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 ¼ .06), systolic blood pressure of 110 mmHg (range: 65-180) vs 125 mmHg (range: 90-184) (p ¼ .009), respectively. Digoxin concentrations 4.4 nmol/L (range: 3.3-9) vs 4.2 (range: 2-11.2) (p ¼ .42) and potassium concentrations 5.4 mmol/L (range: 3-11) vs 5.1 mmol/L (range: 3.5-8.2) (p ¼ .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 À2.5%; 95% CI: À14 to 9%; p ¼ .68). The median LOS was six days in both groups. Mean changes in potassium concentration [À0.5 ± 0.1 vs. À0.4 ± 0.1 mmol/L; difference À0.1 (95% CI: À.02, 0.4), p ¼ .70] and HR within 4 h [8 ± 1 vs. 7 ± 3 bpm; difference À1.0 (95% CI: À6.7, 4.8), p ¼ 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.

Use of digoxin antibodies to treat digoxin poisoning: a subanalysis of the DIGITOX study

“…Esta propuesta ha sido evaluada clínicamente, obteniendo un buen resultado en pacientes con intoxicación aguda 17 y crónica 14 , si bien en este último caso la administración de AcAD no pareció reducir la mortalidad, por lo que otros factores (como la presencia de insuficiencia renal, niveles de potasio, uso concomitante de otras medicaciones, etc. ), deben influir en el pronóstico final de los pacientes intoxicados 18 . No se debe olvidar que, en ausencia de la posibilidad de determinar la concentración plasmática de digoxina libre, la respuesta a la administración de AcAD debe basarse en criterios clínicos y electrocardiográficos 19,20 .…”

Diagnosis and practical management of digoxin toxicity: a narrative review and consensus

“…The intention was to identify a simple and practical approach that can be rapidly implemented without the need for time-consuming calculations. Most patients with chronic toxicity have digoxin levels <5 ng/ml, and so 1-2 vials of digoxin immune Fab should usually be sufficient for full neutralisation [38][39][40]. The recommendation for an initial dose of five vials of digoxin immune Fab for patients in cardiac arrest is directed at balancing the clinical urgency of achieving neutralisation with the often limited supplies of digoxin Fab immediately available.…”

A Case of Digoxin Toxicity Due to Acute Renal Failure

“…Most patients that present with digoxin toxicity are elderly, have other cardiac and noncardiac comorbidities, and take multiple medications including those known to potentially interfere with serum digoxin concentrations (SDC) [12]. The most common presentation of digoxin toxicity is due to unintentional overdose or decreased drug clearance due to hepatic or renal dysfunction, as opposed to acute, intentional ingestions [2,6,12]. Most patients with acute toxicity present with anorexia, nausea, emesis, and fatigue.…”

“…All patients presenting with or suspected of digoxin toxicity should be managed with supportive care, including discontinuation of the medication [ 10 ]. Patients with chronic digoxin toxicity presenting with elevated SDC commonly have multiple acute comorbidities including dehydration and acute renal failure, and supportive care along with management of these comorbidities may have a more significant impact on clinical outcomes than the administration of digoxin-specific antibody [ 6 , 12 ]. Although patients with renal failure and hyperkalemia may meet the criteria for emergent hemodialysis, this is ineffective in digoxin toxicity due to the extensive fat distribution of the drug [ 1 ].…”

“…Observational studies on clinical outcomes in patients treated with digoxin-specific antibody have suggested that it does not significantly improve mortality or length of stay. These studies, however, excluded patients with ventricular arrhythmias and endorsed the current guidelines for digoxin-specific antibody treatment [ 6 , 12 ].…”