To the Editor:
We thank Drs. Megarbane and Baud for the letter discussing the role of prophylactic use of digoxin-Fab in patients with elevated digoxin levels. This is in response to our recent review article on digoxin-specific antibodies in the treatment of digoxin toxicity.Citation1 The prophylactic use of half equimolar dose of digoxin-Fab in patients with ‘a poor prognosis’, elevated digoxin levels, but without any indication of severe digoxin toxicity, is a very expensive strategy. Further, there are no convincing data to suggest that this will improve outcomes compared with observation and treatment of any deterioration with digoxin-Fab.
The suggestion that the group of patients have a poor prognosis is based on analysis of patients with acute digoxin/digitoxin poisoning.Citation2 These 6 prognostic factors have not been validated in chronic digoxin poisoning and some are extremely common. A majority of asymptomatic patients with an elevated digoxin level would meet three or more criteria, which they suggest should indicate prophylactic digoxin-Fab. In their own series, over 95% of patients met two of the three criteria (age > 55 and underlying heart disease). So simply being male, OR having a heart rate of less than 60 bpm after atropine OR having a K value of greater than 4.5mmol/L would on their own be an indication for digoxin-Fab, if the authors’ prognostic criteria were used. The result would be a tenfold increase in the use of digoxin-Fab.Citation3,Citation4
We agree that patients with high digoxin concentrations from ‘chronic toxicity’ have a higher mortality rate. These patients are frequently old, with deterioration in underlying heart, kidney and/or liver disease. The deterioration in organ function might have caused the high digoxin concentration. Many of these patients will still die if digoxin-Fab is given. In a prospective multi-centre study of 150 patients treated with equimolar dose of digoxin-Fab, the mortality rate was 29% (43/150).Citation5 The death in majority of patients was thought to be caused by other medical illnesses. Even if Digoxin-Fab is not given, it is likely that patients, who die, will die ‘with’ rather than ‘from’ chronic digoxin toxicity.
We are currently conducting a prospective non-randomised study on acute and chronic digoxin poisoning and have frequently found that digoxin-Fab does not improve symptoms of patients with chronic digoxin toxicity even when half molar neutralising doses are used. It is even harder to measure an effect of prophylactic digoxin-Fab in asymptomatic patients. Thus, we would endorse the merit of conducting a randomised clinical trial to test the benefits of prophylactic digoxin-Fab, as it is plausible (but not likely) that there is a small benefit, and it will be impossible to determine this with less stringent research designs.
Declaration of interest
The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References
- Chan BSH, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol (Phila) 2014; 52:824–836.
- Dally S, Alperovitch A, Lagier G, Bismuth C, Fournier E.[Prognostic factors in acute digitalis poisoning (author’s transl)]. Nouv Presse Med 1981; 10:2257–2260.
- Lapostolle F, Borron SW, Verdier C, Taboulet P, Guerrier G, Adnet F, et al. Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning. Crit Care Med 2008; 36:3014–3018.
- Lapostolle F, Borron SW, Verdier C, Arnaud F, Couvreur J, Mégarbane B, et al. Assessment of digoxin antibody use in patients with elevated serum digoxin following chronic or acute exposure. Intensive Care Med 2008; 34:1448–1453.
- Antman EM, Wenger TL, Butler VP Jr, Haber E, Smith TW. 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.