Microencapsulated Charcoal Hemoperfusion: A Possible Therapeutic Adjunct in Digoxin Toxicity

Abstract

Attempts to remove substantial quantities of digoxin by either peritoneal or hemodialysis, have been unsuccessful due to their low clearance rate. The present study determined the in-vivo clearance rate for digoxin of a single microcapsule of 300 gm of activated charcoal. The clearance rate was 55 ± 5 ml/ min (mean ± SEM) in the first hour and 48.4 ± 4 ml/min in the second; these values are approximately five-fold higher than with other dialysis techniques. No evidence of a post-dialysis rebound increase in serum digoxin levels was found, implying that peripheral tissues can rapidly release digoxin to the diminishing serum pool. Preliminary data obtained suggest a beneficial effect on arrhythmias and lowering of the myocardial to serum ratio of digoxin after hemoperfusion. The incidence of digoxin toxicity remains too high. Of patients admitted to hospital taking this drug, as many as one in five receive an excessive dose (1–3). Recognition of the role of the kidneys in digoxin excretion, and consequently, the need for reduced dosage in patients with impaired renal function has undoubtedly diminished, but not eliminated the risk of toxicity (4). Unfortunately, risk remains because renal function may rapidly and unexpectedly deteriorate in patients taking digoxin. As well, some patients with renal failure still require digoxin to treat arrhythmias or heart failure. Further, in such patients, if toxic, the duration of risk may well be longer than in those with normal renal function. Thus, we decided to explore a new method to facilitate digoxin removal. Previous experience with either peritoneal or hemodialysis to remove digoxin has been unsatisfactory since the clearance rate with either technique is quite low (5). Recently, charcoal hemoperfusion - a dialysis technique that combines absorption as well as diffusion - has been shown successful in treatment of certain drug intoxications, in addition to its initial use in renal failure (6). Since the vast majority of digoxin is tissue bound, any dialysis method requires a high clearance rate from serum and rapid equilibration from the tissue to plasma compartments. The present study examines these questions in dogs made acutely toxic with intravenous digoxin.