What is the workup for suspected digoxin (digitalis glycoside) toxicity?

Workup of Suspected Digoxin Toxicity

The workup for suspected digoxin toxicity should include assessment of characteristic rhythm disturbances, ancillary symptoms, serum digoxin concentration, electrolytes (especially potassium), and renal function, with prompt administration of digoxin-specific antibody fragments (digoxin-Fab) for severe toxicity. 1

Clinical Presentation

• Typical arrhythmias suggestive of digoxin toxicity include enhanced atrial, junctional, or ventricular automaticity (with ectopic beats or tachycardia) often combined with atrioventricular block 1
• Ventricular tachycardia that is fascicular or bidirectional in origin is particularly suggestive of digoxin toxicity 1
• Severe digoxin overdose can cause hyperkalemia and cardiac standstill 1
• Ancillary symptoms include visual disturbances (blurred or yellow vision), nausea, vomiting, anorexia, changes in mentation (confusion, anxiety, depression, delirium, hallucination), and weakness 1, 2
• Gastrointestinal symptoms account for approximately one-fourth of adverse reactions, while CNS manifestations are less common 2

Diagnostic Workup

1. Serum Digoxin Concentration

   • Obtain serum digoxin level just before the next scheduled dose or at least 6-8 hours after the last dose 2
   • Therapeutic range: 0.5-1.0 ng/mL; toxicity often occurs at levels >2.0 ng/mL 2
   • Note that toxicity can occur even at therapeutic levels, especially with electrolyte abnormalities 2

2. Electrocardiogram (ECG)

   • Look for characteristic changes: PR prolongation, ST segment depression 2
   • Assess for arrhythmias: bradyarrhythmias, AV block, ventricular ectopy (especially bigeminy or trigeminy), ventricular tachycardia 2

3. Electrolyte Panel

   • Measure serum potassium, magnesium, and calcium 1
   • Hyperkalemia (>5.0 mEq/L) is a marker of severity in acute digoxin poisoning and is associated with poor prognosis 1
   • Hypokalemia and hypomagnesemia can sensitize the myocardium to digoxin and precipitate toxicity even at lower serum digoxin concentrations 2

4. Renal Function Tests

   • Assess serum creatinine and estimated glomerular filtration rate 2
   • Renal dysfunction is a common precipitating factor for digoxin toxicity due to reduced clearance 2, 3

5. Thyroid Function Tests

   • Consider checking thyroid function, as hypothyroidism may reduce digoxin requirements and predispose to toxicity 2

6. Medication Review

   • Evaluate for drug interactions that may increase digoxin levels (e.g., amiodarone, verapamil, quinidine, propafenone, erythromycin, clarithromycin) 2

Management Based on Severity

Mild Toxicity

• Discontinue digoxin 1
• Monitor cardiac rhythm 1
• Maintain normal serum potassium and magnesium levels 1

Moderate to Severe Toxicity

• For bradydysrhythmias: Consider atropine administration 1
• For ventricular dysrhythmias: Consider lidocaine or phenytoin until digoxin-Fab can be administered 1
• For recurrent torsades de pointes: Administer intravenous magnesium sulfate 1
• For bradycardia refractory to medical management: Consider temporary pacing 1

Life-Threatening Toxicity

• Administer digoxin-specific antibody fragments (digoxin-Fab) for severe toxicity, particularly with:

  • Serum digoxin concentrations exceeding 4 ng/mL 1
  • Serious arrhythmias such as ventricular tachycardia 1
  • Hyperkalemia >5.0 mEq/L in acute poisoning 1
  • Hemodynamic instability 1

• Dosing of digoxin-Fab:

  • If ingested dose is known: 2 vials for every milligram of digoxin ingested 1
  • For chronic toxicity or unknown ingestion: Calculate vials using formula: serum digoxin concentration (ng/mL) × weight (kg)/100 1
  • For critical cases requiring immediate treatment: Empirically administer 10-20 vials 1

Important Considerations

• Digoxin concentration monitoring becomes unreliable after antidigoxin antibody administration 1
• Response to digoxin-Fab is typically rapid (30 minutes to 4 hours) 1
• Hemodialysis, hemofiltration, hemoperfusion, or plasmapheresis are not recommended for digoxin toxicity 1
• Potentiating factors for toxicity include hypothyroidism, hypokalemia, hypomagnesemia, and renal dysfunction 1, 2
• Most cases of digoxin toxicity occur in elderly patients, with 88% of cases occurring in patients >65 years old 4

Follow-up After Treatment

• Monitor for rebound toxicity after digoxin-Fab administration 5
• Reassess the need for digoxin therapy before restarting 5
• If digoxin therapy is to be continued, address factors that contributed to toxicity (adjust dose, correct electrolytes, manage drug interactions) 3