What is the recommended antidote for a patient with digoxin toxicity?

Digoxin Antidote

Digoxin-specific antibody fragments (digoxin-Fab) are the definitive antidote for digoxin toxicity and should be administered immediately in patients with life-threatening manifestations. 1

Primary Antidote: Digoxin-Fab

The American Heart Association gives a Class 1 (strongest) recommendation for administering digoxin-Fab in digoxin or digitoxin poisoning. 1 This represents the highest level of guideline support for any intervention in digoxin toxicity.

Mechanism and Efficacy

• Digoxin-Fab is a monovalent immunoglobulin that rapidly binds to intravascular digoxin, with clinical response rates of 80-90% in acute settings 1
• Dysrhythmia resolution typically occurs within 30-45 minutes of administration 1
• Each 40 mg vial binds approximately 0.5 mg of digoxin 1
• In observational studies of cardiac arrest from digoxin poisoning, survival was 54% (30 of 56 patients) with digoxin-Fab treatment 1

Specific Indications for Digoxin-Fab

Administer digoxin-Fab immediately for: 2

• Life-threatening tachyarrhythmias or bradyarrhythmias
• Serum digoxin concentrations exceeding 4 ng/mL
• Hyperkalemia >5.0 mEq/L (particularly >6 mmol/L) 3, 2
• Hemodynamic instability
• Ventricular tachycardia, ventricular fibrillation, high-degree AV block, or sinus arrest 4

Dosing Strategies

For acute life-threatening toxicity requiring immediate treatment: 2

• Administer 10-20 vials (400-800 mg) empirically when calculation is not feasible

For acute poisoning with known ingestion: 3

• Give 80 mg bolus initially, repeated as required based on clinical response
• Most patients require less than half the calculated neutralizing dose with this approach
• This strategy is more cost-effective than full calculated doses

For chronic toxicity: 3, 2

• Start with 40 mg (1 vial) and repeat after 60 minutes if symptoms persist
• Typically 40-120 mg (1-3 vials) is sufficient
• Give sooner if patient is clinically unstable

Administration Details

• Infuse over at least 30 minutes after dilution 4
• Repeat dosing may be necessary, particularly in chronic use due to large volume of distribution 1
• Response is typically rapid, occurring within 30 minutes to 4 hours 2

Adjunctive Therapies (Temporizing Measures)

For Bradydysrhythmias

Atropine may be reasonable as a temporizing measure for bradydysrhythmias while awaiting digoxin-Fab administration 1, 4. However, evidence is limited to case reports with variable effects 1.

Temporary cardiac pacing may be reasonable for refractory bradydysrhythmias 1, though complications are common (36% in one series) 1.

For Ventricular Dysrhythmias

Lidocaine, phenytoin, or bretylium may be reasonable to treat ventricular dysrhythmias until digoxin-Fab can be administered 1, 4.

Electrolyte Management

• Correct hypokalemia to maintain serum potassium between 4.0-5.5 mmol/L 4
• Avoid potassium supplementation in patients with bradycardia or heart block 4
• In acute massive overdose with hyperkalemia, do NOT give potassium - the hyperkalemia results from skeletal muscle potassium release and will resolve with digoxin-Fab 4
• Monitor for hypokalemia after digoxin-Fab administration 1

Ineffective Interventions

The American Heart Association gives a Class 3 (harm/no benefit) recommendation against hemodialysis, hemofiltration, hemoperfusion, or plasmapheresis for digoxin removal 1. Digoxin has a large extravascular volume of distribution (5-10 L/kg) making dialysis ineffective 4, 3.

Critical Pitfalls to Avoid

• Do not delay digoxin-Fab administration in life-threatening toxicity while calculating exact doses - give empiric doses immediately 2
• Digoxin concentration monitoring becomes unreliable after digoxin-Fab administration 2
• Avoid full calculated neutralizing doses in most cases - they are expensive and often unnecessary; titrate to clinical effect instead 3
• Monitor potassium levels closely both before and after digoxin-Fab administration, as levels can shift dramatically 1, 4
• Activated charcoal should be given in acute ingestions regardless of time since ingestion, as digoxin undergoes enterohepatic recirculation 4

Broader Applicability

Digoxin-Fab is also reasonable for poisoning from related cardiac glycosides including yellow oleander and Bufo toad venom 1, with similar efficacy demonstrated in observational studies 1.