Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
Objectives
DrugChoicesandOutcomesin
Neuroanesthesia
or“Don’tTouchThatVaporizer!”
DanielJ.Janik,MD
AssociateProfessor
UniversityofColoradoatDenverand
HealthSciencesCenter
• Beawareofthemultiplegoalstobemet
whenprovidinganesthesiaforpatientswith
intracranialpathology
• Understandtheeffectsofvolatileand
intravenousanestheticagentsonintracranial
dynamics
• Beabletooutlinearationalchoiceof
anestheticwhencaringforpatientswith
variousintracranialsituations
Overview
•
•
•
•
•
•
•
Goalsofanesthesia
Effectsofvolatileanesthetics
Effectsofintravenousanesthetics
Comparisonofvolatileanesthetics
Comparisonofintravenousanesthetics
Volatilevs.intravenousanesthetics
What’sbest?
GoalsofAnestheticManagement
•
•
•
•
•
•
Hemodynamicstability
Maintenanceofcerebralperfusionpressure
Controlofintracranialpressure
Optimalsurgicalconditions(slackbrain)
Smoothemergence
Rapidawakeningforearlyneurologic
assessment
NormalValues
IdealAnestheticAgent
• MaintainCBFwithoutaffectingautoregulation
• MinimizedetrimentalchangesinIntracranial
Pressure(ICP)
• PreservereactivityofcerebralarteriolestoPaCO2
changes
• DecreaseCMRO2 withcerebralprotectioneffects
• Devoidofseizureactivity
• Preservehemodynamicstability,especiallyCerebral
PerfusionPressure(CPP)
• Devoidofarrhythmogeniceffect
•
PatelPMandDrummondJCinMiller’sAnesthesia,6th Ed;p.814
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
DeterminantsofICP
WhyDoesICPMatter?
(andWhatWeCanControl)
• Braintissue
• IntraͲ andextracellularfluid
(edema)
• CSF
• Blood(arterial/venous)
• Airwayorintrathoracic
pressure
• Jugularvenouspressure
•
•
•
•
•
•
•
•
PaCO2
PaO2
Anesthetics
Vasodilators
Seizures
Temperature
Arousal
Pain
• SustainedICP>20mmHgisabnormal
• ICP20– 40mmHgisconsideredmoderate
intracranialhypertension
• ICP>40mmHgislifeͲthreatening
• IncreasedICPresultsinsecondaryinjurydue
toischemiafromreducedCPPanddistortion
ofintracranialstructuressuchasthe
brainstem
EffectsofVolatileAgents
(Aretheyallcreatedequal?)
•
DrummondJCandPatelPMinMiller’sAnesthesia,6th Ed;p.2128
•
•
PatelPMandDrummondJCinMiller’sAnesthesia,6thEd;p.817
EffectsofVolatileAgents
EffectsofVolatileAgents
(Aretheyallcreatedequal?)
(Aretheyallcreatedequal?)
PatelPMandDrummondJCinMiller’sAnesthesia,6th Ed;p.826
•
PatelPMandDrummondJCinMiller’sAnesthesia,6th Ed;p.830
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
EffectsofVolatileAgents
EffectsofVolatileAgents
(AreTheyAllCreatedEqual?)
(Aretheyallcreatedequal?)
• Isofluranehasbeenthe“goldstandard”ofvolatileagentsfor
sometime,but–
• Atboth0.5and1.5MACSevofluraneincreasesVmca less(4
and17%)thanIsoflurane(19and72%)
MattaBFet.al.,Anesthesiology1999;91:677Ͳ80
• SevofluranepreservesautoregulationbetterthanIsoflurane
SummorsACet.al.AnesthAnalg1999;88:341Ͳ5
• At0.4MACinnormalvolunteers,Sevofluraneproducedless
increaseinCBVthanIsoflurane
LorenzIHet.al.,JNeurosurgAnesthesiol2001;Vol13(4):288Ͳ295
• Atboth1.0and1.5MACSevofluraneincreasedVmca less(max
7%)thanDesflurane(max65%)
BedforthNMet.al.,AnesthAnalg2000;91:152Ͳ5
•
MattaBFet.al.,Anesthesiology83:980Ͳ985,1995
ButWhatHappensDuringBrain
Surgery?
•
BedforthNMet.al.
EffectsofVolatileAgents
EffectsofVolatileAgents
(ComparativeStudies,IntracranialSurgery)
(ComparativeStudies,IntracranialSurgery)
• Inastudyofpatientswith
supratentorialmasslesions
andmasseffectonCT,in
thepresenceof
hyperventilation(PaCO2=25
mmHg),1MACDesflurane
inair:O2 increased
CerebrospinalFluid
Pressuregreaterthan
Isoflurane(18vs.8mmHg)
MuzziDAet.al.,Anesthesiology1992;76:720Ͳ
724
• Inastudyofpatientswithintracranialmasslesions(withandwithout
evidenceofincreasedICP,PetCO2=21mmHg),CBFwasslightlyhigherat
1.0MACIsofluranethanDesflurane,buttherewerenodifferencesat1.25
and1.5MAC
• CBFunderanesthesiawas17Ͳ35ml/100g/min
OrnsteinEet.al.,Anesthesiology1993;79:498Ͳ502
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
EffectsofVolatileAgents
(ComparativeStudies,IntracranialSurgery)
• Inpatientsundergoingcraniotomywitha
backgroundofThiopental/Sufentaniland
hyperventilation(PaCO2=30Ͳ35mmHg),
Sevofluranehadearlierrecoveryprofilethan
Isoflurane(movingfeet:24minutesSevovs.
43minutesIso).Hemodynamicvariablesand
brainrelaxationscoresweresimilar
GauthierAet.al.,AnesthAnalg2002;95:1384Ͳ8
EffectsofVolatileAgents
EffectsofVolatileAgents
(ComparativeStudies,IntracranialSurgery)
(ComparativeStudies,IntracranialSurgery)
• Inastudyofchildren(meanage20months)withsuspected
ICPabovenormalgivenabackgroundofFentanyl/N2O60%
andnormocarbia,0.5Ͳ1.0MACIsoflurane,Sevoflurane,and
DesfluranesimilarlyincreasedICPanddecreasedMAPand
CPPinadoseͲdependentmanner.ICPincreasedmore(n.s.)
withhigherbaselinevalueswithDesflurane
SponheimSet.al.,ActaAnaesthesiolScand2003;47:932Ͳ8
• Inastudycomparing0.5,1.0,or1.5MACIsofluraneor
SevofluraneinairwithSufentanil(PetCO2=35Ͳ40mmHg)there
wasnochangeinICPandadecreaseinCBFwithbothagents;
CPPdecreasedat0.5MACwithSevofluraneandalllevelsof
Isoflurane;MAPandCPPwerelowerwithIsoflurane
comparedtoSevoflurane.
• Inpatientswithsupratentorialtumorsandnoevidenceof
midlineshiftreceiving60%N2O/Fentanyl(PetCO2=35mmHg),
bothIsofluraneorDesflurane1.0MACcausednochangein
ICP,a19%decreaseinMAP,anda22%decreaseinCPP.
FragaMet.al.,Anesthesiology2003;98:1085Ͳ90
• Inpatientswithsupratentoriallesionswithmasseffect,there
wasnochangefrombaselineordifferencebetween1.2MAC
IsofluraneorDesfluranewithhypocapnia(PaCO2=30mmHg)
inCSFPorMAP;Therewasnodifferencebetweenagentsin
CPP(DesfluraneCPPtendedtobelowerthanbaselineas
durationincreased).Timetorespondtocommandswas50%
shorterwithDesflurane(30vs.72minutes,n.s.)
KayeAet.al.,AnesthAnalg2004;98:1127Ͳ32
ArtruAAet.al.,AnesthAnalg1997;85:587Ͳ92
EffectsofVolatileAgents
(ComparativeStudies,IntracranialSurgery)
EffectsofIntravenousAgents
•
PatelPMandDrummond JCinMiller’sAnesthesia,6th Ed.,p.821
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
EffectsofIntravenousAgents
(ComparativeStudies,IntracranialSurgery)
ButWhatHappensDuringBrain
Surgery?
• Inpatientswithtumorsandabackgroundof60%N2Oand
normocarbia(PaCO2=36mmHg)Sufentanil(89%)and
Alfentanil(22%)increasedCSFPcomparedtoFentanyl,andall
decreasedCPP(Fentanyl=14%;Sufentanil25%;Alfentanil
37%)
MarxWet.al.,JNeurosurgAnesthesiol1989;Vol1(1):3Ͳ7
• Inpatientswithtumorsreceiving60Ͳ70%N2OwithPetCO2=25
mmHgandeitherAlfentanil,Fentanyl,orSufentanil,although
theAlfentanilgroupreceivedephedrinemorefrequently,
therewasnodifferenceinrecoveryprofilesorintraoperative
brainconditions
FromRPet.al.,Anesthesiology1990;73:896Ͳ904
EffectsofIntravenousAgents
EffectsofIntravenousAgents
(ComparativeStudies,IntracranialSurgery)
(ComparativeStudies,IntracranialSurgery)
• Insedatedpatientswithheadtrauma(GCS=6Ͳ
7)andPaCO2=30Ͳ35mmHg,Propofol(2mg/kg
boluswith150mcg/kg/mininfusion)
decreasedICP(11.3Ͳ9.2mmHg),decreased
MAP(25%),decreasedCBF(35Ͳ26
ml/100g/min),anddecreasedCPP(82Ͳ59mm
Hg)
PinaudMet.al.,Anesthesiology1990;73:404Ͳ9
• Inpatientswithheadtrauma(GCS=6)andhypocapnia
(PaCO2=27mmHg),bolusesofFentanyl(3mcg/kg)or
Sufentanil(0.6mcg/kg)increasedICP(F=8mmHg,S=6mm
Hg)anddecreasedMAP(F=11mmHg,S=10mmHg)
SperryRJetal,Anesthesiology1992;77:416Ͳ420
EffectsofIntravenousAgents
EffectsofIntravenousAgents
(ComparativeStudies,IntracranialSurgery)
(ComparativeStudies,IntracranialSurgery)
• InpatientswithtumorsandabackgroundofIsoflurane0.3Ͳ
0.8%in66%N2OandPaCO2<30mmHg,bolusesof
Remifentanil(0.5mcg/kgand1.0mcg/kg)orAlfentanil(10
mcg/kgand20mcg/kg),neithercausedachangeinICP.
EffectsonMAPweresimilar(decreased)
WarnerDSet.al.,AnesthAnalg1996;83:348Ͳ53
• InpatientswithtumorsgivenIsoflurane(lowdose,
unspecified)/66%N2OandPaCO2=28mmHg,Remifentanil
andFentanyldidnotdifferinICP,CPP,MAP(exceptfor
intubation),braincondition,orrecoveryvariables.
GuyJet.al.,Anesthesiology1997;86:514Ͳ24
• InpatientswithtumorsreceivingPropofolorIsofluranewith
orwithoutN2O,theuseofFentanyl(customarymanner)was
associatedwithdelayedemergence(at10minutesbutnot
20)andgreaterIsofluraneusecomparedwithRemifentanil
(d/catdressing)
BalakrishnanGet.al.,AnesthAnalg2000:91:163Ͳ9
• InpatientsforcraniotomywithPropofolandPaCO2=30Ͳ35
mmHg,RemifentanilrequiredlessPropofolcomparedto
FentanylandAlfentanil,andwasassociatedwithmorerapid
recoverythanAlfentanil(butnotFentanyl).Allagents
decreasedMAPpostͲinduction
ColesJPet.al.,JNeurosurgAnesthesiol2000;Vol12(1):15Ͳ20
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
Volatilevs.Intravenous
(Comparisons,IntracranialSurgery)
HowdotheVolatileAgents
ComparetoIntravenousAgents?
• PatientswithoutsignsofhighICPgiveneither
Isoflurane(0.5Ͳ1.5%)orPropofolinfusion(N2O
50%giventobothafterduralopening)found
lowerCPP(81vs.70mmHg)atinduction,
lowerCSFP(15.2vs.11.6mmHg)andbetter
recoveryvariablesat20Ͳ30minuteswith
Propofol
RavussinPet.al.,JNeurosurgAnesthesiol1991;Vol3(2):85Ͳ95
•
Volatilevs.Intravenous
Volatilevs.Intravenous
(Comparisons,IntracranialSurgery)
(Comparisons,IntracranialSurgery)
InpatientswithtumorsgiveneitherPropofol/Fentanyl,Isoflurane/N2O,or
Fentanyl/N2OwithPaCO2=30mmHg,therewerenodifferencesinmeanICP
(ISO/N2OwasassociatedwithagreaternumberofpatientswithICP>24mmHg)or
braincondition.MAPandCPPwaslowerwithIso/N2O.Emergencewasmore
rapidwithFentanyl/N2O.
ToddMMet.al.,Anesthesiology1993;78:1005Ͳ1020
• Inpatientswithpituitarytumorsandnomasseffect,after
inductionwithFentanyl/Propofol/N2Oandnormocarbia,
DesfluraneandIsoflurane0.5and1.0MACincreasedCSFP(5and4
mmHg)anddecreasedCPP(12and15mmHG)comparedto
Propofolinfusion(nochange)
TalkePet.al.,Anesthesiology1996;85:999Ͳ1004
• Inpatientswithpituitarytumorsandnomasseffect,similar
conditionstoabove,SevofluraneincreasedCSFP(2mmHg)and
decreasedCPP(11Ͳ15mmHg)at0.5and1.0MACcomparedto
Propofolinfusion(nochange)
TalkePet.al.,Anesthesiology1999;91:127Ͳ30
• InpatientswithsupratentorialtumorsgivenN2O,theuseofeither
aPropofolinfusion,Isoflurane,orIsofluraneswitchingtoPropofol
atduralclosurewasnotassociatedwithanydifferencesin
hemodynamicorrecoveryvariables.
TalkePet.al.,AnesthAnalg2002;95:430Ͳ5
Volatilevs.Intravenous
Volatilevs.Intravenous
(Comparisons,IntracranialSurgery)
(Comparisons,IntracranialSurgery)
• InpatientswithtumorsmaintainedwithFentanyl,theuseofa
PropofolinfusionwasassociatedwithalowerICP(7mmHg)
andhigherCPP(80mmHg)comparedtoIsoflurane(12/60
mmHg)orSevoflurane(11/63mmHg)
PetersenKDet.al.,ActaNeurochirSuppl2002;81:89Ͳ91
• Inpatientswithmasslesionsinducedwith
Propofol/Fentanyl/airandPaCO2=35mmHg,therewasno
differenceinbrainconditionorrecoveryvariablesbetween
Sevoflurane/FentanylorPropofol/Remifentanil.Therewas
morehypotensionintheTIVAgroup.
MagniGet.al.,JNeurosurgAnesthesiol2005;Vol17(3):134Ͳ8
•
InpatientswithtumorsandPetCO2=30Ͳ40mmHg,receivingeither
Propofol/Fentanyl,Isoflurane/Fentanyl,orSevoflurane/Fentanyl,ICPwaslower
andMAPandCPPhigherwithTIVA.Duraltensionwassignificantlylowerwith
TIVAandSevo.CerebralswellingafterduralopeningwaslowerwithTIVA.No
differenceinICP,CPP,orCO2 reactivitybetweenvolatiles.
PetersenKDet.al.,Anesthesiology2003;98:329Ͳ36
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
CBF,ICP,CBV,orCPP?
•
•
•
•
CPP=MAP– ICP
WanttomaintainCPP=70– 90mmHg
ICPaffectedbyintracranialvolume
Intracranialvolumehas4components:
Tissuevolume
CSFvolume
Fluidcompartment(edema)
Bloodvolume(arterialandvenous)
• CBFreflectsarterialvolume– howmuchdoesthis
reallyaffecttotalCBV?
CBF,ICP,CBV,orCPP?
CBF,ICP,CBV,orCPP?
• Approximately10%ofCBVisinthearteriolesandcapillaries– the
compartmentwhichreactstoCO2 andanestheticagents
SchmidekHHet.al.,Neurosurgery1985;17:663Ͳ78
HeistadDDet.al.inHandbookofPhysiology;AmericanPhysiologicSociety,1983
• Indogsbreathing60Ͳ70%N2OandexposedtoFentanyl,1.4%
Isoflurane,0.8%Halothane,or2.2%Enfluranefor3.5hours:
Halothane:јCBV(11%),јICP(stable)
EnŇurane:јCBV(9%),јICP(conƟnuedtorise,evenaŌerEnfoī)
IsoŇuraneјCBV(10%),јICP(onlyfor20min,thenreturnedtobaseline)
Fentanyl:љCBV(8%),љICP(onlyforĮrst20min,thenreturnedto
baseline)
ArtruAA,Anesthesiology1983;58:533Ͳ9
ArtruAA,Anesthesiology1984;60:575Ͳ9
Volatilevs.IntravenousAgents
(IsThereReallyaDifferenceinMechanism?)
• InratsexposedtoPropofol,Pentobarbital,orIsofluraneanesthesia,
thoughCBFwas2.0Ͳ2.6timesgreaterwithIsothanProporPento,CBV
wasonly10Ͳ18%greaterwithIsothanwithProporPento
ToddMMandWeeksJ,JNeurosurgAnesthesiol1996;Vol8(4):296Ͳ303
Volatilevs.IntravenousAgents
(IsOneReallyBetter?)
• Itdependsonhowyoudefine“better”
Quickeremergence(shorttermoutcome)
Easeoftitration/administration
Hemodynamicstability
Brainconditions
Longtermoutcomes(nodata)
¢versus$(costcontainment)
• PatelPMandDrummondJCinMiller’sAnesthesia,6th Ed.,p.815
OneMoreNote
• Inmanyofthestudiescomparingvolatile
agents,orvolatiletointravenousagents,
exclusioncriteriaincludedevidenceof
increasedintracranialpressuresuchasmass
shift,alteredmentalstatus,orabnormal
measuredICP
Janik, Daniel, MD
Drug Choices and Outcomes in Neuroanesthesia
MyOpinion
• Forallagents,theultimateconditionofthepatientwillbe
determinedbythesumoftheeffectsofthechosenagentonCBF,
CMRO2,vasculartone,MAP,CO,CSFformation/reabsorption,and
CBV.
• Thepreponderanceofevidenceisthatintravenousagents
(Propofol,Barbiturates,Etomidate,Benzodiazepines,synthetic
opiates(phenylpiperidine))havelessdeleterious,andmore
salutaryeffectsthataremorepredictableonintracranialdynamics
thanvolatileagents,especiallyifMAPismaintained.
• Isoflurane,Sevoflurane,andDesfluranearesimilar,thoughthe
edgeprobablyshouldgotoSevoflurane,andtheirultimate
effectsonICP/CPParelesspredictable.
• Thereisnooverwhelmingevidencethatonetechniqueissuperior
toanyotherintermsofshorttermrecoveryprofile,iftheagents
chosenareproperlyadministered.
• Chooseyourpoison(agents)wiselygiventhegoalsofanesthesia
andsurgery,andtheconditionofthepatientsuchas………
MyOpinion
• Ifthepatienthassignsorsymptomsofhigh
ICP(alteredmentalstatus,headinjury,
ventriculostomy/ICPmonitorinplace,midline
shiftonCT/MRI,etc.):
ͲManagementoftheICP/CBF/CBV/CPPiscritical
ͲTIVAispreferable,atleastuntilthedurais
openedandtheeffectsofanestheticsonthebrain
bulkcanbeassesseddirectly
ͲKeepaverycloseeyeonCPP(>70mmHg)
ͲThink/Think/Think:MAPͲICP
THEEND
MyOpinion
• Ifthepatientiswideawake,appearingforelective
surgery,andiswellͲcompensatedintermsofintracranial
dynamics:
EithervolatileorTIVAareappropriatetakingcaretoavoid
badthingslike–
Hypotension(rememberCPP)
Hypertension
Hypoxemia
Hypercarbia
Inadequateanesthesiaatcriticalpoints
Remember– it’smoreimportanthowyoudoit,thanwhat
youuse.
ComparativeCosts
• 1993:
Propofol/Fentanyl=$152
Isoflurane/N2O=$49
Fentanyl/N2O=$15
• 2002:
Isoflurane/N2O=$17
Propofol/Fentanyl/N2O=$114
Isoflurane/N2OthenPropofol=$31