title: Human dose confirmation for self-expanding intra-abdominal foam: A translational, adaptive, multicenter trial in recently deceased human subjects.
abstract: BACKGROUND
  Noncompressible abdominal bleeding accounts for significant mortality in both military and civilian populations. There is an emergent need for a temporary hemostatic intervention whenever surgical care is not immediately available. Our team previously described a self-expanding polyurethane foam for the treatment of exsanguinating abdominal hemorrhage. The objective of this study was to translate a safe and effective swine dose into an appropriate human dose through foam administration in recently deceased humans with representative tissue compliance.
  
  
  METHODS
  With institutional review board oversight and informed consent at three centers, terminal patients were identified. Within 3 hours of death, the abdomen was accessed, and fluid was added to simulate hemorrhage. Foam was percutaneously administered using a prototype delivery system at multiple doses (45, 55, 65, 75, and 100 mL). Intra-abdominal pressure was monitored for 15 minutes, and then, foam was removed via laparotomy to assess abdominal tissue contact.
  
  
  RESULTS
  Twenty-one recently deceased patients ranging in age from 20 years to 92 years and body mass index from 18 kg/m to 39 kg/m were enrolled in the study. Foam was administered at a mean (SD) of 146 (34) minutes after death. Three subjects were screen failures, and three subjects were excluded from the analysis because of experimental errors. Change in intra-abdominal pressure and semiquantitative organ contact were used as surrogates to compare findings between humans and swine. Doses of 45, 55, and 65 mL resulted in peak pressures of 37 (20), 28 (8.1), and 33 (20) mmHg, respectively, within the acceptable range established in swine studies. Foam deployments of 75 mL and 100 mL exceeded acceptable pressures defined in swine. Higher foam doses tended to improve contact with the diaphragm, paracolic gutters, and liver.
  
  
  CONCLUSIONS
  The use of recently deceased humans demonstrates a novel approach to device evaluation in representative human anatomy, particularly when tissue compliance is critical. Sixty-five milliliters was determined to be the clinically appropriate dose for foam treatment in bleeding human patients.
authors.affiliation: From the Division of Trauma, Emergency Surgery and Surgical Critical Care (T.M., A.L., P.F., D.R.K.), Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston; and Arsenal Medical, Inc. (J.M., U.S., A.P.R.), Watertown, Massachusetts; Division of Acute Care Surgery (R.L., J.P., B.C., J.B.H.), Department of Surgery, Center for Translational Injury Research, University of Texas Health Science Center at Houston, Houston, Texas; Division of Trauma, Critical Care and Acute Care Surgery (D.M., M.C., S.U., M.S.), Department of Surgery, Oregon Health & Science University, Portland, Oregon.
authors.forename: Tomaz
authors.initials: T
authors.lastname: Mesar
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Ryan
authors.initials: R
authors.lastname: Lawless
authors.forename: Jeanette
authors.initials: J
authors.lastname: Podbielski
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Cook
authors.forename: Sam
authors.initials: S
authors.lastname: Underwood
authors.forename: Andreas
authors.initials: A
authors.lastname: Larentzakis
authors.forename: Bryan
authors.initials: B
authors.lastname: Cotton
authors.forename: Peter
authors.initials: P
authors.lastname: Fagenholz
authors.forename: Martin
authors.initials: M
authors.lastname: Schreiber
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
authors.forename: John
authors.initials: J
authors.lastname: Marini
authors.forename: Upma
authors.initials: U
authors.lastname: Sharma
authors.forename: Adam P
authors.initials: AP
authors.lastname: Rago
authors.forename: David R
authors.initials: DR
authors.lastname: King
mesh_terms: D000368:Aged; D058734:Exsanguination / Q000628:therapy*; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011140:Polyurethanes / Q000008:administration & dosage*
chemical_list: D006490:Hemostatics; D011140:Polyurethanes; C028279:polyurethane foam