Risk factors for acute delirium in critically ill adult patients

12 Pages·2017·0.77 MB·English

by  Caroline Fixter

Risk factors for acute delirium in critically ill adult patients:
a systematic review
MATTAR, Ihsan, CHAN, Moon Fai and CHILDS, Charmaine
<http://orcid.org/0000-0002-1558-5633>
Available from Sheffield Hallam University Research Archive (SHURA) at:
http://shura.shu.ac.uk/7247/
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publisher's version if you wish to cite from it.
Published version
MATTAR, Ihsan, CHAN, Moon Fai and CHILDS, Charmaine (2013). Risk factors for
acute delirium in critically ill adult patients: a systematic review. ISRN Critical Care,
2013.
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See http://shura.shu.ac.uk/information.html
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ISRNCriticalCare
Volume2013,ArticleID910125,10pages
http://dx.doi.org/10.5402/2013/910125
Review Article
Risk Factors for Acute Delirium in Critically Ill Adult Patients:
A Systematic Review
IhsanMattar,MoonFaiChan,andCharmaineChilds
AliceLeeCentreforNursingStudies,YongLooLinSchoolofMedicine,NationalUniversityofSingapore,Level2,
ClinicalResearchCentre,BlockMD11,10MedicalDrive,Singapore117597
CorrespondenceshouldbeaddressedtoIhsanMattar;[email protected]
Received14January2013;Accepted26February2013
AcademicEditors:F.Cavaliere,J.A.Llompart-Pou,andJ.F.Stover
Copyright©2013IhsanMattaretal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Background.Deliriumischaracterizedbydisturbancesofconsciousness,attention,cognition,andperception.Deliriumisaserious
butreversibleconditionassociatedwithpoorclinicaloutcomes.Thishasimplicationsforthecriticallyillpatient;theeffectsof
deliriumcauselongtermsequelae,principallycognitivedeficits,andfunctionaldecline.Objectives.Theobjectiveofthepaper
wastodescriberiskfactorsassociatedwithdeliriumincriticallyilladultpatients.Methods.Publishedandunpublishedliterature
from1990to2012,limitedtoEnglish,wassearchedusingtendatabases.Results.Twenty-twostudieswereincludedinthispaper.
Alargenumberofriskfactorswerepresentedintheliterature;someofthesewerecommonacrossallsettingswhilstotherswere
exclusivetothetypeofsetting.Benzodiazepinesandopioidswereshowntoberiskfactorsfordeliriumindependentofsetting.
Conclusion.Withregardtopatientsadmittedtomedicalandsurgicalintensivecareunits,riskfactorsofolderageandcomorbidity
were common. In the cardiac ICU, older age and lower Mini-Mental Status Examination scores were cited most often as risk
factorsfordelirium,butotherriskfactorsexclusivetothesettingwerealsosignificant.Benzodiazepineswereidentifiedasthe
mostsignificantpharmacologicalriskfactorfordelirium.
1.Introduction deliriumsoftengounrecognizeddespitebeingmorecommon
thanhyperactivedelirium[3,8],resultinginundertreatment
Deliriumisasyndromecharacterizedbydisturbancesofcon- andpooreroutcomes[8,9].Suchfactorspresentachallenge
sciousness,attention,cognition,andperception[1].Delirium to clinicians to identify factors and possibly to prevent
has multiple aetiologies, but the predisposing risk factors deliriumincriticallyillpatients.
most frequently cited are older age, cognitive impairment,
severityofillness,andiatrogeniccauses[2,3].Deliriumhas
2.Methods
an acute onset. Symptoms fluctuate over a 24-hour period
[4, 5]. Althoughitspresentationistypically associated with This systematic paper is an abridged version of a full
symptoms of hyperactive delirium (restlessness, agitation) online publication available at the Joanna Briggs Institute
[4], two other subtypes exist, “hypoactive” and “mixed” [1]. LibraryofSystematicReviews(http://connect.jbiconnectplus
Hypoactive delirium is characterized by lethargy, reduced .org/JBIReviewsLibrary.aspx)[31].
activity, and apathy [5], whereas mixed delirium features
characteristicsofbothhyperactiveandhypoactivedeliriums. 2.1. Inclusion and Exclusion Criteria. This paper consid-
Although associated with poor clinical outcomes, delirium eredstudiesincludingrandomisedcontrolledtrials,nonran-
is typically reversible [6, 7]. This has implications for man- domised controlled trials, and before and after studies. In
agement of the critically ill patient; not only is the patient’s their absence, cohort and case control studies were consid-
lifethreatenedbytheprimaryillness,butalsotheeffectsof eredforinclusion.Participantswereadults(aged21yearsand
deliriummaycauselongtermsequelae,principallycognitive above) presenting with delirium (hyperactive, hypoactive,
deficits, and functional decline [8]. Hypoactive and mixed andmixed)intheintensivecareunit(ICU).Synonymssuch
2 ISRNCriticalCare
Table1:Keywordcategories. tools:theDiagnosticStatisticalManual-IV(DSM-IV),Con-
fusionAssessmentMethod(CAM),IntensiveCareDelirium
Keywords
Screening Checklist (ICDSC), Nursing Delirium Screening
(i)Electrolyteimbalance Scale (Nu-DESC), and Delirium Rating Scale (DRS). Only
(ii)Fever one of the studies used randomized sampling [25], whilst
theremainderpredominantlyusedlargecohort(rangefrom
(iii)Urinarytractinfection
20 to 1367 patients) convenience sampling. Due to the
(iv)Sepsis
heterogeneous nature of the included studies, findings are
(v)Pneumonia
presentedinanarrativereview.
(vi)Anaesthetic
∗
Concept1:factors (vii)Postoperativecomplication
2.4.AssessmentofMethodologicalQuality. Studieswereiden-
(viii)Hypoxia tified for relevance via title, abstract, and keywords. Two
(ix)Anoxia independentreviewersassessedcontentrelevance.Fulltexts
(x)Dementia of eligible studies were retrieved and reviewed using the
(xi)Age appropriate critical appraisal instruments from the Joanna
∗ BriggsInstitute(JBI)[31].
(xii)Older
(xiii)Headinjury
3.Results
(xiv)Subduralhematoma
(i)Delirium
3.1. Patients Admitted to the Medical Intensive Care Unit.
∗
(ii)Confusion Peterson et al. [25] examined delirium and its motoric
∗
(iii)Agitation subtypesinamedicalICU(MICU).Dataondemographics
(iv)Attention∗ (age,gender,andrace),AcutePhysiologyandChronicHealth
∗ Evaluation-II(APACHE-II)scores,andintubationorextuba-
(v)Disorientation
Concept2:acutedelirium tionwerecollectedfrom614randomisedparticipants.Delir-
(vi)Stupor
ium assessments were extensive and rigorous, generating
(vii)Hallucination
7,323CAM-ICUand21,931RASSassessments.Resultsshow
(viii)Incoherence∗ thatpatientsaged65yearsandolder(𝑛 = 156)experienced
(ix)ICUpsychosis hypoactive delirium more frequently (71.8% versus 57.4%)
(x)Acuteconfusionalstate thanyoungerpatients(𝑛 = 458),andolderagewasstrongly
associated with hypoactive delirium. Mixed type (hyper-,
(xi)ICUSyndrome
hypoactive)deliriumwasthemostcommon(54.9%)amongst
Concept3:criticallyill (i)Criticalcare
othersubtypes.
patients (ii)Intensivecareunit
Incontrast,Linetal.[20]examinedriskfactorsforearly-
onset delirium in mechanically ventilated MICU patients.
However,“earlyonset”wasnotdefinedinthestudy,andno
asICUpsychosisandICUsyndromewereincluded.Critically time measures were recorded. Data was obtained from the
ill patients not in the ICU (e.g., those in the general ward) medicalrecordsof143patients(includingAPACHE-IIscores,
wereexcluded. patient’s medical history, and alcohol use). Data collection
was rigorous; the questionnaires used were previously pilot
2.2.SearchStrategy. Athree-stepsearchstrategywasutilised. tested,andresearchprocedureswerestandardisedtoensure
An initial search was undertaken using the search terms reliability.Astepwiselogisticregressionrevealedhypoalbu-
“factors,” “delirium,” and “critical care.” A comprehensive minemiaandpresenceofsepsisonadmissionassignificant
searchstrategywasthendevelopedusingidentifiedkeywords factorsinthedevelopmentofearlyonsetdelirium.
and MeSH headings (Table1). Finally, the reference lists of
all identified studies were examined for additional studies 3.2. Patients Admitted to the Surgical Intensive Care Unit.
relevanttothereview.Publishedandunpublishedliterature Robinson et al. [27] recruited 144 patients who were listed
from 1990 to 2012, limited to the English language, was for surgery and required postoperative ICU admission. A
searchedusingtendatabases. pilot study was conducted to assess interrater reliability
using the CAM-ICU. A high interrater reliability (kappa
2.3.SearchResults. Twenty-twostudieswereincludedinthe statistic > 0.96) ensured internal validity of the results. It
paper(Figure1;Table2).Thestudieswereconductedinmed- was shown that preoperative variables such as older age,
ical,surgical,andcardiacintensivecareunits.Twentystudies hypoalbuminemia, impaired functional status, preexisting
wereprospectiveandtworetrospectivecohortstudies. dementia, and preexisting comorbidities were significantly
Fifteen studies used the Confusion Assessment Method associated with delirium [27]. This supports the finding of
fortheIntensiveCareUnit(CAM-ICU),withtheRichmond Peterson et al. [25] who showed that preexisting dementia
Agitation Sedation Scale (RASS) for the diagnosis of delir- was the most significant risk factor for the development of
ium.Theremainingstudiesusedotherdeliriumassessment postoperativedelirium.
ISRNCriticalCare 3
Databases searched
∙CINAHL Initial search identified 4275 studies on
∙Scopus basis of keywords
∙Medline 4095 titles were excluded
on the basis of title and
∙PsycINFO
abstract
∙The Cochrane
180 studies appeared consistent with the
Library
∙The Joanna inclusion criteria based on title and
abstract
Briggs Library
of Systematic
127 duplicates removed
Reviews
∙Web of Science 53 studies appeared consistent with the
∙JSTOR inclusion criteria based on title and
∙ProQuest abstract
∙Mednar 21 studies excluded
because not suitable after
the abstracts were checked
thoroughly
32 studies with full text were retrieved
and critically appraised
22 studies included in the 2 studies excluded after full text review
paper 8 studies excluded following critical
appraisal
Search results and selection
Figure1
ExaminingthecourseofdeliriuminolderSICUpatients, fordelirium.Afteradjustingforinjuryseverityscore,oxygen
Balas et al. [15] recruited 117 participants. It contrasts with saturation, blood transfusions, and blood pressure, it was
Robinson et al. [27] in that the Informant Questionnaire revealedthatthenumberofventilatordaysandEDpulserate
onCognitiveDeclineintheElderly(IQCODE)wasusedto weresignificantlyassociatedwithdelirium.
assessthepresenceofdementia.TheIQCODEisavalidated
toolinwhichdementiaisassessedbyobtaininginformation 3.3. Patients Admitted to the Cardiac Intensive Care Unit.
fromasurrogate.Itwasfoundthatolderadultsadmittedto Afonsoetal.[10]createdapredictivemodelforpostoperative
theSICUwereathighriskofdevelopingdelirium.18.4%of delirium in 112 cardiac surgical patients. Surgery included
the participants had dementia on admission, 28.3% of the coronary artery bypass graft (CABG), valve replacement,
participants developed delirium in the SICU, and 22.7% of and aortic surgery. The incidence of delirium was 34%.
theparticipantsdevelopeddeliriuminthepost-SICUperiod. Increased age and increased duration of surgery were the
The study used descriptive statistics only. Furthermore, the mostsignificantriskfactorsforpostoperativedelirium.
effectsofdementiawerenotexplored. Detroyeretal.[16]alsoexaminedpostoperativedelirium
Anglesetal.[13]examinedriskfactorsfordeliriumafter in 104 patients focusing on anxiety and depression as risk
major trauma in patients admitted to the trauma intensive factors for postoperative delirium. Unlike Afonsoet al. [10]
care unit. Results from this group are reported because the thetypeofsurgicalprocedurewasnotrecorded.Prolonged
majorityoftraumapatientsrequireemergencysurgery.The intubation time and a low intraoperative lowest body tem-
study had a small number of participants (𝑛 = 59). It was peraturewerethemostsignificantpredictorsofdelirium.
shown that a GCS of 12 or less, higher blood transfusions, Similar to Afonso et al. [10], Bakker et al. examined
and higher multiple organ failure score were significantly predictorsofdeliriumaftercardiacsurgeryin201patients.A
associatedwithdelirium. Mini-MentalStatusExamination(MMSE)wasconductedto
Inastudyexaminingtheeffectofhypoxiaoncognition, assess“globalcognitivefunctioning”[14]intheparticipants
Guillamondegui et al. [18] recruited 97 ICU patients with before surgery, and medical records were evaluated. In the
multiple traumas without evidence of intracranial haemor- final logistic regression model, lower MMSE scores, higher
rhage.Datasuchasage,race,lengthofICUstay,andinjury creatininelevels,andlongerextracorporealcirculationtime
severityscorewasrecorded,andoxygensaturationwasmea- were independent predictors of delirium. Mortality during
sured.UsingtheCAM-ICU,57%ofpatientswere“positive” the first 30 days after surgery was significantly higher in
4 ISRNCriticalCare
Results𝑃<0.0001Increasedage(OR=2.5,C.I.=1.6–3.9,and,per10years)andincreaseddurationofsurgery(OR=1.3,CI=1.1–1.5,and𝑃=0.0002)werethemostsignificantriskfactorsforpostoperativedelirium.Benzodiazepineswerefoundtobeindependentriskfactorsforthe𝑃<0.001developmentofdelirium(OR=6.8,CI=3.1–15.0,and).𝑃<0.001𝑃=0.02Opiates()andmethadone()appearedtohaveprotectiveeffects,beingassociatedwithalowerriskofdelirium.Administeringadoseoffentanylabove1.4mgincreasedthepossibilityofdevelopingseveredelirium(OR=29.4,CI=4.1–210.3,𝑃<0.001and).Longeraorticclampingtimewasalsonotedasanindependentpredictorofseveredelirium(OR=8.0,CI=1.7–37.2,𝑃<0.001and).PostoperativedeliriumprolongedthelengthofstayintheICUby8.4days.12±1.015±0.1𝑃<0.01AGCSof12orless(versus,),increased2.8±0.70.5±0.3𝑃<0.01bloodtransfusions(versus,),andhigher1.2±0.20.1±0.1𝑃<0.01multipleorganfailurescores(versus,)weresignificantlyassociatedwithdelirium.SubjectswithdeliriumhadlongerhospitalandICUstaysandweremorelikelytorequirepostdischargeinstitutionalization.63patientsdevelopeddeliriumaftercardiacsurgery.LowerMMSEscores(OR=2.32,CI=1.20–4.46),highercreatininelevels(OR=1.02,CI=1.00–1.03),andlongerextracorporealcirculationtime(OR=1.01,CI=1.01–1.02)wereindependentpredictorsofdelirium.OlderpatientsadmittedtotheSICUwereathighriskfordevelopingdeliriumduringhospitalization.Prolongedintubationtime(OR=1.10,CI=1.05–1.15)andalowintraoperativelowestbodytemperature(OR=0.86,CI=0.74–0.99)werethemostsignificantpredictorsofdelirium.Comorbidity,presenceofinfection,abloodureanitrogen/creatinineratioof18ormore,andagewerethemostsignificantvariables,withasensitivityof100%andaspecificityof90%.55of97ICUpatientswereCAM-ICUpositivefordelirium.Numberofventilatordays(OR=1.16,CI=1.05–1.29)andEDpulserate(OR=1.02,CI=1.00–1.04)weresignificantlyassociatedwithdelirium. Aunivariateanalysisshowedthatpostoperativedeliriumoccurredmorefrequentlyinpatientsundergoingvalvesurgerywithorwithout𝑃=0.01CABGasopposedtoCABGalone().
er. U U d d
ncludedinthepap Outcomemeasures ASSandCAM-ICscores CAM-ICUscores ASSandCAM-ICscores CAM-ICUscores AM-ICUscoresanMMSE CAM-ICUscores AM-ICUscoresanDI DSMIIIandCAMscores CAM-ICUscores ICDSCscores
i R R C C
s
e
di
u
Table2:St Intervention/control Patientsw/outdelirium Patientsw/outdelirium Nil Patientsw/outdelirium Patientsw/outdelirium Patientsw/outdelirium Patientsw/outdelirium Patientsw/outdelirium Patientsw/outdelirium Nonsurgicalcontrolsandpatientsundergoingcoronaryarterybypassgraft(CABG)alone
r
Population 112adultpostoperativecardiacsurgicalpatients 82adultventilatedburnpatients 90patientswithpostoperativedeliriumaftecardiacsurgeryoncardiopulmonarybypass 59patientsadmittedtothetraumaintensivecareunit 201patientswhowentforcardiacsurgeryaged70yearsandolder 117SICUpatients 104patientsadmittedforelectivecardiacsurgery 20elderlypatientsinacriticalcaresetting 97patientswithmultipleinjuries,requiringICUmanagement 44patientsundergoingelectivecardiacsurgeryaged55yearsormore
Author(s) Afonsoetal.,2010[10] Agarwaletal.,2010[11] AndrejaitieneandSirvinskas,2011[12] Anglesetal.,2008[13] Bakkeretal.,2012[14] Balasetal.,2007[15] Detroyeretal.,2008[16] Edenetal.,1998[17] Guillamondeguietal.,2011[18] Hudetzetal.,2011[19]
ISRNCriticalCare 5
ResultsHypoalbuminemia(OR=5.94,CI=1.23–28.77)andpresenceofsepsisonadmission(OR=3.65,CI=1.03–12.9)aresignificantfactorsinthedevelopmentofearlyonsetdelirium.Eightfactorswereindependentpredictorsofdelirium,whichwereagemorethan65years(OR=3.82,CI=1.44–10.12),peripheralvasculardisease(OR=2.80,CI=1.11–7.04),aEuroSCORE(EuropeanSystemforCardiacOperativeRiskEvaluation)moreorequalto5(OR=2.46,CI=1.16–2.51),preoperativeintra-arterialbloodpressuresupport(OR=8.51,CI=1.81–40.03),bloodproductusage(OR=4.59,CI=2.10–10.06),andpostoperativelowcardiacoutputsyndrome(OR=8.04,CI=1.1–60.6).Ahistoryofhypertension(OR=1.88,CI=1.3–2.6),alcoholuse(OR=2.03,CI=1.2–3.2),higherAPACHEIIscore(OR=1.25,CI=1.03–1.07),andadministrationofsedativeandanalgesicdrugswereassociatedwithdelirium(OR=3.2,CI=1.5–6.8).Lorazepamwasanindependentriskfactor(OR=1.2,CI=1.1–1.4)for𝑃=0.09dailytransitiontodelirium.Midazolam(),fentanyl𝑃=0.09𝑃=0.24𝑃=0.18(),morphine(),andpropofol()werenotsignificant,althoughtheywere“associatedwithtrendstowardssignificance.”𝑃=0.002Midazolam(OR=2.75,CI=1.43–5.26,)wasastrongriskfactorfortransitiontodelirium.Opiateexposurewasinconclusiveinthatopiatessuchasfentanylwereariskfactorfordeliriuminthe𝑃=0.007𝑃=0.936SICU(),butnotintheTICU().Opiatessuchas𝑃=0.024morphinewerelinkedtoalowerrisktodelirium().Patients65yearsandaboveexperiencedhypoactivedeliriummore𝑃<0.001frequentlythanyoungerpatients(41.0%versus21.6%,),andolderagewasstronglyassociatedwithhypoactivedelirium(OR=3.0,CI=1.7–5.3).Mixedtype(hyper-,hypoactive)deliriumwasthemostcommon(54.9%)amongstothersubtypes.Deliriumwasfoundin29.2%ofthepatients,ofwhich13.7%developeddeliriumintheICU.Heavyalcoholuse(OR=6.1,CI=1.8–19.6),polypharmacy(7ormoredrugs)(OR=1.9,CI=1.1–3.2),andtheuseofbladdercatheterarepredictorsofdelirium(OR=2.7,CI=1.4–4.9).Severalpreoperativevariablesweresignificantlyassociated:olderage𝑃<0.001𝑃<0.001(),hypoalbuminemia(),impairedfunctional𝑃<0.001𝑃<0.001status(),preexistingdementia(),andpreexisting𝑃<0.001comorbidities().
U U U U
2:Continued. Outcomemeasures CAM-ICUscores DSMIVcriteria ICDSCandRASSscores RASSandCAM-ICscores RASSandCAM-ICscores RASSandCAM-ICscores CAMandMMSEscores RASSandCAM-ICscores
e
l
b
a
T Intervention/control atientsw/outdelirium atientsw/outdelirium atientsw/outdelirium atientsw/outdelirium atientsw/outdelirium oungerMICUpatientsagedlowerthan65 atientsw/outdelirium atientsw/outdelirium
P P P P P Y P P
Population 143mechanicallyventilatedpatients 1367adultpatientsundergoingCABG 820ICUpatients 198mechanicallyventilatedpatients 100surgicalandtraumaICUpatientsrequiringmechanicalventilationfor>24hours 156medicalintensivecareunit(MICU)patients 401subintensivecareunitpatients60yearsandabove 144patientsolderthan50yearsadmittedtopostoperativeintensivecareunit
Author(s) Linetal.,2008[20] Norkieneetal.,2007[21] Ouimetetal.,2007[22] Pandharipandeetal.,2006[23] Pandharipandeetal.,2008[24] Petersonetal.,2006[25] Ranhoffetal.,2006[26] Robinsonetal.,2009[27]
6 ISRNCriticalCare
Results𝑃=0.005Olderage(OR=4.30,CI=1.54–12.04,and),lowerMMSE𝑃=0.018scores(OR=6.50,CI=1.75–24.13,and),neuropsychiatric𝑃=0.001disease(OR=6.22,CI=2.02–19.16,and),andlowerpreoperativecerebraloxygensaturationscores(OR=3.27,CI=𝑃=0.0271.14–9.37,and)wereindependentpredictorsforpostoperativedelirium.Predictivefactorsofdeliriumwereincreasingage(OR=2.646,CI=1.431–4.890),historyofpreviousstroke(OR=4.499,CI=1.228–16.481),highAPACHEIIscoreonSICUadmission(OR=1.391,CI=1.201–1.621),andhighserumcortisollevel(OR=3.381,CI=1.690–6.765)onthefirstpostoperativeday. Theprevalenceofdeliriumrangedfrom37.7%to44.3%.Foreveryadditionalmilligramofmidazolamadministered,patientswere7-8%𝑃=0.06morelikelytodevelopdelirium(CI:1.00–1.14,). 𝐵=0.10Independentpredictorsofdeliriumwereadvancedage(,𝑃=0.02𝐵=1.37),higherlevelofserumpotassiumatadmission(,𝑃=0.04𝐵=4.85𝑃<0.001),andexperienceofcardiacarrest(,)duringMI.
2:Continued. Outcomemeasures RASS,CAM-ICUandMMSEscores NursingDeliriumScreeningScale RASSandCAM-ICUscores DSMIVcriteriaandDRS
e
l
b
a
T
m m m m
ol u u u u
ontr eliri eliri eliri eliri
c d d d d
n/ ut ut ut ut
o o o o o
nti w/ w/ w/ w/
Interve Patients Patients Patients Patients nit.
U
e
ar
C
Author(s)Population 231patientsscheduledforSchoenetal.,2011[28]elective/urgentcardiacsurgery 164surgicalintensivecareShietal.,2010[29]unitpatientsafternoncardiacsurgery 122participantsrequiringTaipaleetal.,2012nonemergencysurgeryfor[30]coronaryarteryorvalvularheartdisease 212coronaryintensivecareUguzetal.,2010[1]unitpatients CAM-ICU:ConfusionAssessmentMethodfortheIntensiveDI:deliriumindex.DSM:DiagnosticStatisticalManual.DRS:DeliriumRatingScale.ICDSC:IntensiveCareDeliriumScreeningChecklist.MMSE:Mini-MentalStatusExamination.RASS:TheRichmondAgitationSedationScale.
ISRNCriticalCare 7
deliriouspatients(14%versus0%)ascomparedtonondeliri- Theassociationbetweennurse-administeredmidazolam
ous patients, and adverse events after surgery were more andincidentdeliriumwasexaminedbyTaipaleetal.[30]ina
frequent. prospectiveobservationalstudy.122participantsundergoing
InaretrospectivestudybyAndrejaitieneandSirvinskas cardiac surgery were recruited. In this ICU setting, there
[12] examining risk factors for early postcardiac surgery werenoformalsedationprotocolsotherthanthephysician’s
delirium,participants(𝑛 = 90)werestudiedastwodistinct standingordersandsedativeswhichwereadministeredpro
groups: light-to-moderate delirium and severe delirium. re nata (PRN) by nurses. This study was notable in the
However,thecriteriadeterminingseverityofdeliriumwere creation of study variables when the diagnosis of delirium
notdescribed.Theterm“early”wasnotdefined.Inaddition, didnotmatchthoseofthephysicians’(overallagreement=
thereisnocomparatorgroup,castingambiguityonthe“true” 71.3%);thishadnotbeendonepreviously.Therewasalsoa
incidence of delirium (4.17%). As such, the assertion that detailedaccountingofrecruitment,andmeasuresweretaken
deliriumcausedprolongedhospitalstaycannotbejustified. to enhance reliability of CAM-ICU assessments between
It was shown that administering a dose of fentanyl above researchers. Results showed that, for every additional mil-
1.4mgincreasedthepossibilityofdevelopingseveredelirium. ligramofmidazolamadministered,patientswere7-8%more
Longer aortic clamping time was also noted as an inde- likelytodevelopdelirium.
pendentpredictorofseveredelirium.Newatrialfibrillation
(AF)episodesalsooccurredmorefrequentlyinpatientswith 3.5. Evaluation by Other Instruments. In the medical ICU,
severedeliriumthanthosewithlight-to-moderatedelirium. three studies were reviewed. Eden et al. [17] applied four
The study by Schoen et al. [28] aimed to examine previously studied predictive models designed to predict
preoperative and intraoperative cerebral oxygen saturation susceptibleICUpatients.ThisstudyusedtheCAMandDSM
and its association with postoperative delirium in patients criteria for delirium diagnosis. Unlike other studies, this
undergoingon-pumpcardiacsurgery.231participantswere studyhasasmallsamplesize;ithasanelderlysampleoften
recruited. Cerebral oxygen saturation was assessed using deliriousandtencontrolpatientsonly.Fourteenindependent
cerebral oximetry, detecting “imbalances in the cerebral variables were operationalised and incorporated into data
oxygensupply/demandratio”[28].Olderage,lowerMMSE collection tools. A composite of these predictive models
scores,neuropsychiatricdisease,andlowerpreoperativecere- was synthesized and showed that co-morbidity, presence of
bral oxygen saturation scores were independent predictors infection, a blood urea nitrogen/creatinine ratio of 18 or
forpostoperativedelirium.However,thepatient’ssedatives, more, and age were the most significant variables, with a
which may have a profound effect on the development of sensitivity of 100% and a specificity of 90%. Ranhoff et al.
delirium,werenotrecorded. [26]conductedtheirstudyinasubintensivecareunitforthe
elderly,recruiting401patients.Theresearchersalsousedthe
3.4. Pharmacological Factors. Pandharipande et al. [23] CAMtodiagnosedelirium.Deliriumwasfoundin29.2%of
examinedsedativesandanalgesicsasriskfactorsfor“patients’ thepatients,ofwhich13.7%developeddeliriumintheICU.
transition to delirium.” One hundred and ninety-eight Heavyalcoholuse,polypharmacy(7ormoredrugs),andthe
mechanically ventilated patients admitted to medical or useofbladdercatheterwerepredictorsofdelirium.Ouimet
coronary ICUs were recruited. Using a Markov regression etal.[22]examineddeliriumin820ICUpatientsusingthe
model, it was found that lorazepam was an independent ICDSC.Ahistoryofhypertension,alcoholuse(similartothe
risk factor for daily transition to delirium. Other sedatives previous study by Ranhoff et al. [26]), higher APACHE II
andanalgesics,suchasmidazolam,fentanyl,morphine,and score,andadministrationofsedativeandanalgesicdrugswas
propofol,werenotsignificant,althoughtheywere“associated associatedwithdelirium.
withtrendstowardssignificance”[23]. In the surgical ICU, one study was reviewed. Shi et al.
In a follow-up study, Pandharipande et al. [24] inves- [29]conductedastudyinaChineseICUexaminingboththe
tigated the effects of sedatives and analgesics in patients incidence and risk factors of delirium in 164 patients after
admitted to the surgical ICU (SICU) and trauma ICU noncardiac surgery. The researchers used the Nu-DESC, a
(TICU).Onehundredmechanicallyventilatedpatientswere deliriumscreeningtoolvalidatedintheChinesepopulation.
recruited. Midazolam was found to be a strong risk factor The results showed the predictive factors of delirium to be
for transition to delirium. However, opiate exposure was increasingage, history of previous stroke, high APACHE II
inconclusiveinthatopiatessuchasfentanylwereariskfactor score on SICU admission, and high serum cortisol level on
for delirium in the SICU, but not in the TICU. In addition, thefirstpostoperativeday.
opiates such as morphine were linked to a lower risk to InthecardiacICU,threestudieswerereviewed.Hudetz
delirium. et al. [19] examined the incidence of delirium in patients
Agarwal et al. [11] recruited eighty-two adult ventilated undergoing valve surgery with or without CABG as com-
patients in burns ICU. Benzodiazepines were found to be paredtopatientsundergoingCABGalone.Forty-four“edu-
independent risk factors for the development of delirium. cation balanced” patients were recruited from the ICU of
Resultssuggestthatbenzodiazepineswereastrongriskfactor one veteran affairs medical centre. The ICDSC was used
forthetransitiontodelirium.Incomparisontothestudyby to diagnose delirium before surgery and five days after
Pandharipandeetal.[24],opiatesandmethadoneappeared surgery.Postoperativedeliriumoccurredmorefrequentlyin
tohaveprotectiveeffects,beingassociatedwithalowerrisk patientsundergoingvalvesurgerywithorwithoutCABGas
ofdelirium. opposed to CABG alone. Uguz et al. [1] conducted a study
8 ISRNCriticalCare
which measured the incidence of delirium as it relates to Withregardtopharmacologicalfactors,benzodiazepines
acute myocardial infarction (AMI) as opposed to surgical wereidentifiedasasignificantriskfactorforICUdelirium.
procedures. Two hundred and twelve patients who were Benzodiazepines increase the effect of the neurotransmitter
admitted to the coronary intensive care unit were recruited GABA,resultinginincreasedsedationandhypnosis[23].The
and assessed using DSM-IV criteria and the DRS. Inde- effect on GABA may cause an imbalance in the action and
pendent predictors of delirium were advanced age, higher quantityoftheotherneurotransmitters,causingsymptomsto
level of serum potassium at admission, and experience of manifestasdelirium.Inaddition,benzodiazepinesmaycause
cardiacarrestduringMI.TheretrospectivestudybyNorkiene behavioural disinhibition and aggression [24], symptoms
et al. [21] had a very large sample size (𝑛 = 1367). The similartohyperactivedelirium.
researchersstudiedtheprecipitatingfactorsfordeliriumafter In this paper, two retrospective cohort studies were
CABG and screened for delirium using the DSM criteria. includedinamajorityofprospectivestudies.Incomparison,
Eightfactorswereindependentpredictorsofdelirium,which prospective studies are preferred to retrospective studies as
were age more than 65 years, peripheral vascular disease, patients are available for accurate assessment and examina-
a EuroSCORE (European System for Cardiac Operative tion; in a retrospective review, it is not possible to confirm
Risk Evaluation) more or equal to 5, preoperative intra- thepatient’scondition.Aretrospectivereviewfurthercom-
arterial blood pressure support, blood product usage, and poundsaprobleminherentindelirium:diagnosis.Physician’s
postoperativelowcardiacoutputsyndrome. diagnoses may be subjective; as such, one physician may
viewapatientasdeliriouswhilstanothermightregarditas
4.Discussion preexisting dementia. The propensity for misinterpretation
andincorrectdiagnosismaybesignificantinclinicalsettings
From the studies reviewed, there are a variety of candidate which do not use standardised criterion such as the CAM-
factorsassociatedwithdeliriuminthesettingoftheintensive ICU to determine diagnosis. Though the methodology and
care unit. Some are common across all settings, whereas results of retrospective studies may be apocryphal, they are
others are exclusive to the type of setting. For example, includedinthispaperforthesakeofcompleteness.
the importance of valve surgery as a risk factor for delir-
ium [10] is of key importance in a cardiac ICU but lacks
4.1.ImplicationsforPracticeandResearch
importance in the medical ICU, where one is more likely
to see cases of sepsis, acute respiratory failure, and renal (i)Bycreatingapredictivemodelfordelirium,clinicians
disease. maybeabletoidentifypatientsatriskofdeveloping
InthemedicalICU,olderage,sepsis,co-morbidity,and delirium and implement preemptive measures. This
heavyalcoholusewerethemostcommonlycitedriskfactors. canbefurtherdevelopedintoanICU-specificmodel.
Older age is considered a highly significant risk factor for Forexample,apatientinthemedicalICUwillhave
deliriumduetoareducedsynthesisofcerebralneurotrans- adifferentsetofriskfactors,suchasthepresenceof
mitters[32].Fluctuationsintheneurotransmitterlevelslead sepsis,co-morbidity,andalcoholuse,fromapatient
to impairment in neurotransmission, resulting in increased in the cardiac ICU. A protocol based on this model
susceptibilitytodeliriuminolderpatients.Themechanismby willassistthenurseinmonitoringpatientsathigher
whichsepsiscausesdeliriumispoorlyunderstood;however risk for developing delirium, identifying modifiable
several theories have been postulated; these include brain risk factors to prevent or reduce the severity of
activation by inflammatory mediators, oxidative stress, and delirium.
blood-brain barrier breakdown [33]. It is possible that all
(ii)Clinicians should prescribe benzodiazepines judi-
thesetheoriesarevalid;themanifestationofdeliriumislikely
ciously, moderated by an understanding of the
multifactorial,precipitatedbycytokinepathwaysresultingin
patient’smentalstatusandpropensityfordeveloping
the derangement of neurological function. The presence of
delirium. Conversely, the precipitation of delirium
co-morbidity is not easily explained, although it might be
in a patient prescribed benzodiazepines must be
expectedthateffectsonincreasingphysiologicalburdenmay
considered in the context of the patient’s condition
playapart.Heavyalcoholuseisknowntobeassociatedwith
andnotattributedtopharmacologicalreasonsalone.
deliriumtremens,aformofdeliriumcausedbywithdrawal
ofalcohol[34].
(iii)Analternativetousingbenzodiazepinesassedatives
InthesurgicalICU,olderage,presenceofco-morbidity
may be haloperidol. van den Boogard et al. [35]
(including previous history of stroke and dementia), and
foundthathaloperidolprophylaxisresultedinlower
highAPACHE-IIscorearethemostcitedriskfactors.With
delirium incidence and more delirium free days as
a higher APACHE-II score, there is a greater physiological
comparedtothecontrolgroup.However,theresults
stresswithconcomitantincreaseinriskfordelirium.
still need to be verified via a reliable randomised
In the cardiac ICU, there were no factors which stood
controlledtrial.
outmoresignificantlythanothers(otherthanolderageand
lowerMMSEscores).Allotherfactorsarelikelytobeequally (iv)Randomised control trials should be conducted to
significant.Astudyexaminingallthesefactorsinacomposite investigatetheefficacyofotherpossiblesedativessuch
model is required to determine the most significant factors as dexmedetomidine or opioids in comparison to
causingdeliriumintheCICU. benzodiazepines.
ISRNCriticalCare 9
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4.2. Limitations. This paper was limited by the parameters
[11] V.Agarwal,P.J.O’Neill,B.A.Cottonetal.,“Prevalenceandrisk
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