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DepartmentofAnesthesiologyCivicCampusAnoteforthoseatthelecture•ThoseIwasabletokeepawakemightnoticethatI’veadded/modifiedacoupleoftheslidestobetterre

flecttheinformationinthelatestversionsofyourtextbooks.•MuchthematerialonCVandRSeffectscanbeannoyinglyinconsistentbetweentextsandeditio

ns•Forthosewhoaskedabout“protection”andvolatileanesthesiaI’veappendedacoupleofrecentarticles“foryourinterest”•“FYI”me

ansthatIwon’texamineyouonthisstuffbuttheRoyalCollegemight!•Thisstuffisrelativelynewandpartofabroaderareaofresearchinis

chemicpreconditioning–youknow,ratstuff•Thanksforattending!DepartmentofAnesthesiologyCivicCampusObjectivesI•Chemicalstructure•Struct

ure-functionrelationships•Physiochemicalproperties•Mechanismofaction•PharmacokineticsofInhaledAgents•UptakeandDistribution•Fa/Ficurves,andfactors

whichaffectthem•MetabolismofInhalationAnestheticsDepartmentofAnesthesiologyCivicCampusObjectivesII•DefinitionofMAC•FactorswhichaffectMA

C•Cardiovasculareffects•Pulmonaryeffects•CNSeffects•Neuromusculareffects•Hepaticeffects•Renaleffects•Uterineeffects•

MarroweffectsDepartmentofAnesthesiologyCivicCampusThereality•There’sanawfullotofstuffhere-noneofitis“new”•Allofitisi

nthetextbooks•Barash4thEdition•Chapter15.InhalationAnesthesia.377-417.•Miller5thEdition•Chapter3.MechanismsofAction.48

-73•Chapter4.UptakeandDistribution.74-95•Chapter5a.CardiovascularPharmacology.96-124•Chapter5b.PulmonaryPharmacology.125-146•Chapte

r6.MetabolismandToxicity.147-173•Muchofitrequiresrotememorization•Someofituseful-allofit“test-able”•Ican’tcoverallofiti

n3hoursDepartmentofAnesthesiologyCivicCampusGreg’sgoalsforthislecture•Inflictmyviewofwhatyoushouldknow•Putthisina

clinical(read:useful)context•Explainthatwhichneedsexplaining•Leavethememoryworktoyou•Bebackonmyporch,beerinhand,by

1730DepartmentofAnesthesiologyCivicCampusChemicalstructureINitrousOxideDiethylEtherHalothaneDepartmentofAnesthesiolog

yCivicCampusFunwithchemistry•Halogenationreducesflammability•Fluorinationreducessolubility•Trifluorcarbongroupsaddstability•Alkanesprecip

itatearrythmiasDepartmentofAnesthesiologyCivicCampusChemicalstructureIIIsofluraneSevofluraneDesfluraneDepartmentofAnesthesiologyCivicCampusPhysic

alcharacteristics•Pleasecramthecontentsoftheappropriatetable15.1fromBarash4thEdthenightbeforetheexam.Takehomepointsincl

ude:•desfluraneboilsat24OC•halothaneispreservedwiththymol•vaporpressuresareneededforsomeexamquestions•knowledgeofblood:gaspartitionco

efficientsmayactuallybeusefulDepartmentofAnesthesiologyCivicCampusPartitioncoefficients•Representtherelativeaffinityofagasfor2differe

ntsubstances(solubility)•Measuredatequilibriumsopartialpressuresareequal,but...•Theamountsofgasdissolvedineachsubstance(concentration

)aren’tequal.•Wemostcommonlyrefertoblood:gaspc•Thelargerthenumber,themoresolubleinbloodDepartmentofAnesthesiologyCivicCampusBlood:gasparti

tioncoefficientsAnestheticBlood:GasPCDesflurane0.42Nitrousoxide0.46Sevoflurane0.65Isoflurane1.46Enfl

urane1.91Halothane2.50Table15-1.Barash4thEdition.p378.DepartmentofAnesthesiologyCivicCampusTheblood:gas

pcisuseful,really.•Anesthesiaisrelatedtothepartialpressureofthegasinthebrain.•Ifadrugisdissolvedinblood,iti

sn’tavailableasagas•Moremoleculesofasolublegasarerequiredtosaturateliquidphasebeforeincreasingpartialpressure•Speedofonset/offsetcloselyrelatedtosol

ubility•Thelowertheblood:gaspc-thefastertheonsetDepartmentofAnesthesiologyCivicCampusUptakeanddistribution•Anest

hesiadependsuponbrainpartialpressure•Alveolarpartialpressure(PA)=Pbrain•ThefasterPAapproachesthedesiredlevelthefasterthepatientisanesthe

tized•PAisabalancebetweendeliveryofdrugtothealveolusanduptakeofthatdrugintotheblood•TimeforananalogyDepartmentofAnesthesiologyCiv

icCampusToinduceanesthesiathebucket(PA)mustbefull.Unfortunatelythebuckethasaleak(uptake).Tofillthebucketyoumusteither(a)

pouritinfaster(increasedelivery)or(b)slowdowntheleak(decreaseuptake).abDepartmentofAnesthesiologyCivicCampusFactorsinfluencingdelivery•Alve

olarventilation•Breathingsystem•volume•freshgasflow•Inspiredpartialpressure(PI)•concentrationeffect•second

gaseffectDepartmentofAnesthesiologyCivicCampusConcentrationand2ndgaseffectsDepartmentofAnesthesiology

CivicCampusFactorsinfluencinguptake•Solubility(blood:gaspc)•Cardiacoutput•Alveolar-venouspressuregradient•Forthoseofyouwholikeformulae:Up

take=•Q•(PA-Pv)/BPDepartmentofAnesthesiologyCivicCampusFA/FICurvesDepartmentofAnesthesiologyCivicCamp

usV/Qdistributionanduptake•Ventilation<perfusion•bloodleavingshuntdilutesPAfromnormallung•inductionwithlowsolubilit

yagentwillbedelayed•littledifferencewithsolubleagents(slowanyway)•Ventilation>perfusion•uptakeisdecreasedwhichenh

ancesriseinFA•mayspeedinductionforsolubleagents•lessdifferencewithlowsolubilityagents(fastanyway)DepartmentofAnesthesiologyCivicCa

mpusNitrousOxide•N20leavesblood34xmorethanN2absorbed•Sure,otheragentsaremoresolublebutwedon’tgivethemat70%end-tidalconcentration•d

istensionofclosedairspaces•70%N2Owilldoubleapneumoin10minutesAgentBlood:GasPCNitrousOxide0.47Nitrogen

0.014DepartmentofAnesthesiologyCivicCampusMechanismofAction•Meyer-OvertonTheory•lipidsolubleagentspreadsmembranesd

istortingmembraneproteins(ieionchannels).•ProteinReceptorHypothesis•inhaledagentbindstomembraneproteinandchangesionconductance•NeurotransmitterAvai

lability•inhaledagentpreventsbreakdownofGABA•Greg’sPostulate•ifmorethanonetheory-thennoonereallyknowsD

epartmentofAnesthesiologyCivicCampusMetabolismofinhaledanesthetics•Fairlysmallcomponentofelimination•Occursatcytochromep450•Inducible•Oxidative•o-

dealkylation•dehalogenation•epoxidation•Reductive•occursonlywithhalothaneinhypoxicconditionsDepartmentofAnesthesiologyCiv

icCampusThreedeterminantsofmetabolism•Chemicalstructure•etherbond•carbon-halogenbond•Hepaticenzymeactivity•Bloodconcentra

tionDepartmentofAnesthesiologyCivicCampusMetabolismofinhaledanestheticsIIAgent%metabolizedHalothane20Sevoflurane2-5Enflura

ne2.4Isoflurane0.2Desflurane0.02NitrousOxide0.004Table15-1.Barash4thEdition.p378.DepartmentofAnesthesio

logyCivicCampusBreakDepartmentofAnesthesiologyCivicCampusMinimumalveolarconcentration•Alveolarconcentrationrequiredtopreventmovementin50%ofsubjec

ts•standardstimulus•representsbrainconcentration•consistentwithinandbetweenspecies•additiveDepartmentofAnesthesiologyCivicCamp

usMACValuesAgentMACNitrousoxide104Desflurane6.6Sevoflurane1.8Enflurane1.63Isoflurane1.17Halothane0.75Table15-

1.Barash4thEdition.p378.DepartmentofAnesthesiologyCivicCampusFactorsincreasingMAC•Hyperthermia•ChronicETOHabuse•Hypernatremia•IncreasedCNStransmit

ters•MAOI•Amphetamine•Cocaine•Ephedrine•L-DOPATable15.4.Barash4thEdition.P389DepartmentofAnesthesiologyCivicCampusFact

orsdecreasingMAC•Increasingage•Hypothermia•Hyponatremia•Hypotension(MAP<50mmHg)•Pregnancy•Hypoxemia(<38mmHg)•O2content(<4.3mlO2/dl)•Metabolicacidos

is•Narcotics•Ketamine•Benzodiazepines•2agonists•LiCO3•Localanesthetics•ETOH(acute)•Andmanymore...Table15.5.Barash4t

hEdition.P390DepartmentofAnesthesiologyCivicCampusFactorswithnoinfluenceonMAC•Durationofanesthesia•Sex•Alkalosis•PCO2•Hypertensi

on•Anemia•Potassium•Magnseium•AndothersDepartmentofAnesthesiologyCivicCampusEffectsonorgansystems•Cardiovascular•Pulmonary•CNS•Neuromuscul

ar•Hepatic•Renal•Uterine•MiscellaneousDepartmentofAnesthesiologyCivicCampusInhaledanestheticsandtheCVsystem•Effectcanbeh

ardtoquantify•Invitroandinvivoeffectscanbequitedifferent•Sympatheticstimulation•Baroreceptorreflexes•Animalmodelvshumansubject•Informationpr

ovidedinthislectureisabroadoverview.•PleaserefertoMillerforadetaileddiscussionofthetopicDepartmentofAnesthesiologyCivicCampusBloodpressure

•AlldecreaseBP,exceptN2O•Effectcausedbyacombinationof•Vasodilation•Myocardialdepression’•DecreasedCNStone•Relativecontributionofeac

hisdrugdependentDepartmentofAnesthesiologyCivicCampusHeartrate•Effectsvariableandagent-specific•halo

thanedecreasesHR•Sevofluraneandenfluraneneutral•Desfluraneassociatedwithtransienttachycardia•occurswithrapidincreasesinMAC•ass

ociatedwithincreasesinserumcatecholamines•similareffectmaybeseenwithisofluraneDepartmentofAnesthesiologyCivicCampusMyocardialcontractility•Allvolat

ileanestheticsaredirectmyocardialdepressantsinvitro,includingN2O.•Effectoncirculationinvivomodifiedbyeffec

tsonpulmonarycirculationandsympatheticstimulation.•Asbestaswecantell,at1MACanestheticsdepresscontractilityin

thefollowingorder•H=E>I=D=S.DepartmentofAnesthesiologyCivicCampusCardiacoutput•Despitemyocardialdepressioncardiacoutputiswell-mai

ntainedwithisofluraneanddesflurane•preservationofheartrate•greaterreductioninSVR•preservationofbaroreceptorreflexesDepartmentofAn

esthesiologyCivicCampusSystemicvascularresistance•Allaredirectvasodilators,exceptN2O•relaxvascularsmoothmuscle•cAMP

-Ca2+andornitricoxideinvolved•variableeffectsonindividualvascularbedsDepartmentofAnesthesiologyCivicCampusDysrhytmias•Halothanepotentiatescatec

holamine-relateddysrhythmias•ED50ofepinehrineproducingdysrhythmiasat1.25MAC•halothane2.1g•kg-1•isoflurane6.9g•kg-1•enflurane10.9g•

kg-1•LidocainedoublesED50ofepinephrine•ChildrensomewhatmoreresistantDepartmentofAnesthesiologyCivicCampusCoronarybloodflow•Isofluraneisapoten

tcoronaryvasodilator•Intheory,dilationofnormalcoronaryvesselscandirectbloodflowawayfromstenoticcoronaries•Steal-proneanatomy•totalocclusionof1

majorcoronaryvessel•collateralperfusionwith90%stenosis•Inpractice,doesn’tseemtobeaproblemDepartmentofAnesthesiologyCivicCampusRespiratorypattern•In

creasedfrequency•Decreasedtidalvolume•Decreasedminuteventilation•Attributed(incats)tosensitizationofpulmonarystretchrecep

tors-notsupportedinhumansDepartmentofAnesthesiologyCivicCampusMechanoreceptors•Sensetensioninmuscles/tendonsinintercostalmuscles•Incr

easedresistancedetectedandincreasedrespiratoryeffortrecruited•Responsestoinspiratoryandexpiratoryloadsdiminished•Furtherinhibitionin

patientswithCOPDDepartmentofAnesthesiologyCivicCampusChemoreceptors•Apneicthresholdraised•ResponsetoPCO2blunted•PCO2increasedwhilespontaneouslyventi

lating•E>D=I>S=H•hypoxicdriveabolishedby0.1MACDepartmentofAnesthesiologyCivicCampusBronchialmusculature•Reducevagaltone•Dir

ectrelaxation•increasedcAMP(butnotviaadrenoreceptormediated)•Whenbronchospastic,adosedependentreductioninRawoccurswithmo

stagentsDepartmentofAnesthesiologyCivicCampusHypoxicpulmonaryvasoconstriction•Inhaledanestheticsappear

tobluntHPVandincreaseshunt•ShuntandPO2appearunchangedinstudiesofinhaledanestheticsduringonelungventilation•IntrinsicchangesinHPVco

nfoundedby•changesincardiacoutput•pulmonaryarterypressure•positionDepartmentofAnesthesiologyCivicCampusCentralnervoussyste

m•Increasecerebralbloodflow•IncreaseICP•DecreasedCMRO2•Decreasedfrequency-increasedvoltageonEEG•2MACenflura

neincreasesseizureactivity•Decreasedamplitude-increasedlatencyonSSEPDepartmentofAnesthesiologyCivicCampusNeuromu

scularfunction•Skeletalmusclerelaxation•PotentiateNDMR•TriggerMHDepartmentofAnesthesiologyCivicCampusHepatic•Hepaticarterialbloodflowdecrease

dbyhalothane•Clearanceofdrugsdecreasedinkeepingwithreductionsinhepaticbloodflow•Hepatotoxicity•mild,transient,postoperativeincreaseinLFTs•?duetotrans

ienthypoxia±reductivemetabolites•massivehepaticnecrosis•oxidativemetabolitebindstohepatocyte•repeatexposureleadstoimmune-media

tednecrosisDepartmentofAnesthesiologyCivicCampusRenal•Dose-dependentdecreasesin•renalbloodflow•glomerularfiltrationrate•urineout

put•RelatedtochangesinCOandBPnotADH•Fluoridenephrotoxicityatserumconc.50mol/l•F-opposesADHleadingtopolyuria•methoxyflurane2.5M

AC-hours•enflurane9.6MAC-hoursDepartmentofAnesthesiologyCivicCampusObstetrical•N2Ohasnoeffect•Halogenatedvolatilesleadt

odose-dependent•uterinerelaxation•reductionsinuterinebloodflowDepartmentofAnesthesiologyCivicCampusMiscellaneous•N2O-relatedmyelosupr

essionif>12hrexposure•inhibitionofmethionine-synthetase•megaloblasticanemia•Inhaledanesthetics,N2Oinparticular,decreasel

eukocytefunction•Teratogenesiswithprolongedexposureinrats•Increasedrisk(RR=1.3)ofspontaneousabortionwithchronicexposuretoN20更多精品资请访问更多品资源请访

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