Beta-2 receptor antagonists for acute traumatic brain injury.
BACKGROUND
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral oedema, the accumulation of fluid within the brain, is believed to be an important contributor to the secondary brain damage that occurs following injury. The release of kinins is thought to be an important factor in the development of cerebral vasogenic oedema and the use of beta-2 receptor antagonists, which prevent the release of these kinins, have been proposed as a potential therapeutic intervention.


OBJECTIVE
The objective was to assess the safety and effectiveness of beta-2 receptor antagonists for TBI.


METHODS
We searched the Cochrane Injuries Group's specialised register, CENTRAL, MEDLINE, EMBASE, National Research Register, LILACs, Zetoc, Web of Knowledge and Current Controlled Trials. We also searched the internet and checked the reference lists of relevant papers to identify any further studies. The searches were conducted in March 2007.


METHODS
Randomised controlled trials of beta-2 receptor antagonists versus placebo for TBI.


METHODS
Two authors independently screened search results and assessed the full texts of potentially relevant studies for inclusion. Data were extracted and methodological quality was examined. Relative risks (RR) and 95% confidence intervals (CIs) were calculated and data were pooled using a fixed effect model.


RESULTS
Three studies were included, involving 178 participants. All three studies reported the effects of beta-2 receptor antagonists on mortality. The pooled RR for mortality was 0.63 (95% CI 0.36 to 1.10). Two studies measured disability, the RR of death or severe disability with beta-2 receptor antagonists was 0.81 (95% CI 0.59 to 1.09). Two studies measured the effect on intracranial pressure (ICP), although in only one did this finding reach statistical significance. There was no evidence for the presence of heterogeneity.


CONCLUSIONS
There is no reliable evidence that beta-2 receptor antagonists are effective in reducing mortality or disability after TBI. Further well conducted randomised controlled trials are required.
Ker
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London School of Hygiene and Tropical Medicine, Nutrition & Public Health Intervention Research Unit, Room 280, North Courtyard, Keppel Street, London, UK, WC1E 7HT. katharine.ker@lshtm.ac.uk
Blackhall
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D000208:Acute Disease; D058672:Adrenergic beta-2 Receptor Antagonists; D001929:Brain Edema / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007427:Intracranial Pressure; D010455:Peptides / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D058672:Adrenergic beta-2 Receptor Antagonists; C403051:LF 16-0687; D010455:Peptides; D011804:Quinolines; C071326:deltibant