Mortality Risk Across Early RBC-Equivalent Transfusion Burden in the Whole Blood Era

Background: Concepts of massive transfusion and transfusion-associated futility were largely established during the component therapy era. Increasing whole blood use may alter the relationship between transfusion burden and mortality. We characterized the continuous association between RBC-equivalent transfusion burden and in-hospital mortality in a contemporary national trauma cohort. Study Design: Adult trauma patients receiving ≥1 unit of packed red blood cells within 4 hours of admission were identified in American College of Surgeons TQIP from 2020 to 2023. RBC-equivalent transfusion burden was defined as packed red blood cells plus whole blood units administered within 4 hours. The primary outcome was in-hospital mortality. Multivariable spline-based logistic regression modeled mortality across transfusion burden and identified the maximum mortality slope, 50% predicted mortality, and plateau onset. Results: Among 126,271 patients, 85,832 (68.0%) sustained blunt and 40,439 (32.0%) penetrating injury. Mortality increased nonlinearly with escalating RBC-equivalent transfusion burden. Maximum slope occurred at 21.1 units, the 95th percentile of transfusion burden. Predicted mortality reached 50% at 41.9 units, the 99th percentile, and plateau onset occurred at 55.3 units. Mortality did not approach 100% despite extreme transfusion requirements. Conclusions: In a contemporary national trauma cohort, mortality increased nonlinearly across RBC-equivalent transfusion burden, with distinct high-risk regions near 21, 42, and 55 units. These reference points may contextualize trajectories during active resuscitation while demonstrating that extreme transfusion requirements are not synonymous with universal mortality.