Sivelestat, a neutrophil elastase inhibitor, reduces mortality rate of critically ill patients

Many studies have suggested that neutrophil elastase (NE) may contribute to multiple organ failure (MOF) and acute injury of lung endothelial cells. It is therefore conceivable that NE inhibitors may improve the outcome of MOF patients. A synthetic NE inhibitor, sivelestat, which was developed and released in Japan, inhibited inflammatory reactions in various animal models. We examined the medical records of patients requiring more than two days of respiratory care in four intensive care units to investigate whether sivelestat contributed to improvement of their conditions. A total of 110 patients were divided into two groups (sivelestat treated group of 57 patients and untreated group of 53 patients). The conditions and age of the patients were similar in both groups. Sivelestat (0.2 mg/kg/hr) was administered continuously for 14 days beginning on the day of the intensive care unit (ICU) admission or for less than 14 days until discharge from the ICU. Hospital mortality differed significantly between the two groups (treated: 19% and untreated: 40%, p < 0.05). The severity of acute lung injury is defined by the ratio of arterial oxygen partial pressure (PaO2)/fraction concentration of oxygen in the inspired air (FiO2). When the PaO2/FiO(2) ratio is more than 200 mmHg, the morbidity is lower. In patients with PaO2/FiO2 ratio more than 200 mmHg, the hospital mortality was 33.3% (7/21) in the untreated group and 6.0% (1/18) in the treated group (p = 0.0236). We conclude that administration of sivelestat reduces mortality of critically ill patients.