麻醉與器官保護(hù)課件

Anesthesia&OrganProtection

麻醉與器官保護(hù)麻醉與器官保護(hù)OrganFunction器官功能Time時(shí)間EffectsofAnaesthesiaonOrganFunction

麻醉對(duì)于器官功能的影響Liver肝臟KidneyGut腎臟，消化道Vascularresistance血管阻力Contractility收縮力Respiration呼吸Consciousness意識(shí)麻醉與器官保護(hù)Aretheeffectsreversible-e.g.brain?

這些影響可逆轉(zhuǎn)嗎–例如：腦？OrganFunction器官功能Time時(shí)間Eyeopening睜眼Orientation定向Emotional情感Cognitive認(rèn)知麻醉與器官保護(hù)Recoverydifferences-otherorgans

恢復(fù)的差別–其他器官OrganFunction器官功能Time時(shí)間Respiratory呼吸Cardiovascular心血管Nausea+Vomiting惡心和嘔吐麻醉與器官保護(hù)Rangeofrecovery

恢復(fù)的范圍OrganFunction器官功能Time時(shí)間Expectation期望值Range范圍麻醉與器官保護(hù)Cananaestheticscauseharm?

麻醉是有害的嗎？HarmProtection麻醉與器官保護(hù)Doyoupracticeanaesthesiawiththefirmbelief,thatwhenyouswitchofftheanaesthetic,thattheeffectsarefullyreversibleandthatnoharmisdonetothepatients?

實(shí)施麻醉時(shí)您是否堅(jiān)信在停藥后麻醉藥物的影響是否可以完全逆轉(zhuǎn)而對(duì)病人沒(méi)有傷害？麻醉與器官保護(hù)Ifyousaidyes…thenwhydoweget………

如果你的回答是“YES”，那么為什么我們還會(huì)遇到……..

prolongednauseaandvomiting術(shù)后長(zhǎng)時(shí)間的惡心和嘔吐agitation躁動(dòng)disorientation定向障礙postoperativecognitivedysfunction(POCD)術(shù)后認(rèn)知功能障礙sometimesprolongedhypotension有時(shí)發(fā)生長(zhǎng)時(shí)間的低血壓casesofgoodversusbadrecovery患者恢復(fù)有好有壞麻醉與器官保護(hù)Whatwedoknow

我們所知的：AnaestheticsalonecancausePOCDinmiceafterrepeatedexposure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(rèn)知功能的障礙Anaestheticscanalterhippocampalgeneexpressionlastingweeks,indicatingthatlongertermintracellularchangesoccurs麻醉藥能夠持續(xù)數(shù)周改變海馬基因的表達(dá)，提示發(fā)生了遠(yuǎn)期的細(xì)胞內(nèi)改變BianchiSL,TranT,LiuCetal.Brainandbehaviorchangesin12-month-oldTg2576andnontransgenicmiceexposedtoanesthetics.NeurobiolAging2007.CulleyDJ,YukhananovRY,XieZetal.Alteredhippocampalgeneexpression2daysaftergeneralanesthesiainrats.EurJPharmacol2006;549:71-8.麻醉與器官保護(hù)Whatwedon’tknow-whatisthetriggerforharm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(shí)間Repeatedexposure反復(fù)用藥Patientsusceptibility病人的易感性Importanceofco-morbidities并存疾病的重要性Areallanaestheticsequal???所有的麻醉藥都一樣嗎？麻醉與器官保護(hù)Areallanaestheticsallequal?

所有的麻醉藥都一樣嗎？Harm傷害Protection保護(hù)麻醉與器官保護(hù)Weshouldnotassumethatallanaestheticsareequal,norshouldweassumethatalldrugsfromthesameclassarethesame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HarmProtection??麻醉與器官保護(hù)Example-effectoncontractility

舉例–對(duì)心肌收縮力的影響RoyseCF,LiewDF,WrightCEetal.Persistentdepressionofcontractility

andvasodilationwithpropofolbutnotwithsevofluraneordesflurane

inrabbits.Anesthesiology2008;108:87-93麻醉與器官保護(hù)Example-effectonMAP

舉例–對(duì)平均動(dòng)脈壓的影響麻醉與器官保護(hù)Conceptoforganprotection

器官保護(hù)的概念Requiresapotentialorganinjury存在潛在的器官損害因素Ischaemiaandreperfusion缺血和再灌注Trauma創(chuàng)傷Chemical/drugtoxicity化學(xué)/藥物毒性Differentorgansmayhavedifferenteffects對(duì)不同的器官可能有不同的影響

麻醉與器官保護(hù)ModeloforganprotectionDrugswith

noorganprotection器官保護(hù)藥物本身并無(wú)直接的器官保護(hù)作用：模型說(shuō)明OrganFunction器官功能Time時(shí)間OrganInsult器官損傷DrugthatcausesHarm造成傷害的藥物DrugwithminimalHarm造成傷害很小的藥物Perceivedorganprotection表現(xiàn)出（相對(duì)的）器官保護(hù)作用麻醉與器官保護(hù)Organprotection器官保護(hù)OrganFunction器官功能Time時(shí)間OrganInsult器官傷害ActualOrganProtection實(shí)際的器官保護(hù)麻醉與器官保護(hù)Organprotection器官保護(hù)Harm傷害 Protection保護(hù)麻醉與器官保護(hù)Mechanisms機(jī)制OrganProtection器官保護(hù)

receptoreffects受體效應(yīng)stabilizemitochondrialmembranes穩(wěn)定線粒體膜preservedmembraneintegrity保護(hù)膜的完整性loweroxygenconsumption降低氧耗freeradicalScavenging清除自由基

reduceinflammatorycascades減輕多級(jí)炎癥反應(yīng)麻醉與器官保護(hù)Receptors受體Protectivevolatiles保護(hù)性的（揮發(fā)性氣體）ATPaseK+iNOSdependentModulationofglutamatetransport谷氨酸鹽的轉(zhuǎn)運(yùn)調(diào)節(jié)GABA(A)2PK+channels(TREK-1)*AdenosineA1Protectivepropofol保護(hù)性（丙泊酚）Glutamateuptake谷氨酸鹽的攝取(propofol)Antioxidantaction抗氧化反應(yīng)PreservesfunctionofNa+/H+exchanger維護(hù)Na+/H+泵的功能GABA(A)ZhengS,ZuoZ.Neuroscience2003;118:99-106.HeurteauxC,GuyN,LaigleCetal.EmboJ2004;23:2684-95.LiuC,CottenJF,SchuylerJAetal.BrainRes2005;1031:164-73.BicklerPE,FahlmanCS.AnesthAnalg2006;103:419-29,tableofcontents.ZhanX,FahlmanCS,BicklerPE.Anesthesiology2006;104:995-1003.HaelewynB,YvonA,HanouzJLetal.BrJAnaesth2003;91:390-6.VellyLJ,GuilletBA,MasmejeanFMetal.Anesthesiology2003;99:368-75.YoungY,MenonDK,TisavipatNetal.EurJAnaesthesiol1997;14:320-6麻醉與器官保護(hù)OrganProtection-whatwedoknow

器官保護(hù)–我們知道什么Goodhumanandanimalevidenceforcardiacprotectionduringischaemiaandreperfusionwithvolatileanaesthetics人體和動(dòng)物試驗(yàn)均證明了揮發(fā)性麻醉藥在缺血和再灌注時(shí)對(duì)心肌的保護(hù)作用Allanaestheticsreduceoxygenconsumption所有的麻醉藥都會(huì)降低氧耗Animalevidenceforreductioninstrokesizewithvolatileanaesthetics動(dòng)物試驗(yàn)證明吸入麻醉藥降低腦梗塞的范圍Verylittledataonotherinjurytypes對(duì)于其他類型傷害的保護(hù)功能尚無(wú)足夠數(shù)據(jù)支持e.g.trauma,drugtoxicity例如，創(chuàng)傷，藥物中毒麻醉與器官保護(hù)Cardiacprotection-factorfiction?

心臟保護(hù)–事實(shí)還是神話？“IhaveusedpropofolandIhaveusedvolatiles-andIcan’ttellthedifferenceinmycardiacpatients.Idon’tbelievethatvolatilesarecardiacprotective!”Quotefromacolleagueofmine!“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(wú)法說(shuō)出有什么不同。我不相信揮發(fā)性麻醉藥有心肌保護(hù)的作用！”----這是我一個(gè)同事的看法麻醉與器官保護(hù)DeHertstudiessuggestiveofsimilareffectbetweensevofluraneanddesflurane

DeHert的研究提示地氟烷和七氟烷具有相似的效果DeHertSG,CromheeckeS,tenBroeckePWetal.Anesthesiology2003;99:314-23.DeHertSG,VanderLindenPJ,CromheeckeSetal.Anesthesiology2004;101:9-20.麻醉與器官保護(hù)Datafrommylab(DrDavidAndrewsPhDstudent)

本實(shí)驗(yàn)室數(shù)據(jù)麻醉與器官保護(hù)Methods方法Randomisation隨機(jī)化NewZealandWhiterabbits新西蘭白兔(n=48)Receivedoneofthreedifferentanaestheticagents接受其以下麻醉藥品中的一種propofol丙泊酚(70mg/kg/h)desflurane地氟烷(8.9%)sevoflurane七氟烷(3.8%)Withineachanaestheticgroup-furtherrandomisation在每個(gè)麻醉組中，進(jìn)一步隨機(jī)實(shí)施ISRperfusionprotocolISR再灌注方案non-ischaemictime-matchedcontrol(TC)perfusionprotocol非缺血性時(shí)間匹配對(duì)照再關(guān)注方案麻醉與器官保護(hù)Methods方法PerfusionProtocol再灌注方案Ischaemia-reperfusionprotocol缺血-再灌注方案Temporaryocclusionoftheleftanteriordescending(LAD)coronaryarteryfor30minfollowedbyreperfusionfor120min暫時(shí)性阻斷左前降支動(dòng)脈血管30分鐘，然后再灌注120分鐘Timecontrolprotocol時(shí)間對(duì)照方案Anaesthetisedwiththecorrespondinganaestheticfor150minwithoutischaemiabeinginduced根據(jù)相應(yīng)的麻醉藥品進(jìn)行麻醉150分鐘，不誘導(dǎo)缺血麻醉與器官保護(hù)Animaldata:Infarct/areaatrisk

動(dòng)物數(shù)據(jù)：梗死/受累區(qū)域EvansBlue伊文思藍(lán)Notatrisk沒(méi)有危險(xiǎn)TTCstainTTC染色

SmallAMI小面積急性心肌梗死TTCStainTTC染色LargeAMI大面積急性心肌梗死麻醉與器官保護(hù)Resultsareaatrisk

發(fā)生缺血危險(xiǎn)的區(qū)域麻醉與器官保護(hù)Infarctsize/Areaofrisk

梗死面積/受累范圍麻醉與器官保護(hù)麻醉與器官保護(hù)麻醉與器官保護(hù)麻醉與器官保護(hù)Takehomemessage

提示Eventhoughyoumaynotdetectanydifferenceduringtheoperation,theanaestheticthatyouchoosemaypreventprogrammedcelldeath,andmakeadifferencetolongtermmyocardialfunction盡管在手術(shù)中沒(méi)有發(fā)現(xiàn)任何的區(qū)別，您選擇的麻醉藥仍可能會(huì)預(yù)防程序性的細(xì)胞死亡，對(duì)遠(yuǎn)期的心肌功能保護(hù)有很大的意義麻醉與器官保護(hù)Otherorgans(mainlyanimalevidence)

其他器官（主要是動(dòng)物試驗(yàn)驗(yàn)證）IschaemiaandReperfusion缺血和再灌注Volatilesbetterforlungs,kidney,brain對(duì)肺、腎臟和腦而言，揮發(fā)性吸入麻醉藥較好Concernofrenaltoxicitywithsevoflurane-prevalentinratsbutnothumans對(duì)七氟烷造成的腎毒性的考慮–在大鼠中普遍，但是沒(méi)有人相關(guān)的數(shù)據(jù)Inflammation(aciddamage/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(presumedantioxidant可能存在的抗氧化作用)Trauma-nogooddatayet創(chuàng)傷–尚無(wú)較有力的數(shù)據(jù)麻醉與器官保護(hù)Combinations-propofol+volatile?

聯(lián)合–丙泊酚+吸入麻醉藥？Nodataontheharm/protectionwithacombinationvs.eachagent沒(méi)有數(shù)據(jù)比較過(guò)聯(lián)合用藥比單獨(dú)用藥在臟器傷害/保護(hù)作用方面的差異Wedonotknowenoughtodecideifthereisadifferenceinharmbetweenthedrugs尚無(wú)足夠證據(jù)證明不同藥物（吸入和靜脈麻醉藥物）對(duì)臟器功能的損害確實(shí)存在區(qū)別Wedoknowthatinthesettingofmyocardialischaemia,sevofluraneordesfluranewillbeprotective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(hù)作用麻醉與器官保護(hù)Combination:consequencesduringIR

聯(lián)合用藥：在IR的后果Bestpossibility最好的可能:Propofoldoesnotpreventcardioprotectionfromthevolatile(doesnoharm),and丙泊酚不能阻止吸入麻醉藥的心臟保護(hù)作用That1/2MACvolatile=1MACVolatileinefficacy合用時(shí)?MAC吸入麻醉藥的心肌保護(hù)作用等于單獨(dú)使用1個(gè)MAC吸入麻醉藥的心肌保護(hù)作用Worstpossibility最壞的可能:Propo