Clinical utility of the neutrophil elastase inhibitor Sivelestat for the treatment of sepsis asscociated with both acute respiratory distress syndrome and Septic cardiomyopathy patients

Abstract Background: Acute respiratory distress syndrome(ARDS) and Septic cardiomyopathy(SCM) are most serious complications of sepsis. We aimed to evaluate the effects of the neutrophil elastase inhibitor sivelestat for the treatment of sepsis induced ARDS and SCM. Methods: Seventy patients who were diagnosed with ARDS and SCM between January 2019 and December 2021 at our hospital were randomly divided into sivelestat-treated group and the control group. Serum concentrations of IL-6, IL-8, TNF-α and HMGB1 were compared at five time points(baseline, 12h, 24h, 48h and 72h after ICU admission). Cardiac function evaluation by color Doppler ultrasound and Heart rate variability evaluation by 24h Holter recording was assessed at the time of ICU admission and 72h after sivelestat treatment. Results:The levels of IL-6, IL-8, and TNF-αwere significantly lower in the sivelestat-treated group at different time points(12h, 24h, 48h and 72h). HMGB1 levels were significantly lower 72 h after ICU admission in the sivelestat-treated group(19.46±2.63pg/mL vs. 21.20±2.03pg/mL, P = 0.003). The SV, TAPSE, E/A, e’, and a’value were significantly low in the control group compared with the sivelestat-treated group. Tei index was high in the control group compared with the sivelestat-treated group (0.60±0.08 vs. 0.56±0.07, P = 0.029). The result of Heart rate variability showed there were significant differences in SDNN, LF and LF/HF between two groups. Conclusions: Sivelestat can significantly reduce the level of plasma inflammatory factors, improve cardiac function and reduce heart rate variability in patients with sepsis induced ARDS and SCM. The trial registration number: ChiCTR-OPC-17013149