Barbiturates commonly used to reduce pressure on brain after severe head injury but no evidence that they reduce death rate

Roberts I, Sydenham E

Published Online:

October 7, 2009

Severe head injury can lead to the brain swelling from leaking blood or from clotting, or an imbalance in fluid around the brain. As space inside the skull is limited, this can cause dangerous levels of pressure on the brain (raised intracranial pressure − ICP). Barbiturates are sedatives that are commonly used to treat ICP. They slow down brain action and this can reduce the production of fluid. The review of six trials found no evidence that barbiturates reduce death rates for people with brain injuries because although they do lower ICP, one in four people have problems because barbiturates also cause low blood pressure.

Abstract (click to read)

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 ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume. However, barbiturates also reduce blood pressure and may, therefore, adversely effect cerebral perfusion pressure.

Objectives:

To assess the effects of barbiturates in reducing raised ICP, mortality and morbidity in people with acute traumatic brain injury. To quantify any adverse effects resulting from the use of barbiturates.

Search strategy:

We searched the following electronic databases: CENTRAL (The Cochrane Library 2009, Issue 2), MEDLINE (Ovid SP) 1950 to 2009, PubMed (searched 6 July 2009), EMBASE (Ovid SP) 1980 to 2009, PsycINFO (Ovid SP) 1806 to 2009. We also searched the reference lists of relevant papers and where necessary contacted trialists for information on ongoing research. Searching was not restricted by date, language or publication status. The searches were last updated in June 2009.

Selection criteria:

Randomised or quasi-randomised trials of one or more of the barbiturate class of drugs, where study participants had clinically diagnosed acute traumatic brain injury of any severity.

Data collection and analysis:

The author extracted the data and assessed the quality of allocation concealment in the trials.

Main results:

Data from six trials are included in this review. The pooled risk ratio 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 was 1.15 (95% CI 0.81 to 1.64). Two studies examined the effect of barbiturate therapy on ICP. In one, a smaller proportion of patients in the barbiturate group had uncontrolled ICP (68% versus 83%); RR for uncontrolled ICP was 0.81 (95% CI 0.62 to 1.06). In the other, mean ICP was also lower in the barbiturate group. Barbiturate therapy results in increased occurrence of hypotension (RR=1.80, 95% CI 1.19 to 2.70). For every four patients treated, one developed clinically significant hypotension. Mean body temperature was significantly lower in the barbiturate group. One study found pentobarbital was less effective than mannitol for control of raised ICP. There was no substantial difference in mortality between the two study groups (RR=1.21; 95% CI 0.75 to 1.94). The risk ratio for death with pentobarbital vs thiopental was 1.78 (95% CI 1.03 to 3.08) in favour of thiopental. Fewer patients had uncontrollable ICP with thiopental (RR=1.64, 95% CI 1.03 to 2.60). There was no significant difference in the effects of pentobarbital vs thiopental for neurological outcome, as measured using the Glasgow Outcome Scale, (RR=1.31, 95% CI 0.88 to 1.94), or hypotension (RR=0.95, 95% CI 0.81 to 1.12).

Authors' 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 one in four patients. This hypotensive effect will offset any ICP lowering effect on cerebral perfusion pressure.

This record should be cited as:

Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No.: CD000033. DOI: 10.1002/14651858.CD000033

Assessed as up to date:

June 1, 2009

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Primary Review Group:

Injuries Group

Health topics:

Neurology > Head injury > Treatments

Orthopaedics & trauma > Head injury > Treatment

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Barbiturates commonly used to reduce pressure on brain after severe head injury but no evidence that they reduce death rate

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