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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Heme/OncICU

Chemotherapy Toxicities

Recognition and management of life-threatening chemo side effects: cardiotoxicity, mucositis, typhlitis, hemorrhagic cystitis, immune checkpoint toxicities, and infusion reactions.

🔍 Overview

Overview

Chemotherapy toxicities are a leading cause of treatment discontinuation, ICU admission, and death in cancer patients. The intern must recognize organ-specific toxicities by drug class: anthracyclines (cardiotoxicity), bleomycin (pulmonary fibrosis), cisplatin (nephro/oto/neurotoxicity), vinca alkaloids (neuropathy), cyclophosphamide (hemorrhagic cystitis), checkpoint inhibitors (immune-related adverse events in any organ). Key principle: know which chemo the patient received and its expected toxicity profile.

irAE Grading and Management

Grade	Severity	Action	Steroids
Grade 1	Mild symptoms	Continue checkpoint therapy, close monitoring	None (topical steroids for skin if needed)
Grade 2	Moderate, interferes with ADLs	Hold checkpoint therapy until resolves to Grade ≤ 1	Oral prednisone 0.5–1 mg/kg/day, taper over 4–6 weeks
Grade 3	Severe, hospitalization required	Hold checkpoint therapy, inpatient management	IV methylprednisolone 1–2 mg/kg/day, taper over ≥ 4 weeks
Grade 4	Life-threatening	Permanently discontinue checkpoint therapy	IV methylprednisolone 1–2 mg/kg + specialty consult (infliximab for colitis, MMF for hepatitis)

Common irAEs by Organ System

Organ	Presentation	Workup	Treatment
Skin	Maculopapular rash, pruritus, vitiligo	Clinical exam, biopsy if severe	Topical steroids, oral antihistamines; systemic steroids if Grade ≥ 3
GI (Colitis)	Diarrhea (watery, may be bloody), crampy abdominal pain	C. diff (rule out), CT abdomen, colonoscopy with biopsy	Steroids; infliximab if steroid-refractory
Hepatitis	AST/ALT elevation, usually asymptomatic	LFTs, hepatitis panel, autoimmune markers, imaging	Steroids; mycophenolate if refractory (NOT infliximab, hepatotoxic)
Pneumonitis	Cough, dyspnea, hypoxia	CT chest (ground-glass opacities), PFTs, bronchoscopy/BAL	Hold therapy, high-dose steroids, infliximab or MMF if refractory
Endocrine	Thyroiditis → hypothyroidism, adrenal insufficiency, new-onset T1DM, hypophysitis	TSH/free T4, AM cortisol, ACTH, glucose, pituitary MRI	Hormone replacement (levothyroxine, hydrocortisone, insulin), often lifelong
Neuro	Myasthenia gravis, encephalitis, Guillain-Barré, peripheral neuropathy	EMG/NCS, MRI brain, LP, AChR antibodies	High-dose steroids, IVIG, plasmapheresis; permanently discontinue therapy
Cardiac	Myocarditis (chest pain, dyspnea, arrhythmia, high mortality)	Troponin, BNP, ECG, echo, cardiac MRI, endomyocardial biopsy	High-dose IV steroids immediately; permanently discontinue; cardiology consult

Classic Chemo Toxicities, Know the Drug, Know the Organ: Bleomycin = Lungs (pulmonary fibrosis, avoid high FiO₂). Doxorubicin = Heart (dilated cardiomyopathy, lifetime dose limit). Cisplatin = Kidneys + Ears (nephrotoxicity, ototoxicity, neuropathy). Vincristine = Nerves (peripheral neuropathy, constipation/ileus). Cyclophosphamide = Bladder (hemorrhagic cystitis, prevent with MESNA). Methotrexate = Liver + Mucositis (hepatotoxicity, mucositis, rescue with leucovorin).

🧪 Workup

Workup

Know the regimen -review the chemo protocol. Each drug has specific toxicities.
CBC with differential -nadir timing varies: 7-14 days for most agents, 4-6 weeks for nitrosoureas
BMP, LFTs, LDH -organ toxicity screening
Troponin + BNP + echo -if anthracycline cardiotoxicity suspected
CT chest -bleomycin/checkpoint pneumonitis
UA -hemorrhagic cystitis (cyclophosphamide/ifosfamide)
TSH -checkpoint inhibitor thyroiditis (most common irAE)
AM cortisol -checkpoint hypophysitis
Lipase -checkpoint pancreatitis

🚨 Management

Management

Anthracycline cardiotoxicity: Echo (EF decline > 10% to below 50% = hold). Dexrazoxane for cardioprotection if cumulative dose high. Standard HF therapy if cardiomyopathy develops. Lifetime dose limits: doxorubicin 450-550 mg/m².
Bleomycin lung toxicity: Stop bleomycin. Steroids (prednisone 1 mg/kg). Avoid high FiO₂ -oxygen worsens bleomycin lung injury (free radical mechanism). Keep SpO₂ 88-92% target.
Typhlitis (neutropenic enterocolitis): CT abdomen (bowel wall thickening, pneumatosis). Broad-spectrum abx (pip-tazo + vanc). NPO + IV fluids. Surgery if perforation/peritonitis.
Hemorrhagic cystitis: Aggressive IVF hydration. Continuous bladder irrigation (CBI). MESNA prophylaxis with cyclophosphamide/ifosfamide (binds acrolein metabolite). Urology if severe clot retention.
Checkpoint inhibitor irAEs: Grade 1 → continue + monitor. Grade 2 → hold checkpoint, prednisone 0.5-1 mg/kg. Grade 3 → hold checkpoint, methylprednisolone 1-2 mg/kg. Grade 4 → permanently discontinue, methylprednisolone 1-2 mg/kg ± infliximab (colitis) or mycophenolate (hepatitis). [NCCN irAE Guidelines]

💊 Medications

Medications

Drug	Dose	Route	Notes
MESNA	60-100% of cyclophosphamide dose	IV	Prevents hemorrhagic cystitis. Binds acrolein (toxic metabolite) in bladder. Give with cyclo/ifosfamide.
Dexrazoxane	10:1 ratio to doxorubicin	IV	Iron chelator. Cardioprotection for cumulative anthracycline doses ≥ 300 mg/m².
Amifostine	910 mg/m² IV pre-cisplatin	IV	Nephroprotection for cisplatin. Free radical scavenger. Causes hypotension.
Prednisone	1-2 mg/kg daily	PO	irAEs Grade 2+. Taper over 4-6 weeks minimum. Too-rapid taper → flare.
Infliximab	5 mg/kg IV	IV	Steroid-refractory checkpoint colitis. NCCN irAE, 2024
Ondansetron	8 mg IV pre-chemo	IV	Acute emesis. Add dexamethasone + NK1 antagonist for high emetogenic regimens.
Palonosetron	0.25 mg IV	IV	Longer-acting 5-HT3 for delayed emesis prevention.

🏥 Rounds

Pimp Questions

❓ What is the most common immune-related adverse event from checkpoint inhibitors?

Thyroiditis/hypothyroidism (up to 10-20% with anti-PD-1). Often painless thyroiditis → transient hyperthyroidism → permanent hypothyroidism requiring levothyroxine. Check TSH q4-6 weeks. Unlike most irAEs, hypothyroidism does NOT require holding checkpoint therapy.

❓ Why should you avoid high FiO₂ in bleomycin lung toxicity?

Bleomycin causes pulmonary injury via free radical generation. High concentrations of oxygen provide more substrate for free radical production, worsening the lung injury. Target SpO₂ 88-92%. This is critical during surgery in patients with bleomycin history -anesthesia must avoid high FiO₂ even years later.

❓ What is MESNA and how does it work?

MESNA (2-mercaptoethane sulfonate sodium) binds acrolein, the toxic metabolite of cyclophosphamide and ifosfamide that causes hemorrhagic cystitis. MESNA is renally excreted and acts directly in the bladder lumen to neutralize acrolein. Always give with cyclophosphamide (especially high-dose) and ifosfamide.

❓ What is the cumulative dose limit for doxorubicin and why?

450-550 mg/m² lifetime. Above this threshold, risk of irreversible dilated cardiomyopathy increases sharply. Doxorubicin causes cardiotoxicity via free radical damage to cardiomyocytes + topoisomerase IIβ inhibition. Can occur during treatment (acute) or years later (late-onset). Monitor with serial echocardiography. Dexrazoxane is cardioprotective at high cumulative doses.

❓ How do you grade and manage checkpoint inhibitor hepatitis?

Grade 1 (AST/ALT 1-3× ULN): continue checkpoint, monitor LFTs weekly. Grade 2 (3-5× ULN): hold checkpoint, prednisone 0.5-1 mg/kg. Grade 3 (5-20× ULN): hold, methylprednisolone 1-2 mg/kg. Grade 4 (> 20× ULN): permanently discontinue, methylprednisolone 2 mg/kg, add mycophenolate (NOT infliximab -hepatotoxic). Rule out viral hepatitis and autoimmune hepatitis first.

❓ What is typhlitis and which patients get it?

Typhlitis (neutropenic enterocolitis) = inflammation/necrosis of the cecum in severely neutropenic patients (ANC < 500), usually during chemo nadir. Presents with RLQ pain, fever, diarrhea (often bloody). CT: cecal wall thickening > 4mm, pericecal fat stranding, ± pneumatosis. Treatment: broad-spectrum antibiotics, NPO, IVF. Surgery only if perforation/peritonitis. Mortality 20-50%.

❓ When should you permanently discontinue checkpoint inhibitor therapy?

Grade 4 irAEs (life-threatening) require permanent discontinuation. Additionally, any grade of the following mandates permanent discontinuation: myocarditis (mortality up to 50%), encephalitis, myasthenia gravis, Guillain-Barré syndrome, and Grade 3+ pneumonitis that recurs after rechallenge. Grade 3 irAEs that do not improve to Grade ≤ 1 within 12 weeks of steroids should also lead to permanent discontinuation. Exception: endocrinopathies (thyroid, adrenal) managed with hormone replacement can allow continuation.

❓ Which irAE requires lifelong hormone replacement even after resolution?

Endocrine irAEs, particularly hypothyroidism (from checkpoint thyroiditis) and adrenal insufficiency (from hypophysitis destroying ACTH-producing cells). Unlike colitis, hepatitis, or pneumonitis, which can fully resolve with steroids, endocrine gland destruction is irreversible. Patients need lifelong levothyroxine (hypothyroidism) or hydrocortisone (adrenal insufficiency). New-onset type 1 diabetes from checkpoint therapy also requires lifelong insulin. These patients can often continue checkpoint therapy while on hormone replacement.

Clinical Examples

📋 Case 1, Checkpoint Inhibitor Colitis

Patient: 62M with metastatic melanoma on nivolumab (cycle 6). Presents with 4 days of watery diarrhea (8 episodes/day), diffuse crampy abdominal pain, low-grade fever. No blood in stool.

Diagnosis: Grade 3 immune-mediated colitis.

Key findings:

Grade 3, ≥ 7 stools/day over baseline, requires hospitalization
C. diff negative, must rule out infectious etiologies first
CT abdomen: diffuse pancolitis with wall thickening and fat stranding
Hold nivolumab, do not continue checkpoint therapy during Grade 3 irAE

Treatment: IV methylprednisolone 1–2 mg/kg/day. GI consult for colonoscopy with biopsy. If no improvement in 48–72 hours → infliximab 5 mg/kg. Slow steroid taper over ≥ 6 weeks once improved.

Sample Presentation

Mr. Davis is a 58-year-old man with metastatic melanoma on pembrolizumab (cycle 8) presenting with 5 days of watery diarrhea (8-10 episodes/day), crampy abdominal pain, no blood. Afebrile. Exam: diffuse abdominal tenderness, no peritoneal signs. Labs: WBC 11K, Cr 1.4 (baseline 0.9). C. diff negative. CT: diffuse colonic wall thickening. TSH 12 (baseline 2.5).

Key Points: Checkpoint inhibitor colitis (Grade 3 -≥ 7 stools/day over baseline) + new hypothyroidism. Hold pembrolizumab. Start methylprednisolone 1 mg/kg IV. If no improvement in 3 days → infliximab 5 mg/kg. Start levothyroxine for hypothyroidism. GI consult for possible colonoscopy with biopsy.

Hodgkin vs Non-Hodgkin Lymphoma Comparison

Feature	Hodgkin Lymphoma	Non-Hodgkin Lymphoma
Frequency	~10% of lymphomas	~90% of lymphomas
Age	Bimodal (20s and 60s)	Median age 60-70
Pathognomonic cell	Reed-Sternberg cell (CD15+/CD30+)	Varies by subtype (CD20+ B-cell most common)
Spread pattern	Contiguous (node to adjacent node)	Non-contiguous (can skip nodal groups)
Mediastinal mass	Very common (especially nodular sclerosis)	Less common (except primary mediastinal B-cell)
B symptoms	Common, affects staging	Present but less impact on staging
Extranodal disease	Rare at presentation	Common (GI, skin, CNS, bone marrow)
Prognosis	Excellent (> 80% cure)	Varies: indolent (incurable but long survival) to aggressive (curable with chemo)
Treatment	ABVD or BV-AVD ± radiation	Depends on subtype: R-CHOP (DLBCL), watch-and-wait (follicular), intensive chemo (Burkitt)

Ann Arbor Staging System

Stage	Definition	Clinical Relevance
I	Single lymph node region	Early stage, favorable prognosis. HL: ABVD × 2-4 + radiation. DLBCL: R-CHOP × 3 + radiation or R-CHOP × 6.
II	Two or more lymph node regions on the same side of the diaphragm
III	Lymph node regions on both sides of the diaphragm	Advanced stage. HL: ABVD × 6 or BV-AVD. DLBCL: R-CHOP × 6. Follicular: treat if symptomatic.
IV	Extranodal involvement (bone marrow, liver, lung parenchyma)

Staging Modifiers: A = no B symptoms. B = B symptoms present (fever > 38°C, drenching night sweats, weight loss > 10% in 6 months). E = extranodal extension from adjacent node. S = splenic involvement. X = bulky disease (> 10 cm or > 1/3 thoracic diameter). Example: Stage IIBS = both sides of diaphragm + B symptoms + spleen.

B Symptoms, Definition and Significance

B Symptoms (must know for rounds): (1) Fever > 38°C (unexplained, not from infection). (2) Drenching night sweats (requiring change of clothes/sheets). (3) Weight loss > 10% body weight in 6 months. B symptoms indicate higher tumor burden and worse prognosis. In HL, B symptoms upstage the disease (Stage IIB is treated as advanced stage). Note: pruritus and alcohol-induced lymph node pain (Hodgkin-specific) are NOT B symptoms but are associated findings.

📋 Case 2, Checkpoint Inhibitor Thyroiditis

Patient: 54F with NSCLC on pembrolizumab (cycle 4). Routine labs show TSH 45 mIU/L (baseline 2.1), free T4 0.3 ng/dL (low). Patient reports fatigue, weight gain, constipation.

Diagnosis: Checkpoint inhibitor thyroiditis → hypothyroid phase.

Key findings:

TSH markedly elevated with low free T4, overt hypothyroidism
Painless thyroiditis, may have had transient hyperthyroid phase (often missed)
Most common endocrine irAE, occurs in 10–20% of anti-PD-1 patients
Does NOT require holding checkpoint therapy, unlike most other irAEs

Treatment: Start levothyroxine 1.6 mcg/kg/day. Continue pembrolizumab. Monitor TSH q6–8 weeks and titrate. This is typically permanent, lifelong levothyroxine replacement needed.

📋 Case 3, Checkpoint Inhibitor Hepatitis

Patient: 48M with advanced RCC on ipilimumab/nivolumab (cycle 3). Labs: AST 580 (14x ULN), ALT 640 (16x ULN), T. bili 2.1, ALP 180. Asymptomatic.

Diagnosis: Grade 3 immune-mediated hepatitis.

Key findings:

AST/ALT > 10x ULN, Grade 3 hepatitis (5–20x ULN)
Hepatitis panel negative, rule out viral hepatitis (HBV reactivation with immunotherapy)
Ipilimumab/nivolumab combo, highest rate of irAEs (~60%), hepatitis in ~15%
Often asymptomatic, caught on routine monitoring LFTs

Treatment: Hold ipilimumab/nivolumab. IV methylprednisolone 1–2 mg/kg/day. If refractory → add mycophenolate (NOT infliximab, it is hepatotoxic). Monitor LFTs daily until downtrending. Taper steroids over ≥ 4 weeks.

Monitoring

CBC nadir -typically day 7-14 (day 21-28 for nitrosoureas). Check CBC before each cycle.
Echo/MUGA q3 months on anthracyclines -stop if EF drops > 10% below baseline to < 50%
PFTs before and during bleomycin -stop if DLCO drops > 20%
Cr + Mg with cisplatin (nephrotoxicity + magnesium wasting)
Audiometry with cisplatin (ototoxicity -irreversible high-frequency hearing loss)
TSH q4-6 weeks on checkpoint inhibitors (thyroiditis → hypothyroidism)
LFTs q2-4 weeks on checkpoint inhibitors (hepatitis)
Urine output + UA with cyclophosphamide (hemorrhagic cystitis)

📋 Summary

Summary

Cardiotoxicity

Anthracyclines (doxorubicin). Echo q3mo. Lifetime limit 450-550 mg/m². Dexrazoxane if high dose.

Pulmonary

Bleomycin → fibrosis. Stop drug. Steroids. Avoid high FiO₂ (even years later).

Hemorrhagic Cystitis

Cyclophosphamide/ifosfamide. Prevent with MESNA. Treat with CBI + hydration.

Checkpoint irAEs

Grade 1→monitor. Grade 2→hold+steroids. Grade 3-4→high-dose steroids ± infliximab/MMF.

Typhlitis

Neutropenic cecal inflammation. RLQ pain + fever + ANC<500. CT: cecal wall thickening. Abx + NPO.

Key Rule

Always know the regimen. Each drug has predictable toxicities. Ask: "What chemo did they get?"

📄 One Pager

One-Pager

Chemo Toxicities

Know the drug, predict the toxicity

Drug → Toxicity Map

Anthracyclines → heart. Bleomycin → lungs. Cisplatin → kidneys + ears + nerves. Vincristine → peripheral neuropathy. Cyclophosphamide → bladder. Checkpoint inhibitors → any organ (thyroid most common).

Antidotes/Prevention

MESNA (hemorrhagic cystitis). Dexrazoxane (anthracycline cardiotoxicity). Amifostine (cisplatin nephrotoxicity). Leucovorin (methotrexate rescue). Aggressive hydration (cisplatin, ifosfamide, TLS prevention).