Cardiovascular · Year 1 · from Cardiovascular

Case 1: Digoxin Toxicity - Na+/K+-ATPase Inhibition

Clinical Image

Source: Wikimedia Commons - Digoxin effect ECG - CC BY-SA 3.0

Patient Presentation

A 78-year-old woman is brought to the emergency department by her family after 2 days of nausea, vomiting, confusion, and visual disturbances. She describes seeing yellow-green halos around lights and everything looks "yellowish." She has atrial fibrillation and heart failure and was recently started on a new medication for a urinary tract infection.

Demographics

  • Age: 78 years
  • Sex: Female
  • Past Medical History: Atrial fibrillation, HFrEF (EF 35%), CKD stage 3 (baseline Cr 1.6)
  • Medications: Digoxin 0.125 mg daily, lisinopril, carvedilol, furosemide, and newly started clarithromycin for UTI

Chief Complaint

Nausea, vomiting, confusion, and yellow-tinged vision

Physical Examination

  • Blood pressure: 102/64 mmHg
  • Heart rate: 42 bpm (markedly bradycardic)
  • Temperature: 36.8°C
  • General: Confused, appears ill
  • Cardiovascular: Bradycardic, irregularly irregular rhythm with long pauses
  • Neurological: Disoriented to time and place, no focal deficits
  • Pupils: Normal

Workup

  • Serum digoxin level: 3.6 ng/mL (toxic; therapeutic 0.8-2.0 ng/mL)
  • Serum potassium: 5.8 mEq/L (elevated)
  • Serum creatinine: 2.4 mg/dL (worsened from baseline 1.6)
  • ECG: Atrial fibrillation with complete heart block and slow junctional escape rhythm (40 bpm), frequent PVCs with coupling, "scooped" ST segments (digoxin effect)
  • Additional findings: Bidirectional ventricular tachycardia noted transiently

Diagnosis

Severe Digoxin Toxicity precipitated by:

  1. Drug interaction with clarithromycin (P-glycoprotein inhibitor, increases digoxin levels)
  2. Acute kidney injury (decreased digoxin clearance)

Treatment

  1. Discontinue digoxin immediately
  2. Digoxin-specific antibody fragments (DigiFab) for:
  • Life-threatening arrhythmias (complete heart block, ventricular arrhythmias)
  • Potassium >5.5 mEq/L
  1. Cardiac monitoring in ICU
  2. Avoid calcium administration (can worsen digoxin toxicity)
  3. Treat hyperkalemia if severe (insulin/glucose, not calcium)
  4. Temporary pacing if symptomatic bradycardia persists
  5. Discontinue clarithromycin
  6. Review and adjust future digoxin dosing based on renal function

Physiological Principles Demonstrated

  • Digoxin mechanism: Digoxin inhibits the Na+/K+-ATPase, increasing intracellular sodium. This reduces the gradient driving the Na+/Ca2+ exchanger, leading to increased intracellular calcium and enhanced contractility.
  • Toxicity mechanism: Excessive inhibition causes calcium overload, leading to delayed afterdepolarizations and triggered arrhythmias. Hyperkalemia further inhibits the Na+/K+-ATPase, worsening toxicity.
  • Drug interaction: Clarithromycin inhibits P-glycoprotein, which normally pumps digoxin out of cells and into the gut lumen. Inhibition increases digoxin absorption and tissue concentrations.
  • Digibind mechanism: Fab fragments bind free digoxin, preventing it from binding to the Na+/K+-ATPase. The bound complex is renally excreted.

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