The evaluation of sivelestat sodium hydrate in acute lung injury/acute respiratory distress syndrome patients in the intensive care unit

Abstract

The onset mechanism of ALI/ARDS and subsequent tissue injury are considered to be associated with neutrophil elastase, and the main causes of ALI/ARDS are considered to be sepsis or aspiration pneumonia. In Japan, sivelestat sodium hydrate (Elaspol), a selective elastase inhibitor, was approved in 2002 for ALI/ARDS accompanied by SIRS, and this medicine has been evaluated in a clinical situation. In this study, we performed a retrospective comparison of the sivelestat sodium administration between two groups of patients: Group Elaspol, consisting of 308 patients (209 males and 99 females, aged 66 ± 15 years) with ALI/ARDS accompanied by SIRS who were treated with sivelestat sodium at a dose of 0.2 mg/kg/hour for 72 hours or more, after approval of this drug; and Group Control, consisting of 41 patients (28 males and 13 females, aged 66 ± 14 years) with ALI/ARDS accompanied by SIRS who were treated in the ICU under similar conditions, but using traditional methods for respiratory control, prior to approval sivelestat sodium. The APACHE II scores of Group Elaspol and Group Control were 23 ± 9 and 23 ± 8, SOFA scores were 8.7 ± 3.8 and 8.9 ± 4.1, and the lung injury scores were 2.1 ± 0.7 and 2.1 ± 0.6, respectively, with no significant differences between the groups. The initial PEEP value of Group Elaspol was 5.9 ± 3.3, which was significantly higher than that of Group Control (3.4 ± 2.7 cmH2O). The PaO2/FIO2 ratios under mechanical ventilation management 24, 48 and 72 hours after the beginning of drug administration were 209 ± 87, 222 ± 92, and 222 ± 82 mmHg in Group Elaspol, and were 191 ± 91, 207 ± 91, and 211 ± 100 mmHg in Group Control. The ventilator-free days of Group Elaspol and Group Control were 18 ± 9 and 10 ± 12 days, respectively, and these values showed a significant difference (P < 0.001). Furthermore, the survival rate after 28 days was significantly higher in Group Elaspol than in Group Control (Group Elaspol: 75%, Group Control: 52%; P < 0.001). These results suggest that sivelestat sodium hydrate is a good option as a treatment strategy for neutrophil elastase-associated septic ALI/ARDS accompanied by SIRS.