Transfusion Thresholds and Neurological Functional Outcome After Acute Brain Injury: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Background/Objectives: The benefits of liberal transfusion strategies for neurological outcomes in critically ill patients with acute brain injuries (ABIs) remain uncertain due to conflicting evidence and potential risks. This study aimed to evaluate the efficacy and safety of a liberal transfusion strategy in adults with ABI. Methods: A systematic review of PubMed, Scopus, and the Cochrane Library was conducted from inception until 18 December 2024. Randomized clinical trials (RCTs) comparing liberal and restrictive transfusion strategies in adult patients admitted to intensive care units with ABI were included. The primary outcome was unfavorable neurological function at the last follow-up, defined as Glasgow Outcome Scale (GOS) score <4, Extended GOS score <5, or modified Rankin Scale score >3. Results: Among 5859 screened records, five RCTs (2385 patients) met the inclusion criteria. Liberal transfusion significantly reduced unfavorable neurological outcomes (RR, 0.88; 95% CI, 0.82-0.95; p = 0.0009) without affecting mortality (RR, 0.97; 95% CI, 0.84-1.11; p = 0.66). A meta-analysis of two studies (n = 1465 patients) showed improved functional independence with liberal strategies (MD, 6.70; 95% CI, 2.07-11.33; p = 0.005) but no difference in quality of life (p = 0.30). Sepsis or septic shock occurred less frequently in the liberal group (RR, 0.68; 95% CI, 0.50-0.92; p = 0.01). Subgroup analysis indicated that liberal strategies improved neurological outcome in traumatic brain injury (TBI) patients (RR, 0.89; 95% CI, 0.82-0.97; p = 0.01) but did not yield significant differences in spontaneous subarachnoid hemorrhage (p = 0.09). Conclusions: Liberal transfusion strategies safely improve neurological outcomes in adults with ABI, specifically in the subgroup of TBI, whereas further studies are needed in patients with SAH.

Keywords: Glasgow Outcome Scale; blood transfusion; intensive care unit; subarachnoid hemorrhage; traumatic brain injury.

Figure 1

Study selection: PRISMA flowchart presenting the selection of eligible studies.

Figure 2

Forest plot of unfavorable neurological outcome and subgroup analyses. Forest plot for the primary outcome in the entire population (A), for the subgroup of traumatic brain injury patients (B), and for the subgroup of subarachnoid hemorrhage patients (C). Squares indicate the point estimates for individual studies, with their size proportional to the statistical weight of each study. Horizontal lines beside the squares indicate the confidence intervals for each study. Diamonds indicate the pooled effect estimates, with their width representing the 95% confidence interval. The vertical line represents the null effect; diamonds that do not cross this line indicate a statistically significant effect [6,7,8,9].

Figure 3

Forest plot for mortality and other secondary outcomes. (A) displays the forest plot for mortality at the last follow-up, (B) presents the forest plot for hospital length of stay, (C) illustrates the forest plot for the Functional Independence Measure, (D) shows the forest plot for quality of life. Squares indicate the point estimates for individual studies, with their size proportional to the statistical weight of each study. Horizontal lines beside the squares indicate the confidence intervals for each study. Diamonds indicate the pooled effect estimates, with their width representing the 95% confidence interval. The vertical line represents the null effect; diamonds that do not cross this line indicate a statistically significant effect [6,7,8,9,22].