title: Self-expanding foam for prehospital treatment of intra-abdominal hemorrhage: 28-day survival and safety.
abstract: BACKGROUND
  Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield and in the homeland. We previously demonstrated the hemostatic efficacy of an in situ self-expanding poly(urea)urethane foam in a severe, closed-cavity, hepatoportal exsanguination model in swine. We hypothesized that treatment with, and subsequent explantation of, foam would not adversely impact 28-day survival in swine.
  
  
  METHODS
  Following a closed-cavity splenic transection, animals received either fluid resuscitation alone (control group, n = 6) or resuscitation plus foam treatment at doses of 100 mL (n = 6), 120 mL (n = 6), and 150 mL (n = 2). Foam was allowed to polymerize in situ and was explanted after 3 hours. The animals were recovered and monitored for 28 days.
  
  
  RESULTS
  All 18 animals in the 100-mL, 120-mL, and control groups survived to the 28-day endpoint without complications. The 150-mL group was terminated after the acute phase (n = 2). En bloc explantation of the foam took less than 2 minutes and was associated with millimeter-sized remnant particles. All foam animals required some level of enteric repair (imbrication or resection). Excluding the aborted 150-mL group, all animals survived, with no differences in renal or hepatic function, serum chemistries, or semiquantitative abdominal adhesion scores. Histologic analysis demonstrated that remnant particles were associated with a fibrotic capsule and mild inflammation, similar to that of standard suture reaction. In addition, safety testing (including genotoxicity, pyrogenicity, and cytotoxicity) was performed consistent with the ISO-10993 standard, and the materials passed all tests.
  
  
  CONCLUSIONS
  For a distinct dose range, 28-day recovery after foam treatment and explantation for noncompressible, intra-abdominal hemorrhage is not associated with significant physiologic or biochemical evidence of end-organ dysfunction. A foam volume exceeding the maximum tolerable dose was identified. Bowel repair is required to ensure survival.
authors.affiliation: From the Arsenal Medical, Inc. (A.R., J.M., P.H., G.Z., R.B., M.H., U.S.), Watertown; and Department of Surgery (M.J.D., J.B., M.P.P., J.O.H., G.V., M.A.D., D.D.Y., P.J.F., D.R.K.), Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Rago
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duggan
authors.forename: John
authors.initials: J
authors.lastname: Beagle
authors.forename: Miroslav P
authors.initials: MP
authors.lastname: Peev
authors.forename: John
authors.initials: J
authors.lastname: Marini
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Patricia
authors.initials: P
authors.lastname: Hannett
authors.forename: Greg
authors.initials: G
authors.lastname: Zugates
authors.forename: Rany
authors.initials: R
authors.lastname: Busold
authors.forename: Marc
authors.initials: M
authors.lastname: Helmick
authors.forename: George
authors.initials: G
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 R
authors.initials: DR
authors.lastname: King
mesh_terms: D000007:Abdominal Injuries / Q000401:mortality / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D058734:Exsanguination / Q000401:mortality / Q000628:therapy*; D006489:Hemostatic Techniques / Q000009:adverse effects / Q000401:mortality*; D058105:Polymerization; D011140:Polyurethanes / Q000009:adverse effects / Q000627:therapeutic use*; D013552:Swine
chemical_list: D011140:Polyurethanes