目的:观察丁苯酞对非体外循环冠脉搭桥手术术后认知功能的影响。方法:选取2021年7月~2022年2月于青岛大学附属医院择期进行非体外循环冠脉搭桥手术的患者80例,ASA分级为II~III级,随机分为丁苯酞组和对照组,各40例。丁苯酞组在常规全身麻醉基础上于麻醉诱导后15分钟开始静脉滴注丁苯酞氯化钠注射液50 mg,对照组在常规全身麻醉基础上于麻醉诱导后15分钟开始静脉滴注等容量生理盐水。检测两组患者术前1天与术后1天、3天血清肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S-100β蛋白和神经元特异性烯醇化酶(NSE)水平,并采用简易精神状态评价量表(MMSE)和蒙特利尔认知评估量表(MoCA)评估病人认知功能。结果:2组患者外周血肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S-100β蛋白、神经元特异性烯醇化酶(NSE)水平在术后1天和术后3天均较术前有不同程度的升高(P < 0.05);丁苯酞组外周血肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S-100β蛋白和神经元特异性烯醇化酶(NSE)水平在术后1天和术后3天均明显低于对照组(P < 0.05);丁苯酞组术后1天、3天MMSE和MoCA评分明显高于对照组;丁苯酞组术后认知功能障碍的发生率为17.5%,对照组术后认知功能障碍的发生率为55%,丁苯酞组术后认知功能障碍的发生率明显低于对照组(P < 0.05)。结论:丁苯酞能改善非体外循环冠脉搭桥病人术后认知功能,降低术后认知功能障碍的发生率,其机制可能与减轻机体炎症反应有关。 Objective: To observe the effect of butylphthalide on cognitive function after off-pump coronary ar-tery bypass surgery. Methods: A total of 80 patients selected for off-pump coronary artery bypass surgery in The Affiliated Hospital of Qingdao University from July 2021 to February 2020 were se-lected, with American Society of Anesthesiologists (ASA) II-III, and randomly divided into bu-tylphthalide group and control group, with 40 patients in each group. In the butylphthalide group, intravenous infusion of butylphthalide sodium chloride injection 50 mg was started 15 minutes af-ter induction of anesthesia on the basis of conventional general anesthesia, while in the control group, intravenous infusion of isovolume normal saline was started 15 minutes after induction of anesthesia on the basis of conventional general anesthesia. Serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), S-100β protein and neuron specific enolase (NSE) in 2 groups were detected 1 day before surgery, 1 day after surgery and 3 days after surgery. Cognitive function was assessed by Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA). Results: The levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), S-100β protein and neuron specific enolase (NSE) in peripheral blood of 2 groups were increased 1 and 3 days after surgery compared with those before surgery (P < 0.05). The levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), S-100β protein and neuron specific enolase (NSE) in peripheral blood of butylphthalide group were significantly lower than those of control group 1 and 3 days after sur-gery (P < 0.05). MMSE and MoCA scores of butylphthalide group were significantly higher than those of control group at 1 and 3 days after operation. The incidence of postoperative cognitive dysfunc-tion was 17.5% in the butylphthalide group and 55% in the control group, and the incidence of postoperative cognitive dysfunction in the butylphthalide group was significantly lower than the control group (P < 0.05). Conclusion: Butylphthalide can improve postoperative cognitive function and reduce the incidence of postoperative cognitive dysfunction in patients with off-pump coronary artery bypass grafting, and the mechanism may be related to the reduction of inflammatory re-sponse.
目的:观察丁苯酞对非体外循环冠脉搭桥手术术后认知功能的影响。方法:选取2021年7月~2022年2月于青岛大学附属医院择期进行非体外循环冠脉搭桥手术的患者80例,ASA分级为II~III级,随机分为丁苯酞组和对照组,各40例。丁苯酞组在常规全身麻醉基础上于麻醉诱导后15分钟开始静脉滴注丁苯酞氯化钠注射液50 mg,对照组在常规全身麻醉基础上于麻醉诱导后15分钟开始静脉滴注等容量生理盐水。检测两组患者术前1天与术后1天、3天血清肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S-100β蛋白和神经元特异性烯醇化酶(NSE)水平,并采用简易精神状态评价量表(MMSE)和蒙特利尔认知评估量表(MoCA)评估病人认知功能。结果:2组患者外周血肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S-100β蛋白、神经元特异性烯醇化酶(NSE)水平在术后1天和术后3天均较术前有不同程度的升高(P < 0.05);丁苯酞组外周血肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S-100β蛋白和神经元特异性烯醇化酶(NSE)水平在术后1天和术后3天均明显低于对照组(P < 0.05);丁苯酞组术后1天、3天MMSE和MoCA评分明显高于对照组;丁苯酞组术后认知功能障碍的发生率为17.5%,对照组术后认知功能障碍的发生率为55%,丁苯酞组术后认知功能障碍的发生率明显低于对照组(P < 0.05)。结论:丁苯酞能改善非体外循环冠脉搭桥病人术后认知功能,降低术后认知功能障碍的发生率,其机制可能与减轻机体炎症反应有关。
丁苯酞,术后认知功能障碍,冠状动脉搭桥手术
Xiaoli Sun1, Junqiong Gao1, Changxin Jia2, Mei Duan1, Bojue Qiu1, Shilei Wang2*
1Qingdao University Medical College, Qingdao Shandong
2The Affiliated Hospital of Qingdao University, Qingdao Shandong
Received: Jul. 1st, 2022; accepted: Jul. 28th, 2022; published: Aug. 4th, 2022
Objective: To observe the effect of butylphthalide on cognitive function after off-pump coronary artery bypass surgery. Methods: A total of 80 patients selected for off-pump coronary artery bypass surgery in The Affiliated Hospital of Qingdao University from July 2021 to February 2020 were selected, with American Society of Anesthesiologists (ASA) II-III, and randomly divided into butylphthalide group and control group, with 40 patients in each group. In the butylphthalide group, intravenous infusion of butylphthalide sodium chloride injection 50 mg was started 15 minutes after induction of anesthesia on the basis of conventional general anesthesia, while in the control group, intravenous infusion of isovolume normal saline was started 15 minutes after induction of anesthesia on the basis of conventional general anesthesia. Serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), S-100β protein and neuron specific enolase (NSE) in 2 groups were detected 1 day before surgery, 1 day after surgery and 3 days after surgery. Cognitive function was assessed by Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA). Results: The levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), S-100β protein and neuron specific enolase (NSE) in peripheral blood of 2 groups were increased 1 and 3 days after surgery compared with those before surgery (P < 0.05). The levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), S-100β protein and neuron specific enolase (NSE) in peripheral blood of butylphthalide group were significantly lower than those of control group 1 and 3 days after surgery (P < 0.05). MMSE and MoCA scores of butylphthalide group were significantly higher than those of control group at 1 and 3 days after operation. The incidence of postoperative cognitive dysfunction was 17.5% in the butylphthalide group and 55% in the control group, and the incidence of postoperative cognitive dysfunction in the butylphthalide group was significantly lower than the control group (P < 0.05). Conclusion: Butylphthalide can improve postoperative cognitive function and reduce the incidence of postoperative cognitive dysfunction in patients with off-pump coronary artery bypass grafting, and the mechanism may be related to the reduction of inflammatory response.
Keywords:Butylphthalide, Postoperative Cognitive Dysfunction, Coronary Artery Bypass Surgery
Copyright © 2022 by author(s) and Hans Publishers Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).
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术后认知功能障碍(Postoperative cognitive dysfunction, POCD)是冠状动脉旁路移植术(Coronary artery bypass grafting, CABG)术后最常见的并发症之一,主要特征为手术后出现精神活动、人格、社交活动以及认知能力等功能的变化,临床表现为记忆受损、认知功能减退、焦虑、人格的改变以及精神错乱,严重影响患者术后的生活质量。丁苯酞是从食用植物芹菜籽中提取的有效成分,目前广泛应用于急性脑卒中的治疗中。已有动物实验证明,丁苯酞可以通过减轻氧化应激损伤而改善脑缺血大鼠的认知功能 [
选择我院2021年7月至2022年2月于非体外循环下行冠脉搭桥手术的患者80例为研究对象。随机分为两组,丁苯酞组(实验组) (n = 40)和对照组(n = 40)。两组患者在年龄、性别、ASA分级和术前合并基础疾病等指标方面无显著差异(均P > 0.05),见表1。
组别 | 年龄/(岁) | 性别 | 合并症/[例(%)] | ||
---|---|---|---|---|---|
男 | 女 | 高血压 | 糖尿病 | ||
实验组(n = 40) | 66.98 ± 6.09 | 17 | 23 | 10 (25) | 8 (20) |
对照组(n = 40) | 64.70 ± 8.75 | 22 | 18 | 9 (22.5) | 10 (25) |
检验值 | t = 0.101 | x2 = 1.251 | 0.069 | 0.287 | |
p值 | 0.920 | 0.371 | 0.793 | 0.790 |
表1. 实验组与对照组一般情况比较
纳入标准:① ASA分级II~III级;② 术前认知功能正常(简易精神状态量表(MMSE)评分 ≥ 27分);③ 年龄55~75岁。
排除标准:① 有长期饮酒史;② 有脑血管、神经肌肉、内分泌系统、精神疾病史;③ 既往有心脏手术病史的患者;④ 文盲或文化程度难以完成评估问卷的患者。
本实验经本院医学伦理委员会批准后开展,患者及家属已知晓研究内容并签署知情同意书。
患者进入手术室后建立静脉通路,监测心电图、心率、脉搏氧饱和度和有创血压。两组患者均采用丙泊酚1 mg/kg、依托咪酯0.3 mg/kg、咪达唑仑0.05 mg/kg、苯磺顺阿曲库铵0.3 mg/kg、舒芬太尼1 μg/kg进行麻醉诱导。待患者意识消失药物完全起效后行经口明视气管内插管,调整呼吸机参数潮气量6~7 mL/kg、呼吸频率12~16/min、吸呼比1:1.5~2,维持呼气末CO2在35~45 mmHg (1 mmHg = 0.133 kPa)。行右侧颈内静脉穿刺,置入三腔静脉导管用于测定中心静脉压及泵注血管活性药物。静脉持续泵注丙泊酚4~12 mg/kg/h、苯磺顺阿曲库铵0.1 mg/kg/h,根据需要间断静脉注射舒芬太尼。术中监测脑电双频指数(BIS)并维持BIS位于40~60之间。丁苯酞组于麻醉诱导后15分钟开始静脉滴注丁苯酞氯化钠注射液50 mg,对照组于麻醉诱导后15分钟开始静脉滴注等容量生理盐水。于取完乳内动脉后经颈内静脉注射肝素1 mg/kg,测定激活全血凝固时间(active clotting time, ACT)达300 s后开始冠脉搭桥手术。
术中记录两组患者于T0 (麻醉诱导前)、T1 (开胸前)、T2 (搭前降支)、T3 (搭后降支)、T4 (缝皮前)五个时间点的心率(HR)、平均动脉血压(MAP)、中心静脉压(CVP)、脑电双频指数(BIS)值。术前1天、术后1、3天给予患者简易精神状态量表(MMSE)和蒙特利尔认知评估量表(MoCA)评分并抽取静脉血,用酶联免疫吸附试验(ELISA)检测肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)、S100β蛋白、血清神经元特异性烯醇化酶(NSE)水平。
术后任意一次MMSE评分量表评分比术前低2分,即认为术后发生POCD。
应用IBM SPSS23.0统计学软件进行数据处理。正态分布的计量资料以均数 ± 标准差( x ¯ ± s)表示,比较采用独立样本t检验;计数资料以率(%)表示,比较采用X2检验。P < 0.05为差异有统计学意义。
两组患者在不同时间点(T0-T4)的生命体征(HR、MAP、CVP、BIS)及手术时间差异均无统计学意义(均P > 0.05,见表2)。
组别 | 时间 | HR(次/min) | MAP(mmHg) | CVP(mmHg) | BIS | 手术时间(min) |
---|---|---|---|---|---|---|
实验组(n = 40) | T0 | 69.68 ± 7.26 | 92.95 ± 10.37 | 7.90 ± 1.98 | 97.2 ± 1.20 | 207.46 ± 17.92 |
T1 | 58.25 ± 5.71 | 83.40 ± 8.59 | 8.07 ± 1.36 | 52.22 ± 4.10 | ||
T2 | 68.67 ± 7.29 | 83.67 ± 9.37 | 9.20 ± 1.30 | 49.12 ± 2.93 | ||
T3 | 76.87 ± 6.85 | 83.50 ± 5.23 | 11.72 ± 2.34 | 46.72 ± 3.65 | ||
T4 | 75.85 ± 5.50 | 84.95 ± 4.88 | 7.95 ± 1.82 | 49.12 ± 3.06 | ||
对照组(n = 40) | T0 | 67.28 ± 8.17 | 93.50 ± 13.14 | 7.62 ± 2.15 | 97.10 ± 1.00 | 206.31 ± 14.78 |
T1 | 58.72 ± 8.80 | 84.40 ± 11.32 | 7.82 ± 2.46 | 51.35 ± 2.96 | ||
T2 | 67.87 ± 9.29 | 86.30 ± 9.915 | 9.07 ± 2.34 | 48.97 ± 3.15 | ||
T3 | 74.07 ± 9.40 | 86.75 ± 10.10 | 11.45 ± 2.85 | 47.47 ± 2.77 | ||
T4 | 74.10 ± 9.04 | 83.70 ± 6.695 | 8.90 ± 2.68 | 49.52 ± 2.84 |
表2. 实验组与对照组围手术期生命体征比较( x ¯ ± s )
两组患者术前1天TNF-α、IL-6、S-100β蛋白、NSE水平差异均无统计学意义(均P > 0.05)。与术前1天相比,两组患者在术后1天和术后3天的TNF-α、IL-6、S-100β蛋白、NSE水平显著升高,差异有统计学意义(均P < 0.05,见表3、表4)。在术后1天和术后3天,实验组与对照组相比,实验组的TNF-α、IL-6、S-100β蛋白、NSE水平均降低,差异有统计学意义(均P < 0.05,见表3、表4)。
组别 | TNF-α | IL-6 | ||||
---|---|---|---|---|---|---|
术前1天 | 术后1天 | 术后3天 | 术前1天 | 术后1天 | 术后3天 | |
实验组(n = 40) | 23.52 ± 1.97 | 42.84 ± 6.72*† | 29.93 ± 6.66*† | 16.56 ± 2.24 | 27.43 ± 4.52*† | 20.90 ± 5.12*† |
对照组(n = 40) | 22.95 ± 2.13 | 48.13 ± 7.77* | 36.66 ± 7.67* | 17.75 ± 3.31 | 34.12 ± 5.76* | 28.19 ± 5.47* |
表3. 实验组与对照组不同时间点TNF-α、IL-6比较(ng/L, x ¯ ± s )
注:与术前1天相比,*P < 0.05;术后1天和术后3天,实验组与对照组相比,†P < 0.05。
组别 | S-100β | NSE | ||||
---|---|---|---|---|---|---|
术前1天 | 术后1天 | 术后3天 | 术前1天 | 术后1天 | 术后3天 | |
实验组(n = 40) | 0.17 ± 0.05 | 0.26 ± 0.12*† | 0.20 ± 0.08*† | 0.15 ± 0.06 | 0.21 ± 0.11*† | 0.16 ± 0.08*† |
对照组(n = 40) | 0.15 ± 0.03 | 0.40 ± 0.13* | 0.31 ± 0.13* | 0.14 ± 0.04 | 0.34 ± 0.11* | 0.29 ± 0.18* |
表4. 实验组与对照组不同时间点S-100β、NSE比较(ng/L, x ¯ ± s )
注:与术前1天相比,*P < 0.05;术后1天和术后3天,实验组与对照组相比,†P < 0.05。
两组患者术前1天MMSE和MoCA评分差异无统计学意义(P > 0.05)。与术前1天相比,两组患者在术后1天和术后3天的MMSE和MoCA评分显著降低,差异有统计学意义(均P < 0.05)。在术后1天和术后3天,实验组与对照组相比,实验组的MMSE和MoCA评分显著高于对照组,差异有统计学意义(均P < 0.05,见表5、表6)。实验组术后认知功能障碍发生率为17.5% (7/40),对照组术后认知功能障碍发生率为55% (22/40),差异有统计学意义(x2 = 12.17, P = 0.000)。
组别 | 总分 | 记忆力 | ||||
---|---|---|---|---|---|---|
术前1天 | 术后1天 | 术后3天 | 术前1天 | 术后1天 | 术后3天 | |
实验组(n = 40) | 28.28 ± 0.75 | 26.37 ± 1.25*† | 26.90 ± 1.35*† | 5.77 ± 0.42 | 5.40 ± 0.74*† | 5.55 ± 0.64*† |
对照组(n = 40) | 28.10 ± 0.63 | 24.97 ± 1.64* | 25.32 ± 1.65* | 5.82 ± 0.38 | 4.55 ± 0.78* | 5.03 ± 0.80* |
组别 | 注意力 | 执行能力 | ||||
术前1天 | 术后1天 | 术后3天 | 术前1天 | 术后1天 | 术后3天 | |
实验组(n = 40) | 6.80 ± 0.41 | 5.85 ± 0.58*† | 6.15 ± 0.62*† | 4.95 ± 0.22 | 4.10 ± 0.55*† | 4.50 ± 0.51*† |
对照组(n = 40) | 6.68 ± 0.47 | 5.20 ± 0.85* | 5.65 ± 0.89* | 4.85 ± 0.36 | 4.80 ± 0.76* | 4.15 ± 0.12* |
表5. 实验组与对照组手术前后MoCA评分比较(分, x ¯ ± s )
注:与术前1天相比,*P < 0.05;术后1天和术后3天,实验组与对照组相比,†P < 0.05。
组别 | MMSE评分(分, x ¯ ± s ) | POCD/[例(%)] | ||
---|---|---|---|---|
术前1天 | 术后1天 | 术后3天 | ||
实验组(n = 40) | 29.30 ± 0.723 | 28.12 ± 1.399*† | 28.67 ± 0.997*† | 7(17.5) |
对照组(n = 40) | 29.10 ± 0.632 | 26.40 ± 1.918* | 27.32 ± 1.141* | 22(55) |
表6. 实验组与对照组手术前后MMSE评分和POCD发生情况比较
注:与术前1天相比,*P < 0.05;术后1天和术后3天,实验组与对照组相比,†P < 0.05。
老年患者因为器官功能退化、血管条件差等问题,极易发生围术期并发症,尤其是脑缺血缺氧性并发症。据报道,老年患者术后发生POCD的概率高达10% [
丁苯酞由食用植物芹菜籽中提取,主要成分为消旋体-3-正丁基苯酞。已有动物实验研究证明 [
POCD的发生机制目前尚不明确,目前研究 [
ZHANG X等 [
S-100β蛋白是一种主要由中枢神经系统星形胶质细胞分泌的酸性钙离子结合蛋白,当中枢神经系统受损时血清S-100β表达水平随之上升。中枢神经系统受损时,S-100β蛋白水平能够预测术后认知功能障碍的发生 [
本研究中,丁苯酞组患者POCD发生率为17.5%,与对照组(55%)相比具有明显差异。丁苯酞组患者术后TNF-α、IL-6、S-100β、NSE水平较实验组明显降低,说明丁苯酞的使用能够减轻机体炎症反应和神经系统损伤,对改善术后认知功能障碍具有积极意义。而这一现象也与既往研究得出的丁苯酞可能减轻机体由于手术应激引起的神经细胞内钙离子的升高,改善脑缺血及循环不良,保护脑功能;并减轻机体由于手术应激产生中枢神经系统炎症反应的推测相吻合。
综上所述,非体外循环冠脉搭桥手术术后认知功能障碍发生率较高,丁苯酞可减轻手术过程中机体的炎症反应,并减轻围手术期脑损伤,降低冠脉搭桥手术术后认知功能障碍的发生率。
山东省医药卫生科技发展计划(编号:202104110960)。
孙晓丽,高俊琼,贾长新,段 梅,仇伯珏,王士雷. 丁苯酞对非体外循环冠脉搭桥手术术后认知功能的影响Effect of Butylphthalide on Cognitive Function after Off-Pump Coronary Artery Bypass Surgery[J]. 临床医学进展, 2022, 12(08): 7097-7103. https://doi.org/10.12677/ACM.2022.1281022