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Comment on: clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning

Dear Editor, We recently reviewed the article “Clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning” [1]. Given the significant cost of digoxin-fab, this article describes an approach to treatment using titrated doses of digoxin-fab rather than a standard bolus regimen based on serum digoxin concentration or reported amount ingested. Acute digoxin toxicity is rare and potentially life-threatening. This paper defines acute digoxin toxicity as a “history of acute digoxin overdose, elevated serum digoxin concentration, and signs and symptoms of toxicity” [1]. Patients with digoxin toxicity present with neurologic and cardiac manifestations; gastrointestinal symptoms are more prominent in acute toxicity [2]. Since all of the patients in this study were previously taking digoxin, except for one, it would be more appropriate to classify these patients as “acute-on-chronic” overdose rather than “acute” digoxin overdose. Furthermore, classifying patients as having digoxin toxicity based on a serum concentration is problematic since digoxin is a two-compartment model in vivo; toxicity is unlikely to correlate with a predistribution serum digoxin concentration [3,4]. The inherent subjectivity in determining which patients have “signs and symptoms” of digoxin toxicity limits both the internal and external validity of the study. Further information such as details on the specific signs and symptoms and the correlating digoxin-fab doses administered would be useful. One of the benefits of an initial bolus of digoxin-fab in acute digoxin toxicity is to bind digoxin in the blood compartment prior to tissue distribution. Given digoxin’s large volume of distribution [3], digoxin-fab is also useful in chronic digoxin toxicity as digoxin-fab diffuses into the extracellular space, binds digoxin, and creates a gradient for the diffusion of intracellular digoxin [5]. The initial titrated doses of digoxin-fab varied and there are no details as to how the precise doses were determined. For example, three patients in this cohort presented with ventricular tachycardia/fibrillation. Were these critically ill patients treated with bolus or titrated dosing? Furthermore, Figure 2 illustrates three groups of select patients in which groups A, B, and C received bolus doses, large titrated doses, and small titrated doses, respectively. If group A were the first patients included in this study and received bolus doses, then how were the patients subsequently chosen to be in groups B and C? In addition, when and how were the patients reassessed for improvement after digoxin-fab administration considering the expected lag between administration of antidote and clinical response? The authors’ goal of titrating digoxin-fab to reduce cost and enable stocking of antidote in otherwise unable hospitals is admirable. Although this method of titrated dosing hypothetically saved $267,000US dollars, the theoretical cost savings spanned a period of 7 years with only a modest $10,000 dollar savings per potentially critically ill patient. It is unknown if titrating digoxin-fab antibodies improved drug costs but was offset by other expenses such as intensive care admission, critical care time billing, and length of hospital stay. In a resource-limited environment, the method of titrated dosing also requires more frequent reassessments and redosing of antidote which might excessively burden the workload of hospital staff.