解读2008年儿科部分脓毒血症与感染性休克管理国际指南课件

广州市妇女儿童医疗中心广州市儿童医院PICU杨镒宇 解读2008年脓毒血症与感染性休克管理国际指南 儿科部分 广州 2009 12 18 SurvivingSepsisCampaign Internationalguidelinesformanagementofseveresepsisandsepticshock 2008 广州市妇女儿童医疗中心 SurvivingSepsisCampaign历史 SocietyofCriticalCareMedicine2007ThearticlewillalsobepublishedinCriticalCareMedicine Sponsorof2004guidelines Sponsorof2008guidelinesbutdidnotparticipateformallyinrevisionprocess Membersofthe2007SSCGuidelinesCommitteearelistedinAppendixI PleaseseeAppendixJforauthordisclosureinformation 广州市妇女儿童医疗中心 跨洲 跨国的多中心联合 SponsoringOrganizations AmericanAssociationofCritical CareNurses AmericanCollegeofChestPhysicians AmericanCollegeofEmergencyPhysicians CanadianCriticalCareSociety EuropeanSocietyofClinicalMicrobiologyandInfectiousDiseases EuropeanSocietyofIntensiveCareMedicine EuropeanRespiratorySociety InternationalSepsisForum JapaneseAssociationforAcuteMedicine JapaneseSocietyofIntensiveCareMedicine SocietyofCriticalCareMedicine SocietyofHospitalMedicine SurgicalInfectionSociety WorldFederationofSocietiesofIntensiveandCriticalCare 广州市妇女儿童医疗中心 Table1DeterminationoftheQualityofEvidence UnderlyingmethodologyARCTBDowngradedRCTorupgradedobservationalstudiesCWell doneobservationalstudiesDCaseseriesorexpertopinion Factorsthatmaydecreasethestrengthofevidence1 PoorqualityofplanningandimplementationofavailableRCTssuggestinghighlikelihoodofbias2 Inconsistencyofresults includingproblemswithsubgroupanalyses 3 Indirectnessofevidence differingpopulation intervention control outcomes comparison 4 Imprecisionofresults5 Highlikelihoodofreportingbias Mainfactorsthatmayincreasethestrengthofevidence1 Largemagnitudeofeffect directevidence relativerisk RR 2withnoplausibleconfounders 2 VerylargemagnitudeofeffectwithRR 5andnothreatstovalidity bytwolevels 3 DoseresponsegradientRCT randomizedcontrolledtrial RR relativerisk 广州市妇女儿童医疗中心 Table2FactorsDeterminingStrongvs WeakRecommendation WhatshouldbeconsideredRecommendedProcessQualityofevidenceThelowerthequalityofevidencethelesslikelyastrongrecommendationRelativeimportanceoftheoutcomesIfvaluesandpreferencesvarywidely astrongrecommendationbecomeslesslikelyBaselinerisksofoutcomesThehighertherisk thegreaterthemagnitudeofbenefitMagnitudeofrelativeriskincludingLargerrelativeriskreductionsorlargerbenefits harms andburdenincreasesinrelativeriskofharmmakeastrongrecommendationmoreorlesslikelyrespectivelyAbsolutemagnitudeoftheeffectThelargertheabsolutebenefitsandharms thegreaterorlesserlikelihoodrespectivelyofastrongrecommendationPrecisionoftheestimatesoftheeffectsThegreatertheprecisionthemorelikelyisastrongrecommendationCostsThehigherthecostoftreatment thelesslikelyastrongrecommendation 广州市妇女儿童医疗中心 Table3InitialResuscitationandInfectionIssues Initialresuscitation first6hours StrengthofrecommendationandqualityofevidencehavebeenassessedusingtheGRADEcriteria presentedinbracketsaftereachguideline Foraddedclarity Indicatesastrongrecommendationor werecommend indicatesaweakrecommendationor wesuggest Beginresuscitationimmediatelyinpatientswithhypotensionorelevatedserumlactate 4mmol l donotdelaypendingICUadmission 1C Resuscitationgoals 1C EGDT Centralvenouspressure CVP 8 12mmHg Meanarterialpressure 65mmHg Urineoutput 0 5mL kg 1 hr 1 Centralvenous superiorvenacava oxygensaturation 70 ormixedvenous 65 IfvenousO2saturationtargetnotachieved 2C 广州市妇女儿童医疗中心 Table3InitialResuscitationandInfectionIssues 续一 IfvenousO2saturationtargetnotachieved 2C considerfurtherfluid transfusepackedredbloodcellsifrequiredtohematocritof 30 and or dobutamineinfusionmax20 g kg 1 min 1 AhighertargetCVPof12 15mmHgisrecommendedinthepresenceofmechanicalventilationorpre existingdecreasedventricularcompliance Diagnosis Obtainappropriateculturesbeforestartingantibioticsprovidedthisdoesnotsignificantlydelayantimicrobialadministration 1C Obtaintwoormorebloodcultures BCs OneormoreBCsshouldbepercutaneous OneBCfromeachvascularaccessdeviceinplace 48h Cultureothersitesasclinicallyindicated Performimagingstudiespromptlyinordertoconfirmandsampleanysourceofinfection ifsafetodoso 1C 广州市妇女儿童医疗中心 Table3InitialResuscitationandInfectionIssues 续二 Antibiotictherapy Beginintravenousantibioticsasearlyaspossible andalwayswithinthefirsthourofrecognizingseveresepsis 1D andsepticshock 1B Broad spectrum oneormoreagentsactiveagainstlikelybacterial fungalpathogensandwithgoodpenetrationintopresumedsource 1B Reassessantimicrobialregimendailytooptimiseefficacy preventresistance avoidtoxicitylongerifresponseslow undrainablefociofinfection orimmunologicdeficiencies 1D Stopantimicrobialtherapyifcauseisfoundtobenon infectious 1D 广州市妇女儿童医疗中心 Table3InitialResuscitationandInfectionIssues 续三 Sourceidentificationandcontrol Aspecificanatomicsiteofinfectionshouldbeestablishedasrapidlyaspossible 1C andwithinfirst6hrsofpresentation 1D Formallyevaluatepatientforafocusofinfectionamenabletosourcecontrolmeasures eg abscessdrainage tissuedebridement 1C Implementsourcecontrolmeasuresassoonaspossiblefollowingsuccessfulinitialresuscitation 1C Exception infectedpancreaticnecrosis wheresurgicalinterventionbestdelayed 2B Choosesourcecontrolmeasurewithmaximumefficacyandminimalphysiologicupset 1D Removeintravascularaccessdevicesifpotentiallyinfected 1C 广州市妇女儿童医疗中心 I ManagementofSevereSepsisA InitialResuscitation I ManagementofSevereSepsisA InitialResuscitation1 Werecommendtheprotocolizedresuscitationofapatientwithsepsis inducedshock definedastissuehypoperfusion Hypoperfusion hypotension bloodlactate 4mmol L ThisprotocolshouldbeinitiatedassoonashypoperfusionisrecognizedandshouldnotbedelayedpendingICUadmission Duringthefirst6hrsofresuscitation thegoalsofinitialresuscitationofsepsis inducedhypoperfusionshouldincludeallofthefollowingasonepartofatreatmentprotocol EGDT 广州市妇女儿童医疗中心 includeallofthefollowingasonepartofatreatmentprotocol EGDTCentralvenouspressure CVP 8 12mmHgMeanarterialpressure MAP 65mmHgUrineoutput 0 5mL kg 1 hr 1Centralvenous superiorvenacava ormixedvenousoxygensaturation 70 or 65 respectively Grade1C 广州市妇女儿童医疗中心 LimitationsOFCVP Therearerecognizedlimitationstoventricularfillingpressureestimatesassurrogatesforfluidresuscitation 28 29 CVPisthemostobtainabletargetforfluidresuscitation Othertechnologiesadvantagestoflow volumetricindicesandmicrocirculationchangesattheICUbedside 30 33 34 35 butinaccessibleduringthecriticalearlyresuscitationperiodandresearchtovalidateutility 广州市妇女儿童医疗中心 Nextstepafterfluidresuscitation Wesuggestthatduringthefirst6hrstheCVPtargetISachievedBUTSCVO2orSvO2of70 or65 respectivelyisnotachievedthentransfusionofpackedredbloodcellstoachieveahematocritof 30 And ordobutamineinfusion uptoamaximumof20 g kg 1 min 1 beutilizedtoachievethisgoal Grade2C 广州市妇女儿童医疗中心 Rationale DO2 CO Hb SaO2 1 34 PaO2 0 003 HR Earlystage XPre loadCVP Early mid andlate SVMyodobutamine mid andlate Post loadregitine Early mid andlate BPVascularResistance 广州市妇女儿童医疗中心 Table4HemodynamicSupportandAdjunctiveTherapy 1 Fluidtherapy Fluid resuscitateusingcrystalloidsorcolloids 1B TargetaCVPof 8mmHg 12mmHgifventilated 1C Useafluidchallengetechniquewhileassociatedwithahaemodynamicimprovement 1D Givefluidchallengesof1000mlofcrystalloidsor300 500mlofcolloidsover30min Morerapidandlargervolumesmayberequiredinsepsis inducedtissuehypoperfusion 1D Rateoffluidadministrationshouldbereducedifcardiacfillingpressuresincreasewithoutconcurrenthemodynamicimprovement 1D Vasopressors 广州市妇女儿童医疗中心 Table4HemodynamicSupportandAdjunctiveTherapy 2 Vasopressors MaintainMAP 65mmHg 1C Norepinephrineordopaminecentrallyadministeredaretheinitialvasopressorsofchoice 1C Epinephrine phenylephrineorvasopressinshouldnotbeadministeredastheinitialvasopressorinsepticshock 2C Vasopressin0 03units minmaybesubsequentlyaddedtonorepinephrinewithanticipationofaneffectequivalenttonorepinephrinealone Useepinephrineasthefirstalternativeagentinsepticshockwhenbloodpressureispoorlyresponsivetonorepinephrineordopamine 2B Donotuselow dosedopamineforrenalprotection 1A Inpatientsrequiringvasopressors insertanarterialcatheterassoonaspractical 1D Inotropictherapy 广州市妇女儿童医疗中心 Table4HemodynamicSupportandAdjunctiveTherapy 3 Inotropictherapy Usedobutamineinpatientswithmyocardialdysfunctionassupportedbyelevatedcardiacfillingpressuresandlowcardiacoutput 1C Donotincreasecardiacindextopredeterminedsupranormallevels 1B Steroids Considerintravenoushydrocortisoneforadultsepticshockwhenhypotensionremainspoorlyresponsivetoadequatefluidresuscitationandvasopressors 2C ACTHstimulationtestisnotrecommendedtoidentifythesubsetofadultswithsepticshockwhoshouldreceivehydrocortisone 2B Hydrocortisoneispreferredtodexamethasone 2B Fludrocortisone 50 gorallyonceaday maybeincludedifanalternativetohydrocortisoneisbeingusedwhichlackssignificantmineralocorticoidactivity Fludrocortisoneisoptionalifhydrocortisoneisused 2C 广州市妇女儿童医疗中心 Table4HemodynamicSupportandAdjunctiveTherapy 4 Steroids Steroidtherapymaybeweanedoncevasopressorsarenolongerrequired 2D Hydrocortisonedoseshouldbe 300mg day 1A Donotusecorticosteroidstotreatsepsisintheabsenceofshockunlessthepatient sendocrineorcorticosteroidhistorywarrantsit 1D RecombinanthumanactivatedproteinC rhAPC ConsiderrhAPCinadultpatientswithsepsis inducedorgandysfunctionwithclinicalassessmentofhighriskofdeath typicallyAPACHEII 25ormultipleorganfailure iftherearenocontraindications 2B 2Cforpost operativepatients Adultpatientswithseveresepsisandlowriskofdeath e g APACHEII 20oroneorganfailure shouldnotreceiverhAPC 1A 广州市妇女儿童医疗中心 J BloodProductAdministration 1 OncetissuehypoperfusionhasresolvedwerecommendthatHb 7 0g dL 70g L redbloodcelltransfusiontotargetaHbof7 0 9 0g dL 70 90g L Grade1B intheabsenceofextenuatingcircumstances myocardialischemia severehypoxemia acutehemorrhage cyanoticheartdisease orlacticacidosis 广州市妇女儿童医疗中心 J BloodProductAdministration 3 3 Wesuggestthatfreshfrozenplasmanotbeusedtocorrectlaboratoryclottingabnormalitiesintheabsenceofbleedingorplannedinvasiveprocedures Grade2D 5 Inpatientswithseveresepsis wesuggestthatplateletsshouldbeadministeredwhencountsare Grade2D 5000 mm3 5 109 L regardlessofapparentbleeding 5 000 30 000 mm3 5 30 109 L WITHsignificantriskofbleeding 50 000 mm3 50 109 L forsurgeryorinvasiveprocedures 广州市妇女儿童医疗中心 LungProtectedStrategyProtocol ARDSNETVentilatorManagement 96 Assistcontrolmode volumeventilation Reducetidalvolumeto6mL kgleanbodyweight Keepinspiratoryplateaupressure Pplat 30cmH2O ReduceTVaslowas4mL kgpredictedbodyweighttolimitPplat MaintainSaO2 SpO288 95 AnticipatedPEEPsettingsatvariousFIO2requirementsFiO20 30 40 40 50 50 60 70 70 70 80 90 90 91 0PEEP558810101012141414161820 24 PredictedBodyWeightCalculation Male 50 2 3 height inches 60 or50 0 91 height cm 152 4 Female 45 5 2 3 height inches 60 or45 5 0 91 height cm 152 4 TV tidalvolume SaO2 arterialoxygensaturation PEEP positiveend expiratorypressure 广州市妇女儿童医疗中心 III PediatricConsiderationsinSevereSepsis Whilesepsisinchildrenisamajorcauseofmortality theoverallmortalityfromseveresepsisinchildrenismuchlowerthatthatinadults estimatedatabout10 298 Thedefinitionsforseveresepsisandsepticshockinchildrenaresimilarbutnotidenticaltothedefinitionsinadults 299 Inadditiontoage appropriatedifferencesinvitalsigns thedefinitionofsystemicinflammatoryresponsesyndrome SIRS requiresthepresenceofeithertemperatureorleukocyteabnormalities SepsisisdefinedasinfectionplusSIRS 12 Severesepsisisdefinedassepsisplussepsis inducedorgandysfunctionortissuehypoperfusion Thepresenceofseveresepsisrequiressepsispluscardiovasculardysfunction tissuehypoperfusion orARDSor2ormoreotherorgandysfunctions 299 Septicshockisdefinedasseveresepsisplustissuehypoperfusion amajorhealthcareproblems affectingmillionsofindividualsaroundtheworldeachyear killingoneinfour andoftenmore andincreasinginincidence 1 5 广州市妇女儿童医疗中心 A Antibiotics 1 Werecommendantibioticsbeadministeredwithinonehouroftheidentificationofseveresepsis afterappropriatecultureshavebeenobtained Grade1D Earlyantibiotictherapyisascriticalforchildrenwithseveresepsisasitisforadults 广州市妇女儿童医疗中心 B MechanicalVentilation Nogradedrecommendations Duetolowfunctionalresidualcapacity younginfantsandneonateswithseveresepsismayrequireearlyintubation 300 Drugsusedforintubationhaveimportantsideeffectsinthesepatients forexample concernshavebeenraisedaboutthesafetyofusingetomidate 依托味酯 inchildrenwithmeningococcalsepsisbecauseofadrenalsuppressioneffect 301 Theprinciplesoflung protectivestrategiesareappliedtochildrenastheyaretoadults 广州市妇女儿童医疗中心 C FluidResuscitation 1 Wesuggestinitialresuscitationbeginwithinfusionofcrystalloidswithbolusesof20mL kgover5 10minutes titratedtoclinicalmonitorsofcardiacoutput includingheartrate urineoutput capillaryrefill andlevelofconsciousness Grade2C Intravenousaccessforfluidresuscitationandinotrope vasopressorinfusionismoredifficulttoattaininchildrenthaninadults butit sencouragedearlyinPALS 302 Onthebasisofanumberofstudies itisacceptedthataggressivefluidresuscitationwithcrystalloidsorcolloidsisoffundamentalimportancetosurvivalofsepticshockinchildren 303 308 ThreeRCTscomparetheuseofcolloidtocrystalloidresuscitationinchildrenwithdengueshock 303 307 308 Nodifferenceinmortalitybetweencolloidorcrystalloidresuscitationwasshown 广州市妇女儿童医疗中心 BloodPressure Volume Children sfallinbloodpressurecanbepreventedbyvasoconstrictionandincreasingheartrate Therefore bloodpressurebyitselfisnotareliableendpointforassessingtheadequacyofresuscitation Oncehypotensionoccurs cardiovascularcollapsemaysoonfollow Hepatomegalyoccursinchildrenwhoarefluidoverloadedandcanbeahelpfulsignofadequacyoffluidresuscitation Largefluiddeficitstypicallyexistandinitialvolumeresuscitationusuallyrequires40 60mL kgbutcanbemuchhigher 304 308 Therateoffluidadministrationshouldbereducedsubstantiallywhenthereare clinical signsofadequatecardiacfillingwithouthemodynamicimprovement 广州市妇女儿童医疗中心 D Vasopressors Inotropes D Vasopressors Inotropes shouldbeusedinvolumeloadedpatientswithfluidrefractoryshock 1 Wesuggestdopamineasthefirstchoiceofsupportforthepediatricpatientwithhypotensionrefractorytofluidresuscitation Grade2C Intheinitialresuscitationphase vasopressortherapymayberequiredtosustainperfusionpressure evenwhenhypovolemiahasnotyetbeenresolved Childrenwithseveresepsiscanpresentwithlowcardiacoutput CO andhighsystemicvascularresistance SVR highCOandlowSVR orlowCOandlowSVRshock HighCOandhighSVR earlyormildsepticshock mixedshock Atvariousstagesofsepsisorthetreatmentthereof achildmaymovefromonehemodynamicstatetoanother accordingtowhichVasopressororinotropetherapyshouldbeusedselectivelyandsimulatedly Dopamine refractoryshockmayreversewithepinephrineornorepinephrineinfusion 309 广州市妇女儿童医疗中心 BalancebetweenCOandSVR 2 WesuggestthatpatientswithlowCOandelevatedSVRstates coolextremities prolongedcapillaryrefill decreasedurineoutputbutnormalbloodpressurefollowingfluidresuscitation begivendobutamine Grade2C Thechoiceofvasoactiveagentisdeterminedbytheclinicalexamination ForthechildwithapersistentlowCOstatewithhighSVRdespitefluidresuscitationandinotropicsupport vasodilatortherapymayreverseshock 310 WhenpediatricpatientsremaininanormotensivelowCOandhighSVRstatedespiteepinephrineandvasodilatortherapy theuseofaphosphodiesteraseinhibitormaybeconsidered 311 313 InthecaseofextremelylowSVRdespitetheuseofnorepinephrine vasopressinusehasbeendescribedinanumberofcase reports Thusfarthereisnoclearevidencefortheuseofvasopressininpediatricsepsis 314 315 广州市妇女儿童医疗中心 E TherapeuticEndPoints 1 1 Wesuggestthatthetherapeuticendpointsofresuscitationofsepticshockbe normalizationoftheheartrate capillaryrefillof1mL kg 1 hr 1 and normalmentalstatus 290 Grade2C Capillaryrefillmaybelessreliableinacoldenvironment Otherendpointsincludedecreasedlactateandimprovedbasedeficit ScvO2 70 orSvO2 65 CVPof8 12mmHgorothermethodstoanalyzecardiacfilling Optimizingpreloadoptimizescardiacindex Arterial venousoxygencontentdifferenceassistinginidentifyingacceptableCOisabettermarker氧摄取率 oxygenextractionratio O2ER SaO2 SvO2 SaO2 广州市妇女儿童医疗中心 E TherapeuticEndPoints 2 Bloodpressure BP byitselfisnotareliableendpointforresuscitation Throughthermodilution therapeuticendpointsarecardiacindex CI 3 3and 6 0L min 1 m 2withnormalcoronaryperfusionpressure meanarterialpressure centralvenouspressure forage 290 Usingclinicalendpointssuchasreversalofhypotensionandrestorationofcapillaryrefillforinitialresuscitationatthecommunityhospitallevelbeforetransfertoatertiarycenterwasassociatedwithsignificantlyimprovedsurvivalratesinchildrenwithsepticshock 305 DevelopmentofatransportsystemincludingpublicizingtolocalhospitalsandtransportwithmobileintensivecareservicessignificantlydecreasedthecasefatalityratefrommeningococcaldiseaseintheUnitedKingdom 316 广州市妇女儿童医疗中心 F ApproachtoPediatricSepticShock Figure1showsaflowdiagramsummarizinganapproachtopediatricsepticshock 317 HospitalsshouldimplementtwodifferentSevereSepsisBundles Eachbundlearticulatesrequirementsforspecifictimeframes SepsisResuscitationBundle Tasksthatshouldbeginimmediately butmustbedonewithin6hoursforpatientswithseveresepsisorsepticshock SepsisManagementBundle Tasksthatshouldbeginimmediately butmustbedonewithin24hoursforpatientswithseveresepsisorsepticshock 广州市妇女儿童医疗中心 Figure1showsaflowdiagramsummarizinganapproachtopediatricsepticshock 广州市妇女儿童医疗中心 G Steroids 1 Wesuggestthathydrocortisonetherapybereservedforuseinchildrenwithcatecholamineresistanceandsuspectedorprovenadrenalinsufficiency Grade2C Patientsatriskforadrenalinsufficiencyincludechildrenwithseveresepticshockandpurpura 318 319 childrenwhohavepreviouslyreceivedsteroidtherapiesforchronicillness andchildrenwithpituitaryoradrenalabnormalities Childrenwhohaveclearriskfactorsforadrenalinsufficiencyshouldbetreatedwithstressdosesteroids hydrocortisone50mg m2 24hr Adrenalinsufficiencyinpediatricseveresepsisisassociatedwithapoorprognosis 320 Nostrictdefinitionsexist butabsoluteadrenalinsufficiencyinthecaseofcatecholamine resistantsepticshockisassumedatarandomtotalcortisolconcentration 18 g dL 496nmol L 广州市妇女儿童医疗中心 G Steroids 2 Apost30 or60 minACTHstimulationtestincreaseincortisolof 9 g dL 248mmol L hasbeenusedtodefinerelativeadrenalinsufficiency Thetreatmentofrelativeadrenalinsufficiencyinchildrenwithsepticshockiscontroversial Theuseof