Barbiturates for acute traumatic brain injury.

BACKGROUND: Raised intracranial pressure (ICP) is an important complication of severe brain injury, and is associated with a high mortality rate. Barbiturates are believed to reduce intracranial pressure by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and therefore may adversely effect cerebral perfusion pressure.

OBJECTIVES: To assess the effects of barbiturates in reducing raised intracranial pressure, mortality and morbidity in people with acute traumatic brain injury. To quantify any side effects resulting from the use of barbiturates.

SEARCH STRATEGY: The review draws largely on the search strategy developed for the Cochrane Injuries Group as a whole. However, in addition the Cochrane Library was searched in December 1996 using the text terms "barbiturate*," "pentobarb*," "phenobarb*," "head," and "brain." An updated search was done in April 1999.

SELECTION CRITERIA: Randomised or quasi randomised trials of any one or more of the barbiturate class of drugs (amobarbital, barbital, hexobarbital, mephobarbital, methohexital, murexide, pentobarbital, phenobarbital, secobarbital, thiobarbiturate) where study participants had a clinically diagnosed acute traumatic brain injury of any severity.

DATA COLLECTION AND ANALYSIS: The reviewer extracted the data and assessed the quality of allocation concealment in the trials.

MAIN RESULTS: The pooled relative risk for death (barbiturate vs no barbiturate) was 1.09 (95%CI 0.81 to 1.47). The pooled effect of barbiturates on adverse neurological outcome, measured using the Glasgow Outcome Scale (death, persistent vegetative state or severe disability) was 1.15 (95% 0.81 to 1.64). Two studies examined the effect of barbiturate therapy on intracranial pressure. In the study by Eisenberger et al, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% vs 83%). The relative risk for uncontrolled ICP was 0.81 (95%CI 0.62 to 1.06). Similarly, in the study by Ward et al, mean ICP was lower in the barbiturate treated group. Barbiturate therapy results in an increase in the occurrence of hypotension (RR=1.80 95%CI 1.19 to 2.70). For every four patients treated one will develop clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate treated group. Schwartz et al compared pentobarbital with mannitol in the control of intracranial pressure. Pentobarbital was less effective than mannitol for control of raised ICP. 68% of patients in the pentobarbital treated group required a second drug for the treatment of raised intracranial pressure compared to 39% in the mannitol treated group (RR=1.75 95%CI 1.05 to 2.92). There was no substantial difference in mortality between the two study groups (RR=1.18 95%CI 0.73 to 1.92).

REVIEWER'S CONCLUSIONS: There is no evidence that barbiturate therapy in patients with acute severe head injury improves outcome. Barbiturate therapy results in a fall in blood pressure in 1 in 4 treated patients. The hypotensive effect of barbiturate therapy will offset any ICP lowering effect on cerebral perfusion pressure.