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Abstract：
BACKGROUND: We aimed to assess the efficacy of the neutrophil elastase inhibitor, sivelestat, in the treatment of sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM).
METHODS: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment.
RESULTS: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e\') and late (a\') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups.
CONCLUSIONS: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.
METHODS: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment.
RESULTS: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e\') and late (a\') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups.
CONCLUSIONS: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.
摘要：
背景：我们旨在评估中性粒细胞弹性蛋白酶抑制剂的疗效，sivelestat,在脓毒症诱导的急性呼吸窘迫综合征（ARDS）和脓毒性心肌病（SCM）的治疗中。
方法：在2019年1月至2021年12月之间，我们在武汉协和医院对被诊断为脓毒症诱发的急性呼吸窘迫综合征（ARDS）和脓毒症心肌病（SCM）的患者进行了一项随机试验。采用随机包络法将患者分为两组,Sivelestat组和对照组。我们测量了血清白细胞介素（IL）-6，IL-8，肿瘤坏死因子-α（TNF-α）的浓度，和高流动性组盒1(HMGB1)在五个时间点，这是基线，12h,24h,48h,入住ICU后72小时。我们通过超声检查评估了心脏功能和心率变异性（HRV），并在入住重症监护病房（ICU）至Sivelestat治疗后72小时之间进行了24小时Holter记录。
结果：从2019年1月至2021年12月，本研究共纳入70例患者。不同时间点Sivelestat组IL-6、IL-8、TNF-α水平均显著降低(12h,24h,48h,和72小时)。在Sivelestat治疗后72小时，HMGB1水平显着降低（19.46±2.63pg/mL与21.20±2.03pg/mL，P=0.003)。冲程容积(SV),三尖瓣环平面收缩期偏移(TAPSE),早期至晚期舒张血流速度（E/A），与Sivelestat组相比，对照组的早期（e\'）和晚期（a\'）舒张明显较低。与Sivelestat组相比，对照组的Tei指数较高（0.60±0.08vs.0.56±0.07,P=0.029)。HRV结果显示正常到正常间隔（SDNN）的标准偏差存在显着差异，低频（LF），和LF/HF（高频）两组之间。
结论：西维来司可显著降低血清炎症因子水平，改善心脏功能，并降低脓毒症诱导的ARDS和SCM患者的心率变异性。
方法：在2019年1月至2021年12月之间，我们在武汉协和医院对被诊断为脓毒症诱发的急性呼吸窘迫综合征（ARDS）和脓毒症心肌病（SCM）的患者进行了一项随机试验。采用随机包络法将患者分为两组,Sivelestat组和对照组。我们测量了血清白细胞介素（IL）-6，IL-8，肿瘤坏死因子-α（TNF-α）的浓度，和高流动性组盒1(HMGB1)在五个时间点，这是基线，12h,24h,48h,入住ICU后72小时。我们通过超声检查评估了心脏功能和心率变异性（HRV），并在入住重症监护病房（ICU）至Sivelestat治疗后72小时之间进行了24小时Holter记录。
结果：从2019年1月至2021年12月，本研究共纳入70例患者。不同时间点Sivelestat组IL-6、IL-8、TNF-α水平均显著降低(12h,24h,48h,和72小时)。在Sivelestat治疗后72小时，HMGB1水平显着降低（19.46±2.63pg/mL与21.20±2.03pg/mL，P=0.003)。冲程容积(SV),三尖瓣环平面收缩期偏移(TAPSE),早期至晚期舒张血流速度（E/A），与Sivelestat组相比，对照组的早期（e\'）和晚期（a\'）舒张明显较低。与Sivelestat组相比，对照组的Tei指数较高（0.60±0.08vs.0.56±0.07,P=0.029)。HRV结果显示正常到正常间隔（SDNN）的标准偏差存在显着差异，低频（LF），和LF/HF（高频）两组之间。
结论：西维来司可显著降低血清炎症因子水平，改善心脏功能，并降低脓毒症诱导的ARDS和SCM患者的心率变异性。
