title: Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in Swine.
abstract: BACKGROUND
  An effective hemostatic agent capable of stopping severe arterial bleeding and sustaining hemostasis over a prolonged time is required. The U.S. Army recently distributed fibrin sealant (under an Investigational New Drug-approved protocol) and chitosan dressings among deployed medics for treating severe external hemorrhage on the battlefield. The purpose of this study was to evaluate the efficacy of these dressings, as compared with the standard gauze army field dressing, to provide initial and sustained hemostasis up to 96 hours in a lethal uncontrolled arterial hemorrhage model.
  
  
  METHODS
  Anesthetized pigs were splenectomized and chronically instrumented for fluid/drug administration and continuous monitoring of vital signs. An infrarenal aortotomy was created using a 4.4-mm aortic hole punch and free bleeding was allowed for 5 seconds. While bleeding profusely, a dressing was applied and pressed into the wound for 4 minutes (occluding the distal flow) and then released. If hemostasis was not obtained, the dressing was replaced with a new one (maximum, two dressings per experiment) with another 4-minute compression. If hemostasis was achieved, the abdomen was closed; the animal was then recovered and monitored up to 96 hours. Initial hemostasis, duration of hemostasis, survival time, blood loss, and other variables were measured.
  
  
  RESULTS
  Application of army field dressing (gauze) did not stop the arterial hemorrhage and led to exsanguination of all the pigs (n = 6) within 10 to 15 minutes of the injury. Chitosan dressing produced initial hemostasis in five of seven pigs. However, the dressings failed to maintain hemostasis for more than 1.6 hours (range, 28-102 minutes), resulting in secondary bleeding and death of the animals. Fibrin sealant dressing produced initial hemostasis in all the pigs (n = 6) and maintained hemostasis in five cases, with one failure at 2.2 hours. These pigs resumed normal activities and lived for the 96-hour experiment duration. Computed tomographic images and histologic sections of the aortas from surviving fibrin sealant dressing-treated animals showed formation of pseudoaneurysms and early granulation tissue at the aortotomy site. The posttreatment blood loss, duration of hemostasis, and survival time were significantly different in the fibrin sealant dressing group than the chitosan dressing and army field dressing groups.
  
  
  CONCLUSIONS
  Both chitosan dressing and fibrin sealant dressing stopped initial arterial bleeding that could not be controlled by the standard army field dressing. However, although the fibrin sealant dressing secured hemostasis for up to 4 days, the chitosan dressing consistently failed within 2 hours after application. There may be a risk of rebleeding for high-pressure arterial wounds treated with chitosan dressings, particularly in situations where definitive care is delayed substantially.
authors.affiliation: U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 8234-6315, USA. bijan.kheirabadi@cen.amedd.army.mil
authors.forename: Bijan S
authors.initials: BS
authors.lastname: Kheirabadi
authors.forename: Eric M
authors.initials: EM
authors.lastname: Acheson
authors.forename: Rudolfo
authors.initials: R
authors.lastname: Deguzman
authors.forename: Jill L
authors.initials: JL
authors.lastname: Sondeen
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Ryan
authors.forename: Angel
authors.initials: A
authors.lastname: Delgado
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dick
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001012:Aorta, Abdominal / Q000293:injuries*; D048271:Chitosan / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use*; D006470:Hemorrhage / Q000628:therapy*; D006489:Hemostatic Techniques; D009779:Occlusive Dressings; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013552:Swine; D016896:Treatment Outcome
chemical_list: D015718:Fibrin Tissue Adhesive; D048271:Chitosan