Lorazepam conjugation is unimpaired in burn trauma

A previous clinical study documented impaired hepatic metabolism of diazepam (phase I reaction) after burn injury. In this study, using lorazepam as a marker of hepatic glucuronidation, we tested the hypothesis that after burn injury, phase II reactions may be less impaired than phase I reactions. Ten burned patients and 10 age-, weight-, and sex-matched control subjects were studied after a 2 mg bolus dose of lorazepam. Burned patients had received multiple medications, whereas control patients were not taking any medication. The burned patients were studied at a mean (+/- SE) of 22 (+/- 4.6) days after burn injury. The burned patients had increases in total volume of distribution (2.66 +/- 0.55 vs. 1.39 +/- 0.1 L/kg; P less than 0.02) and clearance (4.28 +/- 1.20 vs. 1.16 +/- 0.1 ml/min/kg; P less than 0.01), whereas the half-life was significantly reduced in the burned group (9.6 +/- 1.3 vs. 13.9 +/- 0.9 hours; P less than 0.025). The significantly increased clearance and decreased elimination half-life in burned patients indicates that the elimination kinetics of lorazepam are not impaired and in fact may be enhanced in burned patients.