title: Self-expanding foam for prehospital treatment of severe intra-abdominal hemorrhage: dose finding study.
abstract: BACKGROUND
  Noncompressible abdominal bleeding is a significant cause of preventable death on the battlefield and in the civilian trauma environment, with no effective therapies available at point of injury. We previously described the development of a percutaneously administered, self-expanding, poly(urea)urethane foam that improved survival in a lethal Grade V hepatic and portal vein injury model in swine. In this study, we hypothesized that survival with foam treatment is dose dependent.
  
  
  METHODS
  A high-grade hepatoportal injury was created in a closed abdominal cavity, resulting in massive noncompressible hemorrhage. After injury, the animals were divided into five groups. The control group (n = 12) was treated only with fluid resuscitation, and four polymer groups received different dose volumes (Group 1, n = 6, 64 mL; Group 2, n = 6, 85 mL; Group 3, n = 18, 100 mL; and Group 4, n = 10, 120 mL) in addition to fluids. Ten minutes after injury, the foam was percutaneously administered, and animals were monitored for 3 hours.
  
  
  RESULTS
  Survival with hepatoportal injury was highest in Group 4 (90%) and decreased in a dose-dependent fashion (Group 3, 72%; Group 2, 33%; Group 1, 17%). All polymer groups survived significantly longer than the controls (8.3%). Hemorrhage rate was reduced in all groups but lowest in Group 4 versus the control group (0.34 [0.052] vs. 3.0 [1.3] mL/kg/min, p < 0.001). Increasing foam dose volume was associated with increased peak intra-abdominal pressure (88.2 [38.9] in Group 4 vs. 9.5 [3.2] in the controls, p < 0.0001) and increased incidence of focal bowel injuries.
  
  
  CONCLUSIONS
  The self-expanding foam significantly improves survival in a dose-dependent fashion in an otherwise lethal injury. Higher doses are associated with better survival but resulted in the need for bowel resection.
authors.affiliation: From the Division of Trauma, Emergency Surgery and Surgical Critical Care (M.S.P., J.O.H., M.J.D., J.B., G.S.V., M.A.D., D.D.Y., P.J.F., D.R.K.), Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston; and Arsenal Medical, Inc. (A.R., J.M., G.Z., R.B., T.F., U.S.), Watertown, Massachusetts.
authors.forename: Miroslav P
authors.initials: MP
authors.lastname: Peev
authors.forename: Adam
authors.initials: A
authors.lastname: Rago
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duggan
authors.forename: John
authors.initials: J
authors.lastname: Beagle
authors.forename: John
authors.initials: J
authors.lastname: Marini
authors.forename: Greg
authors.initials: G
authors.lastname: Zugates
authors.forename: Rany
authors.initials: R
authors.lastname: Busold
authors.forename: Toby
authors.initials: T
authors.lastname: Freyman
authors.forename: George S
authors.initials: GS
authors.lastname: Velmahos
authors.forename: Marc A
authors.initials: MA
authors.lastname: Demoya
authors.forename: Daniel Dante
authors.initials: DD
authors.lastname: Yeh
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fagenholz
authors.forename: Upma
authors.initials: U
authors.lastname: Sharma
authors.forename: David Richard
authors.initials: DR
authors.lastname: King
mesh_terms: D000007:Abdominal Injuries / Q000628:therapy*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004632:Emergency Medical Services / Q000379:methods; D005260:Female; D006470:Hemorrhage / Q000628:therapy*; D006489:Hemostatic Techniques; D011140:Polyurethanes / Q000008:administration & dosage / Q000627:therapeutic use*; D012151:Resuscitation; D013552:Swine; D055682:Viscoelastic Substances / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D011140:Polyurethanes; D055682:Viscoelastic Substances; C028279:polyurethane foam