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老年人在接受重大、急诊手术之后,容易出现术后认知功能障碍(postoperative cognitive dysfunction,POCD)。肝脏外科手术一般创伤较大、术后引流管较多,更是增加病人感染和POCD的发生。研究[1-4]发现由手术引起的全身炎症反应在POCD的发生发展中起重要作用,抑制炎症反应对遏制POCD具有积极意义。因此,肝硬化进展成肝癌需要行手术切除时,合理应用麻醉药物,积极控制炎症,对预后具有积极作用。有研究发现,右美托咪定(dexmedetomidine,Dex)不仅可以通过减轻全身和神经系统炎症反应抑制老年动物POCD[5-6],还可明显降低老年腹腔镜胆囊切除术病人、老年食管癌病人的炎症反应,减少POCD的发生[7-8]。但是,右美托咪定是否可以改善肝硬化病人术后认知功能,目前尚无定论。本研究拟通过观察Dex对肝硬化病人围手术期外周血炎性因子水平及术后认知功能的影响,为此类病人的麻醉管理提供参考。
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本研究已获得医院伦理委员会批准并与所有受试病人签署知情同意书。收集2016年6月至2019年10月择期行肝癌切除术的老年肝硬化病人52例,其中男29例,女23例,年龄63~82岁,平均(70.4±8.7)岁,Child-Pugh肝功能分级均为A级,ASA Ⅱ~Ⅲ级,随机均分为Dex组和对照组(Con组)。排除标准:术前已进行介入或射频消融治疗,对Dex有过敏等不良反应,合并心、脑、肾等重要脏器严重疾病,有明显精神疾病,术前服用α肾上腺素能受体激动剂及镇痛镇静药。2组病人性别、年龄、体质量指数、ASA分级、手术时间、术中出血量差异均无统计学意义(P>0.05)(见表 1),具有可比性。
分组 n 男 女 年龄/岁 体质量指数/ (kg/m2) ASA Ⅱ~Ⅲ 手术时间/h 术中出血量/mL Con组 26 16 10 68.76±9.57 22.25±2.74 17/9 2.69±0.48 404.57±50.81 Dex组 26 13 13 72.12±9.05 22.67±3.07 14/12 2.82±0.74 397.73±67.24 t — 0.70* 1.30 0.52 0.72* 0.75 0.41 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示χ2值 表 1 2组病人一般资料比较(x±s)
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2组病人术前常规禁食8 h,入室后即刻建立静脉通路。采用多功能麻醉监护仪及脑电双频指数监护仪连续监测呼吸频率、心率、血压。Dex组病人麻醉诱导前静脉泵注Dex(0.5 μg/kg,10 min给药完毕),后以0.4 μg·kg-1·h-1维持至关腹;Con组病人于诱导前静脉泵入等量0.9%氯化钠溶液。麻醉诱导:静注舒芬太尼0.3 μg/kg、丙泊酚2 mg/kg、顺式阿曲库铵0.2 mg/kg,待咬肌松弛后气管插管,机械通气维持PaCO2 35~45 mmHg,SpO2>95%。麻醉维持:静脉持续泵注丙泊酚4~6 mg·kg-1·h-1、瑞芬太尼0.1~0.3 μg·kg-1·min-1、顺式阿曲库铵0.2 mg·kg-1·h-1。肝癌切除术均由同样2名高年资医生完成,时间在3 h之内。在手术过程中,2组的术中麻醉诱导与维持方法均相同,2组术中阻断肝门时间[(18.4±5.9) min vs.(17.6±7.4) min, P>0.05)]、术后病房观察期间再出血率(7.69% vs.11.54%, P>0.05)、循环障碍发生率(0 vs.0, P>0.05)等情况差异无统计学意义。
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术前1 d(T0)、术后即刻(T1)、术后24 h(T2)、术后48 h(T3)抽取病人外周静脉血,经5 000 r/min(4 ℃)离心20 min取上清液后放入-80 ℃冰箱保存备用,ELISA法检测S-100β、白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α。并分别于术前、术后1、3、7 d采用简易精神状态检查量表(mini-mental state examination,MMSE)[9]对病人进行认知功能评定,凡术后有1次MMSE评分量表比术前低2分,即认为术后发生POCD。
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采用t检验、χ2检验、方差分析和Dunnett t检验。
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2组病人T0时间点S-100β、IL-6和TNF-α水平差异均无统计学意义(P>0.05)。2组S-100β、IL-6和TNF-α于T1、T2、T3时间点均较T0时间点有不同程度的升高(P < 0.05~P < 0.01),Dex组在T1~T3各时间点S-100β、IL-6和TNF-α水平均明显低于Con组(P < 0.05~P < 0.01)(见表 2)。
分组 n T0 T1 T2 T3 F P MS组内 S-100β /(μg/L) Con组 26 0.35±0.11 1.05±0.34** 1.12±0.53** 0.96±0.45** 21.18 < 0.01 0.153 Dex组 26 0.34±0.09 0.74±0.22** 0.64±0.18** 0.45±0.11* 33.66 < 0.01 0.025 t — 0.36 3.90 4.37 5.61 — — — P — >0.05 < 0.01 < 0.01 < 0.01 — — — IL-6 /(ng/L) Con组 26 3.39±1.72 7.95±2.86** 9.62±3.32** 9.24±4.02** 22.26 < 0.01 9.580 Dex组 26 3.42±1.94 6.42±2.25** 4.85±1.26* 4.41±1.12* 13.91 < 0.01 2.917 t — 0.06 2.14 6.85 5.90 — — — P — >0.05 < 0.05 < 0.01 < 0.01 — — — TNF-α /(μg/L) Con 26 26.56±4.62 48.38±7.59** 41.26±7.47** 35.52±6.84** 48.77 < 0.01 45.385 Dex 26 27.12±6.31 43.62±6.42** 35.93±5.73** 30.84±5.82* 35.91 < 0.01 36.935 t — 0.37 2.44 2.89 2.66 — — — P — >0.05 < 0.05 < 0.01 < 0.05 — — — Dunnett t检验:与T0时间点比较*P < 0.05,**P < 0.01 表 2 2组病人S-100β及炎症因子水平比较(x±s)
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2组病人共有16例(30.77%)发生术后POCD,其中Con组12例(46.15%),Dex组4例(15.38%),Dex组POCD发生率明显低于Con组(χ2=5.98,P < 0.05)。
右美托咪定对老年肝癌病人术后炎症及认知功能的影响
Effect of dexmedetomidine on the postoperative cognitive function and inflammatory cytokines in elderly patients with cirrhosis
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摘要:
目的 观察右美托咪定(Dex)对老年肝癌病人术后炎症细胞因子和早期认知功能的影响。 方法 选取择期进行肝癌切除术的老年肝硬化病人52例,Child-Pugh肝功能分级为A级,ASA Ⅱ~Ⅲ级,随机分为对照组(Con组)和右美托咪定组(Dex组),各26例。Con组采用常规全身麻醉,Dex组在常规全身麻醉基础上于麻醉诱导前泵注Dex(0.5 μg/kg)10 min,并以0.4 μg·kg-1·h-1持续泵注至关腹。检测2组病人术前1 d与术后即刻、术后24 h、术后48 h血S-100β蛋白、炎症细胞因子等指标,并采用简易精神状态评价量表(MMSE)评估病人认知功能。 结果 2组外周血S-100β蛋白、白细胞介素-6、肿瘤坏死因子α水平在术后不同时间点均较术前不同程度的升高(P < 0.05~P < 0.01);Dex组S-100β蛋白、IL-6、TNF-α水平在术后即刻、术后24 h和术后48 h均明显低于对照组(P < 0.05~P < 0.01)。Dex组术后认知功能障碍发生率明显低于Con组(P < 0.05)。 结论 Dex能降低老年肝癌病人术后认知功能障碍的发生率,其机制可能与减轻炎症反应有关。 Abstract:Objective To investigate the effects of dexmedetomidine(Dex) on the postoperative cognitive function and plasma inflammatory cytokines in elderly patients with cirrhosis. Methods Fifty-two type ASA Ⅱ-Ⅲ elderly patients with cirrhosis scheduled by liver resection were divided into the control group and Dex group(26 cases in each group).In the control group, the routine general anesthesia was used, while in the DEX group, on the basis of routine general anesthesia, the Dex(0.5 g/kg) was pumped for 10 min before anesthesia induction, and 0.4 μg·kg-1·h-1 infusion until the peritoneum was suture.The serum levels of S-100β protein, inflammatory cytokines and other indexes in two groups were detected before 1 day of surgery, immediately after surgery, and after 24 h and 48 h of surgery, and the cognitive function of patients was evaluated using MMSE. Results The serum levels of S-100β protein, IL-6 and TNF-α in two groups after operation significantly increased compared with before operation(P < 0.05 to P < 0.01).The serum levels of S-100β protein, IL-6 and TNF-α in Dex group at the end of operation, 24 h and 48 h after operation were significantly lower than those in control group(P < 0.05 to P < 0.01).The incidence rate of postoperative cognitive dysfunction(POCD) in Dex group was significantly lower than that in control group(P < 0.05). Conclusions Dex can decrease the incidence rate of POCD in the elderly cirrhosis patients treated with liver resection, which might be mediated by the inhibition of perioperative inflammatory response. -
Key words:
- cirrhosis /
- dexmedetomidine /
- elderly /
- postoperative cognitive dysfunction /
- inflammatory cytokine
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表 1 2组病人一般资料比较(x±s)
分组 n 男 女 年龄/岁 体质量指数/ (kg/m2) ASA Ⅱ~Ⅲ 手术时间/h 术中出血量/mL Con组 26 16 10 68.76±9.57 22.25±2.74 17/9 2.69±0.48 404.57±50.81 Dex组 26 13 13 72.12±9.05 22.67±3.07 14/12 2.82±0.74 397.73±67.24 t — 0.70* 1.30 0.52 0.72* 0.75 0.41 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示χ2值 表 2 2组病人S-100β及炎症因子水平比较(x±s)
分组 n T0 T1 T2 T3 F P MS组内 S-100β /(μg/L) Con组 26 0.35±0.11 1.05±0.34** 1.12±0.53** 0.96±0.45** 21.18 < 0.01 0.153 Dex组 26 0.34±0.09 0.74±0.22** 0.64±0.18** 0.45±0.11* 33.66 < 0.01 0.025 t — 0.36 3.90 4.37 5.61 — — — P — >0.05 < 0.01 < 0.01 < 0.01 — — — IL-6 /(ng/L) Con组 26 3.39±1.72 7.95±2.86** 9.62±3.32** 9.24±4.02** 22.26 < 0.01 9.580 Dex组 26 3.42±1.94 6.42±2.25** 4.85±1.26* 4.41±1.12* 13.91 < 0.01 2.917 t — 0.06 2.14 6.85 5.90 — — — P — >0.05 < 0.05 < 0.01 < 0.01 — — — TNF-α /(μg/L) Con 26 26.56±4.62 48.38±7.59** 41.26±7.47** 35.52±6.84** 48.77 < 0.01 45.385 Dex 26 27.12±6.31 43.62±6.42** 35.93±5.73** 30.84±5.82* 35.91 < 0.01 36.935 t — 0.37 2.44 2.89 2.66 — — — P — >0.05 < 0.05 < 0.01 < 0.05 — — — Dunnett t检验:与T0时间点比较*P < 0.05,**P < 0.01 -
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