麻醉与器官保护

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1、Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auAnesthesia & Organ Protection麻醉与器官保护麻醉与器官保护Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auOrganFunction器官功能Time时间Effects of Anaesthesia on Organ Function麻醉对于器官功能的影响麻醉对于器官功能的影响Liver肝脏Kidney Gut肾脏，

2、消化道Vascular resistance血管阻力Contractility收缩力Respiration呼吸Consciousness意识Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auAre the effects reversible - e.g.brain?这些影响可逆转吗这些影响可逆转吗 例如：脑？例如：脑？OrganFunction器官功能Time时间Eye opening睁眼Orientation定向Emotional情感Cognitive认知Anaesthesia and Pai

3、n Management Unit; Cardiovascular Therapeutics UnitH.auRecovery differences-other organs恢复的差别恢复的差别 其他器官其他器官OrganFunction器官功能Time时间Respiratory呼吸Cardiovascular心血管Nausea +Vomiting恶心和呕吐Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auRange of recovery恢复的范围恢复的范围OrganFunction器官功能T

4、ime时间Expectation期望值Range范围Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auCan anaesthetics cause harm?麻醉是有害的吗？麻醉是有害的吗？HarmProtectionAnaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auDo you practice anaesthesia with the firm belief, that when you swit

5、ch off the anaesthetic, that the effects are fully reversible and that no harm is done to the patients?实施麻醉时您是否坚信在停药后麻醉药物的影响是否可以完全逆转而对病人没有伤害？Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auIf you said yes then why do we get如果你的回答是如果你的回答是“YES”，那么为什么我，那么为什么我们还会遇到们还会遇到. prolon

6、ged nausea and vomiting 术后长时间的恶心和呕吐 agitation躁动 disorientation定向障碍 postoperative cognitive dysfunction (POCD)术后认知功能障碍 sometimes prolonged hypotension有时发生长时间的低血压 cases of good versus bad recovery患者恢复有好有坏Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auWhat we do know我们所知的：我们所

7、知的： Anaesthetics alone can cause POCD in mice after repeated exposure反复使用麻醉药这一单一因素即可导致小鼠术后认知功能的障碍 Anaesthetics can alter hippocampal gene expression lasting weeks, indicating that longer term intracellular changes occurs麻醉药能够持续数周改变海马基因的表达，提示发生了远期的细胞内改变Bianchi SL, Tran T, Liu C et al. Brain and behav

8、ior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 2007.Culley DJ, Yukhananov RY, Xie Z et al. Altered hippocampal gene expression 2 days after general anesthesia in rats. Eur J Pharmacol 2006;549:71-8.Anaesthesia and Pain Management Unit; Cardiovascula

9、r Therapeutics UnitH.auWhat we dont know- what is the trigger for harm我们不知道的我们不知道的 导致伤害的诱因导致伤害的诱因是什么？是什么？ Drug药物 Dose剂量 Depth麻醉深度 Duration用药时间 Repeated exposure反复用药 Patient susceptibility病人的易感性 Importance of co-morbidities并存疾病的重要性 Are all anaesthetics equal?所有的麻醉药都一样吗？Anaesthesia and Pain Management

10、 Unit; Cardiovascular Therapeutics UnitH.auAre all anaesthetics all equal?所有的麻醉药都一样吗？所有的麻醉药都一样吗？Harm伤害伤害Protection保护保护Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auWe should not assume that all anaesthetics are equal, nor should we assume that all drugs from the same clas

11、s are the same既不能假设所有的麻醉药是一样的，也不应该假既不能假设所有的麻醉药是一样的，也不应该假设同类药物中所有的药是相同的设同类药物中所有的药是相同的HarmProtection?Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auExample - effect on contractility举例举例 对心肌收缩力的影响对心肌收缩力的影响Royse CF, Liew DF, Wright CE et al. Persistent depression of contractil

12、ity and vasodilation with propofol but not with sevoflurane or desflurane in rabbits. Anesthesiology 2008;108:87-93Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auExample- effect on MAP举例举例 对平均动脉压的影响对平均动脉压的影响Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics

13、UnitH.auConcept of organ protection器官保护的概念器官保护的概念 Requires a potential organ injury存在潜在的器官损害因素 Ischaemia and reperfusion缺血和再灌注 Trauma创伤 Chemical / drug toxicity化学/药物毒性 Different organs may have different effects对不同的器官可能有不同的影响 Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.au

14、Model of organ protection Drugs withno organ protection器官保护药物本身并无器官保护药物本身并无直接的器官保护作用：模型说明直接的器官保护作用：模型说明OrganFunction器官功能Time时间OrganInsult器官损伤Drug that causesHarm造成伤害的药物Drug with minimalHarm造成伤害很小的药物Perceived organ protection表现出（相对的）器官保护作用Anaesthesia and Pain Management Unit; Cardiovascular Therapeut

15、ics UnitH.auOrgan protection器官保护器官保护OrganFunction器官功能Time时间OrganInsult器官伤害Actual Organ Protection实际的器官保护Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auOrgan protection器官保护器官保护Harm伤害伤害Protection保护保护Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.au M

16、echanisms机制机制Organ Protection器官保护器官保护 receptor effects受体效应 stabilize mitochondrial membranes稳定线粒体膜 preserved membrane integrity保护膜的完整性lower oxygen consumption降低氧耗free radicalScavenging清除自由基 reduce inflammatory cascades 减轻多级炎症反应Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.a

17、uReceptors受体受体 Protective volatiles保护性的（挥发性气体） ATPase K+ iNOS dependent Modulation of glutamate transport谷氨酸盐的转运调节 GABA (A) 2PK+ channels (TREK-1)* Adenosine A1 Protective propofol保护性（丙泊酚） Glutamate uptake 谷氨酸盐的摄取(propofol) Antioxidant action抗氧化反应 Preserves function of Na+/H+ exchanger维护Na+/H+ 泵的功能

18、GABA (A)Zheng S, Zuo Z. Neuroscience 2003;118:99-106.Heurteaux C, Guy N, Laigle C et al. Embo J 2004;23:2684-95.Liu C, Cotten JF, Schuyler JA et al. Brain Res 2005;1031:164-73.Bickler PE, Fahlman CS. Anesth Analg 2006;103:419-29, table of contents.Zhan X, Fahlman CS, Bickler PE. Anesthesiology 2006;

19、104:995-1003.Haelewyn B, Yvon A, Hanouz JL et al. Br J Anaesth 2003;91:390-6.Velly LJ, Guillet BA, Masmejean FM et al. Anesthesiology 2003;99:368-75.Young Y, Menon DK, Tisavipat N et al. Eur J Anaesthesiol 1997;14:320-6Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auOrgan P

20、rotection - what we do know器官保护器官保护 我们知道什么我们知道什么Good human and animal evidence for cardiac protection during ischaemia and reperfusion with volatile anaesthetics人体和动物试验均证明了挥发性麻醉药在缺血和再灌注时对心肌的保护作用 All anaesthetics reduce oxygen consumption所有的麻醉药都会降低氧耗 Animal evidence for reduction in stroke size with

21、volatile anaesthetics动物试验证明吸入麻醉药降低脑梗塞的范围 Very little data on other injury types对于其他类型伤害的保护功能尚无足够数据支持 e.g. trauma, drug toxicity例如，创伤，药物中毒Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auCardiac protection - fact or fiction?心脏保护 事实还是神话？ “I have used propofol and I have used v

22、olatiles-and I cant tell the difference in my cardiac patients. I dont believe that volatiles are cardiac protective!” Quote from a colleague of mine!“我使用了丙泊酚，也使用了挥发性麻醉药，在我的心脏手术病人中我无法说出有什么不同。我不相信挥发性麻醉药有心肌保护的作用！”-这是我一个同事的看法Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auDe H

23、ert studies suggestive of similar effect between sevoflurane and desfluraneDe Hert的研究提示地氟烷和七氟烷具有相似的效果的研究提示地氟烷和七氟烷具有相似的效果De Hert SG, Cromheecke S, ten Broecke PW et al. Anesthesiology 2003;99:314-23.De Hert SG, Van der Linden PJ, Cromheecke S et al. Anesthesiology 2004;101:9-20. Anaesthesia and Pain

24、Management Unit; Cardiovascular Therapeutics UnitH.auData from my lab (Dr David Andrews PhD student)本实验室数据本实验室数据Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.au Methods方法方法Randomisation随机化New Zealand White rabbits 新西兰白兔(n=48)Received one of three different anaesthetic agent

25、s接受其以下麻醉药品中的一种propofol 丙泊酚(70 mg/kg/h)desflurane 地氟烷(8.9%)sevoflurane 七氟烷(3.8%)Within each anaesthetic group - further randomisation在每个麻醉组中，进一步随机实施ISR perfusion protocol ISR再灌注方案non-ischaemic time-matched control (TC) perfusion protocol非缺血性时间匹配对照再关注方案Anaesthesia and Pain Management Unit; Cardiovascu

26、lar Therapeutics UnitH.au Methods方法方法Perfusion Protocol 再灌注方案Ischaemia-reperfusion protocol 缺血-再灌注方案Temporary occlusion of the left anterior descending (LAD) coronary artery for 30 min followed by reperfusion for 120 min暂时性阻断左前降支动脉血管30分钟，然后再灌注120分钟Time control protocol时间对照方案Anaesthetised with the co

27、rresponding anaesthetic for 150 min without ischaemia being induced根据相应的麻醉药品进行麻醉150分钟，不诱导缺血Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.au Animal data: Infarct / area at risk动物数据：梗死动物数据：梗死/受累区域受累区域Evans Blue伊文思蓝伊文思蓝Not at risk没有危险没有危险TTC stainTTC染色染色 Small AMI小面积急性心肌梗死小面积急

28、性心肌梗死TTC StainTTC染色染色Large AMI大面积急性心肌梗死大面积急性心肌梗死Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auResults area at risk发生缺血危险的区域发生缺血危险的区域SevofluranePropofolDesflurane0255075100Anaesthetic AgentSevofluranePropofolDesflurane0255075100Anaesthetic AgentAAR (%LV)Anaesthesia and Pai

29、n Management Unit; Cardiovascular Therapeutics UnitH.auInfarct size / Area of risk梗死面积梗死面积/受累范围受累范围SevofluranePropofolDesflurane0255075100Anaesthetic AgentSevofluranePropofolDesflurane0255075100*Anaesthetic AgentInfarct Size (%AAR)Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics Uni

30、tH.auAnaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auAnaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auAnaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auTake home message提示提示 Even though you may not detect any difference durin

31、g the operation, the anaesthetic that you choose may prevent programmed cell death, and make a difference to long term myocardial function尽管在手术中没有发现任何的区别，您选择的麻醉药仍可能会预防程序性的细胞死亡，对远期的心肌功能保护有很大的意义Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auOther organs (mainly animal eviden

32、ce)其他器官（主要是动物试验验证）其他器官（主要是动物试验验证） Ischaemia and Reperfusion缺血和再灌注 Volatiles better for lungs, kidney, brain对肺、肾脏和脑而言，挥发性吸入麻醉药较好 Concern of renal toxicity with sevoflurane - prevalent in rats but not humans对七氟烷造成的肾毒性的考虑 在大鼠中普遍，但是没有人相关的数据 Inflammation (acid damage/toxins/MODS)炎症（酸中毒损害/毒素类/多器官功能不全） Pro

33、pofol丙泊酚 volatiles 挥发性吸入麻醉药(presumed antioxidant可能存在的抗氧化作用) Trauma - no good data yet 创伤 尚无较有力的数据Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auCombinations - propofol + volatile?联合联合 丙泊酚丙泊酚+吸入麻醉药？吸入麻醉药？ No data on the harm/protection with a combination vs. each agent没有数据比

34、较过联合用药比单独用药在脏器伤害/保护作用方面的差异 We do not know enough to decide if there is a difference in harm between the drugs尚无足够证据证明不同药物（吸入和静脉麻醉药物）对脏器功能的损害确实存在区别 We do know that in the setting of myocardial ischaemia, sevoflurane or desflurane will be protective已确证在心肌缺血的状态下，七氟烷和地氟烷具有心肌保护作用Anaesthesia and Pain Mana

35、gement Unit; Cardiovascular Therapeutics UnitH.auCombination: consequences during IR联合用药：在联合用药：在IR的后果的后果 Best possibility最好的可能: Propofol does not prevent cardioprotection from the volatile (does no harm), and丙泊酚不能阻止吸入麻醉药的心脏保护作用 That 1/2 MAC volatile = 1 MAC Volatile in efficacy 合用时 MAC吸入麻醉药的心肌保护作用等于

36、单独使用1个MAC吸入麻醉药的心肌保护作用 Worst possibility最坏的可能: Propofol blocks cardioprotection of volatile丙泊酚阻止了吸入麻醉药的心脏保护作用 1/2 MAC volatile is ineffective vs. 1 MAC 合用时 MAC吸入麻醉药的心肌保护作用低于单独使用1个MAC吸入麻醉药时的心肌保护作用Anaesthesia and Pain Management Unit; Cardiovascular Therapeutics UnitH.auWhat do I do我的做法我的做法In the absen

37、ce of good data, I know that a volatile anaesthetic will be cardioprotective in cases of potential ischaemia - therefore I avoid propofol to allow me to deliver a “full dose” of volatile虽然尚缺乏有力数据（证明吸入麻醉药优于静脉麻醉药），但如果有潜在的缺血发生时，吸入麻醉药是有心肌保护的作用的 因此，我会避免使用丙泊酚，而是“给足”吸入麻醉药的剂量Anaesthesia and Pain Management

38、Unit; Cardiovascular Therapeutics UnitH.auConclusions结论结论 Organ protection is a balance between harm and protection器官的保护是伤害和保护的一个平衡 Good evidence of cardiac protection for ischaemia and reperfusion在缺血和再灌注方面有很好的数据证明心脏的保护作用 Similar mechanisms are likely for different organs对不同的器官其保护机制是相似的 Emerging data for other organs有关其他器官的数据也逐渐出现 Brain protection may yet be the most important effect 脑保护还是最重要的影响