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Background: Hemorrhage remains the primary cause of preventable death in civilian and military trauma. The Committee on Tactical Combat Casualty Care recommends prehospital (PH) resuscitation with whole blood (WB). However, 6% hetastarch in lactated electrolyte (HEX) and crystalloids are more commonly available and used for PH resuscitation in military and civilian environments, respectively. The mechanistic benefits of PH WB resuscitation have not been well studied and remain to be elucidated., Study Design and Methods: The aim of this study was to evaluate the differences in simulated PH WB and HEX resuscitation, specifically with regards to coagulation, physiologic, and metabolic outcomes to better elucidate the mechanistic benefits of WB. In a randomized study, the physiologic, coagulation, and metabolic responses to simulated PH WB (n = 12) or HEX (n = 12) were evaluated in a nonhuman primate model of severe polytraumatic hemorrhagic shock., Results: Notable findings included 1) equivalence of shock reversal between simulated PH WB and HEX treatment groups as determined by hemodynamics and base deficit and 2) prevention of coagulopathy at simulated hospital arrival with initial WB resuscitation as determined by viscoelastic and plasmatic coagulation assays., Conclusion: The major benefit of WB, as compared to HEX, in simulated PH resuscitation appears to be prevention of coagulopathy at hospital arrival. Both fluids effectively reversed shock in this model, implying that efficacious provision preload (cardiac output support and hence oxygen delivery) and coagulation proteins (prevention of coagulopathy) are mechanisms underlying WB's effectiveness in early resuscitation of hemorrhagic shock., (© 2019 AABB.)

Introduction: The contributions of type and timing of fluid resuscitation to coagulopathy in trauma remain controversial. As part of a multifunctional resuscitation fluid research effort, we sought to further characterize the coagulation responses to resuscitation, specifically as compared to whole blood. We hypothesized that early whole blood administration mitigates the acute coagulopathy of trauma by avoiding the coagulopathy of CR resuscitation., Methods: Anesthetized rhesus macaques underwent polytraumatic, hemorrhagic shock, then a crossover study design resuscitation (n = 6 each) with either whole blood first (WB-1st) followed by crystalloid (CR); or CR-1st followed by WB. Resuscitation strategies were the following: WB-1st received 50% shed blood in 30minutes, followed by twice the shed blood volume (SBV) of CR over 30minutes and one times the SBV CR over 60minutes, where CR-1st received twice the SBV of CR over 30minutes, followed by 50% of shed blood in 30minutes, and one times the SBV CR over 60minutes. Blood samples were collected at baseline, end-of-shock, end-of-first and end-of-second resuscitation stages, and end-of-resuscitation for assessment (thromboelastometry, platelet aggregation, and plasmatic coagulation factors). Statistical analyses were conducted using two-way analysis of variance ANOVA with Bonferroni correction and t-tests; significance was at p < 0.05., Results: Survival, blood loss, hemodynamics, and shock duration were equivalent between the groups. Compared to baseline, parameters measured at first and second resuscitation stage time points directly following CR infusion revealed abnormalities in thromboelastometry (clot formation time, α angle, and maximum clot firmness), platelet aggregation response (to collagen, arachidonic acid, and adenosine diphosphate), and plasmatic coagulation (prothrombin time, anti-thrombin 3, and fibrinogen), while whole blood infusion resulted in stabilization or correction of these parameters following its administration., Conclusions: These data suggest that in the setting of trauma and hemorrhagic shock, the coagulation alterations begin before intervention/resuscitation; however, these are significantly aggravated by CR resuscitation and could perhaps be best termed acute coagulopathy of resuscitation., Study Type: Translational animal model.

Background: Hemorrhage is the leading cause of preventable death in traumatically injured civilian and military populations. Prehospital resuscitation largely relies on crystalloid and colloid intravascular expansion, as whole blood and component blood therapy are logistically arduous. In this experiment, we evaluated the bookends of Tactical Combat Casualty Care Guidelines recommendations of prehospital resuscitation with Hextend and whole blood in a controlled hemorrhagic shock model within non-human primates, as means of a multifunctional resuscitative fluid development., Methods: In the nonhuman primate, a multiple injuries model was used, consisting of a musculoskeletal injury (femur fracture), soft tissue injury (15-cm laparotomy), and controlled hemorrhage to a mean arterial pressure of 20 mm Hg, demarcating the beginning of the shock period. Animals were randomized to prehospital interventions of whole blood or Hextend at T = 0 minutes, and at T = 90 minutes definitive surgical interventions and balanced sanguineous damage control resuscitation could be implemented. All animals were euthanized at T = 480 minutes. Data are expressed as mean ± SEM; significance, p < 0.05., Results: No significant differences in survival (83% vs. 100%; p = 0.3), tissue perfusion (EtCO2 and StO2) or endpoints of resuscitation (base deficit, lactate, pH) between Hextend and whole blood were identified. Second, whole blood compared with Hextend demonstrated significantly earlier normalization of clot formation time, maximal clot firmness, and α angle., Conclusion: A future multifunctional resuscitative fluid including an asanguineous, oncotic, non-oxygen-carrying component to facilitate intravascular volume expansion, and a component with synthetic coagulation factors and fibrinogen to deter coagulopathy may show equivalence to whole blood., Level of Evidence: N/A: Study type: translational animal model.