Mortality in Critically Ill Patients with Liberal Versus Restrictive Transfusion Thresholds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis

Background/Objectives: Anemia is common in critically ill patients, yet red blood cell (RBC) transfusion without active bleeding does not consistently improve outcomes and carries risks such as pulmonary injury, fluid overload, and increased costs. Optimal transfusion thresholds remain debated, with some guidelines recommending a restrictive target of 7 g/dL instead of a more liberal target of 9 g/dL. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, EMBASE, and LILACS from January 1995 to October 2024. Thirteen randomized controlled trials involving 13,705 critically ill adults were included, with 6855 assigned to liberal and 6850 to restrictive transfusion strategies. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2, and the pooled effect sizes were estimated with a random-effects model. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CDR42024589225). Results: No statistically significant difference was observed in 30-day mortality between restrictive and liberal strategies (odds ratio [OR] 1.02; 95% confidence interval [CI], 0.83–1.25; I² = 49%). Similarly, no significant differences emerged for the 90-day or 180-day mortality, hospital or intensive care unit (ICU) length of stay, dialysis requirement, or incidence of acute respiratory distress syndrome (ARDS). However, patients in the restrictive group received significantly fewer RBC units. The trial sequential analysis (TSA) indicated that the evidence accrued was insufficient to definitively confirm or exclude an effect on the 30-day mortality, as the required sample size was not reached. Conclusions: In conclusion, while our meta-analysis found no statistically significant difference in the short-term mortality between restrictive and liberal transfusion strategies, larger trials are needed to fully determine whether any clinically meaningful difference exists in critically ill populations.