title: Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage.
abstract: 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 as needed for hypotension (maximum: 100 mL/kg) for up to 3 h. Survival was improved with PTG (3-h survival: 8/8, 100%) compared with 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 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, prothrombotic microparticles improved survival and 2 indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds.
authors.affiliation: *Michael Smith Laboratories, University of British Columbia, Vancouver, Canada †Division of Emergency Medicine, University of Washington, Seattle, Washington ‡Centre for Drug Research and Development, Vancouver, Canada.
authors.forename: James R
authors.initials: JR
authors.lastname: Baylis
authors.forename: Alexander E
authors.initials: AE
authors.lastname: St John
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Esther B
authors.initials: EB
authors.lastname: Lim
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Statz
authors.forename: Diana
authors.initials: D
authors.lastname: Chien
authors.forename: Eric
authors.initials: E
authors.lastname: Simonson
authors.forename: Susan A
authors.initials: SA
authors.lastname: Stern
authors.forename: Richard T
authors.initials: RT
authors.lastname: Liggins
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: White
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
mesh_terms: D000818:Animals; D001458:Bandages; D004195:Disease Models, Animal; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy* / Q000628:therapy*; D006490:Hemostatics; D015233:Models, Statistical; D013552:Swine; D013917:Thrombin / Q000008:administration & dosage* / Q000627:therapeutic use*; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D006490:Hemostatics; D014148:Tranexamic Acid; D013917:Thrombin