Recombinant Factor XIIIA and ACTH(1‐24) as Adjuncts During Prolonged Hypotensive Resuscitation in swine ( Sus scrofa domesticus ): Optimizing Outcomes for the Prolonged Field Care Environment

Background Traumatic injuries with hemorrhage are the leading cause of potentially survivable death in trauma. A permissive hypotension strategy (Goal resuscitation systolic blood pressure (SBP) of 80–90 mmHg) plus early blood product administration over a short transport interval has been linked to improved survival. If blood products are unavailable during this pre‐hospital time, crystalloids and colloids such as hydroxy ethyl starch (Hextend®) remain the standard fielded resuscitative fluid. However, studies have demonstrated the correlation of kidney injury and failure, increased risk of coagulopathy, and higher mortality risk with this treatment. To improve outcomes in this prolonged field care (PFC) setting, in the absence of blood products, we investigated the survival and therapeutic benefits of ACTH(1‐24) and rFXIIIA treatment as an adjunct to Hextend® in a permissively hypotensive PFC model of hemorrhagic shock in swine. Methods Anesthetized male swine (n = 16) underwent pressure‐targeted, decompensated hemorrhagic shock (MAP = 30–35 mmHg) for 45 minutes followed by permissively hypotensive (SBP = 80–90) resuscitation with Hextend® for 8 hours (with or without adjuncts such as ACTH(1‐24)), simulating a PFC environment. At the end of PFC, animals were fully resuscitated (return of shed blood plus normal saline). Animals were then monitored for 24 hours and assessed for neurocognitive function via latency to food reward. Sham animals (n = 5) received only anesthesia for the same time period. Tissues and serum were isolated at euthanasia for histopathological and biomarker analysis. Results reported as mean ± SD, Statistics: two‐way ANOVA with P < 0.05 significance. Results Initial results from this experiment indicate successful use of 500 mL (n = 5) versus 1L (n = 5) of Hextend® to model a survivable permissively hypotensive state (SBP 80–90) for up to 8 hours in swine. Hextend® treatment amount shows no significant deleterious cardiovascular (HR, BP; p > 0.05) or metabolic effects (lactate, BD; p > 0.05) following initial shock treatment. ROTEM analysis indicated ACTH treatment (n = 1) decreased the latency for clot formation time in the later stages of PFC compared to the Hextend® + vehicle control. Additionally, there were no significant neurological detriments induced by the prolonged permissive hypotensive state, which makes this model ideal for PFC studies of shock (p > 0.05). Conclusion This swine model of prolonged permissively hypotensive resuscitation was designed to align with pre‐hospital hemorrhage control. The use of ACTH as an adjunct to standard treatments may improve outcomes, specifically with regard to bleeding. These results extend beyond military application to the rural civilian environment, where extended pre‐hospital times are commonplace. Further investigation is underway to elucidate whether rFXIIIA + ACTH, as a combination treatment, could improve PFC outcomes. Support or Funding Information This work was supported by the Defense Medical Research and Development Program, Joint Program Committee 6/Combat Casualty Care Research Program. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .