Sivelestat Lowers ARDS Risk, Mortality Following Cardiovascular Surgery

Acute respiratory distress syndrome (ARDS) remains one of the most serious complications following cardiovascular surgery, contributing to prolonged intensive care unit (ICU) stays, higher costs, and increased mortality.¹ New findings suggest that sivelestat may help reduce the risk of ARDS and improve survival outcomes in patients undergoing major cardiovascular procedures.

This randomized clinical trial is published in JAMA Network Open.

“In this single-center, randomized, placebo-controlled clinical trial, postoperative infusion of sivelestat significantly reduced the incidence of ARDS and 90-day all-cause mortality among patients undergoing cardiovascular surgery,” wrote the researchers of the study. “These results suggest that sivelestat may be an effective preventive strategy for postoperative ARDS in high-risk populations.”

Sivelestat is an investigational small-molecule drug that functions as a selective neutrophil elastase inhibitor, a serine protease released by activated neutrophils during inflammatory responses.² By blocking neutrophil elastase activity, sivelestat helps limit tissue damage and reduce inflammatory signaling pathways that contribute to lung injury.

To evaluate this approach, researchers conducted a single-center, randomized, placebo-controlled clinical trial at a tertiary academic medical center in China.¹ The study enrolled 424 adult patients scheduled for cardiovascular surgery between February 2024 and April 2025. Eligible procedures included coronary artery bypass grafting, valve surgery, ascending aortic reconstruction, congenital heart defect repair, cardiac tumor resection, and combined procedures.

Participants were randomly assigned in a 1:1 ratio to receive either continuous intravenous sivelestat or placebo after surgery. The sivelestat group received a dose of 0.2 mg/kg per hour starting immediately after ICU admission and continuing for up to 7 days or until ICU discharge. The control group received a volume-matched saline infusion on the same schedule. Patients were followed for 90 days postoperatively.

The primary end point was the incidence of ARDS following surgery. Secondary outcomes included inflammatory biomarker levels—including interleukin (IL)-6, IL-8, tumor necrosis factor, and neutrophil elastase—measured on postoperative days 1, 3, 5, and 7. Additional clinical outcomes included pneumonia, reintubation, and mortality.

Of the 424 randomized patients, 382 completed the trial. The mean (SD) age was 62.9 (6.2) years, and 55% of participants were male. Safety monitoring showed no significant differences in adverse events between the sivelestat and placebo groups.

Patients treated with sivelestat experienced significantly lower rates of postoperative ARDS compared with those receiving placebo. ARDS occurred in 16.8% of patients in the treatment group vs 31.2% in the placebo group (P < .001). The therapy was also associated with improved survival: 90-day mortality was 1.1% among patients receiving sivelestat compared with 5.2% in the placebo group (P = .02).

Biomarker analyses provided additional evidence supporting the drug’s anti-inflammatory mechanism. Patients treated with sivelestat showed significantly lower postoperative levels of neutrophil elastase and key inflammatory cytokines such as IL-6, indicating reduced neutrophil-driven inflammation following surgery.

The findings suggest that targeting neutrophil elastase may help interrupt the inflammatory cascade that contributes to lung injury after major cardiovascular procedures. By attenuating this response, sivelestat could potentially reduce the development of ARDS and improve postoperative outcomes.

Despite these promising results, the authors noted that the trial was conducted at a single center, which may limit generalizability to other populations and health systems. Larger multicenter studies will be needed to confirm the findings and determine whether the therapy should be incorporated into routine postoperative management strategies.

If validated in future research, sivelestat could represent a pharmacologic strategy to reduce ARDS risk in cardiovascular surgery—a complication that remains challenging to prevent and treat in critically ill patients.

References

1. Pan T, Xu C, Wang Y, et al. Sivelestat and incidence of acute respiratory distress syndrome after cardiovascular surgery: a randomized clinical trial. JAMA Netw Open. 2026;9(3):e260390. doi:10.1001/jamanetworkopen.2026.0390

2. Sivelestat. Drug Bank. Updated January 29, 2025. Accessed March 11, 2026. https://go.drugbank.com/drugs/DB12863