ALM Resuscitation Without Transfusion Improves Platelet Function and Survival After Liver Injury and Uncontrolled Hemorrhage

<i>Background and Objectives</i>: Traumatic hemorrhage is a leading cause of death. Our aim was to examine the effect of adenosine, lidocaine and magnesium (ALM) resuscitation therapy with and without fresh frozen plasma (FFP) or fresh whole blood (FWB) in a rat model of non-compressible hemorrhage. <i>Materials and Methods</i>: Anesthetized adult male Sprague-Dawley rats (439 ± 46 g) randomly assigned to (1) Shams (surgical trauma and liver isolation only without hemorrhage) (n = 34), (2) Saline controls (n = 34), or (3) ALM therapy (n = 34), underwent liver resection and uncontrolled bleeding. After 5 h 3% NaCl ± ALM bolus and 0.9% NaCl ± ALM drip fluid resuscitation, each group was randomized to receive no transfusion (NT) (n = 10 per treatment group), FFP (n = 12), or FWB (n = 12), and monitored for 72 h. Survival, hemodynamics, lactate, hematology, coagulation, platelet function, and lung histopathology were measured. <i>Results</i>: Sham, Saline and ALM NT survival were 50%, 0% and 100%. Sham survival increased to 75% with FFP, but not FWB (50%), and only marginally in the Saline group (8% and 17%, respectively). ALM protection was lost after 1-2 days with FFP and FWB (8% and 0% survival). Mortality was associated with acute lung injury, inflammation, activation of innate immunity, intrinsic hypocoagulopathy, and metabolic acidosis. Survival was associated with maintained platelet count and aggregation. Acute phase protein fibrinogen increased ~2.5 times in both survivors and non-survivors. <i>Conclusions</i>: ALM therapy without FFP or FWB transfusion significantly improved survival, reduced lung injury, preserved platelet function, and decreased immune and metabolic dysfunction. Blood products administered 5 h after injury did not significantly improve survival after non-compressible hemorrhage. Surgical trauma (laparotomy and liver isolation) also contributed to poor outcomes. The trauma and transfusion-related multi-system failure requires further investigation.