【作者】 王颖；

【导师】 李龙云；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2023， 硕士

【摘要】 目的:大多数手术需要全身麻醉,其中七氟醚和丙泊酚是最常用的吸入和静脉麻醉药。根据生物物理和动物模型研究,小剂量吸入麻醉药确实促进β淀粉样蛋白（Aβ）寡聚。高浓度的丙泊酚也会使Aβ寡聚,而由β淀粉样蛋白肽的寡聚原纤维组成的致密细胞外斑块以及磷酸化微管蛋白（tau）的不溶性聚合物组成的神经元内缠结,会大量出现在认知障碍及阿尔兹海默症患者中。因此,研究在临床相关浓度下广泛使用的丙泊酚是否对Aβ寡聚有任何作用,从而引发脑损伤,产生认知障碍是很重要的。在这种系统的丙泊酚-Aβ相互作用的研究中,研究丙泊酚（以临床相关浓度）与较小剂量的麻醉剂（如七氟烷）共同使用是否促进的Aβ寡聚,从而产生术后认知障碍也同样重要。本实验旨在探讨中型麻醉剂丙泊酚单独使用与中型麻醉剂丙泊酚和七氟烷共同给药后对腹腔镜肠道手术老年患者术后神经认知功能的影响。方法:选取全麻下于我院行择期腹腔镜下肠道手术的患者,患者ASA分级为Ⅰ～Ⅱ级,年龄在60～75岁之间,BMI在19～30kg/㎡之内。采用随机数字表法,将患者分为两组,分别于术前1d进行简易精神状态检查（Mini-mental state Examination,MMSE）量表、数字广度（Digital span test,DST）、数字符号、Boston命名（中文版BNT-30）、画钟测验评估,MMSE术前评分（文盲≤17分,小学≤20分,初中及以上≤24分）的患者排除,其余患者入组。并于术后3d、30d再对患者行数字广度（DST）、数字符号、Boston命名（中文版BNT-30）、画钟测验测试,与术前进行对比,进行统计学分析,同时随机纳入除未进行手术外其余纳入条件与实验组相同的研究对象60例作为对照组,分为静脉麻醉组、静吸复合组、对照组。依次静脉注射舒芬太尼0.4ug/kg、丙泊酚2mg/kg、顺阿曲库铵0.2mg/kg,进行常规诱导后。D1组:静脉麻醉组麻醉维持:静脉泵注丙泊酚（4-8mg/（kg·h））,瑞芬太尼（0.1-0.5ug/kg/min）;D2组:静吸复合组麻醉维持:吸入七氟烷（1%-1.5%）,静脉输注丙泊酚（2-4mg/（kg·h））,瑞芬太尼（0.1-0.5ug/kg/min）;P组:对照组,随访期间未进行手术。气管插管后行机械通气（V_T8～10ml/kg,RR 8～12次/分,I:E1;1.5,氧流量2L/min）,控制P_ETCO₂30～40mm Hg。术中血压维持在基线的±30%,鼻咽温度36-37.2℃。通过调整丙泊酚、七氟烷及瑞芬太尼的剂量使术中BIS维持在45-55之间。根据术中情况间断追加适量顺阿曲库铵及血管活性药（升压用麻黄碱、间羟胺;升心率用阿托品）。术毕前40分钟补充舒芬太尼0.15ug/kg进行术后镇痛。记录手术期间和术后直至患者出院的不良事件。术后使用镇痛泵（舒芬太尼:体重的2～3倍）缓解疼痛。术中及术后避免使用右美托咪定、激素、非甾体类抗炎药和长效镇静剂。记录下述指标,并进行统计学分析与对比:三组患者的一般资料:患者的手术持续时间、记录麻醉前（T0）、气管插管后15min（T1）、手术开始后1h（T2）、手术结束时（T3）和手术后24h（T4）的心率、血氧饱和度、无创平均血压。记录患者的清醒拔管时间,术后恶心呕吐等不良反应;记录术后24h的RASS评分,CAM-ICU评分;记录术后3d和30d两次随访的数字广度、数字符号、Boston命名、画钟试验等4种量表评分结果,并用Z计分法处理评分结果,诊断神经认知恢复延迟（DNR）。结果:实验研究过程中,共有86名患者参与了这项研究。其中6例不符合纳入标准,最后,共纳入80例受试者。在纳入的患者中,6例患者未接受分配干预（5例患者手术改为开放手术,1例患者撤回同意参与）,2例患者失去随访,2例患者因接受了应避免的药物而被排除。因此,静脉麻醉D1组35例患者和静吸复合D2组35例患者,按照方案完成了研究。术后认知障碍评定标准为与术前相比,4个测试量表参数中至少有2个有临床意义的下降（z值<-1.96）。术后第3天,静脉麻醉组术后神经认知恢复延迟（Delayed neurocognitive recovery,DNR）的发生率为0,术后第30的术后神经认知恢复延迟（DNR）的发生率为2.9%（n=35）;静吸复合组术后第3天神经认知恢复延迟（DNR）的发生率为2.9%（n=35）,术后第30天下降为8.6%（n=35）;神经认知恢复延迟（DNR）的发生率在两组间没有统计学差异。但术后两组患者的注意力,运动速度—执行能力、工作记忆、视空间方面都受到影响,测试参数比术前低,差异具有统计学意义（P<0.05）。语言能力,在静脉麻醉组,主要在手术后第30天出现受损,但在术后第3天时并未表现出与术前的明显差异。而在静吸复合组,言语能力在术后不久就出现能力受损,而在术后第30天,言语能力逐渐恢复。两种不同的麻醉方式都会对术后患者的认知产生影响,影响程度不存在差别,且神经认知恢复延迟（DNR）的发生与术后谵妄的发生并无相关性。与静吸复合麻醉相比,单纯静脉麻醉后患者清醒拔管时间更短,术后恶心呕吐发生率更低,但其对术中的血流动力学影响较大（P<0.05）。结论:两种不同的麻醉方式都会对术后患者的认知产生影响,两组间神经认知恢复延迟（DNR）的发生率不存在差别。更多还原

【Abstract】 Objective:Most procedures require general anesthesia,with sevoflurane and propofol being the most commonly used inhalation and intravenous anesthetics.According to biophysical and animal model studies,low doses of inhaled anesthetics do promote Aβoligomerization.High concentrations of propofol also oligomeric Aβ.And dense extracellular plaques composed of oligomeric fibulles of beta-amyloid peptide and insoluble polymers of phosphorylated tubulin（tau）are found in large numbers in patients with cognitive impairment and Alzheimer’s disease.Therefore,it is important to investigate whether propofol,which is widely used at clinically relevant concentrations,has any effect on Aβoligomerization,resulting in brain damage and cognitive impairment.In such systematic studies of propofo-Aβinteractions,it is also important to investigate whether the combination of propofol（at clinically relevant concentrations）with lower doses of anesthetics（e.g.,sevoflurane）promotes Aβoligopoly and thus postoperative cognitive impairment.The purpose of this study was to investigate whether propofol alone and sevoflurane combined administration of medium anesthetic propofol have a difference in postoperative neurocognitive outcomes in elderly patients undergoing laparoscopic intestinal surgery.Methods:Selected patients underwent laparoscopic intestinal surgery under general anesthesia in our institution.Individuals with BMIs between 19 and 30 kg/m2,ASA grades Ⅰ or Ⅱ,and age 60 to 75.The patients were split into two groups using a random number table method.One day prior to surgery,the patients had evaluations using Mini-mental state Examination,The Boston Naming Test（Chinese version of BNT-30）,Digital span test（DST）,Symbol Digit Modalities Test,and the clock drawing test.Patients with MMSE preoperative scores（illiterate≤17 points,primary school≤20 points,junior high school and above≤24 points）were excluded,and other patients were enrolled.In addition,the patients underwent The Boston Naming Test（Chinese version of BNT-30）,Digital span test（DST）,Symbol Digit Modalities Test,and the clock drawing test at 3 and 30 days following surgery.The preoperative comparison was then done for statistical analysis.As a control group,60 participants were chosen at random from the identical inclusion criteria as the experimental group,with the exception of those who did not have surgery.groups were created for intravenous anesthesia,intravenous absorption complex,and control.Routine induction was carried out,and sufentanil 0.4ug/kg,propofol 2mg/kg,and cisatracurium 0.2mg/kg were administered intravenously.Group D1:Remifentanil（0.1-0.5ug/kg/min）and propofol（4-8mg/（kg·h））intravenous pumps are used to maintain anesthesia;D2 group:Intravenous aspiration combined group anesthetic maintenance with sevoflurane（1%～1.5%）,propofol（2～4mg/（kg·h））,and remifentanil（0.1～0.5ug/kg/min）intravenous infusions;Group P:control group;follow-up operations were not conducted on this group.After endotracheal intubation,mechanical breathing was carried out(VT 8～10 ml/kg,RR 8～12 times/min,I:E:1:1.5,oxygen flow 2L/min,control P_ETCO₂30～40mm Hg).Nasopharyngeal temperature was maintained at 36～37.2°C,and intraoperative blood pressure was kept at 30%of baseline.By modifying the dosages of propofol,sevoflurane,and remifentanil,BIS was kept between 45 and 55.The right dosage of cisatracurium and vasoactive medications（ephedrine and m-hydroxyamine for pressors;Atropine for heart rate increase）.For postoperative analgesia,sufentanil 0.15ug/kg was added 40 minutes before to surgery.Up until the patient was released from the hospital,adverse events were documented both during and after operation.Analgesic pump for postoperative pain management（Sufentanil:2～3 times body weight）.Dexmedetomidine,hormones,non-steroidal anti-inflammatory medications,and long-acting sedatives should not be used during or after surgery.General information about the patients in the three groups was recorded,statistically analyzed,and compared,including the length of the procedure,heart rate,oxygen saturation,and noninvasive mean blood pressure recorded before anesthesia（T0）,15 minutes after endotracheal intubation（T1）,1 hour after the procedure（T2）,at the conclusion of the procedure（T3）,and 24 hours after the procedure（T4）.Recorded adverse reactions included postoperative nausea and vomiting as well as the awake extubation time.Following surgery,the RASS and CAM-ICU scores were reported.At the third and thirty-day postoperative follow-ups,the results of four scales,comprising The Boston Naming Test（Chinese version of BNT-30）,Digital span test（DST）,Symbol Digit Modalities Test,and the clock drawing test,were recorded.Z-score approach was used to analyze the score findings to identify delayed neurocognitive recovery（DNR）.Results:The study included 86 patients in total.Six of them didn’t match the requirements for inclusion.80 subjects in all were eventually included.Six patients who were included in the study were not given the prescribed intervention（5 had their surgeries altered to open surgery,and 1 withdrew consent to participate）;two lost follow-up;and two were omitted because they were given medicines that should not have been given.In line with the protocol,35 patients in the D1 group under intravenous anesthesia and 35 patients in the D2 group receiving intravenous aspiration completed the study.A clinically significant decline in at least two of the four test scale characteristics（Z<-1.96）relative to preoperative values was used to determine postoperative cognitive impairment.The incidence of delayed neurocognitive recovery（DNR）was 0 in the intravenous anesthetic group on day 3 after surgery and2.9%on day 30 after surgery（n=35）in that group.On the third postoperative day（n=35）,the frequency of delayed neurocognitive recovery（DNR）was 2.9%;by the30th postoperative day（n=35）,it had dropped to 8.6%.Across the two groups,there were no differences in the incidence of delayed neurocognitive recovery（DNR）.In addition,the test parameters were lower after surgery for the two groups in terms of attention,working memory,motor speed-executive ability,and visual space,and the difference was statistically significant（P<0.05）.Speech in the intravenous anesthetic group was largely impaired on day 30 following surgery,but did not differ significantly from day 3 before to surgery.However,the static inhalation group’s reduced speech skills first surfaced shortly after the operation and only fully recovered on day 30.There was no difference in the strength of the two forms of anesthesia’s effects,and there was no connection between postoperative delirium and delayed neurocognitive recovery（DNR）.Compared with the combination of intravenous anesthesia,patients with simple intravenous anesthesia had shorter waking extubation time and a lower incidence of postoperative nausea and vomiting,but it had a greater effect on intraoperative hemodynamics（P<0.05）.Conclusion:Both types of anesthesia had an effect on postoperative cognition,and there was no difference in the incidence of delayed neurocognitive recovery（DNR）between the two groups.更多还原