1、Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Anesthesia&Organ Protection 麻醉与器官保护 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Organ Function 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，消
2、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 Unit H.au Are the effects reversible-e.g.brain?这些影响可逆转吗 例如：脑？Organ Function 器官功能 Time时间 Eye opening睁眼 Orientation定向 Emotional情感 Cognitive认知 Anaesthesia and P
3、ain Management Unit;Cardiovascular Therapeutics Unit H.au Recovery differences-other organs 恢复的差别 其他器官 Organ Function 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 Unit H.au Range of recovery 恢复的范围恢复的范围 Organ Funct
4、ion 器官功能 Time时间 Expectation 期望值 Range范围 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Can anaesthetics cause harm?麻醉是有害的吗？麻醉是有害的吗？Harm Protection Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Do you practice anaesthesia with the firm belief,t
5、hat when you switch 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 Unit H.au If you said yes then why do we get 如果你的回答是“YES”，那么为什么我们还会遇到.?prolong
6、ed 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 Unit H.au What we do know 我们所知的：我们
7、所知的：?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 behavio
8、r 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;Cardiovascular Therap
9、eutics Unit H.au What we dont know-what is the trigger for harm 我们不知道的 导致伤害的诱因是什么？?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 Unit;Cardiovascular Th
10、erapeutics Unit H.au Are all anaesthetics all equal?所有的麻醉药都一样吗？Harm 伤害 Protection 保护 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au We should not assume that all anaesthetics are equal,nor should we assume that all drugs from the same class are the same既不能假设所有的麻醉药是一样的，也不应
11、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 Harm Protection?Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Example-effect on contractility 举例 对心肌收缩力的影响 Royse CF,Liew DF,Wright CE et al.Persistent depression of contractility and vasodilation with propofol but not w
12、ith sevoflurane or desflurane in rabbits.Anesthesiology 2008;108:87-93 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Example-effect on MAP 举例 对平均动脉压的影响 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Concept of organ protection 器官保护的概念器官保护的概念?R
13、equires 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 Unit H.au Model of organ protection Drugs with no organ prot
14、ection 器官保护药物本身并无直接的器官保护作用：模型说明 Organ Function 器官功能 Time时间 Organ Insult器官损伤 Drug that causes Harm造成伤害的药物 Drug with minimal Harm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 Therapeutics Unit H.au Organ protection器官保护器官保护 Organ Function 器官功能 T
15、ime时间 Organ Insult器官伤害 Actual Organ Protection 实际的器官保护 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Organ protection 器官保护 Harm 伤害 Protection 保护 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Mechanisms 机制 Organ Protection 器官保护 receptor effect
16、s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 radical Scavenging 清除自由基 reduce inflammatory cascades 减轻多级炎症反应 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Receptors受体受体?Protective volatiles保护性的（挥发性气体
17、）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 GABA(A)Zheng S,Zuo Z.Neuroscience 2003;118:99-106.Heurte
18、aux 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;104:995-1003.Haelewyn B,Yvon A,Hanouz JL et al.Br J Anaesth 2003;91:390
19、-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;14:320-6 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Organ Protection-what we do know 器官保护 我们知道什么?Good human and animal evidence for cardi
20、ac 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 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
21、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 Unit H.au Cardiac protection-fact or fiction?心脏保护 事实还是神话？“I have used propofol and I have used volatiles-and I cant tell the difference in my cardiac patients.I dont believe that volatile
22、s 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 Unit H.au De Hert studies suggestive of similar effect between sevoflurane and desflurane De Hert的研究提示地氟烷
23、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 Management Unit;Cardiovascular Therapeutics Unit H.au Data from my lab(Dr David Andrews PhD stud
24、ent)本实验室数据 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.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 agents 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 anaest
25、hetic 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;Cardiovascular Therapeutics Unit H.au Methods方法方法 Perfusion Protocol 再灌注方案 Ischaemia-reperfusion protocol 缺血-
26、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 corresponding 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 An
27、aesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Animal data:Infarct/area at risk 动物数据：梗死/受累区域 Evans Blue 伊文思蓝 Not at risk 没有危险 TTC stain TTC染色 Small AMI 小面积急性心肌梗死 TTC Stain TTC 染色 Large AMI 大面积急性心肌梗死 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au
28、Results area at risk 发生缺血危险的区域 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Infarct size/Area of risk 梗死面积/受累范围 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Anaesthe
29、sia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Take home message 提示提示 Even though you may not detect any difference during the operation,the anaesthetic that you choose may prevent programmed cell death,an
30、d 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 Unit H.au Other organs(mainly animal evidence)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 f
31、or 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）Propofol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
32、有力的数据 Anaesthesia and Pain Management Unit;Cardiovascular Therapeutics Unit H.au Combinations-propofol+volatile?联合 丙泊酚+吸入麻醉药？?No data on the harm/protection with a combination vs.each agent没有数据比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 dr
33、ugs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 Management Unit;Cardiovascular Therapeutics Unit H.au Combination:consequences during IR 联合用药：在IR的后果?Best poss
34、ibility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 vo
35、latile 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 Unit H.au What do I do 我的做法我的做法 In the absence of good data,I know that a volatile anaesthetic will be cardioprotective in cases of potential ischaemia-therefo
36、re 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 Unit;Cardiovascular Therapeutics Unit H.au Conclusions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
