Development and evaluation of VIE-PNN, aknowledge-based system for calculating the

parenteral nutrition of newborn infants

WernerHorn��� �

, ChristianPopow�, Silvia Miksch

� � �,

LieselotteKirchner�, AndreasSeyfang

� � �

�Departmentof MedicalCyberneticsandArtificial Intelligence, University of Vienna

Freyung6, A-1010Vienna,AustriaE-mail: werner@ai.univie.ac.at�

AustrianResearch Institutefor Artificial Intelligence�NICU, Division of Neonatology, Departmentof Pediatrics,University of Vienna

Instituteof Software Technology, ViennaUniversity of Technology

Abstract

Calculatingthe daily changingcompositionof parenteralnutrition for small newborn in-fantsis troublesomeandtime consumingroutinework in neonatalintensive care.Thetaskneedsexpertiseandexperienceand is proneto inherentcalculationerrors.We designedVIE-PNN, aknowledge-basedsystemin orderto reducedaily routinework andcalculationerrors.VIE-PNN wasredesignedseveral timesbecausethecliniciansacceptedthesystemonly whenit savedtime.Themostrecentversionof VIE-PNN usesa HTML-basedclient-server architectureandis integratedinto theintranetof thelocal patientdatamanagementsystem.Sincemorethanthreeyearsall parenteralnutritionplansarecalculatedusingVIE-PNN. Evaluatingthesystem’s performanceandtheuserscontentedness,we compared50nutrition planscalculatedin parallelusingVIE-PNN or a hand-heldcalculator, retrospec-tively analyzedmorethan5000nutrition plansstoredin VIE-PNNs databaseandevalu-ateda userquestionnaire.Nutrition planswerecalculatedin a meantime of 2.4 vs. 7.1minutesusingVIE-PNN or thehand-heldcalculator. Errorsandomissionsin thenutritionplansweredetectedin 22 vs.56%anderrorsin theVIE-PNN’s plansoccurringonly withinteractively changedvalues.Reviews of storedplansshow thata meanof 4 out of 16 pa-rameterswereinteractively changed.VIE-PNN waswell accepted.Most importantreasonsfor thesuccessfuloperationof VIE-PNN in thedaily routinework weretime savingsandrobustnessof thesystem.

Key words: Knowledge-basedsystem,intensive careunit, parenteralnutrition,neonates,intranetapplication,integrationwith patientdatamanagementsystem

Preprintsubmittedto Elsevier Preprint 10October2000

1 Introduction

The planningandcalculationof an adequatenutritional supportfor meetingthemetabolicrequirementsof sickor prematureneonatesis animportantdaily routinetask.It is time consuming,needspracticalexpert knowledgeandexperience,andinvolves the risk of introducingpossiblyfatal errors[5,7,15,16].The daily timerequiredper patientis approximately10 minutessummingup to more than onehour for a eightbedsneonatalintensive careunit (NICU). Approximately5–50%of all parenteralnutrition solution (PNS) sheetscontaincalculationor omissionerrorsrequiring recalculationor even remixtureof the nutrition solution.This iscostlyandrequiresadditionaltimeof physiciansandnurses.

Computerprogramssupportingthe calculationof parenteralnutrition plansareavailableat a few hospitals.Most of themaredesignedfor adult or pediatricuse(e.g.,[10,14]) without giving specificconsiderationto the specificneedsof new-born infants.Therearea few pediatricprogramsfor parenteralnutrition planningcoveringalsothegroupof newbornandprematureinfants[6,11,12].

Suchprograms,however, do not cover thespecificmetabolicandnutritionalneedsof extremelow birth-weightnewborninfants(birth-weight500–1000grams).Onlya few programswerespecificallytailoredto the needsof small newborn infants:therearesimplecalculationprograms[2,3,8,11]andmorecomplex rule-basedandknowledge-basedsystems[4,6]. Both typesof programsreducethe routineworkload,andleadto amoreoptimizednutritionsupply. Mostsystemsaretailoredto theneedsof aspecificneonatalintensivecareunit,andtheirportability to otherunitsisvery limited becauseof differencesin theclinical approach(policy of fluid supply,speedof increments,inclusionor exclusionof variousminor nutrients,exactnessof calculations,availability of varioussolutionsandbrandsetc.)

WedesignedVIE-PNN (ViennaExpertSystemfor ParenteralNutritionof Neonates)aiming to createa programfor the routinesupportof our NICU combiningstan-dardtextbookknowledgeaboutneonatalnutrition with thepracticalknowledgeofexpertneonatologists.

In the year1991we startedthe implementationof VIE-PNN with the followingmaingoals:

creatinganinteractive supportsystemfor calculatingthedaily nutritionalplans(PNS,parenteralnutritionsolution), reducingthetimeneededfor thecalculation, creatinga systemableto combineparenteralandenteralfeedings, providing acontinuousincreaseof thedaily nutritionsupplyandaforcedchangefrom parenteralto oral nutrition. This requiresreasoningmethodstaking intoaccountthedataof thepreviousdays, outputof a printedPNSscheduleto becomepart of the casehistory. The PNS

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Table1Input andoutputparametersof VIE-PNN.

Inputparameters Outputparameters Statisticalmeasurements

Body weight Parenteralsupply Energy rates

Age Enteralsupply Parenteralinfusionrate

Totalfluid allowance Glucose Fat infusionrate

Enteralproducts Proteins/ aminoacids

Drugs Electrolytes

Serumvalues Vitamins

Clinical problems Traceelements

Fat

Bypassmedication

scheduleis furtherusedby thenursesto composethedaily mixtureof thenutri-tion solution, maintainingthehospital’s standardfor neonatalnutrition managementandpro-viding adequatecontrolof fluid, electrolyte,fat,nitrogen,andcaloricneeds.Thestandardis definedin termsof rulesof expertneonatologists,and enablingtheexpertsto keeptherulesup-to-date.

2 The VIE-PNN system

VIE-PNN consistsof threemain modules:patientadministration,computationofthedaily PNSschedule,andmaintenanceof theknowledgebase.Patientadminis-tration is neededfor addingnew patients(name,sex, dateof birth, venousaccess)andfor archiving thedataof dischargedinfants.Themaintenancemodulesupportseditingof nutrition rules,parameterlimits, roundingfactors,andupdatingof oralnutritionpreparations.

Themainmoduleof VIE-PNN interactively calculatesthedaily PNSschedule.Itstartswith yesterday‘sPNSvaluesof the infant (or plausibledefault valuesat theday of hospitaladmission).Thesevaluesdeterminethe input parametersof thesystem(seetable1).

VIE-PNN determinesthePNSscheduleby

applyingrulesfor thedaily increaseof nutritioncomponents, applyingrulesfor nutritionneedsbasedon today’sserumvalues, applyingrulesfor adaptingthenutritionalrequirementsto theclinical problemsof theinfant,

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decreasingparenteralnutritioncomponentsby theratioof enteralto total supply(for componentswhich arecontainedin oral products), checkingfor rangelimits of thecomponents, applyingroundingmethodsbasedon knowledgeabouttheprecisionneededforeachcomponent, combiningdrugsfor bypassmedication, solving the problemif the total fluid allowanceis too small to cover the nutri-tional requirements.

A samplerule is givenin Figure1. It determinesthedaily prescriptionof glucosebasedon age,actualserumglucoseconcentrationandthe former glucosesupply.VIE-PNN’s rulesareappliedin a forward chainingmannerto determinetoday’svaluesof all outputparameters.

if (Age == 1) {Glucose mg/kg/min = 4;

} elsif (New patient eq ’yes’) {Glucose mg/kg/min = 6;

} else {if (Serum glucose mg/dl > 200) {Glucose mg/kg/min = 4;

} elsif (Serum glucose mg/dl > 150) {Glucose mg/kg/min = Glucose yesterday - 1.0;

} elsif (Serum glucose mg/dl > 120) {Glucose mg/kg/min = Glucose yesterday;

} elsif (Serum glucose mg/dl >= 60) {Glucose mg/kg/min = Glucose yesterday + 0.5;

} else {Glucose mg/kg/min = Glucose yesterday + 1;

}}

Fig. 1. SampleVIE-PNN rule:daily glucoseprescription.

The final PNSscheduleconsistsof the outputparametersshown in table1. VIE-PNN is interactive allowing thephysicianto modify eachof the input andoutputparameters.

Thefirst four versionsof VIE-PNN [9] werestand-alonePC versions.The initialthreeversionswereimplementedusinganexpertsystemshell(“Intelligence/Compiler(I/C)”). Theseversionsweretoo slow to beusefulin daily routine.Thefourth ver-sion wasa redesignin C++ with a userinterfacewritten in TurboVision. It wasfast,but inflexible. It wasnot acceptedby mostof the cliniciansdueto the rigidway theuserinterfacebehaved.Furthermore,it wasimpossiblefor theexpertstoadaptVIE-PNN’s decisionrules to changingnutritional standards.Suchchangesin the knowledgebaserequiredsourcecodechangesby the knowledgeengineersandrecompilationof thesystem.Thesystemwasintroducedat theNICU including

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someinitial training. It wasevaluatedsuccessfullyfor its correctness[1] but wasusedby only a few physiciansandthennot on a regular basis.The main reasonswereits inflexible userinterfaceandits installationon a stand-alonePC: The PCwaslocatedin a roomoff-siteandit wasoftenusedfor otherurgenttasks.

3 Integrating VIE-PNN into the clinical intranet

The negative experienceswith the stand-aloneversionof VIE-PNN motivatedusto try a completelydifferentapproach.TheNICU is equippedwith an intranetofworkstations.The workstations(two mirroredservers,a bedsideworkstationforeachbed,andseveral workstationsin the nurses’andthe physicians’rooms)runthepatientdatamanagementsystem(PDMS)Hewlett-PackardCareVue9000.Allpatientrecordsarehandledelectronicallyby this PDMS.Our goalwasto integrateVIE-PNN into this system.Unfortunately, HPCareVueis acompletelyclosedsys-tem.Therewasno possibilityto integrateknowledge-basedmoduleswhich wouldbe the ideal solutionfor a parenteralnutrition supportsystem.We werethereforeforcedto choosethesecondbestsolution:usingtheworkstationsasa displayforour VIE-PNN system.We addedan additionalserver to the intranetwhich runsVIE-PNN on requestof any clientworkstation.

The redesignof VIE-PNN (version5) for a client-server architectureis basedonthe Hypertext Markup Language(HTML). A button in the HP CareVue systemallowsto invokeanHTML browseronany of theclientworkstations.Thisbrowsersendsrequeststo the HTTP server of the VIE-PNN server workstation.All thereasoningandcalculationsaredoneby cgi-programswritten in theprogramminglanguagePERL. Requestsfor datainput andresultsof VIE-PNN aresentto theclient workstationin theform of HTML pages.Thefinal PNSscheduleis printedon the NICU’s laserprinter. The system’s knowledgeis codedin PERL-like IF-THEN rules.It is revisableby theexpertsusingtheHTML browser.

Using eight HTML pagesVIE-PNN asksfor input andverificationof the nutri-tional parameters.Minimal input is requiredfrom the physician.Manual input ismandatoryfor serumvaluesfrom the laboratory(if new valuesareavailable),forchangesin the amountor kind of oral feedingandfor changesin drug adminis-tration (bypassmedication).If thereareno changesthe physicianmay acceptallpagesby clicking the OK button. The systemrecommendsvaluesfor nutritionalcomponentsbasedon its knowledgerules.Figure2 shows sucha pagefor elec-trolytevalues.Thephysicianmaychangeavaluein casethenutritionrequirementsdiffer from standardrulesdueto a problemof the neonatewhich is not includedin the knowledgebaseof VIE-PNN. Pressingthe I(nformation)button givesanin-depthexplanationaboutthecomputationof the recommendedvalue(includingbasicvalues,roundingfactors,andrulesused).Thefinal pageshows thecompletePNSschedule(seeFigure3). The usermay acceptit andprint the PNSsheetor

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Fig. 2. Samplepageshowing recommendationsof VIE-PNN for supplyingelectrolytes.Thephysicianmay changethevalues.TheI(nformation)button activatesan explanationpagewith detailsaboutthecomputationof electrolytesupply.

againmodify singleparameters.

One of the most important featuresof knowledge-basedsystemsis the easeofmaintenance.Expert neonatologistsmust have good supportto keepthe knowl-edgeaboutoral products,drugs,plausiblelimits of parametersand prescriptionrulesup-to-date.VIE-PNN hasa HTML-basedmaintenancemodulewhich allowsthe supervisingneonatologistto edit the knowledge.Figure4 shows the menuofpossiblemaintenanceactionsavailableto the physician(left). Using a rule editorhe/shemayalterprescriptionrules(right). Suchchangedrulesarecheckedfor cor-rectsyntaxandconsistency. If thevalidationsucceedsthey areconvertedto PERLcodeandput in useimmediately.

4 Routine use and evaluation of VIE-PNN

We installedtheclient-server intranetsystemof VIE-PNN at theNICU by endofJune1996. It was immediatelyacceptedby the physiciansof the NICU. Only afew minutesof initial trainingwererequired.After two yearsof successfulopera-tion VIE-PNN wasinstalledatasecondNICU of theUniversityof ViennaMedical

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Fig. 3. VIE-PNN’s HTML pageshowing thefinal compositionof theparenteralnutritionsolution.Thetop partgivesadministrative data.Theleft columnshows thecomponentsofthePNS.Theright columngivesstatisticalmeasurementsandtoday’s serumvalues.

School.VIE-PNN is now in continuousoperationat thesetwo NICUs.It calculatesapproximately5000nutritionsheetsperyear. TherearenomorePNSsheetscalcu-latedby hand.Wehavenot receivedany complaintsabouterrorsin thePNSsheets.Onemaysuspectthatthis is dueto theinteractivenessof thesystem:thephysicianeliminatesall erroneouscomputationsof thesystem.However, we haveno reportsaboutchangesrequiredonstandardcases.Weareconvincedthatknowledge-basedsystemslike VIE-PNN have to be interactive. Thereis no possibility to cover allpossibleextremesituationswhich requirea modificationof thecommonnutritionschedule.

The continuousoperationat two NICUs over yearsunderwritesthat VIE-PNN is

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Fig. 4. VIE-PNN maintenance:(left) themenuof possiblemaintenanceactions,(right) theruleeditorwith therule for sodiumprescription.

trustedandusedin thedaily routine.Failureof thecomputersystemdisablingVIE-PNN is hardly toleratedby theclinicians.We neverthelesswantedto examinetheperformanceof VIE-PNN moreclosely. After two yearsof operationweperformedaclinical studyto evaluatethesystemandits performance:

we prospectively evaluated50 routinePNScalculatedin parallelby usingVIE-PNN or by the traditionalway usinga hand-heldcalculator. Both calculationswereperformedby variousphysiciansin charge, weretrospectively reviewedthePNSstoredin thesystemsdatabasefor two years(July1996to 1998)for thenumberof interactively changedparametersandnec-essaryprogramupdates,and we evaluateda questionnairedistributedto all neonatologistsworking with thesystem.

For the 50 routinePNSwe comparedthe time neededfor calculatinga PNSpre-scriptionand the differencesin the amountof PNScomponentsexceedingmorethanoneunit (e.g.,1 mmol/kg Na, 0.5 g/kg aminoacids).Both PNSsheetswerelater reviewedby a seniorneonatologistwho ratederrorsandomissionsaspoten-tially life threatening(like prescribingdangerousconcentrationsof potassiumorbypassmedication),major(e.g.,prescribingtoo little amountsof calciumwhich isneededfor bonemineralization)or minor or clinically not relevant(like forgettingto calculatethetotal energy supply).

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Theusersquestionnaireaskedfor thefrequency of systemuse,thedegreeof con-tentednesswith thesystem(on a 5 gradescale),variousreasonsfor usingthesys-tem, and for desiredmodifications.The questionnairewasmadeavailable to allattendingphysicians.It wasansweredby all 11 physiciansof theNICU.

We foundsignificant(� ����������� , pairedt-test)time savingsof a meanof 4.7min-utesperPNSprescription(seeFigure5). Themeantimeneededto calculateaPNSwas2.4 minutes(VIE-PNN) vs. 7.1 minutes(hand-heldcalculator).This sumsupto about �� to 1 hourdaily timesavingsfor 8–12PNSprescriptions.

Fig. 5. Comparisonof time physiciansneededto calculatea parenteralnutrition solutionusingahand-heldcalculatorversususingVIE-PNN.

Therewereonly little andnosystematicdifferencesin thecompositionof thePNSandno life threateningerrors.Therewere lessmajor (10% vs. 18%) andminor(12%vs.66%)errorsandomissionsin theVIE-PNN calculatedprescriptions.Ma-jor errorswererelatedto prescribingglucose(0% vs.10%),electrolytes(10% vs.6%) or bypassmedication(0% vs. 2%), minor errorsto prescribingglucose(0%vs. 14%), fat (6% vs. 2%), electrolytes(0% vs. 16%),vitamins(6% vs. 6%) andto forgettingto calculatethe energy contentof the PNS(0% vs. 28%).All errorsdetectedin theVIE-PNN calculatedprescriptionswererelatedto valuesthatwereinteractively changedby theprescribingphysician.

Retrospective evaluationof the 5593 PNS of 643 patientsstoredin the systemsdatabaseshowed that in the meanfour out of 16 parameterswere interactivelymodified.Throughoutthestudyperiodtherulesfor calculatingaPNSwererevisedor changedfor clinical reasonsincluding the rulesfor prescribingmacronutrients(glucose,fat, aminoacids),bypassmedicationandoral nutrition (e.g.addingnewbrands),andthemodificationof roundingfactors.

The overall rating of the systemsperformanceandusability wasgood(mean1.9on a 5 gradescale,1 is best).VIE-PNN wasmainly usedfor its timesaving (73%)andaccuracy improving (73%)features.Theattendingphysiciansrequestedseveral

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amendments:the implementationof new rulesfor vitaminsandcalciumprescrip-tion in extremelow birth-weightinfants,additionof new bypassmedications,andthe adaptationof valuerangestoleratedandroundingrules.Theserequestshavebeeneasilyfulfilled by useof the maintenancemodule(after discussionwith theexpertneonatologists.)

5 Discussion

Thesuccessof theHTML-basedsystemhasto beexplainedmainly by theeaseofuseandthe benefitsin termsof time savings andaccuracy. Similar benefitswerereportedby Puangcoet al.[13].

Comparingthestand-alonePCversionandtheclient-serverversiontherearenoes-sentialchangesof theprogramflow andtheknowledgeused.Eventhefinal printoutof the PNSscheduleis the same.Identifiablefactorsaddingto the successof theHTML-basedversionare:

VIE-PNN is run in theroutinecomputerenvironmentof thelocalPDMS; theHTML browseris classifiedasan intuitive userinterface.Without any spe-cific trainingit is immediatelyclearto theuserwhichboxacceptsaninput,whichbuttonsto pressandwhich links to follow; theHTML browserprovidestherequiredflexibility for theuser. Especially, theBACK andFORWARD buttonsallow to review andrevisepages; theexplanationfacility (usingtheI(nformation)button)addsmuchto thecon-fidencein theconclusionsof VIE-PNN. Oftena parameterlooking unplausibleappearscorrectafterlookingattheexplanationpage.An exampleof suchacom-plicatedcalculationis theproportionalsubtractionof componentsfrom thepar-enteralnutritionwhicharecontainedin theenteralproduct.Suchacalculationisusuallynot doneby hand; mostimportant,physiciansbenefitfrom thetimesavings.Thishasbeenverifiedby the evaluationstudy. From the subjective physicians’view the savings aredramatical:noonewouldcalculateany morePNSsheetsby handbecauseof thetime required.

The integrationof VIE-PNN into the intranetof workstationsrunningthe patientdatamanagementsystem(PDMS)wasanimportantstepin bringingaknowledge-basedsysteminto daily routine use.However, it is far from perfect.We wouldlike to integratethePNSschedulecompositionasa moduleinto theHP CareVuePDMS.At the momentthis is impossibledueto the operationof the PDMS asaclosedsystem.More seriously, it is evennot possibleto get the laboratoryvaluesrequiredby VIE-PNN from the PDMS at the requiredtime. Thereis an exportfacility in the PDMS which we try to use,but it is too rigid to be usefulfor dataexchange.The automaticinclusionof the ten serumvaluesinto VIE-PNN would

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bea greatstepforward in minimizing manualinput. We tried to find solutionsforthis taskby interfacinglaboratoryequipment.

The currentdesignof VIE-PNN supportsportability to other hospitals.It is anencapsulatedHTTP-applicationcurrentlyrunningat two NICUsandatademositeoutsidethe hospital.It canbe installedat every hospitalrunningan HTTP-server(with PERLsupportfor CGIs)andclinical workstationswith accessto this server.Useof themaintenancemodulesimplifiesthecustomizationof prescriptionrules,enteralproductsanddrugsto local requirements.

A further stephasbeena reimplementationof VIE-PNN in Java (VIE-PNN 6.0).The whole PNSscheduleis computedat the client sideusinga Java applet.Thiscodeincludesthe currentnutrition rulesand the PNSdataof the previous days.Theclient appletcommunicateswith a dedicatedVIE-PNN server deliveringandtakingover thePNSdata.This versionlookspromisingandsavesevenmoretimebecausedataareenteredonly onthreecomparedto formerlyeightscreens.Becausethestabilityof theJavasolutionis still questionable,thisnew versionhas,however,not beenintroducedinto the daily routine. In addition, the Java implementationonceagainwill makemaintenancea tricky issue.

6 Lessons learned

VIE-PNN is a knowledge-basedsystem(KBS) which solves a time-consumingproblemin daily routine.It is lessthe amountandcomplexity of the knowledgecoveredwhich makes it a success,but its ability to implementpracticalclinicalknowledgein thedaily routine.

Fromthis successstorywehave learnedthefollowing:

A systemcontainingtextbookandclinical knowledgemaybea successevenifphysiciansdohavethatknowledgeathand.OurexperienceshowsthatsuccessfulKBS arenot restrictedto complex domainsof applicationwith very specializedknowledge.A KBS is valuablein thehecticnessof theclinical routinebecauseitimprovestheaccuracy andthequality of care. It is essentialto implementpracticalknowledge.Two examplesarethe knowl-edgeabout the precisionneededfor eachcomponent(expressedin roundingrules),andthe codingof supportmethodsfor patientswherethe total fluid al-lowanceit too small to incorporateall the necessarynutritional components.This problem,normally solved by weak estimations,hasbeenvery elegantlysolvedby amanageablestepwiseapproach.Suchpracticalsolutionsaccountfortheacceptanceanduseof asystem. Explanationfacilitiesareessentialfor establishingconfidencein thesystem,es-pecially in thefirst trials. VIE-PNN createsexplanationsfor all its calculations.

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Theexplanatorypageswereparticularlyofteninspectedby new userswho alsowantedto verify their knowledge. It is necessaryto produceprinted output sheetsusableas part of the medicalrecord.The electronicstorageof all datadoesnot releasefrom the needfor aprintedoutputusedby physiciansandnursesfor manualremarks; Thecontinuouschangeof knowledgeaboutnutritional requirementsrequiresasystemmaintainedby expertphysicians.A KBS will notbeusedin thelong runif maintenanceactionsarerestrictedto knowledgeengineers.In addition,physi-cianswill not trust the systemif the knowledgeis hiddenby some(complex)formalism; Integrationof KBS into clinical softwaresystems(e.g.,PDMS) is a necessityfor wide-spreaduse.Evenlooseintegrationlike usingthesamehardwareasthePDMSis sufficient in thefirst run. However, a strongintegrationof all systemsincludingdataexchangeis thedesirefor thefuture; Finally, never try to install a systemwhich requiresadditionaltime from physi-ciansor nurses.Timesavingsarethekey issuefor thesuccessof systemsin dailyroutineuse.

VIE-PNN is an exampleof a successfulKBS in daily routine use.First of all,it considerablysavesphysicians’time. This is achieved by replacinga complexmanualcomputationby a supportsystemwhich knows aboutclinical prescriptionrules.The knowledgecontainedin VIE-PNN helpsthe physicianto avoid errorsandto maintainthehigh qualitystandardsof neonatalintensivecare.

Acknowledgements

We greatlyappreciatethesupportgivento theAustrianResearchInstituteof Arti-ficial Intelligence(OFAI) by theAustrianFederalMinistry of Education,ScienceandCulture.

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