Percutaneous delivery of self-propelling thrombin-containing powder increases survival from noncompressible truncal hemorrhage in a swine model of coagulopathy and hypothermia.

J Trauma Acute Care Surg

From the Michael Smith Laboratories, Department of Biochemistry and Molecular Biology (M.F.C., N.A.-M., H.Z.G., C.J.K.); School of Biomedical Engineering (M.F.C.); Department of Mechanical Engineering (H.Y., D.G.), The University of British Columbia, Vancouver, British Columbia, Canada; Blood Research Institute (H.Y., C.J.K.), Versiti; Departments of Surgery (H.Y., C.J.K.), Biochemistry (H.Y., C.J.K.), Biomedical Engineering (H.Y., C.J.K.), and Pharmacology and Toxicology (H.Y., C.J.K.), Medical College of Wisconsin, Milwaukee, Wisconsin; CoMotion Drug Delivery Systems (J.R.B.), Vancouver, British Columbia, Canada; Toronto Research Centre (H.P.), Defense Research and Development Canada; Department of Surgery (J.R.-N., A.B.), St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Emergency Medicine (N.J.W.), Harborview Medical Center, University of Washington, Seattle, Washington; and Suffield Research Centre (C.T., H.A.S.), Defense Research and Development Canada, Medicine Hat, Alberta, Canada.

Published: August 2022

Background: Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care. We previously reported that a self-propelling thrombin-containing powder (SPTP) can be delivered percutaneously into the abdomen as a minimally invasive intervention and can self-disperse through pooled blood to deliver the hemostatic agents thrombin and tranexamic acid locally to noncompressible intracavitary wounds. We hypothesized that, in swine with massive NCTH, dilutional coagulopathy, and hypothermia, delivering SPTP could extend survival times.

Methods: Ten swine (n = 5 per group) underwent NCTH from a Grade V liver injury following a midline laparotomy. The laparotomy was closed with sutures afterwards, creating a hemoperitoneum, and animals were managed with crystalloid fluid resuscitation, or crystalloid resuscitation and SPTP. Self-propelling thrombin-containing powder was delivered into the closed abdomen using a CO 2 -powered spray device and a catheter placed into the hemoperitoneum, entering through the upper right quadrant using the Seldinger technique. Survival to 1 and 3 hours was recorded. In an additional animal, hemorrhage was created laparoscopically, and SPTP was imaged in situ within the abdomen to visually track dispersion of the particles.

Results: Self-propelling thrombin-containing powder dispersed as far as 35 ± 5.0 cm within the abdomen. It increased survival to 1 and 3 hours (Kaplan-Meier p = 0.007 for both). The median survival time was 61 minutes with SPTP and 31 minutes without ( p = 0.016).

Conclusion: Self-propelling thrombin-containing powder effectively disperses medications throughout a hemoperitoneum and increases survival in a model of NCTH. It is a promising strategy for nonsurgical management of NCTH, warranting further testing of its safety and efficacy.

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http://dx.doi.org/10.1097/TA.0000000000003670DOI Listing

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