Recombinant factor VIIa reduces rebleed hemorrhage volume in a swine aortotomy model: a randomized double-blinded study.

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.