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DepartmentofAnesthesiologyCivicCampusAnoteforthoseatthelecture•ThoseIwasabletokeepawakemightnoticethatI’veadded/modifiedacoupleofthe

slidestobetterreflecttheinformationinthelatestversionsofyourtextbooks.•MuchthematerialonCVandRSeffectscanbeann

oyinglyinconsistentbetweentextsandeditions•Forthosewhoaskedabout“protection”andvolatileanesthesiaI’veappendedacou

pleofrecentarticles“foryourinterest”•“FYI”meansthatIwon’texamineyouonthisstuffbuttheRoyalCollegemight!•Thisstuf

fisrelativelynewandpartofabroaderareaofresearchinischemicpreconditioning–youknow,ratstuff•Thanksforattending

!DepartmentofAnesthesiologyCivicCampusObjectivesI•Chemicalstructure•Structure-functionrelationships•Physiochemicalproperties•M

echanismofaction•PharmacokineticsofInhaledAgents•UptakeandDistribution•Fa/Ficurves,andfactorswhichaffectthem•M

etabolismofInhalationAnestheticsDepartmentofAnesthesiologyCivicCampusObjectivesII•DefinitionofMAC•FactorswhichaffectMAC•Cardiov

asculareffects•Pulmonaryeffects•CNSeffects•Neuromusculareffects•Hepaticeffects•Renaleffects•Uterineeffects•MarroweffectsDepartmentofAn

esthesiologyCivicCampusThereality•There’sanawfullotofstuffhere-noneofitis“new”•Allofitisinthetextbooks•Barash4thEdition•Ch

apter15.InhalationAnesthesia.377-417.•Miller5thEdition•Chapter3.MechanismsofAction.48-73•Chapter4.UptakeandDis

tribution.74-95•Chapter5a.CardiovascularPharmacology.96-124•Chapter5b.PulmonaryPharmacology.125-146•Chapter6.MetabolismandToxicity.

147-173•Muchofitrequiresrotememorization•Someofituseful-allofit“test-able”•Ican’tcoverallofitin3hoursDepartmentofAnesthesiolo

gyCivicCampusGreg’sgoalsforthislecture•Inflictmyviewofwhatyoushouldknow•Putthisinaclinical(read:useful)context•Explaint

hatwhichneedsexplaining•Leavethememoryworktoyou•Bebackonmyporch,beerinhand,by1730DepartmentofAnesthesiologyCi

vicCampusChemicalstructureINitrousOxideDiethylEtherHalothaneDepartmentofAnesthesiologyCivicCampusFunwithchemis

try•Halogenationreducesflammability•Fluorinationreducessolubility•Trifluorcarbongroupsaddstability•AlkanesprecipitatearrythmiasDepartmentofAnest

hesiologyCivicCampusChemicalstructureIIIsofluraneSevofluraneDesfluraneDepartmentofAnesthesiologyCivicCampusPhysicalcharacterist

ics•Pleasecramthecontentsoftheappropriatetable15.1fromBarash4thEdthenightbeforetheexam.Takehomepointsinclude:•desfluranebo

ilsat24OC•halothaneispreservedwiththymol•vaporpressuresareneededforsomeexamquestions•knowledgeofblood:gaspartitioncoefficientsma

yactuallybeusefulDepartmentofAnesthesiologyCivicCampusPartitioncoefficients•Representtherelativeaffinityofagasfor2differentsubstances(solubilit

y)•Measuredatequilibriumsopartialpressuresareequal,but...•Theamountsofgasdissolvedineachsubstance(concentration)aren’tequal.•Wemostcommonlyreferto

blood:gaspc•Thelargerthenumber,themoresolubleinbloodDepartmentofAnesthesiologyCivicCampusBlood:gaspar

titioncoefficientsAnestheticBlood:GasPCDesflurane0.42Nitrousoxide0.46Sevoflurane0.65Isoflurane1.46Enflurane1.91Halothane2.50Table15-1.Barash4thEditi

on.p378.DepartmentofAnesthesiologyCivicCampusTheblood:gaspcisuseful,really.•Anesthesiaisrelatedtothepartialpressureofthegasinthebrain.•Ifadr

ugisdissolvedinblood,itisn’tavailableasagas•Moremoleculesofasolublegasarerequiredtosaturateliquidphasebeforeincreasingpartialpressure•Speedofonset/of

fsetcloselyrelatedtosolubility•Thelowertheblood:gaspc-thefastertheonsetDepartmentofAnesthesiologyCivicCampusUptake

anddistribution•Anesthesiadependsuponbrainpartialpressure•Alveolarpartialpressure(PA)=Pbrain•ThefasterPAapproachesthedesiredlevelthefasterthepa

tientisanesthetized•PAisabalancebetweendeliveryofdrugtothealveolusanduptakeofthatdrugintotheblood•Tim

eforananalogyDepartmentofAnesthesiologyCivicCampusToinduceanesthesiathebucket(PA)mustbefull.Unfortunatelythebuckethasaleak(uptake).Tof

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

tmentofAnesthesiologyCivicCampusFactorsinfluencingdelivery•Alveolarventilation•Breathingsystem•volume•freshgasflow•Inspiredpartialpress

ure(PI)•concentrationeffect•secondgaseffectDepartmentofAnesthesiologyCivicCampusConcentrationand2ndgaseffectsDepartme

ntofAnesthesiologyCivicCampusFactorsinfluencinguptake•Solubility(blood:gaspc)•Cardiacoutput•Alveolar-venouspressuregradient•Fort

hoseofyouwholikeformulae:Uptake=•Q•(PA-Pv)/BPDepartmentofAnesthesiologyCivicCampusFA/FICurvesDepartmentofAnesthesiologyCi

vicCampusV/Qdistributionanduptake•Ventilation<perfusion•bloodleavingshuntdilutesPAfromnormallung•inductionwithlowsolubilityagentwillbedelayed•litt

ledifferencewithsolubleagents(slowanyway)•Ventilation>perfusion•uptakeisdecreasedwhichenhancesriseinFA•mayspeedinductionf

orsolubleagents•lessdifferencewithlowsolubilityagents(fastanyway)DepartmentofAnesthesiologyCivicCampusNitrousOxide•N2

0leavesblood34xmorethanN2absorbed•Sure,otheragentsaremoresolublebutwedon’tgivethemat70%end-tidalconce

ntration•distensionofclosedairspaces•70%N2Owilldoubleapneumoin10minutesAgentBlood:GasPCNitrousOxide0.47Nitrogen0.014DepartmentofA

nesthesiologyCivicCampusMechanismofAction•Meyer-OvertonTheory•lipidsolubleagentspreadsmembranesdistorti

ngmembraneproteins(ieionchannels).•ProteinReceptorHypothesis•inhaledagentbindstomembraneproteinandchangesionconductance•Neurotransmitt

erAvailability•inhaledagentpreventsbreakdownofGABA•Greg’sPostulate•ifmorethanonetheory-thennoonereallyknowsDepartmen

tofAnesthesiologyCivicCampusMetabolismofinhaledanesthetics•Fairlysmallcomponentofelimination•Occursatcytochromep450•Indu

cible•Oxidative•o-dealkylation•dehalogenation•epoxidation•Reductive•occursonlywithhalothaneinhypoxicconditionsD

epartmentofAnesthesiologyCivicCampusThreedeterminantsofmetabolism•Chemicalstructure•etherbond•carbon-halogenbond•He

paticenzymeactivity•BloodconcentrationDepartmentofAnesthesiologyCivicCampusMetabolismofinhaledanestheticsIIA

gent%metabolizedHalothane20Sevoflurane2-5Enflurane2.4Isoflurane0.2Desflurane0.02NitrousOxide0.004Table15-1.Barash4thEdition.p37

8.DepartmentofAnesthesiologyCivicCampusBreakDepartmentofAnesthesiologyCivicCampusMinimumalveolarconcentration•Alveolarconc

entrationrequiredtopreventmovementin50%ofsubjects•standardstimulus•representsbrainconcentration•consistentwithinandbetweenspecies•additiveDep

artmentofAnesthesiologyCivicCampusMACValuesAgentMACNitrousoxide104Desflurane6.6Sevoflurane1.8Enflurane1.63Isoflurane1.17Halothane0.75

Table15-1.Barash4thEdition.p378.DepartmentofAnesthesiologyCivicCampusFactorsincreasingMAC•Hyperthermia•ChronicET

OHabuse•Hypernatremia•IncreasedCNStransmitters•MAOI•Amphetamine•Cocaine•Ephedrine•L-DOPATable15.4.Barash4thEdition.P389DepartmentofAnesthesiolog

yCivicCampusFactorsdecreasingMAC•Increasingage•Hypothermia•Hyponatremia•Hypotension(MAP<50mmHg)•Pregn

ancy•Hypoxemia(<38mmHg)•O2content(<4.3mlO2/dl)•Metabolicacidosis•Narcotics•Ketamine•Benzodiazepines•2agonist

s•LiCO3•Localanesthetics•ETOH(acute)•Andmanymore...Table15.5.Barash4thEdition.P390DepartmentofAnesthesiologyCivicCampusFactorswithno

influenceonMAC•Durationofanesthesia•Sex•Alkalosis•PCO2•Hypertension•Anemia•Potassium•Magnseium•Andot

hersDepartmentofAnesthesiologyCivicCampusEffectsonorgansystems•Cardiovascular•Pulmonary•CNS•Neuromuscular•Hepatic•Renal•Uterine•Misc

ellaneousDepartmentofAnesthesiologyCivicCampusInhaledanestheticsandtheCVsystem•Effectcanbehardtoquantify•Invitroandinvivoeffectscanbequitedifferent•S

ympatheticstimulation•Baroreceptorreflexes•Animalmodelvshumansubject•Informationprovidedinthislectureis

abroadoverview.•PleaserefertoMillerforadetaileddiscussionofthetopicDepartmentofAnesthesiologyCivicCampusBloodp

ressure•AlldecreaseBP,exceptN2O•Effectcausedbyacombinationof•Vasodilation•Myocardialdepression’•DecreasedCNStone•Relativecontr

ibutionofeachisdrugdependentDepartmentofAnesthesiologyCivicCampusHeartrate•Effectsvariableandagent-specific•halothanedecreasesHR•Sevofluran

eandenfluraneneutral•Desfluraneassociatedwithtransienttachycardia•occurswithrapidincreasesinMAC•associatedwithincreasesinserumc

atecholamines•similareffectmaybeseenwithisofluraneDepartmentofAnesthesiologyCivicCampusMyocardialcontractility•Allvolatileanesthetics

aredirectmyocardialdepressantsinvitro,includingN2O.•Effectoncirculationinvivomodifiedbyeffectsonpulmonarycirculationandsympatheticstimulation.•Asb

estaswecantell,at1MACanestheticsdepresscontractilityinthefollowingorder•H=E>I=D=S.DepartmentofAnesthesiologyCivicCam

pusCardiacoutput•Despitemyocardialdepressioncardiacoutputiswell-maintainedwithisofluraneanddesflurane•preservationofheartrate

•greaterreductioninSVR•preservationofbaroreceptorreflexesDepartmentofAnesthesiologyCivicCampusSystemicvascularresistance•Allaredirectvasodilato

rs,exceptN2O•relaxvascularsmoothmuscle•cAMP-Ca2+andornitricoxideinvolved•variableeffectsonindividualvascularbedsDepartmentofAnesthe

siologyCivicCampusDysrhytmias•Halothanepotentiatescatecholamine-relateddysrhythmias•ED50ofepinehrineproducingdysrhythmiasat1.25MAC•h

alothane2.1g•kg-1•isoflurane6.9g•kg-1•enflurane10.9g•kg-1•LidocainedoublesED50ofepinephrine•ChildrensomewhatmoreresistantDepartmentofAnesth

esiologyCivicCampusCoronarybloodflow•Isofluraneisapotentcoronaryvasodilator•Intheory,dilationofnormalcoronary

vesselscandirectbloodflowawayfromstenoticcoronaries•Steal-proneanatomy•totalocclusionof1majorcoronary

vessel•collateralperfusionwith90%stenosis•Inpractice,doesn’tseemtobeaproblemDepartmentofAnesthesiologyCivicCampusRes

piratorypattern•Increasedfrequency•Decreasedtidalvolume•Decreasedminuteventilation•Attributed(incats)tosensitizationofpulmonarystr

etchreceptors-notsupportedinhumansDepartmentofAnesthesiologyCivicCampusMechanoreceptors•Sensetensioninmuscles/tendonsinintercostalmuscles

•Increasedresistancedetectedandincreasedrespiratoryeffortrecruited•Responsestoinspiratoryandexpiratoryloadsdiminished•Furtherinhibitioninpatient

swithCOPDDepartmentofAnesthesiologyCivicCampusChemoreceptors•Apneicthresholdraised•ResponsetoPCO2blunted•PCO2increasedwhilespont

aneouslyventilating•E>D=I>S=H•hypoxicdriveabolishedby0.1MACDepartmentofAnesthesiologyCivicCampusBronchialmus

culature•Reducevagaltone•Directrelaxation•increasedcAMP(butnotviaadrenoreceptormediated)•Whenbronchospastic,adosedependentred

uctioninRawoccurswithmostagentsDepartmentofAnesthesiologyCivicCampusHypoxicpulmonaryvasoconstriction•Inhaledanestheticsappeartoblu

ntHPVandincreaseshunt•ShuntandPO2appearunchangedinstudiesofinhaledanestheticsduringonelungventilation•Intrinsicchan

gesinHPVconfoundedby•changesincardiacoutput•pulmonaryarterypressure•positionDepartmentofAnesthesiologyCivicCampusCentralnervoussystem•Incre

asecerebralbloodflow•IncreaseICP•DecreasedCMRO2•Decreasedfrequency-increasedvoltageonEEG•2MACenfluran

eincreasesseizureactivity•Decreasedamplitude-increasedlatencyonSSEPDepartmentofAnesthesiologyCivicCampusNeuromuscularfuncti

on•Skeletalmusclerelaxation•PotentiateNDMR•TriggerMHDepartmentofAnesthesiologyCivicCampusHepatic•Hepa

ticarterialbloodflowdecreasedbyhalothane•Clearanceofdrugsdecreasedinkeepingwithreductionsinhepaticbloodflow•Hepatotoxicity•mild,transient,posto

perativeincreaseinLFTs•?duetotransienthypoxia±reductivemetabolites•massivehepaticnecrosis•oxidativemetabolitebindstohepatocyte•repeatexposureleadst

oimmune-mediatednecrosisDepartmentofAnesthesiologyCivicCampusRenal•Dose-dependentdecreasesin•renalbloo

dflow•glomerularfiltrationrate•urineoutput•RelatedtochangesinCOandBPnotADH•Fluoridenephrotoxicityatserumconc.50mo

l/l•F-opposesADHleadingtopolyuria•methoxyflurane2.5MAC-hours•enflurane9.6MAC-hoursDepartmentofAnesthesiologyCivicCampusObstetrical•N2O

hasnoeffect•Halogenatedvolatilesleadtodose-dependent•uterinerelaxation•reductionsinuterinebloodflowDepartmentofAnesthe

siologyCivicCampusMiscellaneous•N2O-relatedmyelosupressionif>12hrexposure•inhibitionofmethionine-synthetase•megaloblasticanem

ia•Inhaledanesthetics,N2Oinparticular,decreaseleukocytefunction•Teratogenesiswithprolongedexposureinrats•Increased

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