Aprotinin Versus Placebo in Major Orthopedic Surgery: A Randomized, Double-Blinded, Dose-Ranging Study

Abstract

We conducted a prospective, multicenter, double-blinded, dose-ranging study to compare the risk/benefit ratio of large- and small-dose aprotinin with placebo after major orthopedic surgery. Fifty-eight patients were randomized into three groups: Large-Dose Aprotinin (4 M kallikrein inactivator unit [KIU] bolus before surgery followed by a continuous infusion of 1 M KIU/h until the end of surgery), Small-Dose Aprotinin (2 M KIU bolus plus 0.5 M KIU/h), and Placebo. Bleeding was measured and calculated. Bilateral ascending venography was systematically performed on the third postoperative day. Measured and calculated blood loss decreased in the Large-Dose Aprotinin group (calculated bleeding, whole blood, hematocrit 30%, median [range], 2,023 mL [633–4,113] as compared with placebo, 3,577 mL [1,670–21,758 mL]). The total number of homologous and autologous units was also significantly decreased in the Large-Dose Aprotinin group (2 U [0–5 U] as compared with placebo, 4 U [0–42 U]). No increase in deep vein thrombosis or pulmonary embolism was observed in the aprotinin groups. Large-dose aprotinin was safe and effective in dramatically reducing the measured and calculated bleeding and the amount of transfused red blood cell units after major orthopedic surgery.