What is the management of digitalis (digoxin) toxicity?

Management of Digoxin Toxicity

Immediately administer digoxin-specific Fab antibody fragments (Digibind) for any patient with life-threatening manifestations of digoxin toxicity, including sustained ventricular arrhythmias, ventricular fibrillation, progressive bradyarrhythmias, advanced AV block, asystole, or severe hyperkalemia (>6.0 mmol/L). 1, 2, 3

Initial Assessment and Severity Stratification

Recognize Life-Threatening Toxicity

• Life-threatening manifestations requiring immediate Fab therapy include: 1, 3
  • Sustained ventricular tachycardia or ventricular fibrillation
  • Progressive bradyarrhythmias or advanced AV block causing hemodynamic compromise
  • Asystole or cardiac arrest
  • Severe hyperkalemia (>6.0 mmol/L) in the setting of digoxin toxicity
  • Serum digoxin concentration >10 ng/mL (often results in cardiac arrest)
  • Ingestion of >10 mg in adults or >4 mg in children

Identify Characteristic Clinical Features

• Cardiac manifestations include enhanced atrial, junctional, or ventricular automaticity with ectopic beats or tachycardia, often combined with AV block—bidirectional or fascicular ventricular tachycardia is highly suggestive of digoxin toxicity 2
• Gastrointestinal symptoms include anorexia, nausea, and vomiting 2, 4
• Neurological symptoms include confusion, changes in mentation, and visual disturbances (blurred or yellow vision) 2
• Diagnosis requires the combination of characteristic arrhythmias, ancillary symptoms, and elevated serum digoxin levels (typically >2 ng/mL), though toxicity can occur even within the therapeutic range of 0.5-1.2 ng/mL 2, 4

Management Algorithm by Severity

Severe/Life-Threatening Toxicity

Administer digoxin-specific Fab antibody fragments immediately as first-line therapy—this is a Class I recommendation with Level of Evidence A. 1, 2, 3

• Response occurs within 30-45 minutes in most cases, with survival rates of 54% even in patients presenting with cardiac arrest 1, 2
• Do NOT delay Fab administration to correct electrolytes or attempt other temporizing measures in life-threatening scenarios 1, 2
• Avoid potassium supplementation in massive overdose with severe hyperkalemia—the potassium shift is due to Na-K-ATPase inhibition and will reverse with Fab therapy; giving potassium can be hazardous 3
• Treat acute life-threatening hyperkalemia with glucose and insulin if needed while preparing Fab 3

Mild to Moderate Toxicity

For patients without life-threatening manifestations: 1, 2, 3

1. Discontinue digoxin immediately and initiate continuous cardiac rhythm monitoring 1, 2, 3
2. Correct electrolyte abnormalities:
   • Restore serum potassium to >4.0 mmol/L, ideally 4.0-5.5 mmol/L, through oral or IV supplementation 1, 3
   • Correct hypomagnesemia 1, 3
   • Ensure adequate oxygenation 1
3. Monitor for 24-48 hours and recheck digoxin level to confirm declining trend 2

Specific Arrhythmia Management

For ventricular arrhythmias:

• Magnesium sulfate is reasonable as temporizing therapy (Class IIa recommendation) 1, 2
• Lidocaine, phenytoin, or bretylium may be reasonable only as temporizing measures until Fab can be administered 1
• Do NOT use lidocaine or phenytoin as primary therapy for severe toxicity (Class III recommendation) 1

For bradyarrhythmias:

• Atropine may be reasonable for symptomatic bradycardia (Class IIa recommendation) 1
• Temporary cardiac pacing may be reasonable for severe bradyarrhythmias or heart block, though complications occur in 36% of cases and higher-than-normal current may be required 1, 2
• Avoid potassium supplementation in patients with bradycardia or heart block unless primarily related to supraventricular tachycardia 3

Critical Management Pitfalls

What NOT to Do

• Do NOT use hemodialysis, hemofiltration, hemoperfusion, or plasmapheresis—digoxin has a large volume of distribution and is not effectively removed by these methods (Class III recommendation) 1
• Do NOT give potassium in massive overdose with severe hyperkalemia—this can be fatal 3
• Do NOT use lidocaine or phenytoin as primary therapy for severe toxicity 1

Special Considerations for Acute Massive Overdose

If ingestion occurred within 30 minutes: 3

• Administer large doses of activated charcoal to prevent absorption and bind digoxin during enteroenteric recirculation
• Consider gastric lavage only if very recent ingestion and patient is alert
• Do NOT induce emesis in obtunded patients or if >2 hours post-ingestion, as vagal stimulation can worsen arrhythmias

Post-Treatment Monitoring

After Fab Administration

• Monitor for rebound toxicity over 24-48 hours 2, 4
• Digoxin concentration monitoring becomes unreliable after Fab administration due to antibody interference 5, 2
• Watch for side effects of Fab therapy: 5, 2
  • Worsening heart failure (due to loss of inotropic effect)
  • Increased ventricular rate in atrial fibrillation
  • Paradoxical hypokalemia (as potassium shifts back intracellularly)

Reinitiating Digoxin Therapy

If digoxin must be restarted after toxicity resolves: 5, 2

• Use significantly lower doses: 0.125 mg daily or every other day for patients with risk factors 5, 2
• Target serum concentration of 0.5-0.9 ng/mL—levels >1.0 ng/mL are not associated with superior outcomes 6
• Avoid loading doses to minimize toxicity risk 5, 6
• Avoid concomitant medications that increase digoxin levels: amiodarone, clarithromycin, erythromycin, verapamil, quinidine, propafenone, dronedarone, itraconazole, cyclosporine 2

Risk Factors Requiring Enhanced Vigilance

Maintain heightened awareness in patients with: 2

• Advanced age (>70 years) or low lean body mass
• Renal dysfunction
• Hypokalemia, hypomagnesemia, or hypothyroidism
• Concomitant medications that increase digoxin levels

In these high-risk patients, maintain serum potassium >4.0 mmol/L (ideally 4.0-5.5 mmol/L) at all times to prevent toxicity. 1, 6, 3