Evaluating the Whole Blood Survival Advantage: How Citrate and Calcium Levels Drive Mortality in a Translational Swine Model of Polytrauma

Objectives Whole blood (WB) is increasingly used for trauma resuscitation, but clinical comparisons with component therapy (COMP) have reported mixed survival results, and physiologic contributors to any differences remain incompletely defined. We evaluated the association between excess citrate exposure, calcium (Ca 2+ ) supplementation, hemodynamic stability, and survival during massive transfusion. Methods In a randomized swine ( Sus scrofa ) polytrauma model, 32 castrated male and nonpregnant females underwent tibial fracture, blunt liver injury, 30% controlled hemorrhage, and a 30-minute shock period. Animals were assigned to WB without Ca 2+ supplementation (WB/−Ca), WB with Ca 2+ supplementation (WB/+Ca), simulated component therapy without Ca2+ supplementation (COMP/−Ca), or simulated component therapy with Ca 2+ supplementation (COMP/+Ca). Resuscitation occurred during continued hemorrhage, followed by 4 hours of monitoring. The primary outcome was mean arterial pressure (MAP) after completion of transfusion. Secondary outcomes included survival, ionized and serum Ca 2+ , potassium, and lactate. Results Baseline values were similar across groups. Survival was 3 of 8 animals in COMP/−Ca and 8 of 8 animals in each other group (log-rank P < .001). MAP differed significantly between groups over time ( P < .001), with lower MAP in COMP/−Ca compared with WB/−Ca ( P = .0036), WB/+Ca ( P = .0046), and COMP/+Ca ( P = .0076). Ionized Ca2+ was lowest in COMP/−Ca. Conclusions In this polytrauma model, simulated COMP with excess citrate and without Ca 2+ supplementation was associated with lower ionized Ca 2+ , hemodynamic instability, and decreased survival. These findings support further investigation into how citrate burden and Ca 2+ supplementation strategies influence massive transfusion physiology during WB and COMP-based resuscitation.