PREHOSPITAL PLASMA IS NONINFERIOR TO WHOLE BLOOD FOR RESTORATION OF CEREBRAL OXYGENATION IN A RHESUS MACAQUE MODEL OF TRAUMATIC SHOCK AND HEMORRHAGE.

ABSTRACT: Introduction: Traumatic shock and hemorrhage (TSH) is a leading cause of preventable death in military and civilian populations. Using a TSH model, we compared plasma with whole blood (WB) as prehospital interventions, evaluating restoration of cerebral tissue oxygen saturation (CrSO 2 ), systemic hemodynamics, colloid osmotic pressure (COP) and arterial lactate, hypothesizing plasma would function in a noninferior capacity to WB, despite dilution of hemoglobin (Hgb). Methods: Ten anesthetized male rhesus macaques underwent TSH before randomization to receive a bolus of O(-) WB or AB(+) plasma at T0. At T60, injury repair and shed blood (SB) to maintain MAP > 65 mm Hg began, simulating hospital arrival. Hematologic data and vital signs were analyzed via t test and two-way repeated measures ANOVA, data presented as mean ± SD, significance = P < 0.05. Results: There were no significant group differences for shock time, SB volume, or hospital SB. At T0, MAP and CrSO 2 significantly declined from baseline, though not between groups, normalizing to baseline by T10. Colloid osmotic pressure declined significantly in each group from baseline at T0 but restored by T30, despite significant differences in Hgb (WB 11.7 ± 1.5 vs. plasma 6.2 ± 0.8 g/dL). Peak lactate at T30 was significantly higher than baseline in both groups (WB 6.6 ± 4.9 vs. plasma 5.7 ± 1.6 mmol/L) declining equivalently by T60. Conclusions: Plasma restored hemodynamic support and CrSO 2 , in a capacity not inferior to WB, despite absence of additional Hgb supplementation. This was substantiated via return of physiologic COP levels, restoring oxygen delivery to microcirculation, demonstrating the complexity of restoring oxygenation from TSH beyond simply increasing oxygen carrying capacity.

Prehospital adenosine, lidocaine, and magnesium has inferior survival compared with tactical combat casualty care resuscitation in a porcine model of prolonged hemorrhagic shock.

BACKGROUND: Adenosine, lidocaine, and magnesium (ALM) is a cardioplegic agent shown to improve survival by improving cardiac function, tissue perfusion, and coagulopathy in animal models of shock. We hypothesized prehospital ALM treatment in hemorrhagic shock would improve survival compared to current Tactical Combat Casualty Care (TCCC) resuscitation beyond the golden hour. METHODS: Swine were randomized to: (1) TCCC, (2) 2 mL·kg vehicle control (VC), (3) 2 mL·kg ALM + drip, (4) 4 mL·kg ALM + drip, 5) 4 mL·kg ALM + delayed drip at 0.5 mL·kg·h, 6) 4 mL/kg VC, 7) 4 mL·kg ALM for 15 minutes + delayed drip at 3 mL·kg·h. Animals underwent pressure controlled hemorrhage to mean arterial pressure (MAP) of 30 mm Hg (S = 0). Treatment was administered at T = 0. After 120 minutes of simulated prehospital care (T = 120) blood product resuscitation commenced. Physiologic variables were recorded and laboratories were drawn at specified time points. RESULTS: Tactical Combat Casualty Care demonstrated superior survival to all other agents. The VC and ALM groups had lower MAPs and systolic blood pressures compared with TCCC. Except for the VC groups, lactate levels remained similar with correction of base deficit after prehospital resuscitation in all groups. Kidney function and liver function remained comparable across all groups. Compared with baseline values, TCCC demonstrated significant hypocoagulability. CONCLUSION: Adenosine, lidocaine, and magnesium, as administered in this study, are inferior to current Hextend-based resuscitation for survival from prolonged hemorrhagic shock in this model. In survivors, ALM groups had lower systolic blood pressures and MAPs, but provided a protective effect on coagulopathy as compared to TCCC. Adenosine, lidocaine, and magnesium do not appear to be a suitable low volume replacement to current TCCC resuscitation. The reduced coagulopathy compared to TCCC warrants future studies of ALM, perhaps as a therapeutic adjunct.

Whole blood and Hextend: Bookends of modern tactical combat casualty care field resuscitation and starting point for multifunctional resuscitation fluid development.

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.

Development of a Nonhuman Primate (Rhesus Macaque) Model of Uncontrolled Traumatic Liver Hemorrhage.

Hemorrhage is the leading cause of potentially survivable trauma mortality, necessitating the development of improved therapeutic interventions. The objective of this study was to develop and characterize a reproducible clinically translatable nonhuman primate model of uncontrolled severe hemorrhage. Such a model is required to facilitate the development and meaningful evaluation of human-derived therapeutics. In Rhesus macaques, a laparoscopic left-lobe hepatectomy of 25% (n = 2), 50% (n = 4), or 60% (n = 6) was performed at T = 0 min, with no attempt at hemorrhage control until T = 120 min. A constant-rate infusion of normal saline was administered between T = 15 and 120 min to a total volume of 20 mL/kg. At T = 120 min, a laparotomy was performed to gain surgical hemostasis and quantify blood loss. Physiological parameters were recorded, and blood samples were collected at defined intervals until termination of the study at T = 480 min. Statistical analyses used Student t tests, with P < 0.05 considered statistically significant. Results are reported as mean ± SEM. The calculated percent blood loss for the 25% hepatectomy group was negligible (2.3% ± 0.2%), whereas the 50% and 60% hepatectomy groups exhibited 26.6% ± 7.1% and 24.9% ± 3.8% blood loss, respectively. At T = 5 min, blood pressure for the 25%, 50%, and 60% hepatectomy groups was reduced by 13.8%, 60.8%, and 63.2% from the respective baseline values (P < 0.05). In the 60% hepatectomy group, alterations in thromboelastometry parameters and systemic inflammatory markers were observed. The development of a translatable nonhuman primate model of uncontrolled hemorrhage is an ongoing process. This study demonstrates that 60% hepatectomy offers a significant reproducible injury applicable for the evaluation of human-derived therapeutics.