11/30/2016 Emergencydepartmentmanagementofacuteexacerbationsofchronicobstructivepulmonarydiseaseandfactorsassociatedwithhospitalization

JResMedSci.2014Apr19(4):297303. PMCID:PMC4115343

Emergencydepartmentmanagementofacuteexacerbationsofchronic
obstructivepulmonarydiseaseandfactorsassociatedwith
hospitalization
BharatKhialani, 1PathmanathanSivakumaran, 1,2GerbenKeijzers, 2,3,4andKrishnaBajeeSriram1,2
1
DepartmentofRespiratoryMedicine,GoldCoastUniversityHospital,Australia
2
SchoolofMedicine,ParklandsDrive,GriffithUniversity,Queensland,Australia
3
DepartmentofEmergencyMedicine,GoldCoastUniversityHospital,1HospitalBoulevard,Southport,Queensland4215,Australia
4
SchoolofMedicine,BondUniversity,4UniversityDr,RobinaQueensland4226,Australia
Addressforcorrespondence:Dr.KrishnaBajeeSriram,DepartmentofRespiratoryMedicine,GoldCoastUniversityHospital,1Hospital
Boulevard,Southport,QLD4215,Australia.Email:bajeekrishna@gmail.com

Received2013Aug1Revised2014Jan17Accepted2014Jan29.

Copyright:JournalofResearchinMedicalSciences

ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract

Background:
Currentlythereisapaucityofinformationaboutbiomarkersthatcanpredicthospitalizationforacute
exacerbationsofchronicobstructivepulmonarydisease(AECOPD)patientspresentingtotheemergency
department(ED).ThereislimiteddataontheconsistencyofEDmanagementofAECOPDwithlocal
COPDguidelines.Theaimofthisstudywastoidentifybiomarkersassociatedwithhospitalizationin
AECOPDpatientsandtodetermineiftheEDmanagementwasconcordantwithlocalCOPDguidelines.

MaterialsandMethods:
WeperformedaretrospectiveauditofconsecutiveAECOPDpatientspresentingtotheGoldCoastHospital
EDovera6monthperiod.

Results:
Duringthestudyperiod,122AECOPDpatients(51%male,meanage(SE)71(11)years)presentedtothe
ED.Ninetyeight(80%)patientswerehospitalized.Univariateanalysisidentifiedcertainfactorsassociated
withhospitalization:Olderage,formersmokers,homeoxygentherapy,weekdaypresentation,SpO2<92%,
andraisedinflammatorymarkers(whitecellcount(WCC)andCreactiveprotein(CRP)).Afteradjustment
formultiplevariable,increasedagewassignificantlyassociatedwithhospitalization(oddsratio(OR)1.09
95%confidenceinterval(CI):1.001.18P=0.05).Radiologyassessmentandpharmacologicalmanagement
wasinaccordancewithCOPDguidelines.However,spirometrywasperformedin17%ofpatientsand28%
ofpatientswithhypercapneicrespiratoryfailurereceivednoninvasiveventilation(NIV).

Conclusion:
Weidentifiedseveralfactorsonunivariateanalysisthatwereassociatedwithhospitalization.Furtherresearch
isrequiredtodeterminetheutilityofthesebiomarkersinclinicalpractice.Also,whileoveralladherenceto
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localCOPDguidelineswasgood,thereisscopeforimprovementinperformingspirometryandprovisionof
NIVtoeligiblepatients.

Keywords:Emergencies,lungdisease,obstructive

INTRODUCTION
Chronicobstructivepulmonarydisease(COPD)isamajorcauseofmorbidityandmortalitybothin
Australia[1]andworldwide.[2]Itisestimatedthatabout2.1millionAustralianssufferfromCOPD.[1]The
clinicalcourseofCOPDisaggravatedbyexacerbations,characterizedbyincreasedcough,dyspnea,and
productionofpurulentsputum.[3]PatientswithanacuteexacerbationofCOPD(AECOPD)oftenpresentto
theemergencydepartment(ED)andmanysubsequentlyrequirehospitalizationforongoingmanagement.In
20082009,COPDrelatedhospitalizationaccountedfor56,201hospitaladmissionsforAustraliansaged55
yearsandover.[4]Inthiscontext,itisestimatedthatCOPDisthesecondleadingcauseofavoidablehospital
admissionsinAustralia.[5]

ClinicalguidelineshavebeendevelopedandwidelypromotedtoassistEDandhospitalandcommunity
cliniciansinprovidingevidencebasedmanagementforAECOPDpatients.Mostprominentamongthemare
theGlobalInitiativeforCOPD(GOLD),NationalInstituteforClinicalExcellence(NICE)clinicalguideline
onmanagementofCOPD,[6,7]andtheCOPDXPlan(specificallyforAustraliaandNewZealand).[8]The
COPDXplanprovidesrecommendationstoassistcliniciansinconfirmingtheexacerbationandcategorizing
severity(spirometry,bloodgasmeasurements,chestXray,andelectrocardiography)andoptimizing
treatment(bronchodilators,glucocorticoids,antibiotics,controlledoxygentherapy,andventilatory
assistance).[9]AdherencetoguidelinebasedmanagementofAECOPDisnotonlyexpectedtoachievegood
outcomesfortheimmediatetreatmentoftheexacerbation,butalsolongtermoutcomessuchaslung
function,morbidity,andmortality.[3]TodatetherehaveonlybeenafewEDvalidationstudiesoftheCOPD
managementguidelines.[10,11,12]TothebestofourknowledgetherehasbeenonlyoneAustralianstudy,
whichwasaretrospectiveauditperformedacrossfiveMelbourneEDs.[10]However,thestudyonly
measuredcompliancewithevidencebasedrecommendationsregardinguseofbronchodilators,
methylxanthines,steroids,andnoninvasiveventilation(NIV).[10]Morerecentstudiesontheactual
standardsofclinicalcareprovidedtoAECOPDpatientsintheEDarelacking.

Thecurrentstudyexaminedthecharacteristics,assessment,management,andoutcomeofAECOPD
presentationstoalargeregionalAustralianhospitalED.Theobjectiveofthestudywastodeterminethe
factorsassociatedwithhospitalizationandtoexaminecompliancewiththeCOPDXPlan2011[9]
recommendations(mostcurrentversionatthetimeofthestudy)forassessmentandmanagementof
AECOPDpatients.

MATERIALSANDMETHODS
AretrospectivecohortstudywasconductedattheGoldCoastHospital,SouthportCampus.Thisisa570
bedmajorregionalteachinghospitalwithallmajorspecialties,exceptforcardiacsurgeryandburns.TheED
oftheGoldCoastHospitalprovidescareforamixedadultandpediatric(approximately70and30%,
respectively)population.In2012,thereweremorethan67,000presentationstotheGoldCoastHospitalED.
Includedinthestudywereadultpatients(age18years)diagnosedwithCOPDbyamedicalpractitioner,
whohadpresentedtotheEDovera6monthperiod(December15,2011June15,2012).COPDpatients
whoseprimaryreasonforadmissionwasnotduetoanacuteexacerbationwereexcludedfromthestudy.
WhenpatientspresentedwithAECOPDmorethanonceinthestudyperiod,onlythefirstpresentationwas
usedfortheprimaryanalysis.TheGoldCoastHealthServicesDistrictHumanResearchEthicsCommittee
approvedthestudy(EthicsReferenceNumber:HREC/12/QGC/99).

PotentialstudysubjectswereidentifiedonthebasisofInternationalClassificationofDiseases(ICD)10
codesofE65AandE65B(complexandnoncomplexCOPD).Eligiblepatientselectronicmedicalrecord
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(EMR)entries,EDinformationsystem(EDIS)records,andelectronicdischargesummarieswerereviewed.
BiochemistryresultswereobtainedthroughtheAUSLABlaboratoryinformationsystem.Thefollowing
informationwascollected:

Patientdemographics(age,gender,smokingstatus,livingsituation,andcomorbidities)
Characteristicsofunderlyingdisease(oxygentherapyathomeandCOPDrelatedhospitaladmissions
inthepreceding12months)
Featuresofcurrentexacerbation(dayofweekofpresentation,clinicalsymptomsonpresentation,and
vitalsigns)
InvestigationsperformedinED(spirometry,chestXray,fullbloodcounts,biochemistry,andblood
gasanalysis)
TreatmentsprovidedinED(oxygen,systemicsteroids,antibiotics,andbronchodilators)
Outcomes(admissionordischargefromED)
Followup:COPDrelatedEDpresentationsoverthesubsequent3months.

AccordingtotheCOPDXPlan,NIVisindicatedforseveredyspneathatrespondsinadequatelytoinitial
emergencytherapy,confusion,lethargyorevidenceofhypoventilation,persistentorworseninghypoxemia
despitesupplementaloxygen,worseninghypercapnia(PaCO2>70mmHg),orsevereorworsening
respiratoryacidosis(bloodpH<7.3).However,thestrongestindicationforNIVinAECOPDpatientsisfor
acutehypercapnicrespiratoryfailure(arterialbloodpHoflessthan7.35andPaCO2>45mmHg).
AdherencetotheCOPDXPlanregardingtheevaluationandtreatmentofAECOPDwasassessed.[9]

Statisticalanalysis
AllstatisticalanalyseswereperformedusingStatisticalPackageforSocialSciences(SPSS)version20.0
(SPSS,Chicago,IL,USA).KolmogorovSmirnovandShapiroWilktestswereusedtoassessfornormality
ofthedata.Normallydistributeddatawasanalyzedfordifferencesbetweenindividualgroupsusingthe
Student'sttestandpresentedasmeanandstandarderror.Nonparametricdatawasanalyzedfordifferences
betweengroupsusingtheMannWhitneyUtestandresultsexpressedasmedianandinterquartilerange.
Logisticregressionanalysiswasusedtoidentifyfactorsassociatedwithhospitalization.Variablesfromthe
univariateanalysisthatwhichhadPvalues<0.05wereevaluatedforthemultivariatelogisticregression
analysis.StatisticalsignificancewasindicatedbyPvalueoflessthan0.05.

RESULTS
Duringthe6monthstudyperiod,188patientswereidentifiedusingtheICD10codes.Afterreviewofthe
medicalcaserecords,12presentationswereexcludedfromanalysisastheywerefoundtobeeither
incorrectlycodedorAECOPDwasnottheprimaryreasonforpresentationtotheED.Finalanalysiswas
performedon122patientswhohad176AECOPDpresentations.Baselinecharacteristicsandinformation
abouttheEDpresentationandmanagementaresummarizedinTable1.Meanage(standarderror(SE))of
thepatientswas71(11)yearsand51%weremale.Twentyeightpercentofpatientswerelivingaloneand
23%werecurrentsmokers.Onethirdofpatientsusedhomeoxygentherapyandalmost40%ofpatientshad
beenhospitalizedforAECOPDinthepreceding12months.

EightypercentofAECOPDpatientswhopresentedtotheEDwerehospitalized.Admittedpatientsin
comparisontodischargedpatients,wereolder(75vs65years,P=0.005),receivedhomeoxygen(39vs
13%,P=0.016),presentedonaweekday(62vs37%,P=0.038),hadloweroxygensaturations(median
SpO2,92vs94%,P=0.034),andhadahighermedianwhitecellcount(WCC109/L)(10.5vs9.2,P=
0.046)andCreactiveprotein(CRP20vs8.65mg/L,P=0.032).AECOPDpatientswhowereeventually
hospitalizedreceivedsupplementaloxygen(82vs42%,P<0.001)andsystemiccorticosteroids(81vs71%,
P=0.046),moreoftencomparedtoAECOPDpatientswhoweredischargedfromtheED.Overall,34%(n
=43)ofpatientsrepresentedwithinthestudyperiodwithanotherepisodeofAECOPD,butthisproportion
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ofrepresentationswasthesamebetweenthehospitalizedpatientscomparedtopatientswhoweredischarged
fromtheED(representationrate:37vs29%,P=0.635).Multivariateanalysiswasperformedonthe
predictorsofadmission[Table2].Amongthevariables,onlyincreasedagewasindependentlyassociated
withhospitalization(oddsratio(OR)1.0995%confidenceinterval(CI):1.001.18P=0.05).

Overall,adherencetotheCOPDXPlanguidelinewasgood[Table3].Adherencetoguideline
recommendationsregardingchestradiographswasexcellent(100%).Mostpatientsreceivedbronchodilators
(88%)andsystemiccorticosteroids(79%),butonly67%ofpatientswithappropriateindications,received
antibiotics.Therewasalsogoodadherencetotheguidelinerecommendationsforhospitalization.The
majorityofpatientswithmarkedincreaseinintensityofsymptomsorthosewhohadfailedtoimprovewith
ambulatorytreatment(75%)andhadworseninghypoxia(88%)werehospitalized.However,adherenceto
certainguidelinerecommendationswassuboptimal:Objectivemeasurementofpulmonaryfunction,whilein
theEDwasobtainedinonly17%ofpatientsandevaluationofarterialbloodgaseswasperformedinonly
28%overall.However,whenonlypatientswithasevereexacerbation(SpO2<92%)areconsidered,an
arterial(ABG)orvenousbloodgas(VBG)analysiswasperformedin77%ofpatients.

UsinganarterialbloodpHoflessthan7.35asthecutoffvalue,therewere39admissionswheretreatment
viaNIVwasindicated.Themedian(interquartilerange(IQR))PaCO2forthese39admissionswas59(48
102)mmHg.DespitesuitableNIVequipmentbeingavailable,thistreatmentwasprovidedforonly11(29%)
patients.InterestinglytherewasnodocumentationastoreasonswhyNIVwasnotprovidedtothe71%(n=
28)ofpatientswithtype2respiratoryfailure.

DISCUSSION
OurstudyevaluatedtheEDmanagementinpatientswithanAECOPDovera6monthperiodinaregional
tertiaryhospital.Eightypercentofthesepatientswerehospitalized.Overalltherewasgoodadherenceto
manyoftherecommendationsoftheCOPDXPlan.However,therearecertainclinicalmanagementareas
withpotentialforimprovement.WeidentifiedseveralfactorsinAECOPDpatientsthatwereassociatedwith
hospitalization.ThismayfacilitatefutureEDmanagementofAECOPDpatients.

Inourstudy,80%ofCOPDpatientspresentingtoEDwerehospitalized,whichissimilartopreviousreports.
[10,13]Abetterunderstandingofthefactorsassociatedwithhospitalizationmaytranslatetomorerapid
decisionmakingforatriskpatients,resultinginlesstimespentintheEDandbetterclinicaloutcomes.This
isofparticularinterestwiththeintroductionoftheNationalEmergencyAccessTarget(NEAT)toaddress
growingEDdemand(http://www.health.gov.auandhttp://www.ecinsw.com.au/neat).However,currently
therearenoreliablemethodsofriskstratificationforpatientswithCOPDexacerbationspresentingtothe
ED.Recently,GarciaSanzetal.,[14]evaluated409exacerbationsin239COPDpatientsovera12month
periodandfoundthatimpairedoxygenation,presenceofneutrophilia,andadministrationofantibioticsinED
wereassociatedwithhospitalization.Interestingly,impairedoxygenationandneutrophiliawereassociated
withhospitalizationinourstudyaswell.WealsofoundthatanelevatedCRPwasalsoassociatedwith
hospitaladmission.CRPisaninflammatorybiomarkerthathasbeenpreviouslybeenassociatedwithsevere
COPD.[15,16]Furthermore,inCOPDexacerbations,raisedCRPhasbeenassociatedwithbacterial
infections[17]andadverseclinicaloutcomes.[18]HenceitisnotsurprisingthataraisedCRPisabiomarker
forsevereAECOPDexacerbationsthatrequirehospitaladmissions.Wefoundthathospitaladmission
occurredmorefrequentlyduringweekdayscomparedwithweekends,potentiallyduetopatientspostponing
presentationtillaftertheweekendorreviewbyowngeneralpractitioner(GP).Ourresultsareconsistentwith
thoseofarecentlargemulticenterstudyofnineEDs,whichreportedthataweekdaypresentationwas
associatedwithlongerlengthofstayinEDandincreasedlikelihoodofhospitalization.[19]

Interestingly,wefoundthatwhilethealterationsintheindividualvariableswereassociatedwithadmission,
onlyincreasedagewassignificantlyassociatedwithhospitalization.Othervariablesdidnotachieve
statisticalsignificance.Thisismostlikelyduetotherelativelysmallsamplesizeinourstudy.Theclinical

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utilityofEDphysiciansbeingawareoftheseadmissionassociatedfactorsinimprovingoutcomesfor
AECOPDpatientswillneedtobeevaluatedinmulticenterprospectivestudies.Ifvalidated,thenthefactors
mayneedtobeincorporatedintofutureversionsofAECOPDguidelines.

Inthisstudy,wefoundgenerallygoodconcordanceofEDmanagementwithguidelinerecommendations,
suchasthetestableindicatorsforhospitalizationintheCOPDXPlan.Notunexpectedlywefoundthatolder
ageandhomeoxygentherapywereassociatedwithhospitalization.Thesetwofactors,whilenotpresentin
theCOPDXPlan,arerecommendedininternationalCOPDguidelines.[6,7]Withregardstotreatmentgiven
intheED,bronchodilators,systemiccorticosteroids,andantibioticswereprovidedinthegreatmajorityof
patients.TheseresultsareconsistentwithapreviousstudyofAustralianEDs,withourstudyhavingahigher
prescriptionrateofsystemiccorticosteroids(79vs57%).[10]Thehigheradherencetoguideline
recommendationsinourstudymaybeexplainedinpartbythedifferenttimeperiodsofthetwostudies(2011
2012vs20062007[10]).Thetrendforincreasedprescriptionofsystemicsteroidsmorerecentlyisconsistent
withthefindingsofTsaietal.,whonotedthatbetween2000and20052006,therewasanincreased
prescriptionsofsystemiccorticosteroidsandantibioticsinaBostonED.[13]Thisfindingmaybedueto
increasedawarenessofguidelinerecommendationsamongEDphysicians.

AspertheCOPDXguidelines,theappropriatemanagementofhypercapneicrespiratoryfailurebeginswith
theperformanceofanarterialbloodgas(ABG)whentheforcedexpiratoryvolumein1s(FEV1)isless
than1.0Lorlessthan40%ofpredictedorifthereareanysignsofrespiratoryfailureorcorpulmonale.[9]
OverallwefoundthatanABGwasperformedin28%ofpatients,butthatabloodgasanalysis(ABGand/or
VBG)wasperformedinhypoxicpatientsin77%ofpatients.Inourexperience,thedecisiontoperforma
bloodgasanalysisisbasedonbaselineoxygensaturationsandclinicalacumenratherthanspirometric
values.Inourstudy,asizeableproportionofpatientshadaVBGinsteadofanABG.Thepracticeof
measuringVBGinAECOPDpatientsissupportedbyrecentstudies,whichhaveshownthataVBGin
conjunctionwithoxygensaturationhassimilarclinicalutilitytoanABGinidentifyinghypercapneic
respiratoryfailure.[20,21,22]So,wefoundthateventhoughspirometryinEDwasnotperformed
commonly,thedecisiontoperform(arterialorvenous)bloodgasanalysiswasbasedonappropriateclinical
judgment.

ThebenefitsofNIVinthetreatmentofhypercapneicrespiratoryfailureinAECOPDincludeimproved
survival,reducedlengthofstay,andneedforintubation.[23]HoweverinourstudyNIVwasprovidedto
only29%ofeligiblepatients.Interestingly,verysimilarresultshavebeenreportedinothernationaland
internationalCOPDaudits.[24,25,26,27]Previousstudieshavealsonotedthatoftennoreasonisprovidedin
themedicalnotesastowhyNIVisnotprovidedtoeligiblepatients.Possibleexplanationsforsuchlow
provisionofNIVineligiblepatientsincludeapoorunderstandingoftheclinicalindicationsforNIV,limited
experienceand/orlackofstaffeducation.[26]Educationalinitiativesincludingchecklistshavebeenshownto
improveadherencetoguidelinesintheprovisionofNIVforeligiblepatients.[28]Furtherstudyisrequiredto
understandwhyNIVprovisionislowinED(bothinAustraliaandworldwide)andmeasuresthatneedtobe
undertakentoimprovethispractice.

WefoundthatspirometryhadbeenperformedintheEDinonly17%ofpatients.Thisisparticularly
divergentfromtheCOPDXPlanwhichrecommendsthatspirometrycanbeperformedeveninthesickest
ofpatients,unlesstheyareconfusedorcomatose.[9]Ithasbeensuggestedthatincreasedratesofspirometry
eitheratpresentationoratsomestageduringtheadmissioncouldbeexpectedtoallowbettercharacterization
ofdiseaseseverity,andhenceimprovedmanagement.[26]However,thefeasibilityandaccuracyof
spirometryintheEDhasbeenquestionedintheGOLDguidelines[29]andithasbeennotedthatitisrarely
performedintheED.[11]Analternativetoconsiderforfuturestudieswillbetoobtainanaccurate
assessmentofsmokinghistory,andtousethisinformationasaproxymeasureofspirometrysincepackyears
ofsmokingisasurrogatemeasureoftheseverityofCOPD.[11,30]

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Weacknowledgethatourstudydesignandresultshaveseverallimitations.First,becauseourstudyisa
retrospectivereviewofmedicalrecordsitsuffersfromtheprincipalassumptionthatdocumentationisan
accuratereflectionofclinicalpractice.Second,itispossiblethatbyusingICDcodesasastrategyof
identifyingCOPDpatientsforourstudy,wemayhavemissedpatientsduetotheproblemsof
underreporting,incorrectEDISdiagnosis,and/orICDcoding.Weidentified176EDpresentationsin6
monthswhichequatestoapproximately7.6per1,000presentations,whichissimilartoreportsintheUS
whereCOPDaccountsfor10per1,000EDpresentations.[31]Third,sincewedidnotinterviewED
physicians,wecannotdetermineiftherewereindividualphysicianfactorsthatmayhavebeenassociated
withhospitalization.Fourth,potentiallyimportantmeasurementswerenotobtainedinallpatients,
particularlyspirometryandbloodgasanalysis.However,sinceourstudywasdesignedtostudyactualreal
worldEDpractice,wedonotconsiderthistobeastudyrelatedproblem.

CONCLUSION
Wealsoidentifiedseveralfactorsthatareassociatedwithhospitaladmission.Awarenessofthesefactorsin
thedesignoffutureAECOPDmanagementguidelinesmayallowEDphysicianstotriagepatientswhoare
likelytobeadmittedrapidlyandefficiently.Wealsofoundthatingeneral,EDcliniciansadheredwelltothe
COPDXPlanformanagementofAECOPDpatients.Howeverthereisscopeforimprovementinthe
performanceofspirometryandprovisionofNIVtobemoreinconcordancewithnationalCOPDguidelines.

Footnotes
SourceofSupport:Nil

ConflictofInterest:Nonedeclared.

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FiguresandTables

Table1

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11/30/2016 Emergencydepartmentmanagementofacuteexacerbationsofchronicobstructivepulmonarydiseaseandfactorsassociatedwithhospitalization

Demographicandbaselineclinicalcharacteristicsofpatientspresentingtotheemergencydepartment
accordingtohospitalizationstatus

Table2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115343/?report=printable 9/11
11/30/2016 Emergencydepartmentmanagementofacuteexacerbationsofchronicobstructivepulmonarydiseaseandfactorsassociatedwithhospitalization

Oddsratiobybinarylogisticregressionforhospitalization

Table3

ObservedfrequenciesfordiagnosticproceduresandclinicalmanagementofAECOPDpatientsintheED

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115343/?report=printable 10/11
11/30/2016 Emergencydepartmentmanagementofacuteexacerbationsofchronicobstructivepulmonarydiseaseandfactorsassociatedwithhospitalization

ArticlesfromJournalofResearchinMedicalSciences:TheOfficialJournalofIsfahanUniversityofMedical
SciencesareprovidedherecourtesyofMedknowPublications

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115343/?report=printable 11/11