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Cau, Massimo Francesco

University of British Columbia

Hemorrhage is a leading cause of preventable death in civilian and military trauma settings. Noncompressible truncal hemorrhage (NCTH) is the most lethal type of hemorrhage; 67% of hemorrhage deaths are from the thorax, abdomen, or pelvis. NCTH can currently only be definitively managed by surgery. During delays to surgery, prehospital interventions prevent the development of coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care. Topical hemostatic agents commonly used during surgery are not currently used for managing NCTH as they cannot be locally delivered to internal sites of bleeding. The central hypothesis of this thesis is that increasing the local delivery of hemostatic agents within truncal wounds will enable them to manage NCTH. Hemostatic powders propelled through catheters could address internal non-compressible bleeding. A highly hemostatic and flowable powder called self-propelling thrombin powder (SPTP) was formulated and tested in vivo. When delivered endoscopically using a CO2 powered spray device, it achieved rapid hemostasis in 100% of bleeds using swine models of upper gastrointestinal bleeding (UGIB), and led to normal wound healing without rebleeding. SPTP was delivered into the trunk of swine as a minimally invasive procedure. The safety of the procedure, and the ability of powder to self-propel (or self-disperse) throughout high volumes of bleeding was evaluated. The delivery procedure achieved near 100% target delivery. No adverse effects were observed, and the hemostatic powder group demonstrated a trend to increased median survival compared to control animals. Following refinement of the delivery device, the hemostatic powder formulated with thrombin and tranexamic acid significantly increased survival compared to control animals in a reproducible, lethal model of NCTH based on a Grade V liver injury with coagulopathy and hypothermia. The powder effectively dispersed within the abdomen and into the site of liver injury. In conclusion, increasing the local delivery of hemostatic agents within truncal wounds by formulating them as a self-dispersing hemostatic powder improves clinical outcomes from NCTH. Delivery of the hemostatic powder is readily achieved using a minimally invasive procedure without requiring surgical techniques, and could be translated for future management of NCTH in humans.  

Text

2023-04-20

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/84379

Biomedical Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/