诱发等电位脑电图的七氟烷最低肺泡有效浓度及其临床价值

发布时间：2018-03-30 06:26

本文选题：吸入麻醉　切入点：七氟烷　出处：《华中科技大学》2014年博士论文

【摘要】：研究背景最低肺泡有效浓度(Minimal alveolar concentration, MAC)是评价吸入麻醉药物效能的重要指标。由其衍生出一系列相关参数,包括抑制对言语命令反应的MACawake和抑制切皮时血流动力学反应的MACBAR等等。作为常用的挥发性麻醉药物之一,七氟烷的这些参数此前已经有许多研究,但目前尚无关于七氟烷浓度和脑电活动之间的关系的报道。深度麻醉下脑电活动会进入抑制状态,期间高电压活动(爆发)和平坦脑电状态(抑制)交替。随着麻醉加深,平坦脑电状态所占时间逐步延长,最终进入持续平坦,即等电位脑电状态。早期研究显示,在颅脑或心脏手术中,为保护脑部避免缺血缺氧风险,曾特意使用大剂量麻醉药物诱发等电位或爆发抑制脑电活动。但近来也有研究显示,无论是心脏还是非心脏手术中,过低的脑电麻醉深度指数可能与不良预后相关。因此,探索吸入麻醉药物浓度和异常脑电活动(爆发抑制或等电位脑电活动)之间的关系,可以帮助麻醉医师在高危(高龄、低ASA评分等)患者中避免不必要的深麻醉,同时在缺血风险下迅速对脑电活动进行暂时性抑制而达到脑保护的作用。因此本研究将测定七氟烷在中年人群诱发等电位或爆发抑制脑电活动的最低肺泡有效浓度。大部分吸入麻醉药物主要通过增强γ-氨基丁酸(GABA)的活性,增加额部剂量依赖性的慢波活动,起到镇静作用。但氧化亚氮是一个例外,作为N-甲基-D-天冬氨酸(NMDA)受体的拮抗剂,氧化亚氮在增强高频脑电活动的同时,还抑制额部慢波活动。因此通过一个前瞻性随机双盲平行组的序贯临床试验,我们将探索氧化亚氮对七氟烷诱发等电位脑电活动的最低肺泡有效浓度的影响。既往研究表明丙泊酚诱发脑电图出现爆发抑制,可能在缺血缺氧风险提供脑保护作用。但七氟烷作为主流吸入麻醉药,其诱发的爆发抑制和等电位脑电活动是否有与丙泊酚类似的脑保护作用未见报道。本研究探讨七氟烷麻醉期间发生的爆发抑制或等电位脑电活动对脑氧代谢的影响,并进一步研究对神经损伤的血清学指标和术后认知功能行为学的影响,为临床提供参考。研究方法和结果 1.诱发等电位脑电图的七氟烷最低肺泡有效浓度方法：我们纳入了31例中年患者,其中30人最终完成试验方案。全身麻醉采用七氟烷吸入诱导和维持,维持期每例患者接受的呼气末七氟烷浓度按照序贯法决定：初始浓度1.7%，如果前一个患者出现等电位脑电活动,则后一个患者呼气末七氟烷浓度下降0.2%，，反之如果前一个患者没有出现等电位脑电活动,则后一个患者呼气末七氟烷浓度上升0.2%。切皮前等待至少30min,以保证七氟烷在体内分布平衡。监护仪上爆发抑制率100%并持续超过1min定义为等电位脑电状态。同时记录在该脑电活动状态下维持血流动力学稳定需要的血管活性药物,和对切皮刺激产生的血压心率变化。结果：中年患者中七氟烷诱导等电位脑电活动的MACie为3.5%(95%可信区间3.4-3.7%)。与未出现等电位脑电活动患者相比,出现等电位脑电活动的患者需要更多去氧肾上腺素注射才能维持血流动力学稳定(班0vs.10/10,P=0.001),但同时切皮刺激后较少出现血压心率反应(1/10vs.11/20,P=0.024)。 2.氧化亚氮对诱发等电位脑电图七氟烷最低肺泡有效浓度的影响方法：在前瞻性随机双盲平行组设计的序贯试验中,共纳入66名患者,均接受七氟烷吸入诱导插管和麻醉维持,之后被随机分为两组：S组使用氧含量40%的空气氧气混合气体,SN组使用60%氧化亚氮与氧气的混合气体。每例患者接受的呼气末七氟烷浓度按照序贯法决定：初始浓度2.5%，如果同组前一个患者出现等电位脑电活动,则后一个患者呼气末七氟烷浓度下降0.2%,反之如果同组前一个患者没有出现等电位脑电活动,则后一个患者呼气末七氟烷浓度上升0.2%。同时记录在该脑电活动状态下两组患者对切皮刺激产生的血压心率变化。结果：60%氧化亚氮中七氟烷诱导等电位脑电活动的MACieSN为3.9±0.4%,高于空气氧气混合气体中MACieS3.5±0.2％(P=0.007).与空气相比,加入60%氧化亚氮可减少对切皮刺激出现血压升高(P=0.031)和心率加快反应(P=0.008)。结论：加入60%氧化亚氮可增加七氟烷诱导等电位脑电活动的MACie,同时抑制对切皮刺激产生的肾上腺素能反应。 3.七氟烷诱发爆发抑制和等电位脑电活动对脑氧耗和术后认知功能的影响方法：55例患者常规诱导插管后七氟烷吸入维持,并随机分为两组：在Narcotrend监测下E组麻醉维持在E0-2期,F组麻醉维持在F0-1期。使用血管活性药物维持血压,30min平衡期后抽取桡动脉和颈内静脉血液进行血气分析,计算动脉-颈内静脉氧含量差(Ca-jvO2),并使用彩超测定双侧颈内动脉和椎动脉血流量。术前及术后24h,48h,72h用Elisa试剂盒测定血清S100β蛋白含量,术后24h,48h,72h使用CAM-ICU评估术后谵妄,术后7天使用MMSE评估术后认知功能障碍。结果：F组Ca-jvO2明显低于E组(1.69±0.77vs.3.38±0.93),差异有统计学意义(P0.001),颈内动脉和椎动脉平均血流量两组差异没有显著统计学意义。血清S100β蛋白含量组内不同时间和组间差异均无统计学意义,术后谵妄和术后认知功能障碍发生率两组没有显著差异。研究总结1.主要研究结果本研究发现七氟烷诱导等电位脑电活动的最低肺泡有效浓度为3.5±0.2%。加入60%氧化亚氮可将七氟烷诱导等电位脑电活动的最低肺泡有效浓度升高至3.9±0.4%,同时加深对切皮刺激产生的肾上腺素能反应的抑制作用。七氟烷诱导等电位或爆发抑制脑电活动可在不影响脑血流的情况下显著降低脑氧耗,对术后血清S100β蛋白含量,术后谵妄和术后认知功能障碍发生率没有明显影响。 2.研究结论七氟烷诱导等电位脑电活动的最低肺泡有效浓度(MACie)大约等于2.1倍MAC,接近抑制切皮时肾上腺素能反应的MAGBAR。加入氧化亚氮可以使MACie升高,MACBAR下降。使用七氟烷诱导等电位或爆发抑制脑电活动可逆性抑制脑氧代谢,无明显神经损伤和认知影响,在高危患者脑保护方面或有潜在的应用价值。 3.创新之处本研究首次提出新的吸入麻醉药物效能MACie的概念,并探索其临床价值,为进一步研究打下基础。
[Abstract]:Background of the study

Minimal alveolar concentration ( MAC ) is an important index to evaluate the efficacy of inhalation anesthetic drugs . It is derived from a series of related parameters including MACBAR inhibiting the response to speech commands and MACBAR for inhibiting the haemodynamic response at the time of cut - off . As one of the commonly used volatile anesthetic drugs , these parameters have been studied previously , but there are no reports on the relationship between the concentration of heptafluoroalkane and brain electrical activity .

In order to protect the brain from the risk of ischemia and hypoxia , it is possible to avoid unnecessary deep anesthesia in patients with high risk ( advanced age , low ASA score , etc . ) . Therefore , it can help anesthesiologists to avoid unnecessary deep anesthesia in patients with high risk ( advanced age , low ASA score , etc . ) .

Most inhaled anesthetic drugs play a sedative role mainly by enhancing the activity of gamma - aminobutyric acid ( GABA ) , increasing the dose - dependent slow wave activity . However , nitrous oxide is an exception . As an antagonist of the N - methyl - D - aspartate ( NMDA ) receptor , nitrous oxide also inhibits the frontal slow wave activity as an antagonist of the N - methyl - D - aspartate ( NMDA ) receptor .

Previous studies have shown that propofol - induced electroencephalogram ( EEG ) can inhibit the occurrence of cerebral ischemia , and may provide brain protection at the risk of ischemia and hypoxia . However , there is no reported effect on cerebral oxygen metabolism in patients with cerebral ischemia . However , the study explores the effects of explosion - inhibiting or isoelectric - brain electrical activity on cerebral oxygen metabolism during the period of anesthesia , and further studies the influence of the serological index and postoperative cognitive function behavior on neural injury and provides a reference for clinical practice .

Study methods and results

1 . The minimum alveolar effective concentration of isoflurane induced by iso - potential EEG

Methods : Thirty patients were enrolled in 31 middle - aged patients , and 30 of them completed the trial protocol . Total anesthesia was induced and maintained by isoflurane inhalation .

Results : In middle - aged patients , the MACie was 3.5 % ( 95 % CI 3.4 - 3.7 % ) .

2 . Effect of nitrous oxide on the lowest alveolar effective concentration in the induction of equipotential EEG

Methods : Sixty - six patients were randomly divided into two groups : group S with oxygen content of 40 % air oxygen mixed gas , SN group using mixed gas of 60 % nitrous oxide and oxygen .

Results : Compared with air , 60 % nitrous oxide could reduce the increase of blood pressure ( P = 0.031 ) and heart rate ( P = 0.008 ) . Compared with air , 60 % nitrous oxide could reduce the increase of blood pressure ( P = 0.031 ) and heart rate ( P = 0.008 ) .

Conclusion : The addition of 60 % nitrous oxide can increase the MACie of potential brain electrical activity induced by Heptafluoroalkane and inhibit the adrenergic response induced by incision stimulation .

3 . Effects of electric activity on brain oxygen consumption and postoperative cognitive function in patients with cerebral oxygen consumption and post - operative cognitive function induced by heptafluoroalkane

Methods : Fifty - five patients were randomly divided into two groups : group E under the monitoring of Narcotrend : Group E was maintained in the period of E0 - 2 , and the F group was maintained in F0 - 1 . After 30 min , the blood flow of the radial artery and the internal jugular vein was measured . After the operation and 24 h , 48 h and 72 h after operation , the serum S100 尾 protein content was determined . After operation , the patients were treated with the CAM - ICU for 24 h , 48 h and 72 h after operation .

Results : Ca - jvO 2 in F group was significantly lower than that in E group ( 0.69 卤 0.77 vs . 3.38 卤 0.93 ) . There was no significant difference in the difference between the two groups ( P 0.001 ) . There was no significant difference between the two groups .

Study Summary 1 . Key Findings

In this study , the lowest alveolar effective concentration was 3.5 卤 0.2 % . The lowest alveolar effective concentration was 3 . 9 卤 0 . 4 % .

2 . Conclusions of the study

The lowest alveolar effective concentration ( MACie ) was approximately equal to 2.1 times that of MAC , which was close to that of MAGBAR , which inhibited the response of adrenaline . The addition of nitrous oxide could increase the MACie level and decrease the MACBAR . The use of heptafluoroalkane induced equipotential or outbreak inhibited the brain oxygen metabolism , had no obvious nerve injury and cognitive effects , and had potential application value in the protection of brain in high - risk patients .

3 . Innovation

For the first time , a new concept of drug efficacy MACie for inhalation anesthesia was proposed and its clinical value was explored .

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R614

【共引文献】