The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. O rthotopic liver transplantation (OLT) is a procedure associated with a substantial risk for massive hemorrhage and consequent massive transfusion. When this occurs, it entails considerable use of blood and blood products, with the attendant risks and use of resources. In addition, greater transfusion requirements are associated with greater incidences of both mortality and postoperative morbidity, 1 possibly related to modifications of the inflammatory response. 2 The coagulopathy that occurs during OLT is multifactorial, resulting from a combination of insufficient procoagulants and thrombocytopenia of end-stage liver disease, along with fibrinolysis occurring during the anhepatic phase and at reperfusion. 3,4 Aprotinin, a naturally occurring nonspecific serine protease inhibitor, inhibits fibrinolysis, may reduce platelet dysfunction, and inhibits the inflammatory response. 5 It has been shown to decrease blood loss in cardiac surgery. 5 For these reasons, it has been investigated as an agent to potentially reduce blood and blood-product transfusion requirements during OLT. Although several studies have reported decreased blood and/or blood-product use with aprotinin during OLT, the majority of these have been either nonrandomized or retrospective in nature. [6][7][8][9][10][11][12] Placebo-controlled randomized studies published to date have shown either significant decreases in transfusion requirements with aprotinin 13,14 or no beneficial effect. 15,16 Thus, the clinical efficacy of aprotinin during OLT remains to be determined: a recent editorial accompanying the study of Porte et al 14 noted that further clinical studies are required. 17 The aim of this investigation is to assess the effects of a continuous infusion of aprotinin on blood and bloodproduct transfusion requirements during OLT and evaluate effects on measured intraoperative coagulation parameters.
MethodsAfter institutional review board approval and written informed consent were obtained, candidates for primary OLT were recruited between 1996 and 1998. Patients with a pre-OLT diagnosis of hepatorenal syndrome or established renal failure requiring dialysis were excluded because of concerns of worsening renal dysfunction with aprotinin use. Anesthesia was induced with thiopental and lorazepam, then maintained with fentanyl and isoflurane. Succinylcholine was administered to facilitate tracheal intubation, followed by pancuronium for intraoperative neuromuscular blockade. Dopamine (2 g/kg/min) was administered to all patients throughout the procedure. OLT was accomplished using a vena cava preservation te...
