Pediatric-Poisoning-Emory-University：小儿中毒-埃默里大学课件

PediatricPoisoningsMarkSutter,MDPediatricPoisoningsMarkSutte1OverviewEpidemiologyImportantLegislationPackagingandMarketingProblemsPhysiologicDifferencesIronPesticidesDeadlyPediatricPoisonsOverviewEpidemiology2EpidemiologyUSPoisonCentersreceive1.5millioncallsayearregardingpediatricingestions.79%ofthesecallsinvolvechildrenyoungerthanagesix.56%ofpediatricexposuresarefromproductsaroundthehouseincludingmedicines,cleaningagents,pesticides,plantsandcosmetics.EpidemiologyUSPoisonCenters3Epidemiology99%ofingestionsbychildrenunder6areunintentional.Approximately40%ofingestionsreportedtothepoisoncenterbyadolescentsareintentional.Approximately56%ofadolescentingestionsarebyfemales.Epidemiology99%ofingestions4EpidemiologyEpidemiology5LegislationThePoisonPreventionPackagingActof1970.(PPPA)Requireschildprotectivepackagingofhazardoushouseholdproducts.Overthelast30yearsthelistofsubstancesregulatedbythePPPAhaveexpandedtoincludemedicines,solvents,andoils.Datashowsreductionof45%mortalityofpediatricpatientssincetheintroductionandexpansionofPPPA.LegislationThePoisonPreventi6SpecialPediatricIssuesALLTHINGSTENDTOENDUPINTHEMOUTHSOFYOUNGCHILDREN!!SpecialPediatricIssuesALLTH7WhichisCandy?WhichisCandy?8SweetTartsvs.EcstacySweetTartsvs.Ecstacy9PoisonCenterCampaignPoisonCenterCampaign10PhysiologicDifferencesBloodbrainbarrierstillmorepermeabletotoxicologicsubstancesuntilaround4months.Nostudiesdemonstratingincreasedpermeability,ratherthisisanestimatebasedontoxicitynotedwithsmallerdosesthanexpected.Highermetabolicdemands.Decreasedabilitytoglucuronidateintheinfantperiod.Secondtrimesterpregnanciesthatwereterminatedshowedonly10%activityoftheP-450system.Nobetterstudiestodate,butmostbelievebetweenages2-4yearsthatglucuronidationisequivalenttoadults.Decreasedglycogenstores.PhysiologicDifferencesBloodb11PhysiologicDifferencesIncreasedbodysurfaceareacanleadtothermoregulatoryissues.Childrenresidelowertotheground.Thisputsthemathigherriskforingestingcompoundsheavierthanair.OftenadultswillNOThavethesameexposure.Inabilitytoavoidhazards–theydonotreadwarninglabelsor“DoNotEnter”signs.PhysiologicDifferencesIncreas12IronThemostcommoncauseofdeathintoddlers.Classicallytaughtashavingfiveclinicalstages.Rememberprenatalvitamins,supplements,and“naturalproducts”.IronThemostcommoncauseofd13IronToxicdosesoccurat10-20mg/Kgofelementaliron.Prenatalvitaminstypicallycontainabout65mgofelementaliron.Childrensvitaminscontainabout10-18mgofelementaliron.IronToxicdosesoccurat10-2014TheFiveStagesStage1Nausea,vomitting,abdominalpainanddiarrhea.Stage2Thisisthelatentphaseoftenbetween6-24hoursasthepatientresolvesGIsymptoms.Stage3Shockstageinvolvingmultipleorgansincludingcoagulopathy,poorcardiacoutput,hypovolemia,lethargyandseizures.Stage4Continuingofhepaticfailureandongoingoxidativedamagebytheironinthereticuloendothelialsystem.Stage5Gastricoutletobstructionsecondarytoscarringandstrictures.TheFiveStagesStage115ManagementDetailedhistoryandphysicalincludingarectalexamforfrankblood.Aggressivefluidresuscitationandintravenousaccess.WholebowelirrigationandKUBtolookforpills.LaboratoryanalysisforCBC,chemistry,andironlevels(peakaround4hours).Willoftenrequirerepeatlevelswitharepeatchemistry.TIBChasnoutilityintheacuteoverdosesetting.ManagementDetailedhistoryand16ManagementManagement17ManagementIfthepatientisinshock,remembertoatleasttypeandscreen(ifnotcrossmatch)forblood.Givedeferoxaminebeforeironlevelisbackifthepatientisinshock.Deferoxaminewasderivedfromstreptomycespilosus.Hypotensionandallergicreactionsareseen.ARDSisaknowncomplicationandusuallylimititsuseto24hoursorless.ManagementIfthepatientisin18PesticidesSpecificallyorganophosphatesandcarbamates.Theyworkbyinhibitingacetylcholinesterase.PresentwithcholinergicsymptomsPesticidesSpecificallyorganop19CholinergicSymptomsCholinergicSymptoms20NicotinicSymptomsRememberthedaysoftheweek!MydriasisTachypneaWeaknessTachycardiaFasiculationsPediatricpatientstendtopresentwithapredominanceofnicotinicsymptoms!!!NicotinicSymptomsRememberthe21WeaknessfromPesticidesWeaknessfromPesticides22TreatmentAtropine0.02mg/KgIV.Repeatasneededandtitratetorespiratorysecretions.Itwilllikelytakemassivedoses!!Pralidoxime(2-Pam)20-40mg/Kgbolusfollowedby10-20mg/Kg/hourinfusion.RemembertosendRBCandPlasmaCholinesteraselevelsuponarrivalanddaily.TreatmentAtropine0.02mg/Kg23TheExpanded“OnePillKill”TheExpanded“OnePillKill”24TheDeadlyPediatricPoisonsCalciumChannelBlockersCyclicAntidepressantsLomotilOpiates/OpiodsSalicylates(methyl)ToxicAlcoholsSulfonylureasCamphorClonidineandimidazolinesAntimalarialsTheDeadlyPediatricPoisonsCa25CalciumChannelBlockersThreemajorclassesPhenylalkylamineBenzothiazepineDihydropyridineBlockL-typechannelsCausehypotension,bradycardia,andarrythmias.Immediateandsustainedrelease.Usuallynotthechildsmedication.CalciumChannelBlockersThree26CalciumChannelBlockersManageA,B,C’sCheckLabsandEKGFluidsCalciumGlucagonPressorsHighDoseInsulinAtorpineandPacingCalciumChannelBlockersManage27CalciumChannelBlockersMaybeabletoweanpressorswithinsulin.Insulindosageis1unit/kgbolusand0.5units/kg/hourdrip.MonitorsugarQ20minutesforthefirstfewhours.MostwillNOTbecomehypoglycemic.CalciumChannelBlockersMaybe28CyclicAntidepressantsTheyweretheleadingcauseofpoisoningfatalityuntil1993.Theyinterferewithreuptakeofbiogenicaminesandserotoninatthenerveterminal.Manifesttoxicitybyanticholinergiceffects,alpha-1inhibition,sodiumchannelblockade,andcaninhibitGABA.CauseCNSandcardiovasculartoxicitywitharrythmiasleadingtomortality.CyclicAntidepressantsTheywer29EKGFindingsEKGFindings30EKGFindingsEKGFindings31CyclicAntidepressantManagmentManageA,B,C’saggressivelyOptimizeelectrolytesFollowserialEKG’sanduseBicarbif:QRS>100or110msecaVr>3mmIfbicarbonateandmagnesiumarenoteffective,lidocaineistheantidysrhythmicofchoice.Norepinephrineisthepressorofchoiceforrefractoryhypotension.CyclicAntidepressantManagmen32IsittheSodiumortheBicarb?TheanswerisBOTH!Sodiumovercomesthepartialblockadefromcyclicantidepressants.Alkalinizationdoeschangebindingproperties.IsittheSodiumortheBicarb33Howdoesthebicarbwork?InitiallythoughttoincreaseproteinbindingthuslimitingfreedruginthebloodRatstudyusingalpha-1acidglycoprotein(AAG)onlydecreasedarrhythmiasatmassivedoses.AAGisaprovenTCAbinder.CurrenttheoriesisthattheionicformoftheTCAbindstothesodiumchannelcausingblockadeandthebicarbonatechangestheTCAfromtheionicformtotheneutralformcausinglessblockade.Howdoesthebicarbwork?Initi34LomotilAntidiarrhealagentcontainingbothdiphenoxylateandatropine.BothagentsareabsorbedbytheGItractandabsorptionmaybedelayedinoverdoseduetoinhibitoryeffectsonsmoothmusclemotility.Diphenoxylateisanopoidthatismetabolizedtodifenoxinwhichis5timesmorepotentthantheparentcompoundandhashalflifeof12-14hours.LomotilAntidiarrhealagentcon35LomotilPatientsmanifestsignsandsymptomsofopiatetoxicity.Respondwelltonaloxoneandsupportivecare.Currentrecommendationsareforaminimumof24hourobservation.LomotilPatientsmanifestsigns36Opiates/OpiodsTypicallypresentwithrespiratorydepression,alteredmentalstatus,andmiosis.Addressthepatientlikeanyother“alteredmentalstatus”Keypointistoremembertoconsideranopiateingestion.Opiates/OpiodsTypicallypres37NaloxoneDosingUsuallystartwith0.01-0.1mg/Kg.Repeatasfrequentlyasneededtoreversesymptoms.Ifadripisrequired,calculatehowmuchnaloxonewasusedinthefirsthourandstartthedripat2/3thatdose.NaloxoneDosingUsuallystartw38SalicylatesSalicylates39PharmacologyIrreversiblyinhibitstheenzymecyclooxygenase.Thisinhibitsprostaglandinsynthesis.Sinceprostaglandinsarenotsynthesized,theirdownstreambyproductsareneverreleasedsuchas:IL-6,TNF,andalphaandbetainterferons.Believedtodirectlyinhibitneutrophilstodecreasetheinflammatoryresponse.PharmacologyIrreversiblyinhib40SalicylateMetabolismSalicylateMetabolism41PathophysiologySalicylatesstimulatethebrainstemtocausehyperventilation(respiratoryalkalosis).Multifactorialrenalimpairmentleadstoaccumulationofsulfuricandphosphoricacids.InterferewiththeKrebsCyclelimitingsubstratesforATPgeneration.PathophysiologySalicylatessti42PathophysiologyContinuedUncouplesoxidativephosphorylationwhichleadstoincreasedpyruvicandlacticacidlevelandgeneratesheat.Causessalicylateinducedfattyacidmetabolismwhichproducesketonebodies.Thisketoacidosiscontributesasignificantportiontotheoverallmetabolicacidosis.PathophysiologyContinuedUncou43ClinicalManifestationsEarlysymptomsareusuallynon-specificsuchasnauseaandvomiting.Tinnituswithorwithouthearinglosscanalsobeanearlysign.Hyperventilationisoftenawarningsignofasignificantingestion.CNSsignscanvaryfromvertigotohallucinationstostupor.Comaisrareexceptinmassiveoverdoses.Inlargeoverdoses,almosteveryorgansystembecomesinvolved.ClinicalManifestationsEarlys44TreatmentAddresstheA,B,C’s.Detailedhistoryandexam.Laboratoryevaluationandconsiderabloodgasifyourhistorysuggestsaningestion.Activatedcharcoalshouldbegiven.Evidenceformultidosecharcoalisequivocal.Theuseofsodiumbicarbonate.Measureserialsalicylatelevelsandchemistries.TreatmentAddresstheA,B,C’s.45SodiumBicarbonateTherapyThegoalistotitratetheurinarypHto8.Potassiummustbemonitoredcloselybecauseifthepotassiumdrops,thekidneywillretainthepotassiumandexcretehydrogen.ExcretionofhydrogenwillmakeitimpossibletotitrateyourtherapytoaurinarypHof8.SodiumBicarbonateTherapyThe46IndicationsforHemodialysisRenalfailure.Congestiveheartfailure(relative).Acutelunginjury.PersistentCNSdisturbance.Severeacid-baseorelectrolyteimbalance,despiteappropriatetreatment.Hepaticcompromisewithcoagulopathy.Salicylateconcentration(acute)>100mg/dL.IndicationsforHemodialysisRe47ToxicAlcoholsEthyleneGlycolAntifreezeCoolantMixturesMethanolWindshieldwiperfluidMoonshineToxicAlcoholsEthyleneGlycol48EthyleneGlycolandMethanolfomepizoleMg,B6folatethiamineEthyleneGlycolandMethanolfo49TheOsmolarGapTheOsmolarGap50ClinicalSymptomsClinicalSymptoms51TreatmentFomepizoleorethanol–bothinhibitalcoholdehydrogenase.CofactorsPyridoximeFolateMagnesiumThiamineTreatmentFomepizoleorethanol52FomepizoleDosingLoadingdose15mg/KgNext4doses10mg/KgSubsequentdoses15mg/KgDosingscheduleisevery12hoursexceptduringdialysis.Thenitisevery4hoursduringdialysisasitgetsdialyzedoff.FomepizoleDosingLoadingdose53SulfonylureasSulfonylureas54MechanismofActionSulfonylureaskeepthepotassiumeffluxchannelclosed.Thiskeepsthecelldepolarizedwhichallowsthevoltage-gatedcalciumchanneltoremainopen.Thisstimulatesinsulinrelease.MechanismofActionSulfonylure55SulfonylureasSincesulfonylureasstimulateinsulinrelease,thiscanresultinprolongedhypoglycemia.Continueddosesofdextrosewillcontinuetostimulateinsulinrelease.Octreotideworksbyantagonizinginsulinrelease.Exactmechanismisstillbeingdebated.SulfonylureasSincesulfonylure56OctreotideThedoseis1-2mcg/KgbolusIVorSC.Somepaperssuggestacontinuousinfusionwhileotherssuggestanevery8hourdosingregimen.Ifplacedonanoctreotideregimen,theoctreotidemustbeoffaminimumof24hourswithoutanotherepisodeofhypoglycemiabeforedischarge.OctreotideThedoseis1-2mcg57KeyFactsAretrospectivestudyshowed4of25patientsdevelopeddelayedhypoglycemiaincluding1at16hourspostingestion.Ifasulfonylureaisingested,aminimumof24hoursofobservationisrecommended.

KeyFactsAretrospectivestudy58CamphorAromaticketonederivedfromplants.Actsasatopicalrubefacient.Usuallyingestedasaliquid.Ofteninpreparationscombinedwithothermedicinessuchassalicylates.CamphorAromaticketonederived59CamphorInitialsymptomsaregastrointestinaldistressandgeneralizedfeelingsofwarmth.Symptomsusuallyprogressquicklytonervoussysteminvolvementfromrestlessnesstoseizures.Delayedseizureshavebeenreportedupto9hoursafteringestion.CamphorInitialsymptomsarega60CamphorIngestionsof1-2gramshavebeenfatalinchildren.A19montholddiedafteringesting5mlof20%camphoratedoil.Asymptomaticpatientsshouldbeobserved6-8hoursanddischargedifnotdevelopingsymptoms.Rememberabouthydrocarbonaspirationifproductisanoilwithahistoryofcoughingorvomitting.CamphorIngestionsof1-2grams61ClonidineandImidazolinesClonidineisanalpha-2agonistthatisusedforhypertension.Imidazolines,suchasoxymetazoline(afrin)areusedasdecongestants.Symptomstypicallypresentlikeanopiateoverdose?

Why?ClonidineandImidazolinesClon62?LikeanOpiateOverdose?TheyareNOTstructurallyrelatedtoopiates.Thealpha-2receptortargetedbyclonidinehassignificantfunctionaloverlapwiththeopiatereceptor.Bothmaybelocatedonthesameneuron,bothcoupledbyviaG-proteintothesamepotassiumchannel.Mayrequirelargerdosesofnaloxonetoreversesymptoms.?LikeanOpiateOverdose?The63AntimalarialsTheseincludecloroquine,hydroxychloroquine,quinineandtheirrelatives.Theyworkbybothsodiumchannelblockadeaswellasblockadeofthepotassiumrectifierchannel.TheseleadtoQRSwideningaswellasQTprolongation.Torsadesisaknowncomplicationofoverdose.AntimalarialsTheseincludeclo64SymptomsSmalltherapeuticindex.Presentswithsymptomatologyknownas“cinchonism”whichistachycardia,nausea,vomitting,hearingloss,tinnitus,headache,vertigo,dystonia,anddiarrhea.Patientsoftenknowntohaveaflushedappearance.SymptomsSmalltherapeuticinde65TreatmentThesepatientsrequireaggressivemanagementofelectrolytes.IftheQRSwidens,treatmentwithsodiumbicarbonateisindicated.MagnesiumshouldbeusedforTorsades.Ifventriculararrythmiasoccurdespiteoptimalmanagement,lidocaineisthetreatmentofchoice.(Avoidclass1a,1c)TreatmentThesepatientsrequir66SelectedToxicDosagesSelectedToxicDosages67SummaryRememberthe“DeadlyPediatricPoisons”Don’tbefooledifthe“lookgood”assignificanttoxicityisstillpossible.ContactthepoisoncenterearlyasknowingthedosageandtimeofingestioncaninfluenceyourmanagementSummaryRememberthe“DeadlyPe68ReviewArticlesMichaelJB,SztanjnkrycerMD.Deadlypediatricpoisons:ninecommonagentsthatkillatlowdoses.EmergencyMedicineClinicsofNorthAmerica2004;(22):1019-1050.Bar-OzB,LevichekZ,KorenG.Medicationsthatcanbefatalforatoddlerwithonetabletorteaspoonful.PediatricDrugs2004;6(2):123-126.ReviewArticles69PediatricPoisoningsMarkSutter,MDPediatricPoisoningsMarkSutte70OverviewEpidemiologyImportantLegislationPackagingandMarketingProblemsPhysiologicDifferencesIronPesticidesDeadlyPediatricPoisonsOverviewEpidemiology71EpidemiologyUSPoisonCentersreceive1.5millioncallsayearregardingpediatricingestions.79%ofthesecallsinvolvechildrenyoungerthanagesix.56%ofpediatricexposuresarefromproductsaroundthehouseincludingmedicines,cleaningagents,pesticides,plantsandcosmetics.EpidemiologyUSPoisonCenters72Epidemiology99%ofingestionsbychildrenunder6areunintentional.Approximately40%ofingestionsreportedtothepoisoncenterbyadolescentsareintentional.Approximately56%ofadolescentingestionsarebyfemales.Epidemiology99%ofingestions73EpidemiologyEpidemiology74LegislationThePoisonPreventionPackagingActof1970.(PPPA)Requireschildprotectivepackagingofhazardoushouseholdproducts.Overthelast30yearsthelistofsubstancesregulatedbythePPPAhaveexpandedtoincludemedicines,solvents,andoils.Datashowsreductionof45%mortalityofpediatricpatientssincetheintroductionandexpansionofPPPA.LegislationThePoisonPreventi75SpecialPediatricIssuesALLTHINGSTENDTOENDUPINTHEMOUTHSOFYOUNGCHILDREN!!SpecialPediatricIssuesALLTH76WhichisCandy?WhichisCandy?77SweetTartsvs.EcstacySweetTartsvs.Ecstacy78PoisonCenterCampaignPoisonCenterCampaign79PhysiologicDifferencesBloodbrainbarrierstillmorepermeabletotoxicologicsubstancesuntilaround4months.Nostudiesdemonstratingincreasedpermeability,ratherthisisanestimatebasedontoxicitynotedwithsmallerdosesthanexpected.Highermetabolicdemands.Decreasedabilitytoglucuronidateintheinfantperiod.Secondtrimesterpregnanciesthatwereterminatedshowedonly10%activityoftheP-450system.Nobetterstudiestodate,butmostbelievebetweenages2-4yearsthatglucuronidationisequivalenttoadults.Decreasedglycogenstores.PhysiologicDifferencesBloodb80PhysiologicDifferencesIncreasedbodysurfaceareacanleadtothermoregulatoryissues.Childrenresidelowertotheground.Thisputsthemathigherriskforingestingcompoundsheavierthanair.OftenadultswillNOThavethesameexposure.Inabilitytoavoidhazards–theydonotreadwarninglabelsor“DoNotEnter”signs.PhysiologicDifferencesIncreas81IronThemostcommoncauseofdeathintoddlers.Classicallytaughtashavingfiveclinicalstages.Rememberprenatalvitamins,supplements,and“naturalproducts”.IronThemostcommoncauseofd82IronToxicdosesoccurat10-20mg/Kgofelementaliron.Prenatalvitaminstypicallycontainabout65mgofelementaliron.Childrensvitaminscontainabout10-18mgofelementaliron.IronToxicdosesoccurat10-2083TheFiveStagesStage1Nausea,vomitting,abdominalpainanddiarrhea.Stage2Thisisthelatentphaseoftenbetween6-24hoursasthepatientresolvesGIsymptoms.Stage3Shockstageinvolvingmultipleorgansincludingcoagulopathy,poorcardiacoutput,hypovolemia,lethargyandseizures.Stage4Continuingofhepaticfailureandongoingoxidativedamagebytheironinthereticuloendothelialsystem.Stage5Gastricoutletobstructionsecondarytoscarringandstrictures.TheFiveStagesStage184ManagementDetailedhistoryandphysicalincludingarectalexamforfrankblood.Aggressivefluidresuscitationandintravenousaccess.WholebowelirrigationandKUBtolookforpills.LaboratoryanalysisforCBC,chemistry,andironlevels(peakaround4hours).Willoftenrequirerepeatlevelswitharepeatchemistry.TIBChasnoutilityintheacuteoverdosesetting.ManagementDetailedhistoryand85ManagementManagement86ManagementIfthepatientisinshock,remembertoatleasttypeandscreen(ifnotcrossmatch)forblood.Givedeferoxaminebeforeironlevelisbackifthepatientisinshock.Deferoxaminewasderivedfromstreptomycespilosus.Hypotensionandallergicreactionsareseen.ARDSisaknowncomplicationandusuallylimititsuseto24hoursorless.ManagementIfthepatientisin87PesticidesSpecificallyorganophosphatesandcarbamates.Theyworkbyinhibitingacetylcholinesterase.PresentwithcholinergicsymptomsPesticidesSpecificallyorganop88CholinergicSymptomsCholinergicSymptoms89NicotinicSymptomsRememberthedaysoftheweek!MydriasisTachypneaWeaknessTachycardiaFasiculationsPediatricpatientstendtopresentwithapredominanceofnicotinicsymptoms!!!NicotinicSymptomsRememberthe90WeaknessfromPesticidesWeaknessfromPesticides91TreatmentAtropine0.02mg/KgIV.Repeatasneededandtitratetorespiratorysecretions.Itwilllikelytakemassivedoses!!Pralidoxime(2-Pam)20-40mg/Kgbolusfollowedby10-20mg/Kg/hourinfusion.RemembertosendRBCandPlasmaCholinesteraselevelsuponarrivalanddaily.TreatmentAtropine0.02mg/Kg92TheExpanded“OnePillKill”TheExpanded“OnePillKill”93TheDeadlyPediatricPoisonsCalciumChannelBlockersCyclicAntidepressantsLomotilOpiates/OpiodsSalicylates(methyl)ToxicAlcoholsSulfonylureasCamphorClonidineandimidazolinesAntimalarialsTheDeadlyPediatricPoisonsCa94CalciumChannelBlockersThreemajorclassesPhenylalkylamineBenzothiazepineDihydropyridineBlockL-typechannelsCausehypotension,bradycardia,andarrythmias.Immediateandsustainedrelease.Usuallynotthechildsmedication.CalciumChannelBlockersThree95CalciumChannelBlockersManageA,B,C’sCheckLabsandEKGFluidsCalciumGlucagonPressorsHighDoseInsulinAtorpineandPacingCalciumChannelBlockersManage96CalciumChannelBlockersMaybeabletoweanpressorswithinsulin.Insulindosageis1unit/kgbolusand0.5units/kg/hourdrip.MonitorsugarQ20minutesforthefirstfewhours.MostwillNOTbecomehypoglycemic.CalciumChannelBlockersMaybe97CyclicAntidepressantsTheyweretheleadingcauseofpoisoningfatalityuntil1993.Theyinterferewithreuptakeofbiogenicaminesandserotoninatthenerveterminal.Manifesttoxicitybyanticholinergiceffects,alpha-1inhibition,sodiumchannelblockade,andcaninhibitGABA.CauseCNSandcardiovasculartoxicitywitharrythmiasleadingtomortality.CyclicAntidepressantsTheywer98EKGFindingsEKGFindings99EKGFindingsEKGFindings100CyclicAntidepressantManagmentManageA,B,C’saggressivelyOptimizeelectrolytesFollowserialEKG’sanduseBicarbif:QRS>100or110msecaVr>3mmIfbicarbonateandmagnesiumarenoteffective,lidocaineistheantidysrhythmicofchoice.Norepinephrineisthepressorofchoiceforrefractoryhypotension.CyclicAntidepressantManagmen101IsittheSodiumortheBicarb?TheanswerisBOTH!Sodiumovercomesthepartialblockadefromcyclicantidepressants.Alkalinizationdoeschangebindingproperties.IsittheSodiumortheBicarb102Howdoesthebicarbwork?InitiallythoughttoincreaseproteinbindingthuslimitingfreedruginthebloodRatstudyusingalpha-1acidglycoprotein(AAG)onlydecreasedarrhythmiasatmassivedoses.AAGisaprovenTCAbinder.CurrenttheoriesisthattheionicformoftheTCAbindstothesodiumchannelcausingblockadeandthebicarbonatechangestheTCAfromtheionicformtotheneutralformcausinglessblockade.Howdoesthebicarbwork?Initi103LomotilAntidiarrhealagentcontainingbothdiphenoxylateandatropine.BothagentsareabsorbedbytheGItractandabsorptionmaybedelayedinoverdoseduetoinhibitoryeffectsonsmoothmusclemotility.Diphenoxylateisanopoidthatismetabolizedtodifenoxinwhichis5timesmorepotentthantheparentcompoundandhashalflifeof12-14hours.LomotilAntidiarrhealagentcon104LomotilPatientsmanifestsignsandsymptomsofopiatetoxicity.Respondwelltonaloxoneandsupportivecare.Currentrecommendationsareforaminimumof24hourobservation.LomotilPatientsmanifestsigns105Opiates/OpiodsTypicallypresentwithrespiratorydepression,alteredmentalstatus,andmiosis.Addressthepatientlikeanyother“alteredmentalstatus”Keypointistoremembertoconsideranopiateingestion.Opiates/OpiodsTypicallypres106NaloxoneDosingUsuallystartwith0.01-0.1mg/Kg.Repeatasfrequentlyasneededtoreversesymptoms.Ifadripisrequired,calculatehowmuchnaloxonewasusedinthefirsthourandstartthedripat2/3thatdose.NaloxoneDosingUsuallystartw107SalicylatesSalicylates108PharmacologyIrreversiblyinhibitstheenzymecyclooxygenase.Thisinhibitsprostaglandinsynthesis.Sinceprostaglandinsarenotsynthesized,theirdownstreambyproductsareneverreleasedsuchas:IL-6,TNF,andalphaandbetainterferons.Believedtodirectlyinhibitneutrophilstodecreasetheinflammatoryresponse.PharmacologyIrreversiblyinhib109SalicylateMetabolismSalicylateMetabolism110PathophysiologySalicylatesstimulatethebrainstemtocausehyperventilation(respiratoryalkalosis).Multifactorialrenalimpairmentleadstoaccumulationofsulfuricandphosphoricacids.InterferewiththeKrebsCyclelimitingsubstratesforATPgeneration.PathophysiologySalicylatessti111PathophysiologyContinuedUncouplesoxidativephosphorylationwhichleadstoincreasedpyruvicandlacticacidlevelandgeneratesheat.Causessalicylateinducedfattyacidmetabolismwhichproducesketonebodies.Thisketoacidosiscontributesasignificantportiontotheoverallmetabolicacidosis.PathophysiologyContinuedUncou112ClinicalManifestationsEarlysymptomsareusuallynon-specificsuchasnauseaandvomiting.Tinnituswithorwithouthearinglosscanalsobeanearlysign.Hyperventilationisoftenawarningsignofasignificantingestion.CNSsignscanvaryfromvertigotohallucinationstostupor.Comaisrareexceptinmassiveoverdoses.Inlargeoverdoses,almosteveryorgansystembecomesinvolved.ClinicalManifestationsEarlys113TreatmentAddresstheA,B,C’s.Detailedhistoryandexam.Laboratoryevaluationandconsiderabloodgasifyourhistorysuggestsaningestion.Activatedcharcoalshouldbegiven.Evidenceformultidosecharcoalisequivocal.Theuseofsodiumbicarbonate.Measureserialsalicylatelevelsandchemistries.TreatmentAddresstheA,B,C’s.114SodiumBicarbonateTherapyThegoalistotitratetheurinarypHto8.Potassiummustbemonitoredcloselybecauseifthepotassiumdrops,thekidneywillretainthepotassiumandexcretehydrogen.ExcretionofhydrogenwillmakeitimpossibletotitrateyourtherapytoaurinarypHof8.SodiumBicarbonateTherapyThe115IndicationsforHemodialysisRenalfailure.Congestiveheartfailure(relative).Acutelunginjury.PersistentCNSdisturbance.Severeacid-baseorelectrolyteimbalance,despiteappropriatetr