文章来源：中国知网

摘要信息：目的 观察西维来司他钠联合亚胺培南西司他丁钠治疗重症肺炎的临床效果及对炎性指标和血气指标的影响。方法 回顾性选取2021年6月—2023年6月福建医科大学附属闽东医院收治的重症肺炎患者62例，按照治疗用药不同分为联合注射组与单药注射组，各31例。单药注射组给予注射用亚胺培南西司他丁钠治疗，联合注射组在单药注射组基础上给予注射用西维来司他钠治疗，2组均用药1周。比较2组用药前后炎性指标[C反应蛋白（CRP）、降钙素原（PCT）、白介素-6（IL-6）、中性粒细胞与淋巴细胞比值（NLR）]、肺炎胸片吸收评价量表（PCRAES）评分、临床肺部感染指数（CPIS）评分、血气指标[动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaCO2）、氧合指数],临床症状消失时间。结果 用药1周后，2组血清CRP、PCT、IL-6水平及NLR均降低，且联合注射组低于单药注射组（P<0.05或P<0.01）;2组PCRAES、CPIS评分均降低，且联合注射组低于单药注射组（P<0.05或P<0.01）;2组PaO2、氧合指数升高，PaCO2降低，且联合注射组升高/降低幅度大于单药注射组（P<0.05或P<0.01）。联合注射组退热时间与咳嗽、胸闷、肺部湿啰音消失时间均短于单药注射组（P<0.05或P<0.01）。结论 西维来司他钠联合亚胺培南西司他丁钠治疗重症肺炎的效果显著，可有效改善临床症状，在减轻机体炎性反应的同时保护肺组织，提高肺功能，加快病情恢复。

文章来源：PubMed

摘要信息：患者平均年龄65岁（35 ~ 87岁），女性2例，男性13例。这些数据最好的描述是一个具有比例残差的单室模型。西维来司他钠表观分布体积和表观清除率分别为20.88 L和1.79 L/h。西维来司他钠清除率受协变量总胆红素（TBIL）的影响，提示建议在TBIL水平升高的患者减少剂量。

摘要信息：Background:Sivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS. Methods:A retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO2), the ratio of PaO2to the fraction of inspired oxygen (PaO2/FiO2), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia. Results:In the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, P < 0.001), more ARDS patients (4.9 % vs. 0.43 %, P < 0.001), and more patients with interstitial lung disease (4.9 % vs. 1.49 %, P = 0.023), but fewer patients with stroke (17.65 % vs. 19.86 %, P < 0.001). Oxygen therapy rates were similar between the groups (79.41 % vs. 80.95 %, P = 0.9). The relative risk reduction in 30-day mortality was 88.45 % (95 % confidence interval [CI] 81.23%-93.21 %) for severe/critical COVID-19 patients treated with sivelestat. Sivelestat significantly decreased cytokine levels of interferon alpha (IFNα), interleukin-1 beta (IL-1β), and interleukin-2 (IL-2).In the sivelestat group, the mortality rate was significantly reduced with standard oxygenation and HFNC therapy(P < 0.05). The treatment with sivelestat did not increase side effects. Conclusion:The administration of the neutrophil elastase inhibitor sivelestat may improve clinical outcomes in COVID-19 patients with ALI/ARDS. These findings suggest that sivelestat could be considered an effective treatment option to alleviate pulmonary inflammatory injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

摘要信息：主要目的： 1）评估西维来司他钠治疗肺炎的临床缓解率； 2）评估西维来司他钠治疗可以减少轻中度肺炎加重的机率； 次要目的： 1）抗生素使用时间 2）药物经济学（住院费用） 3）BALF以及外周血中炎症因子（IL-2R、IL-6、IL-8、IL-1beta、IL-10以及TRAIL）水平及其清除率 4）氧和指数改善率及机械通气使用时间 5）BALF中西维来司他钠的药物浓度 6）BALF中NE水平和清除率 7）28天内的全因死亡率

摘要信息：方案名称：西维来司他钠治疗轻中度肺源性ARDS的前瞻性、多中心、安慰剂、随机双盲对照临床试验方案 试验设计：一项多中心、随机、双盲、安慰剂对照试验 样本良：292例 研究方案：疗程：7天 给药方案：持续静脉泵入 治疗期： (1)试验组：西维来司他钠0.2mg/kg/h (2)对照组：同等量仅含西维来司他钠辅料的生理盐水 纳入标准： (1)年龄≥18岁 (2)符合ARDS柏林诊断标准 (3)肺源性因素所致ARDS (4)100mmHg＜氧合指数≤300mmHg (5)诊断ARDS＜72小时 排除标准： (1)孕妇，哺乳期妇女 (2)肺外因素所致ARDS (3)脑死亡 (4)肿瘤或其他疾病终末期 (5)入ICU后放弃治疗 (6)严重慢性肺病（合并慢性呼吸衰竭） (7)合并充血性心力衰竭 (8)呼吸心跳骤停 (9)严重血流动力学不稳定 (10)拒绝参加本研究或已参加其他研究者 (11)临终关怀者 (12)肺外SOFA≥6分 (13)入组前72小时内应用乌司他丁、胸腺法新、血必净 (14)入组前7天内糖皮质激素使用≥1mg/kg/d (15)已知对西维来司他钠或辅料、对检查时涉及的其他物质过敏 (16)入组前一周内使用过IL-6拮抗剂（如托珠单抗）或JAK抑制剂的人群 观察指标及评价时间点： 1.终点指标 主要终点指标：第8天氧合指数(PFR)改善率（PFRD8-PFR用药前）/PFR用药前 次要终点指标：第8天炎症指标改善率（IL-6, IL-8, IL-10,TNF-α和CRP），第8天肺损伤评分改善率，第8天PFR＞300mmHg的患者比例，第8天ARDS分级改善的比例（中度转为轻度，轻度转为PFR＞300mmHg和中度转为PFR＞300mmHg），28天全因病死率，28天无机械通气时间，28天非ICU住院时间，28天非住院时间，ARDS严重程度进展（轻度-中度，中度-重度）的比例，干预后气管插管率。 2.安全性指标 生命体征、体格检查、实验室检查（血常规、生化，尿常规）、胸片或胸部CT检查及不良事件情况。 3.药物经济学指标 ICU住院费、检查费、药物费用（排除希为纳）

摘要信息：研究目的： 探讨西维来司他钠治疗新冠感染患者的有效性及安全性。 入选标准 (1)年龄≥18岁； (2)确诊为新型冠状病毒感染（原名新型冠状病毒肺炎）； (3)100mmHg≤PaO2/FiO2≤300mmHg。 排除标准 (1)诊疗资料缺失严重的患者； (2)妊娠期、哺乳期女性； (3)西维来司他钠用药时间＜72h； (4)合并恶性肿瘤或其他疾病的终末期； (5)合并严重慢性呼吸系统疾病； (6)经研究者判定不适合入选的其它情况。 研究方案 总体设计 本研究是一项多中心、回顾性、空白对照临床研究，收集本医院2022年11月至2023年11月确诊新冠感染的患者，后期将根据是否使用西维来司他钠进行分组，使用西维来司他钠的患者为西维来司他钠组，未使用西维来司他钠的患者为对照组。患者基本数据从电子病例系统中收集，因本研究为回顾性研究，知情同意得以豁免。病史收集中，以患者的真实诊疗记录为准，直至研究结束。患者治疗和临床管理将根据当地临床实践和适用的法规进行，本研究仅记录真实发生后的诊疗内容。 疗效指标： 主要终点：28天非机械通气时间（h） 次要终点： 用药后第1天、第3天、第5天、第7天、第10天、第14天：氧合指数（PaO2/FiO2）；炎症指标（白细胞计数、C反应蛋白、降钙素原、白介素1-β、白介素-6、白介素-8、白介素-10、肿瘤坏死因子-α）；器官功能指标（血清铁蛋白、总胆红素、肌酐、D-二聚体、PaCO2）；预后指标（肺顺应性、APACHE II评分、Murray肺损伤评分、SOFA评分）；影像学指标（胸片/CT评分）。气管插管时间（h）、ICU住院天数（d）、住院天数（d）、俯卧位情况、气管切开情况、治疗情况。 安全性指标 导致研究药物减量或停药的不良事件。

摘要信息：摘 要 中性粒细胞弹性蛋白酶(NE)是由多形核中性粒细胞释放的弹性蛋白酶,在肺部炎症性疾病发病机制中,既有有利作用,又有不利作用,与体内 NE-抗 NE平衡有关。本文又综述了通过维持 NE-抗 NE平衡来治疗几种炎症性疾病的研究进展及目前存在的问题。

摘要信息：Background:There are conflicting views on the of sivelestat sodium (sivelestat-Na) on acute lung injury. Methods:The efficacy of sivelestat-Na on aspiration-related acute lung injury was analyzed by reviewing case reports published before or after the appearance of the drug on the clinical practice in Japan. Data were analyzed from the 23 sivelestat-treated cases and 5 non-sivelestat cases. Results:Sivelestat-Na was administered by 0.2 mg x kg(-1) x hr(-1) for 10 +/- 4 (mean +/- SD) days. PaO2/ ratio increased significantly from 124 +/- 59 mmHg of baseline to 253 +/- 79 mmHg on the third and to 361 +/- 84 mmHg on the termination of the therapy. Significantly better response was observed if the drug was administered within 24 hours after aspiration for patients with background of neurological disease, in which the increases in the P/F ratio were greater and the duration of the drug administration was shorter compared with other patients. In comparison with the non-sivelestat cases, sivelestat-Na therapy appears to be associated with shorter ventilator days or higher P/F increase, although sivelestat-Na costs higher. Conclusions:These results suggest the possibility of conducting prospective clinical trials to assess the efficacy of early sivelestat-Na therapy for aspiration-related acute lung injury.

摘要信息：The patient was a 67-year-old man with diabetes mellitus who had been to a hot spring spa a few days before his admission. The diagnosis of Legionella pneumonia was made using a urinary antigen assay. Intravenous pazufloxacin and oral clarithromycin were started. However, despite these treatments, he developed acute respiratory distress syndrome (ARDS). He was administered the combination of intravenous pazufloxacin and erythromycin, corticosteroid, and sivelestat for two weeks. Then he was successfully recovered. The outcome suggests that treatment with corticosteroid and sivelestat, in addition to a combination of appropriate anti-Legionella antibiotics, should be considered for patients with severe Legionella pneumonia with ARDS.

摘要信息：It is important to regulate excessive inflammation when patients with severe infectious disease are treated. Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is used in the treatment of lung injury but its effect on bacterial pneumonia is unknown. The authors examined the efficacy of sivelestat in combination with a fluoroquinolone in a Legionella pneumophila pneumonia mouse model. The combination therapy did not show a significant survival improvement compared to the treatment with fluoroquinolone alone, but reduced bacteria number and inflammatory cells in the early phase. The combination therapy can contribute to treatment of L. pneumophila pneumonia with protecting lungs.