儿童肠外营养指南：组织因素

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ClinicalNutritionxxx(2018)1-9

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ClinicalNutrition

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ESPGHAN/ESPEN/ESPRguidelinesonpediatricparenteralnutrition:Organisationalaspects

JWL.Puntisa,I.Hojsakb,*,J.Ksiazyk,theESPGHAN/ESPEN/ESPR/CSPENworkinggrouponpediatricparenteralnutrition¹

aTheGeneralInfirmaryatLeeds,Leeds,UK

bChildren'sHospitalZagreb,Zagreb,Croatia

CTheChildren'sMemorialHealthInstitute,Warsaw,Poland

ARTICLEINF0

Articlehistory:

Received29May2018Accepted29May2018

1.Methods

Literaturesearch

Timeframe:publicationsfrom2004untilDecember2017wereconsidered

Typeofpublications:randomizedtrials,observationalstudies(case-controls,prospectivecohortstudies,caseseries,retrospectivedata),meta-analyses,systematicreviews

Keywords:nutritionsupport;nutritionassessment;nutritionteam;nutritionandmonitoring;nutritionalrehabilitation;paren-teralnutritionandfilter;infusionpumps;anthropometryandparenteralnutrition;nutritionandordering

*Correspondingauthor.

E-mailaddress:ivahojsak@(I.Hojsak).

¹ESPGHAN/ESPENVESPR/CSPENworkinggrouponPediatricParenteralNatrition:BRAECGERChristian,UniversityChildren'sHospital,Zurich,Switzerland;BRONSKYJin,UniversityHospitalMotolPrague,Czechkepublis;CAIWe,ShanghaijiaoTongUniversiy.Shangha,China;CAMPOYCristina,DepartmentofPaediatric,schoolofMedicine,UniversityofGranada,Granada,Spain;CARNIELUVirgli,PolytechicUniversityofMarche,Ancona,Italy;DARMAUNDominigue,UniversitedeNantes,Nante,France;DECSITamas,DepartmentofPeditis,UniversityofPecs,Pecs,Hungary;DOMELLoFMagnus,DepartmentofClinicalSciences,Pediatrics,UmeaUniversity,Sweden;EMBLETONNicholas,NewcasteUniversity,NewcastleuponTyne,TheUnitedKingdom;FEWTRELMary,UCLGreatOrmondStetnsituteofChildHealth,London,UK;FIDLERMISNatasa,UniversityMedicalCentreLjubljana,LJubjana,Slovenia;FRANZAxel,UnivesityChildren'sHospital,Tuebingen,Germany;GOULETOlvier,Universitysordonne-Paris-Cite;Paris-DescartesMedicalschoolParis,France;HARTMANCorina.SchneiderChildre'sMedicalCenterofsrael,PetachTikva.IsaelandCarmelMedicalCenter,Haflsrael;HLSusan,GreatOrmondStretHospitalforChildren,NHSFoundationTrustandUCLInstuteofChildHelth,London,UnitedKingdom;HOJSAKIva,Children'sHospitalZagreb,UniversityofZagrebschoolofMedicine,UniversityofJ.StrossmayeSchoolofMedicineOsiek,Croatia;IACOBELUSivi,CHULaReunion,SaintPiere,Fance;JOCHUMFrank,Ev.WaldkrankenhausSpandau,Berli,Germany;JOOSTEN,Koen,DepartmentofPediticsandPediatricSurgery,IntensiveCare,ErasmusMC-SophiaChildren'sHospita,Roterdam,TheNetherlands;KOLACEKSanja.Children'sHospita,UnivesityofZagrebSchoolofMedicine,Zagreb,Croata;KOLETZKOBerthold,kLMU-Ludwig-Maximilians-UniversitätMunich,DrvonHaunerChildren'sHospital,Munich,Germany;KSIAZYKJanusz,DepartmentofPediatis,NutitionndMetabolicDiseases,TheChildre'sMemoralHealthInstitute.Warsaw;LAPLLONNEAlexandre,Paris-DescatesUnivesity,Paris,France;LOHNERSzimontt,DepartmentofPediatics,UniversityoPecs,Pec,Hungary;MESOTENDiete,KULeuven,Leuven,Belgium;MHALMIKrisztina,DepartmentofPediatrics,UniversityofPecs,Pecs,Hungary;MIHATSCHWaterA.UImUniversity,UIm,andHeiosHospital,Pforzheim,Germany;MIMOUNIFancis,Departmentofediatrics,DvisionofNeonatology,TheWifChildrer'sHospita.theShareZedekMedicalCenterJerusalem,andtheTelAvivUniversity,TelAviv,Israel;MOLGAARDChrstan,DepartmentofNutition,ExerciseandSports,UniversityofCopenhagen,andPaediatricNautitionUni,Rigshospitalet,Copenhagen,Denmark;MoOLTUSiselJ.OsoOUnivesityHospital,oso,Norway;NOMAYOAntoni,Ev.WaldkrankenhausSpandau,Berlin,Germany;PCAUDjeanCharles,LaboratoireCarMEN,CludeBernardUnivesityLyon1,Hopitalcroixrousse,Lyon,France;PRELChristine,LMU-Ludwig-Maximilians-UniversititMunch,DrvonHaunerChidren'sHosptal,Munich,Cermany;PUNTISJohn,TheCenerllnfirmaryateds,Leds,UK;RSKINArieh,BnaiZionMedicalCente,RappaportFacultyofMedicne,Techmion,Haif,Israel;SAENZDEPIPAONMiguel,DepartmentofNeonatology,LaPazUniversityHospital,ReddeSaludMaternolnfantilyDesarolo-SAMID,UniversidadAutónomadeMadrid,Madid,Spain;SENTERREThibault,CHUdeliege,CHRdelacitadlle,UniversitedeLige,Belgiun;SHAMIRRanan,schneiderChildre'sMedicalCenterofsrael,PetachTikva,Israel;TeAvivUniversity,TeAviv,srael;SIMCHOWITZVenetia,GreatormondSretNHSTrust,London,TheUnitedKingdom;SzIANYIPeter,CeneralUniversityHospital,FirstFacultyofMedicine,CharlesUniversityinPrague,CzechRepublic;TABBERSMeritM.,EmmaChildrer'sHospital,AmsterdamUMC,Amsterdam,TheNetherlands;VANDENAKKERChrisH.B,EmmaChidren'sHospital,AmsterdamUMG,Amsterdam,TheNetherlands;VANCGOUDOEVERJohannesB.,EmmaChildren'sHospital,AmsterdamUMC,Amsterdam,TheNetherlands;VANKEMPENAne,OLVG,Amsterdam,theNetherlands;VER-BRUGGENSascha,DepartmentofPediatricsandPediatricSurgery,IntensiveCare,ErasmusMC-SophiaChildren'sHospital,Roterdam,TheNetherlands;wUJiang,XinHuaHospital,Shanghai,China;YANWeihui,DepartmentofGastroenterologyandNutition,XinhuaHospital,chooofMedicine,ShanghaijaoTongUniversity,Shanghai,China.

/10.1016/j.clnu.2018.06.953

0261-5614/02018EuropeanSocietyforClinicalNutritionandMetabolism.PublishedbyElsevierLtd.Allrightsreserved.

Pleasecitethisarticleinpressas:PuntisJWL-gIWL,etal,ESPGHAN/ESPEN/ESPRguidelinesonpediatricparenteralnutrition:Organisational

aspects,ClinicalNutrition(2018),

/10.1016/j.clnu.2018.06.953

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2JWL.Puntisetal./ClinicalNutritionxxx(2018)1-9

Table:Recommendationsonorganizationalaspectsofparenteralnutrition

R11.1

R11.2

R11.3

R11.4

R11.5

R11.6

R11.7

R11.8

R11.9

R11.10R11.11R11.12

R11.13R11.14R11.15R11.16

R11.17R11.18R11.19

Supervisionofnutritionalsupportinintestinalfailuremaybeprovidedbyamultidisciplinarynutritionalsupportteam(LoE2-,RG0,strongrecommendationfor)

AccurateanthropometricsandthoroughclinicalevaluationofpatientsreceivingPNmaybeundertakenbyaskilledpractitioner(GPP,strongrecommendationfor)

Thefrequencyoflaboratoryassessmentmaybebasedonpatientscinicalcondition(fromoncedailyto2-3timesperweek)(LOE4,RG0,strongrecommendationfor)

AllPNsolutionsmaybeadministeredwithacurateflowcontrol;theinfusionsystemshouldbeunderregularvisualinspection;peripheralinfusionsshouldbecheckedfrequentlyforsignsofextravasationorsepsis;thepumpshouldhavefreflowpreventionifopenedduringuse,andhavelockablesttings(GPP,strongrecommendationfor)

PNsolutionsmaybeadministeredthroughaterminalflterlipidemulsions(orall-in-onemixes)canbepassedthroughamembraneporesizeof1.2-1.5μm;aqueoussolutionscanbepassedthrougha0.22μmflter(GPP,strongrecommendationfor)

PNsolutionsfortheprematurenewbornsshouldbeprotectedagainstlightinordertopreventgenerationofoxidants(LoE1-,RCB,strongrecommendation

for)

CyclicalPNmaytartoncepatientsareinastablecinicalconditionandcanmaintainnormoglycaemiaduringaperiodwithoutPNinfusion(GPP,strongrecommendationfor)

Inordertopreventhypo/hyperglycaemiainfusionratemaybetaperedupgraduallyduringthefirst1-2handtapereddownduringthelast1-2hofinfusionwhencyclicPNisadministered(GPP,strongrecommendationfor)

Completeenteralstarvation(ie.TPN)maybeavoidedbygivingsomeenteralfeedwheneverpossible,evenifonlyaminimalamountistolerated(GPpstrongrecommendationfor)

Whenincreasingenteralfeed,onlyonechangeatatimemaybemade,toassesstolerance(GPP,strongrecommendationfor)

Insevereintestinalfailure,feedvolumesmaybeincreasedslowly,accordingtodigestivetolerance(GPP,strongrecommendationfor)

Enteralfeedingmaybeintroducedasaliquidfeedinfusedcontinuouslybytubeover4-24hperiods,usingavolumetricpump(GPP,conditional

recommendationfor)

Bolusliquidfeedmaybegivenviafeedingtube,orbymouthassipfeediftolerated(GPP,conditionalrecommendationfor)

Childrenwhorapidlyrecoverintestinalfunctionmaybeweanedstraightontonormalfood(GPP,conditionalrecommendationfor)

Innewbornsandinfantswithintestinalfailurebreastmilkmaybetheenteralfeedoffrstchoice(GPP,strongrecommendationfor)

Ibreastmilkisnotavailable,thechoiceofsubstitutecanbebasedonclinicalcondition;inearlyinfancyandseverellnessitisreasonabletostartwith

elementalformula,switchingtoextensivelyhydrolysedandthentopolymericfeeds(GPP,strongrecommendationfor)Enteralfeedmaybegivenatnormalconcentrations(i.e.notdiluted)(GPP,conditionalrecommendationfor)

PNshouldbereducedinproportionto,orslightlymorethantheincreaseinEN(GPP,conditionalrecommendationfor)Ifachosenweaningstrategyfails,tryagainmoreslowly(GPP;conditionalrecommendationfor)

Language:English

Search:Searcheswereperformedinthreestages.First,allthetitleswiththerelevantkeywordswereretrievedbytheCochraneCollaborationDepartmentfromBudapest,whoalsoperformedthefirstreduction.MembersoftheWorkingGroupsubsequentlyreadallthetitlesandabstracts,andselectedpotentiallyrelevantones.Thesewereretrievedandfullarticleswereassessed.

2.Orderingandmonitoringparenteralnutritioninhospital

2.1.Introduction

Thepurposeofparenteralnutrition(PN)istocorrectorpre-ventnutritionaldeficiencieswhenadequateenteralnutritionisprecludedbyimpairmentorimmaturityofgastrointestinalfunc-tion.HavingidentifiedapatientinneedofPN,theprocessoforderingandmonitoringisaimedatensuringsafeandeffectivenutritionalsupport.ProvisionofPNshouldbepartofanoverallnutritionalcareplanthatincludesdetailednutritionalassess-ment.Nutritionalgoalsshouldbeset,andanestimatemadeoftheprobabledurationofPN.Thewholeprocessisdynamic:ongoingnutritionalsupportshouldreflectchangesinnutritionalandclinicalstatusandbeoverseenbyamultidisciplinarynutrition

team.

2.2.Nutritionsupportteams

R11.1

Supervisionofnutritionalsupportinintestinalfailuremaybe

providedbyamultidisciplinarynutritionalsupportteam

(LoE2-.RG0.strongrecommendationfor,strongconsensus)

Amultidisciplinarynutritionsupportteam(NST;e.g.doctor,nurse,dietitian/nutritionist,pharmacist,etc.)hasanimportantroleinpromotingandcoordinatingoptimumnutritionalcare,educating

staff,developingguidelines,promotingresearch[1](LoE2-)andreducinginappropriateuseofPN[2](LoE2-).Ateamapproachtonutritionalsupportwasassociatedwithareductionincatheter

relatedbloodstreaminfectionratesinanumberofdifferentstudiesinvolvingadultpatients[3-8](LoE2-).Stafftrainingbyanutritionnursereducestheprevalenceofcathetersepsisininfants[9](LoE2-).Otheraspectsofqualityofcaresuchasmonitoringofnutri-tionalstatusandassessmentofrequirements[8]areimprovedbyamultidisciplinaryapproach[8,10](LoE2-).Savingsmadecanmorethanjustifytheappointmentofspecialisedstaffsuchasnutritionnurseanddietitian[11](LoE2-).ExperienceinpaediatricintensivecaresuggestsintroductionofaNSTbothdecreasesinappropriateuseofPNinfavourofenteralfeedingandreducesmortality[12](LoE2-).Inothersettingsitmaybedifficulttoclearlydocumentimprovementsinnutritionalmanagement,sometimesbecauseofclinicalfactorsthatcannotbeeasilyovercome[13].Implementa-tionofaNSThasbeenrecommendedbytheESPGHANCommitteeonNutrition[14],andteamscanplayanimportantroleinraisingawarenessoftheimportanceofnutritionalmanagementthroughoutthepaediatricdepartment[15].OutcomeforpatientswithPNdependentintestinalfailure(IF)appearstobeimprovedbymanagementunderamultidisciplinaryteam[16](LoE2-)and

suchanapproachistobeencouraged[17-21].ANSTisalsoessentialforfacilitatingandsupportinghomeparenteralnutrition[22,23].

2.3.Nutritionalassessment

R11.2Accurateanthropometricsandthoroughclinicalevaluationof

patientsreceivingPNmaybeundertakenbyaskilledpractitioner(GPP,strongrecommendationfor,strongconsensus)

R11.3Thefrequencyoflaboratoryassessmentmaybebasedonpatient's

clinicalcondition(fromoncedailyto2-3timesperweek)(LoE4,RG0,strongrecommendationfor,strongconsensus)

Pleasecitethisarticleinpressas:PuntisJWL-gIWL,etal,ESPGHAN/ESPEN/ESPRguidelinesonpediatricparenteralnutrition:Organisational

aspects,ClinicalNutrition(2018),

/10.1016/j.clnu.2018.06.953

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JWL.Puntisetal./ClinicalNutritionxxx(2018)1-93

AmultidisciplinaryNSTshouldoverseetheprocessofPN[24]andpatientsberegularlynutritionallyassessed.Thisprovidesabaselineofnutritionparameters,determinesnutritionriskfactors,identifiesspecificnutritiondeficits,establishesnutritionneedsforindividualpatients,andidentifiesfactorsthatmayinfluencetheprescribingandadministeringofnutritionsupporttherapy[25].Nutritionalassessmentisdividedintoclinicalexamination,anthropometry,laboratoryindices,andassessmentofdietaryintake[24].

2.3.1.Clinicalexamination

Clinicalexaminationgivesanimportantoverallimpressionofhealthandincludesthegeneralappearanceandactivitylevelofthepatient[24].Monitoringparametersincludevitalsignsandthor-oughphysicalassessment,togetherwithclinicalindicatorsoffluidandnutrientexcessordeficiency[25].

2.3.2.Anthropometry

Thereshouldbeaccuratemeasurementofanthropometricvar-iablessuchasweight,length/heightandheadcircumference[24,26].Anthropometricmeasuresarereportedwithreferencetopopulationdata,andplottedonappropriategrowthcharts.Thesechartsinclude,inchildren<36monthsofage:length-for-age,weight-for-age,headcircumference-for-age,andweight-for-length,andinchildrenages2-18years:standingheight-for-age,weight-for-age,andbodymassindex(BMI)-for-ageandBMIcen-tile(LoE2+)[27].Measuresareusuallyexpressedaspercentilesorstandarddeviationscores(SDS).SDSallowchangesovertimetobedetectedmoreeasilythanwithpercentiles,whichdonotsoreadilyrevealtheprecisedegreeofdeviationfrompopulationnorms[24]. Anthropometricmeasureshavesomelimitations,forexample,severeillnessisoftenassociatedwithfluidretentionandoedemamakingweightmeasurementsunreliable.Therefore,anassessment

offluidintakeandoutputshouldaccompanyanevaluationofweightgaintodeterminewhetherthesourceoftheweightisanincreaseinfluidorleanbodymass[25].Alternativeanthropometrictoolshavebeenproposedforassessingmalnutritioninpatientsaffectedbylowerextremityoedema,ascites,steroidtreatmentorlargesolidtumourmass.Midupperarmcircumference(MUAC)maybeabetterindicatorthanweightforclassificationofacutemalnutrition(LoE2+)[26-29].MUACtogetherwithtricepsskinfoldthicknessallowscalculationofmidarmfatandmusclearea,givinganinsightintobodycomposition[24].Measurementsshouldbeundertakenbyatrainedandexperiencedindividualsuchasdieticianornutritionsupportnurse,usingstandardizedtechniques.Serialmeasurementsshowchangesovertimeandthereforepro-videadynamicpicture.Thefrequencyofmonitoringwilldependongestationalage,postnatalage,underlyingdisease,severityofillness,degreeofmalnutrition,andlevelofmetabolicstress[25].

2.3.3.Laboratoryassessment

BesideslaboratoryinvestigationofbaselinemetabolicstatusbeforeorderingPN,somelaboratorydatacanbeusedasamarkerofnutritionalassessment.Routineelectrolyte,mineral(calcium,phosphorusandmagnesium),triglycerideandserumureadeter-minationhelptodeterminenutritionaldeficiencies(LoE2+)[30].Somelaboratorytestswhichrelatetovisceralproteinconcentra-tions(e.g.haemoglobin,totallymphocytecount)helpintheiden-tificationofmalnutrition(LoE2+)[31].Proteinswiththeshorterhalf-life(i.e.pre-albuminorretinol-bindingprotein)whensequentiallyassessedreflectimprovingnutritionalstatusbetterthanalbumin(LoE2+)[32].Inhospitalisedpatients,albuminismostcommonlylowaspartofanacutephaseresponsetoinflammationandredistributionofproteinsothathypo-albuminaemiashouldnotbeattributedtomalnutrition.Nosingle

proteinisidealasanindicatorofnutritionalstatussincetheyareallaffectedbyothernon-nutritionalphysiologicalandpathologicstates[24].Otherlaboratorytests,suchasthenitrogenexcretion,nitrogenbalanceandplasmaaminoacidprofilecanhelpcharac-terizeproteindeficit[33]butarenotcommonlyusedinclinicalpractice.Serumvitaminandtraceelementconcentrationsshouldbeevaluatedinlong-termPNdependentpatients(LoE4)[25].Dailymonitoringmayberequiredfornewborns,infants,criticallyillpatients,thoseatriskofrefeedingsyndrome,patientstransitioningbetweenPNandenteralfeeding,orthosethathaveexperiencedcomplicationsassociatedwithnutritionaltherapy(LoE4)[25].Inclinicallystablechildren,measurementsmayberepeated2-3timesperweek(LoE4)[24].

2.3.4.Dietaryintake

Nutritionalassessmentmustincludeestimatesofdietaryandfluidintake(oral,enteral,andparenteral),output(urine,gastroin-testinallosses),andarecordofgastrointestinalsymptoms.Infor-mationshouldbesoughtwithrespecttoreligiousrestrictionsandfoodpreferencesoraversions[24,25].

2.4.PNordering

AcceptedgoalsforPNincludepreventionorcorrectionofweightloss,andmaintenanceofnormalgrowth.AnyprofessionalsorderingPNshouldbetrainedinitsindications,complicationsandadministration[34]andthewholeprocessofPN(prescribing,compounding,deliveringandmonitoring)standardizedasfaraspossibleinordertodecreaseriskandpromoteeffectiveness[35-37].Protocoldrivenimplementationofnutritiontherapymayleadtobetteroutcomesandhas,forexample,beenshowntohelppreserveleanbodymassinintensivecarepatients[38,39](LoE3).Electronicorderingsystemscanreducetheriskofprescriptioner-rors[40]anduseofastandardisedelectronicPNorderingsystemoranordertemplateasaneditableelectronicdocumentisrecom-mended[41].Theprocessoforderingrequiresveryclosecollabo-rationbetweenphysician,clinicalpharmacistanddietitian.Insomecentres,prescribingofPNhasbeenpassedfromdoctorstoanexperiencedandtrainedpharmacistworkingwiththeNST[42].ReferencetoestablishedguidelinesfororderingandmanagingPNencouragesappropriateselectionofpatientsandtailoringpre-scriptionstotheparticularneedsofindividuals[24].ClinicalpracticeguidanceasanaidememoirecanbeincludedonPNorderingforms[43].ThewholeprocessofPNrequiresauditandcriticalscrutinysincelifethreateningerrorsmayoccurduringprescribing,transcription(conversionofprescriptiontovolumesofadditivesinpharmacy),dispensing,deliverytowards,andduringtheadministrationprocess(incorrectinfusionrates)[44].

2.5.Infusionequipmentandinlinefilters

R11.4

R11.5

R11.6

AllPNsolutionsmaybeadministeredwithaccurateflowcontrol;theinfusionsystemshouldbeunderregularvisualinspection;

peripheralinfusionsshouldbecheckedfrequentlyforsignsofextravasationorsepsis;thepumpshouldhavefreeflow

preventionifopenedduringuse,andhavelockablesettings(GPP,strongrecommendationfor,strongconsensus)

PNsolutionsmaybeadministeredthroughaterminalfilter:lipidemulsions(orall-in-onemixes)canbepassedthroughamembraneporesizeof1.2-1.5μm;aqueoussolutionscanbe

passedthrougha0.22μmfilter(GPP,strongrecommendationfor,strongconsensus)

PNsolutionsfortheprematurenewbornshouldbeprotectedagainstlightinordertopreventgenerationofoxidants(LoE1-,RGB,strongrecommendationfor,strongconsensus)

Pleasecitethisarticleinpressas:PuntisJWL-gIWL,etal,ESPGHAN/ESPEN/ESPRguidelinesonpediatricparenteralnutrition:Organisational

aspects,ClinicalNutrition(2018),

/10.1016/j.clnu.2018.06.953

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4JWL.Puntisetal./ClinicalNutritionxxx(2018)1-9

Oneofthegreatesthazardstopatientsduringadministrationofintravenousnutritionarisesfromtheriskoffreefloworpoorratecontroloftheinfusion.Tothepotentialrisksoffluidoverloadandheartfailureareaddedcomplicationssuchashyperglycaemia,hyperkalaemiaandhyper-triglyceridaemia.Amoderninfusionpumpwiththecapabilitytoaccuratelydeliveratlowflowratesshouldbeusedwheneverpossible[45,46](LoE4).Alarmfunctionsareessential,butsensitivityisoftenlimitedatlowratesofflow.Theabilityofchildrentolearntomanipulatedevicesandinterferewithsettingsshouldnotbeunderestimated.Ifpumpsarenotavailable,theuseofportable,batterypowereddropcountingdevicescanprovideeffectivewarningoffreeflowconditions.New'smartpumps'canbeprogrammedsothatstartingandfinishinginfusionratesincreaseanddecreaserespectivelywhendeliveringcyclicalPNinordertopreventhyper-andhypoglycaemia.

PNsolutionscontainparticulatematter[47](LoE2-)andbiochemicalinteractionscanleadtochemicalprecipitatesandemulsioninstability;theyalsoactasamediaformicrobiologicgrowthshouldcontaminationoccur.Particulatesininfusionfluidplayaroleincausingphlebitiswithperipheralvenousinfusion[48](LoE2+).Particlescanalsoharmthepulmonaryendotheliumandprovokeagranulomatouspulmonaryarteritis[47](LoE3).Theroutineuseofin-linefiltrationhasbeenadvocatedinchildrenreceivinglargevolumeparenterals,andarandomisedtrialinapaediatricintensivecareunitshowedthatfilterswereassociatedwithasignificantreductioninoverallcomplicationrate,areduc-tioninsystemicinflammatoryresponsesyndrome,andareductioninlengthofstay[48](LoE1++).Incriticallyillchildrentherefore,itappearsthatinfusedparticlesmayimpairthemicrocirculation,inducesystemichypercoagulabilityandinflammation[49](LoE1++).ACochranereviewofinlinefiltrationinthenewbornfoundfourstudies(lowqualityevidence)thatshowednobenefitsfromuseofflters[50](LoE2-).Someendotoxinretaining0.22μmfil-tersallowcostsaving,throughextendeduseoftheadministrationset.Withtheappropriatefilters,givingsetscanbeusedfor

72-96h.Manysolutionsarestableforextendedhang-timesbutexplicitstabilityadviceshouldbesoughtfromthemanufactureroracompetentindependentlaboratory.Filterblockageismorelikelytoindicateaproblemwiththesolutionthanthefilter,andmustbethoroughlyinvestigated.

IntravenousPNsolutionsthatarenotphotoprotectedgenerateoxidants,whichareharmfultocells.Prematureinfantsinparticularfaceanimbalancebetweenhighoxidantloadsandimmatureantioxidantdefences.Ameta-analysisfoundthatmortalityinpa-tientswithlightprotectedPNwashalfthatinthelightexposedgroup[51](LoE1+).

2.6.CyclicalPN

R11.7

CyclicalPNmaystartoncepatientsareinastableclinical

R11.8

conditionandcanmaintainnormoglycaemiaduringaperiodwithoutPNinfusion(GPP,strongrecommendationfor,

strongconsensus)

Inordertopreventhypo/hyperglycaemiainfusionratemaybe

taperedupgraduallyduringthefirst1-2handtapereddown

duringthelast1-2hofinfusionwhencyclicPNisadministered(GPP,strongrecommendationfor,strongconsensus)

PNisalwaysintroducedasacontinuousinfusionover24h.OncepatientsaretoleratingafullamountofPNandarestablebothclinicallyandbiochemically,theinfusiontimecanbegraduallyreducedbyhourlydecrementsoveraperiodofdays/weekswithfrequentassessmentofvolume/ratetoleranceandbloodglucose[52,53].This'cycling'ofPN(discontinuingnutrientinfusionforaperiodtimeeachday)shouldbeestablishedwhileinhospitalso

thattolerance/safetycanbeconfirmedpriortodischargehome[53].CyclicalPNhasaprotectiveeffectagainstintestinalfailureassociatedliverdisease(IFALD)[54],andisgenerallyaprerequisiteforhomePNsincedaytimefreedomfrominfusionpumpsimprovesqualityoflife.SeveralstudieshaveshownmetabolicdifferencesbetweencyclicalandcontinuousPN[24,55]whilenitrogenbalanceissimilar.Inyoungchildren(<2yr)abruptdiscontinuationofPNinfusionmaycauseshypoglycemia;inolderchildrentheriskismuchlower[55](LoE2++).CalciumlossincreasesduringinfusionofcyclicalPNbutnottotaldailylossofcalcium,phosphorus,magnesium,orvitaminDcomparedwithcontinuousinfusion[55](LoE2++).

ThereissomeevidencethatcyclingPNcanpreventcholestasis[56-58](LoE2-),althoughtheriskwasnotdecreasedinVLBWneonateswhenonlytheaminoacidcomponentofPNwascycled[59](LoE1-).Childrenalmostalwaystoleratenighttimeinfusionover10-14h[24].TheoptimaltimetoinitiatecyclicalPNisun-known,andcyclingmaynotbetoleratedinyounginfantsduetoimmaturegluconeogenesis,limitedglycogenstores,andlargeglucosedemands[56].However,thereisevidencethatcyclingofPNissafeeveninclinicallystablenewborns[56,57](LoE2-).

Cycletimemaybeshortenedby1-2heachoreveryotherdayuntilthedesired/toleratedgoalfordurationofinfusionisachieved(LoE4)[53].Ininfantswithpoorenteraltolerance,infusiontimeshouldbedecreasedin1hsteps.ThemostcommonadverseeventsassociatedwithcyclicalPNarehyperglycemia,andrespiratorydistressduetotheincreaseintherateofdextroseandfluidinfusion[53,55];abruptdiscontinuationofinfusionmayalsoprecipitatehypoglycaemia[55].Inordertopreventtheseadverseevents,useofaninfusionpumpthatallowsagradualincreaseininfusio