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1、CLINICALPHARMACOLOGYOFNEUROMUSCULARBLOCKINGAGENTSJerroldH.Levy,MDProfessorofAnesthesiologyEmoryUniversitySchoolofMedicineDivisionofCardiothoracicAnesthesiologyandCriticalCareEmoryHealthcareAtlanta,GeorgiaHISTORYOFNEUROMUSCULARBLOCKINGAGENTSANDCLINICALDEVELOPMENTHISTORY14
2、94-Talesoftravelerskilledbypoisondarts1551-Ourari”or“cururu”meaning“birdkiller”1812-Curarizedcatkeptalivebyartificialrespiration1912-CurareusedtopreventfracturesduringECT1941-InitialusebyGriffith,Culler,andRovenstine1951-SuccinylcholinechloridefirstusedinStockholmINTRODU
3、CTIONOFNEWDRUGS1494-1942Curare1947-1951Succinylcholinechloride,Gallamine,Metocurine,Decamethonium1960’sAlcuronium1970’sPancuroniumbromide,Fazadinium1980’sVecuroniumbromide,Atracuriumbesylate1990Pipecuroniumbromide1991Doxacuriumchloride1992Mivacuriumchloride1994Rocuronium
4、bromide1999RapacuroniumbromideSTRUCTURALCLASSESOFNONDEPOL.ARIZINGRELAXANTSSteroids:Rocuroniumbromide,Vecuroniumbromide,Pancuroniumbromide,PipecuroniumbromideNaturallyoccurringbenzylisoquinolines:curare,metocurineBenzylisoquinoliniums:Atracuriumbesylate,Mivacuriumchloride
5、,DoxacuriumchlorideTHEIDEALRELAXANTNondepolarizingRapidonsetDose-dependentdurationNoside-effectsEliminationindependentoforganfunctionNoactiveortoxicmetabolitesONSETOFPARALYSISISAFFECTEDBY:Dose(relativetoED95)Potency(numberofmolecules)Keo(chemistry/bloodflow)ClearanceAgeN
6、euromuscularBlockingAgentsandPatientEvaluationAssessingPostoperativeNeuromuscularFunctionSustained5-secondheadliftAbilitytoapposeincisors(clenchteeth)Negativeinspiratoryforce>–40cmH2OAbilitytoopeneyeswidefor5secondsHand-gripstrengthSustainedarm/legliftQualityofspeakingvo
7、iceTongueprotrusionAssessingPostoperativeNeuromuscularFunctionCLINICALASSESSMENTKopmanAF,etal.Anesthesiology,1997:86;765AliHH,etal.BrJAnaesth.1975;47:570AssessingPostoperativeNeuromuscularFunctionTrain-of-Four(TOF)FadeRatio9997100100%959110090%948810080%92829770%*9570916
8、0%100100100Control =100PeakExp.FlowRateInspiratoryForceVitalCapacityTOFRatioAssessingPostoperativeNeuro
