title: Effects of sivelestat on bronchial inflammatory responses after esophagectomy.
abstract: Post-operative pulmonary complications such as systemic inflammatory response syndrome (SIRS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are strongly associated with morbidity and mortality after esophagectomy. Post-operative administration of sivelestat sodium hydrate (sivelestat), a selective inhibitor of neutrophil elastase (NE), has been shown to improve the post-operative clinical course after esophagectomy. This study aimed to evaluate the effect of prophylactic administration of sivelestat on bronchial inflammatory responses. We randomized 24 patients into two groups. One group received 0.2 mg/kg/h sivelestat from the induction of anesthesia to post-operative day 1 (sivelestat group) and the other group received the same amount of physiological saline (control group). Bronchial alveolar epithelial lining fluid (ELF) samples were obtained from both groups at the induction of anesthesia and at the end of surgery. The serum and ELF levels of interleukin (IL)-6 and IL-8 were measured by enzyme-linked immunosorbent assay, and NE activity was spectrophotometrically determined using the same samples. Although IL-6 levels in the ELF significantly increased at the end of surgery compared with the pre-operative levels in both groups, the IL-8 levels and NE activity did not significantly increase at the end of the surgery compared to the corresponding pre-operative values in the sivelestat group. Moreover, IL-8 levels and NE activity in the ELF were significantly reduced at the end of surgery in the sivelestat group compared with corresponding values in the control group. The durations of ALI and ARDS were apparently shorter in the sivelestat group and the duration of SIRS was significantly shorter in the sivelestat group compared to the control group. We demonstrated that prophylactic use of sivelestat mitigated bronchial inflammation by suppressing NE activity and IL-8 levels in the ELF and shortened the duration of SIRS after transthoracic esophagectomy.
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. keisuke@juntendo.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sugasawa
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Toyoki
authors.initials: T
authors.lastname: Kugimiya
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kumakura
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwanuma
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kajiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsurumaru
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.forename: Eiichi
authors.initials: E
authors.lastname: Inada
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology; D000368:Aged; D001991:Bronchitis / Q000188:drug therapy* / Q000209:etiology*; D016629:Esophagectomy; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*; D011292:Premedication; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology; D012129:Respiratory Function Tests; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine