Recombinant Factor VIIa Increases the Pressure at Which Rebleeding Occurs in Porcine Uncontrolled Aortic Hemorrhage Model

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 B P level at which rebleeding occurs in a prospective, randomized, blinded study using a porcine model of uncontrolled hem orrhage and resuscitation. Thirty anesthetized 40-kg pigs were assigned to three groups n 10group control, low-dose rFVIIa 180 microgkg, or high-dose 720 microgkg. 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 mLmin 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 or - 3, 69 or - 5, and 66 or - 6 mmHg in the control, low-dose, and high-dose groups, respectively, P 0.003. Rebleed hemorrhage volume was reduced with rFVIIa 39 or - 9, 22 or - 7, and 2 6 or - 5 mLkg for control, and low and high dose, respectively P 0.055. This is the first study to show that rFVIIa increases the BP at whic h 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 rFVlla.