摘要信息：Background: Total arch replacement necessitating deep hypothermia with circulatory arrest has a greater effect on pulmonary function than other cardiac surgery using cardiopulmonary bypass (CPB). Since April 2004, 100mg of sivelestat sodium hydrate was administrated by bolus injection into pulp circuit at the initiation of CPB in every case performed total arch replacement. We investigated the hypothesis that prophylactic use of the drug attenuates post-pump pulmonary dysfunction. Methods: A retrospective analysis of 120 consecutive patients who underwent total arch replacement from August 2001 to December 2006 was conducted. Patients were divided into two groups according to the date of surgery, April 2004, when we started sivelestat administration. Group A (n=60), operated after April 2004, was administrated sivelestat at the initiation of CPB. Group B (n=60), before April 2004, was not administrated. Time courses of hemodynamic variables were evaluated until 24h after surgery and those of respiratory variables and inflammatory markers until 48 h after surgery. Results: There were no significant differences in patient age, sex, prevalence of chronic obstructive lung disease, preoperative lung function, time of operation and CPB, minimum temperature, and aprotinin usage. Hospital mortality occurred in two patients in the group B (3.3%) and no patient in group A (0%). Postoperative hemodynamic variables were not different between the two groups. Respiratory index, oxygenation index were significantly better in patients pretreated with sivelestat (respiratory index; p<0.001, oxygenation index; p<0.001, respectively). CRP was significantly lower in patients pretreated with sivelestat (p=0.022). Except for patients who required tracheostomy or re-exploration for bleeding, patients pretreated with sivelestat were extubated significantly shorter (group A: 12.6+/-10.8h, group B: 25.5+/-12.9h, p=0.033). No patient with postoperative respiratory failure requiring tracheostomy was noted in sivelestat group. Conclusion: Prophylactic administration of sivelestat at the initiation of CPB results in better postoperative pulmonary function, leading to earlier extubation time. Our study suggests that sivelestat was effective in facilitating postoperative respiratory management in total arch replacement.

摘要信息：Purpose: Unilateral re-expansion pulmonary edema (RPE) is a rare but one of the most critical complications that may occur after re-expansion of a collapsed lung after minimally invasive cardiac surgery (MICS) with mini-thoracotomy. Methods: We performed a total of 40 consecutive patients with MICS by right mini-thoracotomy with single-lung ventilation between January 2013 and June 2016. We divided the patients into control group (n = 13) and neutrophil elastase inhibitor group (n = 27). Neutrophil elastase inhibitor group received continuous intravenous infusion of neutrophil elastase inhibitor at 0.2-0.25 mg/kg per hour from the start of anesthesia until extubation during the perioperative period. Results: There were no relations with operative time, cardiopulmonary bypass (CPB) time, aortic clamp time, and intraoperative water valances for postoperative mechanical ventilation support time. Compared with the neutrophil elastase inhibitor group, the control group had significantly higher initial alveolar-arterial oxygen gradient and significantly lower initial ratio of partial pressure of arterial oxygen to fraction of inspired oxygen at the intensive care unit (ICU). The control group had significantly longer postoperative mechanical ventilation support time and hospital stay compared with the neutrophil elastase inhibitor group. Conclusions: Neutrophil elastase inhibitor may have beneficial effects against RPE after MICS with mini-thoracotomy.

摘要信息：[摘要]目的 回顾性分析西维来司他钠用于体外循环下冠脉搭桥手术患者围术期肺功能保护的作用及其对临床预后的影响。方法本研究回顾性纳入西京医院心血管外科 2021年 1~12月期间行择期体外循环下冠状动脉旁路移植术的 208 例患者，其中 98 例为对照织:110 例患者为西维来司他钠织。患者术后 24h 内氧合指数(PaO,FiO,)为主要结局指标，术后机械通气时间和总体不良事件发生率为复合次要结局指标。结果 本研究人群男性 187 例，女性 21 例，平均年龄 57.2+9.3 岁，院内死亡率为 1.9%。与对照组相比，西维来司他钠组患者在术后 24h内各时间点 PaO,/F0,均显著高于对照组(均 P<0.05)，术后机械通气时间>24 h 例数显著少于对照组(14.5% vs 26.5%，P-0.03)，总体不良事件发生率显著降低(56.4% v 70.4%，P=0.04)。结论，用术期使用西维来司他钠可以改善体外循环下冠脉搭桥患者术后肺功能并降低术后不良事件发生率。

摘要信息：[摘要]:目的 探讨西维来司他钠对主动脉夹层术后急性呼吸功能不全(ARI)及全身炎症反应的临床疗效。方法回顾2021年1月至2021年7月期间收治的A型主动脉夹层患者共90例,术后出现 ARI的共86例,纳入排除标准以后共 62例,其中 16 例为实验组,46 例为对照组。对照组给予常规治疗,实验组在常规治疗基础上应用了西维来司他钠按照 0.2 mg(kg·h)剂量 24h匀速泵人,维持7d。比较两组患者给药前(T1)、第3天(T2)、第5天(T3)第7天(T4)氧合指数之差(APa0,/Fi0,)、白细胞( WBC),中性粒细胞(NEU)、淋巴细胞、C反应蛋白(CRP)、降钙素原(PCT)、白介素 6(Ⅱ-6)、白介素8(I-8)的变化,并比较两组术后呼吸机带机时间、二次插管例数、ICU 停留时间、西药费及总费用。结果 在 T1~T4 时间点实验组的APa0,/Fǐ0,值要明显高于对照组:实验组 WBC在第 T2、T3、T4 时间点较对照组显著降低:实验组 NEU 在 T2、T3、T4时间点较对照组显著降低:实验组 CRP、PCT、I-6均仅在 [4 时间点较对照组显著降低。结论，西维来司他钠可能通过减轻机体炎症反应,降低主动脉夹层术后患者血清炎性因子水平,改善合,使患者获益。

摘要信息：Background:Systemic inflammatory response syndrome (SIRS) after surgery for acute Stanford type A aortic dissection (ATAAD) via cardiopulmonary bypass (CPB) are strongly associated with mortality. Although the sivelestat sodium has been approved for the treatment of patients with acute lung injury, there is currently no enough evidence for improving inflammatory response and reducing the associated mortality. Our study aims to investigate the efficacy and safety of sivelestat sodium for the treatment of inflammatory response in acute Stanford type A aortic dissection. Methods:A total of 71 ATAAD patients who received surgical treatment at our center from January 2021 to December 2021 retrospectively reviewed. Patients were divided into the sivelestat sodium group and the control group. Clinical information including the postoperative oxygenation index (PaO2/FiO2), white blood cell (WBC) count, procalcitonin (PCT) level, interleukin-6 (IL-6) level, duration of ventilator use (hours), intensive care unit stay (days), and 28-day mortality rate, were collected. The statistical inference differences between the groups were compared using the non-paired Student's t-test, Wilcoxon rank sum test, chi squared test and repeated analysis of variance (ANOVA). Results:There were no significant differences between the sivelestat sodium group and the control group in terms of baseline characteristics (all P>0.05). The mortality rate was decreased in the sivelestat sodium group than the control group (10% vs. 13.73%). The subgroup analysis showed that for patients with a mechanical ventilation duration >96 h, the 48-h oxygenation index (149±53 vs. 260±66, P=0.001), and the 72-h oxygenation index (165±66 vs. 288±95, P=0.002) were significantly lower in the control group than the sivelestat sodium group. And the postoperative WBC count (P=0.015) and PCT level (P=0.033) were significantly lower in the sivelestat sodium group than the control group in post-operative day 4. Conclusions:Sivelestat sodium can improves the postoperative oxygenation index and inflammatory response for ATAAD patients requiring mechanical ventilation for extended periods.

摘要信息：Background:Sivelestat, a neutrophil elastase inhibitor, is specifically developed to mitigate the occurrence of acute lung injury (ALI) in individuals who are undergoing cardiovascular surgery. However, its impact on patients who are at a heightened risk of developing ALI after scheduled cardiac surgery has yet to be determined. In order to address this knowledge gap, we undertook a study to assess the efficacy of sivelestat in protecting the lungs of these patients. Methods:We conducted a prospective cohort study involving 718 patients who were at high risk of developing postoperative acute lung injury (ALI) and underwent scheduled cardiac surgery between April 25th, 2022, and September 7th, 2023. Among them, 52 patients received sivelestat (administered at a dosage of 0.2mg/kg/h for 3 days), while 666 patients served as controls, not receiving sivelestat. The control conditions were the same for all patients, including ventilation strategy, extubating time, and fluid management. Subsequently, a propensity-score matched cohort was established, consisting of 40 patients in both the sivelestat and control groups. The primary outcome measure encompassed a composite of adverse outcomes, including 30-day mortality, ALI, acute respiratory distress syndrome (ARDS), and others. Secondary outcomes assessed included pneumonia, ventricular arrhythmias, mechanical ventilation (MV) time, and more. Results:After conducting propensity matching in our study, we observed that there were no significant differences in 30-day mortality between the sivelestat and control groups (0% vs 2.5%, P=0.32). However, the use of sivelestat exhibited a significant reduction in the incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) compared to the control group (0% vs 55%, P<0.01), pneumonia (0 vs 37.5%, P<0.01), MV time (median:8 hours, IQR:4-14.8 hours vs median: 15.2 hours, IQR:14-16.3 hours, P<0.01). Compared to the control group, the sivelestat could significantly decrease white cell count (P<0.01), neutrophile percentage (P<0.01) and C-reactive protein (P<0.01) in the period of postoperative 5 days. Conclusion:The prophylactic administration of sivelestat has shown promising results in reducing the occurrence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with a heightened risk of developing these conditions after elective cardiac surgery. Our study findings indicate that sivelestat may provide protective effects by suppressing inflammation triggered by neutrophil activation, thereby safeguarding pulmonary function.

摘要信息：Background: The sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery. Methods: Firstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc. Results: In propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P<0.01), bilateral pulmonary infiltrates (P<0.01), oxygen index (P<0.01), interleukin-6(P=0.02), procalcitonin(P<0.01) and C-reactive protein(P<0.01). Conclusion: Administration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB.

摘要信息：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.

摘要信息：目的 观察西维来司他钠联合乌司他丁治疗脓毒症所致急性呼吸窘迫综合征(ARDS)的临床疗效。方法 选取2020年1月至2023年5月本院收治的104例脓毒症所致ARDS患者,经计算机随机数字生成器分为对照组(常规治疗+西维来司他钠)、联合组(常规治疗+西维来司他钠+乌司他丁),各52例。比较治疗前后两组Murray肺损伤评分(MLIS)评分、序贯器官功能衰竭(SOFA)评分、血管外肺水指数(ELWI)、动脉血氧分压/吸氧浓度分数(Pa0,i0,)、白细胞计数(WBC)、中性粒细胞百分比(NEUT%)内皮细胞特异性分子(ESM-1)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)及白细胞介素-6(ⅡL-6)水平:比较两组恢复速度、预后情况及不良反应。结果 对照组、联合组治疗前MLIS评分、SOFA评分ELII、PaO.F;O,、WBC、NEUT%、ESM-1、SUPAR及I-6水平比较,差异无统计学意义(P>0.05)。治疗后联合组MLIS评分、SOFA评分、ELWI、WBC、NEUT%、ESM-1、suPAR及I6水平均低于对照组(P<0.05)Pa0,/Fi0,高于对照组(P<0.05);联合组机械通气时间、ICU住院时间均短于对照组(P<0.05).28 d病死率低于对照组(P<0.05)。两组治疗期间均未发生严重不良反应。结论 西维来司他钠联合乌司他丁应用于脓毒症所致ARDS 中可减轻患者肺损伤及炎症反应,加快恢复,改善肺功能及预后,且安全性高。

摘要信息：To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.