Efficacy and safety of novel freeze-dried plasma products in a porcine combat casualty model.

BACKGROUND: Hemorrhagic shock is well documented as a leading cause of preventable fatalities among military casualties. During military operations plasma can be transfused while waiting for whole blood. This study was conducted to assess the safety and efficacy of two new freeze-dried plasma formulations in a porcine model of traumatic hemorrhagic shock. STUDY DESIGN AND METHODS: In the face of species-specific transfusion, transfusible blood products were derived from porcine sources. The efficacy of three lyophilized plasma (LP) formulations was evaluated: lyophilized plasma (LP), concentrated lyophilized plasma (CLP), and platelet-rich concentrated lyophilized plasma (PCLP). Pigs were subjected to multi-trauma and hemorrhagic shock. Ninety minutes post-shock induction, the animals were treated with one of the three lyophilized products. Monitoring included systolic blood pressure and cardiac output. Point-of-care and laboratory diagnostic tests were used to assess renal function, real-time hemostasis (ROTEM), and coagulation. Histological examinations of kidney, lung, and muscle tissues were conducted 4 h after shock induction. RESULTS: CLP and PCLP significantly improved systolic blood pressure and cardiac output and positively influenced base excess, creatinine, various ROTEM, and coagulation markers compared with standard LP without histologic modification. No adverse effect was associated with the transfusion of any of the plasma products throughout the experimental procedures. CONCLUSION: Both CLP and PCLP exhibit promising therapeutic potential for managing hemorrhagic shock in scenario where whole blood supplies are limited. However, the distinct physiological and coagulation characteristics of the swine model necessitate further investigation using humanized preclinical models to fully understand their clinical applicability and constraints.

Danger signals in traumatic hemorrhagic shock and new lines for clinical applications.

Hemorrhage is the leading cause of death in severe trauma injuries. When organs or tissues are subjected to prolonged hypoxia, danger signals-known as damage-associated molecular patterns (DAMPs)-are released into the intercellular environment. The endothelium is both the target and a major provider of damage-associated molecular patterns, which are directly involved in immuno-inflammatory dysregulation and the associated tissue suffering. Although damage-associated molecular patterns release begins very early after trauma, this release and its consequences continue beyond the initial treatment. Here we review a few examples of damage-associated molecular patterns to illustrate their pathophysiological roles, with emphasis on emerging therapeutic interventions in the context of severe trauma. Therapeutic intervention administered at precise points during damage-associated molecular patterns release may have beneficial effects by calming the inflammatory storm triggered by traumatic hemorrhagic shock.

A New Anthropomorphic Mannequin for Efficacy Evaluation of Thoracic Protective Equipment Against Blast Threats.

Exposure to blast is one of the major causes of death and disability in recent military conflicts. Therefore, it is crucial to evaluate the protective capability of the ballistic-proof equipment worn by soldiers against the effects of blast overpressure (i.e., primary blast injuries). A focus will be made on thoracic protective equipment (TPE). An anthropomorphic mannequin, called BOPMAN, and anesthetized swine both wearing soft, hard or no ballistic protection, were subjected to an open-field high-intensity blast. For swine, thoracic wall motion (acceleration and velocity) was recorded during blast exposure and severity of lung injury was evaluated postmortem. Different data were collected from BOPMAN thoracic responses, including reflected and internal pressure, as well as the force at the rear face of the instrumented part. The severity of blast-induced lung injuries (contusion extent, Axelsson Severity Scale) and the thoracic wall motion were decreased in animals protected with thoracic ceramic hard plates as compared to those wearing soft or no protection. There was a clear trend towards greater lung injury in animals protected with the soft body armor used, even when compared to unprotected animals. In line with these experimental data, the measured force as well as the force impulse measured using BOPMAN were also decreased with a ceramic hard plate protection and increased when a soft ballistic pack was used compared to no protection. Comparison of data collected on BOPMAN and swine equipped with the same protection level revealed that those two force parameters were well correlated with the level of blast-induced lung injury (force, R2 = 0.74 and force impulse, R2 = 0.77, p < 0.05). Taken together, our results suggest that the force and the force impulse data from BOPMAN may help estimate the efficiency of existing TPE regarding lung protection under blast exposure and may represent an important tool for development of future TPE.