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

Abstract

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.

Efficacy and safety of CounterFlow in animal models of hemorrhage

“…Mice treated with CounterFlow also exhibited a signifcant decrease in blood loss volume compared with controls. 21 CounterFlow, referred to in some studies as selfpropelled thrombin powder, [26][27][28] was delivered internally into the stomach or into the peritoneal space to treat non-compressible injuries (CounterFlow-Powder), or the powder was coated onto gauze (CounterFlow-Gauze) and applied to external, compressible wounds in multiple large animal models of hemorrhage (Figure 2). [21][22][23][24][25][26][27][28] Tese animal models represent severe or lethal bleeds encountered in military or civilian settings.…”

“…21 CounterFlow, referred to in some studies as selfpropelled thrombin powder, [26][27][28] was delivered internally into the stomach or into the peritoneal space to treat non-compressible injuries (CounterFlow-Powder), or the powder was coated onto gauze (CounterFlow-Gauze) and applied to external, compressible wounds in multiple large animal models of hemorrhage (Figure 2). [21][22][23][24][25][26][27][28] Tese animal models represent severe or lethal bleeds encountered in military or civilian settings. CounterFlow-Gauze halts junctional hemorrhage and increases survival in swine Junctional hemorrhage encompasses bleeding from the junction between the torso and an extremity, including the groin, axilla, and neck.…”

“…Terefore, a subsequent study used a more challenging model of NCIAH that included a more severe injury with added coagulopathy and hypothermia, resulting in lower survival. 28 Te injury involved a complete transection of the lef lateral lobe of the liver and a portion of the lef medial lobe, up to 3 centimetres distal to the hilum. Tis generated a Grade V liver injury that was highly lethal in control animals, displayed low variability, and was similar to other models of NCIAH.…”

“…It uses self-propelling particles and efervescence to deliver hemostatics into damaged vasculature against the outward fow of blood. [21][22][23][24][25][26][27][28] Self-propelling hemostatic particles can advance current options for topical hemostasis, because they can penetrate upstream against the fow of blood to reach leaking vessels at the source of the injury, whereas current topical hemostatic agents are carried away by the outward fow of blood. 21 CounterFlow is biodegradable and contributes to clotting while preventing future rebleeding, and it does not need to be surgically removed from the body because all of its ingredients can be dissolved along with the clot and absorbed systemically.…”

“…By bypassing or decreasing the requirement for compression, Coun-terFlow can be applied to both compressible and noncompressible injuries, providing an adaptable, portable, and efective form of hemorrhage control with ease of use for the care provider. [21][22][23][24][25][26][27][28] A product that remains efective as a hemostatic without compression would be easier for personnel during the care-under-fre phase of TCCC and allow for earlier treatment. Tis narrative review focuses on the safety and efcacy testing of CounterFlow that has been conducted so far in animal models of hemorrhage that represent common injuries in military and civilian settings.…”