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EmergMedClinNAm21(2003)533557

AcuteinhalationinjuryKenMiller,MD,PhDa,*,AndrewChang,MDb

aOrange County Fire Authority, EMS Section,

145 South Water Street, Orange, CA 92866-2123, USAbUniversity of CaliforniaIrvine Medical Center, Department of Emergency Medicine,Route 128, 101 The City Drive South, Orange, CA 92868, USA

Inindustrializedcountries,inhalationalexposurestovarious

toxicantsarecommonplace.Althoughthecasesofinhalationalanthraxinlate2001have

causedrenewedconcernaboutchemicalagentsandbioterrorismingeneral,


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mostacutetoxicinhalationscomefromnonterroristsources,suchasfromindustries,home,andrecreationalsources.Unfortunately,thevariedpresentationsresultinanonspecific

clinicalsyndromeandmakediagnosissomewhatdifficult.Adetailedhistorybecomesevenmore

importantinsuchapatientandmayhelpmakeadifferenceinthe

oftenchaoticsettingoftheemergencydepartment(ED).Fortunately,symptomatic


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andsupportivetherapyisusuallyallthatisneeded,althoughinselectedcasestheadministrationoftheproperantidoteiscriticaltopatientsurvival.

Classificationschemes

Numerousclassificationschemeshavebeendevelopedas

awaytoorganizetheenormousnumbersofpossibleinhaledtoxicants.Mostreviews

ofacutetoxicinhalationsarebasedontheagentsmechanism


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oftoxicity,suchaswhetheritisapulmonaryirritantorsystemictoxicant[1,2].Forthisreview,theauthorshavechosentoorganizethe

toxicantsbasedonthelocationorsourceoftheexposure,becausethisis

oftenhowpatients(especiallymulti-casualtypatients)actuallypresenttotheED.Thegeneral

locationsorsourcesthattheauthorsuseareoccupational/industry,home/


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community,andwar/chemicalweapons(Box1).

*Correspondingauthor.OrangeCountyFireAuthority,EMSSection,145SouthWaterStreet,Orange,CA92866-2123.

E-mail address: [email protected](K.Miller).

0733-8627/03/$-seefrontmatter.2003,ElsevierInc.

Allrightsreserved.doi:10.1016/S0733-8627(03)00011-7


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Box1.Categorizationbysourceofexposure

Industry/occupationHome/communityWar/chemicalweapons

Althoughtheauthorsapproachthisbroad

topicbasedonthesourceofexposure,itisworthwhiletoreviewthe

basicpathogenesisofinhalationalinjuries.Suchinjuriesingeneraloccureitherthroughlocalized

pulmonarydamageorbysystemicabsorptionafterinhalation.Thosethat


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causelocalizedpulmonarydamagecanbesubdividedfurtherintoirritantgasesandthosethatcausepulmonarysensitization(Box2).Thosethatcausesystemictoxicity

canbesubdividedintosimpleandchemicalasphyxiants,organophosphates,hydrocarbons,andmetalfumes

(Box3).AscanbeseeninBox2,therecanbesignificant

overlap,asmanytoxicantscanfitinmultiplecategories.Treatment


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isusuallysymptomaticwiththeexceptionoforganophosphatesandcertainchemicalasphyxiants,suchascyanideandcarbonmonoxide.

Box2.Pulmonaryinhalational

toxicants

Irritantgases

AmmoniaChlorineFormaldehydeNitrogendioxidePhosgene

HydrogenfluorideAcroleinOzone

Antigens/sensitizers

AmmoniaChlorineFormaldehydeNitrogen

dioxideTolueneVinylplasticsAnimalandplantproteinsBacteriaFungi


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Box3.Systemicinhalationaltoxicants

Asphyxiants

CarbonmonoxideHydrogencyanideHydrogensulfideCarbondioxideMethaneHelium

Organophosphates

NervegasesSarin(GB)Tabun(GA)Soman(GD)Venon

XInsecticides

Hydrocarbons

FreonBenzeneTolueneVinylchlorideTricholoroethylene

Tricholoroethane

Metalfumes

BerylliumCadmiumMercury


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NickelZincChromium

Mechanismsofacuteinhalationinjury

Relevant respiratory anatomy

Severalelementsofrespiratoryanatomycontributetoprotectionofthe

airwaysandlungsfrominhaledtoxicantsandparticulates.Intheupperairway,particulates

inthe510-lmrangearetrappedthroughairturbulenceonthemucosalsurface

ofthenasalturbinates.Intheconductingairways,ciliatedand


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mucus-secretingepitheliumconstitutesthemucociliaryescalator,whichmovesinhaledparticlesupproximally.Withinthetracheaandbronchi,thismucociliaryescalatorcanmoveinhaledparticles

uptheairwayatapproximately14cmperhour.


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Inthemoredistalairways,alveolarmacrophagesphagocytoseinhaledparticulates.Thesemacrophagesareabletomovearoundthealveolarunitby

wayoftheairspace,lymphatics,andpulmonarycapillaries.Lysosomescontainingacidhydrolases

destroyparticulates;however,theinteractionsofmacrophageswithinhaledparticulatesalsocantrigger

inflammatoryandimmunologicreactionswithinthelung.Lymphaticclearanceis


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another,albeitlessimportantmechanism,ofremovinginhaledparticulates.

Relevant respiratory physiology and physicochemical principles

Thelungparenchymaiscapableofxenobioticmetabolismofsomecompounds

suchaspolycyclicaromatichydrocarbons,butoverallitisaminorcontributorof

toxicantbiotransformationandclearancecomparedwithrenalandhepaticclearance.Inthecase

ofparaquat,lungbiotransformationtoreactiveoxidativeparaquatintermediatescontributes


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tothepulmonaryparenchymalinjuryofthatcompound.

Inhaledtoxicantscanbeintheformofgases,vapors,particulates,oraerosols(droplets

ofliquidorfineparticulatessuspendedinagas).Gases,vapors,orliquids

canbeadsorbedontothesurfaceofparticulatesandcarriedintotheairways.

Threefundamentalparametersdeterminetheextentofinhaledtoxicantexposure:


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watersolubilityofthetoxicant,durationofexposure,andminuteventilation.

Watersolubilityplaysasignificantroleindeterminingthelocationof

gasorvaporinhalationinjury.Compoundsthataremorewater-solubleaffecttheupper

airwaysastheydissolveandconcentrateintheaqueousphaseofmucus.At

highconcentrationsorwithprolongedexposure,however,water-solublecompounds


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maycauselowerairwayinjuryalso.Compoundsthatarelesswater-solubleaffectthelowerairways,resultingindamagetothealveoliandepitheliumof

therespiratorybronchioles.Damagetopulmonarycapillaryendothelialcellsandalveolarmacrophagescan

contributetolatersuperimposedbacterialinfectionandchemicalpneumonitis.

Characteristicsof

particulatesthatcontributetotoxicityincludeparticlesize,density,and


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shape.Theprinciplecontributortoairwaypenetrationisparticlesize.Particleswithanaerodynamicdiametergreaterthan10lmarefilteredinthenasopharynx

ordepositedonthelarynx.Particles310lminsizearedepositedin

theconductingairways,whereasparticulates0.53lminsizearedepositedindistal

airwaysandalveoli.Particulateslessthan0.5lminsize


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(submicronparticles)behavelikeagasandmaybeexhaledwithexhaledair.Water-solubleparticulatescanbeabsorbedacrosstherespiratorybronchiolaroralveolar

epitheliumintotheblood.Insolubleparticulatesareeliminatedbyexpectoration,swallowing,lymphatics,or

phagocytosisandsubsequentlysis.Phagocytosedparticulatesleadingtolysisofalveolarmacrophagescan

resultinpulmonaryfibrosis,granuloma,oremphysema.


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Clinical anatomic and physiologic correlates

Theeffectsofinhalationexposuretotoxicantscanbethoughtofasfollows:simpleasphyxiants,tissueasphyxiants,nonrespiratorysystemic

toxicantswithpulmonaryabsorption,anddirectairwaycellularinjury.

Simpleasphyxiants,

suchasnitrogen,helium,hydrogen,methane,propane,andnaturalgas,displaceatmosphericoxygen

butareotherwiseessentiallyphysiologicallyinert.Occupationalsafetylimitsestablished


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bytheOccupationalSafetyandHealthAdministration(OSHA)[3]requireatmosphericoxygenconcentrationsinconfinedspacestobebetween19.5%and23.5%.Hypoxicatmospheres

lessthan19.5%canimpairfunctionandjudgmentandcanleadtoaccident

andinjury.Atmosphereslessthan16%oxygenbelow3,000feetaltitudeareconsidered

immediatelydangeroustolifeandhealth(IDLH).Asaltitudeincreases


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andatmosphericpressuredecreases,thishypoxicatmosphericIDLHincreases.Hyperoxicatmospheresgreaterthan23.5%inconfinedspacesincreasetheriskforfire.

Tissueasphyxiants,suchascarbonmonoxide,hydrogencyanide,hydrogensulfide,andazides,inhibit

mitochondrialelectrontransportandoxygenuse.Tissueasphyxiantsandtheirparticipationinthe

syndromeofacuteinhalationinjuryarediscussedinthesection


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onsmokeinhalation.

Manychemicalsexertsystemictoxiceffectswhenabsorbedbywayofthepulmonarycirculationbutcausenodirectacute

airwayorlunginjury.Examplesincludehalogenatedaliphatichydrocarbons,benzeneandotheraromatic

compounds,gasoraerosolformsofthetissueasphyxiants,andmanysolvents.The

discussionofinhalationtoxicologyherefocusesonthosetoxicantscausing


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acutelunginjury.

Directairwaycellularinjuryresultsfromepithelialcellinjuryanddeathandfromairwayedema.Theconsequencesofepithelial

cellinjuryincludereductionofmucociliaryclearanceofinhaledparticulates,leakbetweenintercellular

junctions,andsloughingofdeadepitheliumleadingtoairwayobstruction.Airwayedemaresults

fromepithelialjunctionleakandfromcytokinesandmediatorsreleased


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inresponsetocellularinjury.Thesemediatorscontributetoinflammation,edema,andairwaysmoothmusclecontraction.

Thenasopharynxandlarynxmanifestthese

cellularinjuriesearliestbecausetheyareexposedtothehighestconcentrationsofinhaled

toxicants.Clinicalmanifestationsincludehoarseness,stridor,andlaryngealedema.Mucosalulceration,hemorrhage,and

edema,however,maybedelayeduptoseveralhourspostexposure.


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Tracheobronchitistogetherwithparalyzedciliaandimpairedmucusclearancecanfollowprolongedexposuretoparticulatescontainingadsorbedtoxicants[4].Thereisagradualbut

progressiveairwayresponsetodirectcellularinjury.Withinafewhourspostexposurethere

isextensivebutmildmucosaledema,noulceration,anddeceptivelyminimalclinicalsymptoms.

Overthenext848hoursthereisprogressiveairwayedema,


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mucopurulentmembraneproduction,andbronchorrhea.Within


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 5335574872hoursthereismucosalsloughandevolutionofamembranoustracheobronchitis[5].Bronchoconstriction,peribronchialedema,andbronchialmucosalsloughall

cancontributetothedevelopmentofatelectasis.Inthedistalairwaysandalveoli,

epithelialandendothelialinjuryresultinpermeability-inducededema.Thiscanmanifestanywherefrom

mildinterstitialedematopulmonaryinsufficiency.Alveolarfloodingcanoccur


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atnormalpulmonarycapillaryhydrostaticpressureormayberetrogradefrommoreproximalairwaybronchorrhea.Asinotherformsoftheacuterespiratorydistress

syndrome(ARDS),thisresultsindecreasedlungcompliance,increasedalveolar-arterialoxygengradient,and

increasedpulmonaryvascularresistance.Pulmonaryedemamaybeimmediateinpulmonaryhigh-concentrationtoxicant

exposureormaybedelayed2448hourspost-exposure.There


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maybedifferencesinetiology,treatment,andoutcomebetweenthesyndromeofARDScausedbyasystemicinflammatoryresponse(extrapulmonaryARDS)andthatcaused

byacutelunginjury(primarypulmonaryARDS)[6].Finally,excessivephysiologicresponsesmay

bepartoftheacuteinhalationinjurysyndrome.Cough,mucoussecretion,andbronchoconstriction

areallnormalresponsestoinhaledirritants.Anincapacitatingcough


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mayaccompanypre-existingairwayhyperresponsiveness.Chronicmucushypersecretioncanfollowcontinuedexposuretoirritants(industrialbronchitis).Breathholdingandlaryngospasmmayoccurinconscious

victimsattemptinganescapefromahazardousatmosphere.

Clinicalassessmentand

treatmentofacuteinhalationinjury

Clinical assessment

Symptomsofacuteinhalation

injurycanbedelayedinonset.Theclinicalsettingof


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facialburns,inflamednares,sputumproduction,andwheezinginvictimsoffiresorexplosionsinenclosedspaces,oralteredmentalstatusatthescene

affectingtheabilitytoescape,canallbeconditionsprecedingtheonsetof

symptomsofacuteinhalationinjury.Coughislikelythefirstsymptom.Occasionallycough

mayreflectcough-variantasthmaorirritant-associatedvocalcorddysfunctioncaused


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bydirectvocalcordinflammation[7].Tissueasphyxiantsmaycausedizziness,headache,chestpain,nausea,andvomiting.Themostacuteclinicalproblemmightbe

rapidlyevolvingupperairwayobstructioncausedbythermalorchemicalburnstothe

face,nares,ororopharynx.Anunpredictablefractionofthesepatientsgoonto

life-threateningobstruction.Ifresourcesandconsultativeservicesallowclinicalobservation


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inanintensivecareunitwithserialfiberopticlaryngoscopyandbronchoscopy,theneedfortrachealintubationmaybeminimized.Suchserialexaminations,however,can

beuncomfortableinpatientswithupperairwayinflammation.Whentheseresourcesarenot

available,earlypreemptivetrachealintubationisthebestchoice.


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Spirometrygivesagoodgeneralpictureofairflowdynamics.Theforcedexpiratoryvolumeinonesecondtoforcedvitalcapacityratio

(FEV1/FVC)decreasesinobstructivelungdisease.Peakexpiratoryflowrate(PEFR)canbe

measuredinapatientduringsymptomaticandasymptomaticperiodsandmayreflectearly

airwayobstruction[8].Normalspirometrydoesnotexcludesignificantlung


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diseaseandcanbedifficulttoapplyincriticallyillpatientsormaybeunavailableinatimelyfashionintheED.Themost

availablediagnostictestsintheEDarearterialbloodgases(ABGs)andchest

radiography.ABGscanprovideinformationonoxygenation(PaO2andSaO2),ventilation(PaCO2),acid-base

status(pH),andalveolargasexchange(PA-aO2),butstillcan


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benormalintheimmediatepostexposureperiod.Arterialoxyhemoglobinsaturation(SaO2)shouldbemeasuredbycooximetryratherthanbyinfrared-visibledualwavelengthpulseoximetry,

becausepulseoximetrycannotdistinguishcarboxyhemoglobinormethemoglobinfromoxyhemoglobin.Chestradiographyis

readilyavailablebutitisnonspecific(manypathologiesproducesimilarradiographicchanges),correlates

poorlywithclinicalmanifestationsofinterstitiallungdisease,andmay


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benormalintheimmediatepostexposureperiod.Commonradiographicfindingsinacuteinhalationinjuryarediffuseinterstitial,alveolar,ormixedinfiltrates,segmentalconsolidation,or

hyperinflation.Noncontrastspiralchestcomputedtomographyalsocanbeusedtofurthercharacterize

interstitiallungabnormalities[9].

Fiberopticlaryngoscopyandbronchoscopy,whenavailable,allows

thevisualizationoferythema,edema,ulceration,andhemorrhagefromthe


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leveloftheposteriorpharynxtofourtofivegenerationsofbronchi.Fiberopticinspectioncanprovideearlyinformationonairwayinjuryseverity,andwhen

doneseriallycanassessthesuccessoftherapy.

Treatment

Out-of-hospital management

Dyspnea,tachypnea,hypoxiabypulseoximetry,alteredmentalstatus,andsuspectedcarbon

monoxidetoxicityintheclinicalsettingofacuteinhalationinjury


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areallindicationsforoxygenadministrationbynonrebreathermask(FIO2approximately0.9at15L/min).Ifstridororotherphysicalevidenceofupperairway

edemaispresent,preemptiveintubationmaypreventprecipitousairwayobstructionfromprogressiveairway

edemathatotherwisewouldmakedelayedlaryngoscopydifficultorimpossible.Adjunctiveairwaydevices

suchastheesophageal-trachealCombitube(ETC)orlaryngealmaskairway


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(LMA)mayfacilitateventilationwhenbag-valve-maskventilationisdifficultbecauseoforopharyngealedema.ItisimportanttokeepinmindthattheLMAdoes

notprotecttheairwayfromaspirationandneithertheETCnorLMAcan

protecttheairwayfromevolvinglaryngealedema.Inaddition,anonintubatingLMAcannot

supportpositivepressureventilationgreaterthanpeakairwaypressuresof


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2030cmH2O.Theinherentlysmallerdiameter


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557ofthepediatricairwaypredisposesittoobstruction.Thereisadisproportionateincreaseinairwayresistanceanddecreaseincross-sectionalarea

forequivalentdegreesofedemainpediatricandadultairways.Airwaysuctionalso

maybenecessarytoclearreactivesecretions.Aerosolizedbronchodilatorsshouldbeusedfor

bronchoconstriction.Ifnecessary,aerosolizedbeta-agonistscanbeadministeredbyway


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ofanebulizerinserieswithbag-valveassistedventilationusingamask,endotrachealtube,orairwayadjunct.

Burncenter,traumacenter,andhyperbaric

facilitytriagedecisionsareguidedbylocalstandardsofpracticeandout-of-hospitaltreatment

guidelines.Thedecisiontousehyperbaricoxygenisdiscussedinthesectionon

smokeinhalation.Inphysiologicallyunstablepatients,earlytransportisdesirable


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afteradequateairwaymanagementandnecessaryspinalimmobilizationhavebeencompleted.Intravenousaccessandelectrocardiographicmonitoringcanbeestablishedenroutetothereceiving

hospital.Ifthermalorchemicalcutaneousburnsaccompanytheacuteinhalationinjury,narcotic

analgesiashouldbeconsidered.

Ifthepatientisunabletoprovide

ahistoryoftheinhalationexposureincident,observationsatthe


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scenecanbehelpfulindeterminingfuturetherapy,observationperiods,andlikelyprognosis.Ifanexplosionorfireresultinginpatiententrapmentoraltered

mentalstatuswasassociatedwiththeinhalationinjury,thismayreflectagreater

durationofinhalationexposureandthepotentialfordelayedonsetsymptoms.Ifhazardous

materialsresponseteamshaveconductedreconnaissance,atmosphericmonitoring,orfield


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environmentaltesting,thesedataandanyactualorpresumptiveidentificationofthetoxicantinvolvedcanassistinclinicaldecisionmakinglater.

Emergency department management

AlthoughmoreoptionsareavailableintheEDtoassessandmanage

theairway,managementasawholecontinuesfromthefundamentalprinciplesbegunduring

theout-of-hospitalphaseofpatientcare.Whenequipmentandconsultative


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resourcesareavailable,fiberopticlaryngoscopycanhelpdeterminetheextentofupperairwayinjuryandtheneedforpreemptivetrachealintubation.Ifairwayedema

isalreadyaproblem,thefiberopticlaryngoscope,flexibleintubationguides,specializedlaryngoscopeblades

(eg,theBaintonpharyngealblade),intubatinglaryngealmasks,retrogradeintubation,transtrachealjetventilation,

andcricothyroidotomyarealloptionstoassistorachievetracheal


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intubation.

Bronchodilatorscanbeadministeredbyaerosolinhalationinthespontaneouslybreathingpatientorduringassistedventilation;however,corticosteroidsshouldbeavoided.

Studieshavebeenconflicting,butevidenceofreducedlungbacterialclearanceandincreased

incidenceofbacterialpneumoniaasalatecomplicationofinhalationinjuryoutweighsany

potentialanti-inflammatoryeffects[10,11].


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Diagnosticstudiesthatcanhelpcharacterizetheseverityoftheinhalationinjuryincludechestradiography,arterialbloodgases(ABGs)withcooximetry,

serialpeakexpiratoryflowrates(PEFR),andbedsidespirometrywhenavailable.Itis

importanttokeepinmindthatthesestudiesmaybenormalinthe

immediatepostexposureperiod.Asidefromserialvitalsignmeasurements,other


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studiesthatmayassistinclinicaldecisionmakingare12-leadelectrocardiographytoidentifycardiacischemiaorinfarctionandbloodandurinetoxicologystudiesto

identifycoexistingtoxicitythatmayhavecontributedtothecauseoftheinhalation

injuryandcomplicateitscourse.Pulseoximetrycanbedeceivinginthepresence

ofatoxichemoglobinopathy,socooximetryshouldbeusedto


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determineoxyhemoglobinsaturation.

Persistenthypoxiadespitetrachealintubation,supplementaloxygenadministration,bronchodilators,andsuctionofairwaysecretionsmayreflectearlypulmonaryparenchymal

injuryrequiringmechanicalventilationwithpositiveend-expiratorypressure(PEEP).Fluidmanagementina

patientwithacombinationofcutaneousburnsandinhalationinjurycanbea

complexbalancebetweenreplacingburnfluidlosseswithoutexcessiveinterstitial


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lungwateraccumulationbecauseofthepulmonarycapillaryleakofinhalationinjury.Achievingthisbalancerequiresmonitoringoffluidintakeandoutputandpulmonary

arterycatheterhemodynamicparameters.

Lessseverelyinjuredpatientspresentchallengesalso.

Whenphysicalexaminationrevealsareasonablywellappearingpatient,thehistoryofexposure

maybethecriticaldeterminingfactorinthedurationof


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subsequentobservation.SerialABGs,chestradiography,PEFR,airwayandlungexamination,andbedsidespirometrywhereavailablehelpdetecttheevolutionofdelayed-onsetdistal

airwayandpulmonaryparenchymalinjury.Historyorsuspicionofinhalationinjuryshouldlead

toanobservationperiodofatleast24hours.

Homeand

community

Smoke inhalation

Thesinglemostlikelycause


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ofacuteinhalationinjuryinemergencymedicinepracticeissmokeinhalationfromresidentialorcommercialstructurefires.Inaddition,smokeinhalationemergenciescanpresent

asmulti-casualtyincidents.Smokeinhalationistheleadingcauseofdeathfromstructure

fires,particularlyfromfireinmultistorystructures.Smokeinhalationalsoaddstomortality

fromcutaneousthermalburns.Mortalityratesfromsmokeinhalationare


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approximately5%8%[6].Mortalityratesforcombinedmajorburninjuryandinhalationinjury,however,exceedthatofeitherinjuryalone[6].Earlydeathsare

usuallycausedbyairwaycompromiseormetabolicpoisoning.Smokeinhalationrepresentsacombination

ofdirectpulmonaryinjuryandsystemicandmetabolictoxicities.


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Therearethreetime-relatedbuthighlyvariablephasesofacutesmokeinhalation.Theearlyresuscitationphaseiswithin36hourspostexposure

andischaracterizedbyacutepulmonaryinsufficiency[12].Thefollowingdiscussionfocuseson

thisphase,asitisthetimethepatientismanagedinthe

emergencydepartment.Thepostresuscitationphaseisapproximately25dayspostinjury


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andischaracterizedbymucosalnecrosisandslough,viscoussecretions,anddistalairwayobstructionwithatelectasis,pulmonaryinterstitialedema,andbronchopneumonia.Theinflammatoryinfectionphase

isapproximately5daysandbeyondinthepostinjuryperiodandcontinuesuntil

thereislunghealingandburnwoundclosure.Thisphaseischaracterizedby

nosocomialbronchopneumonia,hypermetabolic-inducedrespiratoryfatigue,andacuterespiratorydistresssyndrome.


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Pathophysiologically,smokeinhalationinjurycanbethoughtofashavingtwoprinciplecomponents:directsmokelunginjuryandsystemicsmokeinhalationsyndrome.

Smoke lung injury

Thecompositionofsmokeisvariableanddifficulttopredictfor

toxicologicassessmentoftheindividualpatient.Smoketoxicitydependsonthefuelsthat

areburning,thecompletenessofcombustion,andthegeneratedheat


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intensity.Inaddition,evenwithinthesamestructure,smokecompositioncanvaryintimeduringtheburningandextinguishmentprocessandlocationwithinthe

structure.Filteredsmokeinroomsremovedfromtheseatofthefirecan

containmetabolictoxicants,ascansmokefromrelativelysmokelesscombustion(eg,internalcombustion

engineexhaust).Inthesecases,metaboliceffectscanexceedpulmonary


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effects.

Clinicalconsequencesofsmokeexposuredependonchemicalcomposition,particulatesize,exposuretime,andminuteventilation.Surrogatemarkersfortheseparameters

includehistoricalexposuretime,neurologicstatus,andcarboxyhemoglobin.Neurologicstatusinterpretationisfrequently

complicatedbycoexistingheadinjuryanddrugoralcoholingestion.

Unless

thepatientisexposedtosteam,directheatinjuryto


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theairwayislimitedtosupraglotticstructuresbecauseoftheheatdissipatingpropertiesoftheupperairway[13].Steamhasapproximately4,000timesthe

heatcarryingcapacityofhotair,soatanygiventemperaturesteamhas

moreheattogiveupthananequalvolumeofdryair[14].

Theconsequencecanberapidlyfatalobstructiveglotticedema,thermal


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tracheitis,andhemorrhagicedemaofthebronchialmucosa.

Gasphaseconstituentsofsmokeincludecarbonmonoxide,hydrogencyanide,acidandaldehydegases,

andoxidants[15].Thesecomponentsaremucosalirritantsandcanleadtobronchorrhea,

bronchoconstriction,andairwayedema.Smokealsocontainsparticulates,thesizeofwhichare

determinedbythenatureofthefuelthatisburning.


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Particlesizeinthe35-lmrangeseemstopredominateinstructurefires,withintherange


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557allowingmoredistalairwaypenetrationandretention.Theseparticulatescanadheretothemucosaandperpetuatelocaltissueinjurybykeeping

adsorbedtoxicantsincontactwiththemucosa.Particulateclearancefromtheairwaysis

inhibitedbythelocalairwayinjury.

Lungpathophysiologicresponsetosmoke

inhalationdependsonseveralfactors.Thepreinjuryhealthstatusof


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thepatientandreactiveairwaydiseaseorchroniclungchangescontributestosmokeinhalationinjuryseverity.Directmucosalinjurycompromisesthemucociliaryescalatorand

particulate,mucus,andbacterialclearance.Increaseinbronchialbloodvesselpermeabilitycontributesto

submucosaledemaandtheincreasedbronchialbloodflowcanleadtovascularengorgement-related

masseffectandairwaylumennarrowing.Tissuedestructionandsecondary


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inflammatoryresponseresultsinmucosalsloughandincreasesmucusproduction.Althoughalveolarfloodingisobservedintheearlypostinjuryperiod,itismorelikely

causedbyretrogradefloodingfromproximalairwayedemaratherthanalveolarcapillaryleak

thatusuallyoccursaftertheinitial2436hours.

Systemic smoke inhalation injury

Early

systemicchangesincludeadecreaseincardiacfillingpressureand


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cardiacindex.Theseeffectsmaybecausedbymyocardialtissueanoxiafromthemitochondrialtoxicityofcarbonmonoxideorhydrogencyanide.Theyalsomay

becausedbydecreasedbloodvolumefromcapillaryleakandfluidandprotein

lossintolungandsystemictissue.Theinflammatoryeffectscausingcapillaryleakare

complimentaryfollowingcutaneousburnsandinhalationinjury.Cutaneousburnsincrease


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thedegreeofpulmonarycapillaryleak,andinhalationinjuryincreasestherateofburnedemaformation.Earlyfluidresuscitationisnecessarytomaintainadequate

perfusion.

Latersystemiceffectsofinhalationinjuryincludeinflammationwithinthe

airwaysandlungparenchymabypostinjuryday2or3.Nosocomialpneumoniaand

thepresenceofcutaneousburnscanexacerbateasystemicinflammatory


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hyperdynamicstatewithincreasedtissueoxygendemandandbloodflowmaldistribution.Facialandneckburnsresultincrosscontamination,colonization,andinfectionofthe

airwaysandlung.

Resuscitation phase: the first 36 hours

Frequentlythediagnosisandtreatmentof

thisphaseestablishesthesubsequentcourseofthesmokeinhalationsyndrome.Earlydiagnosis

maybelargelybasedonclinicalsuspicion.Ahistoryof


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disorientationorunconsciousnessatthescenecanreflecttheresultsofsmokeinhalationorindicateprolongedsmokeexposure.Respiratorysymptomsmaybedelayedin

onset,butcarbonaceoussputum,singednasalorfacialhair,facialburn,cough,or

wheezingcanindicatethepresenceofsmokeinhalationsyndrome.InitialABGsmaybe

normal.Theremaybeametabolicacidosiscausedbycarbon


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557monoxidetoxicityandadecreaseinmeasuredSaO2.ThePaO2/FIO2ratiomayhavesomebearingonprognosis[16].Avaluegreater

than300hasbeenassociatedwithsurvivalafterinitialresuscitation.Theinitialchest

radiographalsoisfrequentlynormal.Theearlyinjuryistotheairwaysrather

thanthelungparenchyma.Peribronchialcuffingandperivascularhazinessmay


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beearlybutnonspecificradiographicsigns.Atelectasis,increasinglungwater,andfocalinfiltratesevolveoverthefirstfewdays.Entrapmentorunresponsivenesswithina

structurefirecanexposethevictimtoatoxicandhypoxicatmosphere.Hypoxia

aloneshouldresultinreversibleneurologicdysfunctionunlessprolonged.

Tissueasphyxiants

releasedduringcombustionincludecarbonmonoxideandhydrogencyanide.Carbon


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monoxideisrapidlytransportedacrossthealveolarmembraneandbindstohemoglobin.Measuredarterialhemoglobinsaturation(SaO2)byco-oximetryisdecreasedbelowthatexpected

forthePaO2.Pulseoximetry(SpO2)isunreliablebecauseofsimilarlightabsorption

bycarboxyhemoglobinandoxyhemoglobinsothatSpO2overestimatesSaO2.Carboxyhemoglobin(HbCO)saturationcan

bedirectlymeasuredbyco-oximetryandmaybelowerby


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thetimeofemergencydepartmentevaluationascomparedwiththescenebecauseofout-of-hospitaloxygenadministration.Carboxyhemoglobinshiftstheoxyhemoglobindissociationcurvetothe

left,therebyimpairingtheunloadingofoxygenatthetissuelevel.Withprolonged

exposure,carbonmonoxidesaturatescellsandbindstocytochromeoxidase,whichthenuncouples

mitochondrialoxidativephosphorylationandreducesATPproduction.Thisresultsin


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ametabolicacidosis.Unlikecyanidepoisoning,mildtomoderatecarbonmonoxidepoisoningiscommon.Patientsoftenpresentwithvaguesymptomssuchasheadache,nausea,

vomiting,dizziness,andconfusion.Withsufficientdurationofexposure,subtleneuropsychiatricsymptomsmay

persist.

Carbonmonoxideisdisplacedfromhemoglobinbytheadministrationof

supplementaloxygen.Thehalf-lifeofcarboxyhemoglobinisaffectedbyseveral


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factors[17].Carbonmonoxideaccumulationintissueandintrapulmonaryshuntingprolongselimination.Anincreasedminuteventilationandtosomeextentareducedcardiacoutput,

allowingmoretimeforalveolargasmasstransfer,increaseselimination.Thehalf-lifeof

carboxyhemoglobin(HbCO)withthepatientbreathingcleanairis46hours.Breathing90%

100%oxygenat1atmosphereabsolutepressure(1ATA)reduces


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theHbCOhalf-lifeto6090minutes.Breathing100%oxygenat3ATA(commonhyperbarictreatmentpressuresare2.43.0ATA)reducestheHbCOhalf-lifeto

2030minutes.Hyperbaricoxygen(HBO)ismoreeffectiveatremovingcarbonmonoxidefrom

mitochondrialcytochromes.ClinicaloutcomestudiesofHBOtreatmentincarbonmonoxidetoxicityhave

beenconflicting[18],andobjectiveclinicalmarkersforpatientselection


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fortreatmentarelacking.HbCOlevelsalonedonotcorrelatewellwithclinicaloutcomes,especiallyneuropsychiatricsymptoms,sotreatmentdecisionsarebasedonmortality

andmorbidityriskfactors.CurrentrecommendationsfortheuseofHBOare


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557HbCO[25%30%,neurologiccompromise,metabolicacidosis,orelectrocardiographicevidenceofmyocardialischemia,infarction,ordysrhythmias[19].Otherconsiderationsfortreatment

includeHbCO[10%inpregnancy(becauseofgreaterfetalhemoglobinaffinityfor

CO),HbCO[15%inpatientswithknownischemicheartdiseaseorfailureofclinical

improvementwithin4hoursoftreatmentwith100%normobaricoxygen


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deliveredbywayofagoodfittingnonrebreathermask[45].

Hydrogencyanideandaerosolizedorparticulate-adsorbedcyanidesaltsareabsorbedacrossthe

alveolarmembrane.Hydrogencyanideisacombustionandpyrolysisproductofnaturaland

syntheticmaterials.Thecontributionofcyanidetoxicityinacutesmokeinhalationsyndromeis

debated[20].Cyanide-relatedfatalitiesarerareandtendtobe


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associatedwithhighHbCOlevels.Inaddition,theuseofthemethemoglobin-producingcomponentsofthecyanideantidotekitwouldfurthercompromiseoxygentransport.Cyanide

bindstomitochondrialcytochromes,leadingtoimpairedmitochondrialATPproductionandtissueATP

depletion.Cyanidedoesnotbindtoreducedhemoglobin(Fe2+)butdoesbindto

oxidizedhemoglobin(Fe3+),formingcyanomethemoglobin.Becausethecentralnervoussystem


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andmyocardiumarethemostsensitivetotissuehypoxiaandATPdepletion,coma,seizure,reducedcardiacoutput,andmetabolicacidosiscanalloccur.Mixed

venousoxygencontent(CvO2)approachesthearterialoxygencontent(CaO2)becauseoxygenextraction

fromtissueisimpaired.Pulseoximetryreflectstheoxyhemoglobinsaturationincyanidetoxicity

intheabsenceofHbCOandifmethemoglobinemiahasnot


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beeninducedaspartofthetherapy.Cyanideisdetoxifiedintissue,especiallytheliver,bysulfurtransferase(rhodanese)tothiocyanatethatisthen

excretedbythekidney.Thisprocessregeneratesmethemoglobinfromthecyanomethemoglobin.Unlikecarbon

monoxide,mildacutecyanidetoxicityisnotcommonlyseenbecauseofthemarked

toxicityofcyanide.Also,unlikecarbonmonoxide,thereisno


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practical,timely,clinicalcyanidetest.Whencyanideismeasured,abnormallevelsareconsideredgreaterthan0.1mg/L[21].Asurrogatemarkerofcyanidetoxicity

isbloodlactatelevelgreaterthan10mmol/Lthatisrefractorytorestoration

ofadequateventilation,oxygenation,andperfusion.Restoringcardiopulmonaryfunctionandtissue(especiallyliver)

perfusionincreasesthesulfurtransferaseclearanceofcyanide.TheUSA


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cyanideantidotekitreliesontwopharmacologicprinciples.Nitritesareadministeredbyinhalation(amylnitrite)orintravenousinfusion(sodiumnitrite)toinduceapproximately8%

methemoglobintofacilitatetransportofcyanideascyanomethemoglobinfromthemitochondrialcytochromesto

hepatocytes.Thesubstratesulfuristhensuppliedbywayoftheintravenousadministration

ofsodiumthiosulfatefortheconversionofcyanidetothiocyanate


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bysulfurtransferase.Whenoxygentransportisalreadycompromised,asincarboxyhemoglobinemia,thesodiumthiosulfatecanbeadministeredalone.Hyperbaricoxygenhasbeentried

incyanidetoxicitybuthasnotbeenproveneffective.Analternativetherapeuticstrategy

istheadministrationofintravenoushydroxycobalamin.


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Inthepresenceofcyanide,hydroxycobalaminisconvertedtocyanocobalamin(vitaminB12).Althoughattractiveasanalternativetomethemoglobinemiaandthiosulfate,

FDA-approvedformulationsofhydroxycobalaminforthetreatmentofperniciousanemiaarefartoo

dilutetopermittheadministrationofthe4-gintravenousdosenecessaryforcyanide

toxicitywithoutexcessivevolumeinfusion.Thesuggestedapproachtosuspected


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cyanidetoxicityinthesettingofsmokeinhalationwithmetabolicacidosis(especiallylacticacidosiswithlactatelevels[10mmol/L)refractorytofluidresuscitation

andoxygen(afterreassessmentoffluidstatus,ventilation,andassociatedinjuries)isthe

intravenousadministrationof12.5gofsodiumthiosulfate.

Anothercomponentof

theearlyresuscitationofthesmokeinhalationvictimisupper


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airwayobstructionfromtissueedema.Inhalationofheatedgasesgreaterthanapproximately150C(300F)resultsinfacial,oropharyngeal,andsupraglotticthermalburns[13].The

immediateeffectsontheupperairwayareedema,whichisprogressiveoverthe

next1218hours,erythema,andulceration.Cutaneousburnsmagnifytheinjurytothe

airwayinproportiontoburndepthandbodysurfacearea


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affectedbecauseoffluidresuscitationvolumeandinflammatorymediators.Steamhasamuchgreaterheat-carryingcapacitythanair(approximately4000timestheheatcapacity)

[7].Consequently,inhalationofsteamtransfersheatmoreefficientlytotheupperairway

structures,resultinginrapidlyfatalobstructiveglotticedema,thermaltracheitisandbronchialmucosal

destruction,andhemorrhagicalveolaredema.

Stridor,dyspnea,and


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increasedworkofbreathingreflectcriticalairwaynarrowing.Upperairwaynoisereflectsairflowturbulenceprecedingobstruction.Airwaynoisefromprofusethickmucosalsecretionsmay

bedifficulttodistinguishfromobstruction.Bythetimesymptomsofairwayedema

develop,extensiveanatomicdistortionispresent.Iftrachealintubationisnotnecessaryinitially,

serialfiberopticlaryngoscopyandbronchoscopycanbeusedtoassess


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theevolutionofairwaymucosalinjuryandtrackedemaofthefirst1824hours.Theneedfortrachealintubationisdeterminedbythe

needtomaintainairwaypatency,protectagainstpulmonaryaspiration,providepulmonarytoiletto

decreasemucouspluggingandriskforinfection,andtoprovidepositivepressureventilation.

Intubationimpairsthecoughmechanismandcanincreasetherisk


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fornosocomialpulmonaryinfection.

Heat,however,isalessercontributortoairwayinjuryfromsmokeinhalationthanischemicalinjurytothe

upperandlowerairways.Combustionandpyrolysisgaseslikeacetaldehyde,formaldehyde,acrolein,ammonia,

hydrogenchloride,sulfurdioxide,andhydrogenfluoridecancauseupperorlowerairway

injurywithairwayclosureandatelectasisresultinginimpairedgas


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exchange.Alveolaredemaisnotacomponentoftheearlystageofsmokeinhalation.Earlyalveolarfloodingmaybecausedbyretrogradebronchorrhea.The

extentofthischemicalairwayinjurymaynotbeevidentfor2448hours.

Earlysymptomsincludebronchospasmandbronchorrhea.Intense


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557earlybronchorrheacanbemistakenforfulminantpulmonaryedema.Sootinairwaysecretionsindicatessmokeexposurebutisnotanecessary

findingtopredicttheoccurrenceorconsequenceofairwayandpulmonaryinjury.There

canbedecreasedlungcompliance,anincreasedworkofbreathing,impairedclearanceof

secretions,andincreasedminuteventilation.ABGsmayreflectventilation/perfusionmismatch


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andanincreasedalveolararterialoxygengradient.

Severalapproachescanbetakenforairwaymaintenanceandpulmonarysupport.Prophylacticcontinuouspositiveairwaypressure

(CPAP)maypreventthedeteriorationofoxygenationandintrapulmonaryshunting.Positiveend-expiratorypressure

(PEEP)maintainssmallairwaypatencyandadequatefunctionalresidualcapacity.PEEPhelpshold

edematousairwaysopenuntiltheedemaresolves.Largerdiameterorotracheal


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tubesarepreferredoversmallerdiametertubestoallowforthemoreefficientclearanceandsuctionofthickairwaysecretionsandtofacilitatefiberoptic

bronchoscopy.Inadditionorotrachealintubationmaybepreferredovernasotrachealintubationinpart

becauseoftrachealtubesizelimitationsbutalsobecauseprolongedplacementofnasotracheal

tubescontributetothedevelopmentofsinusitis.Humidifiedoxygenadministration


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assistswiththeclearanceofsecretionsandmayimproveoxygendelivery.Head-of-bedelevationofapproximately2030.alsocanassistwithsecretionclearancewhennot

otherwisecontraindicated.Aerosolizedbronchodilatorscanhelpreversebronchospasmintheimmediateandearly

postinjuryperiod,butwheezingbeyond1824hourspostinjuryismorelikelycausedby

increasedairwayresistancefromedema.AddingPEEPratherthanbronchodilators


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maycorrectanincreasingalveolararterialoxygengradientinthelaterpostinjuryperiod.Prophylacticantibioticsarenotindicatedbecausetheyselectoutthemoreresistant

organisms.Antibioticuseshouldbebasedinsteadonserialsputumcultures.Corticosteroidsgiven

inthepresenceofacutaneousburnincreasesmortality.Experimentalinterventionsincludeantioxidants,

exogenoussurfactant,andhigh-frequencyventilation[6].

Commonpitfalls


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intheinitialmanagementofsmokeinhalationare:usinginitialPaO2topredictadequacyofoxygenation,placingsmalldiameternasotrachealtubes,intubatingwithoutapplying

PEEP,andrestrictingfluidsinconcomitantinhalationandburninjury.

Cleaning products

Certainhouseholdcleaningproductspossesspropertiesthatcancauseacuteinhalationinjury

whenusedimproperly,whenusedwithoutadequateventilation,orwhen


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mixed.Hypochlorite,anoxidizer,isacomponentofbleachingcleanersanddisinfectants.Householdbleachcontainshypo-chloriteatconcentrationslessthan6%.Mixinghypochlorite

bleachorcleanerswithotherincompatibleproductscangenerateirritantgasesresultingin

coughanddyspnea.Mixinghypochloritesolutionswithacidslike


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557hydrochloricacid,sulfuricacid,orphosphoricacidgenerateschlorine.Mixinghypochloritesolutionswithammoniumhydroxide-containingcleanersgenerateschloramine.Bothchlorineand

chloramineareirritantgases.

Methylenechlorideisacomponentofpaint

remover,paintthinner,andothersolventmixtures.Halogenatedhydrocarbonsolventssuchasmethylene

chlorideandtetrachloroethylene(usedasadrycleaningsolvent)can


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doesnotfollowhalogenatedhydrocarboninhalationunlessotherpulmonaryirritantssuchasphosgeneorhydrogenchloridearealsopresent.Complicationsofhalogenatedhydrocarboninhalation

includeaspirationpneumonia,chemicalhepatitis,andhypoxicencephalopathy.

Methylenechloridehas

theadditionalpropertyofbeingmetabolizedtocarbonmonoxide,similartothemethylene

bridgesofbilirubin.Carboxyhemoglobinemiamayfurthercontributetocardiacischemia


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andinfarction.HbCOlevelsmayincreasegraduallyandnotdeclineasquicklywithoxygenadministrationasexpectedfollowingcarbonmonoxideinhalation.Oxygentherapyand

particularlyhyperbaricoxygenhavenotbeenstudiedincarboxyhemoglobinemiafollowingmethylenechlorideinhalation.

Usingthesamerationaleasintreatingcarbonmonoxidepoisoningfromothersources,

however,morbidityandmortalityriskfactorsorHbCO[25%


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30%arereasonablecriteriaforconsideringHBOtherapy.COproductioncancontinuedespiteeffortsatenhancingitselimination.ClinicalandcellularCOeffectsfollowing

methylenechlorideinhalationarethesameasininhaledCOexposure.Residualcentral

nervoussystemeffectsmayreflectthesolvent,hypoxiaor,lesslikely,CO.

Automobile airbags

Thousandsofairbagdeploymentsoccurannuallywith


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onlysomereportsofphysicalormetabolicinjury.Airbagdeploymentoccurswhenanaccelerometerdetectsextremelyrapiddeceleration,inthecaseoffrontdriver

sideandpassengersideairbags,ordirectimpact,asinside-impactandhead-

protectiveairbags.Theelectricalsignaltheneitherdetonatesmaterialgeneratingagasor

releasesacompressedgastoinflatetheairbag.


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Infrontdriversideandpassengersideairbags,sodiumazideandanoxidizeraredetonatedtogeneratenitrogen.Typicalignitionmaterialsareboronand

potassiumnitratewithnitrocellulosesometimesaddedasanignitionenhancer.Filtersthenpartially

coolthenitrogenandremoveparticulatestoprotecttheairbagfromexcessiveheat.

Deflationoftheairbagis


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557passivewithreleaseofthenitrogenfromventilationportsbehindtheairbag.Althoughsodiumazidecancausemethemoglobinemiaanduncoupleoxidative

phosphorylation,thedisksorpelletsarelocatedwithinacontainmenthousingandpose

virtuallynohazardtothevehicleoccupants.Detonationofthesodiumazide,oxidizer,

andaccelerantsgeneratesgas,principallynitrogen.Somecombustiongasesand


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particulatesarereleasedintothepassengercompartmentascarbondioxide,hydrogen,andsmallamountsofcarbonmonoxide.Instudiesmeasuringthesecombustiongases,passenger

compartmentatmosphericconcentrationswerewellbelowoccupationallimitsforshort-termexposure.Respirableparticulates

aregeneratedthatcanincludelowconcentrationsofsodiumhydroxide.Theprinciplevisible

particulatesgeneratedfollowingairbagdeploymentaretalcthatispresent


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onthesurfaceoftheairbagtoprotectitandensuresmooth,symmetricdeployment.Occasionallyoccupantsandrescuepersonnelexperienceeyeandnoseirritation

andthetraceofsodiumhydroxidecancausechemicalkeratitis.Rarelythesegases

andparticulatesmayexacerbatebronchospasminvictimswithpre-existingreactiveairwaydisease.The

ventednitrogenhascausedsuperficialthermalburnstothedorsum


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ofthehandorforearm.Mildtomoderateeye,orbital,ormaxillofacialinjurieshavebeenreportedfollowingdriversideairbagdeploymentandcervicalspine

injurieshaveoccurredinsmalladultsandchildrenfollowingfrontpassengersideairbag

deployment.Airbagsdeployatavelocityof50200mph,withthegreatervelocity

onthefrontpassengersidetocompensateforthegreater


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distancetheairbagmusttraveltoreachthepassenger.Inhalationinjuriestendtoberareandmild.

Occupationandindustry

Exposuretotoxicinhalationscanoccurinalmostanyoccupation(Box4).For

purposesofthisreview,theauthorsdiscussaselectgroupofindustries.The

readerisreferredtothetextbookbySullivanandKrieger


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foramorethoroughdiscussionoftoxicexposuresthatcanoccurinmanyotherindustries[22].Regardlessoftheindustryoroccupation,however,any

caseofsyncopeinanindustryinwhichgasesorvaporsarepresent

needsathoroughworkplaceinvestigationbyhealthprofessionals[22].

Semiconductor manufacturing

Thousandsofchemicalsmaybeusedtomakeacomputer


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chip.Inaddition,somegasesthatareusedaresotoxicthattheyhaveseparategaslineswithremotestorage.Surprisingly,onlyasmall

groupofworkersdirectlyhandlethechips,buttheycanrequiresignificantattention

becausetheyareexposedtomanychemicalhazards.

Dichlorosilane,trichlorosilane,and

silicontetrachloridearegasesusedextensivelyinthesemiconductorindustry.


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Allthreecompoundsyield


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557Box4.Occupationsandindustries

SemiconductormanufacturingPlasticmanufacturingTireandrubbermanufacturingAerospaceindustryBiotechnologyDentalhealthcare

MiningandsmeltingPulpandpaperindustryHazardous-wastedisposalandwastetreatmentShipbuilding

andshiprepairingHealthcareindustryConstructionindustryFirefightersAgriculturalindustry

hydrochloricacidandothersilicon-containingcompoundsonexposuretowater,


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watervapor,ormoistmucousmembranes[23,24].Inoneurbanaccident,workerswereexposedafteraspillofsilicontetrachloride.Mostdevelopedmildeye

andupperrespiratoryirritation.Chestradiographsandpulmonaryfunctionstudiesdidnotreveal

anyabnormalitiesattributabletothespill[25].

Arsineisextremelytoxic

andathighenoughconcentrationscanbeinstantlylethal.Systemic


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arefindingsubstitutesforarsine.

Phosphineisadirectseverepulmonaryirritantathighconcentrationsandcanleadtodeathbyway

ofpulmonaryedema.Patientsoftenpresentwithnonspecificcomplaintsofnausea,vomiting,cough,

chesttightness,andheadache.

Diboraneisanotherpulmonaryirritantandcan

presentwithcough,dyspnea,wheezing,andchesttightness.Inanimals,


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ithasbeenshowntocausepulmonaryedema[26].

Inertgasessuchasargonandnitrogenareusedextensivelyinthesemiconductor

industry.Althoughconsideredsafe,therehavebeencasesofsyncopefromasphyxiationcaused

byleaksinthesystem.

AlthoughmostEDphysiciansarefamiliar

withthemanagementofhydrofluoricacidinjuriestotheskin


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andeyes,inhalationalexposurealso


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557canoccur.Thereissomeevidencetosuggestabeneficialuseofnebulizedcalciumgluconate(2.5%3.0%)[27].Bothpulmonaryandsystemic

effectscanoccur.

Plastic manufacturing

Plasticsareubiquitousinoursociety.

Duringproduction,manyplasticsareheatedandreleasevariousdegradationproductstowhich

workerscanbeexposed.Thecompositionofthemixtureof


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gasesandvaporsthatevolvesiscomplexanddependsonthechemicalconstituentsandtemperature.Lowertemperatures(300400F,150200C)resultinincompletecombustion,thus

producinglarger,morecomplexmolecules.Highertemperatures([1600F,[870C)producelow

molecular-weightgasesaftercompletecombustion[22].Commonpolymersincludepolyethylene,polyvinylchloride,polystyrene,

fluoropolymers,polyurethane,andphenolicpolymers.Respiratoryandsystemicirritantsare


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generatedasbreakdownproducts.Examplesofdegradationproductsincludecarbonmonoxide,cyanide,ammonia,vinylchloride,phosgene,andnitrogendioxide.Theseandothercombustionproducts

maybereleasedduringafireandmaypresentahealthhazardto

firefightersandthepublic.

Mining

Mining,whichistheprocess

ofremovingmineralresourcesfromtheearth,hasoneof


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thehighestmortalityratesamongalloccupations.Althoughmostdeathsareassociatedwithtraumaticinjuries[28],significantmorbiditycanoccurthroughtoxicinhalationsof

variousminegasesanddusts.

Prolongedexposuretominedustscan

causevariouspneumoconioses,suchassilicosis,asbestosis,coal-workerspneumoconiosis,andotherfibroticlung

diseases.Theseentities,however,areusuallychronicinnatureand


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usuallydonotpresentacutelytotheED.Theaveragetimebeforedetectionofsilicosisisapproximately20years[29].

Variousrespiratory

irritantsandasphyxiantscanbeencountered,includingcarbondioxide,carbonmonoxide,hydrogensulfide,

methane,nitrogenoxides,andsulfurdioxide.Manyoftheseminegasesareproduced

asabyproductoftheminingprocessitself,suchas


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fromblastingoperations.

Agriculture

Farmworkersareexposedtoavarietyofchemicals,fertilizers,pesticides,andfumigants.Notsurprisingly,farmershave

ahigherincidenceofrespiratorydiseasewhencomparedwithnonfarmers[30].Organicdust

toxicsyndromeandacutehypersensitivitypneumonitisoccur412hoursafterexposuretoconcentrated

organicdustorantigens,respectively.Thereissomeevidencethat


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systemicsteroidtherapyisofbenefitinacutehypersensitivitypneumonitis.Farmerslung,whichisahypersensitivitypneumonitis,caused


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557byinhalationofmaterialfrommoldyhaycontainingactinomycesbacteria[31],mayresembleaviralsyndromeclinically.Fatigue,fever,malaise,and

anonproductivecougharethemajorsymptoms.Chestradiographmayshowbilateralreticular

interstitialpatterns.Thediagnosisoftenismadewhenthepatientpresentswithidentical

symptomsafterbeingre-exposedtomoldyhayorgrain.


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Construction

Constructionworkersareexposedtonumerousagentsthatarehazardoustotherespiratorysystem.Intermsofacuteinhalationinjuries,painters

maybeexposedtoacetone,amylacetate,methylethylketone,andn-butyllactate,

whichareusedascomponentsorsolventsinpaints,varnishes,orlacquers[32].

Cementworkersalsomaybeexposedtoamylacetateand


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oftenneedspecificimmediatetreatmentinadditiontotheusualsupportivecare.Suspicionforsuchagentsareobviouslyhigherintimesofwar,criminal

acts,oractsofterrorism.

Anthrax

Therearethreeprincipal

typesofanthrax:cutaneous,gastrointestinal,andinhalational.Inhalationalanthraxhistoricallyresultsfromoccupational

exposuretocontaminatedanimalhides.Untilthefallof2001,


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theincidenceofinhalationalanthraxintheUnitedStateshadaveragedlessthanonecaseperyearforthepast20years[34].The

deadlinessofanthraxwhenmanufacturedasabiologicweaponwasrevealedin1979

whenatleast68peoplediedofinhalationalanthraxinSverdlovskfollowingthe

accidentalreleaseofweapons-gradeanthraxsporesbyaresearchfacility.


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Thisanthraxwasmanufacturedtoasizeof15lm,andcasesinhumansoccurredasfarawayas4kmfromthesite

ofthefacility,withcasesinanimalsoccurringasfarawayas50

km.IraqadmittedproducinganddeployingweaponizedanthraxinmissilesduringtheGulf

War[35].Inaddition,inlate2001,ofthe12


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casesofanthraxthatwerereported,sixwereoftheinhalationalvarietyandthreeofthesepatientsdied.

Bacillusanthracisisa

large,gram-positive,aerobic,spore-formingbacillusthatmeasuresapproximately1.01.5lmby3.010.0lm.

Endosporesthatareinhaledbecomedepositedinthealveolarspaceswheretheyare


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557engulfedbymacrophagesandtransportedtomediastinalandperibronchiallymphnodes.Theythengerminateandbecomeavegetativeformthatcauses

toxemiaandmassivesepticemia.Themedianlethalinhalationaldoseforhumans,extrapolatedfrom

primatedata,hasbeenestimatedtobe2,500to55,000spores[36].

Inhalationalanthraxclassicallypresentsasabiphasicillness[37].


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Afteranincubationphaseof16days,patientsdevelopanonspecificillnesscharacterizedbymildfever,malaise,myalgia,nonproductivecough,andsomechestor

abdominalpain.Within23days,thesecondphasestartsabruptlyandischaracterized

byacutedyspnea,diaphoresis,cyanosis,andpersistentfever.Halfofthepatientsmay

beobtundedbycomplicatinganthraxmeningitis.Afterthestartof


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thesecondstage,shock,hypothermia,anddeathcanoccurwithin2436hours.Itmaybedifficulttodifferentiateinhalationalanthraxfromothermorecommon

viralillnessessuchasinfluenza.Somepossiblecluesthatmightleadoneto

consideranthraxincludeabnormalitiesonchestradiographorhelicalchestcomputedtomography(widened

mediastinum,effusions,andmediastinaladenopathy),abdominalpainconcurrentwiththe


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chestsymptoms,andthelackoffeaturessuchasnasalcongestionandrhinorrhea[34].Anthraxisnotspreadfrompersontoperson.

Presumptivediagnosiscanbemadebywayofgrowthonsheepsblood-agar

culturesorbywayofdirectGramsstainsmearofblood,cerebrospinalfluid,

orskinlesionshowingencapsulated,broad,gram-positivebacilli[38].Confirmatory


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tests,however,mustbeperformedatspecializedlaboratories.

Treatmentofclinicallyevidentinhalationalanthraxshouldstartwithintravenousciprofloxacinordoxycycline.Although

therehavebeennocontrolledstudiessupportingamultipledrugapproach,theCDC

recommendsaddinganotheragentpredictedtobeeffective,suchasrifampin,vancomycin,imipenem,

chloramphenicol,penicillin,ampicillin,clindamycin,andclarithromycin[39].Chemoprophylaxisofasymptomatic


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personsisonlyrecommendedafterpublichealthorlaw-enforcementauthoritieshaveascertainedthatthereisanevidentriskforexposuretoasourceconfirmed

tobeanthrax.

Nerve agents

In1995,terroristsleftaplastic

bagofSarinonanundergroundtraininTokyo.Theythenallegedlypierced

thebagwithumbrellatips.Theresultantvaporcaused12


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deathsand3,796injuries[40].

Nervegasesareorganophosphatecompoundsthatareespeciallytoxic.CommonagentsincludeSarin,Tabun,Soman,andVX.

VX(O-ethyl-S-[2(diisoproprylamine)ethyl]methylphosphoeithioate)hasgreaterpotencybutlowervolatilitythanothernerveagents

[41].Theyactbyinhibitingacetylcholinesterase,resultinginacholinergiccrisis.Atroom

temperaturetheyareliquidsbutproduceavaporcapableof


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penetratingrespiratoryepithelium,cornea,andskin.Patientsthuspresentwithrespiratoryandvisualsymptoms,


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557suchasdimmingofvisionandmiosis.Diaphoresisandfasciculationofmusclegroupsalsomayoccurafterskinabsorption.Inpatients

withsystemicpoisoning,immediatetreatmentwithatropineneedstobestartedandcontinued

untilthepatientdemonstratessignsofatropinization,specificallyreductioninairwaysecretionsand

bronchorrhea[41].Inaddition,oximessuchaspralidoximeshouldbe


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giventoreactivatetheinhibitedacetylcholinesteraseatnicotinicsites.

Mustard gas

Sulfurmustardisablisteragentthathasbeenusedin

variouswarstoincapacitatelargenumbersofsoldiers.Atroomtemperatureitis

anoilyliquidbutbecomesaerosolizedwhendispersedbysprayingorbyexplosive

blastfromashellorbomb.Thevaporcanpenetrate


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ordinaryclothing.Fortunatelythemortalityrateislow(3%duringWorldWarI)[42].

Sulfurmustardisavesicantalkylatingagentwhose

mostimportanteffectisinhibitionofcellularglycolysis.Thereisacharacteristiclatent

periodofapproximately412hoursbeforetheonsetofsymptoms.Althoughthemain

effectsarepartialthicknessburns,thosewithinhalationalinjuriesdevelop


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tracheobronchitiswithsymptomssuchaschestpressure,cough,sorethroat,andhoarseness[43].Sinusitis,sinuspain,increasingcough,andtachypneadevelopassymptomsprogress.

Bronchospasmandbronchiolarobstructionbysloughedepitheliumandsecretionsalsocanoccur.In

severeinhalationalexposures,hemorrhagicpulmonaryedema,secondarypneumonia,andrespiratoryfailurecanoccur

afterjust2448hours.Myelosuppressioncancontributetolatersecondary


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pulmonaryinfections.

Phosgene

Phosgeneisagasthatsmellslikemoldyhay.Severepulmonaryedemacandevelopseveralhoursafterbeing

inhaledbecausephosgenecausesanincreaseincapillarypermeability[43].

Riot control agents

Riotcontrolagentsareusedtocausethetemporaryincapacitationofindividuals

bywayofintenseirritationofmucousmembranesandskin.


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Theyusuallyresultinintensereflexlacrimation,althoughsomecausevomitingandotherscauseuncontrolledsneezingandcoughing.Exposurecanoccurbywayof

inhalational,dermal,andoralroutes.Althoughtheyhavelowtoxicity,theyarenot

entirelywithoutrisk.

Twoofthemostcommonriotcontrolagents

includechlorobenzylidenemalononitrile(CS)andoleoresincapsicum(OC).CShas


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essentiallyreplacedCN(chloroacetophenone).TheU.S.militaryconsidersCNobsolete,althoughitisstillcommoninpoliceagencymixturesandsurvivesastheprincipal

componentinaliquidmixtureunderthetradenameMace[44].


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K. Miller, A. Chang /Emerg Med Clin N Am 21 (2003) 533557CSisnowthemostwidelyusedteargasinriotcontrolsituations[44].OC,alsoknownaspepperspray,is

availableoverthecounterforpersonalprotection.Althoughmostcompoundsactprimarilyon

theeye,theyalsocanaffectthepulmonarysystem.

CSis

awhitecrystallinepowderwithapungentpepper-likeodorthat


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isimmediatelydetectable.Itisusedextensivelyinteargas.Irritationoftherespiratorytractisassociatedwithsneezingandcoughing,increasedtracheobronchialsecretions,

andtightnessofthechest[44].ThelethaleffectsofCSbyinhalation

arecausedbylungdamagethatcanleadtoasphyxiaandcirculatoryfailure.

Rarelyrespiratorytractinjurymaybecomplicatedbysecondarypneumonia.


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OCisamixtureofcompoundsobtainedbyextractingdried,ripefruitofCheyennepeppers.Capsaicinistheprincipalconstituentandis

themajorpungentcomponentinmanypeppers.Itelicitsrespiratory-relatedresponsessuchas

nasalirritation,bronchoconstriction,shortnessofbreath,severecoughing,andsneezing.Althoughgenerallyconsidered

safe,seriouseffectsontherespiratorysystemincludingbronchospasm,pulmonary


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edema,andrespiratoryarresthaveoccurred.

Summary

Thelungscanbeanefficientmeansfortheabsorptionofinhaledtoxicants,

resultinginairwayandpulmonaryinjuryorsystemictoxicity.Althoughafewspecific

antidotesexistforinhaledtoxicants,thesyndromeofacuteinhalationinjuryandclinical

therapeuticsarelinkedbycommonpathwaysofpathophysiology.Understandingthe


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mechanismsofinhalationinjuryandoccupation-orsituation-specifictoxicantscansimplifythedecision-makingprocessfortheout-of-hospitalemergencyresponderandtheemergencyphysicianwhenconfronted

withapatientandthemyriadofpotentialinhaledtoxicants.

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