A randomized, controlled trial of aprotinin in neonates undergoing open-heart surgery.

BACKGROUND: Neonates undergoing open-heart surgery are especially at risk for massive bleeding and pronounced inflammation. The efficacy of aprotinin, a serine protease inhibitor, at ameliorating these adverse effects of cardiopulmonary bypass has not been clearly demonstrated in neonates.

METHODS: Term neonates were enrolled and randomly assigned in a blinded fashion to receive saline (group P, placebo) or high-dose aprotinin (group A). Intraoperative management was standardized: surgeon, anesthesia, cardiopulmonary bypass and hemostasis therapy. Patients were admitted postoperatively to a pediatric cardiac intensive care unit. Primary outcome measure of efficacy was duration of the postoperative mechanical ventilation. Secondary outcome measures were total volume and units of blood products transfused intraoperatively and for 24 h after surgery, duration of chest tube in situ, and intensive care and hospital stays after surgery.

RESULTS: Twenty-six neonates were enrolled; 13 received aprotinin and 13 received placebo. The study was halted prematurely because of US Food and Drug Administration's concerns about aprotinin's safety. Baseline patient, surgery and cardiopulmonary bypass characteristics were similar between groups. No outcome variables differed between groups (P > 0.05). Duration of postoperative ventilation was 115 +/- 139 h (group A); 126 +/- 82 h (group P); P = 0.29, and total blood product exposure was 8.2 +/- 2.6 U (group A); 8.8 +/- 1.4 U (group P); P = 0.1. Postoperative blood creatinine values did not differ between groups. In-hospital mortality rate was 4%.

CONCLUSIONS: Aprotinin was not shown to be efficacious in neonates undergoing open-heart surgery. It is unclear whether adult aprotinin safety data are relevant to neonates undergoing open-heart surgery.