Update The Assessment and Treatment of Delirium€¦ · 3 The Assessment and Treatment of Delirium Summary of Modified Recommendations All modified or added recommendations are presented

Canadian Coalition for Seniors’ Mental Health

Coalition Canadienne pour la Santé Mentale des Personnes Âgées

2014 Guideline Update

The Assessment and Treatment of Delirium

2014 GUIDELINE UPDATE

1 | The Assessment and Treatment of Delirium

AIMS OF THE GUIDELINE: The CCSMH is proud to have been able to facilitate the development of

these clinical guidelines. These are the first interdisciplinary, national best practices

guidelines to specifically address key areas in seniors’ mental health. These guidelines were

written by and for interdisciplinary teams of health care professionals from across Canada.

The aim of these guidelines is to improve the assessment, treatment, management and

prevention of key mental health issues for seniors, through the provision of evidence-based

recommendations. The recommendations are based on the best available evidence at the

time of publication and when necessary, supplemented by the consensus opinion of the

guideline development group.

AIMS OF THE GUIDELINE UPDATE: Guideline Updates summarize significant developments in the

practice since the publication of the original guidelines in 2006. Guideline Updates are

authored and reviewed by experts associated with the original guideline development

project. Please refer to the original guideline, found on our website at www.ccsmh.ca, for

more detailed information regarding the specific practice recommendations.

DISCLAIMER: This publication is intended for information purposes only, and is not intended to

be interpreted or used as a standard of medical practice. Best efforts were used to ensure

that the information in this publication is accurate, however the publisher and every person

involved in the creation of this publication disclaim any warranty as to the accuracy,

completeness or value of the contents of this publication. This publication is distributed

with the understanding that neither the publisher nor any person involved in the creation

of this publication is rendering professional advice. Physicians and other readers must

determine the appropriate clinical care for each individual patient on the basis of all the

clinical data available for the individual case. The publisher and every person involved in

the creation of this publication disclaim any liability arising from contract, negligence, or

any other cause of action, to any party, for the publication contents or any consequences

arising from its use.

SUGGESTED CITATION: Gage L & Hogan DB. (2014). 2014CCSMHGuidelineUpdate:TheAssessment

andTreatmentofDelirium.Toronto:CanadianCoalitionforSeniors’MentalHealth

(CCSMH),www.ccsmh.ca.

ACKNOWLEDGEMENT:ThisGuidelineUpdatewasmadepossiblethrougha2010CIHR-Instituteof

AgingBettyHavensAwardforKnowledgeTranslationinAging.


The Assessment and Treatment of Delirium |2

Introduction Sincethepublicationin2006ofthe

CanadianCoalitionofSeniors’Mental

Health(CCSMH)guidelinesonThe

AssessmentandTreatmentofDelirium

(Hoganetal.2006),progressondelirium

hasbeenincrementalratherthan

transformative.Workdonesincethenhas

reinforcedtheneedtobeawarethat

deliriumcommonlycomplicatesthecareof

olderpersonsadmittedtoacutecare

hospitalsandlong-termcarefacilities

(Siddiqi,House&Holmes2006),andcan

haveseriouslong-termconsequences

especiallyforthosewhosesymptoms

persist(Cole,Ciampi,Belzile&Zhong2010;

Cole2010;Wilcoxetal.2010;Fongetal.

2012;Saczynskietal.2012;Davisetal.

2012;Grossetal.2012;).Alongerduration

ofdeliriumisassociatedwithpre-existing

dementia,multiplemorbidity,increasing

deliriumseverity,hypoactivesymptoms,

andhypoxia(Dasgupta&Hillier2010).As

withotherpsychiatricconditions,delirium

hasaspectrumofseverity(Levkoff,Yang&

Liptzin2004).Atthemilderendofthe

continuum,therearepatientswithoneor

moreofthesymptomsofdeliriumwhodo

notmeetDSM-definedcriteriafordelirium.

Theyarereferredtoashaving

subsyndromaldelirium(SSD).Clinicians

shouldbeawarethatSSDmaybea

prodromalstateand,asnotedinthe2006

guidelines,hasoutcomesthatliebetween

thoseofdeliriousandnon-delirious

patients(Ouimetetal.2007;Coleetal.

2011).Uncertainty,though,remainsabout

howtodiagnoseSSD,theutilityofthis

classificationgiventhefluctuatingcourseof

delirium,andwhattodoaboutit(Blazer&

vanNieuwenhuizen2012).

WhiletheCCSMHguidelinesondelirium

wereadaptedforolderadultsattheendof

life(Allardetal.2010),theyhavenotbeen

otherwisereviewedsincetheirpublication.

In2011,theCCSMHaskedthe2006co-

leadstoprovidealimitedupdateofthe

guidelines.Itwasagreedtoprovideoneon

pharmacologicalinterventionstoeither

preventortreatdelirium.Thisareawasfelt

tohavethegreatestpotentialinterestand

needforanupdate.Itslimitedscopemeant

itcouldbedoneinatimelymannerwiththe

limitedresourcesavailable.Thedecisionto

reviewdrugtherapyforthisupdateinno

waydetractsfromtheimportanceof

addressingreversiblecontributors,

reducingpsychoactivemedications,and

utilizingnon-pharmacologicalinterventions

ineffortstopreventormanagedelirium

(Inouye,Marcantonio&Metzger2014).


3 |The Assessment and Treatment of Delirium

Summary of Modified Recommendations All modified or added recommendations are presented together with the page numbers for

the original guideline recommendations at the beginning of this update for easy reference.

Subsequently, in each section we present the recommendation with a discussion of the

relevant literature since the original publication in 2006. We strongly encourage readers to

refer to the original 2006 guidelines and the discussion below, rather than only using the

summary of modified recommendations.

2006Recommendation:Prevention(page27)

Basedoncurrentevidence,psychopharmacologicinterventionsforunselectedolder

personstopreventthedevelopmentofdeliriumarenotrecommended[D].

ModifiedRecommendations:Prevention

Thereissuggestiveevidencethatgeneralanesthesiacomparedtootherformsof

anesthesiaisassociatedwithanincreasedriskofdevelopingpost-operativecognitive

dysfunction(POCD)butnotpost-operativedelirium(POD).Furtherresearchtoconfirm

theincreasedriskforPOCDanditsconsequencesisrequired[B].

Thereissuggestiveevidencethatshort-term,low-dosemelatoninreducestheincidence

ofdeliriuminolderpatientsadmittedtoanacutemedicalunit,butfurtherresearchis

requiredbeforeitcanberecommendedforroutineuse[B].

Thereissuggestiveevidencethatshort-term,low-dosehaloperidolreducesthe

incidenceand/orseverityofPODinhighriskolderpatientswithoutcontraindications

toitsuse,butfurtherresearchisneededbeforeitcanberecommendedforroutineuse

[B].

Thereissuggestiveevidencethatrisperidoneaftercardiacsurgeryreducestheriskof

PODinpatientswithoutcontraindicationstoitsuse,butfurtherresearchisneeded

beforeitcanberecommendedforroutineuse[B].

Thereissuggestiveevidencethatshort-term,low-doseolanzapinereducestheriskof

POD,butifdeliriumoccursitmightbemoresevereandofalongerduration.Theuseof

olanzapineforthepreventionofPODcannotberecommendedatthistime[B].

Theuseofcholinesteraseinhibitorssolelyforthepreventionortreatmentofdelirium

isnotrecommended[A].

Todecreasetheriskofdeliriuminmechanicallyventilatedpatients,dexmedetomidine

shouldbeconsideredasasedativealternativetobenzodiazepinesandpropofol[A].



Thereisinsufficientevidencetosupporttheroutineuseofanyotherformof

pharmacologicalinterventionforthepreventionofdelirium[B].

2006Recommendation:Antipsychotics(page41-44)

Highpotencyantipsychoticmedicationsarepreferredoverlowpotencyantipsychotics

[B].

Haloperidolissuggestedastheantipsychoticofchoicebasedonthebestavailable

evidencetodate[B].

Atypicalantipsychoticsmaybeconsideredasalternativeagentsastheyhavelower

ratesofextra-pyramidalsigns.[B]

ModifiedRecommendations:Antipsychotics

Inolderpersonswithadeliriumwherepharmacotherapyisindicated,lowdose,short-

termtherapywithhaloperidoloranatypicalantipsychotic(e.g.,olanzapine,quetiapine,

risperidone)canbeconsidered.Haloperidolisnotrecommendedifthereispre-existing

ParkinsondiseaseorLewybodydementia[B].

Methods Thesearchtermsusedwerethesameas

forthe2006Guidelines(Hoganetal.

2006),thoughonthisoccasionthe

databasesearchwaslimitedtoMedline

andrestrictedtoEnglishpaperspublished

betweenJuly2005andJune2011.

Atotalof411paperswereidentified.Both

authorsreviewedthetitlesandabstractsof

thesepapersinordertoselectwhich

shouldundergoafull-textreview.

Controlledtrials(especiallyrandomized),

meta-analyses,reviews(especially

systematic),andpracticeguidelines

potentiallyrelevanttothesubjectarea

werechosen.Eighty-nineofthe411papers

identifiedintheliteraturesearchwere

selectedforfull-textreview.Bothauthors

evaluatedeachpaper.Agreementwas

reachedonallchangesoradditionstothe

2006recommendations.Inthefallof2012,

adraftoftherevisedrecommendations

waspresentedattheannualmeetingofthe

CCSMH.Valuablefeedbackwasobtained,

whichledtominormodifications.

Becauseofthelengthoftimebetweenthe

systematicliteraturereviewandthe

publicationoftheupdate,oneofthe

authors(DH)identifiedadditionalrelevant

papersbypurposefulnon-exhaustive

Medlinesearches,usingtextterms,to

covertheperiodbetweenJuly2011and

September2014.Afterthisupdated

examinationoftheliterature,afewfurther

modificationsweremadetotherevised

recommendations.



Part 2: Prevention Discussion and RecommendationsBasedontheupdatedreview,werecommendthatthefollowing2006recommendationbe

replacedbytheninenewrecommendationssummarizedbelow.

2006Recommendation:Prevention(page27)

Basedoncurrentevidence,psychopharmacologicinterventionsforunselectedolder

personstopreventthedevelopmentofdeliriumarenotrecommended[D].


Intraoperativemonitoringofthedepthofsedationinordertotitrateanestheticdrugsis

apromisingapproachtodecreasingtheriskofpostoperativedeliriumbutfurtherstudy

isrequired[B].

Asystematicreviewofgeneraland

regionalanesthesiaontheincidenceof

postoperativecognitivedysfunction

(POCD)andpostoperativedelirium(POD)

foundthatgeneralanesthesia,comparedto

otherformsofanesthesia,wasnot

associatedwithahigherriskforPOD(odds

ratio0.88,0.51-1.5195%confidence

interval).However,therewasamarginal

increaseintheriskforPOCD(oddsratio

1.34,0.93-1.9595%confidenceinterval)

(Mason,Noel-Storr&Ritchie2010).

Anothersystematicreviewconcludedthat

thelikelihoodofPODwasequivalentfor

neuraxial(i.e.,atypeofregionalanesthesia

thatinvolvestheinjectionofanesthetic

agentsaroundthenervesofthecentral

nervoussystem,suchasspinaland

epiduralanesthesia)andgeneral

anesthesia(pooledincidenceswere17.1%

forboth)(Zhang,Lu,Zou,Wang,Xu&Shi

2013).Athirdreviewreportedno

differencebetweengeneralandregional

anesthesiainratesofPOD(Friedman,

Soleimani,McGonigle,Egol&Silverstein

2014).Titratingthedepthof

intraoperativesedationby

neuromonitoringhasattractedincreasing

interestasapotentialapproachto

preventingPOD.Arandomizedstudyof

olderpatientsundergoinghipfracture

repairunderspinalanesthesiawith

propofolsedationthatwastitratedbythe

bispectralindex(BIS)foundasignificantly

increasedincidenceofPOD[40.4%vs.

19.3%,p=0.014]lastingaboutaday

longerwithdeepcomparedtolight

sedation(Sieberetal.2010).Two

randomizedstudiesofBIS-guided

anesthesiaforelectivesurgeryinolder

patientsreportedlowerratesofPOD

(15.6%vs.24.1%,p=0.01inthefirststudy

and16.7%vs.21.4%,p=0.036inthe

second),comparedtoroutinecare(Chan,

Cheng,Lee,Gin&theCODATrialGroup

2013;Radtkeetal.2013).Potential

mechanismsincludeavoidingextremely

lowBISvaluesand/orreducinganesthetic

drugexposure.Thespecificdrugsusedfor

generalanesthesiahavealsobeen



examined.Asmall[58malepatients]

randomizedcontrolledstudyofketamine

fortheinductionofanesthesiainpatients

undergoingelectivecardiacsurgerywith

cardiopulmonarybypassfounditsusewas

associatedwithasignificantlylower

incidenceofPOD[3%vs.31%,p=0.01])

(Hudetzetal.2009).Howeverthisstudy

hasnotbeenreplicated.Regionalnerve

blocksforhipfracturesareanother

promisingperioperativeprocedurethat

willbediscussedinafollowingsection.We

madeaqualifiedrecommendationand

assignedastrengthgradeof“B”aswefeel

furtherworkisrequiredtoconfirmand

broadentheobservationsmadetodateto

otherpatientpopulations.


Short-termmelatoninorramelteontherapyinordertoreducetheincidenceofPODor

deliriuminolderpatientsadmittedtointensivecareoracutemedicalunitsrequires

furtherstudyandcannotberecommendedatthistime[B].

Melatonin(anaturallyoccurring

compoundproducedbythepinealglandin

humans,knownchemicallyasN-acetyl-5-

methoxytryptamine)isimportantin

sleep/wakeregulation.Ithasbeen

suggestedthatmelatoninsupplementation

mightbehelpfulinpreventingandtreating

delirium(Lewis&Barnett2004;Bourne&

Mills2006;Hanania&Kitain2002).Ina

studyofolderpatientsundergoingahip

arthroplasty,theuseofmelatoninwas


incidenceofPODcomparedtothose

receivingeithernothing,midazolamor

clonidine(9.4%vs.32.7%,44.0%,and

37.3%respectfully,p<0.05)(Sultan

2010).Thereareanumberof

methodologicalconcernsaboutthisstudy,

includingtheexclusionofpatientswith

cognitiveimpairment(DeJonghe,vande

Glind,vanMunster&deRooij2014).A

relativelysmall(149patientsenrolled),

single-site,double-blind,placebo-

controlled,blockrandomizedtrialof

melatonin(0.5mggivenorallyeverydayin

theeveningsuntildischargefromhospital,

death,orday14ofthehospitalstay)in

older(65+)patientsadmittedtoamedical

in-patientservicefoundalowerriskof

delirium(12%vs.31%,p=0.014)with

activetherapy.Theagentwasreportedly

well-tolerated.Nosignificantbenefitwas

seenonanysecondaryoutcome(i.e.,

deliriumseverity,useofsedatives,theuse

ofrestraints,mortality,lengthofstay,

sleep).Asignificantproportionofthose

enrolled(27subjectsor18.1%)were

excludedfromtheassessmentofoverall

effectiveness(Al-Aamaetal.2011).Finally,

adouble-blind,randomizedcontrolledtrial

of378analyzedpatientsfoundthat

melatonin(3mgintheeveningforfive

consecutivedays)inolder(meanage84)

patientsundergoinghipsurgeryhadno



significanteffectontheincidenceof

delirium(29.6%inthemelatoningroupvs.

25.5%withplacebo)(DeJonghe,van

Munsteretal.2014).

Ramelteonisanagonistofmelatonin

approvedintheUnitedStatesandother

countriesforinsomniacharacterizedby

difficultywithfallingasleep.Arandomized

single-blindstudyoframelteon8mgor

placeboadministeredeverynightforseven

daystoasmallgroup(n=67)ofolder(65-

89yearsofage)patientsnewlyadmittedto

hospitalwithaseriousmedicalproblem

reportedasignificantlylowerriskof

delirium(3%vs.32%,p=0.003)with

activetreatment(Hattaetal.2014).There

arenopublishedstudiescomparing

melatonintoramelteonintheirabilityto

preventdelirium.

Thenegativerecommendationwitha[B]

gradewasgivenbecauseofthe

inconsistencyandlimitationsofthe

currentevidence.Largerconfirmatory

studiesindifferentpopulationsare

requiredbeforeitsusecanbeadvocated.

TheNationalInstituteforHealthand

ClinicalExcellence(2012)hasalsomadea

callforadditionalresearchonmelatonin.


Thereisinconsistentevidencethatshort-term,lowdosehaloperidolreducesthe

incidenceand/orseverityofPODinhighriskolderpatientswithoutcontraindications

toitsuse.Furtherresearchisneededbeforeitcanberecommendedforroutineuse[B].

Bypreventingneuroexcitatory

potentiationand/orantagonizingsigma-1

receptors,haloperidolmaybeaneffective

prophylacticagentfordelirium(Caplan

2012).Arandomizedplacebo-controlled

trialofhaloperidol(0.5mgthreetimes

dailystartedpre-operativelyandthen

continuedforuptothreedaysafter

surgery)inolder(70+)patientsat

intermediatetohighriskfordelirium

admittedforacuteorelectivehipsurgery

showednostatisticallysignificant

differenceintheprimaryoutcome

measure,theincidenceofPOD(15.1%

withhaloperidolvs.16.5%withplacebo,

relativerisk0.91,0.6-1.395%confidence

interval).However,thereweresignificant

differencesfavouringhaloperidolinthe

severityandduration(5.4vs.11.8days,p<

0.001)ofdelirium,aswellasashorter

averagelengthofhospitalstay(17.1vs.

22.6days,p<0.001)ifPODoccurred

(Kalisvaart,deJonghe,Bogaardsetal.

2005).Nohaloperidol-relatedadverse

effectswerenoted.Inaprospectivecohort

studyofhipfracturepatients,those

deemedathighriskfordeliriumwere

treatedwithprophylacticlowdose

haloperidol.Thoseidentifiedashighrisk

didhaveahigherincidenceofdelirium,but

usingabefore-afterdesign,prophylactic

treatmentwithhaloperidoldidnotreduce

overalldeliriumincidence(Vochtelooetal.

2011).Arandomized,double-blind,



placebo-controlledtrialofIVhaloperidol

(0.5mgIVbolusinjection,followedby

continuousinfusionatarateof0.1mg/hr.

for12hours)inolder(65+)patients

admittedtointensivecareunitsafternon-

cardiacsurgery,showedasignificantly

lowerincidenceofPODduringthefirst

sevenpostoperativedays(15.3%vs.

23.2%,p=0.031).Thetreatmentwaswell

tolerated(Wangetal.2012).TheHope-ICU

wasadouble-blind,placebo-controlled

randomizedtrialofcriticallyilladults

requiringmechanicalventilation.Patients

receivedhaloperidol2.5mgor0.9%saline

IVeveryeighthoursirrespectiveofcoma

ordeliriumstatusforupto14days.

Haloperidolhadnoimpactonthenumber

ofdaysspentindelirium(Pageetal.2013).

Arandomized,controlled,open-labelstudy

ofolderpatientsundergoingelective

surgeryshowednosignificantdifferencein

theincidenceofdelirium(POD42.4%with

haloperidolvs.33.3%inthecontrolgroup,

p=0.0309)(Fukataetal.2014).

Intravenoushaloperidolisapprovedfor

useinCanadabutQTprolongationand

torsadesdepointescanoccur.Theserare

adverseeventsalmostalwaysarisein

patientswithadditionalriskfactorsand

aftercumulativedosagesof2mgormore

(Eyer-Massettl,Cheng,Sharpe,Meir&

Guglielmo2010).Australianguidelinesfor

themanagementofhipfracturesinolder

personsandaCochranereviewof

interventionsforpreventingdeliriumin

hospitalizedpatientsbothconcludedthat

prophylacticlowdosehaloperidolmight

reducetheseverityanddurationofPOD

andshortenlengthofhospitaladmission

forhipsurgery(Mak,Cameron&March

2010;Siddiqi,Holt,Britton&Holmes

2007).Thepositivestudiesreviewed

targetedhighriskolderpatients(i.e.,older

patientsatintermediatetohighdelirium

riskundergoingorthopedicsurgery,older

patientsadmittedtoanintensivecareunit

afternon-cardiacsurgery)andexcluded

patientswithavarietyofcontraindications

includingParkinsonismandaprolonged

correctedQTintervalonabaselineECG.

The"B”graderecommendationthat

additionalworkisrequiredwasmade

becauseofthelimitedandinconsistent

resultsoftheresearchdonetodate.


Thereissuggestiveevidencethatrisperidoneaftercardiacsurgeryreducestheriskof

PODinpatientswithoutcontraindicationstoitsuse,butfurtherresearchisneeded

beforeitcanberecommendedforroutineuse[B].

Arelativelysmall(126subjects)

randomizedtrialofa1mgsingledoseof

risperidonesublingualuponawakening

afterelectivecardiacsurgerywith

cardiopulmonarybypassshowedalower

incidenceofPOD(11.1%vs.31.7%,p=

0.009)(Prakanrattana&Prapaitrakool

2007).Limitationsofthisstudyincluded



poorblindingprocedures(thecompared

treatmentshadperceptibledifferences)

andtherelativelyyoungageofparticipants

(meanagewasapproximately61).Asmall

(101subjects)randomizedplacebo-

controlledtrialofrisperidone(0.5mg

every12hoursuntil24hoursafter

disappearanceofSSDoruntildelirium

developed)targetedtoolder(65+)

patientswithSSDafteron-pumpcardiac

surgeryshowedasignificantlylower

likelihoodofdevelopingPODwithactive

therapy(13.7%vs.34%,p=0.031)

(Hakim,Othman&Naoum2012).Both

studiespre-screenedparticipantsand

excludedthosewhodidn’tmeeteligibility

criteria.Neitherstudyreportedbeneficial

effectsondeliriumseverity,delirium

duration,lengthofICUstay,orlengthof

hospitalstaywithrisperidone.Larger

studiesoflongerdurationinmorediverse

populationsareneeded.


Thereissuggestiveevidencethatshort-term,lowdoseolanzapinereducestheriskof

POD,butifdeliriumoccursitmightbemoresevereandofalongerduration.Theuseof

olanzapineforthepreventionofPODcannotberecommendedatthistime[B].

Adouble-blind,placebo-controlled,single

site,randomizedtrialevaluatedtheutility

ofolanzapine(5mgorallyimmediately

beforeandaftersurgery)forthe

preventionofPODinolderpatients

undergoingelectivekneeorhip

replacementtherapy.TheincidenceofPOD

wassignificantlylowerifgivenolanzapine

(14.3%vs.40.2%,p<0.0001),andthe

time-to-onsetofdeliriumwasgreater(p<

0.0001).However,ifdeliriumoccurredit

wassignificantlymoresevere(p=0.02)

andlastedlonger(2.2daysvs.1.6days,p=

0.02).Therewerealsoslightlymore

postoperativecardiaccomplicationswith

activetherapy.Astudylimitationwasthat

patientswereonlyfollowedforfourdays

(Larsen,Kelly,Sternetal.2010).Further

researchisrequiredtoclarifytherelative

balanceofbenefitandharm.

Modified Recommendations: Prevention

Theuseofcholinesteraseinhibitorsforthepreventionortreatmentofdeliriumisnot

recommended[A].

Donepezil(5mgperdayfor14daysprior

toand14daysaftersurgery)inpatients

undergoingelectivejointreplacementsdid

nothaveasignificantimpactonthe

incidenceofPOD(20.5%inthosegiven

donepezilvs.17.1%assignedtoplacebo,p

=0.069)(Liptzin,Laki,Garbetal.2005).In

anothersmallstudyofdonepezilforthe



preventionofPODinpatientsundergoing

electivetotalhipreplacements,therewas

nosignificantreductionintheincidenceof

delirium(Sampsonetal.2007).Apilot

studyofdonepezil(5mgdailyinitiated

within24hoursofsurgery)inolderhip

fracturepatientsshowednobenefitand

significantlymoresideeffects

(Marcantonio,Palihnich,Appleton&Davis

2011).Itwasfelttheresultsdidnotjustify

anyfurtherworkonthepossibleutilityof

thisagentforPOD.ACochranereview

concludedtherewasnoevidencefrom

controlledtrialsthatdonepezilwasan

effectiveagentfordelirium(Overshott,

Karim&Burn2008).Inadouble-blind,

randomized,placebo-controlledtrial,

rivastigmine(threedosesof1.5mgoforal

rivastigmineperdaystartingtheevening

beforesurgeryandcontinuinguntilthe

eveningofthesixthpostoperativeday)was

examinedasameanstopreventdelirium

inolderpatientsundergoingelective

cardiacsurgery.Deliriumdevelopedin

30%ofthosetreatedwithrivastigmine

and32%ofpatientsgivenplacebo(p=

0.8).Therewasnotreatmenteffecton

Mini-MentalStateExaminationandclock

drawingresults(p=0.4andp=0.8

respectively),noranysignificantdifference

inthenumberofpatientswhoreceived

haloperidol(p=0.9)(Gamberinietal.

2009).Adouble-blind,placebo-controlled

randomizedtrialexaminedtheeffectof

rivastigmine(initialdoseof1.5mgtwice

dailythatwasincrementallyincreasedto6

mgtwicedailyfromday10onwards)on

thedurationofdeliriumincriticallyill

patients.Thestudywasterminatedearly

becauseofanearlysignificanthigher

mortalityinthetreatedgroup(22%vs.

8%,p=0.07).Aswell,themedianduration

ofdeliriumwasnon-significantlygreaterin

therivastigminegroup(5daysvs.3days,p

=0.06)(VanEijketal.2010).Nocontrolled

studyofgalantaminefordeliriumhasbeen

published.Asidefromthelackofany

evidentefficacy,cholinesteraseinhibitors

haveanumberofpotentialadverseeffects

thatwouldraiseconcernsabouttheiruse

inolderpatientsadmittedtohospitalwith

severemedicalandsurgicalconditions.For

example,theymayincreasetheeffectsof

succinylcholine(amusclerelaxantthatis

usedasananestheticdrug)andcanbe

associatedwithavarietyofcardiac

problems,suchasbradycardia,syncope

andpacemakerinsertion(Gilletal.2009).

Pleasenotethatabruptcessationofa

cholinesteraseinhibitorinpatientson

long-termtherapyfordementiacanbe

associatedwithanacuteworseningof

cognitiveabilitiesandisnotrecommended

ifthereisnoclinicalindicationtostopthe

agentquickly(Singh&Dudley2003;

Minettetal.2003;Bidzan&Bidzan2012).


11 | The Assessment and Treatment of Delirium

Modified Recommendations: Prevention

To decrease the risk of delirium in mechanically ventilated patients, dexmedetomidine

should be considered as a sedative alternative to benzodiazepines and propofol [A].

Dexmedetomidine (a pharmacologically

active dextroisomer of medetomidine, this

is a centrally acting selective α2-adrenergic

receptor agonist) can be used for sedating

mechanically ventilated patients. In a study

comparing dexmedetomidine to lorazepam

for sedation in medical and surgical ICU

patients, its use was associated with more

delirium-free and coma-free days (seven

versus three days, p = 0.01)

(Pandharipande etal.2007).Another

studycomparingdexmedetomidineto

midazolamfoundalowerincidenceof

deliriumwithdexmedetomidine(54%vs.

76%,p<0.001)(Rikeretal.2009).Ina

randomizedstudyofpostoperative

sedationofpatientsundergoingcardiac

valveprocedures,dexmedetomidinewas


incidenceofdeliriumthanpropofol(short-

acting,intravenouslyadministered

hypnoticagent)ormidazolam(10%vs.

44%vs.44%,p<0.001)(Maldonadoetal.

2009).Thereissuggestivebutnot

conclusiveevidencesupportingtheuseof

dexmedetomidineinweaningdelirious

patientsoffventilators(Readeetal.2009;

Yapicietal.2011;Shehabietal.2010).A

systematicreviewcontrasting

benzodiazepinewithnon-benzodiazepine-

basedsedationformechanicallyventilated

adultsconcludedthatfurtherresearchis

requiredontheissueoftheirrespective

impactsondeliriumrisk(Fraseretal.

2013).However,arecentmeta-analysisof

therandomizedcontrolledtrialsthat

compareddexmedetomidinewithother

sedatingagentsconcludedthatitsusewas

associatedwithasignificantreductionin

theincidenceofdelirium(Pasinetal.

2014).


Thereissuggestiveevidencethatregionalnerveblocksforpainmanagementinolder

patientswithahipfractureareassociatedwithalowerrateofdeliriumbutfurther

researchisrequiredtoconfirmthisfinding[B].

Deliriumisacommoncomplicationofhip

fracturesinolderpatients(Chaudhry,

Devereaux&Bhandari2013).Theuseof

regionalnerveblocks(i.e.,fasciailiaca,3-

in-1[femoral,obturator,sciaticnerves],or

continuousepiduralblock)tomanagepain

wasassociatedwithalowerriskof

deliriuminfoursmallrandomized

controlledtrials(Foss,Kristensen,

Kristensen,Jensen&Kehlet2005;Graham,



Baird&McGuffie2008;Mouzopoulosetal.

2009;GodoyMonzon,Vazquez,Jauregui&

Iserson2010).Inthelargestofthese

studies(Mouzopoulosetal.2009),when

deliriumdidoccur,itwaslesssevereand

didn’tlastaslong.Basedonthesereports,

aswellastwocohortstudies,asystematic

reviewconcludedtherewasmoderate

evidencethatregionalnerveblocks

preventeddeliriuminthispatient

population(Abou-Settaetal.2011).

Improvedpaincontroland/orreduced

opioidrequirementswerefelttoexplain

theseresults.Thesepositiveresultshaveto

beinterpretedwithcaution.Inadditionto

thelimitednumberandsmallsizesofthe

studies,anumberofthemexcluded

patientswithsignificantpreoperative

cognitiveimpairment,didn’tprovide

informationonhowdeliriumwas

diagnosed(Rashiqetal.2013),andinthe

Mouzopoulosetal.study(2009),onlythe

participantswereblinded(Inouye,

Westendorp&Saczynski2014).Australian

guidelinesforthemanagementofhip

fracturesinolderpersonsconcludedthat

theuseofregionalanesthesiamight

reducethelikelihoodofpostoperative

confusion(Mak,Cameron&March2010).

TheQuality-BasedProceduresClinical

HandbookforHipFractureforOntario

recommendedthatregionalnerveblocks

beconsideredforpaincontrolespecially

forpatientsathighriskfordelirium

(HealthQualityOntario2013).However,in

theonlystudythatreportedontheissueof

patientrisklevel(Mouzopoulosetal.

2009),deliriumpreventionwasrestricted

tothoseatanintermediateriskforthis

outcome(i.e.,therewasnoevidentbenefit

forthosedeemedathighrisk).Itis

generallybelievedthatregionalnerve

blocksareunderutilizedinCanada

(Haslam,Lansdown,Lee&vanderVyver

2013).Whilethebeneficialeffectonpain

controlwouldbeanotherreasonto

advocatefortheirgreateruse,wefeel

furtherstudiesarerequiredbeforewe

coulddefinitelystatethatregionalnerve

blocksareeffectiveinpreventingdelirium.


Thereisinsufficientevidencetosupporttheroutineuseofanyotherformof

pharmacologicalinterventionforthepreventionofdelirium[B].

Thereisnoconsistenthighquality

evidenceshowingefficacy,tolerability

and/orsafetythatwouldsupportthe

routineuseofotherformsof

pharmacotherapyforthepreventionof

delirium(Diazetal.2001;Aizawaetal.

2002;Leung,Sanda,Vaurio&Wang2006;

Leung,Sands,Ricoetal.2006;Pesonenet

al.2011;Katoetal.2011;Sauer,Slooter,

Veldhuijzen,vanEijk&vanDijk2013;

Robinsonetal.2014).



Part 4.4 Pharmacological Management Discussion and Modified Recommendation Onreviewoftherecentliteratureandthe2006recommendations,werecommend

replacingthethree2006recommendationsbelowwiththemodifiedrecommendation

summarizedbelow.

2006Recommendation:4.4.2Antipsychotics(page41-44)

Highpotencyantipsychoticmedicationsarepreferredoverlowpotencyantipsychotics

[B].

Haloperidolissuggestedastheantipsychoticofchoicebasedonthebestavailable

evidencetodate[B].

Atypicalantipsychoticsmaybeconsideredasalternativeagentsastheyhavelower

ratesofextra-pyramidalsigns[B].

ModifiedRecommendations:Antipsychotics

Inolderpersonswithadeliriumwherepharmacotherapyisindicated,lowdose,short-

termtherapywithhaloperidoloranatypicalantipsychotic(e.g.,olanzapine,quetiapine,

risperidone)canbeconsidered.Haloperidolisnotrecommendedifthereispre-existing

ParkinsondiseaseorLewybodydementia[B].

Thestrengthoftherecommendationwas

assigneda[B]gradebecauseofthemajor

methodologicallimitationswiththe

availablestudies(Seitz,Gill&vanZyl2007;

Flaherty,Gonzales&Dong2011)andthe

increasingconcernsabouttherisksof

antipsychotics.Thereisonlylimited

supportforlowdose,short-term(usually

foroneweekorless)antipsychotictherapy

fordeliriuminrestrictedsituations(i.e.,

whenthereisevidenceofsignificant

distressand/ortopreventtheolder

deliriouspatientfromendangering

themselvesorothersANDnon-

pharmacologicalapproachesareeither

inappropriateorineffective).

Notwithstanding,antipsychoticsare

perceivedasbeneficialbymanyhealthcare

practitionersandarefrequentlyusedfor

thetreatmentofdelirium(Devlin,Bhat,

Roberts&Skrobik2011).Anindicationfor

haloperidol(firstgeneration,highpotency,

typicalantipsychotic)forthemanagement

ofdeliriumisnotedinthe2014editionof

theCompendiumofPharmaceuticalsand

Specialties(CPS)(CanadianPharmacists

Association2014).Thisisnotalisted

indicationforanyoftheatypical(i.e.,

secondgeneration)antipsychotics,and

theirusefordeliriumwouldhavetobe

viewedasoff-label.Systematicreviews

haveconcludedthathaloperidoland

atypicalantipsychoticshavesimilar

efficacyintreatingthesymptomsof



delirium(Lonergan,Britton,Luxenberget

al.2007;Lacasse,Perreault&Williamson

2006;Seitz,Gill&vanZyl2007;Ozbolt,

Paniagua&Kaiser2008;Campbelletal.

2009).Asmallsingle-blind,randomized

trialcomparingtheefficacyofolanzapine,

risperidone,andhaloperidolreported

similarefficacyandtolerability(Grover,

Kumar&Chakrabarti2011).Anothersmall

studyshowedsimilaroverallefficacyfor

olanzapineandrisperidone,butan

exploratoryanalysisthatwillrequire

confirmationsuggestedtheresponseto

risperidonewaspoorerintheolderage

group(Kimetal.2010).Addingtothebody

ofresearchsupportingtheuseofatypical

antipsychotics,tworecentsmall

randomizedcontrolledtrialsshowedfaster

timetodeliriumresolutionwith

quetiapinecomparedwithplacebo(Devlin

etal.2010;Tahiretal.2010).Maneetonet

al.(2013)reportedthatquetiapineand

haloperidolwereequallyeffectiveandsafe

inthetreatmentofdelirium.Yoonetal.

(2013)inanon-randomizedbutassessor-

blindedstudyfoundhaloperidol,

risperidone,olanzapine,andquetiapineto

beequallyefficaciousandsafeinthe

treatmentofdelirium,thoughresponse

rateswerelower(especiallyfor

olanzapine)inpatients75orolder.Atlow

dosesthetolerabilityofhaloperidolis

comparabletoatypicalantipsychotics,but

athigherdosagesextrapyramidalside

effectsbecomemorecommon(Lonergan,

Britton,Luxenbergetal.2007;Campbellet

al.2009).Advantagesforlowdose

haloperidolcomparedtotheatypical

antipsychoticsincludeoralandparenteral

preparations,minimalanticholinergic

effects,andinfrequentdevelopmentof

orthostatichypotension.Haloperidolisnot

recommendedifthereispre-existing

ParkinsondiseaseorLewybodydementia.

Warningshavebeenissuedforatypical

antipsychoticssuchasolanzapine,

quetiapineandrisperidone,statingthat

olderpatientswithdementiatreatedwith

theseagentsareatanincreasedriskof

deathcomparedtoplacebo.Thougha

warningwasnotissued,anincreasein

mortalityhasalsobeenobservedwith

typicalantipsychoticssuchashaloperidol

whenusedtotreatolderpatientswith

dementia(Gilletal.2007).Thereislittle

dataontheimpactofshort-term

antipsychoticuseonmortalityinolder

hospitalizedpatientswithadelirium.Inan

underpoweredstudy,theirusewasnot

associatedwithastatisticallysignificant

increasedmortalityrate(oddsratio1.53,

95%confidenceinterval0.83-2.80)(Elieet

al.2009).Aprospectiveobservational

studyof2,453deliriousolder(meanage

73.5years)in-patientswhoreceived

antipsychoticsreportedthat,intheopinion

oftheinvolvedpsychiatrist,noneofthe

386deathsthatoccurredwasdueto

antipsychoticsideeffects(Hattaetal.

2014).Controlledtrialsusingmore

rigorousmethodologyareneededtoclarify

thisparticularissue.Themajor

modificationtothe2006recommendation

istonowviewhaloperidolandtheatypical

antipsychoticsasequivalentoptionsin

mostpatients.



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Documents

Update The Assessment and Treatment of Delirium€¦ · 3 The Assessment and Treatment of Delirium Summary of Modified Recommendations All modified or added recommendations are presented