【作者】 霍婷婷；

【导师】 熊利泽； 王强；

【作者基本信息】 第四军医大学 ， 麻醉学， 2013， 博士

【摘要】 自维也纳人Koller发现局部应用可卡因有止痛效应后，麻醉药的使用经历了百余年的历程，给外科手术的发展带来了巨大的空间。目前，麻醉学已进入了一个快速发展的阶段。随着麻醉技术和药物的不断更新，因麻醉导致的并发症已经越来越少。1944年Gillespie统计的因麻醉导致的死亡率为1/1000；而到了上世纪60年代Memery（1965）报告的麻省私人医院的麻醉死亡率已经减少到了1:3145，1999年美国医学机构（Institute of Medicine，IOM）下属卫生保健质量委员会的报告指出，近年来麻醉安全大大改善，已证实的麻醉死亡率由二十世纪八十年代的万分之二下降到二十世纪末的二十万至三十万分之一[1-4]，因而麻醉的安全性越来越被人们所认同。但是，这并不能说明麻醉是绝对安全的，在如今的医疗条件下如果再出现因麻醉而导致的死亡，是很不被人们接受和极其严重的事件。2009年美国麻醉学杂志发表了一篇文章，关于调查从1999年至2005年间全美因麻醉导致死亡的病例有2211例[5]，其中有46.6%是因为麻醉药物过量所引起的，又有42.5%是因为麻醉药物的副反应所引起的。并且绝大部分的药物不良反应是因为全身麻醉药物过量应用所导致的，因此减少麻醉药物的用量就成为降低因麻醉所导致死亡的重要策略。区域阻滞麻醉已经被国内外证实在复合全麻的过程中可以明显的减少麻醉药品的用量[6-8]，并且很多手术单独使用区域阻滞麻醉可以避免全麻带来的并发症，因此，区域阻滞麻醉就成为一个非常有效的减少全麻药物所导致并发症的措施之一。而区域阻滞麻醉的安全性如何？它又有哪些并发症呢？为了了解区域阻滞麻醉的情况，法国[9]、瑞典[10]、美国等发达国家针对区域阻滞麻醉的并发症做了很多临床多中心、大样本调查，而我国还没有这方面的资料。因此，调查中国区域阻滞麻醉并发症的现状就成为我们刻不容缓的任务。本研究由第四军医大学西京医院牵头，联合全国11家三级甲等教学医院的麻醉中心，进行了为期25个月的多中心区域阻滞麻醉的临床调查，主要调查目前中国区域阻滞麻醉的并发症发生的类型比例、性别差异、科室分布及相关因素，以了解在中国区域阻滞麻醉并发症的现状，为中国麻醉的发展提供一个可靠的参考数据。除了区域阻滞麻醉可以减少全麻中麻醉药物的用量以外。在上世纪五、六十年代我国临床工作者首先证明，针刺能够有效应用于包括开颅、开胸[11]等高难度复杂手术，起到一定镇痛的作用。我们实验室也证实了针刺具有协同药物麻醉的效应，可以减少全麻中麻醉药物的用量。因此进一步推广针刺麻醉是减少全麻药物用量的途径之一。对针刺麻醉的效应和机制进行研究，有重要的科学意义和应用价值。过去有研究证明针刺运用于麻醉有镇痛效应，这也是其运用于麻醉的一个主要原因。镇静作用是全麻中的另一个重要因素，但针刺是否有镇静作用还不清楚，因此本课题就针刺的镇静作用进行了人体实验研究，并通过功能磁共振的方法进一步探讨了可能的相关机制。第一部分多中心区域阻滞麻醉并发症调查目的调查全国11所三级甲等教学医院麻醉中心临床实施区域阻滞麻醉操作的病人，统计发生区域阻滞麻醉并发症的类型比例、性别差异、科室分布及相关因素。方法首先召集全国11家三级甲等教学医院的相关负责麻醉医生进行调查前培训和统一标准；调查时在上级医生的指导和监管下由临床麻醉医生填写《区域麻醉神经并发症记录单》，并由专职的麻醉医生进行术后并发症的随访调查，并及时将记录单的数据输入建立的ACCESS2003数据库中。该调查共进行了25个月，最后利用SQLserver系统进行数据汇总，分析中国目前区域阻滞麻醉并发症的发生情况和相关的影响因素。结果本课题在25个月的调查研究中，共收集11家三级甲等医院麻醉中心进行区域阻滞麻醉操作的病例106569份，其中因急诊等原因未及时录入而流失了4228例，流失率为4%。完成调查的所有病例中包括硬膜外麻醉35698例，腰硬联合麻醉49673例，腰麻12723例，臂丛麻醉8316例和颈丛麻醉701例。发生各种并发症的一共有313例，发生率为29.4/104，包括：严重并发症37例（其中Horner征9例，喉返神经阻滞6例，心脏骤停1例，血肿2例，抽搐5例，导管折断1例，截瘫1例，马尾综合症2例和异常广泛阻滞10例），发生率3.5/10,000；头痛145例，发生率1.4/103；暂时性神经激惹131例，发生率1.2/103。发生的313例并发症中有23例有超过7天的残余症状。在严重并发症中男性的并发症发生率为3.3/104；女性并发症的发生率为3.4/104，男女间无明显差异。调查中严重并发症发生率最高的科室是血管外科（7.7/104），最少的是产科、胸外科和整形外科。椎管内麻醉中出现严重并发症最高的是骶管麻醉（28/104）。神经阻滞麻醉中严重并发症发生率最高的是颈丛麻醉（1.4%）；在臂丛麻醉中用易感法定位进行麻醉的发生严重并发症的有19例，而应用超声引导的方法进行臂丛麻醉的只有2例出现了严重的并发症。结论通过全国多中心、大样本、前瞻性的临床调查，我们提供了中国区域阻滞麻醉总体并发症的发生率、严重并发症的比例、在临床各个外科分布的情况、男女分布的情况、椎管内麻醉和神经阻滞麻醉中各类麻醉方法所可能发生严重并发症的比例以及临床中使用B超引导下进行的臂丛麻醉发生并发症的数据。本临床调查填补了我国区域阻滞麻醉并发症发生情况的空白，为探讨应对策略提供了资料，对临床区域阻滞麻醉有一定的指导作用。第二部分针麻的镇静作用和机制研究目的探讨针麻是否可以降低BIS值而产生镇静作用，并用功能磁共振的方法探讨针刺产生镇静作用的机制。方法15名年龄在20岁至35岁的年轻受试者，女性8位，男性7位。随机分为3组(n=15)：电针组（EA）：电针刺激双侧风池穴、安眠穴、合谷穴、神门穴、足三里以及三阴交穴；旁开组（Con）：电针刺激所选穴位旁开1-2cm处；对照组(Sham)：将电极片固定在所选穴位上，但不进行电刺激。每位受试者均在随机三天中同一时间段（晚18点-21点）内、相对恒定温度（18-22°C）、湿度（30%-40%）的条件下，避免任何噪音的干扰，分别进行三种不同的实验测试。在实验开始前嘱受试者静卧休息15min后，先进行fMRI扫描17mim，分别按照定位像、T2加权平扫、T1加权薄层平扫、BOLD（血氧水平依赖扫描）和PASL(脉冲动脉自旋标记成像）的顺序，然后立刻进行30min的电针刺激。在电针过程中每5min记录受试者的血压、心率、指脉氧饱和度以及BIS值；电针刺激结束后再进行17min的fMRI扫描，顺序是定位像、T1加权薄层平扫、BOLD（血氧水平依赖扫描）。结果1）BIS值的组内比较：电针组：电针刺激各时间点的BIS值均下降，均与刺激前（0min）的BIS值有差异（P<0.001），而电针过程中各时间点的BIS值间无明显统计学差异；旁开组：仅电针后5min、10min及15min的BIS值略有下降，与0min间均有明显的统计学差异（P分别为0.007，0.004，0.010），但刺激后其余时间点（20min、25min和30min）与0min的BIS值间无明显统计学差异；对照组：除10min的BIS值低于0min的(P<0.05)外，余时间点各组间的BIS值无明显统计学差异。BIS值的组间比较：电针组与另两组的BIS值在0min无差异；5min时电针组均比旁开组及对照组的BIS值低，有统计学差异(分别是P=0.010及P=0.045)；10min时电针组与旁开组及对照组的BIS值均有统计学差异(分别是P=0.035及P=0.014)；15min时电针组与对照组的BIS值也有统计学差异（P=0.036)，与旁开组的BIS值无差别（P=0.067）；20min时电针组与对照组的BIS值有统计学差异（P=0.031)，与旁开组的BIS值也有统计学差异（P=0.008）；25min时电针组与旁开组及对照组的BIS值均有统计学差异(分别是P=0.014及P=0.018)；30min时电针组与旁开组的BIS值也有统计学差异（P=0.043)，但与对照组的BIS值无差别（P=0.229）。2）功能磁共振结果：方差分析结果显示，与旁开组和对照组相比较，电针后ReHo存在差异的脑区有双侧前扣带回、双侧额上回内侧、左侧额上回，这些脑区ReHo都是降低的。在P值小于0.05，采用AlphaSim校正后团块大小超过85个体素的条件下没有发现ReHo增高的脑区。结论1）电针刺激可以明显降低BIS值，证明电针刺激有一定的镇静作用，这可能是针刺麻醉效应的机制之一。2）实验中电针对大脑双侧前扣带回（ACC）、双侧额上回内侧（MPFC）以及左侧额上回具有显著的负激活效应。从而降低人脑默认网络（DMN）的激活使其司职的自发心理状态的监控及其他高级认知活动减弱，从而达到使受试者镇静的效应。更多还原

【Abstract】 BackgroundThe use of narcotics has been developing for a hundred years since the analgesiceffect of local application of cocaine was discovered by Keller of Vienna, which hasbrought great progress for the development of surgry. At present, anesthesiology hasentered a stage of rapid development. With the anesthetic technology and anaestheticconstantly being updated, the anesthesia complications tend to have less. In1944, themortality of anesthesia is1/1000by Gillespie. However, in the60’s of last century,Memery (1965) reported that anesthesia mortality at private hospitals has been reduced to 1:3145. In1999the United States medical institutions (Institute of Medicine, IOM) of thehealth care quality Commission reported that the safety of anesthesia greatly improved,and anesthesia mortality rate which from two hundred thousand to1/300000has beenconfirmed by the2/10000decline in nineteen eighties to the end of the twentiethCentury.The safety of anesthesia is increasingly being recognized. However, this does notmean that anesthesia is safe. It is not accepted if death is due to anesthesia in today’smedical condition, and is a very serious incident. There are a lot of reasons for anesthesiadeath. The main reason is the excessive amount of narcotic drugs. Therefore, in order toreduce the death, an important strategy of anesthesia is that it is should be reducedconsumption of narcotic drugs. Regional anesthesia has been confirmed abroad, whichcombined with general anesthesia can reduce the dosage of narcotic drugs. It is a veryeffective way to reduce the amount of anesthetic drugs that regional anesthesia combinedwith general anesthesia. For regional anesthesia complications, there are a alarge samplesurvey of many clinical center in developed countries, France, Sweden, the United Statesof America, but it is still no information in China. Therefore, the situation allows ofno delay about current investigation situation regional anesthesia complications in China.This study led by The Fourth Military Medical University Xijing Hospital, cooperatedwith11anesthesia Center. The study is for25months by clinical multicenter survey on theregional anesthesia. The major surveys is about patients type, gender differences,distribution of departments and some related factors. It provide a reliable reference dataabout the current Chinese regional anesthesia complications.In addition to regional anesthesia can reduce consumption of narcotic drugs,acupuncture can be used effectively in sedative action in the1950s and1960s, includingcraniotomy in highly complex operation. We also confirmed that acupuncture has asynergistic effect of narcotic drugs, and can reduce the dosage of narcotic drugs in generalanesthesia. It will further promote the acupuncture anesthesia that is one of the ways ofgeneral anesthetics dosage reduction. It is important scientific significance and applicationvalue to study the effect and mechanism of acupuncture anesthesia. In the animalexperiment, acupuncture has been proved to be brain protection, sedation and anesthesia. Sedation is another important mechanism of acupuncture in the general anesthesia. Butthere is not related experiments. In our study, we try to address the sedative action ofacupuncture experimental study in the human body and the further related mechanism bythe method of functional magnetic resonance imaging.Part1: Clinical Investigation on Complications of Regional Anesthesia by MultipulcentersObjectiveTo investigate the patients of neurological complications of regional anesthesia in11anesthesia centers, and patients type, gender differences, distribution of departments andsome related factors.MethodsWe convened anesthesiologist from11national level hospitals to training and uniformstandards, In the doctor’s guidance and supervision, the anesthesia doctors fill in the"regional anesthesia complications record", and follow-up investigation of thepostoperative complications by the anesthesiologist full-time. And timely record the datainput to the ACCESS2003database. The investigations were carried out in25months.Finally we carries on the data collection using the SQL server system, and analysisinfluence and relevant factors of current regional anesthesia complications in China.ResultsIn the research of25months, we collected106569cases that operated egionalanesthesia from11three level of first-class hospital. Because emergency and not timelyinput, the loss cases is4228,and the loss rate is4%. The completion of the investigation inall cases include35698cases of epidural anesthesia,49673cases of combinedspinal-epidural anesthesia,12723cases of spinal anesthesia,8316cases of brachial plexusanesthesia and701cases of cervical plexus anesthesia. Various complications occurred ina total of cases is313. The incidence rate is29.4/104, including:37cases of seriouscomplications (including9cases of Horner syndrome, recurrent laryngeal nerve block in6 cases,1cases,2cases with cardiac arrest,5cases of hematoma, tic catheter fracture in1cases;1cases of paraplegia,2cases of cauda equina syndrome and abnormal widely10cases of block), the incidence is3.5/10000;145cases of headache, the incidence is1.4/103,131cases of temporary nerve irritation, the incidence is1.2/103. Residualsymptoms is23cases. There are more than7days of complications occurred in313patients. Men of the serious complications rate was3.3/104. Women of the incidence ofcomplications is3.4/104,and no significant differences between men and women.Thehighest incidence of serious complications in Investigation Department of is VascularSurgery7.7/104, and the least is obstetric,Orthopaedic Surgery and Department of thoracicsurgery.Spinal anesthesia in serious complications were highest in sacral anesthesia(28/104). Nerve block anesthesia complication rate was highest in the cervical plexusanesthesia (1.4%).In the brachial plexus anesthesia with susceptible method positioning ofserious complications of anesthesia is19cases, and the application method of theultrasonic guided brachial plexus anesthesia occurred complicated with severe disease isonly2case.ConclusionBy the clinical investigation of national multicenter, large sample, prospective, weprovide proportional incidence of serious complications, the proportion, the distribution ofevery clinical surgical, gender distribution, intraspinal anesthesia and nerve blockanesthesia in all kinds of anesthesia methods may be severe complication occurred inChina, overall complications of regional anesthesia and the anesthesia complications dataof B ultrasound guided under brachial plexus. The clinical investigation filled the gaps inthe complications of regional block anesthesia, and provided data for the study of clinicalstrategies and regional anesthesia.Part2: The Mechanism of Acupuncture treatment on SedationObjective Discussion about acupuncture treatment can reduce the BIS value to reach sedation,and mechanism of acupuncture sedative action with the method of functional magneticresonance imaging study.MethodsWe analyzed15volunteers (subjects) age from20to35, including8females and7males. Divided into3groups randomly (n=15): Acupuncture group (EA): Stimulating aimacupoints by EA, Conduction group (Con): Stimulating the conduction acupoints in thesame panel of aim acupoints, Control group (Sham): Fasten the electrode plate on aimacupoints without stimulation. Every subject received all of three projects above, in threerandom days from6pm to9pm. Comparison of the effect themselves before and after thetest carried out under following conditions, same temperature(18-20℃),samehumidity(30%-40%),avoiding of any unnecessary noise, subjects take15min rest beforereceiving the30min test, simultaneously, observe their blood pressure, heart rate, pulseoxygen saturation and BIS Value in every5min.According to location, like T2,T1weighted precontrast scan,BOLD (blood oxygenation level dependent scanning) and PASLsequence,and then immediately17min electroacupuncture stimulation.In the EA processevery5min record subjects blood pressure,heart rate,pulse oxygen saturation and the BISvalue,electroacupuncture stimulation after the end of fMRI scanning17min,sequence ispositioned like,weighted T1scan and BOLD(blood oxygenation level dependent scan).Results1)EA group:Statistical BIS Value difference between0min and other timecheckpoints (P<0.001),no significant BIS Value difference in between other timecheckpoints.Con group:Statistical BIS Value difference between0min and5min,10minand15min(P=0.007,0.004,0.010),no significant BIS Value difference in between othertime checkpoints.Sham group:Statistical BIS Value difference between0min and10min(P<0.05), no significant BIS Value difference in between other time checkpoints; sameBIS Value at0min on all three projects was also observed; Statistical BIS Valuedifference between EA group and other two groups at5min (P=0.010, P=0.045);StatisticalBIS Value difference between EA group and other two groups at10min (P=0.035,P=0.014);Statistical BIS Value difference between EA group and Sham group at15min (P=0.036),no BIS Value difference between EA group and Congroup(P=0.067),Statistical BIS Value difference between EA group and Sham group at20min (P=0.031),Statistical BIS Value difference between EA group and Con group at20min (P=0.008),Statistical BIS Value difference between EA group and other two groups at25min (P=0.014, P=0.018),Statistical BIS Value difference between EA group and Congroup at30min (P=0.043),no significant BIS Value difference between EA group andSham group(P=0.229).2)Functional magnetic resonance imaging results:analysis of variance resultsshow:compared with side group and the control group, after EA,the difference ReHo brainregion are bilateral anterior cingulate gyrus,bilateral superior frontal gyrus,left medialfrontal gyrus.These brain regions of ReHo are reduced.The P value is less than0.05. UsingAlphaSim,we didn’t find increased ReHo brain regions of agglomerate size more than85voxel conditionsConclusions(1) Electroacupuncture could significantly reduce the BIS value, and have a certainsedative effect, which may be one of mechanisms of acupuncture anesthesia effect.(2) In the experiment,there are negative significant effect in brain bilateral anteriorcingulate (ACC),bilateral superior frontal gyrus (MPFC) and in the left superiorfrontal gyrus activation.It reduce the human brain default network(DMN)to monitorspontaneous activation of psychological state of the office of the priesthood andmake other advanced cognitive activity weakened, and achieve the sedation effect ofsubjects.更多还原