β-Blockers for traumatic brain injury: A systematic review and meta-analysis

BACKGROUND Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI). β Adrenergic receptor blockers (β-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of β-blockers on outcomes in patients with TBI. METHODS For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of β-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of β-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes. RESULTS Fifteen studies with 12,721 patients were included. Exposure to β-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30–0.51; I 2 = 66.3%; p < 0.001). β-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09–2.80; I 2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55–1.50; I 2 = 25.9%; p = 0.702). CONCLUSION This meta-analysis demonstrated that administration of β-blockers after TBI was safe and effective. Administration of β-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of β-blockers in the management of TBI. LEVEL OF EVIDENCE Systematic review and meta-analysis, level III.