# Sivelestat for septic patients with acute respiratory distress syndrome: a systematic review and meta-analysis of a deadly duo

## TL;DR

This study finds that sivelestat reduces mortality and improves outcomes in septic patients with acute respiratory distress syndrome.

## Contribution

The study provides new evidence that sivelestat improves survival and clinical outcomes in septic ARDS patients through a systematic review and meta-analysis.

## Key findings

- Sivelestat significantly reduced mortality risk in septic ARDS patients (OR = 0.63).
- It improved PaO2/FiO2 levels on multiple days after treatment and reduced ICU stay and ventilation duration.
- Effectiveness was stronger in subgroups with severe ARDS and higher mortality risk.

## Abstract

Acute respiratory distress syndrome (ARDS) is one of the most common organ dysfunctions in sepsis. The potential benefits of sivelestat, a selective inhibitor of neutrophil elastase, for patients with septic ARDS remain unclear. The current systematic review and meta-analysis aimed to evaluate the effectiveness of sivelestat in reducing mortality and improving other important outcomes in this patient population.

We searched PubMed, EMBASE, and Cochrane Library databases until May 30, 2025, for studies comparing sivelestat in septic patients with ARDS against controls. The primary outcome was mortality. We assessed study quality and conducted subgroup analyses, sensitivity analyses, regression analyses, and GRADE evaluations to explore potential heterogeneity.

A total of 17 studies involving 5,062 patients met the inclusion criteria. Overall, sivelestat significantly reduced the risk of mortality compared to controls (odds ratio [OR] = 0.63; 95% confidence interval [CI], 0.48–0.84; I2 = 39%). Meta-regression showed that differences in baseline PaO2/FiO2 and risk of mortality significantly influence the effectiveness of sivelestat interventions, as shown in sequent subgroup analyses of patients with partial pressure of oxygen/fraction of inspiration oxygen (PaO2/FiO2) < 200 mmHg (OR = 0.61; 95% CI 0.51–0.73) and those with a mortality rate greater than 30% (OR = 0.48; 95% CI 0.37–0.60). A similar result was found when we pooled results from adjusted regression analyses (hazard ratio = 0.48; 95% CI 0.28–0.82). Additionally, sivelestat significantly improved PaO2/FiO2 on days 1, 3, 5, and 7 after treatment and was associated with a significant reduction in the duration of mechanical ventilation (standardized mean difference [SMD] = −0.58 days; 95% CI, −0.96 to −0.19), and length of ICU stay (SMD = −0.76 days; 95% CI, −1.09 to −0.43).

Sivelestat significantly increased PaO2/FiO2 levels after treatment, leading to a improvement in mortality and other clinical outcomes. Further studies with well-designed protocols for administering sivelestat are needed to validate these findings.

https://inplasy.com/wp-content/uploads/2025/06/INPLASY-Protocol-7969.pdf, identifier INPLASY202560111.