From the Guidelines
Management of digitalis (digoxin) toxicity requires prompt administration of digoxin-specific antibody fragments (Digibind or DigiFab) for moderate to severe toxicity, as recommended by the 2023 American Heart Association guidelines 1.
Pathophysiology and Clinical Presentation
Digitalis toxicity can cause severe bradycardia and life-threatening arrhythmias, including ventricular tachycardia, ventricular fibrillation, and high degrees of AV nodal blockade, as noted in the 2010 American Heart Association guidelines 1. Other symptoms may include nausea, vomiting, visual disturbances, and neurological complaints.
Treatment Approach
- For mild toxicity with minimal symptoms, discontinuing digoxin and monitoring may be sufficient.
- For moderate to severe toxicity, administration of digoxin-specific antibody fragments (Digibind or DigiFab) is the cornerstone of treatment, with a typical dose calculated based on the amount of digoxin ingested or the serum digoxin level.
- Supportive care includes correcting electrolyte abnormalities, particularly potassium, as hyperkalemia indicates severe toxicity and hypokalemia can worsen digoxin effects.
- Cardiac monitoring is essential, with specific treatments for arrhythmias including atropine for bradycardia, phenytoin or lidocaine for ventricular arrhythmias, and magnesium sulfate for refractory ventricular arrhythmias.
- Avoid calcium administration as it can worsen digitalis-induced arrhythmias, as cautioned in the 2006 ACC/AHA/ESC guidelines 1.
- Hemodialysis is ineffective for removing digoxin due to its large volume of distribution.
Prevention Strategies
- Regular monitoring of digoxin levels (therapeutic range 0.8-2.0 ng/mL) is crucial.
- Renal function assessment and awareness of drug interactions that increase digoxin levels, such as amiodarone, verapamil, and clarithromycin, are also important.
- The 2009 ACCF/AHA guidelines highlight the need for careful consideration of digoxin therapy in patients with heart failure, particularly in the elderly and those with impaired renal function 1.
Key Recommendations
- Administration of digoxin-specific antibody fragments (Digibind or DigiFab) is recommended for patients with severe life-threatening cardiac glycoside toxicity 1.
- Monitoring of serum potassium levels is essential, as hyperkalemia is a marker of severity in acute cardiac glycoside poisoning 1.
From the FDA Drug Label
However, asymptomatic bradycardia or heart block related to digoxin may require only temporary withdrawal of the drug and cardiac monitoring of the patient. If the rhythm disturbance is a ventricular arrhythmia, consideration should be given to the correction of electrolyte disorders, particularly if hypokalemia (see Administration of Potassium subsection) or hypomagnesemia is present DIGIBIND is a specific antidote for digoxin and may be used to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage. The administration of more than 10 mg of digoxin in a previously healthy adult, or more than 4 mg in a previously healthy child, or a steady-state serum concentration greater than 10 ng/mL often results in cardiac arrest. Massive Digitalis Overdosage: DIGIBIND should be used to reverse the toxic effects of ingestion of a massive overdose Severe digitalis intoxication can cause a massive shift of potassium from inside to outside the cell, leading to life-threatening hyperkalemia. The administration of potassium supplements in the setting of massive intoxication may be hazardous and should be avoided Hyperkalemia caused be massive digitalis toxicity is best treated with DIGIBIND; initial treatment with glucose and insulin may also be required if hyperkalemia itself is acutely life-threatening.
The management of digitalis (digoxin) toxicity involves:
- Temporary withdrawal of the drug and cardiac monitoring for asymptomatic bradycardia or heart block
- Correction of electrolyte disorders, particularly hypokalemia or hypomagnesemia, for ventricular arrhythmias
- Administration of DIGIBIND, a specific antidote, to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage
- Avoidance of potassium supplements in the setting of massive intoxication, as they may be hazardous
- Treatment of hyperkalemia with DIGIBIND, and initial treatment with glucose and insulin if hyperkalemia is acutely life-threatening 2 2 Key considerations:
- Maintain serum potassium concentration between 4.0 and 5.5 mmol/L
- Monitor electrocardiogram for evidence of potassium toxicity and to observe the effect on the arrhythmia
- Use activated charcoal to prevent absorption and bind digoxin in the gut during enteroenteric recirculation in cases of massive digitalis ingestion
From the Research
Digitalis Toxicity Pathophysiology
- Digitalis toxicity occurs when there is an excessive amount of digitalis in the body, leading to inhibition of Na⁺/K⁺ ATPase 3
- This inhibition can cause a range of symptoms, including gastrointestinal, central nervous, and cardiac conduction system disturbances 4
- The therapeutic index of digitalis is narrow, making it easy to overdose and cause toxicity 3, 5
Management of Digitalis Toxicity
- Treatment of digitalis toxicity is mainly supportive, except in acute poisoning, where attempts are made to clear the drug from the gastrointestinal tract 4
- Digoxin-specific antibody fragments (digoxin-Fab) are a safe and effective treatment for acute and chronic digoxin poisoning 3, 6
- The dosage of digoxin-Fab is calculated to be equimolar to the amount of cardiac glycoside in the patient's body, but full neutralizing doses may not be required 3
- In acute poisoning, a small bolus of 80 mg digoxin-Fab, repeated if necessary, titrated against clinical effect, is likely to achieve equivalent benefits with much lower total doses 3
- Activated charcoal may be useful in treating patients with digitoxin toxicity, especially those with renal dysfunction 7
Indications for Digoxin-Fab
- Patients with life-threatening tachy-bradyarrhythmias, hyperkalaemia (> 6 mmol/L), or haemodynamic instability with an elevated digoxin concentration (> 2 μg/L or 2.6 nmol/L) should be treated with digoxin-Fab 3
- Digoxin-Fab is safe and indicated in all patients with life-threatening arrhythmias and an elevated digoxin concentration 3, 6