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AnElectronicToolfortheEvaluationandTreatmentof
SepsisintheICU
ARandomizedControlledTrial
MatthewW.Semler,MDLizaWeavind,MBBCh,MMHCMichaelH.Hooper,MD,MScToddW.Rice,MD,
MScSupriyaSrinivasaGowda,MBBSAndrasNadas,MScYannaSong,MSJasonB.Martin,MD
GordonR.Bernard,MDArthurP.Wheeler,MD
CritCareMed.201543(8):15951602.

AbstractandIntroduction
Abstract

Objectives:Todeterminewhetheradditionofanelectronicsepsisevaluationandmanagementtooltoelectronicsepsisalerting
improvescompliancewithtreatmentguidelinesandclinicaloutcomesinsepticICUpatients.
Design:Apragmaticrandomizedtrial.
Setting:MedicalandsurgicalICUsofanacademic,tertiarycaremedicalcenter.
Patients:Fourhundredandsevenpatientsadmittedduringa4monthperiodtothemedicalorsurgicalICUwithadiagnosisof
sepsisestablishedatthetimeofadmissionorinresponsetoanelectronicsepsisalert.
Interventions:Patientswererandomizedtousualcareortheavailabilityofanelectronictoolcapableofimporting,synthesizing,
anddisplayingsepsisrelateddatafromthemedicalrecord,usinglogicrulestoofferindividualizedevaluationsofsepsisseverity
andresponsetotherapy,informingusersaboutevidencebasedguidelines,andfacilitatingrapidorderentry.
MeasurementsandMainResults:Therewasnodifferencebetweentheelectronictool(218patients)andusualcare(189
patients)withregardtotheprimaryoutcomeoftimetocompletionofallindicatedSurvivingSepsisCampaign6hourSepsis
ResuscitationBundleelements(hazardratio,1.9895%CI,0.755.20p=0.159)ortimetocompletionofeachelement
individually.ICUmortality,ICUfreedays,andventilatorfreedaysdidnotdifferbetweeninterventionandcontrol.Providersused
thetooltoenterordersinonly28%ofavailablecases.
Conclusions:Acomprehensiveelectronicsepsisevaluationandmanagementtoolisfeasibleandsafebutdidnotinfluence
guidelinecomplianceorclinicaloutcomes,perhapsduetolowutilization.
Introduction

SepsisisacommonandlethalillnessfrequentlymanagedintheICU. [13]Earlyresuscitation[4,5]andpromptantibiotic
administration[68]improvemortality.Toaidcliniciansinconsistentimplementationoftheseinterventions,theSurvivingSepsis
Campaign(SSC)outlinedin2005a6hourSepsisResuscitationBundleincorporatingrapidsepsisrecognition,earlyculturesand
antibiotics,andgoaldirectedfluidadministrationandhemodynamicsupport. [9,10]ImplementationofSSC6hourResuscitation
Bundleelementsusingawrittenprotocolhasbeenshowntoimprovecompliancewithrecommendations[1113]andmortality. [14]
However,intheabsenceofongoingfeedbacktoclinicians,evenafterintensiveeducationinsepsisdetectionandmanagement,
compliancewithguidelinesremainslow. [15]Theuseofelectronictoolstoaddressthischallengeinterestsphysiciansand
hospitals.ElectronictoolshavebeensuccessfullyemployedintheICUforventilatorweaning[16]andidentificationofacute
respiratorydistresssyndrome. [17]Onepriorstudyinsepsishasevaluatedacomputerizedtranslationofawrittenprotocolfor
earlyresuscitation. [18]Withrecentadvancesininformationtechnology,asingleelectronictoolcannowcouplerealtime
monitoringofthemedicalrecordtoidentifypatientswithpotentialsepsis[19]withdecisionsupporttoguidecliniciansthrough
severityevaluation,provideeducationaboutsepsisguidelinesgenerallyandidentifyinterventionsindicatedinaspecificpatient,
facilitaterapidentryofsepsismanagementorders,andmonitorthepatient'sresponsetointerventionsthroughouttheICU
course.WehypothesizedthatimplementationofsuchanelectronicevaluationandmanagementtoolinadultICUpatientswith
sepsiswouldimprovecompliancewithsepsistreatmentguidelinesandclinicaloutcomes.

MaterialsandMethods
DefinitionsandTerms

Sepsis.Thecooccurrenceofsuspectedinfectionandtwoormoreofthesystemicinflammatoryresponsesyndrome(SIRS)
criteria:1)temperaturemorethan38Corlessthan36C,2)heartratemorethan90beats/min,3)respiratoryratemorethan20
breaths/minorPaCO lessthan32mmHg,and4)WBCcountmorethan12,000cells/mm3orlessthan4,000cells/mm3or
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breaths/minorPaCO2lessthan32mmHg,and4)WBCcountmorethan12,000cells/mm3orlessthan4,000cells/mm3or
morethan10%immature(band)forms.
ModifiedSIRSCriteria.TwoormoreSIRScriteriametwithinarolling24hourwindow,withatleastonebeingabnormal
temperatureorWBCcount.
ListeningApplication.Anelectronictoolthatmonitorspatientdatainrealtime,evaluatesdataagainstdiagnosticandalerting
rulestoidentifypatientswhonewlymeetmodifiedSIRScriteria,andcommunicateswiththealertingsystemtonotifyproviders.
[19]

AlertingSystem.Anelectronictoolthatreceivesinformationfromthelisteningapplicationonpatientswhohavemetmodified
SIRScriteria,notifiesprovidersofthefinding,andsolicitsanassessmenttodetermineifthepatientclinicallymeetscriteriafor
sepsis. [19]
IntegratedSepsisAssessmentandManagementTool.Asoftwareprogramwithintheelectronicmedicalrecord(EMR)
designedtoimport,synthesize,anddisplaysepsisrelateddatafromdifferentportionsoftherecord,uselogicrulestoofferan
uptodate,individualizedevaluationofsepsisseverityandresponsetotherapy,informusersaboutevidencebasedguidelines,
andfacilitaterapidorderentry.
ClinicalProvider.ICUresidentphysicianornursepractitionerprimarilyresponsibleforpatientmanagementandorderentry.
ScreeningandEnrollment

FromApril1toJuly31,2012,weconductedapragmatic,openlabel,parallelgrouprandomizedtrialinthemedicalICU(MICU)
andsurgicalICU(SICU)ofVanderbiltUniversityHospital.Thisstudywasapprovedbytheinstitutionalreviewboardwithwaiver
ofinformedconsent.
AllpatientsadmittedtoastudyICUandassessedbytheirclinicalproviderashavingsepsiswereenrolled(Fig.1).Patients
assessedassepticviaanautomaticpromptofferedatICUadmissionwereenrolledimmediately.Forallpatientswithoutsepsis
atICUadmission,electronicmonitoringwasemployedtofacilitateearlydetectionofsepsisdevelopment(Fig.S1,Supplemental
DigitalContent1,http://links.lww.com/CCM/B296).Apreviouslyestablishedlisteningapplicationscreenedrealtimedatafrom
thenursingdocumentation,electronichealthrecord,andlaboratorysystemformodifiedSIRScriteria. [19]IfmodifiedSIRS
criteriadevelopedinanICUpatientwhohadnotpreviouslybeenassessedbyaclinicalproviderasseptic,analertingsystem
notifiedtheclinicalproviderviatextpageandaflagappearednexttothepatient'snameontheclinicalprovider'selectronic
patientlist.Usingthisflag,clinicalprovidersrecordedarevisedsepsisassessment.Ifanassessmentwasnotrecordedwithin1
hour,areminderwassent.Nomanagementrecommendationsweregivenbythelisteningapplicationoralertingsystem.If
patientswereassessednottobeseptic,furtheralertsweresuppressedfor48hours,andthenelectronicmonitoringresumed.If
patientswereassessedasseptic,theywereenrolledinthestudyandnofurtheralertsweredeliveredforthathospitalization.
Studyenrollmentoccurredatthetimethefirstprompttowhichtheclinicalproviderconfirmedthepresenceofsepsiswas
offered.Patientswereexcludediftheywereneverassessedassepticbytheirclinicalproviderorhadbeenpreviouslyenrolled
duringthesamehospitalization.Patientswithorderslimitingresuscitationwerenotexcluded.

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Figure1.

Enrollmentandrandomization.Of475patientsassessedasseptic,68hadbeenenrolledinthestudypreviouslyinthe
hospitalizationandwereexcluded.Theremaining407wererandomized,followed,andincludedintheanalysis.
RandomizationandMasking

AllICUpatientsassessedbyaproviderassepticwererandomizedbyacomputerizedalgorithmwithoutuseofpermutedblocks
orstratificationtousualcare(control)ortheavailabilityofanintegratedelectronicsepsisassessmentandmanagementtool
(intervention).Clinicalproviderswereawareofgroupassignment.Separatestudypersonnelremainedblindeduntilthe
completionofdatacollection.
Intervention

Intheinterventiongroup,whenaprovider'sassessmentconfirmedthepresenceofsepsis,theintegratedsepsisassessmentand
managementtool(Video1,SupplementalDigitalContent2,http://links.lww.com/CCM/B297)openedautomaticallyand
remainedavailabletoallprovidersthroughouttheICUadmission.ThetoolresideddirectlywithintheEMRandcontaineda
divideddisplay.Halfpresentedgraphsofcurrentvalue,trend,andgoalrangefortemperature,heartrate,meanarterialpressure,
centralvenouspressure(CVP),WBCcount,hemoglobin,plateletcount,prothrombintime,lactate,andRichmondAgitationand
SedationScore.Theotherhalfcontainedasetoftabsdedicatedtoevaluationofthepatientconditionandmanagement.The
assessmenttabofferedprovidersanevaluationofsepsisseverityusinganalgorithminwhichsepsiswasdefinedasprevious
confirmationofsepsisbyaclinicalproviderinresponsetoaprompt,severesepsiswassepsisplusmeanarterialpressureless
thanorequalto60mmHgoralactateabovethelaboratoryupperlimitofnormal,andsepticshockwassepsisplusvasopressor
useoreithermeanarterialpressurelessthanorequalto60mmHgoralactategreaterthanorequalto4mmol/Ldespitean
orderforgreaterthanorequalto1,000mLofIVcrystalloid.Theprovidercouldagreewithormodifytheseverityassessment,
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whichwouldthenpropagateintothemanagementtabsallowingthetooltohighlightinterventionsrecommendedforthatspecific
patient.ThemanagementtabsweredisplayedinaworkflowmodeledontheSSC6hourResuscitationBundlebeginningwitha
diagnosticspaneladdressingbasiclabs,cultures,andimagingforsourcecontrol,followedbyatherapeuticspaneladdressing
antibioticsandgoaldirectedresuscitationincludingfluidboluses,CVP,vasopressors,seriallactatemeasurements,inotropeuse,
andbloodtransfusion,andconcludedbyasupportivecarepaneladdressinglungprotectiveventilation,adrenalinsufficiency,
glucosecontrol,andvenousthromboembolicandstressulcerprophylaxis.Eachmanagementtabcontainedevidencebased
informationand"singleclick"orderentryenablingproviderstoplacerelatedorderswhilereviewingtheguidelines.Thetoolwas
integratedwithelectronicorderentryfromallpartsofthehospitalsothatproviderscouldseeviaacolorcodedsystemnotonly
whichorderswererecommendedbutwhichordershadalreadybeencompletedintheICUorpriortoICUadmission.Thetool
couldbeminimizedatanytimetoreviewthemedicalrecordandcouldbeclosedandreopenedanytimethroughoutthe
admission.Technicalaspectsofthesepsistool'sdevelopment,architecture,anduserinterfacehavebeenpublished
previously[1923]andaresummarizedintheonlinesupplement(SupplementalDigitalContent1,
http://links.lww.com/CCM/B296).
DataCollection

Patientswerefollowedfor28daysoruntilhospitaldischarge,whicheveroccurredfirst.Demographicandbaselinecharacteristics,
vitalsignsandlaboratoryresults,andclinicaloutcomeswerecollectedbystudypersonnelblindedtogroupassignment.Thedate
andtimeatwhicheachoftheSSC6hourResuscitationBundleelementswascompletedunderwentautomated,electronic
documentationintheEMRasapartofroutineclinicalcare.Thesedatawereprospectivelyabstractedintoadatabasebyblinded
studypersonnel.Listeningapplication,alertingsystem,andtoolusagedatawerecollectedautomaticallyinaseparatedatabase.
Retrospectivereviewofthemedicalrecordbystudyphysiciansusedallavailableinformationtoadjudicatewhethereachpatient
hadbeensepticatthetimeofenrollment.
TheprimaryendpointwastimefromenrollmentuntilcompletionofallindicatedelementsoftheSSC6hourResuscitation
Bundlebloodculturesdrawn,broadspectrumantibioticsordered,CVPmeasured,IVfluidbolusadministeredifindicated,
vasopressorsadministeredifindicated,andlactatemeasured.Lactateclearanceisusedinplaceofvenousoxygensaturationin
ourICUs. [24]Timetocompletionforeachelementwascalculatedastimefromenrollmentuntilthetimethateachbundle
elementwaselectronicallydocumentedascompletedintheEMR.Secondaryendpointsincludedtimetocompletionofeach
individualSSC6hourResuscitationBundleelement,ICUmortality,daysaliveandfreefrommechanicalventilation(ventilator
freedays[VFDs]),daysaliveandoutoftheICU(ICUfreedays),anddaysaliveandfreefromvasopressoradministration
(vasopressorfreedays),alltostudyday28.
StatisticalAnalysis

Basedonpriordatafromthesamesetting, [19]plannedenrollmentof400patientsprovided80%statisticalpowertodetecta1
hourdecreaseintheprimaryendpointoftimetocompletionofallSCC6hourResuscitationBundleelementswithatypeIerror
rateof0.05.Demographicsandbaselinecharacteristicsweresummarizedbymedianandinterquartilerange(IQR)ormeanand
SDforcontinuousvariablesandasnumbersandpercentagesforcategoricalvariablesacrossinterventionandcontrolgroups.To
analyzethetimetocompletionofallSSC6hourResuscitationBundleelementsandeachelementindividually,thecumulative
eventprobabilitieswereestimatedandcomparedusingKaplanMeiermethodwithlogranktestingandCoxproportionalhazards
regression.Alogisticregressionmodelwithprespecifiedcovariateswasfittoassesswhatfactorsimpactedtheuseofthetoolto
enterorders.AllanalyseswereperformedusingthestatisticssoftwareRversion3.0.1(http://www.rproject.org).

Results
EnrollmentandBaselineCharacteristics

Of1,843ICUadmissionsduringthestudyperiod,407wereidentifiedbyprovidersashavingsepsisandwereenrolled(Fig.1).
The218patientsrandomizedtotheintegratedsepsisassessmentandmanagementtoolandthe189patientsrandomizedto
controlhadsimilarbaselinecharacteristicsandprerandomizationmanagement().Patientsaveraged56yearsold,were
predominantlymaleandCaucasian,andweremostfrequentlyadmittedfromtheemergencydepartmentandcaredforinthe
MICU.Apulmonarysourceofsepsiswasmostcommon,andonefifthofpatientsweremechanicallyventilatedatenrollment.
Table1.BaselineCharacteristicsbyTreatmentGroup

Characteristic

Control(n=189) ElectronicTool(n=218)

Age(yr)
Male
Race
Caucasian
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5717

5516

55.0%(104)

54.6%(119)

76.7%(145)

73.9%(161)
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AfricanAmerican

15.9%(30)

18.3%(40)

Asian

1.6%(3)

1.8%(4)

Unknown

5.8%(11)

6.0%(13)

Routeofadmission

Emergencydepartment

45.5%(86)

46.8%(102)

Transferfromanotherhospital

12.7%(24)

16.5%(36)

Floortransfer

25.4%(49)

20.2%(44)

Postanesthesiacareunit/recoveryroom

8.5%(16)

10.6%(23)

Other

7.4%(14)

6.0%(13)

MedicalICU

71.4%(135)

70.6%(154)

Sepsisacknowledgedatadmission

65.1%(123)

54.6%(119)

Ifnotpresentatadmission,timetodevelopment(hr)

1.8(0.529.3)

2.2(0.549.6)

Timefromsepsisprompttopositiveassessment(min)

48.5(16.5152.0)

47.5(18.0154.0)

88.4%(167)

84.4%(184)

Sepsisconfirmedonreview
Sourceofsepsis

Pulmonary

30.2%(57)

22.5%(49)

Urinary

14.3%(27)

14.7%(32)

Abdominal

22.2%(42)

21.1%(46)

Skinandsofttissue

7.4%(14)

7.3%(16)

Bacteremia

16.4%(31)

16.1%(35)

Other

9.5%(18)

18.3%(40)

Fluidin6hrpreenrollment(mL)

858983

777800

Vasopressorsin6hrpreenrollment

6.3%(12)

10.1%(22)

Mechanicallyventilated

20.7%(39)

21.6%(47)

AcutePhysiologyandChronicHealthEvaluationIIscore

20.68.5

20.28.6

DataaregivenasmeanSD,median(25th75thpercentile),orpercentage(number).
MainOutcomes

Therewasnosignificantdifferencebetweentheintegratedsepsisassessmentandmanagementtoolandcontrolwithregardto
theprimaryoutcomeoftimetocompletionofallindicatedSSC6hourResuscitationBundleelementsorthesecondaryoutcome
oftimetocompletionofeachelementindividually(Fig.2).TherewasnodifferencebetweenthegroupsinICUmortality,ICU
freedays,VFDs,orvasopressorfreedays().Sensitivityanalysesshowednodifferenceintheprimaryoutcomebetween
interventionandcontrolinthesubgroupswithsepsisatICUadmission(hazardratio,1.6095%CI,0.455.67p=0.462)or
sepsisrecognizedafterICUadmissioninresponsetoanalert(hazardratio,2.5395%CI,0.5212.16p=0.231).Ina
prospectivelyplannedperprotocolanalysis,patientsforwhomoneormoreorderswereplacedusingthetoolweremorelikelyto
havebloodculturesandlactatedrawninthefirst6hoursthanpatientsforwhomthetoolwasnotusedtoplaceorders(Fig.3),
buttherewasnodifferenceinICUmortality(14.3%vs14.9%p=0.905),ICUfreedays(17.91.4vs19.00.5p=0.473),
VFDs(22.31.3vs23.00.5p=0.576),orvasopressorfreedays(22.21.3vs22.60.5p=0.789).
Table2.ClinicalOutcomesbyTreatmentGroup

Outcome

Control(n=189) ElectronicTool(n=218)

ICUmortality

15.9%(30)

13.8%(30)

0.549

ICUfreedaystoday28

18.70.7

18.90.7

0.901

Ventilatorfreedaystoday28

23.00.7

23.00.7

0.940

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Vasopressorfreedaystoday28 22.40.8

22.50.7

0.909

Figure2.

CompletionofSurvivingSepsisCampaign(SSC)6hrsepsisresuscitationbundleelementsforpatientsrandomizedtothe
electronictool(studyintervention)versususualcare(control).Proportionofpatientsforwhomindicatedbundleelementswere
completedoverthe6hrafterenrollment.Lactatemeasurement,centralvenouspressure(CVP)measurement,andantibiotic
administrationwereconsideredindicatedinallpatientsduringtheirfirst6hrintheICU.Bloodcultureswereconsideredindicated
inallpatientsbutdeemedcompletedatenrollmentifobtainedinthe6hrpriortoenrollment.Fluidbolusadministrationand
vasopressoradministrationwereconsideredindicatedonlyinpatientswhometthehemodynamiccriteriaforeachinterventionas
specifiedintheSSC6hrresuscitationbundle.Therewasnodifferencebetweentheelectronictoolandusualcarewithregardto
timetocompletionoftheSSC6hrresuscitationbundleelements.

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Figure3.

CompletionofSurvivingSepsisCampaign(SSC)6hrsepsisresuscitationbundleelementsbyuseofelectronictoolfororder
entry.Proportionofpatientsforwhomindicatedbundleelementswerecompletedoverthe6hrafterenrollmentforthe
subgroupsofpatientsforwhomthetoolwasusedtoenterordersversuspatientsforwhomitwasnotusedtoenterorders.
Lactatemeasurement,centralvenouspressure(CVP)measurement,andantibioticadministrationwereconsideredindicatedin
allpatientsduringtheirfirst6hrintheICU.Bloodcultureswereconsideredindicatedinallpatientsbutdeemedcompletedat
enrollmentifobtainedinthe6hrpriortoenrollment.Fluidbolusadministrationandvasopressoradministrationwereconsidered
indicatedonlyinpatientswhometthehemodynamiccriteriaforeachinterventionasspecifiedintheSSC6hrresuscitation
bundle.Graphsinthisfiguredisplaypatientsforwhomtheresuscitationbundleelementwasindicatedduringthe6hrafter
enrollmentandexcludepatientsforwhomtheelementwascompletedbeforeenrollmentornotindicated.Patientsforwhomthe
toolwasusedtoenterordersweremorelikelytohavebloodculturesobtainedandlactatemeasured.
ToolUtilization

Ofthepatientsenrolled,60%wereidentifiedassepticatICUadmission.Inthese,themediantimefromelectronicpromptto
provider'scompletedassessmentwas46minutes(IQR,20125min)comparedwith59minutes(IQR,16200min)forthose
assessedassepticlaterinresponsetoanalertfromthelisteningapplication(p=0.982).Of218patientsrandomizedtothe
interventionarm,thetoolwasopenedbyprovidersin126cases(57.8%).Thetoolwasreopenedafterclosure51timesinthe
careof17patients(7.8%).Thetoolwasusedtoenterordersin62cases(28.4%),yielding473individualordersfor37unique
actionsincluding104(38.1%)forhematologicormetaboliclaboratorystudies,62(22.7%)forcultures,31(11.4%)forlactate
measurement,29(10.6%)forantibioticadministration,16(5.9%)forimagingstudies,andtheremainderforfluidadministration,
vasopressors,steroids,glucosecontrol,sedation,prophylaxis,andIVaccess.Orderswereenteredviathetoolfor67.3%ofSICU
patientsversus36.5%ofMICUpatients(p=0.001),andamultivariableanalysisconfirmedthatSICUwastheonlybaseline
factorassociatedwithutilizationofthetooltoenterorders(oddsratio,4.6595%CI,2.0611.0p<0.001)(TableS1,
SupplementalDigitalContent1,http://links.lww.com/CCM/B296).Thetoolwasemployedby87uniqueproviders,primarily
residentphysicians(63.5%ofMICUutilizationsvs7.7%ofSICUutilizationsp<0.001)andnursepractitioners(35.1%ofMICU
utilizationvs90.4%ofSICUutilizationp<0.001).Overthecourseofthestudy,eachprovideraccessedthetoolonamedianof
twooccasions(range,121).
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Discussion
ThispragmaticrandomizedtrialofanintegratedelectronicsepsisevaluationandmanagementtoolintwoICUsatasinglecenter
didnotdemonstrateasignificantdifferenceintheprimaryoutcomeoftimeuntilcompletionofallindicatedSSC6hour
ResuscitationBundleelements.Thereareseveralpotentialexplanationsforthislackofeffect.
Utilizationofthetoolwaslow.Providersopenedthetoolinlessthan60%ofavailablecasesandplacedordersthroughthetool
inlessthan30%.Priorstudiesofcomputerizedclinicaldecisionsupportsystems(CDSSs)haveidentifiedcharacteristics
predictiveofCDSSsuccess,whichmayberelevanttounderstandingourtool'sunexpectedlylowutilization. [2527]Twosystemic
reviews[25,26]suggestthatsuccessfulCDSSsprovidedecisionsupportautomaticallyratherthanrelyingonclinicianinitiative,
deliverdecisionsupportatthetimeandlocationofdecisionmaking,andprovideactionablerecommendationsratherthansimply
assessment.Oursepsistoolopenedautomaticallyatenrollmentbut,onceclosed,reliedonproviderstoreaccessratherthan
promptingwithchangesinpatientstatus.ThetoolresidedintheEMRandbecameavailableimmediatelyafteridentificationof
sepsisbytheICUteam.However,thecapacityofthetooltogenerateordersdirectlyfromtheEMRinterfacewasnovel,and
providersmayhavebeenmorecomfortableenteringordersthroughtheestablishedcomputerizedphysicianorderentrysystem.
Thoughourtoolwentbeyondevaluationtoprovidepatientspecificrecommendations,impactmayhavebeenlimitedbythe
mannerinwhichrecommendationsweredelivered.ColorcodingtherecommendedelementsoftheSSC6hourResuscitation
Bundlereliedontheprovidertoactivelyselecthighlightedorders.Collatingrecommendedordersintoadiscretebundleand
perhapsevenemployinganoptoutapproachwhererecommendedordersoccurredunlessprovidersactivelydisagreedmayhave
beenmoreeffective.Otherpotentialstrengthsofourtool'sdesign(integrationwithEMRandorderentry,minimalcliniciandata
entry,justificationofrecommendationswithevidence,andonsitedevelopmentinaCDSSfriendlyenvironmentviaiterative
refinementwithsupportofICUleaders)[2527]mayhavebeenoutweighedfromtheuser'sperspectivebyshortcomingsineither
usabilityorcontent.Althoughsystemspeed,cliniciantimesavings,andclarityofuserinterface[25]werenotbarriersinpilot
testing,rotationsinICUresidentstaffingmeanteachproviderinteractedwiththetoolanaverageofonlytwotimesduringthe4
monthstudy.Thesuggestionthatthetimeandenergycostsoflearningnewsoftwaremayhavedisincentivizeduseissupported
bytheobservationthatthenursepractitioners,whoworkedcontinuouslyintheICUsthroughoutthestudyperiod,werethe
highestusersofthetool."Informationoverload"isparticularlychallengingtoCDSSstargetingdiseasemanagement,andthe
amountofcontentpresentedinourtoolmayhaveoverwhelmedusers.Similarly,theabundanceofelectronicremindersin
routineuseinourICUs(druginteractionchecks,sedationgoals,anticoagulationmonitoring,insulinadvisors,imagingadvisors,
etc.)coupledwiththesepsisalertsmayhaveprecipitated"alertfatigue"encouragingproviderstonavigatearoundtheelectronic
sepsistoolreflexively.Bypassofthetoolbyprovidersmighthavebeenminimizedbyprovidingperiodicperformancefeedback,
requiringdocumentationofreasoningwhentoolwasnotusedorrecommendationswerenotfollowed,orevenelectronically
forcinguseintheinterventionarm. [28]Provideracceptanceofprotocolizedcaremayhaveinfluencedtoolutilization.Usewas
higherintheSICUandamongnursepractitioners,providergroupsthatinourinstitutionhavegreaterpreexistingfamiliaritywith
protocolizedcare.Finally,althoughthetoolwasavailabletoallprovidersduringthepatient'sICUstay,onlyresidentsandnurse
practitionersreceivedthesepsisalertpage.Giventhatattendingphysiciansatourinstitutionplayasupervisoryroleinwhichthey
areencouragedtodeferorderentry,initialevaluation,andinitialmanagementtotraineeswheneverappropriate,wefeelthat
includingattendingphysiciansonthesepsisalertswouldnothavechangedourfindings.
RestrictionofthetooltoICUsinanacademiccentermayhavefurtherdiminisheditsutility.Incontrasttostudiesinwhichsepsis
managementinterventionswereinitiatedintheemergencydepartment [1113,29]orhospitalfloor, [30]themajorityofpatientsin
ourstudyreceivedelementsoftheSSC6hourResuscitationBundlepriortoenrollment.Theperformanceofbloodcultures,fluid
resuscitation,andvasopressoradministrationbeforeICUadmissioninmorethanhalfofcasesinwhichtheywereindicatedmay
havelimitedtheadditivevalueofthetool.Additionally,ourICUsarestaffed24hoursadaybyphysiciansandnurseswho,
becauseofthehighprevalenceofsepsisinthisenvironment,areexperiencedintheearlyrecognitionandguidelinesbased
managementofsepticpatients.Theimplementationofanelectronicsepsistoolinanemergencydepartment,hospitalward,or
lessresourceintensiveICUmaydemonstratesubstantiallydifferentresults.Furthermore,bundlecomplianceinthecontrolarm
mayhavebeenaugmentedbyproviderawarenessofthestudy(Hawthorneeffect)andcontaminationof"usualcare"byexposure
totheelectronictoolwhenproviderswerecaringforpatientsintheinterventionandcontrolarmsconcurrently(patientlevelrather
thanclusterrandomization).
Lowseverityofillnessmayhaveinfluencedtheoutcomeofthetrial.AlthoughthestudywaslimitedtopatientsrequiringICU
admission,weincludedsepticpatientswithoutorgandysfunction.ThemeanAcutePhysiologyandChronicHealthEvaluationII
scoreof20andoverallICUmortalityof15%arelowerthanthoseinpriorstudiesofsepsisbundleimplementation, [4,1214,31]
andsomeoftheSSC6hourResuscitationBundleelementsmaynothavebeenindicatedinthesubgroupoflessseverelyill
patients.
Inadditiontotheaboveweaknesses,ourstudyhasseveralmajorstrengths.Priorinvestigationshaveexaminedsepsisdetection
viaelectroniclisteningapplications[19,30]andimplementationofsepsismanagementbundlesviawrittenprotocols[1113,29,31]or
computerizedtranslationofawrittenprotocol. [18]However,thisisthefirsttrialofacomprehensiveelectronictoolwithsepsis
detection,alerting,severityassessment,andmanagementfunctions.Ourstudyconfirmsthatdevelopmentandimplementation
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ofsuchacomprehensivetoolforacomplexdiseaselikesepsisisfeasibleandsafe.Thefindingthatpatientsforwhomthetool
wasusedtoenterordersexperiencedhighercompliancewithearlysepsistreatmentmetricssuggeststhat,ifusedmore
consistently,thetoolitselfmayhavebeencapableofimprovingguidelineadherence.Futurestudiesofcomprehensiveelectronic
sepsistoolsshouldtargetmoreseverelyillpatientsinlowerproviderintensitysettings,immediatelyaftersepsispresentation.
IntegrationintotheEMRshouldoccurwhereprovidersenterorders,notwheretheyreviewdata.Theappealofatoolthatis
comprehensiveandeducationalmustbecarefullyweighedagainsttheadvantagesofsimplicity,speed,andeaseofuse.Finally,
attentionandresourcesmayneedtobeshiftedfromtheunderlyingalgorithmstotheuserinterfaceandfromdevelopmentto
implementation.
Sincethecompletionofthisstudy,theSSChasreleasednewsepsisresuscitationguidelinesandrestructuredsepsisbundles
emphasizingperformanceoflactate,bloodculture,antibiotics,andfluidboluselementsinthefirst3hoursandvasopressors,
CVPmeasurement,andlactateremeasurementinthefirst6hours. [32]Evenmorerecently,twolargemulticentertrials
comparingearlygoaldirectedresuscitationwithusualcarefailedtoconfirmthedifferenceinoutcomeonwhichtheearlysepsis
resuscitationguidelinesthemselvesarebased. [33,34]Thesepotentiallymajorchangesinunderstandingearlysepsisresuscitation
donotunderminethepotentialutilityofanelectronicsepsisevaluationandmanagementtool.Asevidenceforbestpracticesin
criticalcaremedicineevolves,translationintoroutineclinicalpracticefrequentlylagsonthescaleofyearstodecades. [35]In
contrast,theclinicallogicalgorithmsandevidencebasededucationstructuredintoanelectronictoolcanbeupdatedrapidlywith
minimaleffortbyasmallnumberofindividuals.WiththeproliferationofEMRsandtherecentpassageoftheHealthInformation
TechnologyforEconomicandClinicalHealthActlinkingincentivepaymenttoimplementationofclinicaldecisionsupporttools,
[36]interestindevelopingsophisticatedelectronicdiseasemanagementtoolsforuseintheICUenvironmentcanbeexpectedto
increase.Ourstudyemphasizesthatthesuccessoffutureelectronictoolsdependsnotonlyonaddressingthetechnical
challengesofmanagingincreasinglylargedatainputs,integratingmultiplecomplexsoftwareplatforms,andprovidinguptodate,
evidencedrivenrecommendationsforanindividualpatientatanyspecificmomentintheclinicalcoursebutalsoonensuringthat
providersusethetoolonceitisbuilt.

Conclusions
Developingandinstitutingacomprehensiveelectronicsepsisevaluationandmanagementtoolisfeasibleandsafe.Additionof
anelectronicsepsisevaluationandmanagementtooltoelectronicsepsisalertingintheICUdidnotchangeguidelinecompliance
orclinicaloutcomes,possiblyduetolowutilization.
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ThisworkwasperformedatVanderbiltUniversityMedicalCenter,Nashville,TN.
Acknowledgments
WethankRachelM.Hayes,PhD,DanielW.Albert,MS,StephenClark,NormentB.Deane,MS,JanosL.Mathe,MSc,Janos
Sztipanovits,PhD,andAnneMiller,PhD,fortheircontributionsinmakingthisstudypossible.
CritCareMed.201543(8):15951602.2015LippincottWilliams&Wilkins
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