文章来源：PubMed

摘要信息：Objective:Sivelestat may reduce postoperative pulmonary injury after total arch replacement (TAR). This study aimed to evaluate whether the preoperative PaO2/FiO2(P/F) ratio affects the efficacy of sivelestat in reducing postoperative pulmonary injury in patients with acute aortic dissection (AAD) who underwent TAR using deep hypothermic circulatory arrest (DHCA). Methods:Data of patients with AAD who underwent TAR using DHCA in a tertiary hospital between February 1, 2022, and December 30, 2022, were retrospectively reviewed. The patients were divided into the sivelestat and control groups. Three subgroup analyses were performed based on the postoperative P/F ratio. The primary clinical outcomes were assessed to determine the efficacy and safety of sivelestat in managing postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass. Results:A total of 187 patients were included, with 95 in the sivelestat group and 92 in the control group. No significant differences were found in the clinical variables between the two groups (all P > 0.05), except for some improvements in the inflammatory biomarker levels (including white blood cell count, neutrophil count, and C-reactive protein). Subgroup analysis revealed that sivelestat treatment significantly increased the P/F ratio on the 4th day and 3rd day after TAR in patients with mild lung injury (P = 0.02) and moderate lung injury (P = 0.03), respectively. Additionally, sivelestat reduced the levels of several postoperative inflammatory biomarkers in both subgroups. Conclusions:Among patients with AAD with mild or moderate preoperative lung injury, defined by a low P/F ratio, sivelestat significantly improved the postoperative P/F ratio and attenuated inflammatory responses after TAR. These findings suggest an important avenue for further research.

摘要信息：研究目标： 评价急性A型主动脉夹层术前低氧血症(PaO2/FiO2≤300mmHg)患者术中应用西维来司他钠缩短术后有创机械通气的有效性和安全性。 研究设计类型、原则与实施方法 总体设计 单中心、安慰剂、双盲、随机平行对照研究。 本研究计划纳入30例急性A型主动脉夹层术前低氧血症(PaO2/FiO2≤300mmHg)患者，受试者按照1:1的比例随机分配至试验组或对照组，分别接受西维来司他钠组与安慰剂组，评价西维来司他钠缩短术后有创机械通气时间。 评价指标 主要终点指标 有创机械通气时间（小时）：从有创机械通气开始至第一次成功拔除气管插管的持续时间。第一次成功拔除气管插管定义为拔除气管插管后患者能够自主呼吸超过48小时。 次要终点指标 全部有创机械通气情况（模式和时间）、全部无创机械通气情况（模式和时间）、全部高流量吸氧情况（流量和时间）。 氧合指数及其曲线下面积、PaO2/FiO2≤300mmHg持续时间（小时）、急性肺损伤、呼吸机相关肺炎、Murray肺损伤评分。 术后ICU滞留时间（天）、术后住院时间（天）、APACHE II评分、SOFA评分。 围术期死亡、脑卒中、截瘫、暂时性神经系统功能不全、癫痫、急性肾损伤、感染、心律失常、心脏骤停、急性胰腺炎、消化道出血、术中、术后输注血制品的情况（种类和数量）。 血流动力学指标、实验室检查指标、影像学指标、卫生经济学指标。 28天无呼吸机时间（天）、术后28天的全因死亡、28天内氧疗、无创机械通气、有创机械通气、俯卧位通气、吸入一氧化碳治疗。 安全性指标 急性肝功能损伤、黄疸、白细胞减少、中性粒细胞减少、血小板减少等不良事件发生情况。 实验室检查（血常规、血生化）

摘要信息：Cardiopulmonary bypass (CPB) evokes activation of a systemic inflammatory response. Sivelestat has been used clinically to treat acute lung injury associated with systemic inflammatory response syndrome. This prospective, doubleblind, randomized study was designed to evaluate the effects of sivelestat in the perioperative period of elective pediatric open-heart surgery with CPB. Twenty-six consecutive pediatric patients weighing between 5 and 10 kg and undergoing open-heart surgery with CPB were divided into a sivelestat group (n = 13) and a control group (n = 13). The patients in the sivelestat group were administered a continuous intravenous infusion of 0.2 mg/kg/hour of sivelestat, and the patients in the control group were administered the same volume of 0.9% saline from the initiation of CPB to 24 hours after surgery. Blood samples were drawn for the measurement of cytokines, polymorphonuclear elastase (PMN-E), white blood cell count (WBC), neutrophil count (NC), and C-reactive protein (CRP). There were no significant differences in cytokine data between the two groups. The peak PMN-E and WBC levels were significantly increased in the control group (P = 0.049, P = 0.039). The WBC and NC levels immediately after surgery in the control group were significantly greater than those in the sivelestat group (P = 0.049, P = 0.044). The peak CRP level in the control group was significantly greater than the sivelestat group (P = 0.04), and the CRP level on postoperative day 4 in the control group was significantly greater than in the sivelestat group (P = 0.014). This study showed that sivelestat attenuates the perioperative inflammatory response in pediatric heart surgery with CPB.

摘要信息：Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response. The neutrophil elastase inhibitor sivelestat is known to suppress this systemic inflammatory response, which can eventually result in acute organ failure. The prophylactic effect of sivelestat on acute lung injury, especially in pediatric cardiac surgery, remains unclear. This prospective double-blind, randomized study evaluated the perioperative prophylactic effect of sivelestat in patients undergoing elective pediatric open heart surgery with CPB. Thirty consecutive patients, weighing 5-10 kg and undergoing open heart surgery with CPB, were assigned to sivelestat (n = 15) or control (n = 15) groups. From CPB initiation to 24 h after surgery, patients in the sivelestat group received a continuous intravenous infusion of 0.2 mg/kg/h sivelestat, whereas patients in the control group received the same volume of 0.9% saline. Blood samples were collected, and levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, polymorphonuclear elastase (PMN-E), C-reactive protein (CRP), as well as the white blood cell (WBC) count, platelet count, and neutrophil count (NC) were measured. PMN-E levels, IL-8 levels, WBC count, NC, and CRP levels were significantly lower, and platelet count was significantly higher in the sivelestat group, according to repeated two-way analysis of variance. The activated coagulation time was significantly shorter in the sivelestat group, similarly, blood loss was significantly less in the sivelestat group. In conclusion, Sivelestat attenuates perioperative inflammatory response and clinical outcomes in patients undergoing pediatric heart surgery with CPB.

摘要信息：摘要:目的 探讨西维来司他钠对急性: Stanford A型主动脉夹层(ATAAD)患者术后谵妄(POD)的预防作用及其机制。方法 纳入急诊行ATAAD手术患者80例,跟据随机数字表法分为西维来司他钠组及对照组各40例。西维来司他钠组于手术麻醉诱导前10 min静脉泵注西维来司他钠直至手术结束,对照组以相同的速率静脉泵注相同体积的生理盐水直至手术结束。术后3d内采用3min谵妄诊断量表(3D-CAM)对患者POD发生情况进行评估;于术后24h时采集患者外周静脉血,采用改良的Ficoll密度梯度离心法提取外周血单个核细胞(PBMCs),比色法检测PBMCs内铁离子(Fe”)浓度、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性,Westem bloting法检测PBMCs内长链脂酰辅酶A合成酶(ACSL4)及谷胱甘肽过氧化物酶4(GPX4)蛋白。记录围手术期情况及不良反应发生情况。结果 西维来司他钠组POD发生率低于对照组(P<0.05),两组POD严重程度评分及POD持续时间比较差异均无统计学意义。西维来司他钠组PBMCS内Fe”浓度及MDA含量低于对照组,SOD活性高于对照组(P均<0.05)。西维来司他钠组 PBMCS内ACSL4蛋白表达低于对照组,GRX4蛋白表达高于对照组(P均<0.05)。西维来司他钠组ICU人住时间及术后住院时间少于对照组(P均<0.05):两组不良反应发生率差异均无统计学意义。结论，西维来司他钠可预防急性ATAAD手术患者POD的发生,其机制可能与抑制铁死亡从而减轻神经损伤有关。

摘要信息：摘要:目的 观察西维来司他钠对行体外循环心脏瓣膜置换术老年患者肺功能的保护作用,探讨其可能机制。方法 2021年10月-2022年10月河南省人民医院行体外循环心脏膜置换术老年患者 76例,38 例麻醉诱导前10 min静脉泵注西维来司他钠 0.2 mg/(kg·h)至机械通气脱机者为观察组,38 例以相同速率静脉泵注生理盐水至机械通气脱机者为对照组。2组分别于切皮前(T)、术毕即刻(T,)、术后 24 h(T)、术后 48 h(T,)采集颈内静脉血,采用Ficoll密度梯度离心法分离外周血单个核细胞(PBMC),采用实时荧光定量 PCR 法检测 PBMCs 中白细胞介素(IL)-18.IL-1β mRNA 相对表达量,采用 Western blot 法检测 PBMCS NLRP3,caspase-1、消皮素 D(GSDMD)蛋白相对表达量,观察 T, 时 PBMCs形态变化。2 组分别于 T、T、T,、T,时采集桡动脉血行血气分析,测定 a(O,)、pa(CO,),计算肺泡-动脉血氧分压差(PDO2)、氧合指数(OI)和呼吸指数(RI)。记录2组体外循环时间、主动脉阻断时间、手术时间、麻醉时间、术中失血量及液体人量,术后机械通气时间、CU 治疗时间、首次下床活动时间、住院时间等;比较2组术中窦性心动过缓/过速、低血压/高血压、呯吸抑制及术后皮肤瘙痒、恶心呕叶、感染等发生情况。结果 观察组,时 pa(0,)pa(CO,)、血氧饱和度、P. DO,、RI、0I与对照组比较差异均无统计学意义(P>0.05),T、T、T;时 PDO,、RI 均低于对照组(P<0.05),01均高于对照组(P<0.05):2 组 T、T、T,时 PDO,,RI均高于 T 时(P<0.05),O1均低于T时(P<0.05)。T,时对照组 PBMCs 肿胀、变圆,气泡状突出物形成,形态大小不一,细胞膜裂解形成碎片,细胞间隙增宽、排列紊乱;观察组 PBMCs形态改变较对照组明显减轻。观察组 PBMCSIL-18、IL-1βmRNA 及 NLRP3、caspase-1.GSDMD蛋白相对表达量 T,时与对照组比较差异均无统计学意义(P>0.05),T、T、T;时均低于对照组(P<0.05);2 组T 、T,、T,时 IL-18、IL-1β mRNA 及 NLRP3,caspase-1、GSDMD 蛋白相对表达量均高于 T,时(P<0.05)。观察组术后机械通气时间[(33.3±8.0)h]、ICU 治疗时间[(51.9±7.8)h]均短于对照组[(39.9±9.6)、(61.7±8.4)h(t=3.256,P=0.002;t=5.270,P<0.001),体外循环时间、主动脉阻断时间、手术时间、麻醉时间、术中失血量及液体入量、围手术期悬浮红细胞及血浆输注量、首次下床活动时间,术后住院时间与对照组比较差异均无统计学意义(P>0.05)。2组术中均无呼吸抑制和深静脉血栓发生,术中窦性心动过缓、窦性心动过速、低血压、高血压及术后恶心呕吐、皮肤瘙痒、感染发生率比较差异均无统计学意义(P>0.05)。结论 西维来司他钠通过调控 NLRP3 炎性信号通路抑制 PBMCs 细胞焦亡保护行体外循环心脏瓣膜置换术老年患者术后肺功能,不增加围手术期不良事件的发生。

摘要信息：【摘要】 目的 探讨西维来司他钠对体外循环(CPB)下心脏瓣膜置换术老年患者术后早期康复的影响。方法 招募于本院手术室接受择期 CPB下心脏瓣膜置换术的患者 80 例,依据随机数字表法将其分成对照组(C组)和西维来司他钠组(S组),每组 40 例。记录术中及术后任何不良事件包括实性心动过缓或低血压/高血压、术后感染等。记录住院时间及 90 天死亡率。3个月后,使用问卷收集与睡眠有关的数据、生活质量、焦虑和疼痛。结果 C组共有 13 例患者(32.5%)在术后3d内发生术后谵妄(POD),S组共有5例患者(12.5%)在术后3d内发生POD,组间比较有显著差异(P、0.05)，两组术后13d时白细胞计数,中性粒细胞计数和中性粒细胞百分比较术前1d均增高,但S组均显著低于C组(P<0.05)。与C组比较,S组患者术后机械通气时间及 ICU入住时间均显著缩短(P<0.05)。术后 90d随访时,MMSE评分与基线相比无差异(P>0.05)。术后共有4例(10.0%)患者出现神经认知功能障碍(POCD)。两组间POCD发生率无差异(P>0.05)。术中心动过缓或低血压/高血压,术后感染等不良事件发生率在两组间均接近,差异无统计学意义(P>0.05)。在术后 90d的随访期内,两组均无患者死亡。两组在术后住院时间上无显著差异(P>0.05)。使用EQ5D问卷对两组患者的生活质量进行评估,结果显示,两组患者在统计学上无显著差异(P>0.05)。术后3个月,两组间的睡眠质量无显著差异(P>0.05)。结论 西维来司他钠可降低 CPB下心脏瓣膜置换术老年患者 POD发生率,缩短术后机械通气时间及 ICU入住时间,有益于术后早期康复。

摘要信息：Background:Despite advances in surgical techniques, the incidence of stroke following acute type A aortic dissection (ATAAD) repair remains markedly high, with substantial immediate and long-term adverse outcomes such as elevated mortality, extended hospital stays, and persistent neurological impairments. The complexity of managing ATAAD extends beyond the operation itself, highlighting a crucial gap in research concerning modifiable preoperative patient conditions and perioperative anesthetic management strategies. Objectives:This investigation aimed to elucidate the incidence, consequences, and perioperative determinants of stroke following surgical intervention for acute type A aortic dissection (ATAAD). Methods:In a multicenter retrospective analysis, 516 ATAAD surgery patients were evaluated. The data included demographic information, clinical profiles, surgical modalities, and outcomes. The primary endpoint was postoperative stroke incidence, with hospital mortality and other complications serving as secondary endpoints. Results:Postoperative stroke occurred in 13.6% of patients (70 out of 516) and was associated with significant extension of the ICU (median 10 vs. 5 days, P < 0.001) and hospital stay (median 18 vs. 12 days, P < 0.001). The following key independent stroke risk factors were identified: modified Frailty Index (mFI) ≥ 4 (odds ratio [OR]: 4.18, 95% confidence interval [CI]: 1.24-14.1, P = 0.021), common carotid artery malperfusion (OR: 3.76, 95% CI: 1.23-11.44, P = 0.02), pre-cardiopulmonary bypass (CPB) hypotension (mean arterial pressure ≤ 50 mmHg; OR: 2.17, 95% CI: 1.06-4.44, P = 0.035), ≥ 20% intraoperative decrease in cerebral regional oxygen saturation (rSO2) (OR: 1.93, 95% CI: 1.02-3.64, P = 0.042), and post-CPB vasoactive-inotropic score (VIS) ≥ 10 (OR: 2.24, 95% CI: 1.21-4.14, P = 0.01). Conclusions:Postoperative stroke significantly increases ICU and hospital durations in ATAAD surgery patients. These findings highlight the critical need to identify and mitigate major risks, such as high mFI, common carotid artery malperfusion, pre-CPB hypotension, significant cerebral rSO2reductions, and elevated post-CPB VIS, to improve outcomes and reduce stroke prevalence.

摘要信息：Background:Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. Methods and results:Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO (2)). Though patients in Group I showed a subtle improvement in certain parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). Conclusion:Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

摘要信息：Cardiopulmonary bypass (CPB) has been implicated as a cause of acute lung injury (ALI) in cardiac surgical patients. We used a bronchoscopic microsampling (BMS) probe to examine alveolar biochemical constituents and evaluated the effect of sivelestat sodium hydrate, a novel synthesized polymorphonuclear (PMN) neutrophil elastase inhibitor, on ALI induced by CPB. Twelve patients undergoing aortic valve replacement were treated with either sivelestat 0.2 mg/kg/h (sivelestat group, n=6) or 0.9% saline (control group, n=6) from the start of surgery. Samples were collected by the BMS probe at three time points: after tracheal intubation, 1 h after CPB introduction, and 3 h after CPB termination. Pulmonary function was assessed perioperatively. There were no differences in baseline characteristics. The concentration of PMN elastase was significantly suppressed in the sivelestat group, compared with the control group (P=0.001). The sivelestat group also had lower levels of interleukin-6 and interleukin-8. Alveolar-arterial oxygen difference markedly increased, and a worsening of the PaO(2)/FiO(2) ratio indicated severe impairment after CPB. However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB.