麻醉與器官保護課件

1、,,Anesthesia & Organ Protection麻醉與器官保護,,,,,,,,OrganFunction器官功能,Time時間,Effects of Anaesthesia on Organ Function麻醉對于器官功能的影響,,Liver肝臟,Kidney Gut腎臟，消化道,,Vascular resistance血管阻力,Contractility收縮力,Respiration呼吸,,Consci

2、ousness意識,,Are the effects reversible - e.g.brain?這些影響可逆轉(zhuǎn)嗎 – 例如：腦？,,,Eye opening睜眼,,Orientation定向,,Emotional情感,,Cognitive認知,,Recovery differences-other organs恢復(fù)的差別 – 其他器官,,Respiratory呼吸,,Cardiovascular心血管,Nausea +Vo

3、miting惡心和嘔吐,Range of recovery恢復(fù)的范圍,,,,OrganFunction器官功能,Time時間,,,,Expectation期望值,Range范圍,Can anaesthetics cause harm?麻醉是有害的嗎？,,,Harm,Protection,Do you practice anaesthesia with the firm belief, that when you switch

4、off the anaesthetic, that the effects are fully reversible and that no harm is done to the patients?實施麻醉時您是否堅信在停藥后麻醉藥物的影響是否可以完全逆轉(zhuǎn)而對病人沒有傷害？,If you said yes… then why do we get………如果你的回答是“YES”，那么為什么我們還會遇到……..,prolonged n

5、ausea and vomiting 術(shù)后長時間的惡心和嘔吐 agitation躁動 disorientation定向障礙 postoperative cognitive dysfunction (POCD)術(shù)后認知功能障礙 sometimes prolonged hypotension有時發(fā)生長時間的低血壓 cases of good versus bad recovery患者恢復(fù)有好有壞,What we do know

6、我們所知的：,Anaesthetics alone can cause POCD in mice after repeated exposure反復(fù)使用麻醉藥這一單一因素即可導(dǎo)致小鼠術(shù)后認知功能的障礙Anaesthetics can alter hippocampal gene expression lasting weeks, indicating that longer term intracellular changes occ

7、urs麻醉藥能夠持續(xù)數(shù)周改變海馬基因的表達，提示發(fā)生了遠期的細胞內(nèi)改變,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

8、et al. Altered hippocampal gene expression 2 days after general anesthesia in rats. Eur J Pharmacol 2006;549:71-8.,What we don’t know- what is the trigger for harm我們不知道的 – 導(dǎo)致傷害的誘因是什么？,Drug藥物Dose劑量Depth麻醉深度Duration用藥時間

9、Repeated exposure反復(fù)用藥Patient susceptibility病人的易感性Importance of co-morbidities并存疾病的重要性Are all anaesthetics equal???所有的麻醉藥都一樣嗎？,Are all anaesthetics all equal?所有的麻醉藥都一樣嗎？,Harm傷害,Protection保護,,,We should not assume tha

10、t all anaesthetics are equal, nor should we assume that all drugs from the same class are the same既不能假設(shè)所有的麻醉藥是一樣的，也不應(yīng)該假設(shè)同類藥物中所有的藥是相同的,,,Harm,Protection,??,Example - effect on contractility舉例 – 對心肌收縮力的影響,Royse CF, Liew D

11、F, 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舉例 – 對平均動脈壓的影響,Concept of

12、 organ protection器官保護的概念,Requires a potential organ injury存在潛在的器官損害因素Ischaemia and reperfusion缺血和再灌注Trauma創(chuàng)傷Chemical / drug toxicity化學/藥物毒性Different organs may have different effects對不同的器官可能有不同的影響,,Model of organ pr

13、otection Drugs withno organ protection器官保護藥物本身并無直接的器官保護作用：模型說明,,,,OrganFunction器官功能,Time時間,OrganInsult器官損傷,,,,Drug that causesHarm造成傷害的藥物,,,,Drug with minimalHarm造成傷害很小的藥物,,,Perceived organ protection表現(xiàn)出（相對的）器官保護作

14、用,Organ protection器官保護,,,,,OrganFunction器官功能,Time時間,OrganInsult器官傷害,,,,,,,,,,,,,,,Actual Organ Protection實際的器官保護,Organ protection器官保護,Harm傷害Protection保護,Mechanisms機制,Organ Protection器官保護,receptor effects受體效應(yīng) st

15、abilize mitochondrial membranes穩(wěn)定線粒體膜 preserved membrane integrity保護膜的完整性,lower oxygen consumption降低氧耗,free radicalScavenging清除自由基,reduce inflammatory cascades 減輕多級炎癥反應(yīng),,,,,Receptors受體,Protective volatiles保護性的（揮發(fā)

16、性氣體）ATPase K+iNOS dependentModulation of glutamate transport谷氨酸鹽的轉(zhuǎn)運調(diào)節(jié)GABA (A)2PK+ channels (TREK-1)*Adenosine A1,Protective propofol保護性（丙泊酚）Glutamate uptake 谷氨酸鹽的攝取(propofol)Antioxidant action抗氧化反應(yīng)Preserves func

17、tion of Na+/H+ exchanger維護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.Bi

18、ckler 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

19、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器官保護 – 我們知道什么,Good human and animal evidence for cardiac pr

20、otection during ischaemia and reperfusion with volatile anaesthetics人體和動物試驗均證明了揮發(fā)性麻醉藥在缺血和再灌注時對心肌的保護作用 All anaesthetics reduce oxygen consumption所有的麻醉藥都會降低氧耗 Animal evidence for reduction in stroke size with volatile

21、anaesthetics動物試驗證明吸入麻醉藥降低腦梗塞的范圍 Very little data on other injury types對于其他類型傷害的保護功能尚無足夠數(shù)據(jù)支持 e.g. trauma, drug toxicity例如，創(chuàng)傷，藥物中毒,Cardiac protection - fact or fiction?心臟保護 – 事實還是神話？,“I have used propofol and I have use

22、d volatiles-and I can’t tell the difference in my cardiac patients. I don’t believe that volatiles are cardiac protective!” Quote from a colleague of mine!“我使用了丙泊酚，也使用了揮發(fā)性麻醉藥，在我的心臟手術(shù)病人中我無法說出有什么不同。我不相信揮發(fā)性麻醉藥有心肌保護的作用！”

23、----這是我一個同事的看法,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 de

24、r Linden PJ, Cromheecke S et al. Anesthesiology 2004;101:9-20.,Data from my lab (Dr David Andrews PhD student)本實驗室數(shù)據(jù),Methods方法,Randomisation隨機化New Zealand White rabbits 新西蘭白兔(n=48)Received one of three different anaes

25、thetic agents接受其以下麻醉藥品中的一種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在每個麻醉組中，進一步隨機實施ISR perfusion protocol ISR再灌注方案non-ischaemic time-match

26、ed control (TC) perfusion protocol非缺血性時間匹配對照再關(guān)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 b

27、y reperfusion for 120 min暫時性阻斷左前降支動脈血管30分鐘，然后再灌注120分鐘Time control protocol時間對照方案Anaesthetised with the corresponding anaesthetic for 150 min without ischaemia being induced根據(jù)相應(yīng)的麻醉藥品進行麻醉150分鐘，不誘導(dǎo)缺血,Animal data: Infarct

28、/ area at risk動物數(shù)據(jù)：梗死/受累區(qū)域,Evans Blue伊文思藍Not at risk沒有危險,TTC stainTTC染色 Small AMI小面積急性心肌梗死,TTC StainTTC染色Large AMI大面積急性心肌梗死,Results area at risk發(fā)生缺血危險的區(qū)域,Infarct size / Area of risk梗死面積/受累范圍,Take home message

29、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盡管在手術(shù)中沒有發(fā)現(xiàn)任何的區(qū)別，您選擇的麻醉藥仍可

30、能會預(yù)防程序性的細胞死亡，對遠期的心肌功能保護有很大的意義,Other organs (mainly animal evidence)其他器官（主要是動物試驗驗證）,Ischaemia and Reperfusion缺血和再灌注Volatiles better for lungs, kidney, brain對肺、腎臟和腦而言，揮發(fā)性吸入麻醉藥較好Concern of renal toxicity with sevoflurane

31、 - prevalent in rats but not humans對七氟烷造成的腎毒性的考慮 – 在大鼠中普遍，但是沒有人相關(guān)的數(shù)據(jù)Inflammation (acid damage/toxins/MODS)炎癥（酸中毒損害/毒素類/多器官功能不全）Propofol丙泊酚 > volatiles 揮發(fā)性吸入麻醉藥(presumed antioxidant可能存在的抗氧化作用)Trauma - no good data y

32、et 創(chuàng)傷 – 尚無較有力的數(shù)據(jù),Combinations - propofol + volatile?聯(lián)合 – 丙泊酚+吸入麻醉藥？,No data on the harm/protection with a combination vs. each agent沒有數(shù)據(jù)比較過聯(lián)合用藥比單獨用藥在臟器傷害/保護作用方面的差異We do not know enough to decide if there is a differenc

33、e in harm between the drugs尚無足夠證據(jù)證明不同藥物（吸入和靜脈麻醉藥物）對臟器功能的損害確實存在區(qū)別We do know that in the setting of myocardial ischaemia, sevoflurane or desflurane will be protective已確證在心肌缺血的狀態(tài)下，七氟烷和地氟烷具有心肌保護作用,Combination: consequences

34、during IR聯(lián)合用藥：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藥的心臟保護作用That 1/2 MAC volatile = 1 MAC Volatile in efficacy 合用時

35、½ MAC吸入麻醉藥的心肌保護作用等于單獨使用1個MAC吸入麻醉藥的心肌保護作用Worst possibility最壞的可能:Propofol blocks cardioprotection of volatile丙泊酚阻止了吸入麻醉藥的心臟保護作用1/2 MAC volatile is ineffective vs. 1 MAC 合用時½

36、 MAC吸入麻醉藥的心肌保護作用低于單獨使用1個MAC吸入麻醉藥時的心肌保護作用,What do I do我的做法,In the absence of good data, I know that a volatile anaesthetic will be cardioprotective in cases of potential ischaemia - therefore I avoid propofol to allow me

37、 to deliver a “full dose” of volatile雖然尚缺乏有力數(shù)據(jù)（證明吸入麻醉藥優(yōu)于靜脈麻醉藥），但如果有潛在的缺血發(fā)生時，吸入麻醉藥是有心肌保護的作用的 – 因此，我會避免使用丙泊酚，而是“給足”吸入麻醉藥的劑量,Conclusions結(jié)論,Organ protection is a balance between harm and protection器官的保護是傷害和保護的一個平衡Good evid

38、ence of cardiac protection for ischaemia and reperfusion在缺血和再灌注方面有很好的數(shù)據(jù)證明心臟的保護作用Similar mechanisms are likely for different organs對不同的器官其保護機制是相似的Emerging data for other organs有關(guān)其他器官的數(shù)據(jù)也逐漸出現(xiàn)Brain protection may yet be