title: Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients.
abstract: BACKGROUND
  Neutrophil elastase, alveolar thrombin generation, and fibrin deposition play crucial roles in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). However, the usefulness of combination therapy with a selective neutrophil elastase inhibitor, sivelestat, and recombinant human soluble thrombomodulin (rhTM) for patients with ARDS and DIC remains unknown.
  
  
  METHODS
  We conducted a retrospective data analysis of 142 ARDS patients with DIC to assess the effects of sivelestat combined with rhTM. Patients were divided into four groups: control (no sivelestat or rhTM treatment), sivelestat treatment alone, rhTM treatment alone, and combined treatment with sivelestat and rhTM. A Cox proportional hazard model was used to assess subject mortality rates. The efficacy of these drugs was evaluated based on survival rate, number of ventilator-free days, and change in PaO2/FIO2 (P/F) ratios and DIC scores before and at 7 days after a diagnosis of ARDS with DIC.
  
  
  RESULTS
  Multivariate analysis showed that patient age, combination therapy, gas exchange, organ failure, cause, associated disease score, and serum C-reactive protein levels were predictors of mortality for patients with ARDS and DIC. As compared with untreated controls, combination therapy significantly improved the 60-day survival rate of patients with ARDS and DIC. There were significantly more ventilator-free days for those who received combination therapy than for untreated controls. P/F ratios and DIC scores were significantly improved with sivelestat alone, rhTM alone, or their combination as compared with untreated controls.
  
  
  CONCLUSIONS
  Our results suggest that combined treatment with sivelestat and rhTM has beneficial effects on survival and the respiratory and DIC status of patients with ARDS and DIC.
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Miyoshi
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ito
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katayama
authors.affiliation: Intensive Care Division, Ehime University Hospital, Toon, Ehime, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Dote
authors.affiliation: Department of Emergency and Critical Care Medicine, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Mayuki
authors.initials: M
authors.lastname: Aibiki
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan ; Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Okura
authors.affiliation: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
mesh_terms: D000368:Aged; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000628:therapy*; D012189:Retrospective Studies; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D018180:Thrombomodulin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D013449:Sulfonamides; D018180:Thrombomodulin; C069195:sivelestat; D005998:Glycine
keywords: acute respiratory distress syndrome; disseminated intravascular coagulation; recombinant human soluble thrombomodulin; sivelestat