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Alternativetherapiesinpediatricrespiratoryfailure·CopyrightbyPICUofSCMCThankyouforyourcooperationHistoryofpediatricrespiratoryfailure1988reviewofpedsARDS5retrospectivestudieswith69kidsoverallmortality59%Historyofpediatricrespiratoryfailure1991(TimmonsODetal.JPeds1991;119:896-899)44childrenwithARDS(1987-1990)FiO2>50%andPEEP>6cmH2Ox12hrsmortalityrateof75%predictorsofdeath:shuntfraction>50%(93%)Paw>23cmH2O(90%)AaDO2>470(81%)HistoryofpediatricrespiratoryfailureNoonebelievedit!Multi-centerevaluationofPICUptsundertakenFiO2>50%andPEEP>6cmH2Ofor>12hrs41hospitalssubmitteddatafor19917,876chartsscreened,739formssubmitted233ptsexcluded470patientsreportedHistoryofpediatricrespiratoryfailure2weeksto18yrsofage,1991calendaryearExcludedcardiacsurgerypatientsandcyanoticheartdiseaseExcludedcontraindicationstoECMObraindeathfixed,dilatedpupilswithdrawalofsupportforfutilityTimmonsODetal.Chest1995;108:789-797.HistoryofpediatricrespiratoryfailureOverallmortality43%lessthan75%butnotgreatSerialevaluationofpaO2andpaCO2notsignificantforpredictingdeathRiskofdeathmodeldevelopedbasedonOIandPRISMscoresOI=OxygenationIndex=(PawxFiO2)/paO2PRISM=PediatricRiskofMortalityTimmonsODetal.Chest1995;108:789-797.CausesofdeathTimmonsODetal.Chest1995;108:789-797.ECMOuseinpedsrespiratoryfailureExaminedpatientsindatacollectionprojectwhoreceivedECMOandcomparedtothosewithoutAnalysisofsurvivalbasedondemographic,treatmentvariables(ECMO,HFOV,etc)andseverityofdisease(PRISM,OI,worstpaO2/paCO2,PIPetc)GreenTPetalCritCareMed1996;24:323-29UseofECMOinpedsrespfailureFoundcorrelatedwithmortalityOIPRISMuseofECMO(bettersurvivalifused)paCO2(highernumberbetter)UseofHFOVandtreatmentinanECMOhospitalnotcorrelatedwithoutcomeGreenTPetalCritCareMed1996;24:323-29Thecircuitiscomplexandexpensive

pumpoxygenatorConditionsofcardiorepiratoryfailuresupportedbyECMOSeverepulmonaryairleaksARDSArrhythmia-refratoryAspirationBurnCardiacArrestCardiacfailureMASMyocarditisPneumoniaPPHNNRDSSepsisStatusasthmaticusTrauma2004summaryofECMOruninneonatestotalrunsruntime/dayspercentsurvivedMAS51775.394CDH3132953Sepsis20885.759PPHN20655.778RDS12685.584pnuemonia151959other7406.864Openbars=ECMOpatients.DotispredictedmortalityGreenTPetalCritCareMed1996;24:323-29ConclusionsECMOpatientsin50-75%quartilehad28%vs71%mortalityinnon-ECMOptsSmallsamplesizeinothergroupsaproblem?Needfornationaldatabasesandcomparisons?randomizedtrialsGreenTPetalCritCareMed1996;24:323-29Recapping:HistoryofPediatricRespiratoryFailure

FiO2>50%andPEEP>6Mortality75%(Timmons)Multi-centerdatacollectionMortality43%(Timmons)DataevaluatedforuseofHFOVandECMOHFOV:nochangeinmortalityECMO:improvedsurvivalRandomizedECMOtrialEntrycriteria:FiO2>50%andPEEP>6cmH2OHighmortality=60%predictedbasedonPRISMandOI(Green)Eligible+Highmortality=randomizedTrialstoppedearlywheninterimanalysisshowedlowmortalityFacklerJCetalpersonalcommunicationVentmanagementstrategypH>7.25PIP<30cmH2OTVaslowas5-6cc/kgSats88-93%PEEPtoreduceFiO2<0.6FacklerJCetalpersonalcommunicationFinalResultsMortality18%inECMOeligibleMortality59%inECMOineligibleWhyarewedoingsowell?PronepositioningpermissivehypercapniaHFOViNOSmarterdocsandcaregiverswhogivebettercareandgetbetteroutcomesPronepositioningandAcuteRespiratoryFailureShowntoimproveoxygenationin60-70%1996-98registrykeptofptswithARF214patientsPaO2/FiO2<200withPEEP>5cmH2OPaO2/FiO2<300withPEEP>10cmH2OMortalityrateof49.5%52ptsrandomlyassignedtoproneorsupinePronepositioningandrespiratoryfailureRandomizedtopronepositioningforatleast6hours/dayfor10days1996-1999,144patientsrandomized53%diedinICUImprovedpaO2/FiO2inproneTVincreasedinprone,decreasedinsupineNodifferenceinincidenceoforgandysfunctionPronepositioning

Lower10daymortalityinptswith:worstpaO2/FiO2ratio(<88),23%vs47%Highesttidalvolume(>12cc/kg),18%vs41%MortalitydifferencesnotevidentafterdischargefromICUPronepositioningandsurvivalinARDSpeds.ptswithp/f<200,Murrayscore>2.518responders,17non-respondersSurvival52%overall(48%mortality)20%innon-responders(80%mortality)61%inresponders(39%mortality)Casado-FloresJetal.IntCareMed2002;28:1792-6.HighFrequencyVentilationMaintainslunginopenpositionbykeepinginflationthroughoutrespiratorycycleSmallbreathsoscillatearoundPawAssociatedwithlessbarotrauma,shearstress,cytokineproduction“Kinder,gentlerventilation”DefinitionofHFOVDevicesoperates2-3timesnormalfreqSlutsky:ventilatedfreqis4timesofnormalbreathingVentilationdeliversaVTthatislessthanthedeadspacevolumeInpediatric,freqisdefinedas>150/minAdvantagesofHFOV

pressure-volumerelationshipsofALIIndication(PICU)PtwithpulmonaryhemorrhagePtwithinadequateoxygenationnotamenabletoCMVpathwaya)OI>15b)PEEP>10cmH2Oc)FiO2>.60d)PIP≥32cmH2Oe)MAP>15cmH2OAdultARDS“HFOV-CaringfortheBabyinAdults”BabyLungSittingonTopofaConsolidatedLungTidalVolumesof6-10ml/kgbasedonweightTidalVolumesof20-50ml/kgbasedonopenlungunitsHistologyissimilartoinfantlunginjuryVentilatorInducedLungInjuryPrematurebaboonmodelCoalsonJ.UnivTexasSanAntonioVentilatorInducedLungInjuryHFOVwithSurfactantasComparedtoCMVwithSurfactantinthePrematurePrimateHFOVresultedinLessRadiographicInjuryLessOxygenationInjuryLessAlveolarProteinaceousDebrisJacksonCAJRCCM1994;150:534VentilatorInducedLungInjuryHighLungVolumeStrategieswithHFOVExtendedSurfactantActivityNormalizedLamellarBodyPhospholipidlevelsImprovedlungmechanicsAllConventionalVentilatorStrategiesResultedinDeathorDecreasedSurfactantPerformanceFroeseA,ARRD1993;148:569HFOVProspectiveRCT’s

OutcomesSummary

TheRandomizedControlledTrialsofthe3100AhaveDemonstratedthatthe3100A:ReducestheseverityofCLDinRDSinfantsDecreasesthecostofhospitalizationforRDSDecreasestheneedforECMOineligiblecandidatesDecreasesairleakinsevereRDSImprovessurvivalwithoutCLDinpediatricARDSCochraneMeta-AnalysisPartofCochraneCollaborativeOnlyHighVolumeHFOVStudiesReducedIncidenceofCLDNoIncreasedNeuromorbidityRiskNullHFOVMeta-AnalysisOnly3100ARandomizedControlledTrialsOutcomedatabasedonmaturityHFOVassociatedwithlessCLD,airleak,bettersurvivalNodifferenceinneuromorbidityPediatricDataArnoldJ,etal:Prospective,randomizedcomparisonofHFOVandCMVinpediatricrespiratoryfailure.CritCareMed1994.58pediatricpatientsSurvivalwithoutsevereCLDforHFOV(83%)ascomparedtoCMV(30%)SurvivalwithCLDforHFOV(11%)ascomparedtoCMV(30%)PediatricData(Arnold)OIatbaseline26+10HFOV,28+14CMVOI>42at24hpredicteddeathOR20.8,sens.62%,spec93%OIinsurvivorsHFOVat24h26vs.41innon-survivorsPediatricRandomizedControlledTrialAt30daysthereweresignificantdifferencesinoutcomemeasuresthatreflectedabenefitfortheuseofHFOVPediatricRandomizedControlledTrialSixmonthfollow-updemonstratedacontinueddifferenceinoutcomemeasuresthatreflectedsignificantbenefitsfortheuseofHFOVforPediatricARDSPediatricRandomizedControlledTrialUseofHFOVHFOVandsurvival26pts>1monthofage(mean3.7yrs)Paw>15andFiO2>0.6forsats>89%HFOVwithhighvolumestrategyEarlyHFOV:<24hrsMV(n=17)LateHFOV:>24hrs(n=9)Overallsurvival42%(mortality58%)EarlyHFOV:survival59%(mortality41%)LateHFOV:survival12.5%(mortality88%)2ptsreceivedECMOFedoraMetal.BratislLekListy2000;101:8-13WhenisHFOVafailure?InitialOI>20andfailuretodecreaseOIby>20%by6hoursofHFOV:death:88%sens,83%spec,OR33InitialpaO2/FiO2<90torrandfailuretoincreaseby>20%at6hours:death:63%sens,91%spec,OR17.5SarnaikA,MeertK,etal:CCM1996;24:1396-1402IntroductionDiscoveredbyaccident(1980)Initiallycalledendothelium-derivedrelaxantfactor(EDRF)Industrialpollutant(cigarettesmoke,etc)ThefirstFDAapprovedgaseouspharmaceuticalExpensive($3,000/d)NOselectivityPAPSVRV/QNO↓NochangeNochangeorimprovedNitroprusside↓↓worsennitrate↓↓worsenProstacycline↓↓worsentolazoline↓↓worsenPAP-pulmonaryarterypressureSVR-systemicvascularresistanceV/Q-ventilation-perfusionmismatchNitricOxide:MoleculeoftheMilleniumMulticentertrialofiNOinPediatricsiNOimprovedoxygenationandOIat4and12hours,nochangefromcontrolby72hPatientswithOI>25orimmunocompromisehadmoresustainedresponsetoiNONodifferenceinmortalitybetweencontrol(43%)andiNO(42%)DobynsE,CornfieldD,etal.JPeds1999;134:406-12InhaledNitricOxide,HFOVLookedthenatpatientswhoreceivedHFOVandCMV,withorwithoutiNODobynsEetalJPediatr1999;134:406;CritCareMed2002;30:2425DobynsEetalJPediatr1999;134:406;CritCareMed2002;30:2425DobynsEetalJPediatr1999;134:406;CritCareMed2002;30:2425iNOandHFOVEvaluationofHFOVvs.CMVwithiNOSurvival:HFOV+iNO=10/14,71%,HFOValone=7/12,58%CMV+iNO=20/35,53%CMV=22/38,58%SurvivalunchangedbetweengroupsDobynsEetalJPediatr1999;134:406;CritCareMed2002;30:2425

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