Beta-blockers in adults with acute traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials

Abstract

Abstract Background Traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Beyond the primary insult, excessive sympathetic activation contributes to secondary brain injury and poor outcomes. Beta-blockers may attenuate this hyperadrenergic surge and provide neuroprotective benefits, but their efficacy in improving long-term functional recovery remains uncertain. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating beta-blockers in adults with acute TBI. We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov for RCTs comparing beta-blockers with placebo, usual care, or non-adrenergic comparators. Our primary outcome was long-term functional outcome, assessed with the Glasgow Outcome Scale (GOS) or its Extended version (GOS-E). Secondary outcomes included mortality, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, and adverse events. Results Seven RCTs (n = 559) met inclusion; six (n = 445) contributed data to meta-analyses. Only two trials (n = 259) reported functional outcomes. Beta-blockers did not significantly reduce the risk of unfavorable neurological outcome (RR 0.81; 95% CI 0.57–1.15; very low certainty). In contrast, beta-blocker therapy was associated with a reduction in mortality (RR 0.57; 95% CI 0.39–0.82; 6 trials, n = 440; low certainty) and a shorter duration of mechanical ventilation (–1.58 days; 95% CI –2.91 to –0.26; 2 trials, n = 85; low certainty). No effect was observed on ICU or hospital stay. Adverse event reporting was sparse, but no consistent safety concerns were identified. Conclusions In adults with acute TBI, beta-blockers did not decrease unfavorable long-term neurological outcomes but were associated with lower mortality and shorter duration of mechanical ventilation. Given the small number of trials and very low certainty of evidence, definitive conclusions cannot be drawn, and routine use cannot be recommended. A large, well-designed RCT is needed to establish the efficacy and safety of beta-blockers in this population. Systematic review registration PROSPERO CRD42024565361.