Clinical outcomes from early use of digoxin-specific antibodies versus observation in chronic digoxin poisoning (ATOM-4)

Abstract

Introduction: In our previous study on chronic digoxin poisoning, there was a minor improvement after treatment with digoxin-specific antibody (digoxin-Fab). We hypothesised patients with elevated digoxin concentrations may derive little benefit from digoxin-Fab because their presenting complaint was more closely related to their multiple co-morbidities. We aimed to compare the outcome of patients who were initially treated with digoxin-Fab with those that received supportive care. Method: Patients were prospectively recruited to the study if they had an elevated digoxin concentration, signs or symptoms of toxicity thought to be from digoxin. Patients who were initially managed with digoxin-Fab were compared with those not initially receiving digoxin-Fab (observation group). Patients presented with ventricular arrhythmias before initial assessment were excluded from the analysis. Primary outcome was mortality. Secondary outcomes were length of stay (LOS), change in heart rate (HR) and potassium concentration. Results: From September 2013 to January 2018, 128 patients were recruited of which 78 (61%) received initial digoxin-Fab. Digoxin-Fab and supportive care groups had an initial median heart rate of 46 (range: 20-120) vs 52 bpm (range: 29-91) (p = .06), systolic blood pressure of 110 mmHg (range: 65-180) vs 125 mmHg (range: 90-184) (p = .009), respectively. Digoxin concentrations 4.4 nmol/L (range: 3.3-9) vs 4.2 (range: 2-11.2) (p = .42) and potassium concentrations 5.4 mmol/L (range: 3-11) vs 5.1 mmol/L (range: 3.5-8.2) (p = .33) were similar. Median dose of digoxin-Fab used was 1.5 vials (IQR: 1-2). There were 9 (12%) deaths in the Fab group compared to 7 (14%) in those treated with supportive care (risk difference -2.5%; 95% CI: -14 to 9%; p = .68). The median LOS was six days in both groups. Mean changes in potassium concentration [-0.5 ± 0.1 vs. -0.4 ± 0.1 mmol/L; difference -0.1 (95% CI: -.02, 0.4), p = .70] and HR within 4 h [8 ± 1 vs. 7 ± 3 bpm; difference -1.0 (95% CI: -6.7, 4.8), p = 0.74] were similar in the two groups. Conclusions: This study did not appear to show any benefit from the routine use of digoxin-Fab in patients thought to have chronic digoxin poisoning. These patients have multiple co-morbidities that may be contributing to their clinical features, other treatments are often equally effective.

Keywords: Digoxin poisoning; digoxin-Fab; digoxin-specific antibody; overdose.