To investigate the protective effect of sivelestat sodium, a neutrophil elastase (NE) inhibitor, on acute lung injury (ALI) after cardiopulmonary bypass (CPB) by regulating alveolar macrophages (AMs) polarization and to analyze its impact on clinical outcomes.

A prospective study was conducted on 65 patients with ALI after CPB admitted to the Department of Critical Care Medicine of the Shaoxing People's Hospital between April 2023 and April 2025. Patients were randomly divided into a Sivel group (n = 32) and a Ctrl group (n = 33) using a single-blind group random number table. The basic information, 30-day mortality, stroke incidence, and the utilization rate of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were collected. The changes of bilateral pulmonary exudation after CPB, ventricular arrhythmia, lactate elevation > 48 h, new-onset atrial fibrillation, mechanical ventilation time, ICU stay time, and the oxygenation index, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), white blood cell (WBC) and neutrophil (Neu) ratio at the time of ICU admission and on the 1st, 3rd and 5th days after surgery were observed. On the 1st day after surgery, bronchoalveolar lavage fluid (BALF) was collected to measure tumor necrosis factor-alpha (TNF-α), IL-10, and high mobility group box 1 (HMGB1) levels. AMs were cultured, and the messenger RNA (mRNA) expression levels of M1 polarization markers [inducible nitric oxide synthase (iNOS), TNF-α, and IL-1β] and M2 polarization marker [arginase-1 (Arg1)] were quantified using real-time fluorescence quantitative PCR. Immunofluorescence was used to assess iNOS and CD206 expression in AMs.

There were no significant differences in the 30-day mortality, ECMO utilization, stroke incidence, or CRRT utilization between the Sivel group and the Ctrl group (all P > 0.05). However, the Sivel group showed significant improvement in reduced bilateral pulmonary exudative changes [28.12% (9/32) vs. 54.55% (18/33), χ² = 5.909, P = 0.015], lower incidence of new-onset atrial fibrillation [6.25% (2/32) vs. 24.24% (8/33), χ² = 4.040, P = 0.044], shorter mechanical ventilation time [(3.7 ± 2.1) d vs. (5.2 ± 2.5) d, χ² = 3.727, P = 0.014], and shorter ICU stay [(75 ± 47) h vs. (97 ± 25) h, χ² = 2.257, P = 0.031] compared with the Ctrl group. In the Sivel group, the oxygenation index improved on the 1st day after surgery, while PCT and CRP levels improved on the 3rd and 5th days as compared with the Ctrl group (all P < 0.05). BALF analysis on the first postoperative day revealed lower TNF-α and HMGB1 levels but higher IL-10 levels in the Sivel group than in the Ctrl group (all P < 0.05). AMs studies showed increased Arg1 mRNA expression and decreased iNOS, TNF-α, and IL-1β mRNA expression in the Sivel group as compared with the Ctrl group (all P < 0.05). Immunofluorescence confirmed increased CD206 positive cells and decreased iNOS positive cells in the Sivel group.

Sivelestat sodium may protect against CPB-induced ALI and improve clinical outcomes by promoting M2 macrophage polarization and reducing inflammation.