High-dose pentobarbital pharmacokinetics in hypothermic brain-injured children

Abstract

The pharmacokinetics of pentobarbital were examined in 11 children with Reye syndrome, hypoxic encephalopathy, or acute head injury. Nine of these patients were hypothermic (less than 32 degrees C). The total systemic clearance and volume of distribution at steady state of pentobarbital were significantly reduced in these patients when compared to previous data in normothermic adult volunteers following intravenous doses of pentobarbital. Pentobarbital elimination half-life was not significantly different from control values. The diminished systemic clearance of pentobarbital may result from decreases in intrinsic enzyme activity that accompany hypothermia, as well as hepatic dysfunction in patients with Reye syndrome. Less extensive distribution of pentobarbital is likely the result of either differences in body fat composition or hypothermia-induced decreases in regional blood flow. The reduced clearance and distribution of pentobarbital may partially explain the enhanced reduction in cerebral metabolism that occurs on addition of hypothermia to barbiturate therapy in patients with elevated intracranial pressure.