What are the symptoms, diagnosis, and management of digoxin (digitalis glycoside) toxicity?

Digoxin Toxicity: Symptoms, Diagnosis, and Management

Digoxin toxicity requires prompt recognition and treatment with digoxin-specific antibody fragments (digoxin-Fab) for patients with severe symptoms or hemodynamic compromise. 1

Clinical Presentation

Symptoms and Signs

• Cardiac manifestations:

  • Arrhythmias (most common and dangerous manifestation)
    • Bradyarrhythmias: Sinus bradycardia, AV blocks (first to third degree)
    • Tachyarrhythmias: Atrial tachycardia with block, junctional tachycardia
    • Ventricular arrhythmias: Premature ventricular contractions (especially bigeminy/trigeminy), ventricular tachycardia, ventricular fibrillation 2
  • Characteristic arrhythmia: Bidirectional or fascicular ventricular tachycardia (highly suggestive of digoxin toxicity) 1

• Gastrointestinal manifestations:

  • Anorexia, nausea, vomiting, diarrhea (common early symptoms) 2, 3
  • Abdominal pain (less common)

• Neurological manifestations:

  • Visual disturbances (blurred or yellow vision - classic finding)
  • Headache, weakness, dizziness
  • Confusion, apathy, delirium, hallucinations 2

Risk Factors

• Advanced age (elderly patients)
• Renal dysfunction (impaired clearance)
• Hypokalemia, hypomagnesemia, hypercalcemia
• Hypothyroidism
• Drug interactions (amiodarone, verapamil, diltiazem, certain antibiotics, quinidine) 4
• Serum digoxin levels >2.0 ng/mL (toxicity can occur even at therapeutic levels) 5

Diagnosis

Laboratory Assessment

1. Serum digoxin concentration:

   • Levels >2.0 ng/mL often associated with toxicity
   • Levels >4.0 ng/mL indicate severe toxicity requiring immediate treatment 1
   • Note: Samples should be drawn at least 6-8 hours after the last dose

2. Electrolytes:

   • Potassium (hyperkalemia is a concerning sign in acute toxicity)
   • Magnesium and calcium levels
   • Renal function (BUN, creatinine)

3. ECG findings:

   • PR prolongation, ST depression (may be present even without toxicity)
   • Bradyarrhythmias or heart blocks
   • Atrial tachycardia with block
   • Accelerated junctional rhythm
   • Ventricular ectopy, especially bigeminy or trigeminy 1

Management

Immediate Interventions

1. Discontinue digoxin in all cases of suspected toxicity 1

2. Administer digoxin-specific antibody fragments (digoxin-Fab):

   • Strong indication (Class I recommendation): 1

     • Life-threatening arrhythmias
     • Hemodynamic instability
     • Serum digoxin concentration >4 ng/mL with serious arrhythmias
     • Severe hyperkalemia (>5.5 mEq/L) in acute toxicity

   • Dosing based on:

     • Amount ingested (in acute overdose)
     • Serum digoxin concentration (when available)
     • Clinical response typically occurs within 30-45 minutes 1
     • Response rates of 50-90% reported 1, 6

3. Correct electrolyte abnormalities:

   • Replete potassium to ≥4.0 mmol/L
   • Replete magnesium to normal values (≥2.0 mmol/L) 1

4. Cardiac monitoring for all patients with suspected toxicity

Management of Specific Arrhythmias

1. For bradyarrhythmias:

   • Atropine may be reasonable (Class IIb recommendation) 1
   • Temporary pacing if unresponsive to medical therapy (Class IIb recommendation) 1

2. For ventricular arrhythmias:

   • Lidocaine, phenytoin, or bretylium may be reasonable until digoxin-Fab can be administered (Class IIb recommendation) 1
   • Avoid cardioversion if possible (may precipitate refractory ventricular fibrillation)

3. For torsades de pointes:

   • IV magnesium sulfate
   • Temporary pacing or isoproterenol to increase heart rate 1

Ineffective Treatments

• Hemodialysis, hemofiltration, hemoperfusion, or plasmapheresis are not recommended for digoxin toxicity (Class III: No Benefit) 1

Post-Treatment Monitoring

• Continue cardiac monitoring for 24-48 hours after digoxin-Fab administration
• Monitor for rebound toxicity (rare but possible) 3
• Serum digoxin levels become unreliable after digoxin-Fab administration 1
• Reassess need for digoxin therapy before restarting

Special Considerations

• In children: Cardiac arrhythmias (especially sinus bradycardia) are often the earliest manifestation of toxicity rather than gastrointestinal symptoms 2
• In cardiac amyloidosis patients: Traditionally considered high-risk, but may be used with careful monitoring and patient selection 7

Prevention of Recurrence

• Adjust maintenance dose based on renal function:
  • Normal renal function: 0.25 mg daily
  • Mild impairment (eGFR 45-59 mL/min): 0.125 mg daily
  • Moderate impairment (eGFR 30-44 mL/min): 0.125 mg daily or every other day
  • Severe impairment (eGFR <30 mL/min): 0.0625-0.125 mg every other day 4
• Target lower therapeutic range (0.6-1.2 ng/mL) 1
• Avoid medications that increase digoxin levels
• Regular monitoring of renal function and electrolytes