The effectiveness of selective neutrophil elastase inhibitors (sivelestat) in acute lung injury or acute respiratory distress syndrome: A systematic review and meta-analysis of randomized controlled trials.

Introduction The neutrophil elastase (NE) inhibitor is a potential treatment strategy for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). However, the clinical effectiveness of sivelestat sodium, a selective NE inhibitor, remains controversial. We performed a systematic review and meta-analysis to evaluate the effects of sivelestat in patients with ALI/ARDS.

Method The literature search, selection, and data extraction were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Statement (PRISMA) guidelines. The randomized controlled trials (RCTs) with reference lists were retrieved from Scopus, PubMed, and Cochrane Library, using the Cochrane risk-of-bias tool for the quality assessment. Logarithm relative risk (logRR), risk difference (RD), and standardized mean difference (SMD) were calculated using the fixed effects model or random effects model, depending on heterogeneity.

Result Ten RCTs involving 1170 patients (583 receiving sivelestat and 587 receiving standard care or placebo) were included. Sivelestat was associated with a significant reduction in 28-30-day mortality, shorter duration of mechanical ventilation, and improvement in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio) in a time-dependent manner. These beneficial effects were more pronounced in patients with sepsis-related ALI/ARDS. The incidence of adverse events did not differ between groups.

Conclusion Sivelestat might be a promising adjunctive treatment for ALI/ARDS, especially in the sepsis etiology, as evidenced by reduced mortality, shortened mechanical ventilation duration, and improved oxygenation. The large-scale, well-designed RCTs are warranted.