Therapeutic Efficacy of Sivelestat Sodium in ARDS Following Aortic Dissection: A Pilot Physiological Trial with...

To evaluate the physiological and clinical effects of sivelestat, a selective neutrophil elastase inhibitor, in patients with aortic dissection-associated acute respiratory distress syndrome (ARDS), and to explore its potential mechanisms using transcriptomic analysis.

This single-center, randomized, placebo-controlled pilot trial enrolled adult patients who developed ARDS with systemic inflammatory response syndrome after aortic dissection surgery. Participants were randomized 1:1 to receive continuous intravenous sivelestat (0.2 mg/kg/h) or placebo for 5 days. The primary outcome was the PaO₂/FiO₂ ratio on Day 5. Secondary outcomes included Sequential Organ Failure Assessment (SOFA) score, requirement and duration of invasive mechanical ventilation, and ICU length of stay. Inflammatory biomarkers were measured on Days 1, 3, and 5. Peripheral blood RNA sequencing was performed on Day 5.

Ten patients were enrolled (sivelestat n=5; placebo n=5). By Day 5, the sivelestat group showed significantly higher PaO₂/FiO₂ (317.2 ± 115.8 vs 168.6 ± 79.4 mmHg; p=0.046), lower SOFA scores (5.8 ± 1.3 vs 9.0 ± 1.9; p=0.014), lower CRP levels on Days 3 and 5 (both p=0.005), and shorter ICU stay (6.0 ± 2.5 vs 13.0 ± 3.6 days; p=0.009). RNA sequencing identified 518 differentially expressed genes, with six hub genes (BPI, ELANE, CEBPE, MPO, CTSG, and DEFA3) enriched in neutrophil protease-related inflammatory pathways.

In this hypothesis-generating pilot study, early sivelestat was associated with preliminary signals of improved oxygenation, reduced systemic inflammation, and shorter ICU stay. Exploratory transcriptomics identified six hub genes (BPI, ELANE, CEBPE, MPO, CTSG, DEFA3) implicating neutrophil protease-centered pathways. These findings support the need for larger, biomarker-integrated multicenter trials to confirm efficacy and define responsive subgroups.