Beta-2 Receptor Antagonists for Traumatic Brain Injury: A Systematic Review of Controlled Trials in Animal Models

A systematic review and meta-analysis of controlled trials was undertaken to assess the effects of beta-2 receptor antagonists in animal models of traumatic brain injury (TBI). Database and reference list searches were performed to identify eligible studies. Outcome data were extracted on functional status, as measured by the grip test or neurological severity score (NSS), and cerebral edema, as measured by brain water content (BWC). Data were pooled using the random-effects model. Seventeen controlled trials involving 817 animals were identified. Overall methodological quality was poor. Results from the grip test suggest that the treatment group maintained grip for a longer period than the control group; pooled weighted mean difference (WMD) = 8.28 (95% CI 5.78-10.78). The treatment group was found to have a lower NSS (i.e., better neurological function); pooled WMD = -3.28 (95% CI -4.72 to -1.85). Analysis of the cerebral edema data showed that the treatment group had a lower BWC than the control; pooled WMD = -0.42 (95% CI -0.59 to -0.26). There was evidence of statistical heterogeneity between comparisons for all outcomes. Evidence for small study effects was found for the grip test and BWC outcomes. The evidence from animal models of TBI suggests that beta-2 receptor antagonists can improve functional outcome and lessen cerebral edema. However, the poor methodological quality of the included studies and presence of small study effects may have influenced these findings.