When to intubate in GCS?

GCS ≤ 8 requires intubation for airway protection. The patient cannot protect their own airway at this level of consciousness. Motor score is the most prognostically important component.

What is the best initial fluid for sepsis resuscitation?

Lactated Ringer's (LR) is the preferred resuscitation fluid. The SMART trial (2018) showed balanced crystalloids reduced death, new renal failure, and persistent renal dysfunction compared to normal saline.

When to start vasopressors in septic shock?

Start norepinephrine (first-line vasopressor) if MAP remains < 65 mmHg after initial 30 mL/kg crystalloid resuscitation, or earlier if patient is profoundly hypotensive. Do not delay pressors to complete full fluid resuscitation.

Why can serum uric acid be normal during acute gout?

During acute inflammation, IL-6 increases renal urate excretion and redistributes urate from plasma to tissues. Up to 40% of acute gout flares have normal serum uric acid. Joint aspiration with polarized microscopy is needed for definitive diagnosis.

How do you distinguish lupus flare from infection in SLE?

Key clues: CRP is low/normal in flare but elevated in infection. Complement (C3/C4) drops in flare but is normal/elevated in infection. Procalcitonin is elevated in bacterial infection but normal in flare. Anti-dsDNA rises in flare, stable in infection.

What is the difference between DKA and HHS?

DKA features acidosis (pH 600), hyperosmolality (> 320), and minimal ketosis -typically in Type 2 DM. DKA requires insulin drip; HHS requires aggressive fluid resuscitation first.

When to give tPA in acute ischemic stroke?

IV alteplase (tPA) can be given within 4.5 hours of last known well time in eligible patients. CT head must rule out hemorrhage first. For large vessel occlusion, mechanical thrombectomy can be performed up to 24 hours with favorable imaging.

What antibiotics for community-acquired pneumonia?

Inpatient non-ICU: ceftriaxone + azithromycin. ICU: ceftriaxone + azithromycin (add vancomycin if MRSA risk). Outpatient healthy: amoxicillin. Outpatient with comorbidities: augmentin + azithromycin or respiratory fluoroquinolone. Duration: 5 days if clinically stable for 48 hours.

How to interpret iron studies?

Iron deficiency: low ferritin (< 30), high TIBC, low iron, low transferrin saturation (< 20%). Anemia of chronic disease: normal/high ferritin (acute phase reactant), low TIBC, low iron. A ferritin of 50-100 in an inflamed patient may still represent iron deficiency.

What is the correction rate for hyponatremia?

Correct sodium no more than 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome (ODS). For symptomatic severe hyponatremia with seizures, give 3% hypertonic saline 100-150 mL bolus over 10-20 minutes. If overcorrected, use D5W + DDAVP rescue protocol.

When to start antibiotics in meningitis?

Within 30-60 minutes. Do NOT delay antibiotics for LP or CT. Draw blood cultures, start empiric antibiotics (vancomycin + ceftriaxone ± ampicillin if > 50 or immunocompromised), then perform LP when possible. Dexamethasone should be given before or with the first antibiotic dose.

DOACs vs warfarin in antiphospholipid syndrome?

DOACs are contraindicated in APS. The TRAPS trial (2018) showed rivaroxaban was inferior to warfarin with more thrombotic events in triple-positive APS patients. Warfarin with INR target 2-3 is the standard for APS, indefinitely.

How to manage scleroderma renal crisis?

ACE inhibitors (captopril) are life-saving -start immediately and titrate aggressively. Do NOT hold for rising creatinine. Steroids > 15 mg prednisone per day precipitate scleroderma renal crisis. ARBs are NOT a substitute -evidence is only for ACEi.

What are the 4 pillars of heart failure treatment?

Guideline-directed medical therapy (GDMT) for HFrEF: (1) ARNI or ACEi/ARB, (2) beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), (3) MRA (spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). All four should be initiated and titrated to target doses.

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Nephrology

Renal Transplant Medicine

Immunosuppression regimens, rejection types, infection timelines, and the critical rule: any transplant patient with rising creatinine is rejection until proven otherwise.

🔍 Overview

Immunosuppression

Standard regimen has three components:

Induction: Basiliximab (IL-2 receptor antagonist, low immunologic risk) or Anti-thymocyte globulin (ATG) (high immunologic risk, repeat transplant, sensitized patients)
Maintenance (triple therapy):
- Tacrolimus (Prograf), calcineurin inhibitor. Target trough varies by time post-transplant: 8-12 ng/mL (month 0-3), 6-10 ng/mL (month 3-12), 4-8 ng/mL (after year 1).
- Mycophenolate (CellCept), 1000 mg PO BID (or mycophenolic acid 720 mg BID). Antiproliferative agent.
- Prednisone, high dose post-op, taper to 5 mg/day by month 3-6. Some centers do steroid-free protocols.

Types of Rejection

Hyperacute rejection: Minutes to hours. Preformed antibodies against donor ABO/HLA. Immediate graft thrombosis and loss. Prevented by crossmatch testing. Essentially eliminated by modern crossmatching.
Acute cellular rejection (ACR): Weeks to months. T-cell mediated. Most common type. Responds well to pulse steroids (methylprednisolone 500 mg IV x 3 days) or ATG for steroid-resistant cases.
Acute antibody-mediated rejection (AMR): B-cell/antibody mediated. Donor-specific antibodies (DSA). Treat with plasmapheresis + IVIG + rituximab. Harder to treat than ACR.
Chronic rejection: Months to years. Progressive interstitial fibrosis and tubular atrophy (IF/TA). No effective treatment. Leads to slow graft loss.

Infection Timeline

Month 0-1: Surgical site infections, UTI, donor-derived infections, CMV (especially D+/R-)
Month 1-6: Opportunistic infections, CMV (most common), BK virus (nephropathy), PJP (all on prophylaxis during this window)
Month 6+: Community-acquired infections, late CMV (after prophylaxis stopped), BK nephropathy, Listeria, Nocardia

🚨 Management

Rising Creatinine in a Transplant Patient

Any transplant patient with rising creatinine = rejection until proven otherwise. Get tacrolimus level STAT, UA, donor-specific antibodies, and call transplant nephrology. Do NOT just "watch the creatinine."

Differential for Rising Creatinine

Rejection (cellular or antibody-mediated)
Tacrolimus toxicity (check trough level, supratherapeutic)
BK virus nephropathy (check BK PCR)
Obstruction (ureteral stricture, lymphocele, renal US)
Pre-renal (dehydration, NSAID use, ACE/ARB)
Recurrent disease (FSGS, IgA, diabetic nephropathy)
CNI nephrotoxicity (chronic tacrolimus injury)

Rejection Treatment

Acute cellular rejection: Methylprednisolone 500 mg IV daily x 3 days. If steroid-resistant, ATG.
Antibody-mediated rejection: Plasmapheresis (5-7 sessions) + IVIG 100 mg/kg after each session + Rituximab 375 mg/m2. Consider bortezomib (Velcade) for refractory cases.
BK nephropathy: Reduce immunosuppression (lower tacrolimus target, decrease mycophenolate). No specific antiviral. Cidofovir and leflunomide have been tried.

Clinical Example: A 55-year-old man 6 months post-renal transplant presents with Cr rising from 1.4 to 2.3 over 2 weeks. He feels well. Tacrolimus trough 4.2 (subtherapeutic). BK PCR negative. UA bland. DSA panel shows new anti-HLA antibodies. Renal biopsy: C4d positive peritubular capillaritis. Diagnosis: acute antibody-mediated rejection. Initiate plasmapheresis + IVIG + rituximab.

🧪 Workup

Workup for Rising Creatinine

Tacrolimus trough, STAT. Supratherapeutic = CNI toxicity. Subtherapeutic = possible rejection.
UA + urine culture, UTI is common post-transplant
BK virus PCR, screen monthly for first 6 months, then q3 months. >10,000 copies = BK viremia requiring immunosuppression reduction.
CMV PCR, if symptomatic or at high-risk period
Donor-specific antibodies (DSA), if AMR suspected
Renal transplant ultrasound with Doppler, evaluate for hydronephrosis, perinephric collections (lymphocele, hematoma), vascular stenosis
Transplant renal biopsy, gold standard for diagnosis. Banff classification. Indicated if creatinine rises >25% from baseline without clear cause.

Routine Surveillance Labs

BMP, CBC, tacrolimus trough, LFTs, fasting glucose, lipid panel
BK PCR monthly x 6 months, then q3 months x 2 years
CMV PCR monthly if D+/R- (highest risk)

💊 Medications

Medications

Drug	Class/Indication	Dose	Notes
Tacrolimus (Prograf)	CNI, maintenance	Varies; target trough 8-12 early, 4-8 late	Nephrotoxic, diabetogenic, tremor, hyperkalemia, hypomagnesemia. Many drug interactions (azoles increase levels, rifampin decreases). Check trough levels.
Mycophenolate (CellCept)	Antiproliferative, maintenance	1000 mg PO BID	GI side effects (diarrhea, nausea). Bone marrow suppression (monitor CBC). Teratogenic. Reduce dose if BK viremia.
Prednisone	Corticosteroid, maintenance	Taper to 5 mg daily	Metabolic effects (hyperglycemia, osteoporosis, weight gain). Some centers do steroid withdrawal.
TMP-SMX (Bactrim)	PJP prophylaxis	1 SS tab daily x 6-12 months	Also provides UTI prophylaxis and Toxoplasma, Nocardia, Listeria coverage.
Valganciclovir (Valcyte)	CMV prophylaxis	900 mg PO daily x 3-6 months	For CMV D+/R- (highest risk) or D+/R+. Monitor CMV PCR. Can cause leukopenia.
Nystatin	Oral candida prophylaxis	5 mL swish and swallow QID x 1-3 months	Prevent oral/esophageal candidiasis while on high-dose immunosuppression.

🏥 Rounds

Pimp Questions

❓ What are the types of rejection and their timelines?

Hyperacute: minutes (preformed antibodies, graft loss). Acute cellular: weeks-months (T-cell mediated, responds to steroids). Acute antibody-mediated: weeks-months (B-cell/DSA, treat with plasmapheresis/IVIG/rituximab). Chronic: months-years (IF/TA, no effective treatment).

❓ What infections occur in each post-transplant time period?

Month 0-1: Surgical site, UTI, donor-derived, early CMV. Month 1-6: CMV (most common), BK virus, PJP, all on prophylaxis. After month 6: Community-acquired, late CMV, BK nephropathy, PTLD.

❓ What is the most important first step when a transplant patient has a rising creatinine?

Check tacrolimus trough level STAT. Supratherapeutic = CNI nephrotoxicity (reduce dose). Subtherapeutic = risk factor for rejection. Then: UA, BK PCR, DSA, renal US. If no clear cause, biopsy. Call transplant nephrology early.

Sample Presentation

Mr. Johnson is a 48-year-old man, 3 months post-deceased donor renal transplant for ESRD from IgA nephropathy. Presenting with creatinine rising from baseline 1.2 to 1.9 over 1 week. No symptoms. Tacrolimus trough: 5.1 (target 6-10, slightly low). BK PCR: negative. CMV PCR: negative. UA: bland. Renal US: no hydronephrosis, normal Doppler flows. DSA: negative. Given rising Cr without clear etiology and subtherapeutic tacrolimus, transplant nephrology recommended renal biopsy. Biopsy showed Banff 1A acute cellular rejection (tubulitis, interstitial inflammation). Started methylprednisolone 500 mg IV x 3 days. Tacrolimus dose increased to target trough 8-10.

Key Points: Rising creatinine in a transplant patient is rejection until proven otherwise. Subtherapeutic tacrolimus was the likely contributing factor. Biopsy is the gold standard. ACR responds well to pulse steroids. Increase maintenance immunosuppression and recheck creatinine in 48-72h.

Monitoring

Tacrolimus trough, check 2-3x/week early, then weekly, then monthly. Target varies by time post-transplant.
BMP weekly initially, creatinine trending, electrolytes (hyperK from tacrolimus, hypoMg)
CBC weekly, leukopenia (mycophenolate, valganciclovir), anemia, thrombocytopenia
BK virus PCR monthly x 6 months, then q3 months x 2 years
CMV PCR monthly for high-risk (D+/R-) during and after prophylaxis
Fasting glucose, post-transplant diabetes (tacrolimus + steroids)
Lipid panel, dyslipidemia common (tacrolimus, sirolimus)
Cancer screening, skin checks annually (SCC risk 65-250x increased), cervical screening, colon cancer per guidelines. PTLD surveillance (EBV PCR if EBV D+/R-).

📋 Summary

Summary

Maintenance

Tacrolimus + Mycophenolate + Prednisone. Check tacrolimus trough regularly.

Rising Cr

Rejection until proven otherwise. Tac level STAT, BK PCR, DSA, US, biopsy if unclear.

ACR Treatment

Pulse methylprednisolone 500 mg IV x 3 days. ATG if steroid-resistant.

AMR Treatment

Plasmapheresis + IVIG + Rituximab. Harder to treat than ACR.

Prophylaxis

TMP-SMX (PJP), Valganciclovir (CMV), Nystatin (candida). Duration varies by risk.

Infections

0-1mo: surgical/UTI. 1-6mo: CMV, BK, PJP. 6mo+: community, late CMV, PTLD.