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Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients

Authors Miyoshi S, Ito R, Katayama H, Dote K, Aibiki M, Hamada H, Okura T, Higaki J

Received 20 May 2014

Accepted for publication 20 June 2014

Published 2 September 2014 Volume 2014:8 Pages 1211—1219

DOI https://doi.org/10.2147/DDDT.S68030

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Seigo Miyoshi,1 Ryoji Ito,1 Hitoshi Katayama,1 Kentaro Dote,2 Mayuki Aibiki,3 Hironobu Hamada,1,4 Takafumi Okura,1 Jitsuo Higaki1

1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, 2Intensive Care Division, Ehime University Hospital, 3Department of Emergency and Critical Care Medicine, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 4Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi, Minami-ku, Hiroshima, Japan

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.
Conclusion: 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.

Keywords: sivelestat, recombinant human soluble thrombomodulin, disseminated intravascular coagulation, acute respiratory distress syndrome
 

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