Clinical Immunotherapeutics

, Volume 4, Issue 4, pp 312–330 | Cite as

Digitalis Intoxication

Therapy with Digoxin-Specific Antibody Fragments
  • Alan Woolf
Review Article Treatment Review

Summary

Digitalis continues to be a commonly prescribed cardiac agent for the treatment of congestive heart failure and atrial fibrillation. The incidence of severe digitalis poisonings and adverse effects may be decreasing for a variety of reasons, but the narrow therapeutic: toxic ratio of digitalis makes toxicity a continuing problem. The advent of immunotherapy using digoxin-specific antibody (ovine) fragments (digoxin immune Fab; Fab) within the past 10 years has radically changed the management of severe digitalis poisoning in both children and adults. Several large clinical trials involving cumulatively more than 1000 patients have established the efficacy of digoxin immune Fab in resolving the signs of digitalis toxicity. Often improvements in dysrhythmias, hyperkalaemia, gastrointestinal complaints and/or neurological symptoms are noted within 30 minutes of infusion, with complete reversal of toxicity in 2 to 4 hours in 85 to 90% of patients. In many instances, those patients having only partial responses are probably undertreated through a miscalculated total body burden of digoxin or digitoxin.

Administration of digoxin immune Fab has been remarkably free of associated adverse effects: allergic reactions (mostly rashes) occur in <1% of recipients. Recurrence of congestive failure due to digitalis withdrawal has been noted in about 1 to 3% of patients who received Fab. Recurrence of atrial fibrillation with a rapid ventricular response has also been seen. Recrudescence of digitalis toxicity occurs in about 3% of Fab recipients, usually within 3 days of the initial Fab dose and often related to undertreatment due to a miscalculation of the Fab needed to counter a total body burden of digitalis. Hypokalaemia has been noted in up to 4% of Fab recipients.

For these reasons, it is recommended that the patient’s medical status be closely watched after administration of digoxin immune Fab, with cardiac monitoring for several days and frequent measurements of serum potassium. Newer laboratory techniques such as ultrafiltration of the sample prior to analysis by immunoassay will improve the clinician’s ability to monitor free serum digoxin concentrations after Fab administration. In this way the clinician can detect late-occurring increases in free digoxin concentrations that might herald recrudescing toxicity and necessitate repeated treatment with Fab.

Indications for use of digoxin immune Fab have been interpreted broadly by clinicians as the antidote has become more widely available. However, most clinicians continue to reserve Fab for those patients who are confirmed, by a reliable history of overdosage and/or an elevated post-distribution serum digitalis concentration, to be experiencing the toxic effects of digitalis and who have life-threatening symptoms and signs. These include cardiac arrhythmias and/or conduction blocks that are haemodynamically compromising, and/or rising levels of potassium in the blood. Clinicians are well advised to base their decision to use Fab in the context of the individual patient’s risks for a poor prognosis, such as: (a) advanced age; (b) history of a massive overdose with early signs of rapidly progressing toxicity; (c) the presence of advanced atrioventricular block and arrhythmias; (d) persistent hyperkalaemia; and (e) pre-existing cardiac conditions or congenital heart disease.

Digoxin immune Fab has also been used with good results in infants and children, in patients with renal failure, and in patients experiencing the effects of other glycosides such as digitoxin or lanatoside C, or advanced toxicity from plant-derived cardiac glycosides. Because of the longer serum half-lives and persistence of other glycosides such as digitoxin, and because of the inefficiency of clearance of digoxin in patients with renal failure, longer monitoring for signs of recrudescing toxicity is recommended in such patients after Fab administration.

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Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Alan Woolf
    • 1
  1. 1.Program in Clinical Pharmacology and ToxicologyChildren’s Hospital/Harvard Medical SchoolBostonUSA

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