title: Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis.
abstract: BACKGROUND
  Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model.
  
  
  RESULTS
  8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias.
  
  
  CONCLUSIONS
  Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.
authors.affiliation: Division of Health Risk Management, Research Center for Urban Safety and Security, Kobe University, Kobe, Japan. kentaroiwata1969@gmail.com
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwata
authors.forename: Asako
authors.initials: A
authors.lastname: Doi
authors.forename: Goh
authors.initials: G
authors.lastname: Ohji
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Oba
authors.forename: Kohei
authors.initials: K
authors.lastname: Takimoto
authors.forename: Wataru
authors.initials: W
authors.lastname: Igarashi
authors.forename: David H
authors.initials: DH
authors.lastname: Gremillion
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shimada
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine