Efficacy and effectiveness of anti-digoxin antibodies in chronic digoxin poisonings from the DORA study (ATOM-1)

Clin Toxicol (Phila). 2016 Jul;54(6):488-94. doi: 10.1080/15563650.2016.1175620. Epub 2016 Apr 27.

Abstract

Context: We hypothesized that in chronic digoxin toxicity, anti-digoxin antibodies (Fab) would be efficacious in binding digoxin, but this may not translate into improved clinical outcomes.

Objective: This study aims to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when anti-digoxin Fab are given.

Materials and methods: This is a prospective observational study. Patients were recruited if they have been treated with anti-digoxin Fab for chronic digoxin poisoning. Data was entered into a standardised prospective form, supplemented with medical records. Their serum or plasma was collected, analysed for free and bound digoxin and free anti-digoxin Fab concentrations.

Results: From September 2013 to February 2015, 36 patients (median age, 78 years; 22 females) were recruited from 18 hospitals. Median heart rate (HR) was 49 beats/min. Initial median digoxin and potassium concentrations were 4.7 nmol/L (3.6 μg/L) (range: 2.3-11.2 nmol/L) and 5.3 mmol/L (range: 2.9-9.2 mmol/L) respectively. Beta-blockers (n = 18), calcium antagonists (n = 6), spironolactone and/or angiotensin blocking agents (n = 24) were also used concomitantly. Renal impairment and gastrointestinal symptoms were present in 31 (86%) and 22 (63%) patients respectively. Five patients died from conditions unrelated to digoxin toxicity. Median change in HR was 8 beats/min post-Fab with no effect on blood pressure; they were 4, 10 and 17 beats/min for the 1, 2 and ≥3 vials of anti-digoxin Fab groups respectively. Concomitant treatments with potassium lowering agents (12/36) and inotropic drugs (7/36) were used. Gastrointestinal effects resolved in all 22 patients. The median decrease for potassium was 0.3 mmol/L. Digoxin concentration reduced from 3.8 to 0 nmol/L post-Fab. There was a rebound observed in the free digoxin concentration in 25 patients but none had associated clinical deterioration.

Conclusions: One to two vials of anti-digoxin Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR and potassium, suggesting bradyarrhythmia and hyperkalaemia may be from other co-morbidities.

Keywords: Digoxin-Fab; digoxin intoxication; overdose.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bradycardia / blood
  • Bradycardia / drug therapy
  • Cardiovascular Agents / blood
  • Cardiovascular Agents / poisoning*
  • Chronic Disease
  • Digoxin / blood
  • Digoxin / poisoning*
  • Drug Overdose / blood
  • Drug Overdose / drug therapy
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hyperkalemia / blood
  • Hyperkalemia / drug therapy
  • Immunoglobulin Fab Fragments / blood
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Male
  • Middle Aged
  • Poisoning / blood
  • Poisoning / drug therapy*
  • Potassium / blood
  • Prospective Studies

Substances

  • Cardiovascular Agents
  • Immunoglobulin Fab Fragments
  • digoxin antibodies Fab fragments
  • Digoxin
  • Potassium