《生儿脓毒症》PPT课件.ppt

新生儿脓毒症 NeonatalSepsis Mostcommoncauseofneonatalmortalityindevelopingcountries Upto20 ofneonatesdevelopsepsisand1 dieofsepsisrelatedcauses Incidenceofsystemicinfectionis3 India withsepticemia 75 andpneumonia 25 NNPNetwork 2005 Early andLate onsetSepsis NeoReviews Vol 11 No 8 August2010 NeonatalSepsis SepticemiaPneumoniaMeningitisArthritisOsteomyelitisUrinarytractinfectionNNPNetwork 2005 NeonatalSepsis Intramuraladmissions Klebsiellapneumoniae 32 5 Staphylococcusaureus 13 6 Extramuraladmissions Klebsiella 27 5 Saureus 38 Sankaretal IndianjPediatr 2008 75 261 6 NeonatalSepsis Definitions Probablesepsis anyonecriteria Maternalfeverorfoulsmellingamnioticfluid PROM 24hrs orgastricpolymorphs 5hpf Positivesepsisscreen anytwocriteria TotalWBCcount 0 2 TotalWBCcount1mg dl microESR 10mm firsthour RadiologicalevidenceofpneumoniaNNF India NeonatalSepsis Definitions Culturepositivesepsis Isolationofthepathogenfromblood CSF urineorabscess 72hoursofagePathologicalevidenceofsepsisonautopsy NNF India NeonatalSepsis Incidence IncidenceofEOSis1 2cases 1000livebirths Thisincidenceis10foldhigherintheVLBWinfants IncidenceofearlyonsetGBShasdeclined80 from1 7cases 1000livebirths 1993 to0 34 1000livebirths 2005 duetointrapartumantibioticprophylaxis Mortality2 6 intermand35 inVLBWinfants SurvivorsofEOSmayhavesevereneurologicsequelaeattributabletomeningitis hypoxemia septicshock PPHNetc PuopoloKM NeoReviews2008 9 e571 579 NeonatalSepsis Classification Earlyonsetsepsis 24hours MorethanthreevaginalexamduringlaborProlongedanddifficultdeliverywithinstrumentationPerinatalasphyxia apgar 4at1min ordifficultresuscitation presenceof3 treat Presenceof2 sepsisscreen Aggarwaletal IndiajPediatr 2001 68 1143 7 NeonatalSepsis Classification Lateonsetsepsis 72hours usuallynosocomialorcommunityacquired Riskfactors NICUadmissionPoorhygieneLowbirthweightPoorcordcarePrematurityBottlefeedingInvasiveprocedureSuperficialinfection pyoderma umbilicalsepsis VentilationAspirationoffeeds Puopolo K NeoReviews2008 9 571 e579 OrganismsCausingNeonatalEarly onsetSepsis OrganismsCausingEarly onsetSepsisinVeryLow birthweightInfants Puopolo K NeoReviews2008 9 571 e579 RiskFactorsforAllCausesofEarly onsetSepsisinInfantsWeighingLessthan2000gatBirthintheEraofIntrapartumAntibioticProphylaxis Puopolo K NeoReviews2008 9 571 e579 RiskFactorsforEarly onsetGBSSepsisintheAbsenceofIAP Puopolo K NeoReviews2008 9 571 e579 Early Pathogens firstweek GroupBStrep GBS Incidenceusedtobe4 6 1000livebirths 0 4 Now 0 1 afterprenatalscreeningguidelinesE coliEveryfewdecadesflipsbackandforthwithGBSasmostcommoncauseGramnegativerods esp inurine OccasionalSalmonellasepsisListeriamonocytogenesHerpesSimplexEnterovirus Late Pathogens 1 2weeks GBSorgroupAstrepEnterics EnterococcusinurineHSVEnterovirus RSV Flu CommunityAcquired after4 6weeks PneumococcusMeningococcusGABHSHaemophilusinfluenzae HIB notreallyaproblemanymore Signs Symptoms TemperatureirregularityFeverHypothermiaToneandBehaviorPoortoneWeaksuckShrillcryWeakcryIrritability SkinPoorperfusionCyanosisMottlingPallorPetechiaeUnexplainedjaundice Mostbythemselvesmeanlittle butthree ortwo strikesandyouareOut Signs Symptoms FeedingProblemsVomitingDiarrheaAbdominaldistensionHypoorHyperglycemia CardiopulmonaryTachypneaRetractionsTachycardiaforageBradycardiainfirstfewdaysoflifeHypotensionforageLowPO2 Signs Symptoms SunkenfontanelleBulgingorpulsatingfontanelleNeckstiffnessCANNOTbeusedBabiescanbebacteremicbutlookwellPresenceofa cold doesnotchangeanything PIDJApril2005 StudyinIndiafoundthatanytwoofthesesignshadanalmost100 sensitivityforsepsisandover90 mortality ReducedsuckingWeakcryCoolextremitiesVomitingPoortoneRetractions NeonatalSepsis Investigations Bloodculture 1mlsampleadequate possibletodetectgrowthin24hoursusingBACTECorBACT ALERTsystemsTotalWBCcount 0 2CRP 1mg dlorMicro ESR 15mm hrLP incidenceofmeningitis0 3 3 InEOSLPisindicatedinthepresenceof bloodcultureorsymptomsofsepticemiaInLOS LPshouldbedoneinallinfantspriortostartingantibiotics NeonatalSepsis Investigations LPshouldnotbedoneinthefollowingcases Asymptomaticbabiesinvestigatedformaternalriskfactors PrematurebabieswithRDS Criticallyillandhemodynamicallyunstablebabies NormalCSFValuesintheNewborn NeonatalSepsis Investigations Urinecultureshouldnotbepartofsepsisevaluationinthefirst72hoursoflife InLOSurinecultureshouldbeobtainedbysuprapubicpunctureorcatheterization UTIdiagnosis 10WBC mmina10mlcentrifugedsample 10organisms mLincatheterizedspecimenAnyorganisminasuprapubicspecimen NeonatalSepsis Investigations ChestXrayincaseofrespiratorydistressorapneaAbdominalXRayifsuspectingnecrotizingenterocolitis NeonatalSepsis NewerDiagnosticTests AcutephasereactantsCellsurfacemarkersGranulocytecolonystimulatingfactorCytokinesMoleculargeneticsMolcellproteomics AcutePhaseReactants TheseendogenouspeptidesareproducedbytheliveraspartofimmediateresponsetoinfectionorinjuryC reactiveproteinProcalcitoninFibronectinHaptoglobinLactoferrinNeopterinOromucosoid HumanC reactiveProteincomplexedwithPhosphocholine Fiveidenticalsubunits protomers thatarearrangedaroundacentralpore NeoReviews 2005 6 e508 515 WhatisCRP Non type specificsomaticpolysaccharidefractionextractedfromStreptococcuspneumoniae FractionC asitwascalledwasprecipitatedbyseraofacutelyinfectedpatientsandseraofconvalescentpatientslosttheabilitytocauseprecipitation Acutephasereactantproteincomposedoffiveidenticalnonglycosylatedpolypeptidesubunits Itissynthesizedinhepatocytes regulatedatthetranscriptionlevelbyinterleukin IL 6andIL 1 beta TheexactfunctionofCRPisnotknown CRPactivatescomplementandhasafunctionaleffectonphagocyticcellsandplayanimportantroleinthefirstlineofhostdefense CRPmaybeakeycomponentinlipidmetabolismandcontributetothepathogenesisofatherosclerosisandmyocardialinfarction CRPValuesintheBlood Inhealthyadults 0 8mg LIninfants 10mg LStartswithin4 6hoursafterstimulationandpeaksaround36 48hours Biologichalflifeis19hourswith50 reductiondailyaftertheacutephasestimulusresolves MeasuringCRPconcentrationinCSFisunreliable CellSurfaceMarkersandGranulocyteColonyStimulatingFactors NeutrophilCD11bandCD64appeartobepromisingmarkers CD64hadsensitivityof80 andspecificityof79 incultureprovensepsis CD11bhadasensitivityof96 100 andspecificityof81 100 incultureprovensepsis GSF mediatorproducedbythebonemarrowfacilitatesproliferationofneutrophilsinsepsis Aconcentrationof 200pg mlhasasensitivityof95 andspecificityof99 Procalcitonin PCT PCTisproducedbythemonocytesandhepatocytesandispropeptideofcalcitonin PCTrises4 6hoursafterexposuretobacterialendotoxinpeakingat6 8hours HalflifeofPCT25 30hours ElevatedconcentrationsarefoundinRDS IDMandhemodynamicallyunstableinfants PCTvaluesof 2 3ng mlandCRP 30mg Lindicatesahighlikelyhoodoflateonsetsepsis CRPConcentrationinSepsis Sensitivity Specificity PredictiveValues Serialmeasurementsinearlyandlateonsetsepsisshowedthebestcutoffvalueof10mg L Stanford CRPconcentrationwasnormalin30 ofallsepsisepisodes PPVwas5 forcultureprovenearlyonsetsepsisand43 inlateonsetsepsis GreaterelevationinCRPconcentrationswereassociatedwithhigherprobabilityofinfection Negativepredictivevaluewashighestbothforearlyandlateonsetsepsisafterthreevalues 99 7and98 7 TwoCRPconcentration 10mg Lobtained24hoursapartmakessepsisunlikely Benitzetal Pediatrics 1998 102 e41 C reactiveProtein rateNephalometry NeoReviews 2005 6 e508 515 LightscatteredisProportionaltoconcentrationofantigen FactorsThatCanInfluenceCRPValues ModeofdeliveryGestationalageTypeoforganismcausingsepsisGranulocytopeniaSurgeryImmunizationsSevereviralinfections eg herpessimplexvirus rotavirus influenza NeoReviews 2005 6 e508 515 CytokinesinSepsis Cytokinesmediatecommunicationbetweencellsofthebodybybindingtospecificcellularreceptorsandtransducingsignalsintodifferenttargetcellswithbiologiceffectsthatplayaroleinthepathogenesisofsepsis Interleukin 6 mononuclearphagocyte hasbeenconsistentlyshowntoincreaseinearlyonsetsepsis butsensitivityisreducedat24 48hoursastheconcentrationrapidlyfallsandbecomesundetectableat24hours NormalplasmaconcentrationofIL6is10pg mL CombinedmeasurementofIL6 earlysensitive withCRP lateandspecific inthefirst48hoursimprovessensitivitycomparedtoeithermarkeralone Mehretal pediatrInfecDisJ 2000 19 879 87 CytokinesinSepsis IL8isproinflammatorycytokine mononuclearphagocyte thatisconsideredtobeanaccuratemarkerwithsensitivitiesrangingfrom80 91 andspecificities76 100 AcombinationofIL8 70pg ml andCRP 10mg L showedasensitivityof80 andaspecificityof87 TNF andmedianIL6valuesweresignificantlyhigherinpatientswithsepsiscomparedtocontrols Franzetal Pediatrics2004 114 1 8 MolecularGeneticsinSepsis Polymerasechainreaction PCR analysisreliesonthefactthatbacteriaspecific16SrRNAgeneisconservedinallbacterialgenomesandisausefulmethodforidentificationofbacteriainclinicalsamples PCRassayischallengingduetosmallamountofresidualDNApresentreagentsresultinginfalsepositivity DetectionbyPCRdoesnotyieldtheantimicrobialpatternofthepathogen RealtimePCRcombinedwithDNAMicroArraytechnologywillallowidentificationandantimicrobialsensitivityoftheorganism Proteomics Significantalterationsinthelevelsofeightserumproteinswerefoundininfectedneonates StartParenteralAntibiotic Ab SendCultures reportin72hrs Culture ve Clinicallywell StopAb Clinicallyill ContAbx7 100 Culture ve Pneumonia Sepsis ContAbx7 100 Meningitis Osteomyelitis ContAbx3