title: Recombinant factor VIIa reduces rebleed hemorrhage volume in a swine aortotomy model: a randomized double-blinded study.
abstract: Noncompressible hemorrhage requires hypotensive resuscitation until definitive measures can be taken to prevent rebleeding by sustaining blood pressure at subphysiological levels. Previous studies have demonstrated that a 180- or 720-microg kg(-1) dose of recombinant factor VIIa (rFVIIa) increases the MAP at which rebleeding occurs in a swine aortotomy model. The purpose of the current study was to determine the efficacy of a lower dose of 90 microg kg(-1) given prophylactically to prevent or reduce rebleeding in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation. Fourteen female 40-kg Yorkshire-cross pigs were splenectomized and instrumented with venous and arterial catheters. The infrarenal aorta was exposed, and suction catheters were placed along the right and left paracolic gutters. After a 10-min baseline, 90 microg kg(-1) (i.v.) of either rFVIIa (n = 6) or vehicle (n = 8) was administered. Five minutes later, an aortotomy was created using a 2.5-mm biopsy punch. The weight of the shed blood was continuously recorded. Lactated Ringer's was given (100 mL kg(-1) min(-1)) 10 min after aortotomy until rebleeding occurred. The MAP at rebleed and the subsequent rebleed hemorrhage volume was recorded over the 2-h study period. After rebleed occurred, lactated Ringer's sufficient to maintain MAP at baseline levels was given. Initial hemorrhage volume and rebleed MAP (P = 0.31) did not differ significantly between groups. Rebleed hemorrhage volume was reduced by 54% in the rFVIIa group from 79 +/- 4 mL kg(-1) in the vehicle group to 43 +/- 6 mL kg(-1) in the rFVIIa group (mean +/- SEM; P < 0.005). The MAP at which rebleed occurred was not different between the groups, 71 +/- 4 mmHg in the rFVIIa group versus 59 +/- 5 in the vehicle group. Prophylactic administration of rFVIIa at 90 microg kg(-1), a dose similar to the recommended dose in hemophilia patients with inhibitors, reduced rebleed hemorrhage volume, suggesting that this dose is effective in this swine aortotomy model.
authors.affiliation: US Army Institute of Surgical Research, San Antonio, Texas, USA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: McMullin
authors.forename: Ulla
authors.initials: U
authors.lastname: Hedner
authors.forename: Mirella
authors.initials: M
authors.lastname: Ezban
authors.forename: Brian
authors.initials: B
authors.lastname: Lauritzen
authors.forename: M Dale
authors.initials: MD
authors.lastname: Prince
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
authors.forename: Jill L
authors.initials: JL
authors.lastname: Sondeen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004311:Double-Blind Method; D015942:Factor VIIa / Q000494:pharmacology*; D006470:Hemorrhage / Q000517:prevention & control*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology*; D012151:Resuscitation / Q000379:methods; D013552:Swine
chemical_list: D011994:Recombinant Proteins; D015942:Factor VIIa