Evaluating the Whole Blood Survival Advantage: How Citrate and Calcium Levels Drive Mortality in a Translational...

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 (Ca²⁺) supplementation, hemodynamic stability, and survival during massive transfusion.

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 Ca²⁺ supplementation (WB/-Ca), WB with Ca²⁺ supplementation (WB/+Ca), simulated component therapy without Ca2+ supplementation (COMP/-Ca), or simulated component therapy with Ca²⁺ 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 Ca²⁺, potassium, and lactate.

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.

In this polytrauma model, simulated COMP with excess citrate and without Ca²⁺ supplementation was associated with lower ionized Ca²⁺, hemodynamic instability, and decreased survival. These findings support further investigation into how citrate burden and Ca²⁺ supplementation strategies influence massive transfusion physiology during WB and COMP-based resuscitation.