title: Recombinant factor VIIa increases the pressure at which rebleeding occurs in porcine uncontrolled aortic hemorrhage model.
abstract: In trauma patients, resuscitation to endpoints below normal blood pressure (BP) levels may reduce further blood loss due to the rebleeding often caused by more aggressive resuscitation. However, patients whose BP is maintained at lower levels for extended periods are at increased risk for organ failure. The purpose of this study was to determine whether recombinant activated factor VII (rFVIIa) raises the BP level at which rebleeding occurs in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation. Thirty anesthetized 40-kg pigs were assigned to three groups (n = 10/group): control, low-dose rFVIIa (180 microg/kg), or high-dose (720 microg/kg). Vehicle or drug was infused 5 min before creating a 2.0-mm infrarenal aortotomy. Ten minutes later, resuscitation with lactated Ringer's (LR) solution at 100 mL/min was begun. Hemorrhage and LR volumes and BP were recorded continuously. We found that pretreatment with rFVIIa increased the mean arterial pressure at which rebleeding occurred during resuscitation (45 +/- 3, 69 +/- 5, and 66 +/- 6 mmHg in the control, low-dose, and high-dose groups, respectively, P = 0.003). Rebleed hemorrhage volume was reduced with rFVIIa (39 +/- 9, 22 +/- 7, and 26 +/- 5 mL/kg for control, and low and high dose, respectively; P = 0.055). This is the first study to show that rFVIIa increases the BP at which rebleeding occurs during resuscitation in an injury to a major artery, suggesting the formation of a tight, stronger fibrin plug in the presence of high concentrations of rFVIIa.
authors.affiliation: U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 78234, USA. jill.sondeen@amedd.army.mil
authors.forename: Jill L
authors.initials: JL
authors.lastname: Sondeen
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pusateri
authors.forename: Ulla
authors.initials: U
authors.lastname: Hedner
authors.forename: Loudon D
authors.initials: LD
authors.lastname: Yantis
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D001011:Aorta / Q000473:pathology*; D001018:Aortic Diseases / Q000503:physiopathology / Q000628:therapy*; D001794:Blood Pressure; D001835:Body Weight; D004195:Disease Models, Animal; D005167:Factor VII / Q000378:metabolism / Q000494:pharmacology*; D015942:Factor VIIa; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006470:Hemorrhage; D011312:Pressure; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology*; D012151:Resuscitation; D055502:Secondary Prevention; D013552:Swine; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D011994:Recombinant Proteins; D005167:Factor VII; D005337:Fibrin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin