How should I manage a patient who develops acute flash pulmonary edema during a doxorubicin infusion?

Management of Acute Flash Pulmonary Edema During Doxorubicin Infusion

Immediately stop the doxorubicin infusion, apply non-invasive positive pressure ventilation (CPAP or BiPAP), and initiate high-dose intravenous nitroglycerin with low-dose furosemide—this combination is superior to diuretics alone and reduces mortality and intubation risk. 1, 2, 3

Immediate Actions (First 5 Minutes)

Stop the Infusion

• Discontinue doxorubicin immediately upon recognition of acute pulmonary edema, as anthracyclines can cause acute cardiotoxicity even after a single dose 4, 5
• Do not resume doxorubicin—acute cardiac decompensation during infusion represents a contraindication to further anthracycline therapy 4

Respiratory Support (Primary Intervention)

• Apply non-invasive ventilation (CPAP or BiPAP) immediately before considering intubation—this reduces mortality (RR 0.80) and need for intubation (RR 0.60) 1, 2, 3
• Start CPAP with initial PEEP of 5-7.5 cmH₂O, titrate up to 10 cmH₂O based on response, with FiO₂ at 0.40 2
• Both CPAP and BiPAP are equally effective 1, 2
• Administer oxygen only if SpO₂ <90%—avoid routine oxygen in non-hypoxemic patients as it causes vasoconstriction and reduces cardiac output 4, 1, 2, 3

Pharmacological Management

High-Dose Nitroglycerin (First-Line)

• Start with sublingual nitroglycerin 0.4-0.6 mg, repeat every 5-10 minutes up to four times if systolic BP remains ≥95-100 mmHg 1, 2, 3
• Immediately initiate IV nitroglycerin at 20 mcg/min, increase rapidly up to 200 mcg/min according to hemodynamic tolerance 1, 2, 3
• Check blood pressure every 3-5 minutes during titration 3
• Titrate to achieve 10 mmHg reduction in mean arterial pressure or systolic BP of 90-100 mmHg 3
• Reduce dose if systolic BP drops below 90-100 mmHg 3

Critical Point: High-dose nitrates are essential—low-dose nitrates have limited efficacy and fail to prevent intubation 2, 3

Low-Dose Furosemide (Adjunctive)

• Administer furosemide 40 mg IV as initial bolus (over 1-2 minutes), never as monotherapy 3, 6
• If inadequate response after 1 hour, increase to 80 mg IV 3, 6
• Never use high-dose diuretics alone—this worsens hemodynamics and increases mortality 2, 3
• Furosemide transiently worsens hemodynamics during the first 1-2 hours (increases systemic vascular resistance and left ventricular filling pressures) 3

Morphine (Selective Use)

• Consider morphine sulfate 2-4 mg IV for patients with severe dyspnea and restlessness 2

Blood Pressure-Based Algorithm

If Systolic BP ≥100 mmHg:

• High-dose IV nitroglycerin + low-dose furosemide 40 mg IV + non-invasive ventilation 2

If Systolic BP 70-100 mmHg:

• Dobutamine 2-20 mcg/kg/min IV and/or dopamine 5-15 mcg/kg/min IV 2
• Use vasodilators with extreme caution 4

If Systolic BP <70 mmHg:

• Norepinephrine 30 mcg/min IV, dopamine 5-15 mcg/kg/min IV 2
• Consider intra-aortic balloon counterpulsation 2

Urgent Diagnostic Evaluation

Assess for Acute Myocardial Injury

• Obtain immediate ECG and cardiac enzymes to exclude acute coronary syndrome, as doxorubicin can cause acute myocardial ischemia 4, 2
• If ST-elevation or new left bundle branch block present, consider urgent cardiac catheterization 4, 2

Echocardiography

• Perform urgent echocardiography to assess left ventricular ejection fraction and exclude mechanical complications 2
• Doxorubicin can cause acute cardiomyopathy with severely reduced EF (as low as 20%) even after a single dose 5

Hemodynamic Monitoring

• Consider pulmonary artery catheter if: 4, 3
  • Patient not responding appropriately to therapy
  • Uncertainty whether pulmonary edema is cardiogenic or non-cardiogenic
  • Need for high-dose vasopressors or inotropes
  • Clinical deterioration despite treatment

Critical Pitfalls to Avoid

• Never use low-dose nitrates—they are ineffective in flash pulmonary edema 2, 3
• Never use high-dose diuretics as monotherapy—this increases mortality 2, 3
• Avoid aggressive simultaneous use of multiple hypotensive agents—this can precipitate iatrogenic cardiogenic shock 2
• Do not administer beta-blockers or calcium channel blockers acutely to patients with frank cardiac failure evidenced by pulmonary congestion 2
• Do not resume doxorubicin—acute cardiac decompensation during infusion is a contraindication 4

Post-Stabilization Management

Cardioprotective Therapy

• Once stabilized, initiate carvedilol 3.125 mg twice daily and lisinopril 5 mg once daily for anthracycline-induced cardiotoxicity 5
• Titrate beta-blocker and ACE inhibitor to maximum tolerated doses 7, 5
• Ejection fraction may improve to baseline after 2.5 months of therapy 5

Long-Term Monitoring

• Cardiac decompensation should be treated conventionally, but there is little evidence of reversibility in the anthracycline-induced myopathic process 4
• Long-term intermittent cardiac assessment is necessary 4

Oncology Consultation

• Modify chemotherapy regimen to remove doxorubicin—consider alternative non-anthracycline regimens 5

Monitoring Parameters

• Continuous monitoring of heart rate, rhythm, blood pressure, and oxygen saturation for at least the first 24 hours 1
• Evaluate dyspnea, orthopnea, and treatment-related adverse effects (symptomatic hypotension) 1
• Monitor urine output—target >15 mL/hour 4