Sivelestat Sodium versus Standard Care for Prevention of Postoperative Lung Injury and Acute Respiratory Distress Syndrome in Adult Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass:A Systematic Review and Meta-Analysis.

BACKGROUND

Cardiopulmonary bypass (CPB) during cardiac surgery induces a systemic inflammatory response that can result in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), with high associated mortality. Sivelestat sodium, a selective neutrophil elastase inhibitor, targets this pathway, but its perioperative efficacy remains uncertain. This study aimed to evaluate the efficacy and safety of perioperative sivelestat sodium versus standard care in adults undergoing cardiac surgery with CPB.

METHODS

PubMed, Embase, and Cochrane databases were searched from inception to May 2026, following PRISMA guidelines (PROSPERO registered). Randomized controlled trials and observational cohort studies were included. The primary outcome was the incidence of ARDS; secondary outcomes included all-cause mortality, arterial partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio, duration of mechanical ventilation, and intensive care unit ICU length of stay (LOS). Random-effects models were used, with Peto odds ratio (OR) for sparse data. Heterogeneity was assessed using the I² statistic, and certainty was evaluated using GRADE.

RESULTS

Six studies (2 RCTs, 4 cohort studies; n = 834 patients) were included, all from East Asia. Pooled estimates favored sivelestat across outcomes but were not statistically significant due to heterogeneity. ARDS incidence (k = 2) showed a Peto OR of 0.19 (95% confidence interval [CI], 0.03-1.16; I² = 91.3%). Mortality (k = 5) yielded an OR of 0.69 (95% CI, 0.35-1.39; I² = 36.7%), with 1 RCT showing significant benefit. Mechanical ventilation duration and ICU LOS were reduced but not significantly so. Evidence certainty was very low.

CONCLUSION

Sivelestat shows consistent directional benefit in CPB-associated pulmonary outcomes, but heterogeneity limits statistical significance. Larger multicenter RCTs are needed to confirm efficacy and define clinical use.