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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
alothane2.1g•kg-1•isoflurane6.9g•kg-1•enflurane10.9g•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.50mo
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