What is the most likely cause of sudden cardiac arrest in a patient on Day 3 of chemotherapy?

Cardiac Arrest on Day 3 of Chemotherapy: Most Likely Cause

The most likely cause of sudden cardiac arrest on Day 3 of chemotherapy is arrhythmia (Option B), driven by direct cardiotoxic effects of chemotherapeutic agents on cardiac ion channels, electrolyte disturbances (particularly hypokalemia and hypomagnesemia), and acute myocardial injury. 1, 2, 3

Why Arrhythmia is the Primary Culprit

Direct Cardiotoxic Mechanisms

• Chemotherapeutic agents cause direct electrophysiological effects on cardiac ion channels, leading to QT prolongation, ventricular tachyarrhythmias, bradycardia, and conduction blocks during or immediately after infusion 1, 3
• Anthracyclines (doxorubicin), alkylating agents (cyclophosphamide), fluorouracil (5-FU), and paclitaxel are the most arrhythmogenic agents, with acute cardiotoxicity manifesting as transient decline in myocardial contractility (incidence <1%) immediately after infusion, creating an arrhythmogenic substrate 1, 2
• The incidence of cardiac arrhythmias with fluorouracil ranges from 1% to 68%, with ischemic ECG changes reported in 68% of patients, while paclitaxel induces ventricular arrhythmias, bradycardia, atrioventricular conduction blocks, and bundle branch block 1, 2

Critical Electrolyte Disturbances

• Electrolyte imbalances, particularly hypokalemia and hypomagnesemia, are recognized risk factors for chemotherapy-induced cardiotoxicity and dramatically lower the arrhythmia threshold 2
• Severe hyperkalemia (>6.5 mmol/L) can cause cardiac arrhythmias and cardiac arrest, particularly in patients with acute kidney injury, which may develop during chemotherapy 4
• Hypokalemia increases the risk of ventricular arrhythmias including ventricular tachycardia, torsades de pointes, and ventricular fibrillation, with ECG manifestations including peaked T waves progressing to flattened P waves, prolonged PR interval, and widened QRS complex 4, 5

Why Sepsis (Option A) is Less Likely

• Day 3 is too early for neutropenic sepsis, which typically develops 7-14 days after chemotherapy when neutrophil counts reach their nadir 1
• Sepsis-induced cardiac arrest would typically present with fever, hypotension, tachycardia, and evidence of infection, none of which are mentioned in this scenario 4
• The sudden nature of the arrest without preceding hemodynamic instability argues against sepsis as the primary mechanism 4

Why Pulmonary Embolism (Option C) is Less Likely

• While cancer patients have increased thrombotic risk, particularly with platinum agents like cisplatin, PE typically presents with dyspnea, chest pain, and hypoxia before progressing to cardiac arrest 1, 6, 7
• PE-induced cardiac arrest would show right ventricular dysfunction on echocardiography and would be an unusual presentation on Day 3 without preceding symptoms 6, 7
• Disseminated microvascular pulmonary tumor embolism (DMPTE) presents with progressive dyspnea and pulmonary hypertension over weeks, not sudden arrest on Day 3 7

Immediate Diagnostic Approach

First-Line Investigations

• Obtain 12-lead ECG immediately to detect QT prolongation (>500 ms), conduction blocks, ischemic changes, or peaked T waves suggesting hyperkalemia 1, 2
• Check electrolytes emergently, focusing on potassium (target 4.0-5.0 mEq/L), magnesium (target >0.6 mmol/L), and calcium, as chemotherapy-induced imbalances potentiate arrhythmias 4, 1, 5
• Review the specific chemotherapy regimen administered to identify known arrhythmogenic drugs (anthracyclines, paclitaxel, 5-FU, alkylating agents) 1, 2
• Perform bedside echocardiography during resuscitation to assess for acute right ventricular dysfunction (suggesting PE), global dysfunction (suggesting cardiomyopathy), or pericardial effusion 1

Secondary Investigations

• Measure cardiac biomarkers (troponin I, BNP) to identify acute myocardial injury or heart failure 8
• Assess renal function (creatinine, eGFR) as acute kidney injury increases hyperkalemia risk and is associated with chemotherapy-induced cardiac arrest 4
• Consider CT pulmonary angiography only if echocardiography shows right ventricular dysfunction and PE remains in the differential 6, 7

Post-Resuscitation Management Priorities

Immediate Stabilization

• Initiate continuous cardiac monitoring for recurrent arrhythmias, as electrical instability persists after initial resuscitation 4, 1
• Correct electrolyte abnormalities aggressively, particularly hypokalemia (target 4.0-5.0 mEq/L) and hypomagnesemia (target >0.6 mmol/L), as these lower the arrhythmia threshold 4, 5, 2
• Avoid QT-prolonging medications (procainamide, sotalol, amiodarone in long-QT syndrome) and reassess the chemotherapy regimen with oncology 4, 1
• Implement targeted temperature management (32-34°C for 24 hours) if the patient remains comatose post-ROSC to improve neurological outcomes 4

Ongoing Surveillance

• Monitor vital signs frequently during any subsequent chemotherapy infusions, particularly with 5-FU or paclitaxel 1
• Perform serial ECGs and echocardiography to detect evolving cardiotoxicity or conduction abnormalities 1, 8
• Consider cardioprotective strategies including dexrazoxane for anthracycline therapy, dose modification, or alternative regimens 2

Critical Pitfalls to Avoid

• Do not assume sepsis without fever, leukocytosis, or identified source, as Day 3 is too early for neutropenic complications 1
• Do not overlook drug-specific arrhythmia risks, particularly with anthracyclines (acute transient contractility decline), paclitaxel (bradycardia, conduction blocks), and 5-FU (coronary vasospasm, ischemia) 1, 2
• Do not delay electrolyte correction while pursuing other diagnoses, as hypokalemia and hypomagnesemia are immediately reversible causes of arrhythmias 4, 5, 2
• Do not confuse 5-FU's ischemic cardiotoxicity with anthracycline-induced cardiomyopathy, as they have completely different mechanisms, time courses, and management strategies 1
• Do not restart cardiotoxic chemotherapy without comprehensive cardiovascular evaluation, including LVEF measurement, ECG, and electrolyte optimization 1, 8