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

Abstract

BackgroundThe 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.MethodsFirstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 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.ResultsIn 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).ConclusionAdministration 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.Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.

Postoperative hyper-inflammation as a predictor of poor outcomes in patients with acute type A aortic dissection (ATAAD) undergoing surgical repair

“…To our best known, postoperative hyper-inflammatory diseases in patients with ATAAD include acute lung injury, malperfusion syndrome, and severe pneumonia [ 8 , 10 , 11 ]. The systemic inflammatory response could induce acute lung injury which could significantly increase in-hospital death [ 6 , 17 ]. The malperfusion syndrome which is actually an ischemia–reperfusion injury (I/R injury), is caused by an immune-inflammatory response, which has been proven the lethal factor of in-hospital death [ 1 , 10 ].…”

“…During CPB in ATAAD surgery, an amplified systemic inflammatory response, involving neutrophile, lymphocyte, platelet, C reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) in body, was demonstrated that had a significant association with unfavorable postoperative outcomes including coagulopathy, surgical bleeding, re-intubation and so on [ 2 – 5 , 12 ]. It has been proven that an early-initiated anti-inflammatory strategy is a promising option after ATAAD surgery [ 6 ]. Therefore, early prediction of hyper-inflammation after ATAAD may be useful and valuable to decrease mortality and morbidity.…”

Targeting formyl peptide receptor 1 with anteiso‐C13‐surfactin for neutrophil‐dominant acute respiratory distress syndrome

“…Furthermore, decreasing toxic mediators produced by activated neutrophils reduced inflammatory injury. Excess elastase activity in inflamed lung tissue of ARDS patients and animal studies induces pulmonary tissue damage and affects recovery (Pan et al, 2023; Tsai, Yang, et al, 2022). Blocking elastase activity attenuates endotoxemic lung injury (Suzuki et al, 2019).…”

Sivelestat (Neutrophil Elastase Inhibitor) as Anti-inflammatory and Anti-viral Agent: An In Silico Study

“…It is currently used in Japan and the Republic of Korea for treating acute lung injury (ALI ) including Acute Respiratory Distress Syndrome (ARDS) in patients with Systemic Inflammatory Response Syndrome (SIRS) and its application has been investigated in several clinical trial studies [ 8 ]. Sivelestat has been shown to reduce both neutrophil elastase levels and interleukin 6 (IL-6) production [ 9 ]. Furthermore, inhibiting human neutrophil elastase (HNE) is a new approach for treating inflammatory lung diseases, such as swine flu (H1N1) and severe acute respiratory syndrome (SARS) virus infections [ 10 ].…”