Reduction of Diazepam Serum Half Life and Reversal of Coma by Activated Charcoal in a Patient with Severe Liver Disease

Abstract

We report a case of prolonged coma (7 days) which arose as a complication of the treatment of alcohol withdrawal seizures and delirium with intravenous phenobarbital and diazepam. In an attempt to enhance the elimination of diazepam and its active metabolites, as well as phenobarbital, 40 grams activated charcoal was given every 4 hours (6 doses). Coma was completely reversed within 12 hours; serum half life (tl/2) of diazepam was reduced from 195 to 18 hours during charcoal administration. We postulate that higher free (unbound) diazepam concentrations secondary to hypoalbuminemia, occuring as a result of liver disease, may have increased the depth of our patient's coma, but paradoxically, by making more drug available for diffusion across the gastrointestinal membrane barrier, may have enhanced the ability of activated charcoal to adsorb diazepam and, therefore, decrease its t1/2.