Gut rest strategy and trophic feeding in the acute phase of ...

Trophic feeding may be an organ-protective strategy in critically ill patients, similar to ventilation with a low tidal volume, restrictive fluid resuscitation ... Skiptomaincontent Accessibilityhelp Weusecookiestodistinguishyoufromotherusersandtoprovideyouwithabetterexperienceonourwebsites.Closethismessagetoacceptcookiesorfindouthowtomanageyourcookiesettings. Cancel Login × × Home OnlysearchcontentIhaveaccessto Hostname:page-component-5bddbd6dd8-wlmbb Totalloadingtime:1.544 Renderdate:2022-08-25T05:24:00.164Z Hasdataissue:true FeatureFlags:{ "shouldUseShareProductTool":true, "shouldUseHypothesis":true, "isUnsiloEnabled":true, "useRatesEcommerce":false, "useNewApi":true } hasContentIssuetrue Home>Journals>NutritionResearchReviews>Volume32Issue2>Gutreststrategyandtrophicfeedingintheacute...English Français NutritionResearchReviewsArticlecontentsAbstractIntroductionGastrointestinaldysfunctionintheacutephaseofcriticalillnessEnteralnutritionintheacutephaseofcriticalillnessAcutegastrointestinalinjuryandenteralnutritionGutreststrategyincriticallyillpatientsConclusionsAuthorORCIDsReferencesGutreststrategyandtrophicfeedingintheacutephaseofcriticalillnesswithacutegastrointestinalinjury PublishedonlinebyCambridgeUniversityPress:  28March2019DongZhang,HongxiangLi[Opensinanewwindow],YutingLi andLaiQuShowauthordetailsDongZhangAffiliation:IntensiveCareUnit,FirstHospitalofJilinUniversity,71XinminStreet,Changchun,People’sRepublicofChina HongxiangLi*Affiliation:IntensiveCareUnit,FirstHospitalofJilinUniversity,71XinminStreet,Changchun,People’sRepublicofChina YutingLiAffiliation:IntensiveCareUnit,FirstHospitalofJilinUniversity,71XinminStreet,Changchun,People’sRepublicofChina LaiQuAffiliation:IntensiveCareUnit,FirstHospitalofJilinUniversity,71XinminStreet,Changchun,People’sRepublicofChina * *Correspondingauthor:HongxiangLi,[email protected] Figures Metrics ArticlecontentsAbstractIntroductionGastrointestinaldysfunctionintheacutephaseofcriticalillnessEnteralnutritionintheacutephaseofcriticalillnessAcutegastrointestinalinjuryandenteralnutritionGutreststrategyincriticallyillpatientsConclusionsAuthorORCIDsReferencesSavePDFSavePDF(0.38mb)ViewPDF[Opensinanewwindow]SavetoDropboxSavetoGoogleDriveSavetoKindleShareCiteRights&Permissions[Opensinanewwindow]AbstractCriticallyillpatientsfrequentlysufferfromgastrointestinaldysfunctionastheintestineisavulnerableorgan.Incriticallyillpatientswhorequirenutritionalsupport,thecurrentguidelinesrecommendtheuseofenteralnutritionwithin24–48handadvancingtowardsoptimalnutritionalgoalsoverthenext48–72h;however,thismaybecontraindicatedinpatientswithacutegastrointestinalinjurybecauseoveruseofthegutintheacutephaseofcriticalillnessmayhaveanadverseeffectontheprognosis.Weproposethattrophicfeedingafter72h,asapartialgutreststrategy,shouldbeprovidedtocriticallyillpatientsduringtheacutephaseofillnessasanorgan-protectivestrategy,especiallyforthosewithacutegastrointestinalinjury.KeywordsAcutegastrointestinalinjuryEnteralnutritionTrophicfeedingGutreststrategy Type ReviewArticle Information NutritionResearchReviews , Volume32 , Issue2,December2019,pp.176-182DOI:https://doi.org/10.1017/S0954422419000027[Opensinanewwindow] CreativeCommons ThisisanOpenAccessarticle,distributedunderthetermsoftheCreativeCommonsAttribution-NonCommercial-ShareAlikelicence(http://creativecommons.org/licenses/by-nc-sa/4.0/),whichpermitsnon-commercialre-use,distribution,andreproductioninanymedium,providedthesameCreativeCommonslicenceisincludedandtheoriginalworkisproperlycited.ThewrittenpermissionofCambridgeUniversityPressmustbeobtainedforcommercialre-use. Copyright ©TheAuthors2019 IntroductionIncriticallyillpatients,theintestineissusceptibletoinjury,andgastrointestinal(GI)injuryiscommon(ReferenceReintam,ParmandKitus1).Evidencesuggeststhatanestimated50%ofpatientshaveenterocytedamageatadmissiontotheintensivecareunit(ICU),andGIsymptomsoccurinapproximately62%ofpatientsintheICU(ReferencePiton,BelonandCypriani2).TheWorkingGrouponAbdominalProblems(WGAP)oftheEuropeanSocietyofIntensiveCareMedicine(ESICM)proposedasetofdefinitionsandgradingsystemforGIdysfunction.TheydefinedacuteGIinjury(AGI)asmalfunctioningoftheGItractincriticallyillpatientsduetotheiracuteillness(ReferenceReintamBlaser,MalbrainandStarkopf3).StudieshaveshownthatcriticallyillpatientswithAGIexperiencehighermortalityratesascomparedwithpatientswithoutAGI(ReferenceReintam,ParmandKitus4–ReferenceLi,ZhangandWang6).AsoneoftheGItractfunctionsistoingest,digestandabsorbnutrientsfromfoodandwater,AGIcanmanifestasfeedingintolerance(definedasintolerancetoenteralnutrition(EN)whereinintakeof≥20kcal(≥84kJ)/kgbodyweightperdcannotbeachievedwithin72hoffeedingattemptsviatheenteralroute)(ReferenceReintamBlaser,MalbrainandStarkopf3).However,clinicalpracticeguidelinesoftheESICMrecommendinitiationofearlyEN(EEN)within24–48hofICUadmission,advancingtowardsoptimalnutritionalgoalsoverthenext48–72h(ReferenceBlaser,StarkopfandAlhazzani7).Therefore,somequestionsremainregardingtheuseofnutritionalsupportincriticallyillpatients:(1)IsENsafeincriticallyillpatientswithAGI?(2)Willthesepatientsbenefitfromusingtheinjuredorgan?(3)DoestheGItractofcriticallyillpatientsrequire‘rest’fortherecoveryofGIfunction?Thepresentreviewseekstoexploreanswerstothesequestionsbasedonthecontemporarybodyofevidence.GastrointestinaldysfunctionintheacutephaseofcriticalillnessTheacutephaseofcriticalillnesslastsforatleast7d(ReferenceStahel,FlierlandMoore8),andhasbeenvariouslydefinedinclinicaltrialsasthefirstfewdaysafteronsetofillness,orthefirst5–7dafteradmissiontotheICU(ReferenceCasaer,MesottenandHermans9–11).Theacutephaseisusuallycausedbyinjury(shock,traumaorinfection)(ReferenceStahel,FlierlandMoore8),whichimposesstressonthebodyduetocompensatorypathophysiologicalchangesinanattempttorestorestabilitywithintheinternalenvironment(ReferenceStratakisandChrousos12).Theadaptiveresponsetoacutecriticalillnessincludesthemetabolicresponsetostress(ReferencePreiser,vanZantenandBerger13),whichinvolvesneuroendocrine,inflammatoryandimmunemechanismsthatcauserapidcatabolismandinduceresistancetoanabolicsignals,includinginsulin.Thisprioritisesthedeliveryofglucosetoorgansthatcannotuseothersubstratesasenergy(ReferenceLena,KalfonandPreiser14,ReferencePreiser,IchaiandOrban15).Theseadaptivechangesarecomplexandsequentialandhavelargelybeenabarriertothesuccessfuldevelopmentoftargetedinterventionstomodulatethemetabolicresponsetocriticalillness(ReferencePreiser,IchaiandOrban15).Inaddition,excessiveorinadequateadaptiveresponsesevokedbyintensivestress(ReferenceStratakisandChrousos12)canhaveanimpactontheGItract,includingnegativeeffectongutmotility(ReferenceGué,PeetersandDepoortere16,ReferenceChrousos17),mucosalbloodflow(ReferenceRichardson,NortonandSales18)andincreasedmucosalpermeability(ReferenceWallon,YangandKeita19)throughneuroendocrineregulation(ReferenceKonturek,BrzozowskiandKonturek20).Inparticular,theadaptiveresponsetoacutestressalsoincludesanadrenergicresponsewiththeconsequentincreaseincatecholaminelevelswhichmaycauseconstrictionofGIvesselsanddecreaseintestinalbloodflow(ReferenceHalter,PflugandPorte21).Inadditiontoendogenousregulation,exogenouscatecholaminesadministeredtotreatshockmayalsodivertbloodflowawayfromthemesentericcirculationanddecreasemicrovascularperfusioninthegut(ReferenceKrejci,HiltebrandandSigurdsson22).GIbloodflowisreducedinsomecriticallyillpatientsdespitetreatmentwithfluidreplacementandinterventionstonormalisebloodpressureandcardiacfunction(ReferenceChapman,FraserandVozzo23).Moreover,intensevasoconstrictionandhypoperfusionoftheintestineshavebeenshowntopersistduringearlysepsiseveninpatientswithnormalbloodpressure(ReferenceHinshaw24).DecreasedGIbloodflowinducesup-regulationofapoptosisanddecreasesproliferationofsmallbowelmucosalcells,whichleadstothinningofthegutmucosaanddecreaseinabsorptivesurfaceofthesmallbowel(ReferenceChung,EversandTownsend25).Withcontinueddiseaseprogression,tissueoedema,endothelialinjury(26)andcapillaryleakingoccurinthegut(ReferenceVerburgh,Reintam-BlaserandKirkpatrick27).Theseinjuriesresultinimproperdigestionandabsorption(ReferenceReintamBlaser,MalbrainandStarkopf3),impairmentoftheintestinalbarrier(ReferenceLi,ChenandHuo28)anddysregulationoftheintestinalmicrobiota(ReferenceLankelma,vanVughtandBelzer29).Thesymptomprofileofimproperdigestionandabsorptionischaracterisedbytemporaryself-limitingGIsymptoms,whichprogresstothefeedingintolerancesyndromeasGIdysfunctionbecomesmoresevere(ReferenceReintam,ParmandKitus1,ReferenceReintamBlaser,MalbrainandStarkopf3).Small-intestinalmucosalintegritymayalsobecompromisedincriticallyillpatients,leadingtoincreasedintestinalpermeability,especiallyinpatientsintoleranttoEN(ReferenceBurgstad,BesankoandDeane30).Furthermore,criticalillnessaltersthegutmicrobiota;thegutmicrobiotaofcriticallyillpatientsischaracterisedbylowdiversity,lowabundanceofkeycommensalgeneraandovergrowthofasinglebacterialgenus(ReferenceLankelma,vanVughtandBelzer29)(Fig.1).Dysbiosisofthegutmicrobiotamayresultinorgandysfunction(ReferenceJacobs,HaakandHugenholtz31),andshouldbepartoftheevaluationofGIfunctioninthefuture.Thegutmicrobiomehaslargepotentialasafuturetherapeuticordiagnostictarget.However,currentevidenceonmicrobiota-targetedtherapiesincriticalillnessremainsunclear(ReferenceJacobs,HaakandHugenholtz31).Fig.1.Acutegastrointestinalinjuryincriticallyillpatients.Acutegastrointestinalinjurymanifestsasimproperdigestionandabsorption(3),impairmentoftheintestinalbarrier(28)anddysregulationoftheintestinalmicrobiota(29).Improperdigestionandabsorption:enteralfeedingisimpactedwhatevertheclinicalreason(vomiting,highgastricresiduals,diarrhoea,gastrointestinalbleedingorpresenceofentero-cutaneousfistulas)(3).Impairmentoftheintestinalbarriermeansincreasedintestinalpermeability(28).Dysregulationoftheintestinalmicrobiotaischaracterisedbylowdiversity,lowabundanceofkeycommensalgeneraandovergrowthofonebacterialgenus.Inthefigure,highgastricresidualsindicateimproperdigestionandabsorption;impairmentoftheintestinalbarrieranddysregulationoftheintestinalmicrobiotaarenotidentifiedwellduetotheshortageofevaluationtools(3).TheESICMWGAPclassificationofAGIincriticalillnessismainlybasedonthedegreeofimpairmentofdigestionandabsorptionfunctions(ReferenceReintamBlaser,MalbrainandStarkopf3,ReferenceVerburgh,Reintam-BlaserandKirkpatrick27).AGIgradeIreferstodevelopmentofnewGIsymptoms(suchasvomiting,gastricresidualvolume,diarrhoea,GIbleeding,paralysisoflowerGItract,orabnormalbowelsounds),whicharerelatedtoaknowncauseandperceivedastransient(riskofdevelopingGIdysfunctionorfailure).LackofimprovementinthesesymptomsandnochangesinthegeneralconditionaregradedasAGIgradeII(GIdysfunction).AGIgradeIIisanindicationforintervention(forexample,prokinetics,postpyloricfeeding)torestoreGIfunction.PersistenceofGIsymptomsorworseningofmultipleorgandysfunctionsyndromeandlackofimprovementinenteralfeedingareclassifiedasAGIgradeIII(GIfailure);thisconnotesastagewhereininterventionscannotrestoreGIfunction.Lastly,presenceofacuteGIproblemsthataredirectlylife-threateningisgradedasAGIgradeIV(GIfailurewithasevereimpactondistantorganfunction)(ReferenceReintamBlaser,MalbrainandStarkopf3)(Table1).However,identificationofanappropriatemethodtoimplementENinpatientswithAGIisthekeytoproblems.Table1.Classificationofacutegastrointestinalinjury(AGI)(ReferenceReintamBlaser,MalbrainandStarkopf3)GI,gastrointestinal;IAH,intra-abdominalhypertension;IAP,intra-abdominalpressure;BW,bodyweight;APP,abdominalperfusionpressure;ACS,abdominalcompartmentsyndrome.EnteralnutritionintheacutephaseofcriticalillnessSufficientandappropriatenutritionisessentialtosustainthebody’smetabolism;therefore,malnutritionresultsinhighmorbidityandmortalityintheICUsetting(ReferenceGiner,LavianoandMeguid32).SomestudieshavesuggestedafavourableimpactofEENonoutcomesincriticallyillpatientssuchasreduceddiseaseseverity,lowerincidenceofinfectiouscomplicationsandshorterlengthofstayintheICU(ReferenceHeyland,StephensandDay33–ReferenceKhalid,DoshiandDigiovine35).Incontrast,inonerandomisedcontrolledtrial(RCT),ENwithin24hofadmissioninICUpatientswasnotassociatedwithareductioninhospitaldischargemortality,durationofhospitalisationorICUlengthofstay(ReferenceDoig,SimpsonandFinfer36);anotherRCTdemonstratednodifferencein30dmortalityorratesofadverseeventsinpatientswhoreceivedparenteralnutrition(PN)orENwithin36hofanunplannedadmissiontotheICU(ReferenceHarvey,ParrottandHarrison10).Furthermore,inasingle-centre,prospective,controlledclinicaltrial,aggressiveEEN(initiatingmechanicalventilation(MV)onday1v.day5)inmechanicallyventilatedpatientswasassociatedwithgreaterinfectiouscomplicationsandprolongedlengthofhospitalstay(ReferenceIbrahim,MehringerandPrentice37).Inanotherrecentstudy,earlyisoenergeticENdidnotreducethemortalityortheriskofsecondaryinfectionincriticallyillpatientswithshock;however,itwasassociatedwithanincreasedriskofdigestivecomplicationscomparedwithearlyisoenergeticPN(ReferenceReignier,Boisramé-HelmsandBrisard38).However,2016SocietyofCriticalCareMedicine(SCCM)andAmericanSocietyforParenteralandEnteralNutrition(ASPEN)guidelinesaswellasclinicalpracticeguidelinesfromESICMrecommendtheuseofENwithin24–48hincriticallyillpatientswhorequirenutritionalsupportinsteadofdelayingENorusingearlyPNbecauseofdecreasedincidenceofinfectiouscomplications(ReferenceBlaser,StarkopfandAlhazzani7,ReferenceMcClave,TaylorandMartindale39),andgreatereconomicbenefitandconvenienceoftheENroute.However,thedecreaseininfectiouscomplicationsmaybeattributabletoimprovementsincurrentmanagementofvascularaccess(ReferenceBion,RichardsonandHibbert40),preventionofventilator-associatedpneumonia(ReferenceLiBassi,SenussiandAguileraXiol41),aswellasdevelopmentsinfeedingtechnology,butnottoENperse(ReferenceHarvey,ParrottandHarrison10,ReferenceBakker,vanBrunschotandvanSantvoort42).Collectively,thesefindingsindicatethattherearenotenoughdatatodeterminethesuperiorityofEENv.delayedENortoassesstheeffectofEENinreducingmortalityratesamongcriticallyillpatients.ConsiderationsforimplementationofENotherthanthetimingofinitialENanddoseofENshouldbeimportantpoints.OneRCTofcriticallyillpatientshasshownthatpermissiveunderfeedinginthefirst7dofanICUstaymaybeassociatedwithlowerhospitalmortalityratesthanthatachievedwithtargetfeeding(ReferenceArabi,TamimandDhar43).Subsequently,alargemulticentreRCTwasperformedtoevaluatetheeffectof2weeksofpermissiveunderfeeding(definedas40–60%ofthecalculatedenergyrequirement)v.thatofstandardEN(definedas70–100%ofthecalculatedenergyrequirement)onthemortalityofcriticallyillpatientsadmittedtotheICUwithin48haftersurgery,medicaltreatmentortrauma(ReferenceArabi,AldawoodandHaddad44).Proteinintakewassimilarinthetwogroups,butthepermissiveunderfeedinggroupreceivedlessnon-proteinenergythanthestandardENgroup(ReferenceArabi,AldawoodandHaddad44).Theresults(ReferenceArabi,TamimandDhar43,ReferenceArabi,AldawoodandHaddad44)showedthatadministrationoflessnon-proteinenergyinthepermissiveunderfeedinggroupwasnotassociatedwithlowermortalitycomparedwiththatassociatedwithadministrationofafullamountofnon-proteinenergyinthestandardENgroup;however,bloodglucoselevels,insulinrequirements,needforrenal-replacementtherapy,anddailyfluidbalancewerelowerinthepermissiveunderfeedinggroup(ReferenceArabi,AldawoodandHaddad44).Inaddition,twoRCToflowerenergyfeeding:initialtrophicfeeding(definedas10–20kcal/h(42–84kJ/h)orupto500kcal/d(2090kJ/d))v.fullENofapproximately1300kcal/d(5440kJ/d)for6dofMVinpatientswithacutelunginjury(ALI)oracuterespiratoryfailureshowedsimilarclinicaloutcomes;however,fewerepisodesofGIintolerancewereobservedwithinitialtrophicfeeding(11,ReferenceRice,MoganandHays45).Furthermore,overfeedingofcriticallyillpatientsmaybeassociatedwithhypercapnia,increasedriskofinfection,metabolicdisturbancessuchashyperglycaemia,liverdysfunctionandextendedtimeonMV(ReferencePreiser,vanZantenandBerger13,ReferenceKlein,StanekandWiles46).Inaddition,earlyenergyoverfeedingwasshowntobeassociatedwithhighmortalityinnon-septicpatientswithcriticalillness(ReferenceWeijs,LooijaardandBeishuizen47).MostresultsshowedthatrestrictiveEN(permissiveunderfeedingincriticallyillpatientortrophicfeedinginpatientswithALI)issuperiorornotinferiortostandardEENorfullEEN.ThesefindingssuggestthatahighdoseofENmaycauseharmintheacutephaseofcriticalillness.Intheacutephaseafterasevereinsult,aggressivenutritionaltherapy(forexample,byprovidingexogenousenergysupportaccordingtoenergyexpenditure)maynothavebeneficialeffects.Infact,thisapproachispotentiallydetrimentalasitmaycauseametabolicoverloadand/orsuppresstheubiquitin–proteasomepathwayandtherelatedautophagypathway,whicharepotentiallyimportantforcellularrepairandorganrecovery(ReferenceHartlandJauch48,ReferenceSchetz,CasaerandVandenBerghe49).Basedonthecurrentlyavailableevidence,earlyoverfeedingmaybeappropriateintheacutephaseofcriticalillness.Althoughwethinkthatoveruseofthegutmayadverselyaffecttheprognosisintheacutephaseofcriticalillness,nostudieshavecomparedearlytrophicfeedingwithnoEN.AcutegastrointestinalinjuryandenteralnutritionStudiesconductedondogshaveshownthatenteralnutrientscanincreasebloodflowtotheGItractduringthe‘postprandialhyperaemicresponse’.Thismaypreservegutintegrityandpreventgut-derivedcomplications(ReferenceKazamias,KotzampassiandKoufogiannis50,ReferencePurcell,DavisandBranson51).OtherevidencesuggeststhattrophiceffectsofENhelpmaintainintestinalphysiology,preventatrophyofgutvilli,reduceintestinalpermeability,protectagainstischaemia–reperfusioninjurybystimulatingintestinalperfusion,andpreservegutimmunitybyaffectinggut-associatedlymphoidtissue(ReferenceSchmidtandMartindale52).However,ENmayleadtoGIcomplications(ReferenceHsu,SunandLin53)(vomiting,diarrhoea,GIbleeding,aspiration-relatedpneumonia,refeedingsyndrome,orgutischaemia)(ReferenceBoullata,CarreraandHarvey54).OnestudyfoundahighfrequencyofEN-relatedGIcomplicationsincriticallyillpatients,ofwhichhighgastricresidualswasthemostcommon;inaddition,GIintolerancetoENseemedtoprolongtheICUstayandincreasemortality(ReferenceMontejo55).OtherstudieshavefoundanassociationofearlynutritionorENwithincreasedincidenceofventilator-associatedpneumoniainpatientswithinvasiveMVandshock(ReferenceReignier,DarmonandSonneville56),andENresultedinupperdigestiveintolerance,whichwasassociatedwithnosocomialpneumonia,prolongedICUstayandahighICUmortalityincriticallyillpatients(ReferenceMentec,DupontandBocchetti57).However,improvementoffeedingprotocolsmayhelpdecreaseorpreventthecomplicationsofEN(ReferenceBoullata,CarreraandHarvey54).However,evenifENissafeinpatientswithAGI,identificationofpatientswhoarelikelytobenefitfromENintheacutephaseofcriticalillnessisakeyimperative.ThereisapaucityofstudiesthathaveinvestigatedtheinfluenceofAGIontheprognosisofcriticallyillpatientswhoreceivedEN.Therefore,theeffectofENincriticallyillpatientswithAGIisnotwellcharacterised.Inaddition,therearefewguidelinesforprovisionofENtopatientswithAGI.TheESICMWGAPrecommendsinitiationofminimalEN(20ml/h),thedoseofwhichisactuallygreaterthanthatoftrophicfeeding,withsubsequentincreaseinENto100%ofthecalculatedenergyrequirementinpatientswithAGIgradeI;inpatientswithAGIgradeIIorIII,itrecommendsinitiationortrialofminimalEN(20ml/h)alongwithothertherapybasedonthesymptoms(forexample,prokinetics)(ENisnotindicatedforpatientswithAGIgradeIV,whotypicallydonottolerateEN)(ReferenceReintamBlaser,MalbrainandStarkopf3).TheaimoftrialENintheESICMWGAPrecommendationsistoimproveGIsymptomsandtosubsequentlyincreaseENto100%ofthecalculatedenergyrequirement(ReferenceReintamBlaser,MalbrainandStarkopf3).The2016SCCM/ASPENguidelinesrecommendevaluationofGIfunctionandcontractilitybeforeinitiationofEN(ReferenceHeidegger,BergerandGraf34);however,theguidelinesdonotaddressthemethodologyforevaluationofGIfunctionandthemodalitiesforinitiationofEN.Inaddition,theserecommendations(ReferenceReintamBlaser,MalbrainandStarkopf3,ReferenceMcClave,TaylorandMartindale39)arenotentirelyevidence-based,especiallywithrespecttoadministrationofENinpatientswithAGI.Theoretically,itseemsreasonabletosuggestthatexcessiveuseofaninjuredGItractmayhavedeleteriouseffects.AlthoughthereisapaucityofevidencepertainingtotheeffectofENinpatientswithAGI,studiesonEENinpatientswithacutepancreatitis(AP)(ReferenceBakker,vanBrunschotandvanSantvoort42),whichisoftenassociatedwithAGI,haveprovidedindirectevidence.AlthoughinthismulticentreRCT,earlynasoenterictubefeeding(<24h)wasnotassociatedwithincreasedincidenceofcomplicationsascomparedwiththatwithanoraldietafter72h,itdidnotreducetherateofinfectionordeath(ReferenceBakker,vanBrunschotandvanSantvoort42).InanotherrecentRCT,earlynasojejunalfeeding(<24h)inpatientswithAPdidnotimprovepersistentorganfailureormortalitycomparedwithnonutritionalsupport(ReferenceStimac,PoropatandHauser58).Inaddition,SCCM/ASPENguidelinesrecommendassessmentofpatientsatthetimeofadmissiontotheICUfornutritionriskandhighnutritionrisk(NutritionRiskScreening2002(NRS2002)>3orNutritionRiskintheCriticallyIll(NUTRIC)score≥5)inordertoidentifypatientswhoaremostlikelytobenefitfromEENtherapybasedonexpertconsensus(ReferenceMcClave,TaylorandMartindale39);however,thesenutritionriskscoresweredesignedtoguidenutritiontherapyincludingENand/orPN(ReferenceHeyland,DhaliwalandJiang59,ReferenceJie,JiangandNolan60),andhighriskscoresmaybeanindicationforimplementingnutritiontherapy,butnotnecessarilyEN.ConsideringthelatestevidencethatshowsthatPNisnotinferiortoEN(ReferenceReignier,Boisramé-HelmsandBrisard38),andmayserveasasubstituteforEN,GIfunctionstillshouldbethemainconsiderationforimplementingENinpatientswithbothhighnutritionriskandAGI.Allinall,ENmayincreaseGIcomplicationswhichthemselvesaremanifestationsofAGI.AlthoughEENmaybesafelyimplementedthroughimprovementoffeedingprotocolsincriticallyillpatients(eventhosewithAP,whichusuallymanifestsasAGI),studiesofEENinpatientswithAPhaveshownnoindicationsofitsbenefitinpatientswithAGI(ReferenceBakker,vanBrunschotandvanSantvoort42,ReferenceStimac,PoropatandHauser58).Itispossiblethatearlyenteralfeedingmaynotbeaseffectiveasweanticipated(ReferenceBakker,vanBrunschotandvanSantvoort42).GutreststrategyincriticallyillpatientsIncriticallyillpatientswithsevereinjury,therapeuticapproachesfocusonthepathology(forexample,trauma,ornecroticorinfectedtissue),oftenallowingsurvivalfromapotentiallylethalcondition.Whiletheadaptivemetabolicresponsetominortraumaisbeneficial,anexaggeratedmetabolicresponsemaycausesecondarymetabolicdamageinpatientswhosurvivesevere,potentiallylethalconditionsduetoadvancesinmodernmedicine(ReferenceHartlandJauch48).Effectivetreatmentmustpreventthissecondarymetabolicdamage;however,theseinterventionsmustnotcauseprogressiveharm.Incriticalcare,evidencesuggeststhattheexcessiveuseofaninjuredorganisassociatedwithapoorprognosisandrestrictivetherapymightprotecttheinjuredorganfromprogressiveharm,forexample,lowtidalvolume(ReferenceNeyandKuebler61)andrestrictivefluidmanagement(62)inacuterespiratorydistresssyndrome(ARDS)/ALI,restrictivestrategyoferythrocytetransfusioninanaemia(ReferenceHébert,WellsandBlajchman63),andrestrictiveusageofdiureticsinacuterenalfailure(ReferenceMehta,PascualandSoroko64,ReferenceBagshaw,GibneyandKruger65).StudiesconductedonpatientswithAPdidnotfindabeneficialeffectofEENonprognosiswhencomparedwithgutrest(72h),whichunderlinesthecaseforgutreststrategy(Table2).Table2.Aggressiveorrestrictivetherapyincriticallyillpatients*ARDS,acuterespiratorydistresssyndrome;AKI,acutekidneyinjury;AGI,acutegastrointestinalinjury;EN,enteralnutrition;MV,mechanicalventilation;ALI,acutelunginjury.*UsingalowertidalvolumewithMVcanreducemortalityandhelpreducethedurationofMVcomparedwithuseofnormalorphysiologicaltidalvolumeinpatientswithARDS/ALI(ReferenceNeyandKuebler61).Aconservative(asagainstaggressive)approachtofluidmanagementimproveslungfunctionandshortensthedurationofMVinpatientswithALI(62).Arestrictivestrategyoferythrocytetransfusionhasbeenshowntobeequallyeffectiveandpotentiallysuperiortoaliberaltransfusionstrategyincriticallyillpatients(ReferenceHébert,WellsandBlajchman63).Useofdiuretics,whichcausesoveruseofresidualkidneyfunction,hasbeenshowntobeassociatedwithanincreasedriskofdeathandnon-recoveryofrenalfunctionincriticallyillpatientswithacuterenalfailure(ReferenceMehta,PascualandSoroko64,ReferenceBagshaw,GibneyandKruger65).Theoretically,‘organrest’strategyreliesoncompleterestoftheorgan,suchaslungrestduringextracorporealmembraneoxygenationinanimalexperiments(ReferenceFrattallone,FuhrmanandKochanek66).However,inclinicalsettings,lungreststrategyimpliesmaintainingasmallworkload,forexample,withlowinspiratorypressure,lowoxygenconcentration,andmoderatepositiveendexpiratorypressureinpatientswithARDS/ALIonMV(ReferencePeek,MugfordandTiruvoipati67);inotherwords,thisrepresentsapartiallungreststrategy.Similarly,trophicfeeding(ReferenceWallon,YangandKeita19)entailsasmallvolumeofENnotintendedtomeetenergyrequirementsbutrathertomaintainthestructuralandfunctionalintegrityoftheGItract;thismaybereferredtoasapartialgutreststrategy.However,itisnecessarytoperformmoretrialstodemonstratethesuperiorityofpartialgutreststrategyincriticallyillpatientswithAGI.Inaddition,comparisonoftrophicfeedingwithgutreststrategyshouldalsobeperformed.PatientswithAGIshouldbeenrolledinRCTonENinfuture.ThepresentreviewmightprovideanewapproachforresearchonENincriticallyillpatients.Weproposethatdelayedtrophicfeeding(after72hfromintensivestress)istheoptimalchoiceforcriticallyillpatientswithAGI.Asaprotectivestrategy,trophicfeedingmayreducethegutburdenandhelpmaintainintestinalphysiology,sufficienttopreventmucosalatrophyandmaintaingutintegrityincriticallyillpatients(ReferenceMcClave,TaylorandMartindale39);therefore,itmaybeapplicabletocriticallyillpatientswithAGI.Tothebestofourknowledge,therearenotrialsthathaveproventhishypothesis;therefore,large-scalestudiesarewarrantedtoinvestigatethisapproach.ConclusionsInjurytotheGItractmanifestsasimproperdigestionandabsorption,impairmentoftheintestinalbarrieranddysregulationoftheintestinalmicrobiota.ENisbelievedtoimproveGIfunctionincriticallyillpatients.However,weproposethatdelayedtrophicfeedingmaybetheoptimalstrategyintheacutephaseofcriticalillnessconsideringtheadaptivemetabolicresponseandAGI.Trophicfeedingmaybeanorgan-protectivestrategyincriticallyillpatients,similartoventilationwithalowtidalvolume,restrictivefluidresuscitationandrestrictivebloodtransfusion.AuthorORCIDsHongxiangLi0000-0002-1399-8039AcknowledgementsTherewasnofinancialsupportforthisstudy.D.Z.andY.L.producedthefirstdraftofthemanuscript.L.Q.madethefigure.H.L.criticallyrevisedthemanuscript.Allauthorssawandapprovedthefinaldraftofthemanuscript.Therearenoconflictsofinterest.References References 1 Reintam,A,Parm,P,Kitus,R,etal.(2009)Gastrointestinalsymptomsinintensivecarepatients.ActaAnaesthesiolScand53,318–324.CrossRefGoogleScholarPubMed 2 Piton,G,Belon,F,Cypriani,B,etal.(2013)Enterocytedamageincriticallyillpatientsisassociatedwithshockconditionand28-daymortality.CritCareMed41,2169–2176.CrossRefGoogleScholarPubMed 3 ReintamBlaser,A,Malbrain,ML,Starkopf,J,etal.(2012)Gastrointestinalfunctioninintensivecarepatients:terminology,definitionsandmanagement.RecommendationsoftheESICMWorkingGrouponAbdominalProblems.IntensiveCareMed38,384–394.CrossRefGoogleScholar 4 Reintam,A,Parm,P,Kitus,R,etal.(2008)Gastrointestinalfailurescoreincriticallyillpatients:aprospectiveobservationalstudy.CritCare12,R90.CrossRefGoogleScholarPubMed 5 Reintam,A,Parm,P,Redlich,U,etal.(2006)Gastrointestinalfailureinintensivecare:aretrospectiveclinicalstudyinthreedifferentintensivecareunitsinGermanyandEstonia.BMCGastroenterol6,19.CrossRefGoogleScholarPubMed 6 Li,H,Zhang,D,Wang,Y,etal.(2016)Associationbetweenacutegastrointestinalinjurygradingsystemanddiseaseseverityandprognosisincriticallyillpatients:amulticenter,prospective,observationalstudyinChina.JCritCare36,24–28.CrossRefGoogleScholar 7 Blaser,AR,Starkopf,J,Alhazzani,W,etal.(2017)Earlyenteralnutritionincriticallyillpatients:ESICMclinicalpracticeguidelines.IntensiveCareMed43,380–398.CrossRefGoogleScholar 8 Stahel,PF,Flierl,MA&Moore,EE(2010)“Metabolicstaging”aftermajortrauma–aguideforclinicaldecisionmaking?ScandJTraumaResuscEmergMed18,34.CrossRefGoogleScholarPubMed 9 Casaer,MP,Mesotten,D,Hermans,G,etal.(2011)Earlyversuslateparenteralnutritionincriticallyilladults.NewEnglJMed365,506–517.CrossRefGoogleScholarPubMed 10 Harvey,SE,Parrott,F,Harrison,DA,etal.(2014)Trialoftherouteofearlynutritionalsupportincriticallyilladults.NewEnglJMed371,1673–1684.CrossRefGoogleScholarPubMed 11 NationalHeart,Lung,andBloodInstituteAcuteRespiratoryDistressSyndrome(ARDS)(2012)Initialtrophicvsfullenteralfeedinginpatientswithacutelunginjury:theEDENrandomizedtrial.JAMA307,795–803.CrossRefGoogleScholar 12 Stratakis,CA&Chrousos,GP(2010)Neuroendocrinologyandpathophysiologyofthestresssystem.AnnNYAcadSci771,1–18.CrossRefGoogleScholar 13 Preiser,JC,vanZanten,AR,Berger,MM,etal.(2015)Metabolicandnutritionalsupportofcriticallyillpatients:consensusandcontroversies.CritCare19,35.CrossRefGoogleScholarPubMed 14 Lena,D,Kalfon,P,Preiser,JC,etal.(2011)Glycemiccontrolintheintensivecareunitandduringthepostoperativeperiod.Anesthesiology114,438–444.CrossRefGoogleScholarPubMed 15 Preiser,JC,Ichai,C,Orban,JC,etal.(2014)Metabolicresponsetothestressofcriticalillness.BrJAnaesth113,945–954.CrossRefGoogleScholarPubMed 16 Gué,M,Peeters,T,Depoortere,I,etal.(1989)Stress-inducedchangesingastricemptying,postprandialmotility,andplasmaguthormonelevelsindogs.Gastroenterology97,1101–1107.CrossRefGoogleScholarPubMed 17 Chrousos,GP(2009)Stressanddisordersofthestresssystem.NatRevEndocrinol5,374–381.CrossRefGoogleScholarPubMed 18 Richardson,RS,Norton,LW,Sales,JE,etal.(1973)Gastricbloodflowinendotoxin-inducedstressulcer.ArchSurg106,191–195.CrossRefGoogleScholarPubMed 19 Wallon,C,Yang,PC,Keita,ÅV,etal.(2008)Corticotropin-releasinghormone(CRH)regulatesmacromolecularpermeabilityviamastcellsinnormalhumancolonicbiopsiesinvitro.Gut57,50–58.CrossRefGoogleScholarPubMed 20 Konturek,PC,Brzozowski,T&Konturek,SJ(2011)Stressandthegut:pathophysiology,clinicalconsequences,diagnosticapproachandtreatmentoptions.JPhysiolPharmacol62,591–599.GoogleScholarPubMed 21 Halter,JB,Pflug,AE&Porte,DJr(1977)Mechanismofplasmacatecholamineincreasesduringsurgicalstressinman.JClinEndocrinolMetab45,936–944.CrossRefGoogleScholarPubMed 22 Krejci,V,Hiltebrand,LB&Sigurdsson,GH(2006)Effectsofepinephrine,norepinephrine,andphenylephrineonmicrocirculatorybloodflowinthegastrointestinaltractinsepsis.CritCareMed34,1456–1463.CrossRefGoogleScholarPubMed 23 Chapman,M,Fraser,R,Vozzo,R,etal.(2005)Antro-pyloro-duodenalmotorresponsestogastricandduodenalnutrientincriticallyillpatients.Gut54,1384–1390.CrossRefGoogleScholarPubMed 24 Hinshaw,LB(1996)Sepsis/septicshock:participationofthemicrocirculation:anabbreviatedreview.CritCareMed24,1072–1078.CrossRefGoogleScholarPubMed 25 Chung,DH,Evers,BM,Townsend,CM,etal.(1992)Burn-inducedtranscriptionalregulationofsmallintestinalornithinedecarboxylase.AmJSurg163,157–163.CrossRefGoogleScholarPubMed 26 LeeWL&SlutskyAS(2010)Sepsisandendothelialpermeability.NEnglJMed363,689–691.CrossRefGoogleScholar 27 Verburgh,P,Reintam-Blaser,A,Kirkpatrick,AW,etal.(2014)Overviewoftherecentdefinitionsandterminologyforacutegastrointestinalinjury,intra-abdominalhypertensionandtheabdominalcompartmentsyndrome.Reanimation23,Suppl.2,379–393.CrossRefGoogleScholar 28 Li,H,Chen,Y,Huo,F,etal.(2017)Associationbetweenacutegastrointestinalinjuryandbiomarkersofintestinalbarrierfunctionincriticallyillpatients.BMCGastroenterol17,45.CrossRefGoogleScholarPubMed 29 Lankelma,JM,vanVught,LA,Belzer,C,etal.(2016)Criticallyillpatientsdemonstratelargeinterpersonalvariationinintestinalmicrobiotadysregulation:apilotstudy.IntensiveCareMed43,59–68.CrossRefGoogleScholarPubMed 30 Burgstad,CM,Besanko,LK,Deane,AM,etal.(2013)Sucrosemalabsorptionandimpairedmucosalintegrityinenterallyfedcriticallyillpatients:aprospectivecohortobservationalstudy.CritCareMed41,1221–1228.CrossRefGoogleScholarPubMed 31 Jacobs,MC,Haak,BW,Hugenholtz,F,etal.(2017)Gutmicrobiotaandhostdefenseincriticalillness.CurrOpinCritCare23,257–263.CrossRefGoogleScholarPubMed 32 Giner,M,Laviano,A,Meguid,MM,etal.(1996)In1995acorrelationbetweenmalnutritionandpooroutcomeincriticallyillpatientsstillexists.Nutrition12,23–29.CrossRefGoogleScholarPubMed 33 Heyland,DK,Stephens,KE,Day,AG,etal.(2011)ThesuccessofenteralnutritionandICU-acquiredinfections:amulticenterobservationalstudy.ClinNutr30,148–155.CrossRefGoogleScholarPubMed 34 Heidegger,CP,Berger,MM,Graf,S,etal.(2013)Optimisationofenergyprovisionwithsupplementalparenteralnutritionincriticallyillpatients:arandomisedcontrolledclinicaltrial.Lancet381,385–393.CrossRefGoogleScholarPubMed 35 Khalid,I,Doshi,P&Digiovine,B(2010)Earlyenteralnutritionandoutcomesofcriticallyillpatientstreatedwithvasopressorsandmechanicalventilation.AmJCritCare19,261–268.CrossRefGoogleScholarPubMed 36 Doig,GS,Simpson,F,Finfer,S,etal.(2008)Effectofevidence-basedfeedingguidelinesonmortalityofcriticallyilladults:aclusterrandomizedcontrolledtrial.JAMA300,2731–2741.CrossRefGoogleScholarPubMed 37 Ibrahim,E,Mehringer,L,Prentice,D,etal.(2002)Earlyversuslateenteralfeedingofmechanicallyventilatedpatients:resultsofaclinicaltrial.JParenterEnteralNutr26,174–181.CrossRefGoogleScholarPubMed 38 Reignier,J,Boisramé-Helms,J,Brisard,L,etal.(2018)Enteralversusparenteralearlynutritioninventilatedadultswithshock:arandomised,controlled,multicentre,open-label,parallel-groupstudy(NUTRIREA-2).Lancet391,133–143.CrossRefGoogleScholar 39 McClave,S,Taylor,B&Martindale,R(2016)Guidelinesfortheprovisionandassessmentofnutritionsupporttherapyintheadultcriticallyillpatient:SocietyofCriticalCareMedicine(SCCM)andAmericanSocietyforParenteralandEnteralNutrition(A.S.P.E.N.).JParenterEnteralNutr40,159–211.CrossRefGoogleScholar 40 Bion,J,Richardson,A,Hibbert,P,etal.(2013)‘MatchingMichigan’:a2-yearsteppedinterventionalprogrammetominimisecentralvenouscatheter-bloodstreaminfectionsinintensivecareunitsinEngland.BMJQualSaf22,110–123.CrossRefGoogleScholarPubMed 41 LiBassi,G,Senussi,T&AguileraXiol,E(2017)Preventionofventilator-associatedpneumonia.CurrOpinInfectDis30,214–220.CrossRefGoogleScholarPubMed 42 Bakker,OJ,vanBrunschot,S,vanSantvoort,HC,etal.(2014)Earlyversuson-demandnasoenterictubefeedinginacutepancreatitis.NEnglJMed371,1983–1993.CrossRefGoogleScholarPubMed 43 Arabi,YM,Tamim,HM,Dhar,GS,etal.(2011)Permissiveunderfeedingandintensiveinsulintherapyincriticallyillpatients:arandomizedcontrolledtrial.AmJClinNutr93,569–577.CrossRefGoogleScholarPubMed 44 Arabi,YM,Aldawood,AS,Haddad,SH,etal.(2015)Permissiveunderfeedingorstandardenteralfeedingincriticallyilladults.NEnglJMed372,2398–2408.CrossRefGoogleScholarPubMed 45 Rice,TW,Mogan,S,Hays,MA,etal.(2011)Randomizedtrialofinitialtrophicversusfull-energyenteralnutritioninmechanicallyventilatedpatientswithacuterespiratoryfailure.CritCareMed39,967–974.CrossRefGoogleScholarPubMed 46 Klein,CJ,Stanek,GS&Wiles,CEIII(1998)Overfeedingmacronutrientstocriticallyilladults:metaboliccomplications.JAmDietAssoc98,795–806.CrossRefGoogleScholarPubMed 47 Weijs,PJ,Looijaard,WG,Beishuizen,A,etal.(2014)Earlyhighproteinintakeisassociatedwithlowmortalityandenergyoverfeedingwithhighmortalityinnon-septicmechanicallyventilatedcriticallyillpatients.CritCare18,701.CrossRefGoogleScholarPubMed 48 Hartl,WH&Jauch,KW(2014)Metabolicself-destructionincriticallyillpatients:origins,mechanismsandtherapeuticprinciples.Nutrition30,261–267.CrossRefGoogleScholarPubMed 49 Schetz,M,Casaer,MP&VandenBerghe,G(2013)Doesartificialnutritionimproveoutcomeofcriticalillness?CritCare17,302.CrossRefGoogleScholarPubMed 50 Kazamias,P,Kotzampassi,K,Koufogiannis,D,etal.(1998)Influenceofenteralnutrition-inducedsplanchnichyperemiaonthesepticoriginofsplanchnicischemia.WorldJSurg22,6–11.CrossRefGoogleScholarPubMed 51 Purcell,PN,Davis,KJr,Branson,RD,etal.(1993)ContinuousduodenalfeedingrestoresgutbloodflowandincreasesgutoxygenutilizationduringPEEPventilationforlunginjury.AmJSurg165,188–193.CrossRefGoogleScholarPubMed 52 Schmidt,H&Martindale,R(2001)Thegastrointestinaltractincriticalillness.CurrOpinClinNutr4,547–551.CrossRefGoogleScholarPubMed 53 Hsu,CW,Sun,SF,Lin,SL,etal.(2009)Duodenalversusgastricfeedinginmedicalintensivecareunitpatients:aprospective,randomized,clinicalstudy.CritCareMed37,1866–1872.CrossRefGoogleScholarPubMed 54 Boullata,JI,Carrera,AL,Harvey,L,etal.(2017)ASPENSafePracticesforEnteralNutritionTherapy.JPENJParenterEnteralNutr41,15–103.CrossRefGoogleScholarPubMed 55 Montejo,JC(1999)Enteralnutrition-relatedgastrointestinalcomplicationsincriticallyillpatients:amulticenterstudy.TheNutritionalandMetabolicWorkingGroupoftheSpanishSocietyofIntensiveCareMedicineandCoronaryUnits.CritCareMed27,1447–1453.CrossRefGoogleScholar 56 Reignier,J,Darmon,M,Sonneville,R,etal.(2015)Impactofearlynutritionandfeedingrouteonoutcomesofmechanicallyventilatedpatientswithshock:aposthocmarginalstructuralmodelstudy.IntensiveCareMed41,875–886.CrossRefGoogleScholarPubMed 57 Mentec,H,Dupont,H,Bocchetti,M,etal.(2001)Upperdigestiveintoleranceduringenteralnutritionincriticallyillpatients:frequency,riskfactors,andcomplications.CritCareMed29,1955–1961.CrossRefGoogleScholarPubMed 58 Stimac,D,Poropat,G,Hauser,G,etal.(2016)Earlynasojejunaltubefeedingversusnil-by-mouthinacutepancreatitis:arandomizedclinicaltrial.Pancreatology16,523–528.CrossRefGoogleScholarPubMed 59 Heyland,DK,Dhaliwal,R,Jiang,X,etal.(2011)Identifyingcriticallyillpatientswhobenefitthemostfromnutritiontherapy:thedevelopmentandinitialvalidationofanovelriskassessmenttool.CritCare15,R268.CrossRefGoogleScholarPubMed 60 Jie,B,Jiang,ZM,Nolan,MT,etal.(2012)Impactofpreoperativenutritionalsupportonclinicaloutcomeinabdominalsurgicalpatientsatnutritionalrisk.Nutrition28,1022–1027.CrossRefGoogleScholarPubMed 61 Ney,L&Kuebler,WM(2000)Ventilationwithlowertidalvolumesascomparedwithtraditionaltidalvolumesforacutelunginjury.NEnglJMed343,813–814.GoogleScholarPubMed 62 NationalHeart,Lung,andBloodInstituteAcuteRespiratoryDistressSyndrome(ARDS)ClinicalTrialsNetwork,WiedemannHP,WheelerAP,etal.(2006)Comparisonoftwofluid-managementstrategiesinacutelunginjury.NEnglJMed354,2564–2575.CrossRefGoogleScholar 63 Hébert,PC,Wells,G,Blajchman,MA,etal.(1999)Amulticenter,randomized,controlledclinicaltrialoftransfusionrequirementsincriticalcare.NEnglJMed340,409–417.CrossRefGoogleScholarPubMed 64 Mehta,RL,Pascual,MT,Soroko,S,etal.(2002)Diuretics,mortality,andnonrecoveryofrenalfunctioninacuterenalfailure.JAMA288,2547–2553.CrossRefGoogleScholarPubMed 65 Bagshaw,SM,Gibney,RTN,Kruger,P,etal.(2017)Theeffectoflow-dosefurosemideincriticallyillpatientswithearlyacutekidneyinjury:apilotrandomizedblindedcontrolledtrial(theSPARKstudy).JCritCare42,138–146.CrossRefGoogleScholar 66 Frattallone,JM,Fuhrman,BP,Kochanek,PM,etal.(1988)Managementofpulmonarybarotraumabyextracorporealmembraneoxygenation,apnea,andlungrest.JPediatr112,787–789.CrossRefGoogleScholarPubMed 67 Peek,GJ,Mugford,M,Tiruvoipati,R,etal.(2009)Efficacyandeconomicassessmentofconventionalventilatorysupportversusextracorporealmembraneoxygenationforsevereadultrespiratoryfailure(CESAR):amulticentrerandomisedcontrolledtrial.Lancet374,1351–1363.CrossRefGoogleScholarPubMed Viewincontent Fig.1.Acutegastrointestinalinjuryincriticallyillpatients.Acutegastrointestinalinjurymanifestsasimproperdigestionandabsorption(3),impairmentoftheintestinalbarrier(28)anddysregulationoftheintestinalmicrobiota(29).Improperdigestionandabsorption:enteralfeedingisimpactedwhatevertheclinicalreason(vomiting,highgastricresiduals,diarrhoea,gastrointestinalbleedingorpresenceofentero-cutaneousfistulas)(3).Impairmentoftheintestinalbarriermeansincreasedintestinalpermeability(28).Dysregulationoftheintestinalmicrobiotaischaracterisedbylowdiversity,lowabundanceofkeycommensalgeneraandovergrowthofonebacterialgenus.Inthefigure,highgastricresidualsindicateimproperdigestionandabsorption;impairmentoftheintestinalbarrieranddysregulationoftheintestinalmicrobiotaarenotidentifiedwellduetotheshortageofevaluationtools(3). Viewincontent Table1.Classificationofacutegastrointestinalinjury(AGI)(3) Viewincontent Table2.Aggressiveorrestrictivetherapyincriticallyillpatients*Youhave Access Openaccess 10CitedbyCitedbyLoading... CrossrefCitations Thisarticlehasbeencitedbythefollowingpublications.Thislistisgeneratedbasedondataprovidedby CrossRef. Tang,Qin-qing Hong,Zhi-wu Ren,Hua-jian Wu,Lei Wang,Ge-fei Gu,Guo-sheng Chen,Jun Zheng,Tao Wu,Xiu-wen Ren,Jian-an and Li,Jie-shou 2020. NutritionalManagementofPatientsWithEnterocutaneousFistulas:PracticeandProgression. FrontiersinNutrition, Vol.7, Issue., CrossRef GoogleScholar MayorgaGarcés,Alejandro OteroRegino,William and PargaBermúdez,JuliánErnesto 2020. Nutriciónenpancreatitisaguda:nuevosconceptosparaunviejoproblema. RevistaColombianadeGastroenterología, Vol.35, Issue.4, p. 465. CrossRef GoogleScholar Mohr,AlexE. Gumpricht,Eric Sears,DorothyD. and Sweazea,KarenL. 2021. Recentadvancesandhealthimplicationsofdietaryfastingregimensonthegutmicrobiome. AmericanJournalofPhysiology-GastrointestinalandLiverPhysiology, Vol.320, Issue.5, p. G847. CrossRef GoogleScholar Jung,ChangYeon and Bae,JungMin 2021. Pathophysiologyandprotectiveapproachesofgutinjuryincriticalillness. YeungnamUniversityJournalofMedicine, Vol.38, Issue.1, p. 27. CrossRef GoogleScholar Li,Hongxiang Lu,Junying Li,Hongyan Duan,Aosong Wang,Yushan and Zhang,Dong 2021. Associationbetweennutritionsupportandacutegastrointestinalinjuryincriticallyillpatientsduringthefirst72hours. ClinicalNutrition, Vol.40, Issue.1, p. 217. CrossRef GoogleScholar Aguila,EnrikJohnT. Lontok,MarieAntoinetteDC. and Raymundo,NikkoTheodoreV. 2021. Commenton“GastrointestinalComplicationsinCriticallyIllPatientsWithCOVID-19”. AnnalsofSurgery, Vol.274, Issue.6, p. e819. CrossRef GoogleScholar Huang,Sisi Chen,Limin Liu,Jiao Zhang,Sheng Zhang,Lidi Wen,Zhenliang Chen,Yizhu and Chen,Dechang 2021. NovelMultiparametricNomogramforOverallSurvivalPredictioninComplicatedIntra-AbdominalInfection:AMulticenterStudyinChina. FrontiersinMedicine, Vol.8, Issue., CrossRef GoogleScholar Gao,Lin Chong,Eric Pendharkar,Sayali Phillips,Anthony Ke,Lu Li,Weiqin and Windsor,JohnAlbert 2021. TheChallengesandEffectsofAscorbicAcidTreatmentofAcutePancreatitis:ASystematicReviewandMeta-AnalysisofPreclinicalandClinicalStudies. FrontiersinNutrition, Vol.8, Issue., CrossRef GoogleScholar Aguila,EnrikJohnT. and Cua,IanHomerY. 2021. Differentbarrierstonutritionaltherapyamongcritically-illpatientswithCOVID-19. ClinicalNutrition, Vol.40, Issue.2, p. 655. CrossRef GoogleScholar Stanculescu,Dominic and Bergquist,Jonas 2022. Perspective:DrawingonFindingsFromCriticalIllnesstoExplainMyalgicEncephalomyelitis/ChronicFatigueSyndrome. FrontiersinMedicine, Vol.9, Issue., CrossRef GoogleScholar GoogleScholarCitations ViewallGoogleScholarcitations forthisarticle. × Cancel Confirm ×