摘要信息：Purpose:We assessed the effects of a neutrophil elastase inhibitor, sivelestat, on respiratory and organ functions as well as on the mortality of patients with acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS). Methods:We retrospectively divided 25 patients who fulfilled the diagnostic criteria for SIRS and ARDS into two groups. One group (S group, n = 12) received a continuous infusion of sivelestat (0.2 mg.kg(-1).h(-1)), and the other did not (C group, n = 13). Results:Between days 1 and 10, the Pa(O2)/FI(O2) ratio in the S group significantly improved from 119.1 +/- 51.1 to 214.4 +/- 88.2 mmHg (P < 0.05). Furthermore, the S group spent significantly fewer days on a ventilator than the C group (16.7 +/- 5.8 vs 26.6 +/- 14.3 days; P < 0.05). The length of the intensive care unit stay was also significantly shorter for the S group than for the C group (18.7 +/- 4.9 vs 27.5 +/- 13.5 days; P < 0.05). However, the mortality rate at 29 days did not statistically differ between the two groups. Conclusion:Our results suggested that sivelestat has a beneficial effect only on the pulmonary function of ARDS patients with SIRS.

摘要信息：Background:Neutrophil elastase, alveolar thrombin generation, and fibrin deposition play crucial roles in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). However, the usefulness of combination therapy with a selective neutrophil elastase inhibitor, sivelestat, and recombinant human soluble thrombomodulin (rhTM) for patients with ARDS and DIC remains unknown. Methods:We conducted a retrospective data analysis of 142 ARDS patients with DIC to assess the effects of sivelestat combined with rhTM. Patients were divided into four groups: control (no sivelestat or rhTM treatment), sivelestat treatment alone, rhTM treatment alone, and combined treatment with sivelestat and rhTM. A Cox proportional hazard model was used to assess subject mortality rates. The efficacy of these drugs was evaluated based on survival rate, number of ventilator-free days, and change in PaO2/FIO2 (P/F) ratios and DIC scores before and at 7 days after a diagnosis of ARDS with DIC. Results:Multivariate analysis showed that patient age, combination therapy, gas exchange, organ failure, cause, associated disease score, and serum C-reactive protein levels were predictors of mortality for patients with ARDS and DIC. As compared with untreated controls, combination therapy significantly improved the 60-day survival rate of patients with ARDS and DIC. There were significantly more ventilator-free days for those who received combination therapy than for untreated controls. P/F ratios and DIC scores were significantly improved with sivelestat alone, rhTM alone, or their combination as compared with untreated controls. Conclusion:Our results suggest that combined treatment with sivelestat and rhTM has beneficial effects on survival and the respiratory and DIC status of patients with ARDS and DIC.

摘要信息：Evidence has linked neutrophil elastase to acute respiratory distress syndrome (ARDS), suggesting that inhibiting the activity of this enzyme could prevent the development and progression of ARDS. However, few clinical trials have examined this notion. We therefore examined the effects of ONO-5046 (sivelestat, a specific inhibitor of neutrophil elastase; sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylaminobenzoyl]amino-acetate tetrahydrate]) in a randomized, double-blinded trial in patients with ARDS. We randomly assigned 24 patients with ARDS to groups that received conventional therapy without or with sivelestat (0.2 mg. kg(-1). h(-1)) for 14 days. The variables of interest associated with clinical outcome were the duration of mechanical ventilation; changes in oxygenation from baseline; changes in cytokine levels from baseline; number of patients alive at 30 days who did not need mechanical ventilation; and mortality rate. The length of intensive care unit stay, number of ventilation days, and mortality rates did not statistically differ between groups. ARDS was more persistent in the control than in the sivelestat group (control, 19.5 +/- 7.4 days; sivelestat, 13.5 +/- 5.9 days; P = 0.039). Neutrophil elastase activity significantly differed between groups at 72 h after treatment. Levels of interleukin-6 were lower in the sivelestat group than in the controls at 24, 48, and 72 h after treatment. ONO-5046 apparently did not affect survival or the duration of mechanical ventilation.

摘要信息：Background and objective:The efficacy of sivelestat, a neutrophil elastase inhibitor, for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains controversial. We investigated the role of sivelestat in ALI/ARDS patients on mortality as an end point between the sivelestat group and the non-sivelestat group within 7 days of admission. Methods:This study was performed using the Japanese nationwide administrative database (Diagnostic Procedure Combination; DPC) in 2012. We employed the propensity score weighting method with a Cox proportional hazards model to compare the mortality between the sivelestat group and the non-sivelestat group. Results:A total of 4276 patients were eligible for this study; 1997 patients were treated with sivelestat and 2279 patients did not receive sivelestat within 7 days of admission. After adjusting for confounds, the mortality within 3 months was significantly lower in the sivelestat group compared with the non-sivelestat group (weighted hazard ratio: 0.83; 95% CI: 0.75-0.93; P < 0.002). Multiple regression analysis revealed that younger age, absence of cancer, no need for haemodialysis and no use of high-dose methylprednisolone were significantly correlated with treatment success (survive). Conclusion:These results of this retrospective and observational study suggest that administration of sivelestat within 7 days of admission may improve the prognosis of patients with ALI/ARDS. To our knowledge, this is the largest study to evaluate the efficacy of sivelestat on ALI/ARDS. Keywords: acute lung injury; acute respiratory distress syndrome; inverse probability of treatment weighting; nationwide administrative database; sivelestat.

摘要信息：Background:Sivelestat is widely used in treating acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), although the clinical efficacy of sivelestat remains controversial. This study aimed to evaluate the impact of sivelestat in patients with ALI/ARDS. Methods:Electronic databases, PubMed, Embase, and the Cochrane Library, were searched to identify trials through April 2017. Randomized controlled trials (RCTs) were included irrespective of blinding or language that compared patients with and without sivelestat therapy in ALI/ARDS. A random-effects model was used to process the data, and the relative risk (RR) and standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to evaluate the effect of sivelestat. Results:Six RCTs reporting data on 804 patients with ALI/ARDS were included. Overall, no significant difference was found between sivelestat and control for the risk of 28-30 days mortality (RR: 0.94; 95% CI: 0.71-1.23; P = 0.718). Sivelestat therapy had no significant effect on ventilation days (SMD: 0.05; 95% CI: -0.27 to 0.38; P = 0.748), arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) level (SMD: 0.48; 95% CI: -0.45 to 1.41; P = 0.315), and intensive care unit (ICU) stays (SMD: -9.87; 95% CI: -24.30 to 4.56; P = 0.180). The results of sensitivity analysis indicated that sivelestat therapy might affect the PaO2/FiO2level in patients with ALI/ARDS (SMD: 0.87; 95% CI: 0.39 to 1.35; P < 0.001). Conclusions:Sivelestat therapy might increase the PaO2/FiO2level, while it had little or no effect on 28-30 days mortality, ventilation days, and ICU stays. These findings need to be verified in large-scale trials.

摘要信息：Background:Acute respiratory distress syndrome (ARDS) is one of the most organ dysfunctions in sepsis. Although the development of therapeutic strategies such as protective mechanical ventilation technology has improved the mortality of ARDS patients, there is currently no effective drug for reducing the associated mortality. Our study aims to investigate the efficacy, safety, and pharmacoeconomics of sivelestat sodium in patients with septic ARDS, for providing the basis on clinical use of this drug. Methods:This was a retrospective study of 140 patients with septic ARDS. Clinical information including general conditions, mechanical ventilation time, drug cost parameters, and adverse reactions. The partial pressure of O2/fraction of inspired oxygen (PaO2/FiO2), acute physiology and chronic health evaluation score (APACHE II score) and sequential organ failure assessment (SOFA score) are for assessing the severity illness. To evaluate the efficacy of sivelestat sodium on septic ARDS patients by comparing length of mechanical ventilation and intensive care unit (ICU) hospitalization, cost of hospitalization and mortality between the two groups. Results:There were no significant differences in the incidence of organ failure, biochemical data, blood gas analysis, acute physiology and chronic health evaluation (APACHE II score), and SOFA score between the two groups on the day of admission. The PaO2/FiO2, APACHE II score, and SOFA score of the sivelestat sodium group were significantly better than in the control group (P<0.05). The length of mechanical ventilation, length of ICU hospitalization, and cost of ICU hospitalization were all lower in the sivelestat sodium group (P<0.05). No adverse events were reported during the study period. Conclusions:Sivelestat sodium significantly improves the oxygenation in patients with septic ARDS, together with reducing mechanical ventilation, ICU hospitalization, and medical costs.

摘要信息：【摘要】目的 探讨中性粒细胞弹性蛋白酶(NE)抑制剂西维来司他钠在重症监护室(ICU)急性肺损伤(ALI)患者中应用的有效性和安全性。方法回顾性分析2020年6月至2021年6月郑州大学第一附属医院 ICU 171 例 ALI患者，其中西维来司他钠组 77 例，常规治疗组 94例。收集患者的临床资料，包括急性生理和慢性健康评分Ⅱ(APACHE Ⅱ)、Mumray 肺损伤评分、氧合指数(PaO,FiO,)、炎症因子(I-6、IL-10、TNF-α )，并统计无呼吸机天数(VED)、ICU 住院天数及 28 d病死率等，来评估西维来司他钠对 ICU 中 ALI治疗的有效性。同时，记录西维来司他钠使用后 30d内患者不良反应及化验指标来评估其应用的安全性。结果与常规治疗相比，西维来司他钠治疗7d后氧合指数、Mumray 肺损伤评分、I-6、IL-10、TNF-a 均明显改善，差异有统计学意义。与常规治疗组相比，西维来司他钠组 VFD 更长(P=0.0119 )，ICU 住院天数更少(P0.0269 )，差异具有统计学意义。西维来司他钠组病死率为 14.29%，常规治疗组病死率为 22.34%,两组间病死率差异无统计学意义。西维来司他钠使用后 30 d内未增加患者不良反应，安全性良好,结论 重症监护室急性肺损伤患者使用西维来司他钠治疗安全性良好，较常规治疗更有效。

摘要信息：【摘 要】 目的 探讨西维来司他钠联合乌司他丁治疗急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)患者的疗效及安全性。方法回顾性选取2020年5月一2022年5月福建医科大学附属闽东医院收治的 60 例 ALV/ARDS患者作为研究对象,根据治疗方法分为对照组和观察组,各30例。患者人院后均进行原发病的对症处理,在此基础上,对照组患者予以乌司他丁单药治疗,观察组患者在对照组基础上予以西维来司他钠治疗,2组均用药7d。比较2 组治疗前及治疗7d后呼吸功能指标[动脉血氧分压(Pa0,)/吸入氧浓度( Fi0,),血管外肺水指数(ELWI)1、实验室指标[白介素6(Ⅱ-6)、肿瘤坏死因子 α(TNF-a)、C反应蛋白(CRP)、降钙素原(PCT)、白细胞计数( WBC)、血肌酐(SCr)、丙氨酸氨基转移酶(ALT)、尿素氮(BUN)1,住院指标[ICU 住院时间,机械通气时间及急性生理学和慢性健康状况Ⅱ(APACEI)评分1、不良反应及28 d存活率。结果 治疗7d后,2组 Pa0,/Fi0,较治疗前升高,ELWI较治疗前降低,且观察组 PaO,/Fi0,较对照组更高,ELWI较对照组更低(P<0.01)。治疗7d后,2组血清 Ⅱ-6、TNF-aCRP、PCT、SCr、ALT、BUN 水平及 WBC 较治疗前降低,且观察组血清 IL-6、TNF-α、CRP、PCT、ALT 水平及 WBC 较对照组更低(P<0.01)。与对照组相比,观察组ICU 住院时间、机械通气时间更短,APACEI评分更低(P<0.01)。2组不良反应总发生率比较,差异无统计学意义(P=1.000)。随访28 d,观察组存活率为90.00%(27/30),高于对照组的66.67%(20/30)(x =4.812,P=0.028)。结论 西维来司他钠联合乌司他丁治疗 AL/ARDS 可有效减轻机体炎性反应,改善肺通气功能,促进疾病快速康复,且可保护主要脏器功能,提高 28 d存活率,且安全性较高。

摘要信息：Background:The efficacy of neutrophil elastase inhibitor sivelestat in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains controversial. A systematic review and meta-analysis were performed in accordance with the PRISMA guidelines assess the effect of sivelestat on ALI/ARDS patients, different studies were included. Methods:Electronic databases, National Knowledge Infrastructure (CNKI), Wan fang data, VIP, PubMed, Embase, Springer, Ovid and the Cochrane Library were searched using the following key words: ("Sivelestat" OR "Elaspol") AND ("ARDS" OR "adult respiratory distress syndrome" OR "acute lung injury"). All databases published from January 2000 to August 2022. The treatment group was treated with sivelestat and the control group was given normal saline. The outcome measurements include the mortality of 28-30 days, mechanical ventilation time, ventilation free days, intensive care unit (ICU) stays, oxygenation index (PaO2/FiO2) on day 3, the incidence of adverse events. The literature search was conducted independently by 2 researchers using standardized methods. We used the Cochrane risk-of-bias tool to assess the quality of the included studies. Mean difference (MD), Standardized mean difference (SMD) and relative risk (RR) were calculated using random effects model or fixed effects model. All statistical analyses were performed using RevMan software 5.4. Results:A total of 2050 patients were enrolled in 15 studies, including 1069 patients in treatment group and 981 patients in the control group. The results of the meta-analysis showed that: compared with the control group, sivelestat can reduce the mortality of 28-30 days (RR = 0.81, 95% CI = 0.66-0.98, p = 0.03) and the incidence of adverse events (RR = 0.91, 95% CI = 0.85-0.98, p = 0.01), shortened mechanical ventilation time (SMD = - 0.32, 95% CI = - 0.60 to - 0.04, p = 0.02) and ICU stays (SMD = - 0.72, 95% CI = - 0.92 to - 0.52, p < 0.00001), increased the ventilation free days (MD = 3.57, 95% CI = 3.42-3.73, p < 0.00001) and improve oxygenation index (PaO2/FiO2) on day 3 (SMD = 0.88, 95% CI = 0.39-1.36, p = 0.0004). Conclusions:Sivelestat can not only reduce the mortality of ALI/ARDS patients within 28-30 days and the incidence of adverse events, shorten the mechanical ventilation time and ICU stays, increase ventilation free days, but also improve the oxygenation index of patients on days 3, which has a good effect on the treatment of ALI/ARDS. These findings need to be verified in large-scale trials.

摘要信息：【摘 要】 目的 观察西维来司他钠联合小潮气量肺保护性通气对急性呼吸窘迫综合征(ARDS)患者氧合水平及机体炎性反应的影响。方法 选取2021年1月-2022年3月海南省肿瘤医院重症医学科收治 ARDS 患者 96 例按照随机数字表法分为对照组、观察组,各48 例。对照组采用小潮气量肺保护性通气治疗,观察组采用西维来司他钠联合小潮气量肺保护性通气治疗。比较2组机械通气时间、人住ICU 时间、住院时间,治疗前后血气指标[血氧分压(Pa0,)、二氧化碳分压(PaC0,)、氧合指数(Pa0,/Fi0,)]、血流动力学指标[心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)1、肺功能指标[用力肺活量(FVC)、第1秒用力呼气容积(FEV,)FEV,/FVC7、炎性因子[白介素6(I6)、C反应蛋白(CRP)、白细胞计数( WBC)1,以及不良反应发生率。结果 观察组机械通气时间、人住 ICU 时间、住院时间短于对照组(t/P=6.414/<0.001、3.881/<0.001、5.290/<0.001);治疗后 24 h、72 h 观察组 Pa0,、Pa0,/FiO,较对照组高,PaC0,较对照组低(F/P=8.451/<0.001、9.785/<0.001、10.265/<0.001):治疗后24 h、72 h2组 HR呈降低趋势,MAP、CVP 均呈升高趋势,且同时间点观察组降低/升高较对照组更显著(F/P=18.621/<0.00125.786/<0.001、26.105/<0.001);治疗后72 h观察组 FVC、FEV,、FEV,/FVC 高于对照组(t/P =5.971/<0.0018.649/<0.001、10.404/<0.001);治疗后 72h观察组血清Ⅱ6、CRP、WBC 水平低于对照组(t/P=7.887/<0.0016.168/<0.001、2.879/0.005):2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 西维来司他钠联合小潮气量肺保护性通气可改善 ARDS 患者血气指标,稳定血流动力学,减轻肺损伤及机体炎性反应,从而改善肺功能缩短机械通气时间、入住 ICU 时间及住院时间,安全性高。