麻醉与器官保护

,Anesthesia & Organ Protection麻醉与器官保护,OrganFunction器官功能,Time时间,Effects of Anaesthesia on Organ Function麻醉对于器官功能的影响,Liver肝脏,Kidney Gut肾脏，消化道,Vascular resistance血管阻力,Contractility收缩力,Respiration呼吸,Consciousness意识,Are the effects reversible - e.g.brain?这些影响可逆转吗 例如：脑？,Eye opening睁眼,Orientation定向,Emotional情感,Cognitive认知,Recovery differences-other organs恢复的差别 其他器官,Respiratory呼吸,Cardiovascular心血管,Nausea +Vomiting恶心和呕吐,Range of recovery恢复的范围,OrganFunction器官功能,Time时间,Expectation期望值,Range范围,Can anaesthetics cause harm?麻醉是有害的吗？,Harm,Protection,Do you practice anaesthesia with the firm belief, that 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？,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.,prolonged 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,What we do know我们所知的：,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 behavior 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.,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？,Are all anaesthetics all equal?所有的麻醉药都一样吗？,Harm伤害,Protection保护,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，也不应该假设同类药物中所有的药是相同的,Harm,Protection,?,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 with sevoflurane or desflurane in rabbits. Anesthesiology 2008;108:87-93,Example- effect on MAP举例 对平均动脉压的影响,Concept of organ protection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,Model of organ protection Drugs withno organ protection器官保护药物本身并无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,Organ protection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,Organ protection器官保护,Harm伤害Protection保护,Mechanisms机制,Organ Protection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,Receptors受体,Protective volatiles保护性的（挥发性气体）ATPase K+iNOS dependentModulation 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.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;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;14:320-6,Organ Protection - what we do know器官保护 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 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,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 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,De Hert 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,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.,Data from my lab (Dr David Andrews PhD student)本实验室数据,Methods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 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,Methods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 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,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 stainTTC染色 Small AMI小面积急性心肌梗死,TTC StainTTC染色Large AMI大面积急性心肌梗死,Results area at risk发生缺血危险的区域,Infarct size / Area of risk梗死面积/受累范围,Take home message提示,Even though you may not detect any difference during 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,Other organs (mainly animal evidence)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）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 尚无较有力的数据,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 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,Combination: consequences during IR联合用药：在IR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单独使用1个MAC吸入麻醉药的心肌保护作用Worst possibil