Approach
The main goal of treatment is to correct cardiac toxicity. Treatment of cardiac toxicity usually leads to resolution of central nervous system and gastrointestinal (GI) symptoms.
Initial treatment includes:
General supportive care
Discontinuation of digoxin therapy and prevention of further exposure
Prevention of further GI absorption
Administration of digoxin-specific antibody fragments (digoxin immune Fab)
Treatment of specific complications: for example, dysrhythmias and electrolyte abnormalities
Treatment of chronic toxicity is based on a clinical syndrome, not the serum digoxin concentration, which might be just above the therapeutic range. If a serum digoxin concentration cannot be obtained, patients are managed based on their presentation, ECG findings, and laboratory results. If toxicity is suspected and the patient is unstable, antidotal therapy is administered prior to confirmatory results. For patients with chronic digitalis poisoning, therapy may require only a few Fab vials. There is no change in therapy for renal failure other than to note that the elimination half-life of digoxin is prolonged in patients with renal failure.
Supportive care
General supportive care includes attaching patients to a cardiac monitor, providing intravenous fluids in patients with hypotension or volume depletion (with caution for patients with congestive heart failure), supplemental oxygen, and/or repletion of electrolytes in patients with electrolyte abnormalities.
Digoxin binding therapy
Digoxin binding (with digoxin immune Fab) is used in patients with the following features:
Severe toxicity or hemodynamic compromise
Symptomatic bradyarrhythmias
Ventricular dysrhythmias
Any patient with digoxin overdose and potassium concentrations >5.0 mEq/L
Acute ingestion of >4 mg in a healthy child (or 0.1 mg/kg)
Acute ingestion of >10 mg in a healthy adult
Serum concentration of ≥10 nanograms/mL 4-6 hours after ingestion (steady state)
Serum concentration of ≥15 nanograms/mL at any time
If indicated, 15 vials of Fab is the quantity typically needed to treat one patient.[27] One study suggests 1-2 vials administered in a stepwise fashion based on clinical response.[28] Patients who receive digoxin immune Fab have a drop in the serum potassium as it moves intracellularly.[29][30][31] Some patients who have been treated for hyperkalemia and who have also received digoxin immune Fab develop profound hypokalemia. Therefore, serial potassium measurements are made when patients receive both digoxin immune Fab and other therapies to decrease potassium.[32]
After administration of digoxin immune Fab, serum digoxin concentrations are usually falsely elevated (10- to 30-fold). Serum digoxin concentration can be measured again 3-4 days after the dose is given, but has been reported to be elevated for up to 10 days, especially in patients with renal insufficiency.[33][34][35] In certain patients with chronic digoxin toxicity, supportive case is suggested to have similar outcomes to digoxin Fab.[36]
Management of electrolyte abnormalities
In patients with chronic digoxin toxicity, hyperkalemia is only corrected (e.g., with insulin/glucose) if it is considered life-threatening, because of the risk of producing hypokalemia. One study showed that insulin interacts directly with Na+/K+ ATPase pumps and alters the effect of digoxin.[37] This supports the finding that for patients with diabetes, insulin does not have cardioprotective effects after digoxin intoxication. Calcium is not used to treat hyperkalemia in patients with suspected digoxin toxicity as it may induce arrhythmia or cardiac arrest.
Patients with acute digoxin toxicity and serum potassium concentrations ≥5.0 mEq/L are treated with digoxin immune Fab; those with hyperkalemia have high mortality rates.
Patients with hypokalemia or hypomagnesemia require additional potassium or magnesium with careful monitoring to restore normal serum levels.
GI decontamination
There is a role for GI decontamination with activated charcoal in patients with an acute ingestion of digoxin with low to moderate toxicity.[38][39][40] The primary goal of activated charcoal is to decrease GI absorption of the drug.[39][40]
Bradycardia management
If digoxin-binding therapy is not immediately available patients with symptomatic bradycardia can be treated with atropine.[32] In adults, atropine can be given every 3-5 minutes until there is a response or the 3-mg maximum dose is reached. Pediatric patients with symptomatic bradycardia require lower doses of atropine. Alternatively, a temporary pacing wire can be inserted in patients with evidence of significant bradycardia or atrioventricular (AV) block and hemodynamic compromise if digoxin-specific antibody (Fab) fragments are not readily available.
Tachyarrhythmia management
Type IB anti-arrhythmics (e.g., phenytoin, lidocaine) can be used if digoxin immune Fab is unavailable or is being prepared and patients have rapid ventricular dysrhythmias unresponsive to supportive measures.
Transthoracic electrical cardioversion for atrial tachyarrhythmias is associated with the development of lethal ventricular dysrhythmias, so is not used.[41]
Overdrive suppression with a transvenous pacemaker is also avoided because of associated iatrogenic complications that have been seen in as many as 36% of patients.[42][43]
Patients with ventricular fibrillation or pulseless ventricular tachycardia require defibrillation along with immunotherapy.
Hemodynamic compromise management
In patients with signs of hemodynamic insufficiency and/or compromise (e.g., hypotension, altered consciousness), digoxin immune Fab is given as primary management. As a bridge to the administration of digoxin immune Fab, intravenous fluids and direct-acting vasopressors (e.g., phenylephrine, norepinephrine) are used. Cardiac contractility (inotropy) is typically preserved in patients with digoxin toxicity. Alternatively, a temporary pacing wire can be inserted in patients with evidence of significant bradycardia or AV block and hemodynamic compromise if digoxin-specific antibody (Fab) fragments are not readily available.
Ongoing monitoring and change of medication
Ideally, digoxin is discontinued and a different medication for rate control or a different inotrope prescribed (for atrial fibrillation, atrial flutter or CHF, respectively). If the patient has to remain on digoxin for some reason, then the dose of digoxin is adjusted for the patient's medication profile. Glomerular filtration rate and serum digoxin concentration is monitored regularly (every 2-4 weeks).
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