How should an acute dipyridamole (Dipyridilium) overdose be managed in the emergency department?

Management of Acute Dipyridamole Overdose in the Emergency Department

Acute dipyridamole overdose should be managed with immediate hemodynamic support using intravenous aminophylline (50-240 mg IV) to reverse vasodilation and hypotension, along with aggressive fluid resuscitation and vasopressors if needed, while activated charcoal and gastric lavage have limited utility given dipyridamole's high protein binding. 1, 2

Immediate Assessment and Stabilization

Airway and Breathing

• Secure the airway immediately if the patient is unresponsive or has respiratory compromise, as severe dipyridamole overdose can progress to respiratory arrest requiring intubation and mechanical ventilation 3
• Assess for concurrent ingestions, particularly benzodiazepines or other CNS depressants, which frequently accompany dipyridamole overdose 4

Hemodynamic Monitoring

• Expect profound hypotension and tachycardia as the primary manifestations of toxicity, resulting from peripheral vasodilation 1, 2
• Monitor continuously for cardiovascular collapse, which can occur rapidly and may require aggressive intervention with fluids and vasopressors (norepinephrine) 3
• Anticipate potential progression to cardiogenic shock in massive overdoses (>5 g), which may require inotropic support 5

Specific Antidotal Therapy

Aminophylline Administration

• Administer aminophylline 50-240 mg IV as the primary antidote to reverse dipyridamole's hemodynamic effects, including vasodilation, hypotension, and tachycardia 1, 2
• Aminophylline (a xanthine derivative) competitively antagonizes dipyridamole's adenosine-mediated vasodilation 1
• The usual dose of aminophylline (50-240 mg) has successfully reversed toxicity even in the highest reported overdose of 1,750 mg dipyridamole 2
• Repeat aminophylline dosing may be necessary given dipyridamole's prolonged half-life and high protein binding 1

Supportive Care

Fluid Resuscitation and Vasopressors

• Initiate aggressive IV fluid resuscitation with normal saline for hypotension 3
• If hypotension persists despite fluids and aminophylline, start norepinephrine infusion titrated to maintain adequate perfusion pressure 3
• Avoid relying solely on vasopressors without first administering aminophylline, as the specific reversal agent addresses the underlying mechanism 1, 2

Gastrointestinal Decontamination

• Gastric lavage should be considered only if the patient presents within 1 hour of ingestion and has ingested a potentially life-threatening dose 1
• Activated charcoal may be administered if the patient presents early, though its benefit is limited because dipyridamole is highly protein-bound (91-99%) 1, 4
• Dialysis is not beneficial and should not be attempted, as dipyridamole's high protein binding prevents effective removal 1

Monitoring for Complications

Cardiovascular Complications

• Monitor for acute myocardial infarction, which has occurred in severe overdoses due to prolonged hypotension and coronary steal phenomenon 3
• Obtain serial ECGs and cardiac biomarkers if chest pain develops or hypotension is prolonged 3

Renal Complications

• Anticipate acute tubular necrosis and renal failure requiring hemodialysis in cases with prolonged hypotension (>several hours) 3
• Monitor urine output, serum creatinine, and electrolytes closely for 48-72 hours 3

Multi-Organ Failure

• In massive overdoses (>10 g), be prepared for multi-organ failure including bowel ischemia requiring surgical intervention, particularly if hypotension is severe and prolonged 5
• Consider early ICU admission for patients with ingestions >5 g or those requiring vasopressor support 5

Clinical Pearls and Pitfalls

Unique Diagnostic Clue

• Intense neon-yellow discoloration of skin and urine is pathognomonic for massive dipyridamole overdose and can aid diagnosis when history is unclear 3
• This yellow color results from the drug's inherent pigmentation and indicates very high serum concentrations 3

Pharmacodynamic Effects

• Peak serum concentrations may reach 9.2 mg/L in severe overdoses (therapeutic range: 0.5-2.0 mg/L), with corresponding impaired platelet activation 4
• Symptoms typically resolve within 17 hours with appropriate treatment, though renal complications may persist for weeks 4, 3

Common Pitfalls to Avoid

• Do not delay aminophylline administration while attempting gastrointestinal decontamination, as hemodynamic reversal is the priority 1, 2
• Do not assume dialysis will be helpful; it is ineffective due to high protein binding and should not delay definitive supportive care 1
• Do not discharge patients with significant ingestions (>400 mg) without extended observation (minimum 12-24 hours), as delayed cardiovascular collapse can occur 5, 3

Observation Period

• Observe all symptomatic patients for at least 12-24 hours after the last dose of aminophylline to ensure hemodynamic stability 4, 3
• Patients with minor symptoms from ingestions <400 mg may be observed for 6-8 hours and discharged if asymptomatic 1, 2