Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Abstract

BackgroundSivelestat is widely used in treating acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), although the clinical efficacy of sivelestat remains controversial. This study aimed to evaluate the impact of sivelestat in patients with ALI/ARDS.MethodsElectronic databases, PubMed, Embase, and the Cochrane Library, were searched to identify trials through April 2017. Randomized controlled trials (RCTs) were included irrespective of blinding or language that compared patients with and without sivelestat therapy in ALI/ARDS. A random-effects model was used to process the data, and the relative risk (RR) and standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to evaluate the effect of sivelestat.ResultsSix RCTs reporting data on 804 patients with ALI/ARDS were included. Overall, no significant difference was found between sivelestat and control for the risk of 28–30 days mortality (RR: 0.94; 95% CI: 0.71–1.23; P = 0.718). Sivelestat therapy had no significant effect on ventilation days (SMD: 0.05; 95% CI: −0.27 to 0.38; P = 0.748), arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) level (SMD: 0.48; 95% CI: −0.45 to 1.41; P = 0.315), and intensive care unit (ICU) stays (SMD: −9.87; 95% CI: −24.30 to 4.56; P = 0.180). The results of sensitivity analysis indicated that sivelestat therapy might affect the PaO2/FiO2 level in patients with ALI/ARDS (SMD: 0.87; 95% CI: 0.39 to 1.35; P < 0.001).ConclusionsSivelestat therapy might increase the PaO2/FiO2 level, while it had little or no effect on 28–30 days mortality, ventilation days, and ICU stays. These findings need to be verified in large-scale trials.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0498-z) contains supplementary material, which is available to authorized users.

Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential

“…Mice deficient in NE are more susceptible to Gram‐negative bacteria, suggesting that NE are required for adequate host defence against invading pathogens and complete inhibition of NE can be harmful . Despite data from preclinical models, sivelestat, a selective NE inhibitor, did not alter 28‐day mortality in a number of clinical trials (Table ) . Although alteration in oxygenation has been observed, the small sample sizes of the majority of clinical trials and heterogenous patient populations potentially mask any benefit in subgroups of patients with ARDS .…”

“…Despite data from preclinical models, sivelestat, a selective NE inhibitor, did not alter 28‐day mortality in a number of clinical trials (Table ) . Although alteration in oxygenation has been observed, the small sample sizes of the majority of clinical trials and heterogenous patient populations potentially mask any benefit in subgroups of patients with ARDS . It is difficult to separate challenges in clinical trial design from limitations of biological importance in this context.…”

Exosomes in Sepsis

“…The injection of exosomes isolated from the serum of LPS-challenged mice increased the number of total and M1 macrophages and the levels of TNF-α and IL-6 in the lungs, which was associated with the increase of miR-155 (52). Although ARDS has attracted clinical attention for decades, none of the proposed therapies for ARDS including sivelestat sodium, neutrophil elastase inhibitor, have yet to show its clinical effect sufficiently (64). We might have overlooked the significance of exosomes as they cause inflammatory response and cell death in lungs independent of neutrophil activity (30,52).…”

Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

“…A meta-analysis of 6 RCTs reporting data on 804 patients with ARDS showed that sivelestat might increase the PaO 2 /FiO 2 level, but with little or no effect on 28–30 days mortality, ventilation days, and ICU stays [ 90 ].…”