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

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.

Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

“…This study specifically included patients with both ALI and ARDS, which might affect ventilation days. Further, the Sato’s study might include more severe ALI/ARDS patients, which was associated with lower respiratory function so that sivelestat became less effective [ 33 ]. Finally, sivelestat therapy did not affect the PaO 2 /FiO 2 level, and ICU stays in ALI/ARDS patients.…”

Polymorphonuclear (PMN) elastase in patients after severe traumatic brain injury

“…However, it had taken decades of basic research until sivelestat was approved in Japan for the treatment of acute lung injuries. Recent studies confirm benefits of sivelestat administration for patients after acute lung injury [ 23 , 24 ]. Analogous to TBI research, this points out that further basic research concerning PMN elastase might be valuable and is necessary.…”

Evaluation of appropriate indications for the use of sivelestat sodium in acute respiratory distress syndrome: a retrospective cohort study

“…8 The ARDS patients with high red blood cell counts might also benefit from sivelestat sodium. 9 However, appropriate indications for sivelestat sodium treatment has not yet been described.…”

“…In acute lung injury secondary to sepsis, a serum procalcitonin level of 0.5 ng/mL or higher at the time of diagnosis suggests efficacy . The ARDS patients with high red blood cell counts might also benefit from sivelestat sodium . However, appropriate indications for sivelestat sodium treatment has not yet been described.…”