Global cerebrovenous oxygenation was evaluated before and after intravenous administration of pentobarbital sodium for the management of refractory intracranial hypertension in 151 comatose patients who had acute traumatic brain swelling. Two groups of patients were identified: a group in which the jugular oxyhemoglobin saturation (SjO2) remained at or above 45% after pentobarbital bolus, and a group in which the SjO2 dropped below 45%. The two groups were matched by predominant findings on computerized tomography scans of the head, as well as age, postresuscitation Glasgow Coma Scale scores, levels of total hemoglobin content, SjO2, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) prior to pentobarbital bolus. Outcomes were significantly worse (p < 0.0001) in patients who developed decreases in SjO2 to levels below 45% than in those whose SjO2 remained at or above 45%, despite the fact that there were no significant differences between the two groups with regard to ICP and CPP after an intravenous bolus of pentobarbital.