Predictors of the therapeutic effect of sivelestat in patients with acute lung injury associated with systemic inflammatory response syndrome.

Takuma Ozawa,Kiyoshi Mihara,Nobuhiro Yasuno

doi:10.1186/s40780-016-0051-x

Abstract

BackgroundSivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome. However, sivelestat produced inconsistent therapeutic benefits. This study aimed to identify factors predicting the therapeutic effects of sivelestat.MethodsWe enrolled 53 mechanically ventilated patients who received sivelestat. The patients were classified as effective (n = 28) if they were weaned from the ventilator within 28 days, or as ineffective groups (n = 25). Patient characteristics were compared between these groups and multivariate logistic regression analysis was used to identify predictive factors. A validation study was then conducted in sivelestat-free patients.ResultsA high red blood cell count and low hydrogen ion concentration were significantly associated with a higher ventilator weaning rate in patients receiving sivelestat. The validation study revealed that the hydrogen ion concentration value also significantly associated with ventilator weaning in patients who did not receive sivelestat.ConclusionsAlthough hydrogen ion concentration was inversely associated with the ventilator weaning rate, it did not predict sivelestat efficacy. This study indicated that acute lung injury patients with a high red blood cell count would derive the most benefit from sivelestat administration.

Highlights

Sivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome
Neutrophil elastase (NE) is one of the proteases released from the neutrophils that accumulate in the lung [2]
Sivelestat was approved in Japan as a therapeutic drug for Acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS), but is used in other situations

Summary

Introduction

Sivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome. Sivelestat is a selective NE inhibitor, which binds directly to NE and inactivates it by a reversible acylationdeacylation mechanism [4,5,6]. It relaxes vascular smooth muscle [7]. Sivelestat was approved in Japan as a therapeutic drug for ALI associated with SIRS, but is used in other situations. Sivelestat shortens the duration of mechanical ventilation, intensive care unit stay, and hospitalization due to severe respiratory failure after thoracic aortic surgery [14]

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