Recurrent event frailty models reduced time-varying and other biases in evaluating transfusion protocols for traumatic hemorrhage

Abstract Objective Transfusion research seeks to improve survival for severely injured and hemorrhaging patients using optimal plasma and platelet ratios over red blood cells (RBCs). However, most published studies comparing different ratios are plagued with serious bias and ignore time-varying effects. We applied joint recurrent event frailty models to increase validity and clinical utility. Study Design and Setting Using the PRospective Observational Multicenter Major Trauma Transfusion study data, our joint random-effects models estimated the association of (1) clinical covariates with transfusion rate intensities and (2) varying plasma:RBC and platelet:RBC ratios with survival over the 24 hours after hospital admission. Along with survival time, baseline patient vital signs, laboratory values, and longitudinal data on types and volumes of transfusions were included. Results Baseline systolic blood pressure, heart rate, pH, and hemoglobin were significantly associated with RBC transfusion rates. Increased transfusion rates (per hour) of plasma ( P = 0.05), platelets ( P