INHALATIONALAGENT-俞卫锋

INHALATIONALAGENTWeifengYuDeptofAnesthesia,EHBH1.HistoricalDevelopmentofinhalationalagent2.Pharmacologyofinhalationalagent3.Mechanismsofinhalationalagent4.HepatotoxicityandNephrotoxicityofHalogenatedInhalationalAnaethetics5.SevofluraneisBestVolatileAnestheticeverdevelopedHistoricalDevelopmentunlucky;rough充满坎坷intenseemotion充满激情joysandsorrows，partingsandreunions-vicissitndesoflife悲欢离合TofinishoperationPressingpatientShorteningtimeDrinkingalcoholicbeveragesBleedingBoxinglowerjaw外科手术犹如酷刑，因此病人宁愿去死，也不愿接受外科手术治疗当年截肢手术时使用的工具Dec.10th,1844Laughing,Sing,Dance,SpeakorFight当天晚会上发生的一件事触动了牙医HoraceWells(1815-1848)SamCooley在笑气的作用下受伤了……JohnMRiggs帮助Wells拔掉了龋齿Wells清醒后的第一句话是：Aneweraintooth–pulling!Wells兴冲冲找到JohnC.WarrenJan.10th,1845病人与其他人一样发出尖叫人们永远无法忘记回荡在麻省总院圆顶演示手术室内“Humbug”的叫喊面对Wells的失败，人们不禁想起几年前著名的外科医生Velpeau的“著名”论断：Eviterladouleurdanslesoperationsestunechimerequ’iln’estpaspermisdepoursuivreaujourd’hui.Instrumentstrachantsetdouleur,enmedecineoperatoire,sontdeuxmotsquinesepresententpointI’unsansI’autreaI’espritdesmalades,etdon’tilfautnecessairementadmettreI’association外科手术必然伴随着疼痛，任何寻找解决外科手术疼痛的努力均是徒劳的不久，Velpeau的预言就被打破了打破Velpeau预言的是另一位牙科医生，他的名字已经被永久地载入了世界医学发展史WilliamT.G.MortonOct,16,1846WilliamThomasGreenMortonEtherDemonstratingMassachusettsGeneralHospitalInhalationAnestheticsDevelopedDIETHYLETHERDIVINYLETHERETHYLVINYLETHERETHYLCHLORIDECYCLOPROPANETRICHLORETHYLENEFLUROXENEMETHOXYFLURANENITROUSOXIDEHALOTHANEENFLURANEISOFLURANEDESFLURANESEVOFLURANEHistoricalDevelopmentETHER1540SynthesizedbyValeriusCordus1846DemonstratedbyWilliamThomasGreenMortonHALOTHANE1951SynthesizedbySukling1956PharmacologicalresearchedbyRaventos1956ClinicalusedbyJohnstoneMETHOXYFLURANE1956SynthesizedbyArtusioandvanPoznak1959ClinicalusedHistoricalDevelopmentENFLURANE1963SynthesizedbyTerrell1963AnimalexperimentedbyKrantz1973ClinicalusedISOFLURANE1965SynthesizedbyTerrell1975AnimalexperimentedbyDobkin,Byles,StevensandEger1981ClinicalusedHistoricalDevelopmentDESFLURANE1959-1966:SynthesizedbyTerrell1990:ClinicalusedbyJohnSEVOFLURANE1968:SynthesizedbyRegan1975:Wallindescribedpharmacologicandtoxicologicalproperties1975:Cook/Mazzedescribedrenalandmetaboliceffectsinanimals.1981:Holadaypublishedphase-1clinicalstudy1984:MaruishiPharmaceuticalspurchaseddrugFDAapproval1994;widelyavailableinUSin19951.HistoricalDevelopmentofinhalationalagent2.Pharmacologyofinhalationalagent3.Mechanismsofinhalationalagent4.HepatotoxicityandNephrotoxicityofHalogenatedInhalationalAnaethetics5.SevofluraneisBestVolatileAnestheticeverdevelopedIdealPropertiesofVolatileAgentsPleasantodour,non-irritanttotheairwayLowbloodgassolubilityChemicallystableinstorageNointeractionwiththeanaestheticcircuitsorsodalimeNeitherflammablenorexplosiveProducingunconciousnesswithanalgesia,preferablywithsomedegreeofmusclerelaxationIdealPropertiesofVolatileAgentsPotentShouldnotbemetabolisedinthebody,nontoxicNoallergicreactionMinimaldepressionofCVSandRSShouldnotinteractwithotherdrugsCompletelyinert,eliminatedcompletelyandrapidlyinunchangedformviathelungsStructureandFunctionalRelationshipHalogenationofhydrocarbonandethersAnaestheticpotencyCardiacarrhythmiaFClBrIEffectofincreasedfluorinesubstitutionWeakanaestheticReducedflammability?increasedstabilityStructureandFunctionalRelationshipIncreasedhalogentoethersleadstoIncreasedconvulsantactivityHalogenationmethylethylethersLeadtomorestableandbetteranaestheticsPharmacokineticsofvolatileagentsPrincipalobjectiveaconstantandoptimalbrainpartialpressureoftheinhaledanaesthetics.EquilibriumPA---Pa---PbrResultthePAistheindirectmeasurementofanaestheticpartialpressureatthebrain.PartialRebreathingSystemGAMACHINEFGFBREATHINGCIRCUITFiFAFaBRAINFactorsaffectingFiTheconcentrationsetonthevaporizerThefreshgasflowrateThevolumeofthebreathingcircuitTheamountofabsorptionbytheanaestheticmachineandbreathingsystemAlveolusUptakeInputbalanceFactorsaffectingFAFiFaFAFactorsaffectingFAInputdependson:1.InspiredconcentrationThehighertheconcentrationthefastertheriseofFA/FIConcentrationeffectSecondgaseffectFactorsaffectingFA2.VentilationIncreasedVAwillincreasethedeliveryofanaesthetictothealveolusHypocarbiareduceddecreaseCBFandreduceddeliveryofagenttobrainTherespiratorydepressanteffectofinhaledagentactasanegativefeedbackFactorsaffectingFAUptakedependson:1.BloodgassolubilityThehigherthebloodgaspartitioncoefficientthegreateritsuptakebythepulmonarycirculation.ThustheriseofFA/FIisslower,sodoesthespeedofinductionandrecovery.FactorsaffectingFA2.Alveolarbloodflow(ie.Cardiacoutput)IntheabsenceofpulmonaryshuntingisessentiallyequaltocardiacoutputIncreasecardiacoutputwillincreaseuptakeofanaestheticagentthusslowtheriseofFA/FIandinductionMyocardialdepressanteffectoftheinhaledanaestheticwillactasapositivefeedbackCalculationoftotalgasuptakeVO2=10xBW(kg)3/4(ml/min)VN20=1000xt-1/2(ml/min)VAN=fxMACxlB/GxQxt-1/2(ml/min)BrodyFormulaSeveringhausFormulaLoweFormulaCalculationoftotalgasuptakeFactorsaffectingFA3.Partialpressuredifferencebetweenalveolar