We read with eager anticipation, “Late rebound digoxin toxicity after digoxin-specific antibody fragments therapy in anuric patient,” by Mehta et al. in the February 2002 issue of the Journal (1). The electrocardiograms provided by the authors nicely illustrate some of the electrocardiographic manifestations of digoxin poisoning, but the title of their report is misleading. The authors provide no evidence that the occurrence of bigeminy 24 h after admission resulted from rebound digoxin poisoning. Other common causes for bigeminy, including intrinsic cardiac disease (for which the patient was likely prescribed digoxin in the first place), cardiac ischemia, electrolyte disturbances and progressive metabolic acidosis were not excluded by the authors.

Even if digoxin were the causative factor, Mehta et al. suggest that underdosing of Digibind® (Glaxo Wellcome Inc., North Carolina) may have contributed to the rebound of free digoxin and subsequent occurrence of the dysrhythmia, but the facts presented in their report make this postulate unlikely. Unfortunately, the authors do not state the patient’s weight or the time of the digoxin level in relation to the patient’s last dose. If the patient weighed up to 50 kg and the digoxin level of 16 ng/mL truly reflected a post-distribution state, then 8 vials would have been appropriate dosing according to the manufacturer’s dosing calculation (# vials = digoxin concentration × patient weight/100) 2, 3. Some rebound in free digoxin may occur from re-distribution from tissue stores to the vascular space after Fab administration, but this is delayed by several days in patients with renal insufficiency since Fab is renally excreted (2). Furthermore, rebound levels from redistribution of free digoxin rarely peak beyond the therapeutic range. In a series of anephric patients, rebound peak levels of free digoxin were noted to be only 1.7 ± 1.3 nmol/mL in 77 ± 46 h after Fab administration (4). Some have suggested dissociation of free digoxin from Fab as a theoretical possibility when Fab elimination is prolonged in patients with renal compromise, but the Ujhelyi report cited by Mehta et al. unequivocally states that there is no evidence for such a phenomenon (5). Only confirmatory serum levels of elevated free digoxin would have justified the title of this report.

It is critical to understand the contraindications and the limitations of any antidote before administration. We fear that provocative titles such as the one used by Mehta et al. would only serve to discourage the appropriate use of an antidote that has proven to be safe, effective, and a model for other effective antibody-fragment antidotes 3, 6.