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29/4/2015 ManagementofIntracranialHypertension

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2452989/ 1/17

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NeurolClin.AuthormanuscriptavailableinPMC2009May1.Publishedinfinaleditedformas:

NeurolClin.2008May26(2):521541.doi:10.1016/j.ncl.2008.02.003

PMCID:PMC2452989NIHMSID:NIHMS56358

ManagementofIntracranialHypertensionLeonardoRangelCastillo,MD,ShankarGopinath,MD,andClaudiaS.Robertson,MD

DepartmentofNeurosurgery,BaylorCollegeofMedicine,OneBaylorPlaza,Houston,TX77030,USA*Correspondingauthor.Emailaddress:[email protected](C.S.Robertson)

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Thepublisher'sfinaleditedversionofthisarticleisavailableatNeurolClinThisarticlehasbeencorrected.Seethecorrectioninvolume26onpagexvii.

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Abstract

Effectivemanagementofintracranialhypertensioninvolvesmeticulousavoidanceoffactorsthatprecipitateoraggravateincreasedintracranialpressure.Whenintracranialpressurebecomeselevated,itisimportanttoruleoutnewmasslesionsthatshouldbesurgicallyevacuated.Medicalmanagementofincreasedintracranialpressureshouldincludesedation,drainageofcerebrospinalfluid,andosmotherapywitheithermannitolorhypertonicsaline.Forintracranialhypertensionrefractorytoinitialmedicalmanagement,barbituratecoma,hypothermia,ordecompressivecraniectomyshouldbeconsidered.Steroidsarenotindicatedandmaybeharmfulinthetreatmentofintracranialhypertensionresultingfromtraumaticbraininjury.

Intracranialhypertensionisacommonneurologiccomplicationincriticallyillpatientsitisthecommonpathwayinthepresentationofmanyneurologicandnonneurologicdisorders.Theunderlyingpathophysiologyofincreasedintracranialpressure(ICP)isthesubjectofintensebasicandclinicalresearch,whichhasledtoadvancesinunderstandingofthephysiologyrelatedtoICP.Fewspecifictreatmentoptionsforintracranialhypertensionhavebeensubjectedtorandomizedtrials,however,andmostmanagementrecommendationsarebasedonclinicalexperience.

Intracranialpressure

Normalvalues

Innormalindividualswithclosedcranialfontanelles,centralnervoussystemcontents,includingbrain,spinalcord,blood,andcerebrospinalfluid(CSF),areencasedinanoncompliantskullandvertebralcanal,constitutinganearlyincompressiblesystem.Thereisasmallamountofcapacitanceinthesystemprovidedbytheintervertebralspaces.Intheaverageadult,theskullenclosesatotalvolumeof1450mL:1300mLofbrain,65mLofCSF,and110mLofblood[1].TheMonroeKelliehypothesisstatesthesumoftheintracranialvolumesofblood,brain,CSF,andothercomponentsisconstant,andthatanincreaseinanyoneofthesemustbeoffsetbyanequaldecreaseinanother,orelsepressureincreases.Anincreaseinpressurecausedbyanexpandingintracranialvolumeis

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distributedevenlythroughouttheintracranialcavity[2,3].

ThenormalrangeforICPvarieswithage.Valuesforpediatricsubjectsarenotaswellestablished.Normalvaluesarelessthan10to15mmHgforadultsandolderchildren,3to7mmHgforyoungchildren,and1.5to6mmHgforterminfants.ICPcanbesubatmosphericinnewborns[4].Forthepurposeofthisarticle,normaladultICPisdefinedas5to15mmHg(7.520cmH O).ICPvaluesof20to30mmHgrepresentmildintracranialhypertensionhowever,whenatemporalmasslesionispresent,herniationcanoccurwithICPvalueslessthan20mmHg[5].ICPvaluesgreaterthan20to25mmHgrequiretreatmentinmostcircumstances.SustainedICPvaluesofgreaterthan40mmHgindicatesevere,lifethreateningintracranialhypertension.

Cerebraldynamicsoverview

Cerebralperfusionpressure(CPP)dependsonmeansystemicarterialpressure(MAP)andICPbythefollowingrelationship:

Asaresult,CPPcanbereducedfromanincreaseinICP,adecreaseinbloodpressure,oracombinationofbothfactors.Throughthenormalregulatoryprocesscalledpressureautoregulation,thebrainisabletomaintainanormalcerebralbloodflow(CBF)withaCPPrangingfrom50to150mmHg.AtCPPvalueslessthan50mmHg,thebrainmaynotbeabletocompensateadequately,andCBFfallspassivelywithCPP.Afterinjury,theabilityofthebraintopressureautoregulatemaybeabsentorimpaired,andevenwithanormalCPP,CBFcanpassivelyfollowchangesinCPP.

WhenCPPiswithinthenormalautoregulatoryrange(50150mmHg),thisabilityofthebraintopressureautoregulatealsoaffectstheresponseofICPtoachangeinCPP[68].Whenpressureautoregulationisintact,decreasingCPPresultsinvasodilationofcerebralvessels,whichallowsCBFtoremainunchanged.ThisvasodilationcanresultinanincreaseinICP,whichfurtherperpetuatesthedecreaseinCPP.Thisresponsehasbeencalledthevasodilatorycascade.Likewise,anincreaseinCPPresultsinvasoconstrictionofcerebralvesselsandmayreduceICP.Whenpressureautoregulationisimpairedorabsent,ICPdecreasesandincreaseswithchangesinCPP.

Intracranialhypertension

Causesofintracranialhypertension

Thedifferentcausesofintracranialhypertension(Box1)canoccurindividuallyorinvariouscombinations.InprimarycausesofincreasedICP,normalizationofICPdependsonrapidlyaddressingtheunderlyingbraindisorder.Inthesecondgroup,intracranialhypertensionisduetoanextracranialorsystemicprocessthatisoftenremediable[911].ThelastgroupiscomposedofthecausesofincreasedICPafteraneurosurgicalprocedure.

Box1.Causesofintracranialhypertension

Intracranial(primary)

BraintumorTrauma(epiduralandsubduralhematoma,cerebralcontusions)NontraumaticintracerebralhemorrhageIschemicstroke

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HydrocephalusIdiopathicorbenignintracranialhypertensionOther(eg,pseudotumorcerebri,pneumoencephalus,abscesses,cysts)

Extracranial(secondary)

AirwayobstructionHypoxiaorhypercarbia(hypoventilation)Hypertension(pain/cough)orhypotension(hypovolemia/sedation)Posture(headrotation)HyperpyrexiaSeizuresDrugandmetabolic(eg,tetracycline,rofecoxib,divalproexsodium,leadintoxication)Others(eg,highaltitudecerebraledema,hepaticfailure)

Postoperative

Masslesion(hematoma)EdemaIncreasedcerebralbloodvolume(vasodilation)DisturbancesofCSF

Intracranialhypertensionsecondarytotraumaticbraininjury

Specialfeaturesshouldbeconsideredinpatientswithtraumaticbraininjury(TBI),inwhichlesionsmaybeheterogeneous,andseveralfactorsoftencontributetoincreasetheICP[12]:

1. Traumaticallyinducedmasses:epiduralorsubduralhematomas,hemorrhagiccontusions,foreignbody,anddepressedskullfractures

2. Cerebraledema[13]3. Hyperemiaowingtovasomotorparalysisorlossofautoregulation[14]4. Hypoventilationthatleadstohypercarbiawithsubsequentcerebralvasodilation5. HydrocephalusresultingfromobstructionoftheCSFpathwaysoritsabsorption6. Increasedintrathoracicorintraabdominalpressureasaresultofmechanicalventilation,posturing,

agitation,orValsalvamaneuvers

Afterevacuationoftraumaticmasslesions,themostimportantcauseofincreasedICPwasthoughttobevascularengorgement[14].Recentstudieshavesuggestedthatcerebraledemaistheprimarycauseinmostcases[15].

AsecondaryincreaseintheICPoftenisobserved3to10daysafterthetrauma,principallyasaresultofadelayedhematomaformation,suchasepiduralhematomas,acutesubduralhematoma,andtraumatichemorrhagiccontusionswithsurroundingedema,sometimesrequiringevacuation[16].OtherpotentialcausesofdelayedincreasesinICParecerebralvasospasm[17],hypoventilation,andhyponatremia.

Neurologicintensivecaremonitoring

Intracranialhypertensionisanimportantcauseofsecondaryinjuryinpatientswithacuteneurologicandneurosurgicaldisordersandtypicallymandatesspecificmonitoring.Patientswithsuspectedintracranialhypertension,especiallysecondarytoTBI,shouldhavemonitoringofICPmonitoringofcerebraloxygenextraction,aswithjugularbulboximetryorbraintissuePO ,mayalsobeindicated.Braininjuredpatientsalsoshouldhaveclosemonitoringofsystemicparameters,includingventilation,oxygenation,electrocardiogram,heartrate,bloodpressure,temperature,bloodglucose,andfluidintakeandoutput.Patientsshouldbemonitoredroutinelywithpulseoximetryandcapnographytoavoidunrecognizedhypoxemiaandhypoventilationor

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hyperventilation.Acentralvenouscathetercommonlyisneededtohelpevaluatevolumestatus,andaFoleycatheterisemployedforaccurateurineoutput.

Intracranialpressuremonitoring

ClinicalsymptomsofincreasedICP,suchasheadache,nausea,andvomiting,areimpossibletoelicitincomatosepatients.Papilledemaisareliablesignofintracranialhypertension,butisuncommonafterheadinjury,eveninpatientswithdocumentedelevatedICP.Inastudyofpatientswithheadtrauma,54%ofpatientshadincreasedICP,butonly3.5%hadpapilledemaonfundoscopicexamination[18].Othersigns,suchaspupillarydilationanddecerebrateposturing,canoccurintheabsenceofintracranialhypertension.CTscansignsofbrainswelling,suchasmidlineshiftandcompressedbasalcisterns,arepredictiveofincreasedICP,butintracranialhypertensioncanoccurwithoutthosefindings[19].

Typesofmonitors

TheventriculostomycatheteristhepreferreddeviceformonitoringICPandthestandardagainstwhichallnewermonitorsarecompared[20].Anintraventricularcatheterisconnectedtoanexternalpressuretransducerviafluidfilledtubing.Theadvantagesoftheventriculostomyareitsrelativelylowcost,theoptiontouseitfortherapeuticCSFdrainage,anditsabilitytorecalibratetominimizeerrorsowingtomeasurementdrift.Thedisadvantagesaredifficultieswithinsertionintocompressedordisplacedventricles,inaccuraciesofthepressuremeasurementsbecauseofobstructionofthefluidcolumn,andtheneedtomaintainthetransduceratafixedreferencepointrelativetothepatientshead.Thesystemshouldbecheckedforproperfunctioningatleastevery2to4hours,andanytimethereisachangeintheICP,neurologicexamination,andCSFoutput.Thischeckshouldincludeassessingforthepresenceofanadequatewaveform,whichshouldhaverespiratoryvariationsandtransmittedpulsepressure.

Whentheventriclecannotbecannulated,otheralternativescanbeused.DifferentnonfluidcoupleddevicesareavailableforICPmonitoringandhavereplacedthesubarachnoidbolt.Themicrosensortransducerandthefiberoptictransducerarethemostwidelyavailable.Thesetransducertippedcatheterscanbeinsertedinthesubduralspaceordirectlyintothebraintissue[21].Themainadvantagesofthesemonitorsistheeaseofinsertion,especiallyinpatientswithcompressedventricleshowever,noneofthetransducertippedcatheterscanberesettozeroaftertheyareinsertedintotheskull,andtheyexhibitmeasurementdriftovertime[22].SubduralandepiduralmonitorsforICPmeasurementsarelessaccuratecomparedtoventriculostomyorparenchymalmonitors.

Forsurgicalpatients,theICPmonitormaybeinsertedattheendofthesurgicalprocedure.ICPmonitoringiscontinuedforaslongastreatmentofintracranialhypertensionisrequired,typically3to5days.AsecondaryincreaseinICPmaybeobserved3to10daysaftertraumain30%ofpatientswithintracranialhypertension[16]secondarytodevelopmentofdelayedintracerebralhematoma,cerebralvasospasm,orsystemicfactorssuchashypoxiaandhypotension.

Typesofintracranialpressurewaveforms

ThevariationsseeninthenormaltracingofICPoriginatefromsmallpulsationstransmittedfromthesystemicbloodpressuretotheintracranialcavity.Thesebloodpressurepulsationsaresuperimposedonsloweroscillationcausedbytherespiratorycycle.Inmechanicallyventilatedpatients,thepressureinthesuperiorvenacavaincreasesduringinspiration,whichreducesvenousoutflowfromthecranium,causinganelevationinICP.

Pathologicwaveforms

AstheICPincreases,cerebralcompliancedecreases,arterialpulsesbecomemorepronounced,andvenouscomponentsdisappear.PathologicwaveformsincludeLundbergA,B,andCtypes.LundbergAwavesorplateauwavesareICPelevationstomorethan50mmHglasting5to20minutes.Thesewavesareaccompaniedbya



simultaneousincreaseinMAP,butitisnotclearlyunderstoodifthechangeinMAPiscauseoreffect.LundbergBwavesorpressurepulseshaveanamplitudeof50mmHgandoccurevery30secondsto2minutes.LundbergCwaveshaveanamplitudeof20mmHgandafrequencyof4to8perminutetheyareseeninthenormalICPwaveform,buthighamplitudeCwavesmaybesuperimposedonplateauwaves[23].

Indicationsforintracranialpressuremonitoring

MonitoringofICPisaninvasivetechniqueandhassomeassociatedrisks.Forafavorablerisktobenefitratio,ICPmonitoringisindicatedonlyinpatientswithsignificantriskofintracranialhypertension[12](Box2).PatientswithTBIwhoareparticularlyatriskfordevelopinganelevatedICPincludethosewithGlasgowComaScaleof8orlessaftercardiopulmonaryresuscitationandwhohaveanabnormaladmissionheadCTscan.Suchabnormalitiesmightincludelowdensityorhighdensitylesions,includingcontusionsepidural,subdural,orintraparenchymalhematomascompressionofbasalcisternsandedema[24].Patientswhoareabletofollowcommandshavealowriskfordevelopingintracranialhypertension,andserialneurologicexaminationscanbefollowed.

Box2:IndicationsforICPMonitoring

GCSScore:38(afterresuscitation)

1. AbnormalAdmissionHeadCTScan

a. Hematomab. Contusionc. Edemad. Herniatione. Compressedbasalcisterns

2. NormalAdmissionHeadCTScanPLUS2ormoreofthefollowing

a. Age>40yearsb. Motorposturingc. Systolicbloodpressure



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Themostcommoncomplicationofventriculostomycatheterplacementisinfectionwithanincidenceof5%to14%colonizationofthedeviceismorecommonthanclinicalinfection[25].Astudyfoundnosignificantreductionininfectionrateinpatientsundergoingprophylacticchangeofmonitorsbeforeday5,comparedwiththosewhosecatheterswereinplacefor5daysormore.[26].FactorsthatarenotassociatedwithinfectionareinsertionofthecatheterintheneurologicICU,previouscatheterinsertion,drainageofCSF,anduseofsteroids.Inagroupofpatientswithprolongedventriculardrainageof10daysormore,anonlinearincreaseindailyinfectionratewasobservedovertheinitial4daysbutremainedconstantdespiteprolongedcatheteruse[27].Useofantibioticcoatedventriculostomycathetershasbeenshowntoreducetheriskofinfectionfrom9.4%to1.3%[28].Othercomplicationsofventriculostomycathetersarehemorrhagewithanoverallincidenceof1.4%,malfunction,obstruction,andmalposition.

Intracranialpressuretreatmentmeasures:briefsummaryofgoalsoftherapy

1. MaintainICPatlessthan20to25mmHg.2. MaintainCPPatgreaterthan60mmHgbymaintainingadequateMAP.3. AvoidfactorsthataggravateorprecipitateelevatedICP.

AnoverallapproachtothemanagementofintracranialhypertensionispresentedinFig.1.

Fig.1Diagramofdiagnosisandtreatmentofintracranialhypertension.

Generalcaretominimizeintracranialhypertension

Preventionortreatmentoffactorsthatmayaggravateorprecipitateintracranialhypertensionisacornerstoneofneurologiccriticalcare.Specificfactorsthatmayaggravateintracranialhypertensionincludeobstructionofvenousreturn(headposition,agitation),respiratoryproblems(airwayobstruction,hypoxia,hypercapnia),fever,severehypertension,hyponatremia,anemia,andseizures.

Optimizingcerebralvenousoutflow

TominimizevenousoutflowresistanceandpromotedisplacementofCSFfromtheintracranialcompartmenttothespinalcompartment,elevationoftheheadofthebedandkeepingtheheadinaneutralpositionarestandardsinneurosurgicalcare.SomeauthorshaveadvocatedkeepingthepatientsheadflattomaximizeCPP[7].OtherstudieshaveshownareductioninICPwithoutareductionineitherCPPorCBFinmostpatientswithelevationoftheheadto30[29].Stillotherauthorshaveobservedthatelevationoftheheadto30reducedICPandincreasedCPP,butdidnotchangebraintissueoxygenation[30].ThereductioninICPaffordedby15to30ofheadelevationisprobablyadvantageousandsafeformostpatients.Whenheadelevationisused,thepressuretransducersforbloodpressureandICPmustbezeroedatthesamelevel(attheleveloftheforamenofMonro)toassessCPPaccurately.

Increasedintraabdominalpressure,ascanoccurwithabdominalcompartmentsyndrome,alsocanexacerbateICPpresumablybyobstructingcerebralvenousoutflow.SeveralcasereportshaveobservedimmediatereductionsinICPwithdecompressivelaparotomyinsuchcircumstances.Aretrospectivereportindicatedthatevenwhenabdominalcompartmentsyndromeisnotpresent,abdominalfascialreleasecanreduceeffectivelyICPthatisrefractorytomedicaltreatment[31].

Respiratoryfailure



Respiratorydysfunctioniscommoninpatientswithintracranialhypertension,especiallywhenthecauseisheadtrauma.HypoxiaandhypercapniacanincreaseICPdramatically,andmechanicalventilationcanaltercerebralhemodynamics.OptimalrespiratorymanagementiscrucialforcontrolofICP.

Thirtysixpercentofcomatoseheadinjurypatientspresentwithhypoxiaandrespiratorydysfunctionrequiringmechanicalventilationonadmission.Pneumoniaandpulmonaryinsufficiencyoccurin42%and28%ascomplicationsduringhospitalization.In227spontaneouslybreathingpatientswithneurologicdisorders,mostwithintracranialhypertension,NorthandJennettfoundthat60%hadbreathingabnormalities,includingperiodicrespirations,tachypnea,andirregularbreathing[32].Periodicbreathingwasnotcorrelated,however,withanyparticularanatomicsiteoftheneurologicinjury.PeriodicepisodesofhypoventilationcanprecipitateincreasedICP[33].ControlledventilationtomaintainanormalPaCO caneliminatethiscauseofintracranialhypertension.

MechanicalventilationalsocanhaveadverseeffectsonICP.PEEP,whichmaybeneededtoimproveoxygenation,canincreaseICPbyimpedingvenousreturnandincreasingcerebralvenouspressureandICP,andbydecreasingbloodpressureleadingtoareflexincreaseofcerebralbloodvolume.ForPEEPtoincreasecerebralvenouspressuretolevelsthatwouldincreaseICP,thecerebralvenouspressuremustatleastequaltheICP.ThehighertheICP,thehigherthePEEPmustbetohavesuchadirecthydrauliceffectonICP.TheconsequencesofPEEPonICPalsodependonlungcompliance,andminimalconsequencesforICPusuallyareobservedwhenlungcomplianceislowasinpatientswithacutelunginjury[34].

Sedationandanalgesia

AgitationandpainmaysignificantlyincreasebloodpressureandICP.Adequatesedationandanalgesiaisanimportantadjuncttreatment.Nosedativeregimenhasclearadvantagesinthispatientpopulation.Ingeneral,benzodiazepinescauseacoupledreductionincerebralmetabolicrateofoxygen(CMRO )andCBF,withnoeffectonICP,whereasthenarcoticshavenoeffectonCMRO orCBF,buthavebeenreportedtoincreaseICPinsomepatients[35].Oneconsiderationinthechoiceofsedativeshouldbetominimizeeffectsonbloodpressurebecausemostavailableagentscandecreasebloodpressure.Hypovolemiapredisposestohypotensivesideeffectsandshouldbetreatedbeforeadministeringsedativeagents.Selectionofshorteractingagentsmayhavetheadvantageofallowingbriefinterruptionofsedationtoevaluateneurologicstatus.

Fever

Feverincreasesmetabolicrateby10%to13%perdegreeCelsiusandisapotentvasodilator.FeverinduceddilationofcerebralvesselscanincreaseCBFandmayincreaseICP.FeverduringthepostinjuryperiodworsensneurologicinjuryinexperimentalmodelsofTBI[36].InanobservationalstudyinpatientswithTBI,Jonesandcolleagues[37]foundasignificantrelationshipbetweenfeverandapoorneurologicoutcome.Whileapatientisatriskforintracranialhypertension,fevershouldbecontrolledwithantipyreticsandcoolingblankets.Infectiouscausesmustbesoughtandtreatedwithappropriateantibioticswhenpresent.

Hypertension

Elevatedbloodpressureisseencommonlyinpatientswithintracranialhypertension,especiallysecondarytoheadinjury,andischaracterizedbyasystolicbloodpressureincreasegreaterthandiastolicincrease.Itisassociatedwithsympathetichyperactivity[38].Itisunwisetoreducesystemicbloodpressureinpatientswithhypertensionassociatedwithuntreatedintracranialmasslesionsbecausecerebralperfusionisbeingmaintainedbythehigherbloodpressure.Intheabsenceofanintracranialmasslesion,thedecisiontotreatsystemichypertensionismorecontroversialandmayneedtobeindividualizedforeachpatient.

Whenpressureautoregulationisimpaired,whichiscommonafterTBI,systemichypertensionmayincreaseCBFandICP.Inaddition,elevatedbloodpressuremayexacerbatecerebraledemaandincreasetheriskofpostoperativeintracranialhemorrhage.

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Systemichypertensionmayresolvewithsedation.Ifthedecisionismadetotreatsystemichypertension,thechoiceofantihypertensiveagentisimportant.Vasodilatingdrugs,suchasnitroprusside,nitroglycerin,andnifedipine,canbeexpectedtoincreaseICPandmayreflexivelyincreaseplasmacatecholamines,whichmaybedeleterioustothemarginallyperfusedinjuredbrain.Sympathomimeticblockingantihypertensivedrugs,suchasblockingdrugs(labetalol,esmolol)orcentralactingreceptoragonists(clonidine),arepreferredbecausetheyreducebloodpressurewithoutaffectingtheICP.Agentswithashorthalflifehaveanadvantagewhenthebloodpressureislabile.

Treatmentofanemia

AnecdotalcaseshavebeenreportedofpatientswithsevereanemiapresentingwithsymptomsofincreasedICPandsignsofpapilledema,whichresolvewithtreatmentoftheanemia[39].ThemechanismisthoughttoberelatedtothemarkedincreaseinCBFthatisrequiredtomaintaincerebraloxygendeliverywhenanemiaissevere.AlthoughanemiahasnotbeenclearlyshowntoexacerbateICPafterTBI,acommonpracticeistomaintainhemoglobinconcentrationataminimumof10g/dL.Inviewofalargerandomizedtrialofcriticallyillpatientsthatshowedbetteroutcomewithamorerestrictivetransfusionthresholdof7g/dL[40],theissueofoptimalhemoglobinconcentrationinpatientswithTBIneedsfurtherstudy.

Preventionofseizures

Theriskofseizuresaftertraumaisrelatedtotheseverityofthebraininjuryseizuresoccurin15%to20%ofpatientswithsevereheadinjury.SeizurescanincreasecerebralmetabolicrateandICP,butthereisnoclearrelationshipbetweentheoccurrenceofearlyseizuresandaworseneurologicoutcome[41].InpatientswithsevereTBI,50%ofseizuresmaybesubclinicalandcanbedetectedonlywithcontinuouselectroencephalographicmonitoring[42].Significantriskfactorsforlaterseizuresarebraincontusions,subduralhematoma,depressedskullfracture,penetratingheadwound,lossofconsciousnessoramnesiaformorethan1day,andage65yearsorolder.

Inarandomizedclinicaltrial,phenytoinreducedtheincidenceofseizuresduringthefirstweekaftertrauma,butnotthereafter[43].Basedonthisstudy,seizureprophylaxisforpatientswithseverebraininjuryisrecommendedforthefirst7daysafterinjury.Treatmentwithanticonvulsantsbeyond7daysshouldbereservedforpatientswhodeveloplateseizures[44].

Measuresforrefractoryintracranialhypertension

ForpatientswithsustainedICPelevationsofgreaterthan20to25mmHg,additionalmeasuresareneededtocontroltheICP.Emergentsurgicalmanagementshouldbeconsideredwheneverintracranialhypertensionoccurssuddenlyorisrefractorytomedicalmanagement.

Medicalinterventions

Heavysedationandparalysis

Routineparalysisofpatientswithneurosurgicaldisordersisnotindicatedhowever,intracranialhypertensioncausedbyagitation,posturing,orcoughingcanbepreventedbysedationandnondepolarizingmusclerelaxantsthatdonotaltercerebrovascularresistance[45].Acommonlyusedregimenismorphineandlorazepamforanalgesia/sedationandcisatracuriumorvecuroniumasamusclerelaxant,withthedosetitratedbytwitchresponsetostimulation.Althoughadisadvantageofthistherapyisthattheneurologicexaminationcannotbemonitoredclosely,thesedativesandmusclerelaxantscanbeinterruptedonceaday,usuallybeforemorningrounds,toallowneurologicassessments.

Majorcomplicationsofneuromuscularblockadearemyopathy,polyneuropathy,andprolongedneuromuscularblockade.Myopathyisassociatedwiththeuseofneuromuscularblockingagents,particularlyincombinationwith



corticosteroids[46].Polyneuropathyhasbeenobservedinpatientswithsepsisandmultipleorganfailure.Prolongedneuromuscularblockadeisseeninpatientswithmultipleorganfailureespeciallywithkidneyandliverdysfunction.Recommendationstominimizethesecomplicationsarelimitingtheuseanddoseofneuromuscularblockingagents,trainoffourmonitoring,measuringcreatinephosphokinasedaily,andstoppingthedrugdailytoevaluatemotorresponse[47].

Hyperosmolartherapy

Mannitolisthemostcommonlyusedhyperosmolaragentforthetreatmentofintracranialhypertension.Morerecently,hypertonicsalinealsohasbeenusedinthiscircumstance.Afewstudieshavecomparedtherelativeeffectivenessofthesetwohyperosmoticagents,butmoreworkisneeded.

IntravenousbolusadministrationofmannitollowerstheICPin1to5minuteswithapeakeffectat20to60minutes.TheeffectofmannitolonICPlasts1.5to6hours,dependingontheclinicalcondition[48].Mannitolusuallyisgivenasabolusof0.25g/kgto1g/kgbodyweightwhenurgentreductionofICPisneeded,aninitialdoseof1g/kgbodyweightshouldbegiven.Arterialhypotension(systolicbloodpressure



Hyperventilation

HyperventilationdecreasesPaCO ,whichcaninduceconstrictionofcerebralarteriesbyalkalinizingtheCSF.TheresultingreductionincerebralbloodvolumedecreasesICP.Hyperventilationhaslimiteduseinthemanagementofintracranialhypertension,however,becausethiseffectonICPistimelimited,andbecausehyperventilationmayproduceasufficientdecreaseinCBFtoinduceischemia.

Thevasoconstrictiveeffectoncerebralarterioleslastsonly11to20hoursbecausethepHoftheCSFrapidlyequilibratestothenewPaCO level.AstheCSFpHequilibrates,thecerebralarteriolesredilate,possiblytoalargercaliberthanatbaseline,andtheinitialreductionincerebralbloodvolumecomesatthecostofapossiblereboundphaseofincreasedICP[57,58].Forthisreason,themosteffectiveuseofhyperventilationisacutelytoallowtimeforother,moredefinitivetreatmentstobeputintoaction.Whenhypocarbiaisinducedandmaintainedforseveralhours,itshouldbereversedslowly,overseveraldays,tominimizethisreboundhyperemia[59].

HyperventilationdecreasesCBF,butwhetherthisreductioninflowissufficienttoinduceischemiaininjuredbrainiscontroversial.OneprospectivestudyshowedthatacutelyreducingPaCO fromanaverageof36mmHgto29mmHgreducedglobalCBFandsignificantlyincreasedthevolumeofbrainthatwasmarkedlyhypoperfuseddespiteimprovementsinICPandCPP[60].Diringerandcoworkers[61]showedsimilarchangesinCBFwithmoderatehyperventilation,butdidnotobserveanychangesinregionalCMRO evenwhenCBFwasreducedtolessthan10mL/100g/minininjuredbraintissue,suggestingthatenergyfailureassociatedwithcerebralischemiawasnotoccurring.

Althoughhyperventilationinducedischemiahasnotbeenclearlyshown,routinechronichyperventilation(toPaCO of2025mmHg)hadadetrimentaleffectonoutcomeinonerandomizedclinicaltrial[59].Theauthorsofthisstudyrecommendedusinghyperventilationonlyinpatientswithintracranialhypertension,ratherthanasaroutineinallheadinjuredpatients.ThisviewisreinforcedinTBIguidelines.

Barbituratecoma

Barbituratecomashouldonlybeconsideredforpatientswithrefractoryintracranialhypertensionbecauseoftheseriouscomplicationsassociatedwithhighdosebarbiturates,andbecausetheneurologicexaminationbecomesunavailableforseveraldays[62].Pentobarbitalisgiveninaloadingdoseof10mg/kgbodyweightfollowedby5mg/kgbodyweighteachhourfor3doses.Themaintenancedoseis1to2mg/kg/h,titratedtoaserumlevelof30to50g/mLoruntiltheelectroencephalogramshowsaburstsuppressionpattern.Althoughroutineuseofbarbituratesinunselectedpatientshasnotbeenconsistentlyeffectiveinreducingmorbidityormortalityaftersevereheadinjury[63,64],arandomizedmulticentertrialshowedthatinstitutingbarbituratecomainpatientswithrefractoryintracranialhypertensionresultedinatwofoldgreaterchanceofcontrollingtheICP[65].

ThemechanismofICPreductionbybarbituratesisunclear,butlikelyreflectsacoupledreductioninCBFandCMRO ,withanimmediateeffectonICP.StudiesbyMesseterandcolleagues[66,67]havesuggestedthatthereductioninICPwithbarbituratesiscloselytiedtotheretentionofcarbondioxidereactivitybythebrain.Complicationsoccurringduringtreatmentwithbarbituratecomaincludehypotensionin58%ofpatients,hypokalemiain82%,respiratorycomplicationsin76%,infectionsin55%,hepaticdysfunctionin87%,andrenaldysfunctionin47%[68].Hypotensioncausedbypentobarbitalshouldbetreatedfirstwithvolumereplacementandthenwithvasopressorsifnecessary.Experimentalstudiessuggestthatforthetreatmentofhypotensionassociatedwithbarbituratecoma,volumeresuscitationmaybebetterthandopamine[69]becausedopamineinfusionincreasedcerebralmetabolicrequirementsandpartiallyoffsetthebeneficialeffectsofbarbituratesonCMRO .

Hypothermia

AlthoughamulticenterrandomizedclinicaltrialofmoderatehypothermiainsevereTBIdidnotshowabeneficialeffectonneurologicoutcome,itwasnotedthatfewerpatientsrandomizedtomoderatehypothermiahadintracranial

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hypertension[70].ApilotrandomizedclinicaltrialofhypothermiainchildrenwithTBIproducedsimilarfindingsnoimprovementinneurologicoutcome,butareductioninICPduringthehypothermiatreatment[71].Althoughroutineinductionofhypothermiaisnotindicatedatpresent,hypothermiamaybeaneffectiveadjunctivetreatmentforincreasedICPrefractorytoothermedicalmanagement.

Steroids

Steroidscommonlyareusedforprimaryandmetastasticbraintumors,todecreasevasogeniccerebraledema.Focalneurologicsignsanddecreasedmentalstatusowingtosurroundingedematypicallybegintoimprovewithinhours[72].IncreasedICP,whenpresent,decreasesoverthefollowing2to5days,insomecasestonormal.Themostcommonlyusedregimenisintravenousdexamethasone,4mgevery6hours.Forotherneurosurgicaldisorders,suchasTBIorspontaneousintracerebralhemorrhage,steroidshavenotbeenshowntohaveabenefit[73,74]andinsomestudieshavehadadetrimentaleffect[75,76].

TheCRASHtrial[75]isarecentlycompleted,large(>10,000patientsenrolled),placebocontrolledrandomizedclinicaltrialofmethylprednisolonefor48hoursinpatientswithTBI.Administrationofmethylprednisoloneresultedinasignificantincreaseintheriskofdeathfrom22.3%to25.7%(relativerisk1.15,95%confidenceinterval1.071.24).ThistrialconfirmedpreviousstudiesandguidelinesthatroutineadministrationofsteroidsisnotindicatedforpatientswithTBI.

Surgicalinterventions

Resectionofmasslesions

IntracranialmassesproducingelevatedICPshouldberemovedwhenpossible.Acuteepiduralandsubduralhematomasareahyperacutesurgicalemergency,especiallyepiduralhematomabecausethebleedingisunderarterialpressure.Brainabscessmustbedrained,andpneumocephalusmustbeevacuatedifitisundersufficienttensiontoincreaseICP.Surgicalmanagementofspontaneousintracerebralbleedingiscontroversial[77].

Cerebrospinalfluiddrainage

CSFdrainagelowersICPimmediatelybyreducingintracranialvolumeandmorelongtermbyallowingedemafluidtodrainintotheventricularsystem.DrainageofevenasmallvolumeofCSFcanlowerICPsignificantly,especiallywhenintracranialcomplianceisreducedbyinjury.ThismodalitycanbeanimportantadjuncttherapyforloweringICP.Ifthebrainisdiffuselyswollen,theventriclesmaycollapse,andthismodalitythenhaslimitedutility.

Decompressivecraniectomy

Thesurgicalremovalofpartofthecalvariatocreateawindowinthecranialvaultisthemostradicalinterventionforintracranialhypertension,negatingtheMonroKelliedoctrineoffixedintracranialvolumeandallowingforherniationofswollenbrainthroughthebonewindowtorelievepressure.Decompressivecraniectomyhasbeenusedtotreatuncontrolledintracranialhypertensionofvariousorigins,includingcerebralinfarction[78],trauma,subarachnoidhemorrhage,andspontaneoushemorrhage.Patientselection,timingofoperation,typeofsurgery,andseverityofclinicalandradiologicbraininjuryallarefactorsthatdeterminetheoutcomeofthisprocedure.

SahuquilloandArikan[79]reviewedtheevidenceintheliteratureforstudiesevaluatingtheeffectivenessofdecompressivecraniectomyafterTBI.Theyfoundonlyonesmallrandomizedclinicaltrialin27childrenwithTBI[80].Thistrialfoundareducedriskratiofordeathof0.54(95%confidenceinterval0.171.72),andariskratioof0.54fordeath,vegetativestatus,orseveredisability6to12monthsafterinjury(95%confidenceinterval0.291.07).Alloftheavailablestudiesinadultsareeithercaseseriesorcohortswithhistoricalcontrols.ThesereportssuggestthatdecompressivecraniectomyeffectivelyreducesICPinmost(85%)patientswithintracranial



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hypertensionrefractorytoconventionalmedicaltreatment[81,82].BrainoxygenationmeasuredbytissuePO andbloodflowestimatedbymiddlecerebralarteryflowvelocityalsoareusuallyimprovedafterdecompressivecraniectomy[83,84].Reportedcomplicationsincludehydrocephalus,hemorrhagicswellingipsilateraltothecraniectomysite,andsubduralhygroma[81].Acasereportofparadoxicalherniationalsohasbeenreportedafteralumbarpunctureinapatientwithadecompressivecraniectomy[85].

Therearelimitedresultsfromrandomizedtrialstoconfirmorrefutetheeffectivenessofdecompressivecraniectomyinadults.Reportssuggest,however,thatdecompressivecraniectomymaybeausefuloptionwhenmaximalmedicaltreatmenthasfailedtocontrolICP.ThereareongoingrandomizedcontrolledtrialsinTBI(RescueICP[86]andDECRAN).InapooledanalysisofrandomizedtrialsinpatientswithmalignantMCAinfarction,decompressivesurgeryundertakenwithin48hofstrokewasassociatedwithreducedmortalityandanincreasedproportionofpatientswithafavourablefunctionaloutcome[87].

Summary

EffectivetreatmentofintracranialhypertensioninvolvesmeticulousavoidanceoffactorsthatprecipitateoraggravateincreasedICP.WhenICPbecomeselevated,itisimportanttoruleoutnewmasslesionsthatshouldbesurgicallyevacuated.MedicalmanagementofincreasedICPshouldincludesedation,drainageofCSF,andosmotherapywitheithermannitolorhypertonicsaline.Forintracranialhypertensionrefractorytoinitialmedicalmanagement,barbituratecoma,hypothermia,ordecompressivecraniectomyshouldbeconsidered.SteroidsarenotindicatedandmaybeharmfulinthetreatmentofintracranialhypertensionresultingfromTBI.

Acknowledgments

ThisarticlewassupportedbyNIHgrantP01NS38660.

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References

1.DocziT.Volumeregulationofthebraintissueasurvey.ActaNeurochir(Wien)1993121:18.[PubMed]

2.LangfittTW,WeinsteinJD,KassellNF.Cerebralvasomotorparalysisproducedbyintracranialhypertension.Neurology.196515:62241.[PubMed]

3.MillerJD,SullivanHG.Severeintracranialhypertension.IntAnesthesiolClin.197917:1975.[PubMed]

4.WelchK.Theintracranialpressureininfants.JNeurosurg.198052:6939.[PubMed]

5.AndrewsBT,ChilesBW,III,OslenWL,etal.Theeffectofintracerebralhematomalocationontheriskofbrainstemcompressionandonclinicaloutcome.JNeurosurg.198869:51822.[PubMed]

6.HlatkyR,ValadkaA,RobertsonCS.PredictionofaresponseinICPtoinducedhypertensionusingdynamictestingofcerebralpressureautoregulation.JNeurotrauma.200421:1152.

7.RosnerMJ,ColeyIB.Cerebralperfusionpressure,intracranialpressure,andheadelevation.JNeurosurg.198665:63641.[PubMed]

2



8.GobietW,GroteW,BockWJ.Therelationbetweenintracranialpressure,meanarterialpressureandcerebralbloodflowinpatientswithsevereheadinjury.ActaNeurochir(Wien)197532:1324.[PubMed]

9.FriedmanDI.Medicationinducedintracranialhypertensionindermatology.AmJClinDermatol.20056:2937.[PubMed]

10.JacobS,RajaballyYA.Intracranialhypertensioninducedbyrofecoxib.Headache.200545:756.[PubMed]

11.DigreK,WarnerJ.IsvitaminAimplicatedinthepathophysiologyofincreasedintracranialpressure?Neurology.200564:1827.[PubMed]

12.AdelsonPD,BrattonSL,CarneyNA,etal.Guidelinesfortheacutemedicalmanagementofseveretraumaticbraininjuryininfants,children,andadolescents:Chapter5.indicationsforintracranialpressuremonitoringinpediatricpatientswithseveretraumaticbraininjury.PediatrCritCareMed.20034:S1924.[PubMed]

13.AsgeirssonB,GrandePO,NordstromCH.Anewtherapyofposttraumabrainoedemabasedonhaemodynamicprinciplesforbrainvolumeregulation.IntensiveCareMed.199420:2607.[PubMed]

14.BruceDA,AlaviA,BilaniukL,etal.Diffusecerebralswellingfollowingheadinjuriesinchildren:thesyndromeofmalignantbrainedemaJNeurosurg.198154:1708.[PubMed]

15.MarmarouA,FatourosPP,BarzoP,etal.Contributionofedemaandcerebralbloodvolumetotraumaticbrainswellinginheadinjuredpatients.JNeurosurg.200093:18393.[PubMed]

16.UnterbergA,KieningK,SchmiedekP,etal.Longtermobservationsofintracranialpressureaftersevereheadinjury:thephenomenonofsecondaryriseofintracranialpressure.Neurosurgery.199332:1723.[PubMed]

17.TanedaM,KataokaK,AkaiF,etal.Traumaticsubarachnoidhemorrhageasapredictableindicatorofdelayedischemicsymptoms.JNeurosurg.199684:7628.[PubMed]

18.SelhorstJB,GudemanSK,ButterworthJF,etal.Papilledemaafteracuteheadinjury.Neurosurgery.198516:35763.[PubMed]

19.KishorePR,LipperMH,BeckerDP,etal.SignificanceofCTinheadinjury:correlationwithintracranialpressure.AJRAmJRoentgenol.1981137:82933.[PubMed]

20.AdelsonPD,BrattonSL,CarneyNA,etal.Guidelinesfortheacutemedicalmanagementofseveretraumaticbraininjuryininfants,children,andadolescents:Chapter7intracranialpressuremonitoringtechnology.PediatrCritCareMed.20034:S2830.[PubMed]

21.GopinathSP,RobertsonCS,ContantCF,etal.Clinicalevaluationofaminiaturestraingaugetransducerformonitoringintracranialpressure.Neurosurgery.199536:113740.[PubMed]

22.CzosnykaM,CzosnykaZ,PickardJD.Laboratorytestingofthreeintracranialpressuremicrotransducers:technicalreport.Neurosurgery.199638:21924.[PubMed]

23.LundbergN.Continuousrecordingandcontrolofventricularfluidpressureinneurosurgicalpractice.ActaPsychiatrScand.196036(Suppl149):1193.[PubMed]

24.OSullivanMG,StathamPF,JonesPA,etal.Roleofintracranialpressuremonitoringinseverelyheadinjuredpatientswithoutsignsofintracranialhypertensiononinitialcomputerizedtomography.JNeurosurg.199480:4650.[PubMed]

25.MayhallCG,ArcherNH,LambVA,etal.Ventriculostomyrelatedinfections:aprospectiveepidemiologicstudy.NEnglJMed.1984310:5539.[PubMed]

26.HollowayKL,BarnesT,ChoiS,etal.Ventriculostomyinfections:theeffectofmonitoringdurationand



catheterexchangein584patients.JNeurosurg.199685:419424.[PubMed]

27.ParkP,GartonHJL,KocanMJ,etal.RiskofInfectionwithProlongedVentricularCatheterization.Neurosurgery.200455:594601.[PubMed]

28.ZabramskiJM,WhitingD,DarouicheRO,etal.Efficacyofantimicrobialimpregnatedexternalventriculardraincatheters:aprospective,randomized,controlledtrial.JNeurosurg.200398:72530.[PubMed]

29.FeldmanZ,KanterMJ,RobertsonCS,etal.Effectofheadelevationonintracranialpressure,cerebralperfusionpressure,andcerebralbloodflowinheadinjuredpatients.JNeurosurg.199276:20711.[PubMed]

30.NgI,LimJ,WongHB.Effectsofheadpostureoncerebralhemodynamics:itsinfluencesonintracranialpressure,cerebralperfusionpressure,andcerebraloxygenation.Neurosurgery.200454:5937.[PubMed]

31.JosephDK,DuttonRP,AarabiB,ScaleaTM.Decompressivelaparotomytotreatintractableintracranialhypertensionaftertraumaticbraininjury.JTrauma.200457:68793.[PubMed]

32.NorthJB,JennettS.Abnormalbreathingpatternsassociatedwithacutebraindamage.ArchNeurol.197431:33844.[PubMed]

33.MillerJD,BeckerDP.Secondaryinsultstotheinjuredbrain.JRCollSurgEdinb.198227:2928.[PubMed]

34.CaricatoA,ContiG,DellaCF,etal.EffectsofPEEPontheintracranialsystemofpatientswithheadinjuryandsubarachnoidhemorrhage:theroleofrespiratorysystemcompliance.JTrauma.200558:5716.[PubMed]

35.AlbaneseJ,ViviandX,PotieF,etal.Sufentanil,fentanyl,andalfentanilinheadtraumapatients:astudyoncerebralhemodynamics.CritCareMed.199927:40711.[PubMed]

36.DietrichWD,AlonsoO,HalleyM,etal.Delayedposttraumaticbrainhyperthermiaworsensoutcomeafterfluidpercussionbraininjury:alightandelectronmicroscopicstudyinrats.Neurosurgery.199638:53341.[PubMed]

37.JonesPA,AndrewsPJD,MidgleyS,etal.Measuringtheburdenofsecondaryinsultsinheadinjuredpatientsduringintensivecare.JNeurosurgAnesth.19946:414.[PubMed]

38.RobertsonCS,CliftonGL,TaylorAA,etal.Treatmentofhypertensionassociatedwithheadinjury.JNeurosurg.198359:45560.[PubMed]

39.BiousseV,RuckerJC,VignalC,etal.Anemiaandpapilledema.AmJOphthalmol.2003135:43746.[PubMed]

40.HebertPC,WellsG,BlajchmanMA,etal.Amulticenter,randomized,controlledclinicaltrialoftransfusionrequirementsincriticalcare.TransfusionRequirementsinCriticalCareInvestigators,CanadianCriticalCareTrialsGroup.NEnglJMed.1999340:40917.[PubMed]

41.LeeST,LuiTN,WongCW,etal.Earlyseizuresaftersevereclosedheadinjury.CanJNeurolSci.199724:403.[PubMed]

42.VespaPM,NuwerMR,NenovV,etal.Increasedincidenceandimpactofnonconvulsiveandconvulsiveseizuresaftertraumaticbraininjuryasdetectedbycontinuouselectroencephalographicmonitoring.JNeurosurg.199991:75060.[PMCfreearticle][PubMed]

43.TempkinNR,DikmenSS,WilenskyAJ,etal.Arandomized,doubleblindstudyofphenytoinforthepreventionofposttraumaticseizures.NEnglJMed.1990323:497502.[PubMed]

44.BrattonSL,ChestnutRM,GhajarJ,etal.AntiseizureProphylaxis.JNeurotrauma.200724(supplement1):S83S86.[PubMed]



45.SchrammWM,PapousekA,MichalekSaubererA,etal.Thecerebralandcardiovasculareffectsofcisatracuriumandatracuriuminneurosurgicalpatients.AnesthAnalg.199886:1237.[PubMed]

46.NatesJL,CooperDJ,DayB,etal.Acuteweaknesssyndromesincriticallyillpatientsareappraisal.AnaesthIntensiveCare.199725:50213.[PubMed]

47.PrielippRC,CoursinDB,ScuderiPE,etal.Comparisonoftheinfusionrequirementsandrecoveryprofilesofvecuroniumandcisatracurium51W89inintensivecareunitpatients.AnesthAnalg.199581:312.[PubMed]

48.KnappJM.Hyperosmolartherapyinthetreatmentofsevereheadinjuryinchildren:mannitolandhypertonicsaline.AACNClinIssues.200516:199211.[PubMed]

49.CruzJ,MinojaG,OkuchiK,etal.SuccessfuluseofthenewhighdosemannitoltreatmentinpatientswithGlasgowComaScalescoresof3andbilateralabnormalpupillarywidening:arandomizedtrial.JNeurosurg.2004100:37683.[PubMed]

50.CruzJ,MinojaG,OkuchiK.Improvingclinicaloutcomesfromacutesubduralhematomaswiththeemergencypreoperativeadministrationofhighdosesofmannitol:arandomizedtrial.Neurosurgery.200149:86471.[PubMed]

51.MuizelaarJP,LutzHA,BeckerDP.EffectofmannitolonICPandCBFandcorrelationwithpressureautoregulationinseverelyheadinjuredpatients.JNeurosurg.198461:7006.[PubMed]

52.BattisonC,AndrewsPJ,GrahamC,etal.Randomized,controlledtrialontheeffectofa20%mannitolsolutionanda7.5%saline/6%dextransolutiononincreasedintracranialpressureafterbraininjury.CritCareMed.200533:196202.[PubMed]

53.VialetR,AlbaneseJ,ThomachotL,etal.Isovolumehypertonicsolutes(sodiumchlorideormannitol)inthetreatmentofrefractoryposttraumaticintracranialhypertension:2mL/kg7.5%salineismoreeffectivethan2mL/kg20%mannitol.CritCareMed.200331:16837.[PubMed]

54.CooperDJ,MylesPS,McDermottFT,etal.Prehospitalhypertonicsalineresuscitationofpatientswithhypotensionandseveretraumaticbraininjury:arandomizedcontrolledtrial.JAMA.2004291:13507.[PubMed]

55.DoyleJA,DavisDP,HoytDB.Theuseofhypertonicsalineinthetreatmentoftraumaticbraininjury.JTrauma.200150:36783.[PubMed]

56.BrattonSL,ChestnutRM,GhajarJ,etal.HyperosmolarTherapy.JNeurotrauma.200724(supplement1):S14S20.[PubMed]

57.StocchettiN,MaasAI,ChieregatoA,etal.Hyperventilationinheadinjury:areview.Chest.2005127:181227.[PubMed]

58.YundtKD,DiringerMN.Theuseofhyperventilationanditsimpactoncerebralischemiainthetreatmentoftraumaticbraininjury.CritCareClin.199713:16384.[PubMed]

59.MuizelaarJP,vanderPoelHG,LiZC,etal.PialarteriolarvesseldiameterandCO2reactivityduringprolongedhyperventilationintherabbit.JNeurosurg.198869:9237.[PubMed]

60.ColesJP,SteinerLA,JohnstonAJ,etal.Doesinducedhypertensionreducecerebralischaemiawithinthetraumatizedhumanbrain?Brain.2004127:247990.[PubMed]

61.DiringerMN,VideenTO,YundtK,etal.Regionalcerebrovascularandmetaboliceffectsofhyperventilationafterseveretraumaticbraininjury.JNeurosurg.200296:1038.[PubMed]

62.BaderMK,ArbourR,PalmerS.Refractoryincreasedintracranialpressureinseveretraumaticbraininjury:



barbituratecomaandbispectralindexmonitoring.AACNClinIssues.200516:52641.[PubMed]

63.SchwartzML,TatorCH,RowedDW,etal.TheUniversityofTorontoHeadInjuryTreatmentStudy:aprospective,randomizedcomparisonofpentobarbitalandmannitol.CanJNeurolSci.198411:43440.[PubMed]

64.WardJD,BeckerDP,MillerJD,etal.Failureofprophylacticbarbituratecomainthetreatmentofsevereheadinjury.JNeurosurg.198562:3838.[PubMed]

65.EisenbergHM,FrankowskiRF,ContantCF,etal.Highdosebarbituratecontrolofelevatedintracranialpressureinpatientswithsevereheadinjury.JNeurosurg.198869:1523.[PubMed]

66.MesseterK,NordstromCH,SundbargG,etal.Cerebralhemodynamicsinpatientswithacutesevereheadtrauma.JNeurosurg.198664:2317.[PubMed]

67.NordstromCH,MesseterK,SundbargG,etal.Cerebralbloodflow,vasoreactivity,andoxygenconsumptionduringbarbituratetherapyinseveretraumaticbrainlesions.JNeurosurg.198868:42431.[PubMed]

68.SchalenW,SonessonB,MesseterK,etal.Clinicaloutcomeandcognitiveimpairmentinpatientswithsevereheadinjuriestreatedwithbarbituratecoma.ActaNeurochir(Wien)1992117:1539.[PubMed]

69.SatoM,NiiyamaK,KurodaR,etal.Influenceofdopamineoncerebralbloodflow,andmetabolismforoxygenandglucoseunderbarbiturateadministrationincats.ActaNeurochir(Wien)1991110:17480.[PubMed]

70.CliftonGL,MillerER,ChoiSC,etal.Lackofeffectofinductionofhypothermiaafteracutebraininjury.NEnglJMed.2001344:55663.[PubMed]

71.AdelsonPD,RaghebJ,KanevP,etal.PhaseIIclinicaltrialofmoderatehypothermiaafterseveretraumaticbraininjuryinchildren.Neurosurgery.200556:74054.[PubMed]

72.KaalEC,VechtCJ.Themanagementofbrainedemainbraintumors.CurrOpinOncol.200416:593600.[PubMed]

73.GudemanS,MillerJ,BeckerD.Failureofhighdosesteroidtherapytoinfluenceintracranialpressureinpatientswithsevereheadinjury.JNeurosurg.197951:3016.[PubMed]

74.SaulT,DuckerT,SalemanM,etal.Steroidsinsevereheadinjury:aprospective,randomizedclinicaltrial.JNeurosurg.198154:596600.[PubMed]

75.EdwardsP,ArangoM,BalicaL,etal.FinalresultsofMRCCRASH,arandomisedplacebocontrolledtrialofintravenouscorticosteroidinadultswithheadinjuryoutcomesat6months.Lancet.2005365:19579.[PubMed]

76.FeiginVL,AndersonN,RinkelGJ,etal.Corticosteroidsforaneurysmalsubarachnoidhaemorrhageandprimaryintracerebralhaemorrhage.CochraneDatabaseSystRev.2005:CD004583.[PubMed]

77.MarchukG,KaufmannAM.Spontaneoussupratentorialintracerebralhemorrhage:theroleofsurgicalmanagement.CanJNeurolSci.200532(Suppl2):S2230.[PubMed]

78.CheungA,TelaghaniCK,WangJ,etal.Neurologicalrecoveryafterdecompressivecraniectomyformassiveischemicstroke.NeurocritCare.20053:21623.[PubMed]

79.SahuquilloJ,ArikanF.Decompressivecraniectomyforthetreatmentofrefractoryhighintracranialpressureintraumaticbraininjury.CochraneDatabaseSystRev.2006:CD003983.[PubMed]

80.TaylorA,ButtW,RosenfeldJ,etal.Arandomizedtrialofveryearlydecompressivecraniectomyinchildrenwithtraumaticbraininjuryandsustainedintracranialhypertension.ChildsNervSyst.200117:15462.[PubMed]

81.AarabiB,HesdorfferDC,AhnES,etal.Outcomefollowingdecompressivecraniectomyformalignant



swellingduetosevereheadinjury.JNeurosurg.2006104:46979.[PubMed]

82.PolinRS,ShaffreyME,BogaevCA,etal.Decompressivebifrontalcraniectomyinthetreatmentofsevererefractoryposttraumaticcerebraledema.Neurosurgery.199741:8492.[PubMed]

83.StiefelMF,HeuerGG,SmithMJ,etal.Cerebraloxygenationfollowingdecompressivehemicraniectomyforthetreatmentofrefractoryintracranialhypertension.JNeurosurg.2004101:2417.[PubMed]

84.BorSengShuE,HirschR,TeixeiraMJ,etal.CerebralhemodynamicchangesgaugedbytranscranialDopplerultrasonographyinpatientswithposttraumaticbrainswellingtreatedbysurgicaldecompression.JNeurosurg.2006104:93100.[PubMed]

85.EngbergJ,ObergB,ChristensenKS,etal.Thecerebralarteriovenousoxygencontentdifference(AVDO )duringhalothaneandneuroleptanaesthesiainpatientssubjectedtocraniotomy.ActaAnaesthesiolScand.198933:642.[PubMed]

86.HutchinsonPJ,CorteenE,CzosnykaM,etal.Decompressivecraniectomyintraumaticbraininjury:therandomizedmulticenterRESCUEicpstudy.ActaNeurochir.2006.pp.1720.www.RESCUEicp.com.[PubMed]

87.VahediK,HofmeijerJ,JuettlerE,etal.Earlydecompressivesurgeryinmalignantinfarctionofthemiddlecerebralartery:apooledanalysisofthreerandomisedcontrolledtrials.LancetNeurol.20076:21522.[PubMed]

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