cleared by hepatic conjugation rather than filtration, and UTI appears nowhere on its FDA label. The same property makes it the easy pick in AKI or on dialysis, where it needs no dose adjustment at all. Convenient in renal failure, useless in the urinary tract.

Ciprofloxacin is not a respiratory fluoroquinolone. Its activity against S. pneumoniae is unreliable, which is why IDSA/ATS does not recommend it for community-acquired pneumonia. The respiratory agents are levofloxacin and moxifloxacin. Reaching for cipro in CAP looks like a reasonable fluoroquinolone choice and leaves the commonest CAP pathogen uncovered.

Dexamethasone before or with first antibiotic dose reduces mortality in S. pneumoniae meningitis. Discontinue if NOT pneumococcus.

Add ampicillin for Listeria if age > 50, immunocompromised, alcoholic, or pregnant. Listeria is NOT covered by cephalosporins.

Ceftriaxone dose for meningitis is 2g q12h -double the standard dose. The blood-brain barrier limits CSF penetration.

Positive UA in an asymptomatic patient is NOT a UTI -it's asymptomatic bacteriuria. Do NOT treat (except pregnancy or pre-urologic procedure).

Start ART in ALL HIV patients regardless of CD4. START 2015: immediate ART reduced serious events vs deferred treatment.

CD4 < 200 = start PCP prophylaxis (TMP-SMX DS daily) AND send a serum cryptococcal antigen: DHHS now screens at CD4 ≤ 200 (was ≤ 100), highest yield at ≤ 50, because antigenemia precedes meningitis by weeks and preemptive fluconazole prevents it. A positive CrAg usually needs an LP to exclude CNS disease, especially if titer ≥ 1:160. CD4 < 50 = risk of CMV retinitis and disseminated MAC.

Vancomycin AUC-guided dosing (target 400-600) has replaced trough-only dosing -reduces nephrotoxicity while maintaining efficacy for MRSA.

ACORN (2023) RCT showed no AKI difference between cefepime and pip-tazo (± vancomycin) -the old observational signal was debunked. The real cefepime tradeoff is neurotoxicity, especially in AKI/elderly.

Bezlotoxumab (Zinplava, anti-toxin B antibody) cut C. diff recurrence from about 27% to 17% in MODIFY I/II, but Merck discontinued it in January 2025 and it is no longer available in the US. To prevent recurrence after a recurrent episode, treat with fidaxomicin and consider the FDA-approved live biotherapeutics Rebyota (rectal) or Vowst (oral) once the antibiotic course is complete.

Zosyn (pip-tazo) can cause hypokalemia (piperacillin acts as a non-reabsorbable anion in the distal tubule, increasing K⁺ loss) and Mg²⁺ wasting, plus a modest sodium load: 8.4 mEq (192 mg) per 3.375 g dose and 11.2 mEq (256 mg) per 4.5 g dose per the label, about 25-45 mEq (0.6-1 g) a day depending on regimen. Check K⁺ and Mg²⁺ during therapy and count the sodium in heart failure or volume-sensitive patients.

Lyme arthritis: 28 d oral doxycycline, amoxicillin or cefuroxime (IDSA/AAN/ACR 2020, none preferred); minimal response: 2–4 wk IV ceftriaxone. Meningitis, cranial neuropathy, radiculoneuropathy: oral doxycycline or IV ceftriaxone, 14–21 d. Brain or spinal cord parenchymal disease: IV, not oral. Under age 8, doxycycline is accepted only for short courses, so use amoxicillin or cefuroxime for 28-day arthritis.

Lyme is diagnosed by two-tiered testing: EIA first (high sensitivity rules OUT), then Western blot if EIA positive/equivocal. IgG + IgM if < 30 days of symptoms; IgG alone if > 30 days.

Rule out active TB with 3 sputum AFB smears ≥ 8 hours apart (at least one morning) PLUS MTB PCR on a morning sample. All must be negative to clear airborne precautions.

Culture-negative endocarditis is usually prior antibiotics, so empiric therapy still covers staph, strep and enterococci. If truly untreated, think Coxiella, Bartonella, Brucella and Tropheryma whipplei and send serologies or PCR; HACEK now grow in standard cultures. Bartonella: doxycycline plus gentamicin, or plus rifampin when gentamicin cannot be used; Coxiella: doxycycline plus hydroxychloroquine for 18 months or more.

HIV post-exposure prophylaxis: THREE drugs for 28 days. CDC 2025 preferred regimens are single-tablet bictegravir/emtricitabine/TAF (Biktarvy) or dolutegravir plus tenofovir (TAF or TDF) plus emtricitabine or lamivudine; raltegravir-based PEP is no longer a preferred option (higher pill burden). Start as soon as possible, ideally within 24 hours and never later than 72 hours.

Rigors (shaking chills) has the highest likelihood ratio for bacteremia on blood cultures, even higher than fever > 100.9. Routine cultures for CAP or cellulitis have low yield and high false-positive risk.

Inducible AmpC: in invasive infection with E. cloacae complex, K. aerogenes, C. freundii or Hafnia, avoid ceftriaxone even if susceptible (resistance can emerge within a few doses). Use cefepime (MIC ≤ 8), a carbapenem, or FQ/TMP-SMX if susceptible. Serratia, Morganella and Providencia rarely derepress: treat per susceptibility, but favor cefepime in endocarditis or CNS infection (IDSA 2026).

Miliary TB often has LOW AFB sputum yield. Go to bronchoscopy with transbronchial biopsy early. Chest CT shows classic 1–3 mm nodules; LP is needed if any neurologic signs (TB meningitis has 50% mortality).

Bismuth subsalicylate (Pepto-Bismol) for traveler's diarrhea: prophylaxis 2 tabs QID ≤3 wk (~65% ↓ risk); tx 2 tabs q30 min PRN (max 8/24h, ~50% stool-frequency ↓, less effective than azithro/rifaximin). Black tongue + black stool = bismuth sulfide, benign, reassure (NOT melena). Avoid: kids <12 (Reye), aspirin allergy, pregnancy, renal failure. Tinnitus = salicylate toxicity → STOP.

Jarisch-Herxheimer reaction: fever, chills, rigors, hypotension, rash 4–12h after giving antibiotics for syphilis, leptospirosis, Lyme, or relapsing fever. NOT an allergy, massive spirochete lysis releases endotoxin-like products. Counsel patients BEFORE starting. Continue the antibiotic. Give antipyretics + IV fluids. Historically fatal in congenital syphilis treatment. Classic pimp: 'Why does your syphilis patient spike a fever right after penicillin?'

Linezolid causes lactic acidosis via mitochondrial toxicity, usually after > 2 weeks of use. Send weekly lactate on prolonged courses. Same drug also causes thrombocytopenia (twice-weekly CBC > 14 days), peripheral and optic neuropathy (> 28 days, may be irreversible), and serotonin syndrome (weak MAOi, avoid with SSRIs/SNRIs/tramadol). Cohen-Woods Type B2.

Among respiratory fluoroquinolones, only levofloxacin covers Pseudomonas (at 750 mg), and only moxifloxacin covers anaerobes. So moxifloxacin can stand alone when an anaerobic source is in play, while levofloxacin needs metronidazole added for the same job. And moxifloxacin in a bronchiectasis exacerbation is a coverage gap, not a stylistic preference.

Endocarditis courses changed in 2026: native-valve staphylococcal and streptococcal IE is 4 weeks, E. faecalis 6 and prosthetic valves 6, all counted from clearance of bacteremia (AHA 2026; staph was 6). Gentamicin is dropped for staphylococcal prosthetic valves and penicillin-susceptible strep, because its kidney toxicity outweighs any benefit.

ESBL complicated UTI does not automatically need a carbapenem. If the isolate is susceptible, TMP-SMX, ciprofloxacin or levofloxacin is preferred (IDSA 2026), and piperacillin-tazobactam is an acceptable alternative when the patient is not critically ill or bacteremic. Outside the urinary tract, a carbapenem remains the standard, because piperacillin-tazobactam lost to meropenem in ESBL-type bacteremia (MERINO).

Mild acute pulmonary histoplasmosis usually needs no antifungal in an immunocompetent patient (IDSA 2025); treat if it lasts over a month, worsens, or the patient is immunocompromised. When itraconazole is used, check a trough level, because absorption is erratic and an undetected low level looks like treatment failure.

S. bovis (gallolyticus) bacteremia or endocarditis requires colonoscopy: in a 2011 meta-analysis (Boleij, Clin Infect Dis) a median 60% of S. bovis-infected patients who had colonic evaluation had adenomas or carcinoma, and the link is strongest for biotype I (S. gallolyticus) and for endocarditis. Scope every patient, even without GI symptoms.

Delay ART 4–6 weeks after starting crypto meningitis treatment. Early ART causes fatal IRIS with CNS inflammation.

Oral step-down therapy (POET trial) for stable left-sided endocarditis is non-inferior to full IV course -shortens hospital stays substantially.

3 sets of blood cultures before antibiotics, from separate venipunctures whenever possible (best practice, but the 2023 Duke-ISCVID criteria no longer require separate sites or spacing). Each set = 1 aerobic + 1 anaerobic bottle. At least 20 mL per set.

S. aureus is the most common cause of endocarditis overall. Viridans strep is #1 in subacute native valve IE.

Neutropenic fever = antibiotics within 60 minutes. Cefepime monotherapy. Do NOT routinely add vancomycin -only for specific indications.

Persistent fever day 4–7 despite antibiotics + ANC still < 500 → add empiric antifungals. CT chest for halo sign (aspergillosis).

Alcohol hand sanitizer does NOT kill C. diff spores. Soap and water with mechanical friction is required. This is not optional.

IV metronidazole is only for fulminant C. diff (as adjunct). Oral metronidazole is inferior to vancomycin -it is no longer first-line for any severity.

Confusion in the elderly + bacteriuria ≠ UTI. AMS is NOT a urinary symptom. Look for other delirium causes before blaming the urine.

Nitrofurantoin is first-line for uncomplicated cystitis. Avoid fluoroquinolones -save them for upper tract or complicated infections.

Non-purulent cellulitis is usually strep, not staph. Cefazolin is sufficient -no MRSA coverage needed. Purulent/abscess = staph → I&D + MRSA coverage.

Up to 30% of 'cellulitis' admissions are misdiagnosed. Top mimic: stasis dermatitis (bilateral, chronic). Bilateral cellulitis is almost never cellulitis.

Cellulitis borders should be marked with pen + date/time -if erythema extends beyond marks at 48h, antibiotics are failing.

FDA-approved microbiota products for C. diff: Rebyota (rectal, one dose 24-72 h after antibiotics) and Vowst (oral, 3 days, starting 2-4 days after). Both are labeled to prevent recurrence after antibiotic treatment of recurrent CDI; neither treats active infection. ACG 2021 and IDSA/SHEA 2017 reserve FMT for a second or later recurrence, when antibiotics alone keep failing (Vowst's trial required 3+ episodes).

Duke criteria were updated in 2023 (Duke-ISCVID). New major criteria: cardiac CT, 18F-FDG PET/CT (uptake within 3 mo of a prosthetic implant is only minor), intraoperative findings, and PCR for Coxiella, Bartonella or T. whipplei. E. faecalis and S. lugdunensis are now typical organisms; blood cultures no longer need timed, separate draws. Injection drug use is still a minor predisposition criterion, as in 1994.

Rapid ART initiation (same day as diagnosis) is now recommended -improves linkage to care and viral suppression without added toxicity.

Empiric bacterial meningitis: vancomycin + ceftriaxone + dexamethasone. ADD ampicillin if age > 50, immunocompromised, pregnant, or alcoholic -covers Listeria.

Dexamethasone in bacterial meningitis must be given BEFORE or WITH the first antibiotic dose -mortality benefit only when timed correctly. Useless once antibiotics have already been started.

Early localized Lyme is a CLINICAL diagnosis, don't send serology (often false-negative early). Start oral doxycycline empirically. Disseminated disease requires serology.

Cryptococcal meningitis presents with markedly elevated opening pressure (> 25 cmH₂O), a hallmark. Serial therapeutic LPs are part of the treatment, not just the workup.

Central lines + fever → draw cultures from BOTH the line AND a peripheral site. Time-to-positivity differential tells you if the line is the source. Culture every line if multiple.

Linezolid is replacing clindamycin as the toxin-suppressing adjunct in necrotizing soft tissue infection: 100% oral bioavailability, less C. diff risk, rising group A strep clindamycin resistance. The evidence is observational so far (no mortality difference in retrospective NSTI and invasive GAS cohorts; a target-trial emulation met non-inferiority), not a randomized head-to-head trial.

Oral terbinafine is first-line for severe onychomycosis. Griseofulvin requires up to 18 months of therapy, frequent labs, and has high relapse, reserved for specific cases.

Late syphilis (tertiary or late latent) = penicillin G 2.4 MU IM weekly × 3 weeks. Early syphilis is a single dose. Tabes dorsalis and aortitis are late manifestations.

Suspect multiple tick-borne illnesses in any patient with one. Occam's razor fails in tick exposure, co-infection with Lyme + anaplasma + babesia is common.

Lyme meningitis 'Rule of 7s' identifies LOW risk: headache < 7 days, < 70% CSF mononuclear cells, and no 7th nerve palsy. Helps distinguish from enteroviral meningitis.

Bacterial conjunctivitis first-line: erythromycin ointment or polymyxin-TMP drops. Use fluoroquinolone drops in contact-lens wearers, higher Pseudomonas risk.

Ecthyma = impetigo that has ulcerated through dermis, usually on legs/feet, almost always streptococcal. Needs systemic (not topical) antibiotics; watch for associated lymphangitis.

Tenofovir alafenamide (TAF) is safe in moderate CKD, avoid tenofovir disoproxil (TDF) when GFR < 60. TAF has better renal/bone safety but more weight gain.

Typhoid fever takes 4–6 days to defervesce AFTER starting antibiotics, persistent fever doesn't mean treatment failure. Complete 10–14 days to avoid the 2–3 week recurrence spike.

Typhoid vaccine is recommended for travel almost everywhere EXCEPT US/Canada and Western Europe. Oral vaccine is LIVE and contraindicated in immunocompromised patients, use the IM Vi polysaccharide instead.

Immunocompetent shingles: start valacyclovir 1 g TID or famciclovir 500 mg TID within 72 hours of rash onset. Acyclovir 800 mg five times daily is preferred only in pregnancy. After 72 hours, antivirals help only if new lesions are still forming.

Right-sided MSSA IE in people who inject drugs: the 2015 AHA 2-week nafcillin or oxacillin course for strictly uncomplicated disease is not carried into the 2026 AHA statement, which lists 4 weeks from clearance for native-valve staph. If outpatient IV therapy is not feasible, dalbavancin 1500 mg IV on days 1 and 8 after clearance is the 2026 option (DOTS included right-sided IE). Gentamicin still adds nephrotoxicity without benefit.

CLL with recurrent sinopulmonary infections → check immunoglobulins. Hypogammaglobulinemia is common; IVIG replacement reduces infection risk in documented cases.

Exposed bone in a stage 4 pressure injury does not prove osteomyelitis: histologic osteomyelitis ranged from about 17% to 86% across studies, under half in most. Probe-to-bone has no validated accuracy in pressure injuries. Bone biopsy with histology and culture is definitive; MRI is sensitive but not specific, and helps decide whom to biopsy.

Asymptomatic bacteriuria in elderly patients with altered mental status is often NOT the cause. Look for other reversible causes of delirium first, treating ASB risks C. diff and resistance without helping the AMS.

Uncomplicated Enterococcus cystitis: nitrofurantoin works (high urinary concentrations). NOT adequate for pyelonephritis or systemic enterococcal infection, tissue levels are too low.

Antibiotic prophylaxis during neutropenia is only indicated if the patient is on active chemotherapy, not for congenital or drug-induced neutropenia. Levofloxacin prophylaxis selects resistance when used inappropriately.

Fever in a returning traveler: first branch, is it travel-related? Pretest probability favors UTI/respiratory over exotic infections. Then stratify by incubation: < 10 days → typhoid, lepto, dengue, malaria; 10–21 days → typhoid, malaria, rickettsia; > 21 days → TB, hepatitis, HIV.

CSF VDRL is highly SPECIFIC but INSENSITIVE for neurosyphilis, a negative result doesn't rule it out. Treat ocular or otosyphilis as neurosyphilis without requiring LP (CSF is often normal).

Clindamycin's place has shrunk, its last real indication is necrotizing fasciitis (toxin suppression). The old 'metro below / clinda above the diaphragm' teaching is obsolete: too much C. diff, too much dosing, too much GI upset.

JAK inhibitors (tofacitinib, upadacitinib, baricitinib) require Shingrix vaccination before starting, high reactivation rate. Also increase VTE and major CV events; use with caution in older patients with CV risk.

Quick rash evaluation: sick vs not sick, then inside vs outside. 'Inside' (systemic) rashes are bilateral/symmetric; 'outside' (contact/topical) rashes are unilateral/asymmetric. Life-threatening fever + rash: meningococcemia, RMSF, TSS.

Permissive hypertension (< 220/120) in stroke maintains collateral perfusion. Only lower BP aggressively if giving tPA; at 220/120 or above without lysis, aim for about a 15% initial reduction.

Do NOT give steroids for GBS -no benefit (unlike CIDP and myasthenia). Treatment: IVIG or PLEX. Never give both together.

Avoid IV magnesium in myasthenia gravis -it blocks presynaptic ACh release and can precipitate myasthenic crisis.

Steroids are CONTRAINDICATED in Guillain-Barré, may worsen outcomes. Treat with IVIG or plasmapheresis (equal efficacy). CIDP is different, steroids work there.

Carbapenems (meropenem, imipenem, ertapenem, doripenem) drop valproic acid levels 50–90% within 24–48h → breakthrough seizures or status epilepticus. Mechanism: inhibition of acylpeptide hydrolase blocks VPA-glucuronide recycling; dose-escalating VPA does NOT rescue it. Avoid co-administration. If a carbapenem is mandatory (CRE, ESBL), bridge the AED to levetiracetam.

Fioricet is butalbital + acetaminophen + caffeine, and the caffeine is an analgesic adjuvant, not a headache drug. Its 40 mg sits below the 100 mg where adjuvant benefit was shown, and daily use sets up caffeine-withdrawal headache. Combination analgesics cause medication-overuse headache at only 10 days/month, barbiturates roughly double the odds of chronic migraine, and abrupt withdrawal after heavy use can cause seizures. AHS: not first-line for recurrent headache.

A normal B12 does not exclude nitrous oxide (whippet) neurotoxicity: send homocysteine and MMA. N₂O inactivates B12 inside the cell, so the deficiency is functional. Sensitivity for cord involvement was 22% for serum B12 and 5% for holotranscobalamin, versus 95% for homocysteine and 93% for MMA. Anemia and macrocytosis are usually absent and MRI is often normal. Treat with parenteral B12, but it fails unless the patient stops using.

After a successful thrombectomy, never target a systolic below 140. The 2026 AHA/ASA stroke guideline calls an intensive SBP target under 140 for the first 72 h harmful (Class 3: Harm), after OPTIMAL-BP and ENCHANTED2/MT showed worse function. Keep BP at or below 180/105 for 24 h instead: the reperfused territory still depends on perfusion pressure.

Thrombectomy for large vessel occlusion is Class 1 up to 24h: since 2026, ASPECTS 6 or more on plain CT is enough in the 6-24h window (perfusion imaging is adjunctive), and large cores (ASPECTS 3-5) qualify too.

Aminoglycosides, fluoroquinolones, and beta-blockers can all worsen myasthenia gravis. Check every medication before prescribing.

First-line for convulsive status epilepticus (AES 2016): lorazepam 0.1 mg/kg IV (max 4 mg/dose, may repeat once), or midazolam 10 mg IM (> 40 kg) if no IV access (beat IV lorazepam in RAMPART). If seizures persist, second-line agents are equivalent (ESETT 2019: 45–47% control at 60 min each): levetiracetam 60 mg/kg (max 4,500 mg), fosphenytoin 20 mg PE/kg (max 1,500 mg PE), or valproate 40 mg/kg (max 3,000 mg).

Myasthenic crisis: hold pyridostigmine -excess secretions make intubation harder. Use IVIG or PLEX, not steroids initially (can worsen).

In acute ICH (presenting SBP 150–220), target SBP 130–150 per AHA 2022 -ATACH-2 showed aggressive lowering to < 140 caused more renal AEs without improving outcomes. Avoid both overshooting and overly aggressive reduction.

PFO closure reduces recurrent stroke in cryptogenic stroke patients < 60 with high-risk PFO features (large shunt, atrial septal aneurysm).

Large vessel occlusion stroke = thrombectomy candidate. Eyes deviate TOWARD the lesion, away from the weak side. L MCA: left gaze deviation + right weakness + aphasia. R MCA: right gaze deviation + left weakness + neglect. Basilar: AMS + cranial nerve palsies + crossed or bilateral signs.

Parkinson psychosis: clozapine and pimavanserin (Nuplazid, FDA-approved 2016) have the best evidence (MDS 2019: efficacious). Quetiapine is often tried first because it needs no ANC monitoring, but its efficacy evidence is insufficient. Avoid other antipsychotics (haloperidol, risperidone, olanzapine): D2 blockade worsens motor symptoms.

Triptans follow the rule of 2s: max 2 days/week, max 2 doses/day. Exceeding this causes medication overuse headache. Worth trying even in tension or cervicogenic headache.

Donepezil is first-line in Alzheimer disease (labeled for mild, moderate and severe); continuing it into severe disease still helps (DOMINO-AD 2012). Rivastigmine patch suits poor GI tolerance. Never combine two cholinesterase inhibitors. Add-on is memantine in moderate-to-severe disease (Tariot 2004), though DOMINO-AD found no gain over donepezil alone. Benefits are modest; set expectations.

A large core no longer rules out thrombectomy. Under the 2026 AHA/ASA guideline, ASPECTS 3-5 is Class 1 up to 24 h (beyond 6 h if age under 80 and no significant mass effect), after SELECT2 and ANGEL-ASPECT showed better function despite more vascular complications. Tenecteplase and alteplase are now both Class 1.

Benadryl (diphenhydramine) is NOT a sleep aid -it's an anticholinergic that causes delirium. Remove it from every inpatient's med list.

ESETT 2019 (N=384): levetiracetam, fosphenytoin and valproate stopped benzodiazepine-refractory status epilepticus at similar rates (47%, 45%, 46% at 60 min), and harms did not differ significantly. Choose by side effects: levetiracetam has no hepatotoxicity or CYP interactions and needs no cardiac monitoring; fosphenytoin causes hypotension and arrhythmia; avoid valproate in pregnancy and liver disease.

Time is brain: every minute of ischemia = ~1.9 million neurons lost. Door-to-needle target for tPA is < 60 minutes.

Tenecteplase is now Class 1 alongside alteplase for acute ischemic stroke (2026 AHA/ASA): 0.25 mg/kg (max 25 mg) as one IV bolus instead of a 60-min infusion, which matters most when the patient is being transferred for thrombectomy.

Always check finger stick glucose before tPA -hypoglycemia mimics stroke and exposes the patient to bleeding risk for no benefit.

Medications are the #1 modifiable risk factor for delirium. Review the med list: stop anticholinergics, benzos, unnecessary opioids.

Non-pharmacologic delirium prevention (reorientation, sleep hygiene, early mobility, glasses/hearing aids) reduces incidence by 30–40%.

GBS respiratory monitoring: FVC < 20 mL/kg, NIF < −30, or FVC decline > 30% → intubate. Do NOT wait for ABG to deteriorate.

Albuminocytologic dissociation (high protein, normal WBC) on CSF = classic GBS finding. May be normal in the first week.

The HELP protocol cut incident delirium from 15.0% to 9.9% (matched OR 0.60, about a one-third relative reduction) in 852 hospitalized patients 70 and older (Inouye 1999). It is entirely non-pharmacologic (reorientation, sleep, early mobility, vision and hearing aids, hydration) and prevents rather than treats delirium. Not free: cost-neutral at intermediate risk, but it raised net costs at high risk (Rizzo 2001).

Mobile stroke units (CT-equipped ambulances) and telestroke both shorten door-to-needle times -advocate for local protocols if available.

Levetiracetam-induced mood changes (irritability, depression) are dose-dependent and reversible -consider switching to lacosamide or brivaracetam.

After a first unprovoked seizure, 2-year recurrence is 21-45% (AAN/AES 2015, Level A). With normal EEG and MRI and no prior brain insult it sits near the low end (one unknown-cause cohort: 10% at 1 year, 24% at 3 years). Prior brain insult or epileptiform EEG (Level A), or an imaging lesion or nocturnal seizure (Level B), raises it about 2-fold. Immediate AED lowers 2-year recurrence but not long-term remission.

The 3D-CAM (3-minute) and bCAM are faster validated delirium screens than full CAM -use them on busy rounds to catch hypoactive delirium.

Always give thiamine BEFORE glucose in any malnourished, alcoholic, or hyperemesis patient -glucose first can precipitate Wernicke's encephalopathy.

Cough-induced headache warrants brain MRI, up to 50% have secondary pathology (most commonly Chiari I). Indomethacin treats both primary and some secondary forms.

Status epilepticus escalation: benzo (lorazepam IV, midazolam IM if no access) → load with fos-phenytoin/valproate/levetiracetam → IV anesthetic (propofol, midazolam gtt).

Well-controlled epilepsy = seizure-FREE, not 'a few a year.' Ongoing seizures carry driving, employment, cognitive decline, suicide, and SUDEP risks (18/1000 vs 1/1000).

MRI is preferred over CT for non-emergent headache workup (American Headache Society Choosing Wisely). Reserve CT for acute presentations or when MRI isn't available.

SLUMS is faster than MoCA and performs better in patients with less formal education (MoCA was validated in a high-education Montreal cohort). Both outperform MMSE (which also misses executive dysfunction).

High ammonia + worsening mental status with NO liver disease → think urea cycle disorder (can present in adults after a stressor). Low-protein diet helps; avoid in cirrhotics who need muscle mass.

SUDEP risk in epilepsy: ~1/1000 baseline, rising to ~1/100 with intractable generalized tonic-clonic seizures on multiple AEDs. Counseling drives adherence, don't sugarcoat it.

Medication overuse headache thresholds (ICHD-3, each for > 3 months): triptans, ergots, opioids and combination analgesics (butalbital, caffeine combos) ≥ 10 days/month; acetaminophen or NSAIDs alone ≥ 15 days/month. Separately, the exposure linked to episodic migraine becoming chronic is about 5 days/month for barbiturates and 8 days/month for opioids. Chronic daily headache requires stopping the offender.

Epilepsy surgery evaluation is warranted after failure of 2 appropriately-dosed antiepileptics, don't keep trying a 3rd and 4th. Resection can be curative; VNS/RNS/DBS are palliative options.

Fingolimod (MS): sequesters lymphocytes in lymph nodes. Monitor for first-dose bradycardia (observe 6 hours) and macular edema risk. Reduces relapse rates ~50% vs placebo.

NEVER transfuse platelets in TTP -you're adding fuel to the fire. Platelets bind ultra-large vWF → more microthrombi → worse.

Fever of 38.5°C (101.3°F) or higher in sickle cell disease is a medical emergency (NHLBI 2014): functional asplenia means encapsulated organisms are not cleared and sepsis can kill within hours. Draw CBC, retic and blood culture, then give ceftriaxone 2 g IV (adults) within the hour; do not wait for culture results. Admit anyone at 39.5°C or higher who looks ill.

S. pneumoniae is the #1 cause of fatal sepsis in SCD. Can progress from well to dead in < 12 hours. Penicillin prophylaxis (age < 5) + pneumococcal vaccines are lifesaving.

HIT is a prothrombotic state despite low platelets. Stop ALL heparin (including flushes). Start argatroban or bivalirudin. Never give warfarin until platelets > 150K.

For malignant cord compression: dexamethasone 10 mg IV STAT. Neurologic status at diagnosis = prognosis.

Never give pRBC before plasmapheresis in hyperviscosity -increases viscosity further.

Screen ALL patients for hepatitis B before rituximab -even resolved HBV can reactivate fatally. Give entecavir.

Idarucizumab (Praxbind) 5 g IV reverses dabigatran. Andexanet alfa (Andexxa) left the US market in Dec 2025 after the FDA judged its thrombotic risk to outweigh benefit (ANNEXA-I, NEJM 2024: thrombotic events 10.3% vs 5.6%). For life-threatening apixaban, rivaroxaban or edoxaban bleeding, stop the drug and give 4-factor PCC (Kcentra, off-label), which replaces clotting factors rather than binding the drug.

Tranexamic acid (1 g IV over 10 min, then 1 g over 8 h) cut trauma mortality in CRASH-2 (14.5% vs 16.0%), but the benefit depends on starting within 3 h of injury; later doses raised bleeding deaths. In postpartum hemorrhage, 1 g IV cut bleeding deaths (WOMAN). Skip it in GI bleeding: HALT-IT (n = 12,009) showed no fewer bleeding deaths (4% vs 4%) and nearly doubled VTE (0.8% vs 0.4%).

HIT: use the 4Ts score first (low score: no PF4 test, no treatment). If intermediate or high, stop ALL heparin (flushes, LMWH) and start argatroban, bivalirudin, fondaparinux or a DOAC (ASH 2018). No routine platelet transfusion: linked to arterial thrombosis; reserve for active bleeding or high bleeding risk. No warfarin until platelets recover (usually ≥ 150K): venous limb gangrene.

TTP rarely presents with the full pentad, < 5% of the time. Dyad of MAHA + thrombocytopenia is enough to start plasma exchange. Fever, AKI, and neuro signs are less common than taught.

Acute limb ischemia: 6 Ps, Pain, Pallor, Pulselessness, Poikilothermia, Paresthesias, Paralysis. Paresthesias and paralysis indicate advanced ischemia, surgical emergency. Heparin bolus immediately while arranging revascularization.

Significant thrombocytopenia: immediately ask about recent heparin exposure (HIT) and look for schistocytes (TTP/HUS/DIC). These have completely different management, rapid triage can be lifesaving.

A patient on ticagrelor can have a falsely NEGATIVE functional HIT assay. Ticagrelor in their serum blocks P2Y12 on the donor platelets the test uses (the label names the HIPA assay), while PF4 antibody tests are unaffected. Tell the lab about the ticagrelor, and do not let a negative functional result overrule a high 4Ts score with a positive PF4 antibody.

Voxelotor (Oxbryta) is off the market: Pfizer withdrew it worldwide in September 2024 and the FDA told prescribers to stop. Its approval rested on a surrogate (a hemoglobin rise), while postmarketing trials showed more vaso-occlusive crises and more deaths than placebo. Pfizer ruled out a US return in August 2026. If an old med list still carries it, stop it and review hydroxyurea.

Restrictive transfusion (Hgb trigger 7) is standard for most hospitalized patients. No mortality benefit from liberal (trigger 10).

Massive transfusion: plasma:platelets:RBC 1:1:1 (PROPPR 2015: no 24-h or 30-day mortality difference vs 1:1:2, but more hemostasis and fewer exsanguination deaths). Citrate chelates calcium: give calcium with the first unit, then every 4 units; keep iCa ≥ 1.2 mmol/L (JTS DCR CPG). Dose by salt: 1 g CaCl2 (270 mg elemental) ≈ 3 g gluconate (93 mg/g); chloride needs a secure or central line (extravasation necrosis).

TTP is lethal untreated; plasma exchange made it survivable (Rock 1991, N=102: 6-mo mortality 22% with exchange vs 37% with plasma infusion). On high suspicion (MAHA + thrombocytopenia, PLASMIC 6–7), start TPE plus steroids without waiting for ADAMTS13 (ISTH 2020). HERCULES 2019 added caplacizumab to TPE: faster platelet recovery (primary), and TTP death, recurrence or major thromboembolism fell from 49% to 12%.

Hydroxyurea (MSH 1995, N=299) cut painful crises 44% (median 2.5 vs 4.5/yr) and halved acute chest syndrome; the 40% lower mortality comes from 9-yr observational follow-up (Steinberg 2003). NHLBI 2014: offer it to adults with ≥ 3 severe crises/yr, pain or anemia limiting daily life, or severe/recurrent ACS, and to all SCA children ≥ 9 mo. After stroke, chronic transfusion stays standard (SWiTCH 2012).

Capnocytophaga canimorsus (dog/cat saliva) causes fulminant sepsis, DIC, and purpura fulminans in asplenic/functionally asplenic patients (including SCD). Any dog or cat bite in SCD → immediate amoxicillin-clavulanate.

Salmonella is the #1 cause of osteomyelitis in sickle cell disease -NOT Staph aureus. Infarcted bone is a perfect growth medium for Salmonella.

4T score ≤ 3 = HIT unlikely (<5%). Score 6–8 = high probability → treat empirically while awaiting PF4 antibody and SRA.

Bleomycin lung toxicity: avoid high FiO₂ even years after exposure. Oxygen fuels free radical injury.

Never FNA a lymph node for suspected lymphoma -excisional biopsy preserves architecture needed for subtyping.

CRAB criteria for myeloma: Calcium > 11, Renal Cr > 2, Anemia Hgb < 10, Bone lytic lesions. SLiM criteria also qualify.

Give oral iron on alternate days: a dose of 60 mg or more raises hepcidin for about 24 h and cuts next-day absorption 35-45%, so a dose 48 h later absorbs 30-50% more (Moretti 2015; Stoffel 2017, 2020). Hb rise is comparable to daily dosing (2025 meta-analysis, 11 RCTs, very low certainty) with similar side effects. Give one morning dose; split dosing raises hepcidin further.

Hold DOAC 24-48h before low-bleeding-risk procedures and 48-72h before high-risk -bridging is not needed for DOACs (unlike warfarin).

B12 deficiency can present with normal MCV if concurrent iron deficiency masks macrocytosis -check B12 in any unexplained neuropathy or cognitive change.

Reticulocyte index < 2 in anemia = underproduction (iron, B12, folate, CKD, marrow). >= 2 = hemolysis or acute blood loss. Frames the workup immediately.

Isolated elevated PTT with normal PT -mixing study corrects = factor deficiency; doesn't correct = inhibitor (lupus anticoagulant, factor VIII inhibitor).

Urgent warfarin reversal: 4-factor PCC (II, VII, IX, X; Kcentra), not FFP. Small volume; INR 1.3 or less at 30 min post-infusion in 55-62% vs ~10% with plasma. Hemostasis was noninferior in major bleeding (72% vs 65%) and superior before urgent surgery (90% vs 75%). Give IV vitamin K at the same time: PCC factors wane within hours and vitamin K needs hours to work.

Hydroxyurea is the ONLY medication with proven mortality benefit in sickle cell disease. Raises HbF, reduces vaso-occlusive crises and mortality. Expect MCV to rise, if it doesn't, check adherence.

Sickle cell pain crisis: scheduled NSAIDs (ketorolac), methadone for long-acting opioid, low threshold for ketamine (2–5 mcg/kg/min). Methadone dosed TID during acute pain (α-elimination is 8–12 h).

AAA screening (USPSTF 2019): one-time abdominal ultrasound for men 65–75 who ever smoked (B). Men 65–75 who never smoked: selectively offer (C). Women 65–75 who ever smoked or have a family history: evidence insufficient (I), decide case by case. Women who never smoked and have no family history: don't screen (D). Repair at 5.5 cm in men (5.0 cm in women, who rupture smaller), growth > 0.5 cm/6 mo, or symptoms.

Pregnancy-associated VTE: LMWH (enoxaparin, dalteparin) over UFH (ASH 2018, strong); warfarin crosses the placenta (embryopathy, fetal bleeding, loss) and DOACs likely do too, so neither is used antepartum. Treat for the rest of pregnancy and at least 6 weeks postpartum, minimum 3 months total (ACCP 2012), as risk peaks postpartum. If breastfeeding, LMWH or warfarin are fine; avoid DOACs (ASH 2018).

ITP no longer starts with a steroid alone. ASH 2026 suggests pairing the corticosteroid with rituximab or a TPO agent for initial therapy, because steroids alone rarely give a lasting remission; after steroids, a TPO agent is the strong recommendation. The treatment threshold is unchanged: below 30,000 or bleeding.

BRIDGE 2015: in AF patients interrupting warfarin for a procedure, heparin bridging raised major bleeding about 2.5-fold (3.2% vs 1.3%) without reducing arterial thromboembolism (0.3% vs 0.4%). Most AF patients should NOT be bridged.

New iron deficiency anemia in a man or postmenopausal woman = GI malignancy until proven otherwise. Always scope.

DIC labs: everything abnormal in the same direction -platelets ↓, fibrinogen ↓, PT/aPTT ↑, D-dimer ↑↑, schistocytes on smear.

TTP: MAHA + thrombocytopenia + NORMAL coags. If coags are abnormal, it's DIC, not TTP. This is the key distinguishing feature.

Do NOT transfuse platelets in TTP -they are 'fuel on the fire' and worsen microvascular thrombosis. Only for life-threatening hemorrhage.

Do NOT transfuse Hgb above 10 in sickle cell disease -increased viscosity paradoxically worsens vaso-occlusion.

Incentive spirometry q1-2h prevents acute chest syndrome in SCD -splinting from pain → atelectasis → hypoxia → sickling.

TRALI = non-cardiogenic edema (low BNP, no fluid overload). TACO = cardiogenic (high BNP, responds to diuretics). Treatment is opposite.

DIC labs: everything is wrong in the same direction -↓ platelets, ↓ fibrinogen, ↑ PT/INR, ↑ D-dimer, schistocytes on smear.

Fibrinogen is an acute-phase reactant. A 'normal' fibrinogen in a septic patient is actually low -it should be elevated. Think DIC.

TTP vs DIC: both have thrombocytopenia + schistocytes. TTP = NORMAL coags (PT, aPTT, fibrinogen). DIC = DERANGED coags.

Incentive spirometry q2h is the single most important intervention to prevent acute chest syndrome during sickle cell VOC admission.

Target Hgb ≤ 10 in sickle cell -transfusing higher increases viscosity and paradoxically worsens vaso-occlusion.

Restrictive transfusion (Hgb < 7) is non-inferior to liberal (Hgb < 10) for most patients. Transfusing above 7 adds risk with no survival benefit.

TRALI vs TACO: both cause post-transfusion respiratory distress. TRALI = low BNP, no response to diuretics. TACO = high BNP, responds to diuretics.

AMPLIFY 2013 (N=5,395): apixaban matched enoxaparin/warfarin for recurrent VTE (2.3% vs 2.7%) with 69% less major bleeding (0.6% vs 1.8%). Head to head, COBRRA 2026 (N=2,760): clinically relevant bleeding 3.3% vs 7.1% with rivaroxaban at 3 months; no trial vs dabigatran or edoxaban. No parenteral lead-in: 10 mg BID x 7 days, then 5 mg BID. Usable in mild to moderate CKD.

Every admitted patient needs VTE risk assessment. Hospital-acquired VTE is the #1 preventable cause of inpatient death.

Ferritin < 30 = iron deficiency. But a 'normal' ferritin of 50-100 in an inflamed patient may still be iron deficient -ferritin is an acute phase reactant.

In HIT, the 4T score 0–3 has > 99% NPV -if low, HIT is essentially ruled out. Don't send PF4 antibody.

VTE provoked by surgery → 3 months anticoag. Unprovoked → extended (indefinite). Cancer-associated → LMWH or DOAC until cancer resolved.

Iron deficiency anemia in any male or postmenopausal female = GI malignancy workup (colonoscopy + EGD) until proven otherwise.

ITP is a diagnosis of exclusion -always review the peripheral smear to rule out TTP, leukemia, and pseudothrombocytopenia.

In ITP, treat the patient not the number. Platelets ≥ 30K without bleeding = observation only.

Wet purpura (oral blood blisters) in ITP indicates higher hemorrhage risk -escalate to IVIG + steroids.

The peripheral blood smear is the single most important test in pancytopenia -it guides the entire workup.

Copper deficiency mimics MDS. Check copper level in unexplained pancytopenia, especially post-bariatric surgery.

Thyroid dysfunction is the most common endocrine irAE (hypothyroidism ~8% on anti-PD-(L)1, ~15% on combination); skin and GI toxicities are commoner overall. Check TSH/fT4 every 4-6 weeks. Treat hypothyroidism with levothyroxine and usually continue the ICI, but check an AM cortisol first: replacing thyroid hormone before steroids in unrecognized adrenal insufficiency can precipitate adrenal crisis.

MESNA prevents hemorrhagic cystitis by binding acrolein (toxic cyclophosphamide metabolite) in the bladder.

Start ATRA immediately if APL suspected (Auer rods + DIC). Don't wait for FISH. ATRA + arsenic trioxide cures > 90%.

Haptoglobin is the most sensitive marker for hemolysis but is an acute phase reactant -can be falsely normal in concurrent inflammation.

G6PD level is falsely normal during acute hemolysis (oldest cells with lowest G6PD are destroyed first). Recheck 2-3 months later.

Daratumumab (anti-CD38) interferes with blood bank crossmatching -notify the blood bank before starting therapy.

DOACs are contraindicated in triple-positive APS [TRAPS 2018] and mechanical valves [RE-ALIGN]. Use warfarin.

Warfarin reversal: vitamin K 10 mg IV + 4-factor PCC for major bleeding. FFP is slower, higher volume, and inferior -reserve for PCC unavailability.

Hold DOACs per PAUSE: low bleed risk, skip 1 day pre-op (last dose 2 days before) and resume 1 day after; high bleed risk, skip 2 days and resume 2 to 3 days after, once hemostasis is secure. Dabigatran with CrCl 30-50 is renally cleared, so skip 2 days (low) or 4 days (high). No heparin bridging: DOAC offset and onset are fast, so bridging only adds bleeding.

Brain metastases, even melanoma or RCC, are not a contraindication to anticoagulation (prophylactic or therapeutic): enoxaparin did not raise 1-year measurable intracranial hemorrhage (19% vs 21%, Donato 2015; meta-analysis OR 1.07, Zwicker 2016). Melanoma/RCC mets bleed more either way. Primary glioma differs (OR 3.75). Hold for active ICH or severe thrombocytopenia; no need to scan for brain mets first.

Idarucizumab is the reversal agent for dabigatran bleeding or urgent procedures (REVERSE-AD: 92% hemostasis). For rivaroxaban and apixaban, 4F-PCC is now the US reversal agent; andexanet alfa was withdrawn in December 2025.

LMWH has LOWER HIT risk than UFH, less platelet binding, less endothelial/macrophage interaction. Also more predictable PK, no routine monitoring needed. Use LMWH when HIT risk matters.

Use patient-first language in sickle cell: 'patient with SCD' and 'acute pain episode', not 'sickler' or 'pain crisis.' Stigmatizing language drives worse pain control and worse outcomes.

Upper-extremity DVT associated with a central line: DO NOT automatically pull the catheter. Anticoagulate and leave it if functional and still needed. Remove only if severe pain/swelling or anticoagulation contraindicated.

Unna boot (zinc-oxide gauze compression) treats venous stasis ulcers and recurrent edema-driven cellulitis. Change weekly. Contraindicated in arterial insufficiency, always check ABI first.

For life-threatening factor Xa inhibitor bleeding in the US, reverse with 4-factor PCC (Kcentra, off-label, typically 50 units/kg or a fixed 2,000 units): andexanet alfa was withdrawn in December 2025. Activated PCC (FEIBA) 50 units/kg is a less-studied alternative. Both are prothrombotic, so reserve them for bleeding that threatens life or a critical organ.

Iron dextran (INFeD) has a boxed anaphylaxis warning: give a 0.5 mL (25 mg) test dose and wait at least 1 hour before the therapeutic dose; fatal reactions occur even after a tolerated test dose. Iron sucrose and ferric carboxymaltose need no test dose and react far less often (serious anaphylactoid 0.1% in Injectafer trials), but fatal reactions are reported with both, so monitor 30 minutes after each infusion.

Pulmonary-renal syndrome (DAH + RPGN) is a medical emergency. Start pulse steroids + cyclophosphamide or rituximab before biopsy.

Start steroids BEFORE temporal artery biopsy in suspected GCA. Vision loss is irreversible. Biopsy stays positive for 2–6 weeks on steroids.

Avoid fluoroquinolones, aminoglycosides, magnesium, beta-blockers, and hydroxychloroquine in myasthenia gravis, all can precipitate a crisis.

Start high-dose prednisone IMMEDIATELY in suspected giant cell arteritis, before temporal artery biopsy. Delay risks permanent vision loss. Biopsy result is preserved up to 2–4 weeks after starting steroids.

ESR ↑ + CRP normal = lupus flare. ESR ↑ + CRP ↑ = infection. This distinction helps differentiate flare vs infection in SLE patients.

Hydroxychloroquine is the cornerstone of SLE treatment -never stop it. Reduces flares, organ damage, thrombosis, and mortality.

Acute gout colchicine: 1.2 mg × 1, then 0.6 mg one hour later, max day 1. If GFR < 30, use single-day dosing only; do not repeat for ≥ 14 days.

DRESS doesn't require eosinophilia, only 82–95% of cases have it. Now often called DIHS (drug-induced hypersensitivity syndrome). Clinical criteria: rash, fever, LAD, organ involvement 2–8 weeks after drug exposure.

Switch mycophenolate to azathioprine 3–6 months before planned conception, MMF is strongly teratogenic (REMS program). Azathioprine is safer in pregnancy and preserves disease control.

Stop the glucosamine. ACR 2026 now strongly recommends against glucosamine and chondroitin for knee, hip and hand OA, because trials show no benefit over placebo. What works is exercise, weight loss (a GLP-1 receptor agonist can help in knee OA with obesity), topical NSAIDs for knee and hand, and intra-articular steroid for flares.

Normal uric acid does NOT rule out gout -40% of acute flares have normal serum UA. You need joint aspiration with polarized microscopy.

Low-dose colchicine (1.2 mg then 0.6 mg 1h later) is as effective as high-dose with far fewer GI side effects.

Check HLA-B*5801 before starting allopurinol in Southeast Asian, Black, and Korean patients -risk of fatal SJS/TEN.

Screen for TB (QuantiFERON) before starting any biologic or JAK inhibitor. TNF is critical for granuloma maintenance -inhibition reactivates latent TB.

Anti-CCP is the most specific antibody for RA (~95% specificity). RF is sensitive but not specific.

Avoid DOACs in high-risk APS: triple-positive or arterial thrombosis. Warfarin (INR 2–3) is standard. TRAPS 2018 (N=120, triple-positive) stopped early: rivaroxaban 19% vs warfarin 3% composite events, 7 arterial thromboses vs 0. Label: not recommended in triple-positive APS. A DOAC is a fallback only in single/double-positive venous APS if INR can't be kept in range despite adherence.

APS lab paradox: aPTT is prolonged in vitro (lupus anticoagulant interferes with assay) but the patient is prothrombotic in vivo.

Scleroderma renal crisis: ACE inhibitors are life-saving. Do NOT hold for rising Cr. Steroids > 15 mg/day PRECIPITATE SRC.

Lupus nephritis class III/IV (proliferative) requires aggressive immunosuppression -mycophenolate or cyclophosphamide, not steroids alone.

In ANCA vasculitis, drug-induced causes (hydralazine, minocycline, PTU) are MPO/p-ANCA positive -always check the med list.

GCA: start glucocorticoids on strong suspicion; don't wait for biopsy, but get it promptly (best yield within 2 weeks of starting; ACR 2021). No cranial ischemia: oral prednisone 40–60 mg daily (EULAR 2025). Threatened vision loss: IV methylprednisolone 500–1,000 mg daily for 3–5 days first (ACR 2021, conditional), because established vision loss is usually permanent and the other eye is at risk.

In RA, treat-to-target: if not at low disease activity by 3 months → escalate therapy. Don't accept smoldering disease.

Avoid DOACs in triple-positive APS and in APS with arterial thrombosis: TRAPS (2018) stopped early with 7 thromboembolic events on rivaroxaban (12%: 4 ischemic strokes, 3 MIs) vs 0 on warfarin, and Ordi-Ros (2019) saw 9 strokes vs 0 in broader thrombotic APS. The Xarelto label says DOACs are not recommended in triple-positive APS. Use warfarin, INR 2–3.

Scleroderma renal crisis: ACE inhibitors (captopril) are life-saving. Do NOT hold for rising Cr. ARBs are NOT a substitute.

Allopurinol hypersensitivity (DRESS, SJS/TEN) risk rises with HLA-B*58:01, CKD, diuretics and high starting doses: test HLA-B*58:01 first in Southeast Asian and African American patients. Start at 100 mg/day or less (50 mg/day or less in CKD stage 3+), then titrate to urate < 6. Continue flare prophylaxis (colchicine, NSAID or low-dose steroid) for 3 to 6 months, longer if flares persist (ACR 2020).

Belimumab is an add-on for moderate-severe SLE (in addition to hydroxychloroquine). MMF or azathioprine for moderate-severe; cyclophosphamide for life-threatening disease. All SLE patients should be on HCQ.

HBV-associated PAN: treat the virus, not just the vasculitis. Start an antiviral (entecavir or tenofovir) with about 2 weeks of steroids and plasma exchange; avoid cyclophosphamide and prolonged steroids, which favor HBV replication. In Guillevin's series this raised HBe seroconversion (49% vs 15%), and seroconverters did not relapse. Clues: livedo, mononeuritis multiplex, renal or mesenteric microaneurysms.

Leflunomide: long half-life, teratogenic. In women of reproductive age, require washout with cholestyramine + documented sub-threshold level before conception. Main side effects: diarrhea and weight loss.

Tocilizumab (IL-6 blockade): boxed warning for serious infections, so screen for latent TB first; herpes zoster is among the common ones. GI perforation, mostly from diverticulitis (use caution with that history). Check lipids 4 to 8 weeks after starting, plus ANC, platelets and LFTs. It suppresses CRP and can blunt fever, so infection and perforation present quietly; a normal CRP does not exclude them.

Sicca syndrome initial treatment: artificial tears + sugar-free candies (stimulate salivation), not immunosuppressants. Reserve methotrexate or hydroxychloroquine for severe joint/systemic disease.

APL has very high early mortality, mostly hemorrhagic. Any suspicion (leukemia plus DIC signs) means start ATRA and coagulopathy support immediately on the blood smear, before genetic confirmation; stop ATRA if PML-RARA is not found. Arsenic trioxide is added once confirmed; with WBC over 10, chemotherapy starts without waiting. Otherwise highly curable.

Hydroxyurea treats leukostasis (blast count > 100k with symptoms). Start chemo ASAP; leukapheresis for severe symptoms, but AVOID leukapheresis in APL (risk of intracranial hemorrhage). ATRA first in APL.

Metastatic NSCLC: send broad NGS (EGFR, ALK, ROS1, BRAF, KRAS G12C, MET ex14, RET, NTRK, HER2, NRG1) plus PD-L1; hold immunotherapy until results return (little benefit in drivers, and prior ICI raises TKI toxicity). ALK: alectinib, brigatinib or lorlatinib. ROS1: entrectinib, repotrectinib, taletrectinib or crizotinib. EGFR: osimertinib ± chemo, or amivantamab-lazertinib. No driver: platinum doublet ± ICI by PD-L1.

Multiple myeloma staging workup: LDH, β2-microglobulin (key for R-ISS staging), SPEP + immunofixation, serum free light chains, and whole-body low-dose CT or PET-CT (preferred over skeletal survey).

In metastatic cancer of unknown primary, biopsy the metastatic site (especially supraclavicular/scalene nodes), superficial, diagnostic, and faster than chasing the primary.

Testicular cancer metastasizes first to retroperitoneal nodes. Stage II seminoma (RPLN involvement) → adjuvant radiation or chemo (chemo if node > 2 cm).

Metastatic colorectal cancer: send KRAS, NRAS, BRAF, and mismatch repair testing at diagnosis. KRAS/NRAS mutations make tumors resistant to anti-EGFR therapy (cetuximab, panitumumab).

Biopsy the metastatic site, not the primary, in metastatic cancer of unknown origin. Superficial scalene/supraclavicular nodes are first-choice: accessible, diagnostic, fewer complications.

Adnexal mass in pregnancy: remove in early 2nd trimester if > 10 cm or complex (concern for ovarian epithelial cancer). Simple cysts can be observed. Tumor markers (CA-125, AFP, β-hCG) are distorted by pregnancy, interpret with caution.

Potentially curable metastatic solid tumors: germ-cell (testicular) and colorectal cancer with fully resectable liver or lung mets, regardless of grade (about 17% actual 10-year survivors after liver resection, nearly all disease-free; Tomlinson 2007). RAI-avid differentiated thyroid cancer can be controlled for decades. Most other metastatic cancers are palliative-intent; ECOG status guides chemo tolerability.

Checkpoint inhibitor colitis (5–10% of anti–PD-1/PD-L1; higher with ipilimumab) = STEROIDS. Diarrhea > 4 stools/day above baseline → hold the checkpoint, start prednisone 1 mg/kg. Refractory → infliximab or vedolizumab.

Carboplatin has more cytopenias than cisplatin, but less nausea, nephrotoxicity, and ototoxicity. Cisplatin requires pre- and post-hydration (bad for volume-sensitive patients). Dose-adjust carboplatin by AUC (Calvert formula).

EGFR-mutated metastatic NSCLC: osimertinib first-line (better CNS penetration, covers T790M). ALK-positive: alectinib, brigatinib, or lorlatinib first-line; ALEX 2017 showed alectinib beat crizotinib (12-month PFS 68% vs 49%, HR 0.47; CNS progression 12% vs 45%). ROS1-positive: crizotinib, entrectinib, repotrectinib, or taletrectinib; alectinib is ALK-only and does not cover ROS1.

Atezolizumab (anti-PD-L1) may have less organ toxicity than anti–PD-1 agents, it doesn't block PD-1/PD-L2 interactions. Lower rates of pneumonitis, colitis, and AKI reported.

Esophageal cancer: squamous cell (upper two-thirds, smoking/alcohol) vs adenocarcinoma (lower third, Barrett's/GERD). Test HER2 and PD-L1 CPS (a score, not a percentage). First-line pembrolizumab plus platinum/fluoropyrimidine chemo requires CPS ≥ 1 (add trastuzumab if HER2-positive GEJ adenocarcinoma); single-agent pembrolizumab after prior therapy requires squamous histology and CPS ≥ 10.

CLL is indolent, main problems are cytopenias from marrow infiltration. CMML is more aggressive with dysplasia + monocytosis. CML has the Philadelphia chromosome (BCR-ABL) and responds beautifully to imatinib.

TCA overdose: QRS > 100 ms = seizure risk. QRS > 160 ms = VT risk. R in aVR > 3 mm. Treatment: sodium bicarbonate to pH 7.45–7.55.

Avoid potassium supplements and ACE-inhibitors in digoxin toxicity, both worsen hyperkalemia. Calcium gluconate is controversial ('stone heart' risk) but now considered probably safe.

Beta-blocker overdose: vasopressors and high-dose insulin (1 U/kg bolus, then 1–10 U/kg/h) are both AHA 2023 Class 1 for hypotension; insulin restores myocardial glucose use and inotropy, so start it with pressors, not after glucagon. Give dextrose; check glucose and K+. Glucagon 2–10 mg IV, then 1–15 mg/h, raises cAMP past the blocked receptor (Class 2a; vomiting). Lipid emulsion: no benefit. VA-ECMO if refractory.

Calcium channel blocker overdose: vasopressors and high-dose insulin (1 U/kg then 1–10 U/kg/h with dextrose) are Class 1 (AHA 2023); IV calcium and atropine are reasonable (2a). Glucagon is of uncertain benefit (2b), unlike in beta-blocker overdose. Routine lipid emulsion is not recommended (Class 3: No Benefit; it may increase gut absorption of oral lipophilic drugs). Drug-refractory shock: VA-ECMO, not Intralipid.

Acetaminophen overdose: N-acetylcysteine works best within 8 hours but has benefit up to 24 hours (and arguably beyond with fulminant failure). Use the Rumack-Matthew nomogram for single ingestions; don't apply it to staggered ingestions.

Methanol and ethylene glycol: fomepizole first (blocks alcohol dehydrogenase, so no toxic acids form); ethanol if unavailable. Dialyze for coma, seizures, AKI, new vision loss (methanol) or severe acidosis: methanol pH ≤ 7.15 or anion gap > 24; EG anion gap > 27 (glycolate > 12 mmol/L). Level alone (EXTRIP): methanol > 70 mg/dL on fomepizole (> 50 with no ADH blocker); EG > 310 mg/dL (50 mmol/L) or osmol gap > 50.

Colchicine + CYP3A4 inhibitors (clarithromycin, fluconazole, diltiazem) can be fatal, risk of rhabdomyolysis, AKI, and pancytopenia from colchicine toxicity. Review the med list before starting.

Sympathomimetic vs anticholinergic: both cause tachycardia + mydriasis. Key difference: sympathomimetic = WET (diaphoresis). Anticholinergic = DRY.

Serotonin syndrome vs NMS: clonus + hyperreflexia = serotonin. Lead-pipe rigidity + hyporeflexia = NMS. Onset: SS = hours, NMS = days.

Xylazine ('tranq') in street opioids: alpha-2 agonist causing sedation, bradycardia, hypotension and respiratory depression, no reversal agent; give naloxone anyway for the co-ingested opioid. Withdrawal (agitation, tachycardia, hypertension despite opioids) is mostly case reports, poorly characterized, with no defined onset; treat with alpha-2 agonists (clonidine, tizanidine, dexmedetomidine).

Naloxone goal: restore respiratory drive, NOT full consciousness. Start low (0.04 mg) in opioid-dependent patients to avoid acute withdrawal.

Correct chronic hyponatremia by no more than 8 mEq/L per 24 h (aim 4–6 if high risk: Na ≤ 105, alcohol, malnutrition, hypokalemia, cirrhosis). Overcorrection risks osmotic demyelination 2–6 days later: quadriparesis, dysphagia, locked-in state. Not always permanent (56% of 1-year ICU survivors were near-normal, Louis 2012), so do not prognosticate early. If the limit is exceeded, re-lower with D5W ± DDAVP.

Thoracentesis: enter over the top of the rib; the intercostal neurovascular bundle runs under the inferior margin. Pneumothorax follows ~6% of taps; real-time US cuts the odds ~70% (OR 0.3, Gordon 2010, 6,605 procedures), and dedicated high-volume teams report < 1% (0.61% of 9,320, Ault 2015). Skip routine CXR; image if symptomatic, air was aspirated, several passes were needed or the patient is ventilated.

Non-convulsive status epilepticus is an underrecognized cause of persistent altered mental status in the ICU -low threshold for EEG in unexplained coma.

Don't stop SSRIs peri-operatively. The small increase in bleeding risk is outweighed by the harm of precipitating depressive relapse. Continue through surgery.

Aripiprazole 2–5 mg q2h PRN is the antipsychotic of choice for agitated delirium when QTc > 500, minimal QT prolongation vs haloperidol/quetiapine. Check ECG after the second dose.

Gabapentinoids don't work for acute pain and cause delirium in the elderly. They're for CHRONIC neuropathic pain. Don't start them for inpatient pain control.

PEth (phosphatidylethanol) is the alcohol biomarker of choice in transplant evaluation. Direct marker formed in RBCs only with ethanol exposure; ~2–4 week detection window. Cutoffs: <20 ng/mL abstinent, 20–200 moderate, >200 heavy use. Unlike CDT/GGT/MCV, it's not confounded by liver disease. Hand sanitizer does NOT meaningfully raise PEth at the 20 cutoff, debunked myth.

Fentanyl is an analgesic first, sedative second. At low dose = pure analgesia. At high dose = analgo-sedation. Often sufficient alone.

Dexmedetomidine causes minimal respiratory depression, so it is labeled for procedural sedation of non-intubated patients and is used to sedate through extubation. Minimal is not none: Precedex procedural trials still recorded slowed breathing, and ketamine also spares respiratory drive. Its main risks are bradycardia and hypotension from alpha-2 sympatholysis, so monitor heart rate and BP as well as the airway.

Prefer propofol or dexmedetomidine over benzodiazepines in ventilated adults (PADIS 2018): shorter ventilation and ICU stay, likely less delirium, no proven mortality gain. MENDS 2007 (vs lorazepam, N=106): delirium/coma-free days 7 vs 3. SEDCOM 2009 (vs midazolam, N=375): delirium 54% vs 77%, extubated 1.9 d sooner, bradycardia 42% vs 19%. Benzos still fit alcohol withdrawal.

Every patient on opioids needs a scheduled bowel regimen from day 1. PEG 3350 with or without senna is the baseline (AGA-ACG 2023 constipation guideline: PEG strong, senna conditional); laxatives are first-line for opioid-induced constipation, and a PAMORA (naldemedine, naloxegol) is next if they fail (AGA 2019). Skip docusate: in Tarumi 2013 (hospice RCT, N=74) adding it to senna changed nothing.

Fleet enema + CKD = fatal hyperphosphatemia. Use tap water enema in any patient with renal impairment.

SIADH is a diagnosis of exclusion. Always check TSH and AM cortisol first -hypothyroidism and adrenal insufficiency both cause hyponatremia.

Right IJ central line: 15–17 cm depth. NEVER lose control of the guidewire. If wire won't thread, reposition -don't force.

INR and platelets are NOT contraindications to paracentesis or thoracentesis. Bleeding < 1% even with coagulopathy. Do NOT transfuse first.

LP: use atraumatic (Sprotte) needles -50% lower post-LP headache rate. Bevel up, parallel to longitudinal dural fibers.

Safe discharge requires: medication reconciliation, follow-up appointments, patient education with red flags, and discharge summary to PCP.

Opioids are the most effective treatment for dyspnea in palliative care. Low doses are safe and do not hasten death.

Goals of care: ask 'What matters most to you?' before 'What do you want us to do?' Values first, interventions second.

USPSTF 2024: mammography screening now starts at age 40, every 2 years (lowered from prior 50). Through age 74.

Colorectal cancer screening starts at 45 (lowered from 50). Colonoscopy q10y, FIT annually, or Cologuard q3y.

Diphenhydramine (Benadryl) is the #1 offender on inpatient med lists for falls and delirium. Remove it from every PRN order set.

Hospice is a Medicare benefit, not giving up. Patients and families consistently say they wish it was offered earlier.

When rotating opioids, ALWAYS reduce the equianalgesic dose by 25-50% for incomplete cross-tolerance. Skipping this causes overdose.

Varenicline (Chantix) is the most effective single agent for smoking cessation (~30% quit rate). FDA removed the neuropsych black box.

For opioid-induced constipation, AGA 2019 recommends laxatives first-line (strong); PEG 3350 plus senna is the usual regimen. If refractory, add a PAMORA (naldemedine or naloxegol, strong; methylnaltrexone, conditional), never with suspected bowel obstruction. Skip docusate: in a hospice RCT (Tarumi 2013) docusate + senna was no better than placebo + senna.

In SIADH, tolvaptan must be started in the hospital -rapid correction risk. Avoid in liver disease (hepatotoxicity).

Adverse drug events are the most common harm after discharge: about 1 in 5 discharged medical patients has an adverse event within 3 weeks, two-thirds are drug-related, and of those causing disability 48% were preventable and 24% ameliorable (Forster 2003). Reconcile every new, changed and stopped medication with the patient at the bedside, and tell them which symptoms should trigger a call.

48–72h post-discharge follow-up for high-risk patients (HF, AKI, new anticoag) reduces readmissions by up to 30%.

USPSTF 2021: annual low-dose CT for adults 50–80 with a ≥ 20 pack-year history who currently smoke or quit within the past 15 years. Stop once 15 years have passed since quitting, or when a health problem substantially limits life expectancy or the ability or willingness to have curative lung surgery. (ACS 2023 drops the years-since-quit rule, but USPSTF, which drives coverage, keeps it.)

Diphenhydramine (and other first-generation antihistamines) is a common, preventable precipitant of delirium, falls and urinary retention in hospitalized older adults: highly anticholinergic, slowly cleared with age, and tolerance to its hypnotic effect develops. AGS Beers 2023: avoid (strong). For insomnia use non-drug sleep measures first, then melatonin; avoid benzodiazepines and Z-drugs too.

WHO pain ladder: Step 1 (non-opioid) → Step 2 (weak opioid) → Step 3 (strong opioid). Always optimize non-opioid adjuvants first.

Varenicline is the most effective single agent: in EAGLES (2016, N = 8,144) it beat patch (OR 1.68) and bupropion (OR 1.75) for abstinence at weeks 9-12 (about 30-38% vs 11-14% on placebo). EAGLES ended at week 24; at 1 year about 22% stay quit (Gonzales, Jorenby 2006), so plan relapse follow-up. Combination NRT (patch plus gum or lozenge) beats one form by about 25% and nears varenicline (Cochrane 2019, 2023).

In patients over 65 or with CrCl under 60, start opioids at about 50% of the usual dose; prefer oral, short-acting, shortest duration. Add scheduled acetaminophen for opioid sparing; it is not nephrotoxic. NSAIDs only as a short course with renal monitoring: avoid if CrCl under 30 or with anticoagulants, antiplatelets or steroids (Beers 2023), and avoid chronic use in older adults and in CKD (KDIGO 2024).

Don't check PSA during acute urinary retention, falsely elevated. In general, PSA screening is rarely indicated after age 70, and almost never after 75.

Chronic prostatitis/chronic pelvic pain syndrome: pregabalin is not first-line. Its only powered RCT (Pontari 2010, n = 324) missed its primary endpoint, and EAU rates it not effective (LE 1b). EAU strong recs: an alpha-blocker and a 6-week quinolone or tetracycline course in treatment-naive men, both if symptoms < 1 year, plus acupuncture; NSAIDs are weak. Reserve neuromodulators for a neuropathic component.

Trospium is the overactive-bladder anticholinergic of choice in liver disease, minimal hepatic metabolism. Oxybutynin has the most side effects but is often the only inpatient option.

Depakote for dementia agitation: Cochrane 2018 (5 RCTs, n = 430) found valproate probably ineffective, with more adverse effects (sedation, GI upset, UTIs) and possibly more serious ones, so it is not recommended. The label warns of somnolence and poor intake in elderly dementia patients. 50–100 mcg/mL is an epilepsy range (mania 50–125), not an agitation target. Treat triggers; nonpharmacologic care first.

Tadalafil 5 mg daily is now a reasonable first-line for BPH in younger men, improves LUTS and quality of life, avoids alpha-blocker orthostasis and 5-ARI sexual side effects.

Central line IJ landmarks: position at SCM apex, direction toward ipsilateral nipple, 30–45° angle, depth ≤ 5 cm. Needle is usually 8 cm, never hub it.

Spasticity control is critical in chronic pressure ulcers, tensed muscles prevent healing and block flap reconstruction. Baclofen is first-line; PM&R gets involved if a baclofen pump is needed.

FAST stage 7 dementia qualifies for hospice (bedbound, incontinent, minimal speech) PLUS a comorbidity (CHF, COPD, CKD, etc.) OR recurrent infections, weight loss, or decreased PO. Don't miss the hospice window.

Chemical restraints are MORE invasive than physical, they affect cognition, can't be rapidly reversed, and carry cardiac/pulmonary risks. First step is always de-escalation. Physical restraints have injury risk but are quickly removable.

Persistent leak from a paracentesis site: place an ostomy bag to collect drainage. If it keeps leaking, close with a figure-of-8 stitch. Don't let continuous soiling cause skin breakdown or infection.

Ask the patient to take a deep breath in and out before thoracentesis, visualizes the diaphragm excursion so you can mark a safe entry well above it. Midscapular line, slightly lateral for wider rib spaces.

Subclavian central lines are more comfortable for patients and have lower infection rates than IJ, but carry higher mechanical complication risk (pneumothorax, subclavian artery, brachial plexus). Usually placed without ultrasound guidance.