Digoxin toxicity can result from inappropriate dosing, worsening of renal function, drug interactions, and intentional or iatrogenic overdose.
When digoxin-specific Fab antibody fragments (Digibind) became available in Canada in 1991 as an antidote for digitalis glycoside poisoning, a centralized distribution model was implemented by the BC Drug and Poison Information Centre (DPIC). In this model, which is unique in Canada, hospitals purchase an initial stock of Digibind. This is replaced free of charge by DPIC if the antidote is administered according to guidelines developed by DPIC and the health care treatment facilities. Data on Digibind use in BC and patient outcomes have been collected from 1991 to 2002.
From 1991 to 2002, DPIC was consulted on 348 cases of digitalis glycoside toxicity. Of these, 286 patients (134 males and 152 females) received Digibind. The majority of these patients, 238 of 286 (83%), presented with chronic digoxin poisoning. The median age of these patients was 78 years (range 17 to 97 years). There were 31 (11%) cases of acute-on-chronic poisoning. The median age of this group was 73 years (range 32 to 93 years). Acute digoxin ingestions occurred in only 17 (6%) patients with a median age of 43 years (range 7 days to 87 years). A 7-day-old preterm neonate received an iatrogenic overdose of digoxin. One adult male ingested a large quantity of foxglove (Digitalis purpurea) leaves.
Renal insufficiency was noted in the majority of the patients with chronic digoxin toxicity. Digoxin drug interactions with amiodarone, calcium channel blockers, quinidine, erythromycin, and clarithromycin accounted for 19 (8%) of the chronic poisonings, and many patients were also receiving diuretics. In some patients there was a combination of both an interaction and renal insufficiency.
Eleven patients who received Digibind died. Five of these patients received Digibind without effect during an arrest. Two patients intentionally ingested digoxin in combination with a beta-blocker (one patient) or a calcium channel blocker (one patient). Four patients died of complications due to their cardiovascular and/or renal disease or from sepsis.
The most common clinical manifestations occurring in the patients presenting with chronic digoxin toxicity were anorexia, nausea, and vomiting. Reported CNS effects included generalized weakness, fatigue, dizziness, and lethargy. Signs of toxic psychosis including confusion, agitation, hallucinations, and paranoia were observed in some patients. Cardiac effects included bradycardia, varying degrees of AV block, atrial and ventricular dysrhythmias, asystole, and cardiac arrest. Two patients complained of halos. Hyperkalemia was noted in the majority of the patients, although hypokalemia and hypomagnesemia may occur with chronic digoxin poisoning, especially in patients on concomitant diuretic therapy.
In this patient series, the median number of vials of Digibind used to treat chronic digoxin poisoning was 3 (range 1 to 8). Following both acute and acute-on-chronic ingestions, the median number of vials used was 7 (range 1 to 20 for acute and 1 to 22 for acute-on-chronic). The current cost of Digibind is $430.62 per vial. In BC in 2002, 45 patients received a total of 149 vials of Digibind, representing an annual cost of $64 162.38.
In BC, chronic digoxin poisoning in the elderly accounts for the majority of serious overdoses requiring Digibind antidotal treatment. Decreased renal function was the major cause of digoxin toxicity in our case series. Drug interactions and concomitant diuretic therapy were contributing factors. The potential benefits of digoxin in this high-risk, elderly population should be carefully assessed. Patients should receive the lowest effective dose and be monitored closely. Initial digoxin levels should be ordered and creatinine clearance assessed. Repeat these as needed if there are increased risk factors for digoxin toxicity such as decreased renal function and potential drug interactions. Digoxin dosing should be adjusted accordingly. Awareness of the risk factors for chronic digitalis glycoside poisoning and early recognition of the symptoms may prevent hospital admissions for digoxin toxicity and obviate the need for expensive antidotal therapy.
Current guidelines for managing digitalis glycoside toxicity can be obtained 24-hours-a-day by calling the Poison Control Centre at (604) 682-5050 (Lower Mainland) or 1 800 567-8911 from other areas of British Columbia.
—Gillian A. Willis, MPS
BC Drug & Poison Information Centre
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