How do you reverse diltiazem (Cardizem) overdose?

Management of Diltiazem (Cardizem) Overdose

Immediate supportive care with intravenous calcium, atropine for bradycardia, vasopressors (dopamine or norepinephrine), and cardiac pacing for refractory cases forms the cornerstone of diltiazem overdose management, with gastrointestinal decontamination if presenting early. 1

Initial Assessment and Stabilization

Expected Clinical Presentation

• Bradycardia (often junctional rhythm), hypotension, high-degree AV block, and cardiac failure are the primary manifestations of diltiazem toxicity 1, 2
• Symptoms typically manifest within 2-6 hours post-ingestion, particularly with sustained-release formulations 2, 3
• Multiorgan dysfunction (cardiac, neurologic, renal, hepatic) can occur in massive overdoses 3

Immediate Interventions

Gastrointestinal Decontamination:

• Administer activated charcoal if patient presents within 1-2 hours of ingestion 1, 2
• Consider gastric lavage for recent, large ingestions 1, 2
• Note: Charcoal hemoperfusion has shown limited efficacy in removing diltiazem, though it has been attempted in severe cases 3

Specific Pharmacologic Management

Bradycardia and AV Block

• First-line: Atropine 0.6-1.0 mg IV for bradycardia and heart block 1
• If no response to atropine, administer isoproterenol cautiously 1
• Cardiac pacing (transvenous or transcutaneous) for fixed high-degree AV block or refractory bradycardia 1, 4, 5
• Pacing has been frequently utilized and is often necessary for sustained bradycardia unresponsive to pharmacologic therapy 1, 6

Hypotension Management

• Intravenous fluids as initial resuscitation 1, 2
• Vasopressors: Dopamine or norepinephrine are recommended 1
• Phenylephrine may be particularly effective when other vasopressors fail, especially in combined overdoses 5
• Dosing should be titrated to achieve adequate mean arterial pressure 5

Calcium Administration

• Intravenous calcium is recommended despite inconsistent effectiveness 1
• Initial bolus: 1 g calcium chloride OR 3 g calcium gluconate IV over 5 minutes 1
• Repeat every 10-20 minutes as necessary 1
• Continuous infusion: 2 g calcium gluconate per hour for up to 10 hours (or longer, up to 24+ hours if needed) 1
• Monitor for hypercalcemia during prolonged infusions 1
• Some cases initially refractory to atropine became more responsive after calcium administration 1, 2

Cardiac Failure

• Inotropic agents: Isoproterenol, dopamine, or dobutamine 1
• Diuretics as adjunctive therapy 1
• Glucagon has been used successfully in some cases, though evidence is limited 2, 5

Advanced Interventions for Refractory Cases

Combination Therapy

• Norepinephrine + dobutamine + cardiac pacing has achieved control in severe cases with hemodynamic compromise 4
• Multiple agents are often required simultaneously for adequate hemodynamic support 5

Extracorporeal Support

• Extracorporeal membrane oxygenation (ECMO) may be lifesaving in massive overdoses with refractory cardiac arrest 3
• Consider early in cases with multiple asystolic arrests unresponsive to high-dose epinephrine 3
• Recovery is possible even after 48 hours of ECMO support 3

Critical Pitfalls to Avoid

• Do not rely on blood levels for management decisions—diltiazem undergoes extensive metabolism with over 10-fold variation in levels after standard dosing 1
• Peritoneal dialysis and hemodialysis are ineffective for diltiazem removal 1
• Plasmapheresis or charcoal hemoperfusion may hasten elimination but have shown limited sustained benefit 1, 3
• Do not delay cardiac pacing in high-degree AV block—it is often essential for survival 1, 4, 6
• Prolonged half-life (8.6-48 hours) in overdose means toxicity can persist for days, requiring extended monitoring and support 3, 6

Monitoring Requirements

• Continuous cardiac monitoring for rhythm disturbances 1
• Serial vital signs (blood pressure, heart rate) 2
• Serum calcium levels during calcium infusions to detect hypercalcemia 1
• Invasive hemodynamic monitoring (pulmonary artery catheter) may be important in severe cases 4
• Urine output monitoring for oliguria 5
• Most patients who recover do so within 48 hours, though severe cases may require 9+ days for return of normal sinus rhythm 2, 3

Prognosis

• Recovery is possible even after massive ingestions (up to 12 g reported) with aggressive supportive care 3
• Toxic effects are reversible with appropriate cardiovascular support 3
• Most patients with known outcomes have recovered, though fatalities typically involve multiple drug ingestions 1
• Sinus rhythm typically returns when plasma diltiazem concentrations fall to therapeutic or near-therapeutic levels 6