The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass

Abstract

Background: The sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery.

Methods: Firstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1^st, 2020 to October 26^th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc.

Results: In propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P<0.01), bilateral pulmonary infiltrates (P<0.01), oxygen index (P<0.01), interleukin-6(P=0.02), procalcitonin(P<0.01) and C-reactive protein(P<0.01).

Conclusion: Administration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB.

Registration: http://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.

Keywords: acute lung injury; cardiopulmonary bypass; cardiovascular surgery; outcomes; sivelestat.

Figure 1

Enrollment flow chart.

Figure 2

univariate analysis for adverse events in pre-propensity matched patients. The figure applied log2 transformation in order to make it easy to read. BMI, Body mass index; LVEF, Left ventricular ejection fraction; ACEi, Angiotensin-converting enzyme inhibitors; ARB, Angiotensin receptor blockers; CCB, Calcium channel blocker; CPB, Cardiopulmonary bypass; DHCA, Deep hypothermic circulation arrest; Betaloc, β-blocker; BPI, Bilateral pulmonary infiltrates on chest X ray.

Figure 3

Kaplan-Meier (K-M) curves showing the primary outcomes had no difference between the two groups in propensity-matched patients during 30-days follow-up.

Figure 4

(A) The oxygen index (PaO₂/FiO₂), P < 0.01; ※:P < 0.05, ^†:P > 0.05. (B) The procalcitonin, P < 0.01; ※:P < 0.05, ^†:P > 0.05. (C) The interleukin-6, P=0.02; ※:P < 0.05, ^†:P > 0.05. (D) The C reactive protein, P < 0.01; ※:P < 0.05, ^†:P > 0.05.