Diagnosis of Delirium and Confusional States

23/2/2016
Diagnosisofdeliriumandconfusionalstates
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Authors
JosephFrancis,Jr,MD,MPH
GBryanYoung,MD,FRCPC
SectionEditors
MichaelJAminoff,MD,DSc
KennethESchmader,MD
DeputyEditor
JanetLWilterdink,MD
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jan2016.|Thistopiclastupdated:Aug22,2014.
INTRODUCTIONDeliriumandconfusionalstatesareamongthemostcommonmentaldisordersencountered
inpatientswithmedicalillness,particularlyamongthosewhoareolder.Theyareassociatedwithmanycomplex
underlyingmedicalconditionsandcanbehardtorecognize.Systematicstudiesandclinicaltrialsaredifficultto
performinpatientswithcognitiveimpairment.Recommendationsforevaluatingandtreatingdeliriumarebased
primarilyuponclinicalobservationandexpertopinion[1].
Knowledgeoftheclinicalepidemiologyofdeliriumandconfusionalstatesinvarioussettingshassubstantially
increasedasaresultofapplyingstandardizeddiagnosticmethods.Theseprospectiveobservationalstudies
provideabasisforunderstandingandmanagingthedisorder.
Theepidemiology,pathogenesis,clinicalfeatures,anddiagnosisofdeliriumandconfusionalstateswillbe
reviewedhere.Thepreventionandtreatmentofthesedisordersarediscussedseparately.(See"Deliriumand
acuteconfusionalstates:Prevention,treatment,andprognosis".)
DEFINITIONANDTERMINOLOGYTheAmericanPsychiatricAssociation'sDiagnosticandStatistical
Manual,5thedition(DSMV)listsfivekeyfeaturesthatcharacterizedelirium[2]:
Disturbanceinattention(reducedabilitytodirect,focus,sustain,andshiftattention)andawareness.
Thedisturbancedevelopsoverashortperiodoftime(usuallyhourstodays),representsachangefrom
baseline,andtendstofluctuateduringthecourseoftheday.
Anadditionaldisturbanceincognition(memorydeficit,disorientation,language,visuospatialability,or
perception)
Thedisturbancesarenotbetterexplainedbyanotherpreexisting,evolvingorestablishedneurocognitive
disorder,anddonotoccurinthecontextofaseverelyreducedlevelofarousal,suchascoma
Thereisevidencefromthehistory,physicalexamination,orlaboratoryfindingsthatthedisturbanceis
causedbyamedicalcondition,substanceintoxicationorwithdrawal,ormedicationsideeffect.
Additionalfeaturesthatmayaccompanydeliriumandconfusionincludethefollowing:
Psychomotorbehavioraldisturbancessuchashypoactivity,hyperactivitywithincreasedsympathetic
activity,andimpairmentinsleepdurationandarchitecture.
Variableemotionaldisturbances,includingfear,depression,euphoria,orperplexity.
Thereisnogenerallyacceptedconsensusregardingthedistinctionbetweendeliriumandconfusionalstates.The
terms"acuteconfusionalstate"and"encephalopathy"areoftenusedsynonymouslywithdelirium.Themore
generalterm"confusion"isusedtoindicateaproblemwithcoherentthinking.Confusedpatientsareunableto
thinkwithnormalspeed,clarity,orcoherence[3].Confusionistypicallyassociatedwithadepressedsensorium
andareducedattentionspan,anditisanessentialcomponentofdelirium.
Theterm"acuteconfusionalstate"referstoanacutestateofalteredconsciousnesscharacterizedbydisordered
attentionalongwithdiminishedspeed,clarity,andcoherenceofthought[3].Althoughthisdefinitionencompasses
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deliriumaswell,someexpertsuse"confusionalstate"toconveytheadditionalmeaningofreducedalertnessand
alteredpsychomotoractivity[3].Inthisparadigm,deliriumisaspecialtypeofconfusionalstatecharacterizedby
increasedvigilance,withpsychomotorandautonomicoveractivitythedeliriouspatientdisplaysagitation,
excitement,tremulousness,hallucinations,fantasies,anddelusions.
Inthisdiscussion,thetermdeliriumwillbeusedinthesenseoftheDSMVdefinition.Theadditionalcomponents
ofagitation,tremor,andhallucinationsareallowedforbutarenotessentialdiagnosticfeaturesofdeliriuminthe
DSMVusage.ConfusionandotherstatesofalteredconsciousnessareencompassedbytheDSMVdefinitionof
delirium.
EPIDEMIOLOGYDeliriumandconfusionhaveprimarilybeenstudiedinhospitalsettings.Nearly30percentof
oldermedicalpatientsexperiencedeliriumatsometimeduringhospitalization[4,5].Amongoldersurgicalpatients,
theriskfordeliriumvariesfrom10togreaterthan50percentthehigherfiguresareassociatedeitherwithfrail
patients(eg,thosewhohavefallenandsustainedahipfracture)orcomplexproceduressuchascardiacsurgery
[6].
Ingeneral,deliriumcanbefoundwherevertherearesickpatients.Whenstandardizedscreeninganddiagnostic
tools(see'Evaluation'below)havebeenappliedprospectivelytoconsecutivepatients,highratesofdeliriumhave
beendemonstratedinintensivecareunits(70percent)[7],emergencydepartments(10percent)[8],hospiceunits
(42percent)[9],andpostacutecaresettings(16percent)[10].Nowthatthecareofsickerpatientshasbecome
fragmentedacrossavarietyofvenues,cliniciansarechallengedtoidentifyandmanagedeliriumefficientlyacross
awidevarietyofsettings.
PATHOGENESISThepathophysiologyofdeliriumandconfusionispoorlyunderstood.Mosttheoriesareoverly
simplified.Withsomanydisparateetiologies(table1),itishighlyunlikelythatasinglemechanismisuniversally
operative.
Thebiologicbasisofdeliriumandconfusionispoorlyunderstoodinpartbecauseitisdifficulttostudyseverelyill
patientswithconventionalelectrophysiologictests,brainimaging,orneurotransmitterassays.Rarelycanthe
observedphenomenaattributedtodeliriumbeseparatedreliablyfromthatofunderlyingillnessanddrugtreatment.
Animalmodelsfordeliriumhavebeenproposedbutareintheirinfancyandstillnotvalidated.
Despitetheselimitations,someimportantdataregardingthepathophysiologyofdeliriumhavebeenreported.Risk
factorsforthedevelopmentofdeliriumhavealsobeenidentified.
NeurobiologyofattentionSinceadisorderofattentionisauniversalfeatureofconfusionalstates,ithelpsto
understandtheneurobiologyofattention.
Arousalandattentionmaybedisruptedbybrainlesionsinvolvingtheascendingreticularactivatingsystem
(ARAS)fromthemidpontinetegmentumrostrallytotheanteriorcingulateregions.
Attentioninbothrightandleftaspectsofextrapersonalspaceisgovernedbythe"nondominant"parietaland
frontallobes.Thuswithinattention,thereistypicallysomedisruptionoftheintegratedfunctionofthese
regions.
Insightandjudgmentaredependentonintacthigherorderintegratedcorticalfunction.Sinceinsightinto
perceptionsisoftenreducedwithdeliriumandconfusionalstates,itseemslikelythathigherordercortical
functionisthereforeimpaired,especiallyregardingfrontallobeinvolvementinscrutinizingincomingsensory
information.
CorticalversussubcorticalmechanismsSeminalworkinthe1940susingelectroencephalography(EEG)in
acutelyillpatientsestablishedthatdeliriumwasadisturbanceofglobalcorticalfunction,characterizedbyslowing
ofthedominantposterioralpharhythmandtheappearanceofabnormalslowwaveactivity[11].Thesefindings
correlatedwiththelevelofconsciousnessandotherobservedbehaviorsregardlessoftheunderlyingetiology,
suggestingafinalcommonneuralpathway.Themajorexceptionappearedtobethatofdeliriumaccompanying
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alcoholandsedativedrugwithdrawal,inwhichlowvoltage,fastwaveactivitypredominated.Thesefindingsareso
consistentthatEEGcanbeusedtoresolveuncertaintyinpatientsinwhomthediagnosisofdeliriumisindoubt.
Theresultsofbrainstemauditoryevokedpotential,somatosensoryevokedpotentials,andneuroimagingstudies
havesupportedanimportantroleforsubcortical(eg,thalamus,basalganglia,andpontinereticularformation)as
wellascorticalstructuresinthepathogenesisofdelirium[12].Thesefindingscorrelatewithclinicalreportsthat
patientswithsubcorticalstrokesandbasalgangliaabnormalities(includingParkinsondisease)haveahigher
susceptibilitytodelirium.
NeurotransmitterandhumoralmechanismsAcetylcholineplaysakeyroleinthepathogenesisofdelirium
[13,14].Anticholinergicdrugscausedeliriumwhengiventohealthyvolunteersandareevenmorelikelytoleadto
acuteconfusioninfrailelderlypersons.Thiseffectcanbereversedwithcholinesteraseinhibitorssuchas
physostigmine.(See"Anticholinergicpoisoning".)
Furthersupportfortheroleofacetylcholineisderivedfromobservationsthatmedicalconditionsprecipitating
delirium,suchashypoxia,hypoglycemia,andthiaminedeficiency,decreaseacetylcholinesynthesisinthecentral
nervoussystem(CNS).Inaddition,serumanticholinergicactivity,measuredwithbindingassaysemploying
purifiedpreparationsofbrainmuscarinicreceptors,correlateswiththeseverityofdeliriuminpostoperativeand
medicalpatients[13,15].Finally,Alzheimerdisease,whichischaracterizedbyalossofcholinergicneurons,
increasestheriskofdeliriumduetoanticholinergicmedications.
Theanticholinergicmechanismisimportantforclinicianstokeepinmind,sincemanydrugsusedbyolderadults
(includingseveralnottraditionallyviewedtohave"anticholinergiceffects")canleadtodetectableserum
anticholinergicactivitymeasuredbycompetitiveradioreceptorbinding[16,17].Psychotropicdrugs,inparticular,
arelikelytocausedetectableserumanticholinergicactivityatdosestypicallyadministeredtoolderpatients.Some
elderlypatientswithdeliriumalsohaveelevatedserumanticholinergicactivityintheabsenceofanticholinergic
druguse,raisingthepossibilitythatendogenousanticholinergicsubstancesmayplayaroleindelirium[13].
Drugsthatareagonistsorantagonistsofanumberofotherneurotransmitterscanproducedeliriumlikeeffects,
althoughthepreciseroleoftheseneurotransmittersystemsisdifficulttodetermine.Cerebrospinalfluid(CSF)
studiesofpatientswithdeliriumrevealalterationsinneuropeptides(eg,somatostatin),endorphins,serotonin,
norepinephrine,andGABA,amongothers[12].However,itisdifficulttoexcludetheconfoundingeffectsof
underlyingillnessordementia.
Proinflammatorycytokinessuchasinterleukinsandtumornecrosisfactoralphaalsomayhavearoleinthe
pathogenesisofdelirium.TheseagentshavestrongCNSeffectswheninjectedintoexperimentalanimalsorwhen
administeredfortherapeuticpurposes(eg,interferonsinchronichepatitis).Cytokineactivationmayaccountfor
delirium(particularlyhyperactiveformsofthedisturbance)insituationssuchassepsis(wherementalchanges
mayactuallyprecedefever),cardiopulmonarybypass[18],andacutehipfracture[19].
RiskfactorsDeliriumisamultifactorialdisorder.Factorsthatincreasetheriskfordeliriumandconfusional
statescanbeclassifiedintothosethatincreasebaselinevulnerabilityandthosethatprecipitatethedisturbance
[20].
Themostcommonlyidentifiedriskfactorsareunderlyingbraindiseasessuchasdementia,stroke,orParkinson
diseasethesearepresentinnearlyonehalfofolderpatientswithdelirium.Inametaanalysisofpublished
prospectivestudiesofdelirium,theprevalenceofdeliriumsuperimposedupondementiarangedfrom22to89
percent[21].Often,thedementiawentunrecognizedpriortotheonsetofdelirium.Similarly,inastudyof78
elderlypatientswithfemoralneckfractureswhowerefollowedforfiveyears,dementiadevelopedin69percentof
the29patientswithpostoperativedeliriumversusonly20percentofthe49patientswithoutpostoperativedelirium
[22].
Otherfactorsthatincreasethevulnerabilitytodeliriumincludeadvancedageandsensoryimpairment.
PrecipitatingfactorsFactorsthatmayprecipitatedeliriumarenumerousandvaried(table1).Somecommon
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examplesincludepolypharmacy(particularlypsychoactivedrugs),infection,dehydration,immobility(including
restraintuse),malnutrition,andtheuseofbladdercatheters.Drugsthatmayprecipitatedeliriumandconfusionare
notedintheTable(table2).
CLINICALPRESENTATIONAspreviouslynoted,severalkeyfeaturescharacterizedeliriumandconfusional
states(see'Definitionandterminology'above)[2].Adisturbanceofconsciousnessandalteredcognitionare
essentialcomponents.Theconditiontypicallydevelopsoverashortperiodoftimeandtendstofluctuateduring
thecourseoftheday.Thedisturbanceistypicallycausedbyamedicalcondition,substanceintoxication,or
medicationsideeffect.Thesecriteriaformausefulframeworkforunderstandingtheclinicalpresentationofthe
disorder.
DisturbanceofconsciousnessOneoftheearliestmanifestationsofdeliriumisachangeinthelevelof
awarenessandtheabilitytofocus,sustain,orshiftattention.Thislossofmentalclarityisoftensubtleandmay
precedemoreflagrantsignsofdeliriumbyonedayormore.Thus,familymembersorcaregiverswhoreportthata
patient"isn'tactingquiteright"shouldbetakenseriously,evenifdeliriumisnotobvioustotheexaminingclinician.
Distractibility,oneofthehallmarksofdelirium,isoftenevidentinconversation.Itisimportantthattheexaminerbe
sensitivetothepatient'sflowofthoughtandnotattributetangentialordisorganizedspeechtoage,dementia,or
fatigue.
Patientswillappearobviouslydrowsy,lethargic,orevensemicomatoseinmoreadvancedcasesofdelirium.The
oppositeextreme,hypervigilance,mayalsooccurincasesofalcoholorsedativedrugwithdrawal,butsucha
presentationislesscommoninolderpersons.(See"Managementofmoderateandseverealcoholwithdrawal
syndromes".)
ChangeincognitionDeliriousindividualshavecognitiveandperceptualproblems,includingmemoryloss,
disorientation,anddifficultywithlanguageandspeech.Formalmentalstatustestingcanbeusedtodocumentthe
degreeofimpairment,butmoreimportantthanthetestscorearethepatient'soverallaccessibilityand
attentivenesswhileattemptingtoanswerthequestions.Itisimportanttoascertainthepatient'slevelof
functioningpriortotheonsetofdeliriumfromfamilymembers,caregivers,orotherreliableinformants,since
dementiacanimpaircognitiveabilityandfrequentlyunderliesdelirium.
Perceptualdisturbancestypicallyaccompanydelirium.Patientsmaymisidentifytheclinicianorbelievethat
objectsorshadowsintheroomrepresentaperson.Vaguedelusionsofharmoftenaccompanythese
misperceptions.Hallucinationscanbevisual,auditoryorsomatosensory,usuallywithlackofinsightthepatients
believetheyarereal.Hallucinationscanbesimple,e.g.,shadowsorshapes,orcomplex,aspeopleandfaces.
Soundscanalsoconsistofsimplesoundsorhearingvoiceswithclearspeech.
Avarietyoflanguagedifficultiescanoccur.Patientsmaylosetheabilitytowriteortospeakasecondlanguage.
OnepersonalexperienceinvolvedapatientwhoimmigratedtoNorthAmericaasanadolescentshespokeonly
Italianduringherdelirium,recoveringhergraspofEnglishafterherpneumoniawastreated.
TemporalcourseDeliriumdevelopsoverhourstodaysandtypicallypersistsfordaystomonths.The
acutenessofthepresentationisthemosthelpfulfeatureindifferentiatingdeliriumfromdementia.Inaddition,the
featuresofdeliriumareunstable,typicallybecomingmostsevereintheeveningandatnight.Itisnotunusualfora
patientwithdeliriumtoappearrelativelylucidduringmorningrounds.Clinicians,particularlyphysicians,areaptto
missthediagnosisiftheyrelyupononlyasinglepointassessmentevidenceofthebehaviorchangeshouldbe
activelysolicitedfromallstaff,especiallythoseworkingeveningandnightshifts.
Thereisoftenaprodromalphase,especiallyinelderlypatients,thatlaterblendsintoquiet/hypoactivedeliriumor
eruptsintoanagitatedconfusionalstate.Prodromalfeaturesincludecomplaintsoffatigue,sleepdisturbance
(excessivedaytimesomnolenceorinsomnia),depression,anxiety,restlessness,irritabilityandhypersensitivityto
lightorsound.Withprogressionthereareperceptualdisturbancesandcognitiveimpairment.Thesesymptoms
mayfluctuate.Hypoactivedeliriumcan,however,beginwithoutaprodromalphaseandagitatedbehaviormay
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appearasthefirstmanifestationofdeliriumwithoutaprodromalorhypoactivephase.
ElderlypatientsPatientswithdeliriumaresickbydefinition.However,olderpatientswithdeliriumoftendonot
looksickapartfromtheirbehavioralchange.Thus,deliriummaybetheonlyfindingsuggestingacuteillnessin
olderdementedpatients.Caregiversmustbeeducatedthatsuddenchangesinmentalfunctioningarenot
expectedwithmostprogressivedementiasandrequirepromptmedicalattention.
OtherfeaturesDeliriummaypresentwithavarietyofclinicalmanifestationsthatarenotessentialdiagnostic
features,includingpsychomotoragitation,sleepwakereversals,irritability,anxiety,emotionallability,and
hypersensitivitytolightsandsounds.Thesefeaturesarenotseeninallpatientswithdeliriumandcanbeevident
inpatientswithdementiatheirpresenceneitherrulesinnorrulesoutthediagnosis.Themostcommon
presentationinolderpatientsisarelativelyquiet,withdrawnstatethatfrequentlyismistakenfordepression.
Therelationshipbetweenclinicalmanifestationsandoutcomehasnotbeenwellstudied,althoughareportof
outcomesofdeliriumfollowinghipfracturerepairsuggestedthatpatientswithmoreseveredelirium,including
psychomotoragitation,hadhigherratesofmortalityandnursinghomeplacement[23].Deliriumthatdoesnot
resolvebeforedischargeisalsoariskfactorfornursinghomeplacement[24].
EVALUATIONTherearetwoimportantaspectstothediagnosticevaluationofdelirium:recognizingthatthe
disorderispresentanduncoveringtheunderlyingmedicalillnessthathascauseddelirium.
RecognizingthedisorderAspreviouslymentioned,cliniciansoftenfailtorecognizedeliriuminsomereports,
thishappensinmorethan70percentofcases.Behavioralproblemsorcognitiveimpairmentmaybereadily
apparentbutwronglyattributedtothepatient'sage,todementia,ortoothermentaldisorders.Inonestudy,over
40percentofpatientsreferredtoaconsultingliaisonpsychiatristfortheevaluationortreatmentofdepression
ultimatelywerefoundtohavedelirium[23].
ClinicalconfirmationTheDSMVcriteria(See'Definitionandterminology'above.)formapracticalframework
forassessingdelirium[25]:
Achangeinthelevelofconsciousnessisoftenthefirstobservableclue.Cliniciansmustnot"normalize"
lethargyorsomnolencebyassumingthatillness,sleeploss,fatigue,oranxietyarecausingthechanges.
Incaseswherethepatientappearsawake,theabilitytofocus,sustain,orshiftattentioncanbeassessed
duringattemptstoobtainahistoryaglobalassessmentofthepatient's"accessibility"duringconversationor
theperformanceofamentalstatusexaminationisasensitiveindicatorofdelirium.
Conversationwiththepatientmayelicitmemorydifficulties,disorientation,orspeechthatistangential,
disorganized,orincoherent.Theclinicianshouldbeawareofsuperficiallyappropriateconversationthat
followssocialnormsbutispoorincontent.
Whenindoubt,formalmentalstatustestingshouldbeperformed,suchastheMiniMentalStateExamination
orbriefbedsidetestsofattention(table3).Serialsevensandspellingawordsuchasfarmorworld
backwardareothersimpletestsofattention.(See"Evaluationofcognitiveimpairmentanddementia",
sectionon'MiniMentalStateExamination'.)
Determiningthatcognitiveimpairmentorperceptualproblemsarenotduetoapriororprogressingdementiacanbe
challengingandrequiresknowledgeofthepatient'sbaselineleveloffunctioning.Thediagnosisismademore
easilyiftherehasbeenapriorassessmentofcognitiveabilities.Inotherinstances,informantsmustbe
immediatelysoughttoestablishchronology.Theseshouldincludeformalcaregivers(eg,nursingstafffamiliarwith
thepatient),familymembers,andinformalcaregivers,particularlythosewhomayhaveobservedfluctuationsin
thepatient'smentalfunctions.
HistorySomehistoricalcluestotheunderlyingetiologyofdeliriumandconfusioncanbeobtainedfrom
relatives,eg,recentfebrileillness,historyoforganfailure,amedicationlist,historyofalcoholismordrugabuse,or
recentdepression.Itisotherwiseoftendifficulttoimpossibletoobtainahistoryintheconfusedoruncooperative
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patient.Asanexample,myocardialinfarctionmaycausesufficientconfusionthatthepatientcannotrelatea
historyofchestpain.
GeneralexaminationAcomprehensivephysicalexaminationisoftendifficultorimpossibleintheconfused
oruncooperativepatient.Cliniciansshouldinsteadperformafocusedassessment,concentratinguponvitalsigns,
thestateofhydration,skincondition,andpotentialinfectiousfoci.
Thepatient'sgeneralappearancemaybesuggestive,eg,theduskyappearanceseenwithchronicpulmonary
disease,thejaundicedappearanceofhepaticfailure,orthestigmataofrenalfailure.Needletracksstrongly
suggestdrugabuse.Cherryredlipsindicatepossiblecarbonmonoxidepoisoning.Thebreathmaysmellof
alcohol,fetorhepaticus,uremicfetororketones.Hyperventilationoffersalimitednumberofpossibleetiologies.
(See'Diagnostictests'below.)
Abittentongueorposteriorfracturedislocationoftheshouldersuggestsaconvulsiveseizure(over40percentof
suchpatientsremaininnonconvulsivestatusepilepticus).Theremayalsobesignsofheadinjury.Subhyaloidor
retinalhemorrhagesraisethepossibilityofanintracranialhemorrhage,usuallyfromarupturedberryaneurysm.
Alcoholorsedativedrugwithdrawalmaycauseadeliriumcharacterizedbyautonomicnervoussystemactivation
(tachycardia,sweating,flushing,dilatedpupils)inyoungerpersons,buttheseresponsesarebluntedorabsentin
thegeriatricpopulation.Anticholinergictoxicityinelderscancausedeliriumwithoutperipheralsignsofatropine
poisoning(eg,fever,mydriasis,tachycardia).Sepsismaypresentasdeliriumwithoutobviousfever(sometimes
evenwithhypothermia)orlocalizingsigns(eg,reboundtendernessfromaperforatedviscus).(See"Evaluationof
infectionintheolderadult".)
Pitfallsintheexaminationmustbekeptinmind:temperaturemaybeunder38.3C(101F)eveninthepresenceof
seriousinfectionsauscultatoryandradiographicfindingsofpneumoniamaybesubtleorabsentandabdominal
catastrophesmaypresentwithoutperitonealsignsinfrailolderpatients.Falsepositivefindingsoccuraswell(eg,
nuchalrigiditymaynotsignifymeningitis).
NeurologicexaminationTheneurologicexaminationisoftenconfoundedbyinattentionandaltered
consciousnessinpatientswithdelirium.Certainaspectsoftheexaminationmaybedifficultorunreliablein
uncooperativepatients(eg,sensorytesting),orreflectchronicratherthanacuteCNSconditions.However,an
assessmentemphasizingthelevelofconsciousness,degreeofattentionorinattention,visualfields,and
unambiguouscranialnerveandmotordeficits,isimportanttoidentifyindividualswithahigherlikelihoodoffocal
neurologicdisease.Posteriorcorticalstrokes,forexample,canpresentasdeliriumwithfewfindingsotherthan
hemianopia,andinsomecasesmaypresentwithnofocalsymptomsorsigns.
Theabsenceoffocalexaminationfindingsdoesnotexcludethepossibilityoffocalormultifocalneurologiclesions
asthecauseofthedelirium.Intheabsenceofanobviouscausefordelirium,furthertestingincluding
neuroimaging,lumbarpuncture,andEEGisindicated.
Thephysicalsignsofmetabolic/toxicdeliriumcanincludenonrhythmic,asynchronousmusclejerking(multifocal
myoclonus),flappingmotionsofanoutstretched,dorsiflexedhand(asterixis),andposturalactiontremor.These
arenonspecificfindingsanddonothelpestablishanyparticularmedicaletiologywithinthemetabolic/toxic
category.Selectivelossofthevestibularocularreflex,ornystagmuswithunexplainedocularpalsiesthatspare
pupillaryreactivitytolight,raisethepossibilityofWernicke'sencephalopathy.
ClinicalinstrumentsTheConfusionAssessmentMethod(CAM)isasimpletoolthatcanbeusedby
clinicianstointegratetheirobservationsandidentifywhendeliriumisthemostprobablediagnosis(table4).In
medicalandsurgicalsettings,theCAMhasasensitivityof94to100percentandaspecificityof90to95percent
[26].TheCAMhasbecomeastandardscreeningdeviceinclinicalstudiesofdelirium,conductedacrossmultiple
settingsincludingemergencyroomsandlongtermcare[27].Ittakesfiveminutestoadministerandmaybe
particularlyhelpfulwhenincorporatedintotheroutinebedsideassessment.Areviewof11bedsideinstruments
usedtoidentifythepresenceofdeliriuminadultsconcludedthatthebestevidencesupportedtheuseoftheCAM
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asthebest,andtheMiniMentalStateExamastheleastaccuratetest[28].
TheCAMICUinstrumenthasbeendevelopedandvalidatedforidentificationofdeliriumintheintensivecareunit
(ICU)[2931].Inmechanicallyventilatedpatientswhoareunabletocommunicateverbally,theinstrument
considersobservedbehaviorsandnonverbalresponsestosimplequestions,aswellasvisualandauditory
recognitiontasks(table4).
Anotherinstrument,theIntensiveCareDeliriumChecklistforScreening(ICDSC),hasalsobeenvalidatedinthe
diagnosisofdeliriumintheICUsettingandhadhighagreementrateswiththeCAMICUinonestudy[32,33].
InvestigatingmedicaletiologiesVirtuallyanymedicalconditioncanprecipitatedeliriuminasusceptible
personmultipleunderlyingconditionsareoftenfound[34].Thehistoryandphysicalexaminationwillguidemostof
theinvestigations.Theconditionsnotedmostcommonlyinprospectivestudiesofthedisorderinclude:
Fluidandelectrolytedisturbances(dehydration,hyponatremiaandhypernatremia)
Infections(urinarytract,respiratorytract,skinandsofttissue)
Drugoralcoholtoxicity
Withdrawalfromalcohol
Withdrawalfrombarbiturates,benzodiazepines,andselectiveserotoninreuptakeinhibitors
Metabolicdisorders(hypoglycemia,hypercalcemia,uremia,liverfailure,thyrotoxicosis)
Lowperfusionstates(shock,heartfailure)
Postoperativestates,especiallyintheelderly
Lesscommoncausesthatshouldbeconsideredincludehypoxemia,hypercarbia,Wernickeencephalopathy,
adrenalfailure,primarycentralnervoussysteminfection,seizures,trauma,andparaneoplasticsyndromes.
Acosteffectiveworkupfordeliriumfocusesuponthesemostlikelypossibilities.(See"Deliriumandacute
confusionalstates:Prevention,treatment,andprognosis".)
MedicationreviewDrugtoxicityaccountsforapproximately30percentofallcasesofdelirium[16].Thus,the
mostimportantinitialstepisamedicationreview.ThemostcommonoffendersarelistedintheTable(table2)
[16].Cliniciansshouldbecarefulnottoneglectoverthecounteragents,drugsprescribedbyotherphysicians,or
drugsbelongingtootherhouseholdmembers.Asimplebuthighyielddiagnosticprocedureistoaskafamily
membertocleanoutthemedicinecabinetandbringthecontentsforreview.
DIFFERENTIALDIAGNOSISCarefulattentiontothekeyfeaturesofacuteonset,fluctuatingcourse,altered
consciousness,andcognitivedeclineshouldreadilydistinguishdeliriumfromdepression,psychoticillness,and
dementia.Whenindoubt,themostusefulruleofthumbistoassumedeliriumandattempttoruleoutcommon
medicaletiologies.Thisistrueevenforpatientswithknownpsychiatricillness(includingdementia),sincethey
alsoaresusceptibletodeliriumwhenacutelyill.
SundowningDeliriumshouldbedistinguishedfrom"sundowning,"afrequentlyseenbutpoorlyunderstood
phenomenonofbehavioraldeteriorationseenintheeveninghours,typicallyindemented,institutionalizedpatients
[35].Sundowningshouldbepresumedtobedeliriumwhenitisanewpattern.Patientswithestablished
sundowningandnoobviousmedicalillnessmaybesufferingtheeffectsofimpairedcircadianregulationor
nocturnalfactorsintheinstitutionalenvironment(eg,shiftchanges,noise,reducedstaffing).
FocalsyndromesAnumberoflobarorfocalneurologicsyndromesmaymimicdelirium.
TemporalparietalPatientswithWernicke'saphasiamayappeardeliriousinthattheydonotcomprehend
orobeyandseemconfused.However,theproblemisrestrictedtolanguage,whileotheraspectsofmental
functionareintact.Furthermore,fluentparaphasiasaretypicallypresentwithWernicke'sandofferamajor
cluetothecorrectdiagnosis.
Bitemporaldysfunction,iftransient,mayproduceatransientglobalamnesia(TGA),inwhichthedeficitis
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restrictedtomemory.Withmoreextensivebitemporaldysfunction,visualagnosiaandcorticaldeafness
(eitherbitemporalorlefttemporal)ortheKluverBucysyndrome(apathy,visualagnosia,increasedsexual
activity,andincreasedoralbehavior)maybeseen.
OccipitalAnton'ssyndromeofcorticalblindnessandconfabulationmightbeconfusedwithdelirium.
Carefulexamination,however,willrevealalackofvision.
FrontalPatientswithbifrontallesions(eg,fromtumorortrauma)oftenshowakineticmutism,lackof
spontaneity,lackofjudgment,problemswithrecentorworkingmemory,bluntedorlabileemotional
responses,andincontinence.Thesefeaturesmaycloselyresembledelirium.Neuroimagingmayberequired
todifferentiatefrontallesionsfromdeliriumandconfusionalstatesindifficultcases.
Confusionordeliriumduetoacuteorsubacutebrainlesions,suchasstrokeormultifocalwhitematter
inflammation,mayoccurwithoutfocaldeficitsonexamination[3639].Oneretrospectivestudyof127consecutive
neurologyconsultationsforisolatedacutementalstatuschangefoundstrokeasthecauseinninepatients(7
percent)[37].Ofthese,threepatients(2.7percent)withstrokehadnofocalneurologicfindings,andoneofthese
wasasubarachnoidhemorrhage.Riskfactorsfordeliriuminthesettingofstrokeincludepreexistingcognitive
impairment,infection,righthemisphericstroke,anteriorcirculationlargevesselstroke,andgreaterstrokeseverity
[39].
Confusionordeliriummayfollowheadinjuryevenintheabsenceoffocalneurologicdeficits.
NonconvulsivestatusepilepticusNonconvulsivestatusepilepticus(NCSE)isunderrecognized,particularly
inolderpatients.NCSErequiresanEEGfordetectionandcontinuousEEGformanagement.Oftenpatientsshow
noclassicictalfeatures,butthefollowingfeaturesshouldsuggestthepossibilityofseizures:prominentbilateral
facialtwitching,unexplainednystagmoideyemovementsduringobtundedperiods,spontaneoushippus,prolonged
"postictalstate,"automatisms(lipsmacking,chewing,orswallowingmovements),andacuteaphasiaorneglect
withoutastructurallesion[40].NCSEshouldalsobeconsideredintheabsenceofthesefindingswhenthe
etiologyofaconfusionalstateremainsobscure[41].
DementiaDementiamaysometimesbeconfusedwithdeliriumorconfusionandviceversa.However,
characteristicdifferencesinprogressionandcognitivefeaturesusuallydistinguishthesedisorders.
Incontrasttodelirium,cognitivechangeinAlzheimerdiseaseistypicallyinsidious,progressive,without
muchfluctuation,andoccursoveramuchlongertime(monthstoyears).Attentionisrelativelyintact,asare
remotememoriesintheearlierstages.(See"ClinicalfeaturesanddiagnosisofAlzheimerdisease",section
on'Clinicalfeatures'.)
DementiawithLewybodies(DLB)issimilartoAlzheimerdiseasebutcanbemoreeasilyconfusedwith
delirium,becausefluctuationsandvisualhallucinationsarecommonandprominent.(See"Clinicalfeatures
anddiagnosisofdementiawithLewybodies".)
PrimarypsychiatricillnessesDeliriumiscommonlymisdiagnosedasdepression.Bothareassociatedwith
poorsleepanddifficultywithattentionorconcentration.Agitateddepressionmaybeespeciallyproblematic.
However,depressionisassociatedwithdysphoria,andthereislessfluctuationthanindelirium.
Maniacanbeconfusedwithhyperactivedeliriumwithagitation,delusions,andpsychoticbehavior.However,
maniaisusuallyassociatedwithahistoryofpreviousepisodesofmaniaordepression.Inschizophrenia,the
delusionsareusuallyhighlysystematized,thehistoryislonger,andthesensoriumisotherwiseclear.
DIAGNOSTICTESTS
LaboratorytestsAnumberoflaboratorytestsmaybeconsideredinthepatientwithdelirium.However,the
desirefordiagnosticcompletenesscanincreasecostsandpossiblydelaytheprompttreatmentofmoreobvious
disorders.Targetedtestingisappropriateinmostinstances.
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Serumelectrolytes,creatinine,glucose,calcium,completebloodcount,andurinalysisandurinecultureare
reasonableformostpatientswhenacauseisnotimmediatelyobvious.
Druglevelsshouldbeorderedwhereappropriate.However,cliniciansmustbeawarethatdeliriumcanoccur
evenwith"therapeutic"levelsofsuchagentsasdigoxin,lithium,orquinidine.
Toxicscreenofbloodandurineshouldbeobtainedfrompatientswithacutedeliriumorconfusionwhena
causeisnotimmediatelyobvious.Again,cliniciansmustbeawarethatsomecommondrugs(eg,
risperidone)arenotassessedinroutinelaboratoryscreens.Therefore,overdoseofthesedrugscannotbe
excludedbynegativeresultsfromatoxicscreen.
Bloodgasdeterminationisoftenhelpful.Inhyperventilatingpatients,respiratoryalkalosisismostcommonly
duetoearlysepsis,hepaticfailure,earlysalicylateintoxication,orcardiopulmonarycauses.Ametabolic
acidosisusuallyreflectsuremia,diabeticketoacidosis,lacticacidosis,latephasesofsepsisorsalicylate
intoxication,ortoxinsincludingmethanolandethyleneglycol.Achestxrayisusuallyperformed.
Furthertesting,suchasliverfunctiontests,shouldbebaseduponthehistoryandclinicalexamination.A
reportofslowcognitivedeclineoverseveralmonths,forexample,willincreasetheimportanceofevaluating
thyroidfunctionandvitaminB12levels.
NeuroimagingNeuroimagingwithheadCTmaybeusedselectivelyratherthanroutinelyformostpatientswith
delirium.However,neuroimagingisnecessary,ifnoobviouscauseofdeliriumisapparentonfirstevaluation.
Theneedforimagingshouldbeguidedbypatienthistoryandfindingsonneurologicexamination.Neuroimaging
maynotbenecessaryifapatientwithacutedeliriummeetsthefollowingconditions:theinitialclinicalevaluation
disclosesanobvioustreatablemedicalillnessorproblem,thereisnoevidenceoftrauma,nonewfocalneurologic
signsarepresent,andthepatientisarousableandabletofollowsimplecommands.However,neuroimaging
shouldbereconsideredifthepatientdoesn'timproveasexpected.
Neuroimagingmaystillberequiredifthedeliriumdoesnotimprovedespiteappropriatetreatmentoftheunderlying
medicalproblem.Inaddition,imagingshouldbeconsiderediftheneurologicexaminationisconfoundedby
diminishedpatientresponsivenessorcooperation.
Therehavebeennowelldesignedprospectivestudiestoassesstheyieldofneuroimaginginpatientswith
delirium.AbnormalitiesonheadCTarecommonlyseen,buttheyusuallyrepresentchronicconditionsthat
predisposetodeliriumratherthanacute,treatablecauses[42].Examplesofretrospectivestudiesinclude:
Aretrospectivestudyof294patientswithacuteconfusionfoundrevealedabnormalCTsin14percentoverall
[43].However,only4percentofpatientswithoutfocalsignshadabnormalCTthelowestyieldofCT(2
percent)wasinpatientswithpremorbiddementiaandnofocalneurologicsigns.
InareviewofCTscansperformedin123medicalintensivecareunitpatients,newCTfindingswerepresent
in26,leadingtoachangeindiagnosisin11andanewtreatmentplanin6[36].Moststudieswereperformed
foranindicationof"alteredmentalstatus"andfindingsincludedcerebralinfarctionin13,intracranial
hemorrhagein2,andtumorin3.
Inanotherreviewof279headCTscansperformedintheemergencydepartmentinpatientsolderthan70
years,42(15percent)revealedanacutecondition[38].Ofthese,40werefoundinpatientswitheither
significantlyimpairedconsciousness(eg,unabletoopeneyes,speak,orfollowsimplecommands)and/or
newfocalneurologicfindings.
FewerdataexistforMRIevaluationofpatientswithdelirium.However,MRIismoresensitivethanheadCTfor
acutestroke,posteriorfossalesions,andwhitematterlesions,however,suchfindingsmaynotinfluence
immediatetreatmentcourseincriticallyillpatients[44].Inpatientswithdeliriumofunknowncauseandnegative
headCT,MRImaybeusefultoexcludeacuteorsubacutestrokeandmultifocalinflammatorylesions(eg,asseen
inreversibleposteriorleukoencephalopathyandacutedisseminatedencephalomyelitis).
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LumbarpunctureOlderpatientswithbacterialmeningitisaremorelikelytopresentwithdeliriumratherthan
theclassictriadoffever,headache,andmeningismus.Bacterialmeningitisisanuncommondisorder,androutine
cerebrospinalfluid(CSF)evaluationmaynotbenecessaryinallfebrileorsepticappearingolderpatientswith
deliriumaslongasotherinfectiousfociareobvious.However,CSFanalysismaybetheonlydiagnostictoolthat
willidentifybacterialorasepticmeningitisandencephalitis.
Inaretrospectivestudyof81elderlypatientswhowereadmittedtothehospitalfortheevaluationoffeverand
mentalstatuschanges,CSFcultureswerenegativeforbacterialgrowthin80of81patients[45].However,one
caseofbacterialmeningitisandonecaseofasepticmeningitiswerediagnosedbyCSFfindings.Ina
retrospectivereviewof232lumbarpuncturesperformedinhospitalizedpatientsfortheindicationofalteredmental
status,11percentwereabnormaltheyieldwashighestinthosesuspectedofcommunityacquiredmeningitis
[46].
Lumbarpunctureismandatorywhenthecauseofdeliriumisnotobvious.Cliniciansshouldalsohavealow
thresholdforobtainingCSFinfebrilepatientswithdelirium,evenwhenalternateexplanatoryconditionsfordelirium
arepresentorsuspected.
Neuroimagingshouldbeobtainedpriortolumbarpunctureinpatientswithcoma,focalsigns,papilledema,or
suspicionofincreasedintracranialpressurebecauseoftheverylowbutrealriskofprecipitatingtranstentorial
herniation.Iflumbarpunctureisdelayedandthesuspicionofbacterialmeningitisishigh,empiricantibiotic
treatmentshouldbeconsidered.(See"Lumbarpuncture:Technique,indications,contraindications,and
complicationsinadults",sectionon'Complications'and"Clinicalfeaturesanddiagnosisofacutebacterial
meningitisinadults".)
EEGtestingElectroencephalography(EEG)isusefulinpatientswithalteredconsciousnessinorderto[47,48]:
Excludeseizures,especiallynonconvulsiveorsubclinicalseizures
Confirmthediagnosisofcertainmetabolicencephalopathiesorinfectiousencephalitidesthathave
characteristicEEGpatterns
Nonconvulsiveseizureslackmotormanifestationsorconvulsions,buttheymayimpairconsciousness.
Nonconvulsivestatusepilepticusmaycausecontinuousorfluctuatingimpairmentofconsciousness,andEEGis
theonlymethodthatcanmakethediagnosis.Onereportevaluated198EEGsperformedfortheindicationof
alteredconsciousnesswithoutconvulsionsandfounddefiniteorprobablenonconvulsivestatusepilepticusin74
(37percent)[49].Inanotherstudy,continuousEEGmonitoringwasperformedforunexplaineddecreasein
consciousnessordetectionofsubclinicalseizuresin570criticallyillpatients[50].Seizuresweredetectedin110
patients(19percent),andtheseizureswereexclusivelynonconvulsivein92percentoftheseindividuals.Coma
patientsfrequentlyrequiredgreaterthan24hoursofmonitoringtodetectthefirstelectrographicseizure.
Metabolicencephalopathiesmayshowdiffusebilateralslowingofbackgroundrhythmandmoderateorhighwave
amplitude.Triphasicwavesareassociatedwithhepaticencephalopathybutcanbeseeninotherseveremetabolic
disturbancesincludinguremicandsepticencephalopathy[51,52].Viralencephalitisistypicallyassociatedwith
diffusebackgroundslowingandoccasionalepileptiformactivityorelectrographicseizures.Herpessimplex
encephalitismaybeassociatedwithhighamplitudeperiodiccomplexesinthetemporallobeleads.
EEGevaluationshouldbeobtainedforanypatientwithalteredconsciousnessofunknownetiology[40].Patients
witharemoteorrecenthistoryofheadtrauma,stroke,seizures,orfocalbrainlesionsmaybeathigherriskof
convulsiveandnonconvulsiveseizures.However,neitherclinicalsignsnorpriorhistorypredictedwhichofthe198
EEGsshowednonconvulsivestatusinthestudycitedabove[49].
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
http://www.uptodate.com/contents/diagnosisofdeliriumandconfusionalstates?topicKey=NEURO%2F4824&elapsedTimeMs=6&source=see_link&view=p
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theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopic(see"Patientinformation:Delirium(confusion)(TheBasics)")
BeyondtheBasicstopic(see"Patientinformation:Delirium(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Deliriumisaclinicalsyndromecausedbyamedicalcondition,substanceintoxicationorwithdrawal,or
medicationsideeffectthatischaracterizedbyadisturbanceofconsciousnesswithreducedabilitytofocus,
sustain,orshiftattention(See'Definitionandterminology'above.)
Nearly30percentofoldermedicalpatientsexperiencedeliriumatsometimeduringhospitalization.The
incidenceishigherinthosewithadvancedageandpreexistingbraindisease(See'Epidemiology'above.)
Adisturbanceofconsciousnessandalteredcognitionareessentialcomponentsofdelirium.Somepatients
aredrowsyandlethargic,othersareagitatedandconfused.Visualhallucinations,tremulousness,and
myoclonus/asterixisarevariablypresent(See'Clinicalpresentation'aboveand'Neurologicexamination'
above.).
Focalorlateralizedneurologicfindingsarenotcharacteristicofdelirium.Acarefulneurologic
examinationcanalsodistinguishbetweenfocalsyndromesthatcanmimicdelirium(See'Focal
syndromes'above.)
Thepastmedicalhistory,areviewofmedications,andaphysicalexaminationmayprovidecluesastothe
underlyingetiology(See'History'aboveand'Generalexamination'above.)
Laboratoryevaluationinpatientswithdeliriumshouldincludeserumelectrolytes,creatinine,glucose,
calcium,completebloodcount,andurinalysisandurineculture.Druglevels,toxicologyscreen,liverfunction
testing,andarterialbloodgasshouldfollowifthecauseremainsobscure(See'Laboratorytests'above.).
Neuroimaging,lumbarpuncture,andelectroencephalogramarenotrequiredinmostpatientswithdelirium,
butarerecommendedinspecificclinicalscenarios,includinginthosewhosecauseremainsobscureafter
routinetesting(See'Diagnostictests'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
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2013.
3.AdamsRD,VictorM,RopperAH.Deliriumandotheracuteconfusionalstates.In:PrinciplesofNeurology,
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18.StefanoGB,BilfingerTV,FricchioneGL.Theimmuneneurolinkandthemacrophage:postcardiotomy
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21.FickDM,AgostiniJV,InouyeSK.Deliriumsuperimposedondementia:asystematicreview.JAmGeriatr
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22.LundstrmM,EdlundA,BuchtG,etal.Dementiaafterdeliriuminpatientswithfemoralneckfractures.J
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23.MarcantonioE,TaT,DuthieE,ResnickNM.Deliriumseverityandpsychomotortypes:theirrelationship
withoutcomesafterhipfracturerepair.JAmGeriatrSoc200250:850.
24.McAvayGJ,VanNessPH,BogardusSTJr,etal.Olderadultsdischargedfromthehospitalwithdelirium:
1yearoutcomes.JAmGeriatrSoc200654:1245.
25.PompeiP,ForemanM,CasselCK,etal.Detectingdeliriumamonghospitalizedolderpatients.ArchIntern
Med1995155:301.
26.InouyeSK,vanDyckCH,AlessiCA,etal.Clarifyingconfusion:theconfusionassessmentmethod.Anew
methodfordetectionofdelirium.AnnInternMed1990113:941.
27.WeiLA,FearingMA,SternbergEJ,InouyeSK.TheConfusionAssessmentMethod:asystematicreviewof
currentusage.JAmGeriatrSoc200856:823.
28.WongCL,HolroydLeducJ,SimelDL,StrausSE.Doesthispatienthavedelirium?:valueofbedside
instruments.JAMA2010304:779.
29.ElyEW,InouyeSK,BernardGR,etal.Deliriuminmechanicallyventilatedpatients:validityandreliabilityof
theconfusionassessmentmethodfortheintensivecareunit(CAMICU).JAMA2001286:2703.
30.LuetzA,HeymannA,RadtkeFM,etal.Differentassessmenttoolsforintensivecareunitdelirium:which
scoretouse?CritCareMed201038:409.
31.MitasovaA,KostalovaM,BednarikJ,etal.Poststrokedeliriumincidenceandoutcomes:validationofthe
ConfusionAssessmentMethodfortheIntensiveCareUnit(CAMICU).CritCareMed201240:484.
32.PlaschkeK,vonHakenR,ScholzM,etal.Comparisonoftheconfusionassessmentmethodforthe
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33.BergeronN,DuboisMJ,DumontM,etal.IntensiveCareDeliriumScreeningChecklist:evaluationofanew
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34.FrancisJ,MartinD,KapoorWN.Aprospectivestudyofdeliriuminhospitalizedelderly.JAMA1990
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39.OldenbeuvingAW,deKortPL,JansenBP,etal.Deliriumintheacutephaseafterstroke:incidence,risk
factors,andoutcome.Neurology201176:993.
40.ShethRD,DrazkowskiJF,SirvenJI,etal.Protractedictalconfusioninelderlypatients.ArchNeurol2006
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41.VeranO,KahaneP,ThomasP,etal.Denovoepilepticconfusionintheelderly:a1yearprospectivestudy.
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42.KoponenH,HurriL,StenbckU,etal.Computedtomographyfindingsindelirium.JNervMentDis1989
177:226.
43.HufschmidtA,ShabarinV.Diagnosticyieldofcerebralimaginginpatientswithacuteconfusion.Acta
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44.MorandiA,GuntherML,VasilevskisEE,etal.Neuroimagingindeliriousintensivecareunitpatients:a
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45.WarshawG,TanzerF.Theeffectivenessoflumbarpunctureintheevaluationofdeliriumandfeverinthe
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199825:S16.
Topic4824Version15.0
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GRAPHICS
Commoncausesofdeliriumandconfusionalstates
Drugsandtoxins
Prescriptionmedications(eg,opioids,sedativehypnotics,antipsychotics,lithium,skeletalmuscle
relaxers,polypharmacy)
Nonprescriptionmedications(eg,antihistamines)
Drugsofabuse(eg,ethanol,heroin,hallucinogens,nonmedicinaluseofprescriptionmedications)
Withdrawalstates(eg,ethanol,benzodiazepines)
Medicationsideeffects(eg,hyperammonemiafromvalproicacid,confusionfromquinolones,
serotoninsyndrome)
Poisons:
Atypicalalcohols(ethyleneglycol,methanol)
Inhaledtoxins(carbonmonoxide,cyanide,hydrogensulfide)
Plantderived(eg,Jimsonweed,Salvia)
Infections
Sepsis
Systemicinfectionsfeverrelateddelirium
Metabolicderangements
Electrolytedisturbance(elevatedordepressed):sodium,calcium,magnesium,phosphate
Endocrinedisturbance(depressedorincreased):thyroid,parathyroid,pancreas,pituitary,adrenal
Hypercarbia
Hyperglycemiaandhypoglycemia
Hyperosmolarandhypoosmolarstates
Hypoxemia
Inbornerrorsofmetabolism:porphyria,Wilson'sdisease,etc.
Nutritional:Wernicke'sencephalopathy,vitaminB12deficiency,possiblyfolateandniacin
deficiencies
Braindisorders
CNSinfections:encephalitis,meningitis,brainorepiduralabscess
Epilepticseizures,especiallynonconvulsivestatusepilepticus*
Headinjury*
Hypertensiveencephalopathy
Psychiatricdisorders*
Systemicorganfailure
Cardiacfailure
Hematologic:thrombocytosis,hypereosinophilia,leukemicblastcellcrisis,polycythemia
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Liverfailure:acute,chronic
Pulmonarydisease,includinghypercarbiaandhypoxemia
Renalfailure:acute,chronic
Physicaldisorders
Burns
Electrocution
Hyperthermia
Hypothermia
Trauma:withsystemicinflammatoryresponsesyndrome,*headinjury,fatembolism
*Disordersthat,whilenottrulysystemicor"medical",mayproducetheclinicalpictureofdeliriumor
confusionalstateinallotheraspects.
Graphic59893Version3.0
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Drugsbelievedtocauseorprolongdeliriumorconfusionalstates*
Analgesics
Corticosteroids
Nonsteroidalantiinflammatoryagents
Dopamineagonists
Opioids(especiallymeperidine)
Amantadine
Antibioticsandantivirals
Bromocriptine
Acyclovir
Levodopa
Aminoglycosides
Pergolide
AmphotericinB
Pramipexole
Antimalarials
Ropinirole
Cephalosporins
Gastrointestinalagents
Cycloserine
Fluoroquinolones
Isoniazid
Interferon
Linezolid
Macrolides
Metronidazole
Nalidixicacid
Penicillins
Rifampin
Sulfonamides
Anticholinergics
Atropine
Benztropine
Diphenhydramine
Scopolamine
Antiemetics
Antispasmodics
Histamine2receptorblockers
Loperamide
Herbalpreparations
Atropabelladonnaextract
Henbane
Mandrake
Jimsonweed
St.John'sWort
Valerian
Hypoglycemics
Hypnoticsandsedatives
Barbiturates
Benzodiazepines
Trihexyphenidyl
Musclerelaxants
Anticonvulsants
Baclofen
Carbamazepine
Cyclobenzaprine
Levetiracetam
OtherCNSactiveagents
Phenytoin
Disulfiram
Valproate
Cholinesteraseinhibitors(eg,donepezil)
Vigabatrin
Interleukin2
Antidepressants
Lithium
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Mirtazapine
Phenothiazines
Selectiveserotoninreuptakeinhibitors
Tricyclicantidepressants
Cardiovascularandhypertensiondrugs
Antiarrhythmics
Betablockers
Clonidine
Digoxin
Diuretics
Methyldopa
*Notexhaustive,allmedicationsshouldbeconsidered.
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Bedsidetestsofattention
Test
Digit
span
Directions
Scoring
Askthesubjecttolistencarefullyandrepeataseriesofrandom
numbers.Beginwithastringof2digits,thenincrease.Readeach
numberinanormaltoneofvoiceatarateofonedigitpersecond,
Inabilityto
repeatastring
ofatleastfive
takingcarenottogroupdigitsinpairsorsequencesthatcouldaid
repetitioneg,352818493638515729
468192756
digitsindicates
probable
impairment.
Vigilance
Readalistof60letters,amongwhichtheletter"A"appearswith
Counterrorsof
"A"test
greaterthanrandomfrequency.Thesubjectisrequiredtoindicate
(eg,bytappingonthedesk)wheneverthetargetletterisspokenby
theexaminer.Theletterlistisreadinanormaltoneatarateofone
letterpersecondeg,LTPEAOAICTDALAANIABFSAMRA
EOZDPAKALUCJTAEO
omissionand
commission.
Morethantwo
errorsis
considered
abnormal.
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Confusionassessmentmethod(CAM)forthediagnosisofdelirium*
Feature
1.Acuteonset
andfluctuating
course
Assessment
Usuallyobtainedfromafamilymemberornurseandshownbypositive
responsestothefollowingquestions:
"Isthereevidenceofanacutechangeinmentalstatusfromthepatient's
baseline?"
"Didtheabnormalbehaviorfluctuateduringtheday,thatis,tendtocomeand
go,orincreaseanddecreaseinseverity?"
2.Inattention
Shownbyapositiveresponsetothefollowing:
"Didthepatienthavedifficultyfocusingattention,forexample,beingeasily
distractibleorhavingdifficultykeepingtrackofwhatwasbeingsaid?"
3.Disorganized
thinking
Shownbyapositiveresponsetothefollowing:
4.Alteredlevel
of
consciousness
Shownbyanyanswerotherthan"alert"tothefollowing:
"Wasthepatient'sthinkingdisorganizedorincoherent,suchasramblingor
irrelevantconversation,unclearorillogicalflowofideas,orunpredictable
switchingfromsubjecttosubject?"
"Overall,howwouldyouratethispatient'slevelofconsciousness?"
Normal=alert
Hyperalert=vigilant
Drowsy,easilyaroused=lethargic
Difficulttoarouse=stupor
Unarousable=coma
*Thediagnosisofdeliriumrequiresthepresenceoffeatures1AND2pluseither3OR4.
19/20
23/2/2016
Disclosures
Disclosures:JosephFrancis,Jr,MD,MPHNothingtodisclose.GBryanYoung,MD,FRCPCNothingtodisclose.MichaelJ
Aminoff,MD,DScEquityOwnership/StockOptions:Trust,whichisindependentlymanagedbyafinancialcompany.Theportfoliomay
includemedicalordrugcompanies.KennethESchmader,MDGrant/Research/ClinicalTrialSupport:Merck[Herpeszoster(Zoster
vaccine)].JanetLWilterdink,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy
20/20

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