Effect of Sivelestat in the Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

Abstract

Background The efficacy of neutrophil elastase inhibitor sivelestat in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains controversial. A systematic review and meta-analysis were performed in accordance with the PRISMA guidelines assess the effect of sivelestat on ALI/ARDS patients, different studies were included. Methods Electronic databases, National Knowledge Infrastructure (CNKI), Wan fang data, VIP, PubMed, Embase, Springer, Ovid and the Cochrane Library were searched using the following key words: (“Sivelestat” OR “Elaspol”) AND (“ARDS” OR “adult respiratory distress syndrome” OR “acute lung injury”). All databases published from January 2000 to August 2022. The treatment group was treated with sivelestat and the control group was given normal saline. The outcome measurements include the mortality of 28–30 days, mechanical ventilation time, ventilation free days, intensive care unit (ICU) stays, oxygenation index (PaO2/FiO2) on day 3, the incidence of adverse events. The literature search was conducted independently by 2 researchers using standardized methods. We used the Cochrane risk-of-bias tool to assess the quality of the included studies. Mean difference (MD), Standardized mean difference (SMD) and relative risk (RR) were calculated using random effects model or fixed effects model. All statistical analyses were performed using RevMan software 5.4. Results A total of 2050 patients were enrolled in 15 studies, including 1069 patients in treatment group and 981 patients in the control group. The results of the meta-analysis showed that: compared with the control group, sivelestat can reduce the mortality of 28–30 days (RR = 0.81, 95% CI = 0.66–0.98, p = 0.03) and the incidence of adverse events (RR = 0.91, 95% CI = 0.85–0.98, p = 0.01), shortened mechanical ventilation time (SMD = − 0.32, 95% CI = − 0.60 to − 0.04, p = 0.02) and ICU stays (SMD = − 0.72, 95% CI = − 0.92 to − 0.52, p < 0.00001), increased the ventilation free days (MD = 3.57, 95% CI = 3.42–3.73, p < 0.00001) and improve oxygenation index (PaO2/FiO2) on day 3 (SMD = 0.88, 95% CI = 0.39–1.36, p = 0.0004). Conclusions Sivelestat can not only reduce the mortality of ALI/ARDS patients within 28–30 days and the incidence of adverse events, shorten the mechanical ventilation time and ICU stays, increase ventilation free days, but also improve the oxygenation index of patients on days 3, which has a good effect on the treatment of ALI/ARDS. These findings need to be verified in large-scale trials.

Efficacy Analysis and Prognostic Impact of Sivelestat Sodium in Coronavirus Disease 2019-Related Acute Respiratory Distress Syndrome

“…The effect of sivelestat sodium on the risk of death in patients with ARDS is still a subject of debate, and different studies have reported conflicting findings. Some studies have suggested that treatment with sivelestat sodium may reduce the risk of death in patients with ALI/ARDS [ 20 , 21 , 28 ]. For example, a large-sample study involving 4276 patients showed that sivelestat sodium treatment within seven days of hospital admission may improve the prognosis of patients with ALI/ARDS [ 11 ].…”

Neutrophil extracellular traps and their implications in airway inflammatory diseases

“…Sivelestat is a selective NE inhibitor and the only specific therapy available for ARDS. A systematic review and meta-analysis revealed that sivelestat not only reduces the mortality rate and incidence of adverse events in ALI/ARDS patients, but also shortens mechanical ventilation time and ICU stay, increases non-ventilated days, and improves patient's oxygenation index (47). However, the efficacy of sivelestat sodium in treating ARDS is still controversial in clinical research (48,49).…”