Tranexamic acid in the management of traumatic brain injury: a systematic review and meta-analysis with trial sequential analysis.

Introduction: Traumatic brain injury is a leading cause of death and disability. Tranexamic acid, an antifibrinolytic agent, holds the potential for managing intracranial hemorrhages secondary to traumatic brain injury. However, its efficacy and safety remain subjects of ongoing debate.

Objective: To better clarify the efficacy and safety of tranexamic acid in that context and to evaluate the need for further studies.

Methods: We conducted a comprehensive search of seven electronic databases, eight study repositories, and tertiary sources between January 2021 and 2022 for randomized controlled trials involving victims of traumatic brain injury aged 15 or older who received tranexamic acid versus placebo or standard care. The primary outcomes were all-cause mortality and hemorrhagic complications during treatment. This review incorporated elements of PRISMA guidelines, Cochrane's Risk of Bias assessment, and GRADE to assess evidence quality. Sensitivity analyses were also conducted.

Results: Out of 6,958 references retrieved, 14 of the 17 randomized controlled trials were analyzed, encompassing a total of 15,017 patients. Analyses for all-cause mortality did not reach statistical significance (RR= 0.95, 95%CI= 0.88-1.02 | trial sequential analysis RR= 0.95, 95%CI= 0.87-1.03). However, the analysis of hemorrhagic complications during treatment showed statistical significance for progressive intracranial hemorrhage (RR= 0.82, 95%CI= 0.68-0.99 | trial sequential analysis RR= 0.82, 95%CI= 0.38-1.78). Analyses of secondary outcomes, namely unfavorable neurological outcome and other adverse effects, did not demonstrate statistical significance.

Conclusion: Tranexamic acid use did not demonstrate efficacy based on all-cause mortality but showed a favorable safety profile. Additional clinical trials may shed light on remaining clinical uncertainties. Prospero database registration: CRD42021221949.