Effects of rapid wound sealing on survival and blood loss in a swine model of lethal junctional arterial hemorrhage

John, Alexander E. St.; Wang, Xu; Lim, Esther B.; Chien, Diana; Stern, Susan A.; White, Nathan J.

doi:10.1097/ta.0000000000000746

Cited by 34 publications

(26 citation statements)

References 14 publications

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“…(16–18) We have previously shown that this model is 100% lethal without treatment, with median survival time of 36 min. (19) All animal handling and procedures were approved by the University of Washington Office of Animal Welfare or the University of British Columbia Animal Care Committee and performed in accordance with the guidelines established by the Canadian Council on Animal Care and the National Institutes of Health guidelines for the use of laboratory animals. Immature female Yorkshire mix swine (25–30 kg) were fasted overnight with water ad libitum prior to the study.…”

Section: Methodsmentioning

confidence: 99%

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Baylis

John

Wang

et al. 2016

Shock

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Hemorrhage is the leading cause of preventable death in trauma, and hemorrhage from noncompressible junctional anatomic sites is particularly difficult to control. The current standard is QuikClot Combat Gauze packing, which requires 3 min of compression. We have created a novel dressing with calcium carbonate microparticles that can disperse and self-propel upstream against flowing blood. We loaded these microparticles with thrombin and tranexamic acid and tested their efficacy in a swine arterial bleeding model without wound compression. Anesthetized immature female swine received 5 mm femoral arteriotomies to induce severe junctional hemorrhage. Wounds were packed with kaolin-based QuikClot Combat Gauze (KG), propelled thrombin-microparticles with protonated tranexamic acid (PTG), or a non-propelling formulation of the same thrombin-microparticles with non-protonated tranexamic acid (NPTG). Wounds were not compressed after packing. Each animal then received one 15 mL/kg bolus of hydroxyethyl starch solution followed by Lactated Ringer’s as needed for hypotension (maximum: 100 mL/kg) for up to 3 hours. Survival was improved with PTG (3-hr survival: 8/8, 100%) compared to KG (3/8, 37.5%) and NPTG (2/8, 25%) (p<0.01). PTG animals maintained lower serum lactate and higher hemoglobin concentrations than NPTG (p<0.05) suggesting PTG decreased severity of subsequent hemorrhagic shock. However, total blood loss, Lactated Ringer’s infusion volumes, and mean arterial pressures of surviving animals were not different between groups (p>0.05). Thus, in this swine model of junctional arterial hemorrhage, gauze with self-propelled, pro-thrombotic microparticles improved survival and two indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds.

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Section: Methodsmentioning

confidence: 99%

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Baylis

John

Wang

et al. 2016

Shock

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“…A recent comparative animal laboratory study of a complex vascular groin injury revealed that all (100%) animals treated with the iTClamp lived through the end of the experiment, compared with 60% in standard gauze treated and 0% of untreated control animals (early and late iTClamp vs control and standard gauze, Fisher's exact, p=0.003) 18. In a lethal swine bleeding model (femoral artery injury), the iTClamp was 100% effective at controlling bleeding,18 packing+iTClamp reported a 100% survival rate and the iTClamp improved survival and decreased haemorrhage in both packed and unpacked wounds 19. Another preclinical reperfused cadaver study demonstrated that the iTClamp was effective at controlling blood loss from multiple compressible zones including the scalp, neck, groin and extremities 23…”

Section: Discussionmentioning

confidence: 97%

“…Preclinical studies have demonstrated the safety and effectiveness of the iTClamp to control bleeding 19. Surprisingly, however, the impact of care under fire medical aid such as tourniquet application has yet to be examined.…”

Section: Introductionmentioning

confidence: 99%

Randomised controlled trial comparing marksmanship following application of a tourniquet or haemostatic clamp in healthy volunteers

et al. 2016

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“…To measure the effects of gauze loaded with spTXA on hemorrhage volumes, plasma TXA concentrations, and survival, we conducted a single‐arm pilot study using a swine femoral artery injury model. Swine experiments, including femoral artery injury, resuscitation, and measurement of hemorrhage volume, plasma concentration of TXA, and survival via mean arterial pressure, were conducted exactly as previously described . This protocol was adapted from one used by the U.S. Army to evaluate topical hemostatic agents and has reached widespread use .…”

Section: Methodsmentioning

confidence: 99%

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles

Baylis

Lee

John

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Endogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately. Objectives To determine whether self‐propelling particles could increase the efficacy of TXA. Methods Using previously developed self‐propelling particles, which consist of calcium carbonate and generate CO2 gas, TXA was formulated to disperse in blood and wounds. The antifibrinolytic properties were assessed in vitro and in a murine tail bleeding assay. Self‐propelled TXA was also tested in a swine model of junctional hemorrhage consisting of femoral arteriotomy without compression. Results Self‐propelled TXA was more effective than non‐propelled formulations in stabilizing clots from lysis in vitro and reducing blood loss in mice. It was well tolerated when administered subcutaneously in mice up to 300 to 1000 mg/kg. When it was incorporated in gauze, four of six pigs treated after a femoral arteriotomy and without compression survived, and systemic concentrations of TXA reached approximately 6 mg/L within the first hour. Conclusions A formulation of TXA that disperses the drug in blood and wounds was effective in several models. It may have several advantages, including supporting local clot stabilization, reducing blood loss from wounds, and providing systemic delivery of TXA. This approach could both improve and simplify prehospital trauma care for penetrating injury.

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Effects of rapid wound sealing on survival and blood loss in a swine model of lethal junctional arterial hemorrhage

Cited by 34 publications

References 14 publications

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage

Randomised controlled trial comparing marksmanship following application of a tourniquet or haemostatic clamp in healthy volunteers

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles

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