Neutrophil Elastase Inhibitor Sivelestat Attenuates Perioperative Inflammatory Response in Pediatric Heart Surgery With Cardiopulmonary Bypass

Abstract

Cardiopulmonary bypass (CPB) evokes activation of a systemic inflammatory response. Sivelestat has been used clinically to treat acute lung injury associated with systemic inflammatory response syndrome. This prospective, doubleblind, randomized study was designed to evaluate the effects of sivelestat in the perioperative period of elective pediatric open-heart surgery with CPB. Twenty-six consecutive pediatric patients weighing between 5 and 10 kg and undergoing open-heart surgery with CPB were divided into a sivelestat group (n = 13) and a control group (n = 13). The patients in the sivelestat group were administered a continuous intravenous infusion of 0.2 mg/kg/hour of sivelestat, and the patients in the control group were administered the same volume of 0.9% saline from the initiation of CPB to 24 hours after surgery. Blood samples were drawn for the measurement of cytokines, polymorphonuclear elastase (PMN-E), white blood cell count (WBC), neutrophil count (NC), and C-reactive protein (CRP). There were no significant differences in cytokine data between the two groups. The peak PMN-E and WBC levels were significantly increased in the control group (P = 0.049, P = 0.039). The WBC and NC levels immediately after surgery in the control group were significantly greater than those in the sivelestat group (P = 0.049, P = 0.044). The peak CRP level in the control group was significantly greater than the sivelestat group (P = 0.04), and the CRP level on postoperative day 4 in the control group was significantly greater than in the sivelestat group (P = 0.014). This study showed that sivelestat attenuates the perioperative inflammatory response in pediatric heart surgery with CPB.