title: Effect of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass: a prospective randomized study.
abstract: Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. The neutrophil elastase inhibitor sivelestat is known to suppress this systemic inflammatory response, which can eventually result in acute organ failure. The prophylactic effect of sivelestat on acute lung injury, especially in pediatric cardiac surgery, remains unclear. This prospective double-blind, randomized study evaluated the perioperative prophylactic effect of sivelestat in patients undergoing elective pediatric open heart surgery with CPB. Thirty consecutive patients, weighing 5-10 kg and undergoing open heart surgery with CPB, were assigned to sivelestat (n = 15) or control (n = 15) groups. From CPB initiation to 24 h after surgery, patients in the sivelestat group received a continuous intravenous infusion of 0.2 mg/kg/h sivelestat, whereas patients in the control group received the same volume of 0.9% saline. Blood samples were collected, and levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, polymorphonuclear elastase (PMN-E), C-reactive protein (CRP), as well as the white blood cell (WBC) count, platelet count, and neutrophil count (NC) were measured. PMN-E levels, IL-8 levels, WBC count, NC, and CRP levels were significantly lower, and platelet count was significantly higher in the sivelestat group, according to repeated two-way analysis of variance. The activated coagulation time was significantly shorter in the sivelestat group, similarly, blood loss was significantly less in the sivelestat group. In conclusion, Sivelestat attenuates perioperative inflammatory response and clinical outcomes in patients undergoing pediatric heart surgery with CPB.
authors.affiliation: Medical Engineer 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: Naoji
authors.initials: N
authors.lastname: Hanayama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Masami
authors.initials: M
authors.lastname: Fujii
authors.forename: Akikazu
authors.initials: A
authors.lastname: Takeda
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: D000367:Age Factors; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D016063:Blood Loss, Surgical / Q000517:prevention & control; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000097:blood / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D007262:Infusions, Intravenous; D007564:Japan; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010976:Platelet Count; D011446:Prospective Studies; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine
keywords: Cardiopulmonary bypass; Neutrophil elastase inhibitor; Pediatric heart surgery; Sivelestat; Systemic inflammatory response