JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Kadoi, Y. Articles by Ieta, K. Search for Related Content PubMed PubMed Citation Articles by Kadoi, Y. Articles by Ieta, K. Related Collections Resuscitation Critical Care

---

CRITICAL CARE AND TRAUMA

Pilot Study of the Effects of ONO-5046 in Patients with Acute Respiratory Distress Syndrome

Yuji Kadoi, MD^*, Hiroshi Hinohara, MD^*, Fumio Kunimoto, MD^*, Shigeru Saito, MD, Fumio Goto, MD, Takayuki Kosaka, MD, and Keisuke Ieta, MD

*Department of Intensive Care, Department of Anesthesiology, and First Department of Surgery, Graduate School of Medicine, Gunma University, Gunma, Japan

Address correspondence and reprint requests to Yuji Kadoi, MD, Department of Intensive Care, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Address e-mail to kadoi{at}med.gunma-u.ac.jp

Evidence has linked neutrophil elastase to acute respiratory distress syndrome (ARDS), suggesting that inhibiting the activity of this enzyme could prevent the development and progression of ARDS. However, few clinical trials have examined this notion. We therefore examined the effects of ONO-5046 (sivelestat, a specific inhibitor of neutrophil elastase; sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylaminobenzoyl]amino-acetate tetrahydrate]) in a randomized, double-blinded trial in patients with ARDS. We randomly assigned 24 patients with ARDS to groups that received conventional therapy without or with sivelestat (0.2 mg · kg^–1 · h^–1) for 14 days. The variables of interest associated with clinical outcome were the duration of mechanical ventilation; changes in oxygenation from baseline; changes in cytokine levels from baseline; number of patients alive at 30 days who did not need mechanical ventilation; and mortality rate. The length of intensive care unit stay, number of ventilation days, and mortality rates did not statistically differ between groups. ARDS was more persistent in the control than in the sivelestat group (control, 19.5 ± 7.4 days; sivelestat, 13.5 ± 5.9 days; P = 0.039). Neutrophil elastase activity significantly differed between groups at 72 h after treatment. Levels of interleukin-6 were lower in the sivelestat group than in the controls at 24, 48, and 72 h after treatment. ONO-5046 apparently did not affect survival or the duration of mechanical ventilation.

IMPLICATIONS: ONO-5046 decreased cytokine levels more rapidly in acute respiratory distress syndrome patients treated with sivelestat than in those who received placebo. However, these decreases did not appear to affect other clinical variables, such as the duration of mechanical ventilation or survival rates.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999