Effects of Half‐dose Aprotinin in Off‐pump Coronary Artery Bypass Grafting

Abstract

The effects of half-dose aprotinin in off-pump coronary artery bypass (OPCAB) surgery have not yet been described. The present prospective study was designed to investigate its effects in OPCAB. Seventy-six patients were randomized into two groups, receiving aprotinin (1 x 10(6) Kallikrein-inactivating units [KIU] loading dose before surgery and 5 x 10(5) KIU/h during surgery, gross dose: 2.5 x 10(6) KIU, n=36) and saline solution (control, n=40) respectively. Perioperative blood samples were collected. Hematologic and hemostatic parameters including platelet adhesion rate, D-dimer, and fibrinopeptide-A (FPA) were analyzed. Perioperative CKMB release was measured. Volume of blood loss, blood transfusion, and other clinical data were recorded throughout the perioperative period. Postoperative blood loss was significantly reduced in patients treated with aprotinin (2 hours; median [25th-75th]: aprotinin: 90.0 [70.0-125.0] ml, control: 145.0 [70.0-180.0] ml, P<0.05; 6 hours: aprotinin: 150.0 [100.0-220.0] ml, control: 225.0 [200.0-347.5.0] ml, P<0.01; 24 hours: aprotinin: 370.0 [220.0-510.0] ml, control: 655.0 [500.0-920.0] ml, P<0.01). The number of patients receiving blood transfusion in each group was similar. Levels of D-dimer rose significantly after surgery, and were significantly lower in the aprotinin group than in the controls (end of surgery, aprotinin, 0.4 [0.2-0.5] mg/l versus controls, 1.4 [0.8-2.3] mg/l; 2 hours, aprotinin, 0.3 [0.2-0.4] mg/l versus controls, 0.9 [0.5-1.4] mg/l; 6 hours, aprotinin, 0.3 [0.2-0.5] mg/l versus controls, 0.6 [0.4-0.9] mg/l; 24 hours, aprotinin, 0.3 [0.2-0.4] mg/l versus controls, 0.5 [0.4-0.9] mg/l; ANOVA for repeated measures, P<0.01). Platelet adhesion rate and FPA levels remained at baseline levels after the operation in the two groups. Early clinical outcomes were similar in the groups. Levels of CKMB were significantly lower in the aprotinin group than in the controls (6 hours after surgery, aprotinin, 10.0 [8.0-16.0] U/l versus controls, 15.5 [11.0-20.3] U/l; 12 hours, aprotinin, 13.5 [10.0-20.0] U/l versus controls, 19.0 [12.8-24.3] U/l; 24 hours, aprotinin, 19.0 [13.5-33.8] U/l versus controls, 25.0 [15.0-43.3] U/l; 72 hours, aprotinin, 13.0 [8.0-18.0] U/l versus controls, 16.0 [10.0-29.0] U/l; ANOVA for repeated measures, P=0.018). The results indicated that half-dose aprotinin limits fibrinolysis and myocardial injury, and reduces blood loss after OPCAB surgery.