title: Effect of additional preoperative administration of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass.
abstract: Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. Our previous reports revealed that prophylactic sivelestat administration at CPB initiation suppresses the postoperative acute inflammatory response due to CPB in pediatric cardiac surgery. The purpose of this study was to compare the effects of sivelestat administration before CPB and at CPB initiation in patients undergoing pediatric open-heart surgery. Twenty consecutive patients weighing 5-10 kg and undergoing ventricular septal defect closure with CPB were divided into pre-CPB (n = 10) and control (n = 10) groups. Patients in the pre-CPB group received a 24 h continuous intravenous infusion of 0.2 mg/kg/h sivelestat starting at the induction of anesthesia and an additional 0.1 mg/100 mL during CPB priming. Patients in the control group received a 24-h continuous intravenous infusion of 0.2 mg/kg/h sivelestat starting at the commencement of CPB. Blood samples were tested. Clinical variables including blood loss, water balance, systemic vascular resistance index, and the ratio between partial pressure of oxygen and fraction of inspired oxygen (P/F ratio) were assessed. White blood cell count and neutrophil count as well as C-reactive protein levels were significantly lower in the pre-CPB group according to repeated two-way analysis of variance, whereas platelet count was significantly higher. During CPB, mixed venous oxygen saturation remained significantly higher and lactate levels lower in the pre-CPB group. Postoperative alanine aminotransferase and blood urea nitrogen levels were significantly lower in the pre-CPB group than in the control group. The P/F ratio was significantly higher in the pre-CPB group than in the control group. Fluid load requirement was significantly lower in the pre-CPB group.Administration of sivelestat before CPB initiation is more effective than administration at initiation for the suppression of inflammatory responses due to CPB in pediatric open-heart surgery, with this effect being confirmed by clinical evidence.
authors.affiliation: Medical Engineering Center, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kohira
authors.forename: Norihiko
authors.initials: N
authors.lastname: Oka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Inoue
authors.forename: Keiichi
authors.initials: K
authors.lastname: Itatani
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oshima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tojo
authors.forename: Shigenori
authors.initials: S
authors.lastname: Yoshitake
authors.forename: Kagami
authors.initials: K
authors.lastname: Miyaji
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006345:Heart Septal Defects, Ventricular / Q000601:surgery*; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D002097:C-Reactive Protein; C069195:sivelestat; D010196:Pancreatic Elastase; D005998:Glycine
keywords: Cardiopulmonary bypass; Inflammatory responses.; Pediatric; Sivelestat