Digoxin

GENERAL PRINCIPLES

• Digoxin is a cardioactive steroid that was previously used in the treatment of CHF and arrhythmias (typically refractory atrial fibrillation).

• Other cardioactive steroids with digoxin-like effects are found in many plants and animals, including foxglove, red squill, oleander, and the Bufo toad.

Pathophysiology

• Digoxin inhibits the sodium/potassium ATPase pump, producing a rise in the intracellular sodium concentration that indirectly leads to an increase in the intracellular calcium concentration.

• The overall effect of digoxin is thus to enhance vagal tone (therefore suppressing conduction of atrial impulses to the ventricles), increase cardiac excitability (which predisposes to arrhythmias), and enhance inotropy.

• Unfortunately, digoxin has a very narrow therapeutic index, and accidental poisoning is relatively common, especially in patients with fluctuating renal function.

DIAGNOSIS

Clinical Presentation

• Digoxin poisoning classically presents with bradycardia, mental status changes, and GI upset.

• Poisoning may occur after an acute overdose, but the more common scenario is chronic poisoning due to changes in renal function or pharmacokinetic interactions.

Diagnostic Testing

LABORATORIES

• Obtain a serum digoxin concentration. Have a low threshold to send this test in any patient taking or prescribed digoxin.

• Obtain a BMP to assess the potassium.

î Hyperkalemia is a marker of severity in digoxin poisoning. In acute poisoning, a potassium over 5.0 mEq/L is an indication for antidote administration. ²³

î Hypokalemia exaggerates the effects of digoxin and may lead to toxicity even at a therapeutic serum digoxin concentration.

î Worsening renal function indicate a risk for digoxin toxicity, as digoxin is renally eliminated.

ELECTROCARDIOGRAPHY

• Digoxin poisoning may cause essentially any dysrhythmia (with the exception of a conducted supraventricular tachycardia).

• Certain dysrhythmia patterns are particularly suggestive of digoxin poisoning:

î Atrial fibrillation with a slow ventricular response

î The combination of AV blocks and significant ectopy

î Bidirectional ventricular tachycardia

The “Salvador Dali mustache” sign (concave sloped ST segments) is an indicator of digoxin effect, not poisoning.

TREATMENT

• The treatment of choice for digoxin poisoning is anti-digoxin Fab (Digifab or Digibind), a monoclonal antibody fragment that binds digoxin.

î Anti-digoxin Fab is indicated in the following circumstances:

#9632; Digoxin-related life-threatening dysrhythmia

#9632; Acute digoxin poisoning with K gt; 5.0 mEq/L ²³

#9632; Chronic digoxin poisoning with dysrhythmia or mental status changes

#9632; Digoxin concentration #8805;15 ng/mL at any time or #8805;10 ng/mL at 6 hours postingestion

#9632; Acute ingestion of #8805;10 mg digoxin in an adult

î The dosing of anti-digoxin Fab is controversial.

#9632; The classic approach (in accordance with the package insert) is to calculate the dose using the amount of digoxin ingested or the digoxin concentration, and to use very high doses for acute empiric treatment of critically ill patients.

#9632; Some experts advocate for the use of only 1-2 vials of anti-digoxin Fab in chronic toxicity. ²⁴

î Do not recheck the serum digoxin concentration after the administration of anti-digoxin Fab; the test cannot distinguish between bound and unbound drug and is not clinically useful.

• Treatment of hyperkalemia in digoxin poisoning is controversial.

î If hyperkalemia is being driven primarily by digoxin poisoning, it should resolve with administration of anti-digoxin Fab.

î If hyperkalemia is due to renal failure or another etiology, usual hyperkalemia care may be necessary.

î Some authors recommend avoiding administration of calcium salts to patients with digoxin poisoning; this is probably reasonable, but no high-quality data demonstrating harm exist.

• Atropine is a reasonable treatment for symptomatic bradycardia in digoxin poisoning, as digoxin directly enhances vagal tone.

î Atropine may be used to temporize patients while awaiting anti-digoxin Fab therapy, or it may be used as monotherapy in patients with isolated atropine-responsive bradycardia and no other indications for Fab.