Liberal Versus Restrictive Red Blood Cell Transfusion in Acute Brain Injury

Background: The optimal hemoglobin (Hb) threshold for red blood cell transfusion in acute brain injury (ABI) remains uncertain, and a restrictive approach has long been the default in neurocritical care. Three pivotal randomized controlled trials (RCTs) published in 2024-2025 each signaled potential benefit from a more liberal strategy but were individually underpowered for neurological outcome and addressed different ABI subtypes. No quantitative synthesis has integrated this contemporary evidence across the ABI spectrum. Methods: We performed a systematic review and meta-analysis of RCTs comparing liberal (Hb trigger 9-10 g/dL) versus restrictive (Hb trigger 7-8 g/dL) transfusion strategies in adults with ABI (traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage). The primary outcome was unfavorable neurological outcome as defined by each trial (mRS ≥4 or GOS-E). Secondary outcomes were cerebral ischemia and all-cause mortality. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using random-effects Mantel-Haenszel models. Robustness was assessed with leave-one-out analysis and a sensitivity analysis applying a fixed GOS-E dichotomy. Risk of bias was evaluated with RoB 2. Results: Three RCTs comprising 2,267 patients were included. A liberal strategy significantly reduced unfavorable neurological outcome compared with a restrictive strategy (RR 0.90, 95% CI 0.84-0.96; p=0.001; I 2 =0%). The effect was confirmed in the sensitivity analysis (RR 0.89, 95% CI 0.83-0.95) and was consistent across leave-one-out iterations, although significance was attenuated when the largest trial was omitted (RR 0.92, 95% CI 0.85-1.00). No significant differences were observed in cerebral ischemia (RR 0.78, 95% CI 0.58-1.04; I 2 =25%) or all-cause mortality (RR 0.98, 95% CI 0.85-1.13; I 2 =0%), with point estimates numerically favoring the liberal strategy and no signal of transfusion-related harm. Conclusions: In this pooled analysis of contemporary RCTs spanning the ABI spectrum, a liberal transfusion strategy improved neurological outcomes without increasing cerebral ischemia or mortality. These findings challenge the prevailing restrictive paradigm and support liberal hemoglobin thresholds as the preferred transfusion approach in acute brain injury. Confirmation in adequately powered trials, ideally via individual-patient-data meta-analysis, is warranted.