title: Comparison of new hemostatic granules/powders with currently deployed hemostatic products in a lethal model of extremity arterial hemorrhage in swine.
abstract: BACKGROUND
  HemCon bandage (HC) and QuikClot granules (QC) have been deployed for the past 5 years for treating external hemorrhage in combat casualties. We examined efficacy and initial safety of three new hemostatic granules/powders in a swine extremity arterial hemorrhage model that was 100% fatal with army standard gauze treatment. The new products were compared with the most advanced forms of HC and QC products.
  
  
  METHODS
  Anesthetized pigs (37 kg, n = 46) were instrumented, splenectomized, and their femoral arteries were isolated and injured (6 mm arteriotomy). After 45 seconds free bleeding, a test agent [WoundStat (WS), super quick relief (SQR), Celox (CX)] or a control product [HC or QC bead bags (advanced clotting sponge plus)] was applied to the wounds and compressed with a large gauze for 2 minutes. Fluid resuscitation (colloid and crystalloid) was given and titrated to a mean arterial pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Computed tomography angiography was performed on survivors and tissue samples were collected form wounds for histologic examination.
  
  
  RESULTS
  No differences were found in baseline measurements and pretreatment blood loss (17.4 mL/kg +/- 0.5 mL/kg, mean +/- SEM) among groups. Advanced clotting sponge plus testing was halted after six unsuccessful attempts (no hemostasis observed) whereas other agents were tested each in 10 animals. Stable hemostasis was achieved in 10 (WS), 7 (SQR), 6 (CX), and 1 (HC) subjects in each group, resulting in the recovery of mean arterial pressure and survival of the animals for 3 hours (p < 0.05, SQR or WS vs. HC). Posttreatment blood loss was significantly reduced with the use of the new agents (CX = 40 +/- 16.6, SQR = 34.5 +/- 16.3, WS = 9.5 mL/kg +/- 5.2 mL/kg) as compared with HC (85.6 mL/kg +/- 10 mL/kg, p < 0.05). The granular treated animals lived for 180 (WS), 164 +/- 8.2 (SQR) and 138 +/- 17.7 (CX) minutes, significantly (p < 0.05) longer than the HC (83.3 +/- 12 minutes) group. A significant (p < 0.05) rise in temperature (53.5 degrees C +/- 1.8 degrees C) over baseline (36.5 degrees C +/- 0.3 degrees C) was measured only in the wounds treated with SQR. Computed tomography images showed no blood flow through treated vessels. Histologic evidence indicated the least tissue damage with HC, moderate damage with WS and CX, and most damage including axonal necrosis with SQR.
  
  
  CONCLUSIONS
  The new hemostatic agents are significantly more effective in treating arterial hemorrhage than currently deployed products. Among them, WS granules appear to be most efficacious, followed by SQR and CX powders. The clinical significance of tissue damage caused by these agents and any potential risk of embolism with procoagulant granular/powder products are unknown and warrant survival studies.
authors.affiliation: US Army Institute of Surgical Research, Fort Sam Houston, Texas 78234-6315, USA. bijan.kheirabadi@cen.amedd.army.mil
authors.forename: Bijan S
authors.initials: BS
authors.lastname: Kheirabadi
authors.forename: Jason W
authors.initials: JW
authors.lastname: Edens
authors.forename: Irasema B
authors.initials: IB
authors.lastname: Terrazas
authors.forename: J Scot
authors.initials: JS
authors.lastname: Estep
authors.forename: Harold G
authors.initials: HG
authors.lastname: Klemcke
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000704:Analysis of Variance; D000792:Angiography; D000818:Animals; D001458:Bandages; D001704:Biopolymers; D005263:Femoral Artery / Q000293:injuries*; D006470:Hemorrhage / Q000628:therapy*; D006489:Hemostatic Techniques; D006490:Hemostatics; D008297:Male; D011208:Powders; D012151:Resuscitation / Q000379:methods; D018709:Statistics, Nonparametric; D013552:Swine; D014057:Tomography, X-Ray Computed
chemical_list: D001704:Biopolymers; C540163:Celox; D006490:Hemostatics; D011208:Powders