SYSTEMATIC REVIEW article
Front. Med.
Sec. Intensive Care Medicine and Anesthesiology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1679717
This article is part of the Research TopicOutcome of Sepsis and Prediction of Mortality Risk - Volume IIView all 11 articles
Sivelestat for septic patients with acute respiratory distress syndrome: a systematic review and meta-analysis of a deadly duo
Provisionally accepted
- 1The Second People’s Hospital affiliated to Fujian University of Traditional Chinese Medicine, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
- 2Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Abstract Background: 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. Methods: 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. Results: 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
Keywords: sivelestat, Neutrophil elastase inhibitors, Acute Respiratory Distress Syndrome, Mortality, Meta-analysis
Received: 05 Aug 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Zheng, Hu, Yu and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hui-Bin Huang, psyc6789@163.com
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