Efficacy of early enteral nutrition in patients with traumatic brain injury: a systematic review and meta-analysis.

BACKGROUND: Severe traumatic brain injury (TBI) induces a hypermetabolic state that heightens the risk of mortality and poor neurological outcomes. Early enteral nutrition (EEN), typically defined as initiation within 48 h of injury, is considered crucial, yet robust evidence of its specific benefits in TBI patients remains limited. METHODS: Following PRISMA guidelines, we systematically searched the PubMed, Embase, Web of Science, and Cochrane Library databases through December 25, 2025, for studies comparing EEN with delayed enteral nutrition (DEN) in adults with TBI. Outcomes included clinical outcomes, nutrition status, and complications. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. The primary outcome was short-term mortality, defined as from hospital admission to 90 days post-discharge. Sensitivity analyses and subgroup analyses explored heterogeneity. RESULTS: Ten studies (6 randomized controlled trials [RCTs]; 4 observational; 13,046 patients) were included. When all studies (RCTs and observational) were pooled, there was no significant difference in short-term mortality risk between EEN and DEN (risk ratio [RR] = 0.64; 95% CI, 0.32-1.31). However, a prespecified sensitivity analysis limited to RCTs showed a significant reduction in mortality with EEN (RR = 0.58; 95% CI, 0.35-0.96). EEN significantly shortened mechanical ventilation duration and reduced both ICU and hospital length of stay. Nutritional status, including serum albumin levels, glucose control, caloric intake, and positive nitrogen balance, was markedly improved with EEN, without increasing hospitalization costs. EEN also significantly lowered rates of sepsis, central nervous system infection, stress ulcer, ventilator-associated pneumonia, and total adverse events (all p values range from <0.00001 to 0.04), though it was associated with a mildly elevated risk of diarrhea (p = 0.02). CONCLUSION: In this meta-analysis, EEN initiated within 48 h of TBI showed a trend toward reduced short-term mortality and improvements in clinical and nutritional outcomes compared to DEN. However, these findings should be interpreted cautiously given the high risk of bias and substantial statistical heterogeneity in the included studies. Future high-quality, large-scale RCTs are needed to confirm these effects and refine optimal feeding strategies in this population. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/wp-content/uploads/2026/01/INPLASY-Protocol-8729.pdf.