Sivelestat and Incidence of Acute Respiratory Distress Syndrome After Cardiovascular Surgery: A Randomized Clinical Trial.
Summary
In a randomized, placebo-controlled trial after cardiovascular surgery, continuous sivelestat infusion significantly reduced ARDS incidence (16.8% vs 31.2%) and 90-day mortality (1.1% vs 5.2%). Neutrophil elastase and IL-6 levels were consistently lower with sivelestat, supporting a mechanism of attenuating neutrophil-driven inflammation.
Key Findings
- ARDS incidence reduced with sivelestat vs placebo: 16.8% (32/190) vs 31.2% (60/192), P<.001
- 90-day all-cause mortality reduced: 1.1% (2/190) vs 5.2% (10/192), P=.02
- Inflammatory biomarkers (neutrophil elastase, IL-6) were significantly lower with sivelestat
- Adverse events monitored for safety were similar between groups
- Trial registered (NCT06276569) with intention-to-treat analysis
Clinical Implications
Sivelestat may be considered for evaluation as perioperative prophylaxis against ARDS in major cardiovascular surgery, pending replication in multicenter trials. Protocolized early initiation in the ICU could be integrated into bundles for high-risk patients.
Why It Matters
This is a well-designed RCT demonstrating prophylactic reduction of ARDS and mortality with a targeted neutrophil elastase inhibitor. It reframes ARDS management toward prevention in high-risk postoperative patients.
Limitations
- Single-center study limits generalizability
- Blinding procedures and adherence details are not described in the abstract; external replication needed
Future Directions
Conduct multicenter, international RCTs to confirm efficacy, explore dose/duration optimization, identify subgroups most likely to benefit, and assess cost-effectiveness.
Study Information
- Study Type
- RCT
- Research Domain
- Prevention
- Evidence Level
- I - Randomized, placebo-controlled clinical trial with patient-centered outcomes
- Study Design
- OTHER