Acute respiratory distress syndrome is a serious condition that can arise following direct or indirect
lung injury. It is heterogeneous and has a high mortality rate. Supportive care is the mainstay of treatment and there is no definitive pharmacological treatment as yet.
Sivelestat is a
neutrophil elastase inhibitor approved in Japan and the Republic of Korea for
acute lung injury, including
acute respiratory distress syndrome in patients with
systemic inflammatory response syndrome. The aim of this review is to examine the clinical utility of
sivelestat in different disease states, using data from nonclinical and clinical studies. In nonclinical studies,
sivelestat appears to show benefit in
acute lung injury without inhibiting the host immune defense in cases of
infection. Clinical studies do not yet provide a clear consensus. Phase III and IV Japanese studies have shown improvements in pulmonary function, length of intensive care unit stay, and
mechanical ventilation, but a non-Japanese multicenter study did not demonstrate
sivelestat to have an effect on
ventilator-free days or 28-day all-cause mortality. Evidence of improvement in various parameters, including duration of stay in
intensive care,
mechanical ventilation, the ratio of partial pressure of arterial
oxygen and fraction of inspired
oxygen (PaO2/FIO2 ratio) ratio, and
lung injury scores, has been shown in patients with
sepsis or gastric aspiration, and following the surgical treatment of
esophageal cancer. To date, there are no particular concerns regarding adverse events, and the available data do not suggest that
sivelestat might worsen
infections. One study has analyzed cost-effectiveness, finding that
sivelestat may reduce costs compared with standard care. The currently available evidence suggests that
sivelestat may show some benefit in the treatment of
acute lung injury/
acute respiratory distress syndrome, although large, randomized controlled trials are needed in specific pathophysiological conditions to explore these potential benefits.