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


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.
a Clinical Toxicology Unit and Emergency Department , Prince of Wales Hospital , Sydney , New South Wales , Australia ;|b New South Wales Poisons Information Centre , Sydney Children's Hospital at Westmead , Sydney , New South Wales , Australia ;
Betty S
BS
Chan
b New South Wales Poisons Information Centre , Sydney Children's Hospital at Westmead , Sydney , New South Wales , Australia ;|c Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|d Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle , Australia ;
Geoffrey K
GK
Isbister
c Clinical Toxicology Research Group, University of Newcastle , Newcastle , Australia ;|d Department of Clinical Toxicology and Pharmacology , Calvary Mater Newcastle , Newcastle , Australia ;
Margaret
M
O'Leary
a Clinical Toxicology Unit and Emergency Department , Prince of Wales Hospital , Sydney , New South Wales , Australia ;|b New South Wales Poisons Information Centre , Sydney Children's Hospital at Westmead , Sydney , New South Wales , Australia ;
Angela
A
Chiew
b New South Wales Poisons Information Centre , Sydney Children's Hospital at Westmead , Sydney , New South Wales , Australia ;|e Department of Clinical Pharmacology , University of Sydney , Sydney , New South Wales , Australia.
Nicholas A
NA
Buckley
D000368:Aged; D000369:Aged, 80 and over; D001919:Bradycardia / Q000097:blood / Q000188:drug therapy; D002317:Cardiovascular Agents / Q000097:blood / Q000506:poisoning*; D002908:Chronic Disease; D004077:Digoxin / Q000097:blood / Q000506:poisoning*; D062787:Drug Overdose / Q000097:blood / Q000188:drug therapy; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000188:drug therapy; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000097:blood / Q000188:drug therapy*; D011188:Potassium / Q000097:blood; D011446:Prospective Studies
D002317:Cardiovascular Agents; D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; D004077:Digoxin; D011188:Potassium
Digoxin-Fab; digoxin intoxication; overdose