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DepartmentofAnesthesiologyCivicCampusAnoteforthoseatthelecture•ThoseIwasabletokeepawakemightnoticethatI’veadded/modifie

dacoupleoftheslidestobetterreflecttheinformationinthelatestversionsofyourtextbooks.•MuchthematerialonCVandRSeffec

tscanbeannoyinglyinconsistentbetweentextsandeditions•Forthosewhoaskedabout“protection”andvolatileanesthesiaI’veappendedacoupleofre

centarticles“foryourinterest”•“FYI”meansthatIwon’texamineyouonthisstuffbuttheRoyalCollegemight!•Thisstuffisrelativelyne

wandpartofabroaderareaofresearchinischemicpreconditioning–youknow,ratstuff•Thanksforattending!DepartmentofAnesthesiologyCivicCampusObjectiv

esI•Chemicalstructure•Structure-functionrelationships•Physiochemicalproperties•Mechanismofaction•Pharmacokinetic

sofInhaledAgents•UptakeandDistribution•Fa/Ficurves,andfactorswhichaffectthem•MetabolismofInhalationAnestheticsDepartmentofAnesthesiologyCivicCa

mpusObjectivesII•DefinitionofMAC•FactorswhichaffectMAC•Cardiovasculareffects•Pulmonaryeffects•CNSeffects•Neuromuscul

areffects•Hepaticeffects•Renaleffects•Uterineeffects•MarroweffectsDepartmentofAnesthesiologyCivicCampusThereality•T

here’sanawfullotofstuffhere-noneofitis“new”•Allofitisinthetextbooks•Barash4thEdition•Chapter15.InhalationAnesth

esia.377-417.•Miller5thEdition•Chapter3.MechanismsofAction.48-73•Chapter4.UptakeandDistribution.74-95•

Chapter5a.CardiovascularPharmacology.96-124•Chapter5b.PulmonaryPharmacology.125-146•Chapter6.Metabolism

andToxicity.147-173•Muchofitrequiresrotememorization•Someofituseful-allofit“test-able”•Ican’tcoverallofitin3hoursDepartmentofAnesthesi

ologyCivicCampusGreg’sgoalsforthislecture•Inflictmyviewofwhatyoushouldknow•Putthisinaclinical(read:useful)context•Explainthatwhichneedsexplaining•Lea

vethememoryworktoyou•Bebackonmyporch,beerinhand,by1730DepartmentofAnesthesiologyCivicCampusChemicalstructureINitrousOxideDiethylEtherHalothaneDep

artmentofAnesthesiologyCivicCampusFunwithchemistry•Halogenationreducesflammability•Fluorinationreducessolubility•Trifluorcarbon

groupsaddstability•AlkanesprecipitatearrythmiasDepartmentofAnesthesiologyCivicCampusChemicalstructureIIIsofluraneSevoflurane

DesfluraneDepartmentofAnesthesiologyCivicCampusPhysicalcharacteristics•Pleasecramthecontentsoftheappropriatetable15.1fromBarash4thE

dthenightbeforetheexam.Takehomepointsinclude:•desfluraneboilsat24OC•halothaneispreservedwiththymol•vaporpressuresarenee

dedforsomeexamquestions•knowledgeofblood:gaspartitioncoefficientsmayactuallybeusefulDepartmentofAnesthesiologyCivic

CampusPartitioncoefficients•Representtherelativeaffinityofagasfor2differentsubstances(solubility)•Measure

datequilibriumsopartialpressuresareequal,but...•Theamountsofgasdissolvedineachsubstance(concentration)aren’tequal.•Wemostcommo

nlyrefertoblood:gaspc•Thelargerthenumber,themoresolubleinbloodDepartmentofAnesthesiologyCivicCampusBlood:gaspartitioncoefficientsAnesthetic

Blood:GasPCDesflurane0.42Nitrousoxide0.46Sevoflurane0.65Isoflurane1.46Enflurane1.91Halothane2.50Table15-1.Barash4thEdition.p378

.DepartmentofAnesthesiologyCivicCampusTheblood:gaspcisuseful,really.•Anesthesiaisrelatedtothepartialp

ressureofthegasinthebrain.•Ifadrugisdissolvedinblood,itisn’tavailableasagas•Moremoleculesofasolublegasarerequiredtosaturateliquidphaseb

eforeincreasingpartialpressure•Speedofonset/offsetcloselyrelatedtosolubility•Thelowertheblood:gaspc-thefastertheonsetDepartmentofAnes

thesiologyCivicCampusUptakeanddistribution•Anesthesiadependsuponbrainpartialpressure•Alveolarpartialpressure(PA)=Pbrain•ThefasterPAapproachesthede

siredlevelthefasterthepatientisanesthetized•PAisabalancebetweendeliveryofdrugtothealveolusanduptakeofthatdrugintotheblood

•TimeforananalogyDepartmentofAnesthesiologyCivicCampusToinduceanesthesiathebucket(PA)mustbefull.Unfortunatelythebuckethasaleak(uptake

).Tofillthebucketyoumusteither(a)pouritinfaster(increasedelivery)or(b)slowdowntheleak(decreaseuptake).abDepar

tmentofAnesthesiologyCivicCampusFactorsinfluencingdelivery•Alveolarventilation•Breathingsystem•volume•freshg

asflow•Inspiredpartialpressure(PI)•concentrationeffect•secondgaseffectDepartmentofAnesthesiologyCivicCampusConce

ntrationand2ndgaseffectsDepartmentofAnesthesiologyCivicCampusFactorsinfluencinguptake•Solubility(blood:gaspc)

•Cardiacoutput•Alveolar-venouspressuregradient•Forthoseofyouwholikeformulae:Uptake=•Q•(PA-Pv)/BPDepartmentofAnesthesiologyCivicCampusFA/FICurvesDe

partmentofAnesthesiologyCivicCampusV/Qdistributionanduptake•Ventilation<perfusion•bloodleavingshuntdi

lutesPAfromnormallung•inductionwithlowsolubilityagentwillbedelayed•littledifferencewithsolubleagents(slowanyway)•Ventilation>perfusion•uptake

isdecreasedwhichenhancesriseinFA•mayspeedinductionforsolubleagents•lessdifferencewithlowsolubilityagents(fastanyway)De

partmentofAnesthesiologyCivicCampusNitrousOxide•N20leavesblood34xmorethanN2absorbed•Sure,otheragentsarem

oresolublebutwedon’tgivethemat70%end-tidalconcentration•distensionofclosedairspaces•70%N2Owilldoubleapneumoin10minutesAgentBlood:GasPCNitr

ousOxide0.47Nitrogen0.014DepartmentofAnesthesiologyCivicCampusMechanismofAction•Meyer-OvertonTheory•

lipidsolubleagentspreadsmembranesdistortingmembraneproteins(ieionchannels).•ProteinReceptorHypothesis•inhaledagen

tbindstomembraneproteinandchangesionconductance•NeurotransmitterAvailability•inhaledagentpreventsbreakdo

wnofGABA•Greg’sPostulate•ifmorethanonetheory-thennoonereallyknowsDepartmentofAnesthesiologyCivicCampusMetabolismofinhaleda

nesthetics•Fairlysmallcomponentofelimination•Occursatcytochromep450•Inducible•Oxidative•o-dealkylation•dehalogenation•epoxidation•

Reductive•occursonlywithhalothaneinhypoxicconditionsDepartmentofAnesthesiologyCivicCampusThreedeterminantsofme

tabolism•Chemicalstructure•etherbond•carbon-halogenbond•Hepaticenzymeactivity•BloodconcentrationDepartmentofAnesthesiologyCivicCampusMetabolis

mofinhaledanestheticsIIAgent%metabolizedHalothane20Sevoflurane2-5Enflurane2.4Isoflurane0.2Desflurane0.02NitrousOxide0.004Table1

5-1.Barash4thEdition.p378.DepartmentofAnesthesiologyCivicCampusBreakDepartmentofAnesthesiologyCivicCampusMinimumalveolarconce

ntration•Alveolarconcentrationrequiredtopreventmovementin50%ofsubjects•standardstimulus•representsbrainconcentration•consistentwithinandbet

weenspecies•additiveDepartmentofAnesthesiologyCivicCampusMACValuesAgentMACNitrousoxide104Desflurane6.6Sevoflurane1.8Enflurane1

.63Isoflurane1.17Halothane0.75Table15-1.Barash4thEdition.p378.DepartmentofAnesthesiologyCivicCampusFactorsincreasingMAC•Hyperthermia•C

hronicETOHabuse•Hypernatremia•IncreasedCNStransmitters•MAOI•Amphetamine•Cocaine•Ephedrine•L-DOPATable15.4.Barash4thEdition.P389Depa

rtmentofAnesthesiologyCivicCampusFactorsdecreasingMAC•Increasingage•Hypothermia•Hyponatremia•Hypotension(MAP<50mmHg)•Pregna

ncy•Hypoxemia(<38mmHg)•O2content(<4.3mlO2/dl)•Metabolicacidosis•Narcotics•Ketamine•Benzodiazepines•2agonists•LiCO3

•Localanesthetics•ETOH(acute)•Andmanymore...Table15.5.Barash4thEdition.P390DepartmentofAnesthesiologyCivicCampusFactorswi

thnoinfluenceonMAC•Durationofanesthesia•Sex•Alkalosis•PCO2•Hypertension•Anemia•Potassium•Magnseium•AndothersDepartmentofAnesthesiologyCi

vicCampusEffectsonorgansystems•Cardiovascular•Pulmonary•CNS•Neuromuscular•Hepatic•Renal•Uterine•MiscellaneousDepartmentofAnesthesiologyCivicCa

mpusInhaledanestheticsandtheCVsystem•Effectcanbehardtoquantify•Invitroandinvivoeffectscanbequitedifferent•Sympatheticstimulation•Barorecep

torreflexes•Animalmodelvshumansubject•Informationprovidedinthislectureisabroadoverview.•PleaserefertoMillerforadetaileddisc

ussionofthetopicDepartmentofAnesthesiologyCivicCampusBloodpressure•AlldecreaseBP,exceptN2O•Effectcausedbyacombinationof•Vasodilation•Myocardialdepre

ssion’•DecreasedCNStone•RelativecontributionofeachisdrugdependentDepartmentofAnesthesiologyCivicCampusHeartrate•Effectsva

riableandagent-specific•halothanedecreasesHR•Sevofluraneandenfluraneneutral•Desfluraneassociatedwithtransienttachycardia•occursw

ithrapidincreasesinMAC•associatedwithincreasesinserumcatecholamines•similareffectmaybeseenwithisofluraneDepartmentofAnesthesiologyCivicCampusM

yocardialcontractility•Allvolatileanestheticsaredirectmyocardialdepressantsinvitro,includingN2O.•Effectoncirculationinvivomod

ifiedbyeffectsonpulmonarycirculationandsympatheticstimulation.•Asbestaswecantell,at1MACanestheticsdepresscontractilityi

nthefollowingorder•H=E>I=D=S.DepartmentofAnesthesiologyCivicCampusCardiacoutput•Despitemyocardialdepressio

ncardiacoutputiswell-maintainedwithisofluraneanddesflurane•preservationofheartrate•greaterreductioninSVR•preserv

ationofbaroreceptorreflexesDepartmentofAnesthesiologyCivicCampusSystemicvascularresistance•Allaredirectvasodilators,exceptN

2O•relaxvascularsmoothmuscle•cAMP-Ca2+andornitricoxideinvolved•variableeffectsonindividualvascularbedsDepartmentofAnest

hesiologyCivicCampusDysrhytmias•Halothanepotentiatescatecholamine-relateddysrhythmias•ED50ofepinehrineproducingdy

srhythmiasat1.25MAC•halothane2.1g•kg-1•isoflurane6.9g•kg-1•enflurane10.9g•kg-1•LidocainedoublesED50ofe

pinephrine•ChildrensomewhatmoreresistantDepartmentofAnesthesiologyCivicCampusCoronarybloodflow•Isofluraneisapotentcoronaryvasodilator•Intheory,dilati

onofnormalcoronaryvesselscandirectbloodflowawayfromstenoticcoronaries•Steal-proneanatomy•totalocclusionof1majorcoronaryve

ssel•collateralperfusionwith90%stenosis•Inpractice,doesn’tseemtobeaproblemDepartmentofAnesthesiologyCivicCampusResp

iratorypattern•Increasedfrequency•Decreasedtidalvolume•Decreasedminuteventilation•Attributed(incats)tosensitizationofpulmonar

ystretchreceptors-notsupportedinhumansDepartmentofAnesthesiologyCivicCampusMechanoreceptors•Sensetensioninmuscles/tendon

sinintercostalmuscles•Increasedresistancedetectedandincreasedrespiratoryeffortrecruited•Responsestoinspiratoryandexpiratoryloadsdimi

nished•FurtherinhibitioninpatientswithCOPDDepartmentofAnesthesiologyCivicCampusChemoreceptors•Apneicth

resholdraised•ResponsetoPCO2blunted•PCO2increasedwhilespontaneouslyventilating•E>D=I>S=H•hypoxicdriveabolishedby0.1MACDepartmento

fAnesthesiologyCivicCampusBronchialmusculature•Reducevagaltone•Directrelaxation•increasedcAMP(butnotviaadrenoreceptormedia

ted)•Whenbronchospastic,adosedependentreductioninRawoccurswithmostagentsDepartmentofAnesthesiologyCivicCampusHypoxicpulmonar

yvasoconstriction•InhaledanestheticsappeartobluntHPVandincreaseshunt•ShuntandPO2appearunchangedinstudiesofinhaledanes

theticsduringonelungventilation•IntrinsicchangesinHPVconfoundedby•changesincardiacoutput•pulmonaryarterypressure•positionDepartmentofAnesthesiolo

gyCivicCampusCentralnervoussystem•Increasecerebralbloodflow•IncreaseICP•DecreasedCMRO2•Decreasedfrequency-increasedvol

tageonEEG•2MACenfluraneincreasesseizureactivity•Decreasedamplitude-increasedlatencyonSSEPDepartmentofAnesthesio

logyCivicCampusNeuromuscularfunction•Skeletalmusclerelaxation•PotentiateNDMR•TriggerMHDepartmentofAnesthesiologyCivicCampusH

epatic•Hepaticarterialbloodflowdecreasedbyhalothane•Clearanceofdrugsdecreasedinkeepingwithreductionsinhepaticbloodflow•Hepatoto

xicity•mild,transient,postoperativeincreaseinLFTs•?duetotransienthypoxia±reductivemetabolites•massivehepaticnecrosis

•oxidativemetabolitebindstohepatocyte•repeatexposureleadstoimmune-mediatednecrosisDepartmentofAnesthesiologyCivicCampusRenal•Do

se-dependentdecreasesin•renalbloodflow•glomerularfiltrationrate•urineoutput•RelatedtochangesinCOandBPnotADH•Fluoridenephroto

xicityatserumconc.50mol/l•F-opposesADHleadingtopolyuria•methoxyflurane2.5MAC-hours•enflurane9.6MAC-hoursDepartmentofAnesthesiolog

yCivicCampusObstetrical•N2Ohasnoeffect•Halogenatedvolatilesleadtodose-dependent•uterinerelaxation•reductions

inuterinebloodflowDepartmentofAnesthesiologyCivicCampusMiscellaneous•N2O-relatedmyelosupressionif>12hrexposure•inhibiti

onofmethionine-synthetase•megaloblasticanemia•Inhaledanesthetics,N2Oinparticular,decreaseleukocytefunction•Teratogenesiswithprolongedexposureinrat

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