Digitalis Toxicity

Key Features

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

• 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

Symptoms and Signs

Acute overdose

• Nausea and vomiting

• Bradycardia

• Atrioventricular (AV) block

• Hyperkalemia

Chronic overingestion

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

• Ventricular arrhythmias; for example

  • Ectopy

  • Bidirectional ventricular tachycardia

  • Ventricular fibrillation

Diagnosis

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

Treatment

• After acute ingestion

  • Administer activated charcoal

    • Dose: 60–100 g orally or via gastric tube, mixed in aqueous slurry; repeated doses may be given

    • Do not use for comatose or convulsing patients unless it can be given by gastric tube and the airway is protected by cuffed endotracheal tube

  • Monitor potassium levels and cardiac rhythm closely

  • Treat bradycardia initially with atropine (0.5–2 mg intravenously) or a transcutaneous external cardiac pacemaker

• 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 ...