Calcium Channel Blocker and Beta Blocker Overdose, and Digoxin Toxicity Management - Pharmacology EXTRA Supplement (Pharmacology CME)

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DigiFab® (Digibind®) Dosing for Digoxin Poisoning

• Introduction
• Points & Pearls
• Why and When to Use, and Next Steps
• Calculator Review Author
• Advice
• Critical Actions
• Instructions
• Evidence Appraisal
• Calculator Creator
• References

Introduction

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Points & Pearls

• Cardioactive steroid toxicity can cause nearly any dysrhythmia except rapidly conducted supraventricular tachydysrhythmia.
• Consider the serum digoxin level in the context of the patient’s clinical presentation; a reliable serum digoxin level must be obtained at steady state (ie, obtained ≥ 6 hours after ingestion). The serum digoxin level may be misleadingly high if obtained < 6 hours after ingestion.
• Digoxin levels measured after administration of digoxin immune Fab will be falsely elevated. If required, free digoxin levels will need to be measured (this is not readily available at all labs).
• Hyperkalemia acts as a marker of poisoning severity in acute digoxin overdose. Correcting mild elevations in serum potassium without administering digoxin immune Fab will not improve survival.
• Impaired creatinine clearance and aging (associated with decreased function of renal, hepatic, and cardiac systems) may result in clinical toxicity at lower serum digoxin levels.
• Electrolyte abnormalities (specifically hypokalemia, but including hypomagnesemia, hypercalcemia, hypernatremia) may result in dysrhythmias at lower serum digoxin levels.
• Certain medications, including quinidine, verapamil, diltiazem, carvedilol, amiodarone, and spironolactone, will result in decreased digoxin protein binding, thereby increasing free digoxin levels.

Tips from the creator:

• The calculator is appropriate for vials containing approximately 40 mg of antibodies.
• Slow infusion (ie, 2 hours) improves digoxin immune Fab efficacy. This method of infusion is preferable when rhythm disturbances are not life threatening.
• In the case of chronic overdose (eg, digoxin level in prehospital setting is missing), a dose of 3 vials is appropriate; this is an experience-based recommendation.

Why and When to Use, and Next Steps

Calculator Review Authors

Scott Lucyk, MD

Advice

Frequent premature ventricular complexes may be closely followed by ventricular dysrhythmias.

Critical Actions

Potassium abnormalities, specifically hypokalemia, may worsen digoxin toxicity, even at therapeutic digoxin levels. If hyperkalemia is mild, correction is not advised, as treatment with digoxin immune Fab will decrease potassium concentrations. Treatment to lower serum potassium concentrations should be performed prior to digoxin immune Fab administration only if (1) hyperkalemia is believed to be worsening atrioventricular nodal block and bradycardia, and (2) digoxin immune Fab is not immediately available. If hypokalemia is present, cautious correction should be performed prior to the administration of digoxin immune Fab. If there is worsening toxicity/dysrhythmia, or if toxicity does not improve with correction of hypokalemia, digoxin immune Fab should be immediately administered. Do not administer calcium salts to patients with hyperkalemia secondary to digoxin toxicity. Transcutaneous and especially transvenous pacing should be avoided in patients with digoxin toxicity due to risk for precipitating dysrhythmias.

Instructions

The therapeutic range for serum digoxin level is 0.8 to 2.0 ng/mL (1.0-2.6 nmol/L). In the case of acute poisoning with serum digoxin level confirmed at > 10 ng/mL, an empiric dose (10-20 vials) should be administered. Additional considerations for treatment of digoxin toxicity include:

• Atropine 0.5 mg administered intravenously for acute toxicity if there are bradydysrhythmias or a high-degree atrioventricular block.
• Cautious correction of electrolyte abnormalities, specifically hypokalemia and hypomagnesemia, which may result in dysrhythmias at lower serum digoxin levels.

Evidence Appraisal

The relationship between serum potassium concentrations and mortality in patients treated for digitoxin toxicity was investigated at the Fernand Widal Toxicology Center in Paris between 1967 and 1972.

Among patients with digitoxin toxicity, the majority of whom (81 of 91 patients) took digitoxin with suicidal intent, all patients with an initial serum potassium level > 5.5 mEq/L died, whereas all patients with an initial serum potassium level < 5 mEq/L survived (Bismuth 1973).

In 1990, Antman et al conducted a nationwide, prospective, open-label, multicenter clinical trial of 148 patients with potentially life-threatening digitalis intoxication who were treated with purified digoxin-specific Fab fragments. Resolution of all signs and symptoms of digitalis toxicity occurred in 119 patients (80%), 14 patients (9%) showed improvement, and 15 patients (10%) showed no response, though this group included moribund patients and patients who were retrospectively believed to not be suffering from digitalis toxicity. Among the 56 patients with cardiac arrest who were treated with Fab fragments, 30 patients (54%) survived hospitalization.

Calculator Creator

Frédéric Lapostolle, MD

References

Original/Primary Reference

• Lapostolle F, Borron SW, Verdier C, et al. Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning. Crit Care Med. 2008;36(11):3014-3018. DOI: 0b013e31818b341c

Addition References

• Antman EM, Wenger TL, Butler VP Jr, et al. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: final report of a multicenter study. Circulation. 1990;81:1744-1752. DOI: 81.6.1744
• Bismuth C, Gaultier M, Conso F, et al. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol. 1973;6(2):153-162. DOI: 15563657308990513
• Digibind® Injection Information Manufacturer's Guidelines. Accessed September 1, 2020.
• Hack JB. Cardioactive steroids. In: Goldfrank's Toxicologic Emergencies. Hoffman R, Howland MA, Lewin N, et al, eds. 10th ed. New York: McGraw-Hill Education/Medical; 2014.
• Howland MA. Digoxin-specific antibody fragments. In: Goldfrank's Toxicologic Emergencies. Hoffman R, Howland MA, Lewin N, et al, eds. 10th ed. New York: McGraw-Hill Education/Medical; 2014.