What is the management of digoxin toxicity?

Management of Digoxin Toxicity

For mild digoxin toxicity, immediately discontinue the medication, monitor cardiac rhythm continuously, and correct electrolyte abnormalities (targeting potassium 4.0-5.5 mEq/L); for severe toxicity with life-threatening arrhythmias, hyperkalemia, or hemodynamic compromise, administer digoxin-specific Fab antibody fragments immediately as first-line therapy. 1, 2

Severity Stratification and Initial Actions

Mild Toxicity

• Discontinue digoxin immediately and initiate continuous cardiac monitoring for at least 24-48 hours 1
• Restore serum potassium to >4.0 mEq/L, ideally 4.0-5.5 mEq/L, through oral or intravenous supplementation 1, 2
• Correct hypomagnesemia and ensure adequate oxygenation 1
• Monitor for characteristic arrhythmias including enhanced atrial, junctional, or ventricular automaticity with atrioventricular block 1
• Recheck digoxin level in 24-48 hours to confirm declining trend 1

Severe/Life-Threatening Toxicity Indicators

• Sustained ventricular arrhythmias or ventricular fibrillation 1
• Progressive bradyarrhythmias or advanced AV block causing hemodynamic compromise 1
• Asystole or cardiac standstill 1
• Severe hyperkalemia (from massive shift of potassium from intracellular to extracellular space) 1, 3
• Serum digoxin concentrations >4 ng/mL 1
• Ingestion of >10 mg in adults or >4 mg in children 3
• Steady-state serum concentration >10 ng/mL 3

Definitive Treatment: Digoxin-Specific Fab Antibodies

Administer digoxin-specific Fab antibody fragments immediately for any life-threatening manifestation (Class I recommendation, Level of Evidence A) 1, 2

Fab Administration Details

• Response typically occurs within 30 minutes to 4 hours 1
• Survival rate of 54% even in severely intoxicated patients presenting with cardiac arrest 1
• Critical caveat: Digoxin concentration monitoring becomes unreliable after Fab administration 1, 2
• Monitor for Fab-related side effects: worsening heart failure, increased ventricular rate in atrial fibrillation, and paradoxical hypokalemia 2
• Longer observation period required in renal dysfunction due to increased risk of rebound toxicity 1

Adjunctive Therapies

For Ventricular Arrhythmias

• Intravenous magnesium sulfate is reasonable (Class IIa recommendation) 1
• DO NOT use lidocaine or phenytoin for severe digoxin toxicity (Class III recommendation) 1, 2

For Bradyarrhythmias/Heart Block

• Temporary cardiac pacing is reasonable for symptomatic bradyarrhythmias or heart block 1
• Consider atropine for symptomatic bradycardia 3

Electrolyte Management

• Maintain serum potassium between 4.0-5.5 mEq/L 1, 2, 3
• Potassium can be administered orally or, when urgent, cautiously by IV route with continuous ECG monitoring for potassium toxicity (peaking T waves) 3
• Critical warning: Potassium salts are dangerous in bradycardia/heart block and in massive overdose with hyperkalemia 3
• In massive intoxication with hyperkalemia, avoid potassium supplementation—treat with Fab antibodies first, with glucose and insulin if acutely life-threatening 3

Gastrointestinal Decontamination (Acute Overdose)

• Administer large doses of activated charcoal to prevent absorption and bind digoxin during enteroenteric recirculation 3
• Consider emesis or gastric lavage if ingestion occurred within 30 minutes 3
• Do not induce emesis in obtunded patients or if >2 hours post-ingestion with toxic manifestations (risk of vagal episode worsening arrhythmias) 3

Ineffective Treatments

Hemodialysis, hemofiltration, hemoperfusion, and plasmapheresis are NOT recommended for digoxin removal due to large volume of distribution and extensive tissue binding 1, 2. The exception is life-threatening hyperkalemia in massive overdose when Fab is unavailable 1. Even continuous venovenous hemodialysis and peritoneal dialysis show minimal efficacy for digoxin clearance 4, 5, 6.

Reinitiating Digoxin Therapy

If digoxin must be restarted after toxicity resolves:

• Use significantly lower maintenance doses (0.125 mg daily or every other day) 1, 2
• Target serum concentration of 0.5-0.9 ng/mL (levels >1.0 ng/mL not associated with superior outcomes) 1, 2
• Avoid loading doses to minimize toxicity risk 1, 2
• Perform careful reassessment of dose and contributing factors 3

High-Risk Populations Requiring Extra Vigilance

• Advanced age (>70 years) and low lean body mass 1
• Renal dysfunction (digoxin is 50-70% renally eliminated) 1, 7
• Hypokalemia, hypomagnesemia, or hypothyroidism 1
• Concomitant medications: amiodarone, clarithromycin, erythromycin, itraconazole, cyclosporine, verapamil, quinidine, propafenone, dronedarone 1

Diagnostic Confirmation

Diagnosis requires the combination of:

• Characteristic arrhythmias (bidirectional or fascicular VT highly suggestive) 1
• Gastrointestinal symptoms (anorexia, nausea, vomiting) 1
• Neurological symptoms (confusion, visual disturbances including blurred or yellow vision) 1
• Elevated serum digoxin concentration, typically >2 ng/mL 1

Important caveat: Toxicity can occur even within therapeutic range (0.5-1.2 ng/mL) in the presence of risk factors 1