Dried Plasma to Improve Outcomes in Polytrauma, Hemorrhage, and Trauma-Associated Sepsis (TAS): Novel Solutions for the Prolonged Field Care Environment

Hemorrhagic shock (HS) remains the leading cause of early death among the severely injured in both the civilian and military settings, and patients that survive HS are prone to sepsis. As the treatment of trauma-associated sepsis (TAS) on the battlefield will be unique to prolonged field care, new therapeutic strategies that are feasible and readily translatable are urgently needed. We are proposing the novel use plasma as a primary resuscitative fluid for TAS as we anticipate that the endothelial protective effects seen after HS will also be present after TAS. However, there are logistical challenges and safety issues with the use of fresh frozen plasma (FFP) in the battlefield. We therefore will study the use of pathogen-reduced freeze dried plasma (FDP) and hypothesize that FDP- based resuscitation after TAS will be equivalent to FFP, superior to hextend, and will reduce the endotheliopathy of sepsis (EOS), mitigate vascular and end organ injury, and decrease mortality, in clinically relevant models of TAS. This hypothesis will be tested first in a rodent model to examine systemic, vascular, organ-specific pathophysiology and survival in a mouse model of HS and prolonged hypotensive resuscitation with TAS and then confirmed and expanded using a swine model of TAS to determine the modulatory effects of SDP compared to hextend on hemodynamics, end-organ function, coagulopathy and survival in a swine model of TAS.