11/22/2015

Acute respiratory distress syndrome: Clinical features and diagnosis in adults

OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate

Acuterespiratorydistresssyndrome:Clinicalfeaturesanddiagnosisinadults
Authors
JohnHansenFlaschen,MD
MarkDSiegel,MD

SectionEditor
PollyEParsons,MD

DeputyEditor
GeraldineFinlay,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Oct2015.|Thistopiclastupdated:Feb10,2015.
INTRODUCTIONAdistincttypeofhypoxemicrespiratoryfailurecharacterizedbyacuteabnormalityofbothlungswasfirstrecognizedduringthe1960s.
MilitarycliniciansworkinginsurgicalhospitalsinVietnamcalleditshocklung,whileciviliancliniciansreferredtoitasadultrespiratorydistresssyndrome[1].
Subsequentrecognitionthatindividualsofanyagecouldbeafflictedledtothecurrentterm,acuterespiratorydistresssyndrome(ARDS).
ARDSisanacute,diffuse,inflammatorylunginjurythatleadstoincreasedpulmonaryvascularpermeability,increasedlungweight,andalossofaeratedtissue
[2].ClinicalhallmarksofARDSarehypoxemiaandbilateralradiographicopacities,whilethepathologicalhallmarkisdiffusealveolardamage(ie,alveolar
edemawithorwithoutfocalhemorrhage,acuteinflammationofthealveolarwalls,andhyalinemembranes).
ARDSisassociatedwithavarietyofriskfactorsandetiologies.TheseconditionsaregroupedtogetherunderthetermARDSbecausetheclinical,physiological
features,pathologicalfeatures,andmanagementaresimilarregardlessoftheincitingevent.
Theclinicalpresentation,course,diagnosticevaluation,anddiagnosticcriteriaofARDSarereviewedhere.Theepidemiology,pathogenesis,etiology,and
managementofARDSarediscussedseparately.(See"Acuterespiratorydistresssyndrome:Epidemiology,pathophysiology,pathology,andetiologyinadults"
and"Acuterespiratorydistresssyndrome:Prognosisandoutcomesinadults"and"Mechanicalventilationofadultsinacuterespiratorydistresssyndrome"and
"Acuterespiratorydistresssyndrome:Supportivecareandoxygenationinadults"and"Acuterespiratorydistresssyndrome:Noveltherapiesinadults".)
CLINICALFEATURES
ClinicalpresentationTheclinicalfeaturesofARDSusuallyappearwithin6to72hoursofanincitingeventandworsenrapidly[3].Patientstypicallypresent
withdyspnea,cyanosis(ie,hypoxemia),anddiffusecrackles.Respiratorydistressisusuallyevident,includingtachypnea,tachycardia,diaphoresis,anduseof
accessorymusclesofrespiration.Acoughandchestpainmayalsoexist.
Arterialbloodgasesrevealhypoxemia,whichisoftenaccompaniedbyacuterespiratoryalkalosisandanelevatedalveolararterialoxygengradient(calculator
1).Highconcentrationsofsupplementaloxygenaregenerallyrequiredtomaintainadequateoxygenation.
Theinitialchestradiographtypicallyhasbilateralalveolarinfiltrates(image1),whilecomputedtomography(CT)usuallyrevealswidespreadpatchyor
coalescentairspaceopacitiesthatareusuallymoreapparentinthedependentlungzones(image2)[46].Theinfiltratesdonothavetobediffuseorsevere,as
bilateralinfiltratesofanyseverityaresufficient[7].
Clinicalfindingsrelatedtotheprecipitantmayalsoexistatpresentation.Asanexample,inpatientswithARDSduetosepsis,theremaybefever,hypotension,
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leukocytosis,lacticacidosis,anddisseminatedintravascularcoagulation(DIC).
ClinicalcourseThefirstseveraldaysofARDSarecharacterizedbyhypoxemiarequiringamoderatetohighconcentrationofinspiredoxygen.Thebilateral
alveolarinfiltratesanddiffusecracklesarepersistentduringthisperiodandpatientsmaybetenuousduetoseverehypoxemia.
Mostpatientswhosurvivethisinitialcoursebegintoexhibitbetteroxygenationanddecreasingalveolarinfiltratesoverthenextseveraldays.Thismaypermit
theamountofventilatorysupporttobedecreasedandweaningtobegin.(See"Weaningfrommechanicalventilation:Readinesstesting"and"Methodsof
weaningfrommechanicalventilation".)
Somepatients,however,havepersistent,severehypoxemiaandremainventilatordependent.Pulmonaryproliferativechangesandfibrosismayprogressively
replacethepathologicalfindingsofdiffusealveolardamageasearlyastendaysaftertheonsetoftherespiratoryfailure.ThefibroproliferativephaseofARDSis
characterizedradiographicallybyprogressionfromairspaceopacificationtoamorecoarselyreticularpatternoflunginfiltration.Thesechangeswithinthelung
parenchymaareoftenaccompaniedbypersistenthypoxemia,lowlungcompliance,highdeadspace,andsometimesbyprogressivepulmonaryhypertension.
Thecoursemaybecomedominatedbypersistentventilatordependenceandvariouscomplications.
Thelungsofpatientswhosurvivethefibroproliferativephaseenterintoanextendedsubsequentphaseofresolutionandrepair.Hypoxemiaandpulmonary
infiltratesgraduallyimproveoverweekstomonths.Cardiopulmonaryfunctionoftenreturnstonearbaselinelevelsby6monthsorlongeraftertheinitiallung
injury.However,manysurvivorsofsevereARDSareleftwithpersistentcognitiveimpairment,emotionaldisturbances,andresidualmuscleweaknessresulting
insubstantiallyreducedqualityoflife[8,9].(See"Acuterespiratorydistresssyndrome:Prognosisandoutcomesinadults".)
ComplicationsPatientswithARDSareathighriskforcomplications.Somecomplicationsarerelatedtomechanicalventilation(eg,pulmonarybarotrauma,
nosocomialpneumonia),whileothersarerelatedtocriticalillnessandbeingintheintensivecareunit(eg,delirium,deepvenousthrombosis,gastrointestinal
bleedingduetostressulceration,andcatheterrelatedinfections).
BarotraumaPatientswithARDSarepredisposedtopulmonarybarotraumaduetothephysicalstressofpositivepressuremechanicalventilationon
acutelydamagedalveolarmembranes[10,11].
ItwaspreviouslycommonforpatientswithARDStodevelopsingleormultiple,sequential,loculatedpneumothoraces.Clinicalexperiencesuggeststhatsuch
complicationsarelesscommonnowthatlowtidalvolumeventilationhasbecomewidespread.Thisissupportedbytheobservationsthat(a)lowtidalvolume
ventilationreducestheplateauairwaypressure[12]and(b)alowerplateauairwaypressureisassociatedwithalowerincidenceofpulmonarybarotrauma.The
latterwasillustratedbyasystematicreviewof14clinicalstudies(2270patientswithARDS)thatfoundastrongcorrelationbetweenpulmonarybarotraumaand
aplateauairwaypressure>35cmH2O[13].
Radiographicallyapparentbarotraumasometimesoccursdespiteanappropriatemechanicalventilationstrategyandcancontributetodeathinpatientswith
otherriskfactorsforapooroutcome[14].Thepathogenesis,riskfactors,prevention,presentation,diagnosis,management,andprognosisofpulmonary
barotraumaarediscussedindetailseparately.(See"Pulmonarybarotraumaduringmechanicalventilation".)
DeliriumARDSandotherformsofacuterespiratoryfailurearecommonlycomplicatedbydelirium[15].Deepsedationandpharmacologicallyinduced
neuromuscularblockadeareoftenusedtotreatagitateddelirium.Whiletheseinterventionsmaycontributetoadverseoutcomessuchasprolongationof
mechanicalventilation,persistentmuscleweakness[16,17],andlongtermimpairmentsincognitionandshorttermmemoryamongsurvivors[18],theymayalso
optimizemechanicalventilation(ie,mitigatederecruitmentassociatedwithpatientventilatordyssynchrony)andpreventdislodgmentoftheendotrachealtube
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andvascularcatheters.OnetrialfoundthatneuromuscularblockadewasassociatedwithimprovedsurvivalinpatientswithsevereARDS[19].
Theuseofsedativesandneuromuscularblockingagentsincriticallyillpatientsisreviewedseparately.(See"Sedativeanalgesicmedicationsincriticallyill
adults:Selection,initiation,maintenance,andwithdrawal"and"Useofneuromuscularblockingmedicationsincriticallyillpatients".)
NosocomialinfectionNosocomialpneumoniaisanimportantcauseofmorbidityandmortalityinpatientswhohaveARDS[2023].(See"Acute
respiratorydistresssyndrome:Prognosisandoutcomesinadults",sectionon'Mortality'.)
TheincidenceofnosocomialpneumoniaamongpatientswithARDSisuncertainbecausethesimilarsymptoms,signs,andradiographicfindingsmakeitdifficult
todistinguishpneumoniafromtheunderlyingARDS[20,24].ThedifficultyidentifyingpneumoniainpatientswithARDSwasillustratedbyanautopsystudythat
foundpneumoniain58percentofpatientswithARDS,althoughpneumoniawassuspectedantemorteminonly20percent[25].Twentypercentofpatients
thoughttohavepneumoniadidnothavehistologicevidenceofpneumonia.
DespitetheuncertaintyabouttheincidenceofnosocomialpneumoniaamongpatientswithARDS,thereisevidencethatnosocomialpneumoniaismore
commonamongpatientswhoaremechanicallyventilatedforARDSthanamongpatientswhoaremechanicallyventilatedforotherreasons.Thiswas
demonstratedbyanobservationalstudyof243consecutivepatientswhorequiredmechanicalventilation,whichfoundthatpatientswithARDSweresignificantly
morelikelytodevelopnosocomialpneumoniathanpatientswithoutARDS(55versus28percent)[26].Apossibleexplanationforthesefindingsisthatpatients
withARDSrequiredalongerdurationofmechanicalventilation.
Thediagnosis,prevention,andmanagementofnosocomialpneumoniaarediscussedseparately.(See"Clinicalpresentationanddiagnosisofventilator
associatedpneumonia"and"Riskfactorsandpreventionofhospitalacquired,ventilatorassociated,andhealthcareassociatedpneumoniainadults"and
"Treatmentofhospitalacquired,ventilatorassociated,andhealthcareassociatedpneumoniainadults".)
OthercomplicationsOthercomplicationsthatfrequentlyoccurduringthehospitalcourseofpatientswithARDSincludethefollowing:
Deepvenousthrombosis(see"Diagnosisofsuspecteddeepveinthrombosisofthelowerextremity")
Gastrointestinalbleedingduetostressulceration(see"Stressulcerprophylaxisintheintensivecareunit")
Poornutrition(see"Nutritionsupportincriticallyillpatients:Anoverview")
Catheterrelatedinfections(see"Diagnosisofintravascularcatheterrelatedinfections"and"Preventionofintravascularcatheterrelatedinfections"and
"Treatmentofintravascularcatheterrelatedinfections")
DIAGNOSTICEVALUATIONThediagnosticevaluationisaimedatidentifyingspecificcausesofARDSthatareamenabletotreatmentandexcludingother
conditionsthatalsopresentwithacutehypoxemia,bilateralalveolarinfiltrates,andrespiratorydistress.Becausethecurrentinternationalconsensusdefinitionof
ARDS(see'Diagnosticcriteria'below)specifiesnocriteriarelatingtotheunderlyingetiologyofacutebilateralinflammatorylunginjury,someuncertainty
remainswithrespecttowhichconditionsshouldorshouldnotbeincludedundertheARDSdiagnosticumbrella.Generallyincludedaredisordersthatareknown
tocausediffusealveolardamageandhavethepotentialtoresolveovertime.Thus,viralordiffusebacterialpneumoniaandacuteinhalationalinjuriesare
included,whereaseosinophilicpneumoniaanddiffusealveolarhemorrhageassociatedwithcollagenvasculardiseasesarenot.Cardiogenicpulmonaryedema
istheprimaryalternativethatneedstobeexcludedbecauseitiscommonandcanbeclinicallyindistinguishablefromARDS.
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ExcludingcardiogenicpulmonaryedemaAnabsenceofcardiacexamabnormalities(eg,anS3orS4gallop,neworchangedmurmur),elevatedright
sidedfillingpressures(eg,elevatedjugularvenouspressure),andcertainradiographicabnormalities(eg,pulmonaryvenouscongestion,KerleyBlines,
cardiomegaly,andpleuraleffusions),helpsdistinguishARDSfromcardiogenicpulmonaryedema.Severaladditionaldiagnostictestsmayalsobehelpful,
includingmeasurementofplasmabrainnatriureticpeptidelevels,echocardiography,andrightheartcatheterization:
Brainnatriureticpeptide(BNP)AplasmaBNPlevelbelow100pg/mLfavorsARDS,buthigherlevelsneitherconfirmheartfailurenorexcludeARDS
[27,28].ThisderivesfromanobservationalstudyofpatientswithARDS(n=33)orcardiogenicpulmonaryedema(n=21)[27].Thestudyfoundthata
plasmaBNPlevellessthan100pg/mLidentifiedARDSwithasensitivity,specificity,positivepredictivevalue,andnegativepredictivevalueof27,95,90,
and44percent,respectively.
EchocardiographyManycliniciansusetransthoracicechocardiographyasthefirstlinediagnostictestifcardiogenicpulmonaryedemacannotbe
excludedbyclinicalevaluationandmeasurementoftheBNPlevel.Whilesevereaorticormitralvalvedysfunction,severediastolicdysfunction,ora
severelyreducedleftventricularejectionfractionfavorscardiogenicpulmonaryedema,thelatterisinsufficienttoconfirmprimarycardiogenicpulmonary
edemabecausesomeprecipitantsofARDS(eg,septicshock)cancauseanacute,severecardiomyopathythatdevelopsconcomitantlywithARDS
[29,30].Inaddition,cardiogenicpulmonaryedemacannotbeexcludedonthebasisofanechocardiogram,sincediastolicdysfunctionandvolumeoverload
mayexisteveniftheleftheartfunctionappearsnormal.
RightheartcatheterizationThereisampleevidencethatthereisgenerallynovaluetoroutinerightheartcatheterizationforeitherthediagnosisor
managementofARDS[31,32].However,pulmonaryarterycatheterizationmaybeconsideredifprimarycardiogenicpulmonaryedemacannotbeexcluded
onthebasisoftheclinicalevaluation,plasmaBNPmeasurement,andechocardiogram.(See"Evaluationofacutedecompensatedheartfailure",section
on'SwanGanzcatheter'.)
ExcludingothercausesofhypoxemicrespiratoryfailurePotentiallytreatablecausesofARDSandalternativeformsofacutehypoxemicrespiratory
failurewithbilateralinfiltratesshouldbeconsideredoncecardiogenicpulmonaryedemahasbeenexcluded.Ifsuchconditionscannotbeidentifiedonthebasis
oftheclinicalcontextandaccompanyingsymptomsandsigns,additionaldiagnostictestingshouldbeperformed:
NoninvasiverespiratorysamplingThelowerrespiratorytractcanbesampledviatracheobronchialaspirationorminibronchoalveolarlavage(miniBAL).
Tracheobronchialaspirationisperformedbyadvancingacatheterthroughtheendotrachealtubeuntilresistanceismetandthenapplyingsuction,while
miniBALisperformedbyadvancingacatheterthroughtheendotrachealtubeuntilresistanceismet,infusingsterilesalinethroughthecatheter,andthen
aspirating.Regardlessofthetechnique,thespecimenthatisobtainedmaybeevaluatedviamicroscopicanalysis(eg,Gramstain,cytology)and
microbiologicculturethesestudiesmayidentifypneumoniaorrapidlyprogressivecancerasthecorrectdiagnosis.(See'Diagnosticevaluation'above.)
FlexiblebronchoscopyFlexiblebronchoscopycanobtainlowerrespiratorysamplesformicroscopicanalysisandmicrobiologiccultureifthenoninvasive
techniquesareunsuccessful.Itcanalsoidentifyabnormalitiesthatmaynotbedetectedwithnoninvasivesampling.Therefore,flexiblebronchoscopyisa
reasonablenextstepwhenevernoninvasivesamplingisnondiagnostic.
Considerthefollowingexamplesoffindingsthatsuggestaspecificetiologyforacutehypoxemicrespiratoryfailure.Frothybloodysecretionsthroughoutthe
airways,increasingredbloodcellsinserialbronchoalveolarlavage(BAL)specimens,andhemosiderinladenmacrophagesintheBALfluidsuggestdiffuse
alveolarhemorrhage.AlargenumberofeosinophilsintheBALfluidsuggestidiopathicacuteeosinophilicpneumonia.And,recoveryoflipidladen
macrophagesorrecognizablefoodparticlessuggestaspirationpneumonitis.
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LungbiopsySurgicallungbiopsymaybeconsideredwhenalternativecausesofacutehypoxemicrespiratoryfailurecannotbeexcludedonthebasisof
theclinicalcontext,symptoms,signs,andbronchoscopy[33,34].Thesafetyoflungbiopsyinselectedpatientswithhypoxemicrespiratoryfailurewas
demonstratedbyaretrospectivestudyof57patientswithARDSwhounderwentopenlungbiopsy[33].Thepatientshadameanratioofarterialoxygen
tensiontofractionofinspiredoxygen(PaO2/FiO2)of145mmHgandtherateofmajorcomplicationswas7percent,withnodeathsattributedtothebiopsy.
Althoughthecomplicationratewas39percent,mostweretolerable(eg,persistentairleaks).Theresultsofthebiopsyresultedintheadditionofspecific
therapyin60percentofpatientsandthewithdrawalofunnecessarytherapyin37percent.
Generallyspeaking,webelievethatlungbiopsyshouldbereservedforcarefullyselectedpatientswhoseacutehypoxemicrespiratoryfailureremainsof
uncertainetiologyafternondiagnosticflexiblebronchoscopyifoneormoreofthediagnosticpossibilitiesunderconsiderationmightwarranttargeted
therapyorwouldsubstantiallychangetheprognosis.Examplesincludecryptogenicorganizingpneumonia,anacutefungallunginfection,anacute
exacerbationofachronicinterstitiallungdisease,vasculitis,ordisseminatedcancer.
DIAGNOSTICCRITERIA
BerlindefinitionARDScanbediagnosedoncecardiogenicpulmonaryedemaandalternativecausesofacutehypoxemicrespiratoryfailureandbilateral
infiltrateshavebeenexcluded.TheBerlinDefinitionofARDSrequiresthatallofthefollowingcriteriabepresenttodiagnoseARDS[2,35]:
Respiratorysymptomsmusthavebegunwithinoneweekofaknownclinicalinsult,orthepatientmusthaveneworworseningsymptomsduringthepast
week.
Bilateralopacitiesconsistentwithpulmonaryedemamustbepresentonachestradiographorcomputedtomographic(CT)scan.Theseopacitiesmustnot
befullyexplainedbypleuraleffusions,lobarcollapse,lungcollapse,orpulmonarynodules.
Thepatientsrespiratoryfailuremustnotbefullyexplainedbycardiacfailureorfluidoverload.Anobjectiveassessment(eg,echocardiography)toexclude
hydrostaticpulmonaryedemaisrequiredifnoriskfactorsforARDSarepresent.
Amoderatetosevereimpairmentofoxygenationmustbepresent,asdefinedbytheratioofarterialoxygentensiontofractionofinspiredoxygen
(PaO2/FiO2).TheseverityofthehypoxemiadefinestheseverityoftheARDS:
MildARDSThePaO2/FiO2is>200mmHg,but300mmHg,onventilatorsettingsthatincludepositiveendexpiratorypressure(PEEP)or
continuouspositiveairwaypressure(CPAP)5cmH2O.
ModerateARDSThePaO2/FiO2is>100mmHg,but200mmHg,onventilatorsettingsthatincludePEEP5cmH2O.
SevereARDSThePaO2/FiO2is100mmHgonventilatorssettingthatincludePEEP5cmH2O.
TodeterminethePaO2/FiO2ratio,thePaO2ismeasuredinmmHgandtheFiO2isexpressedasadecimalbetween0.21and1.Asanexample,ifapatienthas
aPaO2of60mmHgwhilereceiving80percentoxygen,thenthePaO2/FiO2is60mmHg/0.8=75mmHg.DeterminingthePaO2/FiO2requiresarterialbloodgas
(ABG)analysis,whichcanbedifficulttoobtainfromsomepatients.Forsuchpatients,theratioofoxyhemoglobinsaturationmeasuredbypulseoximetry(SpO2)
toFiO2isareasonablesubstitute,accordingtoaretrospectivestudyofABGmeasurementsperformedinadultsreceivingmechanicalventilation[36].Thestudy
foundthataSpO2/FiO2of315predictedaPaO2/FiO2of300(thethresholdforARDS)withasensitivityof91percentandaspecificityof56percent.
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TheBerlinDefinitionofARDS(publishedin2012)replacestheAmericanEuropeanConsensusConferencesdefinitionofARDS(publishedin1994)[16,37].
ThemajorchangestotheBerlinDefinitionarethatthetermacutelunginjuryhasbeeneliminated,thepulmonarycapillarywedgepressure(ie,pulmonary
arteryocclusionpressure)criterionhasbeenremoved,andminimalventilatorsettingshavebeenadded.
PathologyTherelationshipbetweendiffusealveolardamage(DAD)andARDShasbeendescribedinseveralstudies[38,39].Inoneautopsystudyof356
patientswhometclinicalcriteriaforARDSatthetimeofdeath,whenDADwasusedasareferencestandard,thesensitivityandspecificityoftheBerlin
definitionwere89and63percent,respectively[38].AmongpatientsmeetingclinicalcriteriaforARDS,45percenthadDADonautopsy.ThepresenceofDAD
correlatedwithseverity,beingfoundin12,40,and58percentofthosewithmild,moderate,andsevereARDS,respectively.DADwasfoundin69percentof
patientswithsevereARDSwhometclinicalcriteriafor>72hours.Pneumoniawasthemostcommonpathologicfindingamongpatientswhometclinicalcriteria
forARDSbutdidnothaveDAD.ThereiscurrentlynoreadilyavailablewaytodistinguishclinicallybetweenpatientswithandwithouthistologicalDAD.Further
investigationisneededtodeterminewhetherthepresenceorabsenceofDADisclinicallyrelevanttothetreatmentofindividualpatientswithARDS.
DIFFERENTIALDIAGNOSISAvarietyofalternativeconditionsmaypresentasacutehypoxemicrespiratoryfailurewithbilateralalveolarinfiltratesand,
therefore,shouldbeconsideredwheneverARDSissuspected[40].
Cardiogenicpulmonaryedemaisusuallyduetoleftventricularsystolicordiastolicdysfunction,butmayalsobeduetofluidoverload,severehypertension,
renalarterystenosis,orsevererenaldisease.ItspresentationisnearlyidenticaltoARDS,excepttheremaybeevidenceofcardiacdysfunction(eg,anS3
orS4gallop,neworchangedmurmur),elevatedrightsidedfillingpressures(eg,elevatedjugularvenouspressure),orrelatedradiographicabnormalities
(eg,pulmonaryvenouscongestion,KerleyBlines,cardiomegaly,andpleuraleffusions).DistinguishingcardiogenicpulmonaryedemafromARDScanbe
aidedbymeasurementofabrainnatriureticpeptide(BNP)level,echocardiography,and,lessoften,rightheartcatheterization.(See'Excludingcardiogenic
pulmonaryedema'aboveand"Evaluationofacutedecompensatedheartfailure".)
AnacuteexacerbationofidiopathicpulmonaryfibrosisorotherchronicinterstitiallungdiseasescancloselyresembleARDSinbothclinicalpresentation
andchestradiographicabnormalities.LikeARDS,thepathologicalfindingsaredominatedbydiffusealveolardamage,buttheprognosisissubstantially
worse.Thisdiagnosticpossibilityiseasilyoverlookedinpatientswhoseunderlyinginterstitiallungdiseaseisunknownormildormoderateinseverity.The
diagnosisissuggestedbycarefulreviewofpreviouschestradiographicimages,bydiscoveryofsubpleuralreticularchangesintermixedwithalveolar
opacitiesonachestCTscanobtainedshortlyafteronsetofARDS,orbysurgicallungbiopsy.(See"Treatmentofidiopathicpulmonaryfibrosis",sectionon
'Acuteexacerbations'.)
Diffusealveolarhemorrhagemaybeassociatedwithalarge,otherwiseunexplaineddropinthehemoglobinconcentrationandhematocrit.While
hemoptysismaybeminimalorabsent,bronchoscopyoftenrevealsfrothybloodysecretionsthroughouttheairwaysandinvariablydetectsanincreasing
amountofredbloodcellsinserialbronchoalveolarlavagespecimens.Therecoveryofhemosiderinladenmacrophagesfrombronchoalveolarlavagefluid
isstronglysuggestiveofdiffusealveolarhemorrhage.(See"Thediffusealveolarhemorrhagesyndromes".)
Idiopathicacuteeosinophilicpneumonia(IAEP)occursinpreviouslyhealthyindividualsandischaracterizedbycough,fever,dyspnea,andsometimes
chestpain.Bronchoalveolarlavagespecimensalwayscontainalargenumberofeosinophils,typically35to55percentofallrecoveredcells[41,42].
Peripheraleosinophiliamayormaynotbepresent[43].(See"Idiopathicacuteeosinophilicpneumonia".)
Cryptogenicorganizingpneumonia(COP)oftenmimicscommunityacquiredpneumoniawithanonsetthatisheraldedbyaflulikeillnesswithfever,
malaise,fatigue,andcough.Themostcommonfeaturesatpresentationareapersistentnonproductivecough,dyspneawithexertion,andweightloss.
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Bronchoalveolarlavageusuallycontainsasmallerproportionofmacrophagesandhigherproportionsoflymphocytes,neutrophils,andeosinophilsthan
healthypatients.This"mixedpattern"ofincreasedcellularityisthoughttobecharacteristicofCOP.Thediagnosisismadebyrulingoutinfectiouscauses
ofpneumoniaanddocumentingtypicalpathologicchangesintissueobtainedbyopenlungbiopsy.(See"Cryptogenicorganizingpneumonia".)
Acuteinterstitialpneumonia(HammanRichsyndrome)isarareandfulminantformofdiffuselunginjurythathasapresentationsimilartoARDS.Many
peopleconsideracuteinterstitialpneumoniaasubsetofidiopathicARDSsinceitsclinicalmanifestationsaresimilarandbothdemonstratediffusealveolar
damageonhistopathology.ThedistinguishingcharacteristicisthatARDSisoftenassociatedwithaknownriskfactor,whereasacuteinterstitialpneumonia
isnot.(See"Acuteinterstitialpneumonia(HammanRichsyndrome)".)
CancercandisseminatethroughthelungssorapidlythattheensuingrespiratoryfailuremaybemistakenforARDS.Thisismostoftenduetolymphomaor
acuteleukemia,butlymphangiticspreadofsolidtumorsoccasionallybehavesthisway.Cytologicalpreparationofbronchoscopicspecimens(eg,
brushings,lavage)mayrevealmalignantcells.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyondtheBasics.TheBasicspatient
educationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveabouta
givencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatient
educationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatients
whowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocate
patienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Adultrespiratorydistresssyndrome(TheBasics)")
SUMMARYANDRECOMMENDATIONS
Thediagnosisofacuterespiratorydistresssyndrome(ARDS)requiresthatallofthefollowingcriteriabepresent(see'Diagnosticcriteria'above):
Respiratorysymptomsmusthavebegunwithinoneweekofaknownclinicalinsult,orthepatientmusthaveneworworseningsymptomsduringthe
pastweek.
Bilateralopacitiesconsistentwithpulmonaryedemamustbepresentonachestradiographorcomputedtomographic(CT)scan.Theseopacities
mustnotbefullyexplainedbypleuraleffusions,lobarcollapse,lungcollapse,orpulmonarynodules.
Thepatientsrespiratoryfailuremustnotbefullyexplainedbycardiacfailureorfluidoverload.Anobjectiveassessment(eg,echocardiography)to
excludehydrostaticpulmonaryedemaisrequiredifnoriskfactorsforARDSarepresent.
Hypoxemiamustbepresentonminimalventilatorsettings,asdefinedbytheratioofarterialoxygentensiontofractionofinspiredoxygen
(PaO2/FiO2).TheseverityofthehypoxemiadefinestheseverityoftheARDS.MildARDSexistswhenthePaO2/FiO2is>200mmHg,but300
mmHg,oninvasiveornoninvasiveventilatorsettingsthatincludeapositiveendexpiratorypressure(PEEP)orcontinuouspositiveairwaypressure
(CPAP)5cmH2O.ModerateARDSexistswhenthePaO2/FiO2is>100mmHg,but200mmHg,onventilatorsettingsthatincludeaPEEP5cm
H2O.And,severeARDSexistswhenthePaO2/FiO2is100mmHgonventilatorsettingsthatincludeaPEEP5cmH2O.
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PatientswithARDStypicallypresentwithrespiratorydistresscharacterizedbydyspnea,hypoxemia,bilateralalveolarinfiltrates,anddiffusecrackles.
Thesefindingsusuallybeginwithin48to72hoursoftheincitingeventandthenrapidlyworsen.Highconcentrationsofsupplementaloxygenaregenerally
needed.(See'Clinicalpresentation'above.)
Patientswhosurvivetheinitialcourseusuallybegintoexhibitbetteroxygenationanddecreasingalveolarinfiltratesoverthenextseveraldays.Theamount
ofventilatorysupportrequiredmaydecreaseandweaningmaybegin.Somepatients,however,havepersistentinterstitialinfiltratesandremainventilator
dependent.Developmentofpulmonaryfibrosismayfollowandtheclinicalcoursemaybecomedominatedbypersistentventilatordependenceandvarious
complications(eg,pulmonarybarotrauma,nosocomialpneumonia).(See'Clinicalcourse'aboveand'Complications'above.)
ARDSisadiagnosisofexclusion.Therefore,thediagnosticevaluationisaimedatexcludingothercausesofacutehypoxemicrespiratoryfailurewith
bilateralalveolarinfiltrates.Cardiogenicpulmonaryedemaistheprimaryalternativethatneedstobeexcluded.Thismayrequirediagnostictesting(eg,
brainnatriureticpeptide[BNP]levels,echocardiography,and/orrightheartcatheterization).Alternativecausesofacutehypoxemicrespiratoryfailurewith
bilateralinfiltratesshouldbeconsideredoncecardiogenicpulmonaryedemahasbeenexcludedand,ifsuchdiseasescannotbeexcludedonthebasisof
theclinicalcontextandaccompanyingsymptomsandsigns,additionaldiagnostictestingshouldbeperformed.Thismayincludenoninvasiverespiratory
sampling,flexiblebronchoscopy,and/orlungbiopsy.(See'Diagnosticevaluation'above.)
Avarietyofalternativeconditionsmaypresentasacutehypoxemicrespiratoryfailurewithbilateralalveolarinfiltratesand,therefore,shouldbeconsidered
wheneverARDSissuspected.Theyincludecardiogenicpulmonaryedema,diffusealveolarhemorrhage,idiopathicacuteexacerbationofpreexisting
interstitiallungdisease,acuteeosinophilicpneumonia,cryptogenicorganizingpneumonia,acuteinterstitialpneumonia,andrapidlydisseminatingcancer.
(See'Differentialdiagnosis'above.)
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GRAPHICS
Acuterespiratorydistresssyndrome

Chestxrayshowingdiffuse,bilateral,alveolarinfiltrateswithout
cardiomegalyinapatientwithARDS.
CourtesyofStevenEWeinberger,MD.
Graphic53014Version2.0

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ARDSCT

ARDSduetosepsisafterpneumococcalpneumonia.
CourtesyofPaulStark,MD.
Graphic71931Version2.0

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