38-33: Digitalis & Other Cardiac Glycosides Overdose

Cardiac glycosides paralyze the Na⁺-K⁺-ATPase pump and have potent vagotonic effects. Intracellular effects include enhancement of calcium-dependent contractility and shortening of the action potential duration. A number of plants (eg, oleander, foxglove, lily-of-the-valley) contain cardiac glycosides. Bufotenin, a cardiotoxic steroid found in certain toad secretions and used as an herbal medicine and a purported aphrodisiac, has pharmacologic properties similar to cardiac glycosides.

CLINICAL FINDINGS

Intoxication may result from acute single exposure or chronic accidental overmedication, especially in patients with kidney dysfunction taking digoxin. After acute overdosage, nausea and vomiting, bradycardia, hyperkalemia, and AV block frequently occur. Patients in whom toxicity develops gradually during long-term therapy may be hypokalemic and hypomagnesemic owing to concurrent diuretic treatment and more commonly present with ventricular arrhythmias (eg, ectopy, bidirectional ventricular tachycardia, or ventricular fibrillation). Digoxin levels may be only slightly elevated in patients with intoxication from cardiac glycosides other than digoxin because of limited cross-reactivity of immunologic tests.

TREATMENT

A. Emergency and Supportive Measures

After acute ingestion, administer activated charcoal. Monitor potassium levels and cardiac rhythm closely. Treat bradycardia initially with atropine (0.5–2 mg intravenously) or a transcutaneous external cardiac pacemaker.

B. Specific Treatment

For patients with significant intoxication, administer digoxin-specific antibodies (digoxin immune Fab [ovine]; DigiFab). Estimation of the dose is based on the body burden of digoxin calculated from the ingested dose or the steady-state serum digoxin concentration, as described below. More effective binding of digoxin may be achieved if the dose is given partly as a bolus and the remainder as an infusion over a few hours.

1. From the ingested dose

Number of vials = approximately 1.5–2 × ingested dose (mg).

2. From the serum concentration

Number of vials = serum digoxin (ng/mL) × body weight (kg) × 10^–2. Note: This is based on the equilibrium digoxin level; after acute overdose, serum levels may be falsely high for several hours before tissue distribution is complete, and overestimation of the DigiFab dose is likely.

3. Empiric dosing

Empiric titration of DigiFab may be used if the patient’s condition is relatively stable and an underlying condition (eg, atrial fibrillation) favors retaining a residual level of digitalis activity. Start with one or two vials and reassess the patient’s clinical condition after 20–30 minutes. For cardiac glycosides other than digoxin or digitoxin, there is no formula for estimation of vials needed and treatment is entirely based on response to empiric dosing.

Note: After administration of digoxin-specific Fab antibody fragments, serum digoxin levels may be falsely elevated depending on the assay technique.