麻醉与器官保护.ppt

1、,Anesthesia 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

2、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 co

3、ntractility 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 toxi

4、city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,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,Org

5、an protection器官保护,Organ Function 器官功能,Time时间,Organ Insult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,fre

6、e radical Scavenging 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 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 ac

7、tion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, tabl

8、e 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 Prot

9、ection - 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 ana

10、esthetics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 v

11、olatiles 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. Anesth

12、esiology 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

13、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

14、-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

15、,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,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 op

16、eration, 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, k

17、idney, 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

18、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 o

19、f 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 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