Evaluation of appropriate indications for the use of sivelestat sodium in acute respiratory distress syndrome: a retrospective cohort study

Abstract

Sivelestat sodium, a selective neutrophil elastase inhibitor, is the only commercially available, specific therapy for acute respiratory distress syndrome (ARDS); however, its clinical efficacy is controversial. We aimed to evaluate appropriate indications for its use in ARDS. Methods: We studied 66 patients with ARDS who were treated with sivelestat sodium. They were divided into survivors (n = 37) or non-survivors (n = 29) at 60 days, and clinical characteristics were analyzed. Results: Patients' backgrounds evaluated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the sequential organ failure assessment (SOFA) score were significantly different between both groups (survivors versus non-survivors: APACHE II score, 14.7 AE 6.7 versus 20.5 AE 4.7, P < 0.01; SOFA, 7.25 AE 2.5 versus 9.82 AE 3.5, P < 0.01). There were no significant differences in other patients' characteristics. On receiver operator characteristic analysis of APACHE II scores before the use of sivelestat sodium, the estimated cutoff value for survival was calculated to be 18.5. On receiver operator characteristic analysis of the PaO 2 /FIO 2 ratio, the area under the curve was the highest 3 days after the treatment, with the optimal cutoff point at 198. Conclusion: An APACHE II score ≤18, and a PaO 2 /FIO 2 ratio >198 at 3 days after the use of sivelestat sodium predicted a good outcome.

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

“…Specifically, NE facilitates the invasion of SARS-CoV-2 into host cells and can also damage lung tissues directly. The role of NE in patients with ARDS, including COVID-19, and sepsis have been reported in different studies [104][105][106][107]. Moreover, in an experimental mice model, Ogura et al reported that NE deficiency improves myocardial injury in post-myocardial infarction [108].…”

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

“…In a meta-analysis study, sivelestat failed to improve the survival of patients with ARDS ( Tagami et al, 2014 ). However, a retrospective cohort study with 66 ARDS patients demonstrated that sivelestat treatment yields positive outcomes ( Maki et al, 2020 ). In particular, aerosol- or nebulizer-dosed NE inhibitors significantly improved their efficacy and lowered adverse effects ( Barth et al, 2020 ).…”

Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19

“… 226 Sivelestat, a potent NE inhibitor approved in Korea and Japan, can ameliorate acute lung injury. 227 A retrospective cohort study showed that sivelestat exhibited positive outcomes in patients with ARDS, 228 indicating that NE inhibitor might be beneficial for patients with COVID-19. In addition, A randomized, placebo-controlled phase Ib/II clinical trial of Alvelestat treatment for COVID-19 with ARDS has been completed with no results published (NCT04539795).…”