Recombinant aprotinin in coronary artery bypass graft operations

Objective:To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery.Design:An open-label, randomized, controlled study evaluating two dosage levels of recombinant aprotinin.Setting:Two acute care hospitals (Northwestern Memorial Hospital, Chicago, Ill., and the Scott & White Memorial Hospital, Temple, Texas).Patients:Patients undergoing primary and reoperation coronary artery bypass grafting were assigned to groups by means of a computer-generated table of random numbers. Treated (n = 48) and control (n = 36) patients did not differ significantly in age, sex, weight, number of grafts, or preoperative hemoglobin level.Interventions:Recombinant aprotinin was given at two dosages. Dosage level 1 consisted of a bolus of 2 mg/kg intravenously immediately after the induction of anesthesia, 1 mg/kg added to each liter of the oxygenator prime, and 0.5 mg · kg-1 · hr−1 infused continuously during operation. At dosage level 2, doses were doubled. Intraoperative monitoring of anti-factor Xa activity was performed, and additional doses of heparin were given on the basis of anti-factor Xa results.Main outcome measures:Preoperative and postoperative hemoglobin levels, amounts of autotransfusion device and chest tube drainage blood, and transfusions of allogeneic red blood cells. Adverse clinical events (alterations in renal function, graft thrombosis, myocardial infarction, and death) were recorded.Results:Additional heparin was given to 48% patients in the aprotinin group and to 44% of control patients. Overall red blood cell loss (in milliliters, mean ± standard deviation [SD]) was decreased with aprotinin at dosage level 1 for reoperations (1040 ± 162 vs 1544 ± 198, p < 0.01), and at dosage level 2 for all operations (primary operations, 886 ± 362 vs 1333 ± 618, p = 0.02; reoperations, 1191 ± 560 vs 1815 ± 1116, p = 0.2). Fewer patients in the aprotinin than in the control group had transfusions of donated blood (6/48 vs 12/36, p = 0.02) or reinfusion of chest tube drainage blood (12/48 vs 20/36, p < 0.01). Among patients receiving dosage level 1, there were no myocardial infarctions or deaths. At dosage level 2, one patient had profound bradycardia and died on day 12 and two patients had late graft closures. Two control patients had hypotension after bypass necessitating intraaortic balloon pumps, and one of these patients died. Postoperative increases in blood urea nitrogen and creatinine levels were small in both aprotinin and control groups. No hypersensitivity or other allergic reactions occurred.Conclusion:We conclude that, at the dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary artery bypass grafting, but its use requires appropriate monitoring of heparin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger patient sample