Abstract Background Traumatic brain injury (TBI) needs inter-disciplinary care through pre-hospital resuscitation, emergency and neurosurgical care, neurocritical care, and structured neurorehabilitation to maximize survival and post-injury functioning. Objective To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2010 and 2025 assessing contemporary multidisciplinary interventions to manage TBI at the continuum of care, including the emergency control to neurorehabilitation. Methods Systematic searching of the MEDLINE, Embase, Cochrane CENTRAL databases, and clinical trials registers for RCTs published in the English language on TBI interventions (prehospital, neurosurgical, neurocritical, pharmacological, and rehabilitation) was conducted, including those that described the protocolized intervention vs. standard care in terms of mortality, functional outcome, or intracranial pressure (ICP). Risk of bias in the RCTs was analyzed using the Cochrane RoB 2.0 tool. Due to the heterogeneity of the domains, the meta-analysis was strictly restricted to the highly comparable clusters, while for the heterogeneous domains, unpooled visual displays of the study-specific effect size estimates were constructed to avoid the risk of invalid synthesis. Results Eighteen RCTs ( n > 20,000 patients) fulfilled inclusion criteria. Efficacy of treatment was highly dependent on context. Early TXA reduced head injury-related mortality for mild-moderate TBI when given within 3 h. Decompressive craniectomy was highly effective for refractory ICP and mortality reduction, but at the cost of increased survival with severe disability for diffuse injury. Acute-phase neuroprotective strategies (progesterone, citicoline) and prophylactic hypothermia were ineffective. In contrast, structured outpatient rehabilitation and high-intensity gait training were favorable for functional and symptom-related outcomes. GRADE was moderate for mortality and ICP, low for participation. Conclusion However, contemporary RCT evidence suggests that there are no interventions that universally improve the functional prognosis of heterogeneous TBI populations. Rather, clinical benefits are heavily dependent on highly specific applications, such as early hemostasis, careful surgical approaches for decompressive surgeries balancing disability risk, and formal inclusion of structured, goal-directed multidisciplinary rehabilitative approaches.
Yadav et al. (Thu,) studied this question.
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