Home›Rheumatology› Sivelestat-containing regimens reduce all-cause mortality in sepsis-induced ARDS with OR 0.55
Sivelestat-containing regimens reduce all-cause mortality in sepsis-induced ARDS with OR 0.55Sivelestat shows lower mortality for patients with sepsis and ARDS
Frontiers in MedicinePublished October 28, 2026Study authors: Abduwupuer Haibier, Jiawei Ma, Yuanyuan Wang, Tong WuDOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Note that sivelestat-containing regimens are associated with lower mortality in sepsis-induced ARDS.
This meta-analysis evaluated the impact of sivelestat-containing regimens on outcomes in 943 adults with sepsis-induced acute respiratory distress syndrome (ARDS). The analysis synthesized data on all-cause mortality, P/F ratio, duration of mechanical ventilation, and other clinical markers. The primary finding was a significant reduction in all-cause mortality with a sivelestat-containing regimen (OR 0.55; 95% CI 0.36-0.84). Specifically, in randomized trials, the mortality reduction was even more pronounced (OR 0.37; 95% CI 0.16-0.86).
The authors noted several limitations, including sparse reporting of co-interventions and the inability to exclude residual confounding from prone positioning, sedation, neuromuscular blockade, and steroid use. Furthermore, the study lacked the power to test for small-study asymmetry and lacked baseline-stratified data for IL-6, PCT, CRP, or neutrophil elastase to perform quantitative effect-modification analyses.
From a clinical perspective, while sivelestat is associated with lower mortality in sepsis-induced ARDS, the authors conclude that the current aggregate evidence is insufficient to establish a validated phenotype-guided prescribing rule. Clinical application should be approached with caution due to potential confounding factors.
How this fits prior evidence
This meta-analysis addresses a gap in the management of sepsis-induced ARDS. While prior evidence suggests that ARDS subphenotypes may explain variable treatment responses to interventions like corticosteroids and prone positioning, this study provides a specific mortality benefit for sivelestat. However, like the finding that heparin's mortality effect in sepsis is inconclusive, the authors of this meta-analysis state that evidence is currently insufficient to support a validated phenotype-guided prescribing rule.
When a patient develops sepsis and their lungs begin to fail, every moment counts. Doctors are looking for ways to improve survival rates for these critically ill patients. A large review of data involving 943 adults suggests that a specific medication called sivelestat might help lower the risk of death in these cases.
The analysis looked at patients with sepsis-induced acute respiratory distress syndrome. The results showed that those receiving a regimen containing sivelestat had lower mortality rates compared to those who did not. This trend was also seen specifically in randomized trials, which are the gold standard for testing new treatments.
While the results are promising, the evidence is not yet perfect. Because other treatments like steroids or specific positioning were used at the same time, it is hard to say exactly how much of the benefit comes from sivelestat alone. Currently, there is not enough specific data to create a strict rule for exactly which patients should receive the drug.
What this means for you:
Sivelestat is linked to lower death rates in patients with sepsis and severe lung distress.
Common questions
What is sivelestat and how does it help?
Sivelestat is a medication used in a treatment plan for adults with sepsis-induced acute respiratory distress syndrome. The study found that patients receiving a regimen with sivelestat had lower mortality rates compared to those who did not receive it. However, more research is needed to understand exactly how it works in different patient types.
Is sivelestat safe for patients with lung infections?
The study included 943 patients to look at mortality rates. While the data showed lower mortality for those on sivelestat, the specific reports on side effects, serious adverse events, or how well patients tolerated the drug were not available in this specific analysis.
Is this a proven way to treat sepsis?
The data shows a link between sivelestat and lower death rates, including in randomized trials. However, the researchers noted that current evidence is not yet enough to create a specific rule for exactly which patients should get the drug based on their specific symptoms.
Sivelestat sodium hydrate is a selective neutrophil elastase inhibitor that attenuates neutrophil-mediated alveolar–capillary injury and is used in some East Asian countries for acute lung injury/ARDS. We evaluated the efficacy and safety of sivelestat in sepsis-induced acute respiratory distress syndrome (ARDS) and explored whether disease severity, baseline mortality risk, and treatment background modify the mortality effect.
We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, CNKI, Wanfang, and ClinicalTrials.gov from database inception to August 27, 2026. Eligible studies were adult studies of sepsis-induced ARDS comparing a sivelestat-containing regimen with an otherwise comparable regimen without sivelestat. COVID-19-only cohorts, non-septic ARDS, mixed-etiology studies without a separable sepsis subgroup, and comparisons in which both groups received sivelestat were excluded. The primary outcome was all-cause mortality; secondary outcomes included P/F ratio, duration of mechanical ventilation, ICU length of stay, organ-function scores, inflammatory markers, and adverse events. Mortality was pooled as odds ratios (ORs) using a random-effects model with restricted maximum likelihood; Hartung–Knapp intervals were used for the primary and study-design analyses. This review was prospectively registered in PROSPERO.
Fourteen studies were eligible for qualitative synthesis, and 10 studies (943 patients) provided extractable 2 × 2 mortality data. Deaths occurred in 73/431 patients receiving sivelestat and 125/512 controls. Sivelestat was associated with lower mortality (OR=0.55, 95% CI 0.36–0.84; I2 = 0%). The signal persisted in randomized trials (OR=0.37, 95% CI 0.16–0.86; I2 = 0%). Study-level point estimates appeared more favorable in cohorts with baseline P/F 30%; however, interaction tests were not statistically significant and severity analyses were ecological. Leave-one-out analyses were stable. Egger testing did not detect significant small-study asymmetry (P = 0.197), although power was limited. Baseline-stratified treatment effects by IL-6, PCT, CRP, or neutrophil elastase were unavailable for quantitative effect-modification analyses.
In an updated and etiologically strict evidence synthesis, sivelestat was associated with lower mortality in sepsis-induced ARDS, including in randomized trials. Severe hypoxemia and high baseline risk remain plausible enrichment factors, but current aggregate evidence is insufficient to support a validated phenotype-guided prescribing rule. Co-intervention reporting was sparse, and residual confounding by prone positioning, sedation, neuromuscular blockade, and steroid background cannot be excluded.
