Digitalis Toxicity

Essentials of Diagnosis

• Intoxication may result from

  • Acute single exposure

  • Chronic accumulation from accidental overmedication, especially in patients with kidney disease taking digoxin

• Hyperkalemia common after acute overdose

• Many different arrhythmias can occur

General Considerations

• Cardiac glycosides paralyze the Na⁺-K⁺-ATPase pump and have potent vagotonic effects

• Intracellular effects

  • Enhancement of calcium-dependent contractility

  • Shortening of the action potential duration

• Older age and chronic kidney disease are associated with greater risk of digoxin toxicity

Symptoms and Signs

Acute overdose

• Nausea and vomiting

• Bradycardia

• Atrioventricular (AV) block

• Junctional rhythm common in patients with underlying atrial fibrillation

• Hyperkalemia

Chronic overingestion

• Hypokalemia and hypomagnesia are more likely owing to concurrent diuretic treatment

• Ventricular arrhythmias; for example

  • Ectopy

  • Bidirectional ventricular tachycardia

  • Ventricular fibrillation

Differential Diagnosis

• Beta-blocker overdose

• Calcium channel blocker overdose

• Cardiotoxic plant or animal ingestion

  • Oleander

  • Foxglove

  • Lily of the valley

Laboratory Tests

• Serum digoxin level (Note: Levels drawn within 6 h of ingestion may be falsely elevated before complete tissue distribution)

• Serum potassium (frequent measures useful because they correlate with tissue effects)

Diagnostic Procedures

• Continuous ECG monitoring

• Pacemaker may be needed

Medications

Emergency measures

• Ventricular arrhythmias: initially lidocaine, 2–3 mg/kg intravenously, or phenytoin, 10–15 mg/kg intravenously slowly over 30 min if digoxin-specific antibodies are not immediately available (see below)

• Bradycardia: initially atropine, 0.5–2.0 mg intravenously, or transcutaneous external cardiac pacemaker

Gut decontamination

• After acute overdose, administer activated charcoal, 60–100 g orally or via gastric tube, mixed in aqueous slurry

• Emesis not recommended because it may enhance vagotonic effects (eg, bradycardia, AV block)

Activated charcoal

• Repeated doses of activated charcoal, 20–30 g every 3–4 hours, may speed elimination of digitoxin (but not digoxin) by adsorbing drug excreted into gut lumen (gut dialysis)

• Sorbitol or other cathartics should not be used with each dose; resulting large stool volumes may lead to dehydration or hypernatremia

Specific treatment

• Severe intoxication: administer digoxin-specific antibodies [digoxin immune Fab (ovine) DigiFab]

• Dose is estimated based on body burden of digoxin calculated from ingested dose or steady-state serum digoxin concentration

  • Ingested dose

    • Number of vials = ~1.5–2 × ingested dose (mg)

  • Serum concentration

    • Number of vials = serum digoxin (ng/mL) × body weight (kg) × 10^–2

    • Note: This is based on equilibrium digoxin level; after acute overdose, serum levels are falsely high for several hours before tissue distribution is complete, and overestimation of DigiFab dose is likely

  • 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

• Empiric titration of DigiFab

  • May be used if 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 clinical condition after 20–30 min

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

Follow-Up

• Monitor potassium levels and cardiac rhythm closely

Complications

• Cardiac arrest

Prevention

• Monitor kidney function in elderly patients and obtain serum digoxin levels if symptoms of digoxin toxicity