6/12/2015

AcuteRespiratoryDistressSyndrome:Background,Pathophysiology,Etiology

AcuteRespiratoryDistressSyndrome
Author:EloiseMHarman,MDChiefEditor:MichaelRPinsky,MD,CM,Dr(hc),FCCP,MCCMmore...
Updated:Sep14,2015

Background
SinceWorldWarI,ithasbeenrecognizedthatsomepatientswithnonthoracicinjuries,severepancreatitis,massive
transfusion,sepsis,andotherconditionsdeveloprespiratorydistress,diffuselunginfiltrates,andrespiratoryfailure,
sometimesafteradelayofhourstodays.Ashbaughetaldescribed12suchpatientsin1967,usingthetermadult
respiratorydistresssyndrometodescribethiscondition. [1]
Beforeresearchintothepathogenesisandtreatmentofthissyndromecouldproceed,itwasnecessarytoformulate
acleardefinitionofthesyndrome.Suchadefinitionwasdevelopedin1994bytheAmericanEuropeanConsensus
Conference(AECC)onacuterespiratorydistresssyndrome(ARDS). [2]Thetermacuterespiratorydistress
syndromewasusedinsteadofadultrespiratorydistresssyndromebecausethesyndromeoccursinbothadults
andchildren.
Beforeresearchintothepathogenesisandtreatmentofthissyndromecouldproceed,itwasnecessarytoformulate
acleardefinitionofthesyndrome.Suchadefinitionwasdevelopedin1994bytheAmericanEuropeanConsensus
Conference(AECC)onacuterespiratorydistresssyndrome(ARDS). [2]Thetermacuterespiratorydistress
syndromewasusedinsteadofadultrespiratorydistresssyndromebecausethesyndromeoccursinbothadults
andchildren.ARDSwasrecognizedasthemostsevereformofacutelunginjury(ALI),aformofdiffusealveolar
injury.TheAECCdefinedARDSasanacuteconditioncharacterizedbybilateralpulmonaryinfiltratesandsevere
hypoxemiaintheabsenceofevidenceforcardiogenicpulmonaryedema.Theseverityofhypoxemianecessaryto
makethediagnosisofARDSwasdefinedbytheratioofthepartialpressureofoxygeninthepatientsarterialblood
(PaO2)tothefractionofoxygenintheinspiredair(FIO2).ARDSwasdefinedbyaPaO2/FIO2ratiooflessthan
200,andinALI,lessthan300.
Thisdefinitionwasfurtherrefinedin2011byapanelofexpertsandistermedtheBerlindefinitionofARDS. [3]
ARDSisdefinedbytiming(within1wkofclinicalinsultoronsetofrespiratorysymptoms)radiographicchanges
(bilateralopacitiesnotfullyexplainedbyeffusions,consolidation,oratelectasis)originofedema(notfullyexplained
bycardiacfailureorfluidoverload)andseveritybasedonthePaO2/FIO2ratioon5cmofcontinuouspositive
airwaypressure(CPAP).The3categoriesaremild(PaO2/FIO2200300),moderate(PaO2/FIO2100200),and
severe(PaO2/FIO2100).
GotoBarotraumaandMechanicalVentilationandPediatricAcuteRespiratoryDistressSyndromeforcomplete
informationonthesetopics.

Pathophysiology
ARDSisassociatedwithdiffusealveolardamage(DAD)andlungcapillaryendothelialinjury.Theearlyphaseis
describedasbeingexudative,whereasthelaterphaseisfibroproliferativeincharacter.
EarlyARDSischaracterizedbyanincreaseinthepermeabilityofthealveolarcapillarybarrier,leadingtoaninflux
offluidintothealveoli.Thealveolarcapillarybarrierisformedbythemicrovascularendotheliumandtheepithelial
liningofthealveoli.Hence,avarietyofinsultsresultingindamageeithertothevascularendotheliumortothe
alveolarepitheliumcouldresultinARDS.
Themainsiteofinjurymaybefocusedoneitherthevascularendothelium(eg,sepsis)orthealveolarepithelium
(eg,aspirationofgastriccontents).Injurytotheendotheliumresultsinincreasedcapillarypermeabilityandtheinflux
ofproteinrichfluidintothealveolarspace.
Injurytothealveolarliningcellsalsopromotespulmonaryedemaformation.Twotypesofalveolarepithelialcells
exist.TypeIcells,whichmakeup90%ofthealveolarepithelium,areinjuredeasily.DamagetotypeIcellsallows
bothincreasedentryoffluidintothealveolianddecreasedclearanceoffluidfromthealveolarspace.
TypeIIalveolarepithelialcellsarerelativelymoreresistanttoinjury.However,typeIIcellshaveseveralimportant
functions,includingtheproductionofsurfactant,iontransport,andproliferationanddifferentiationintotypelcells
aftercellularinjury.DamagetotypeIIcellsresultsindecreasedproductionofsurfactantwithresultantdecreased
complianceandalveolarcollapse.Interferencewiththenormalrepairprocessesinthelungmayleadtothe
developmentoffibrosis.
NeutrophilsarethoughttoplayakeyroleinthepathogenesisofARDS,assuggestedbystudiesofbronchoalveolar
lavage(BAL)andlungbiopsyspecimensinearlyARDS.Despitetheapparentimportanceofneutrophilsinthis
syndrome,ARDSmaydevelopinprofoundlyneutropenicpatients,andinfusionofgranulocytecolonystimulating
factor(GCSF)inpatientswithventilatorassociatedpneumonia(VAP)doesnotpromoteitsdevelopment.Thisand
otherevidencesuggeststhattheneutrophilsobservedinARDSmaybereactiveratherthancausative.
Cytokines(tumornecrosisfactor[TNF],leukotrienes,macrophageinhibitoryfactor,andnumerousothers),along
withplateletsequestrationandactivation,arealsoimportantinthedevelopmentofARDS.Animbalanceof
proinflammatoryandantiinflammatorycytokinesisthoughttooccurafteranincitingevent,suchassepsis.
EvidencefromanimalstudiessuggeststhatthedevelopmentofARDSmaybepromotedbythepositiveairway
pressuredeliveredtothelungbymechanicalventilation.Thisistermedventilatorassociatedlunginjury(VALI).
ARDSexpressesitselfasaninhomogeneousprocess.Relativelynormalalveoli,whicharemorecompliantthan
affectedalveoli,maybecomeoverdistendedbythedeliveredtidalvolume,resultinginbarotrauma(pneumothorax
andinterstitialair).AlveolialreadydamagedbyARDSmayexperiencefurtherinjuryfromtheshearforcesexerted
bythecycleofcollapseatendexpirationandreexpansionbypositivepressureatthenextinspiration(socalled
volutrauma).
Inadditiontothemechanicaleffectsonalveoli,theseforcespromotethesecretionofproinflammatorycytokines
withresultantworseninginflammationandpulmonaryedema.Theuseofpositiveendexpiratorypressure(PEEP)
todiminishalveolarcollapseandtheuseoflowtidalvolumesandlimitedlevelsofinspiratoryfillingpressures
appeartobebeneficialindiminishingtheobservedVALI.
ARDScausesamarkedincreaseinintrapulmonaryshunting,leadingtoseverehypoxemia.AlthoughahighFIO2is

http://emedicine.medscape.com/article/165139overview

1/6

6/12/2015

AcuteRespiratoryDistressSyndrome:Background,Pathophysiology,Etiology

requiredtomaintainadequatetissueoxygenationandlife,additionalmeasures,likelungrecruitmentwithPEEP,
areoftenrequired.Theoretically,highFIO2levelsmaycauseDADviaoxygenfreeradicalandrelatedoxidative
stresses,collectivelycalledoxygentoxicity.Generally,oxygenconcentrationshigherthan65%forprolongedperiods
(days)canresultinDAD,hyalinemembraneformation,and,eventually,fibrosis.
ARDSisuniformlyassociatedwithpulmonaryhypertension.Pulmonaryarteryvasoconstrictionlikelycontributesto
ventilationperfusionmismatchandisoneofthemechanismsofhypoxemiainARDS.Normalizationofpulmonary
arterypressuresoccursasthesyndromeresolves.Thedevelopmentofprogressivepulmonaryhypertensionis
associatedwithapoorprognosis.
TheacutephaseofARDSusuallyresolvescompletely.Lesscommonly,residualpulmonaryfibrosisoccurs,inwhich
thealveolarspacesarefilledwithmesenchymalcellsandnewbloodvessels.Thisprocessseemstobefacilitated
byinterleukin(IL)1.Progressiontofibrosismaybepredictedearlyinthecoursebythefindingofincreasedlevelsof
procollagenpeptideIII(PCPIII)inthefluidobtainedbyBAL.Thisandthefindingoffibrosisonbiopsycorrelate
withanincreasedmortalityrate.

Etiology
MultipleriskfactorsexistforARDS.Approximately20%ofpatientswithARDShavenoidentifiedriskfactor.ARDS
riskfactorsincludedirectlunginjury(mostcommonly,aspirationofgastriccontents),systemicillnesses,and
injuries.ThemostcommonriskfactorforARDSissepsis.
Giventhenumberofadultstudies,majorriskfactorsassociatedwiththedevelopmentofARDSincludethe
following:
Bacteremia
Sepsis
Trauma,withorwithoutpulmonarycontusion
Fractures,particularlymultiplefracturesandlongbonefractures
Burns
Massivetransfusion
Pneumonia
Aspiration
Drugoverdose
Neardrowning
Postperfusioninjuryaftercardiopulmonarybypass
Pancreatitis
Fatembolism
GeneralriskfactorsforARDShavenotbeenprospectivelystudiedusingthe1994EACCcriteria.However,several
factorsappeartoincreasetheriskofARDSafteranincitingevent,includingadvancedage,femalesex(notedonly
intraumacases),cigarettesmoking, [4]andalcoholuse.Foranyunderlyingcause,increasinglysevereillnessas
predictedbyaseverityscoringsystemsuchastheAcutePhysiologyAndChronicHealthEvaluation(APACHE)
increasestheriskofdevelopmentofARDS.

Geneticfactors
AstudybyGlavanetalexaminedtheassociationbetweengeneticvariationsintheFASgeneandALI
susceptibility.ThestudyidentifiedassociationsbetweenfoursinglenucleotidepolymorphismsandincreasedALI
susceptibility. [5]FurtherstudiesareneededtoexaminetheroleofFASinALI.

Epidemiology
TheincidenceofARDSvarieswidely,partlybecausestudieshaveuseddifferentdefinitionsofthedisease.
Moreover,todetermineanaccurateestimateofitsincidence,allcasesofARDSinagivenpopulationmustbe
foundandincluded.Althoughthismaybeproblematic,recentdataareavailablefromtheUnitedStatesand
internationalstudiesthatmayclarifythetrueincidenceofthiscondition.

UnitedStatesstatistics
Inthe1970s,whenaNationalInstitutesofHealth(NIH)studyofARDSwasbeingplanned,theestimatedannual
frequencywas75casesper100,000population.Subsequentstudies,beforethedevelopmentoftheAECC
definitions,reportedmuchlowerfigures.Forexample,astudyfromUtahshowedanestimatedincidenceof4.88.3
casesper100,000population.
DataobtainedmorerecentlybytheNIHsponsoredARDSStudyNetworksuggestthattheincidenceofARDSmay
actuallybehigherthantheoriginalestimateof75casesper100,000population.Aprospectivestudyusingthe1994
AECCdefinitionwasperformedinKingCounty,Washington,fromApril1999throughJuly2000andfoundthatthe
ageadjustedincidenceofALIwas86.2per100,000personyears. [6]Incidenceincreasedwithage,reaching306per
100,000personyearsforpeopleinaged7584years.
Onthebasisofthesestatistics,itisestimatedthat190,600casesexistintheUnitedStatesannuallyandthatthese
casesareassociatedwith74,500deaths.

Internationalstatistics
Thefirststudytousethe1994AECCdefinitionswasperformedinScandinavia,whichreportedannualratesof17.9
casesper100,000populationforALIand13.5casesper100,000populationforARDS. [7]

Agerelateddifferencesinincidence
ARDSmayoccurinpeopleofanyage.Itsincidenceincreaseswithadvancingage,rangingfrom16casesper
100,000personyearsinthoseaged1519yearsto306casesper100,000personyearsinthosebetweentheages
of75and84years.Theagedistributionreflectstheincidenceoftheunderlyingcauses.

Sexrelateddifferencesinincidence
ForARDSassociatedwithsepsisandmostothercauses,nodifferencesintheincidencebetweenmalesand
femalesappeartoexist.However,intraumapatientsonly,theincidenceofthediseasemaybeslightlyhigher
amongfemales.

Prognosis
http://emedicine.medscape.com/article/165139overview

2/6

6/12/2015

AcuteRespiratoryDistressSyndrome:Background,Pathophysiology,Etiology

Untilthe1990s,moststudiesreporteda4070%mortalityrateforARDS.However,2reportsinthe1990s,one
fromalargecountyhospitalinSeattleandonefromtheUnitedKingdom,suggestedmuchlowermortalityrates,in
therangeof3040%. [8,9]Possibleexplanationsfortheimprovedsurvivalratesmaybebetterunderstandingand
treatmentofsepsis,recentchangesintheapplicationofmechanicalventilation,andbetteroverallsupportivecare
ofcriticallyillpatients.
NotethatmostdeathsinARDSpatientsareattributabletosepsis(apoorprognosticfactor)ormultiorganfailure
ratherthantoaprimarypulmonarycause,althoughtherecentsuccessofmechanicalventilationusingsmallertidal
volumesmaysuggestaroleoflunginjuryasadirectcauseofdeath.
MortalityinARDSincreaseswithadvancingage.ThestudyperformedinKingCounty,Washington,foundmortality
ratesof24%inpatientsbetweenages15and19yearsand60%inpatientsaged85yearsandolder.Theadverse
effectofagemayberelatedtounderlyinghealthstatus.
Indicesofoxygenationandventilation,includingthePaO2/FIO2ratio,donotpredicttheoutcomeorriskofdeath.
Theseverityofhypoxemiaatthetimeofdiagnosisdoesnotcorrelatewellwithsurvivalrates.However,thefailure
ofpulmonaryfunctiontoimproveinthefirstweekoftreatmentisapoorprognosticfactor.
Peripheralbloodlevelsofdecoyreceptor3(DcR3),asolubleproteinwithimmunomodulatoryeffects,independently
predict28daymortalityinARDSpatients.InastudycomparingDcR3,solubletriggeringreceptorexpressedon
myeloidcells(sTREM)1,TNFalpha,andIL6inARDSpatients,plasmaDcR3levelsweretheonlybiomarkerto
distinguishsurvivorsfromnonsurvivorsatalltimepointsinweek1ofARDS. [10]NonsurvivorshadhigherDcR3
levelsthansurvivors,regardlessofAPACHEIIscores,andmortalitywashigherinpatientswithhigherDcR3levels.
Morbidityisconsiderable.PatientswithARDSarelikelytohaveprolongedhospitalcourses,andtheyfrequently
developnosocomialinfections,especiallyventilatorassociatedpneumonia(VAP).Inaddition,patientsoftenhave
significantweightlossandmuscleweakness,andfunctionalimpairmentmaypersistformonthsafterhospital
discharge. [11]
Severediseaseandprolongeddurationofmechanicalventilationarepredictorsofpersistentabnormalitiesin
pulmonaryfunction.SurvivorsofARDShavesignificantfunctionalimpairmentforyearsfollowingrecovery.
Inastudyof109survivorsofARDS,12patientsdiedinthefirstyear.In83evaluablesurvivors,spirometryandlung
volumeswerenormalat6months,butdiffusingcapacityremainedmildlydiminished(72%)at1year. [11]ARDS
survivorshadabnormal6minutewalkingdistancesat1year,andonly49%hadreturnedtowork.Theirhealth
relatedqualityoflifewassignificantlybelownormal.However,nopatientremainedoxygendependentat12
months.Radiographicabnormalitieshadalsocompletelyresolved.
Astudyofthissamegroupofpatients5yearsafterrecoveryfromARDS(9additionalpatientshaddiedand64
wereevaluated)wasrecentlypublishedanddemonstratedcontinuedexerciseimpairmentanddecreasedqualityof
liferelatedtobothphysicalandneuropsychologicalfactors. [12]
Astudyexamininghealthrelatedqualityoflife(HRQL)afterARDSdeterminedthatARDSsurvivorshadpoorer
overallHRQLthanthegeneralpopulationat6monthsafterrecovery. [13]Thisincludedlowerscoresinmobility,
energy,andsocialisolation.

PatientEducation
Forpatienteducationresources,seetheLungandAirwayCenter,theProceduresCenter,andtheBacterialand
ViralInfectionsCenter,aswellasAcuteRespiratoryDistressSyndrome,Bronchoscopy,andSevereAcute
RespiratorySyndrome(SARS).
ClinicalPresentation

ContributorInformationandDisclosures
Author
EloiseMHarman,MDStaffPhysicianandMICUDirector,PulmonaryDivision,GainesvilleVeteransAffairs
MedicalCenter
EloiseMHarman,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanCollegeof
ChestPhysicians,AmericanMedicalWomen&#039sAssociation,AmericanThoracicSociety,PhiBetaKappa,
SigmaXi
Disclosure:Nothingtodisclose.
ChiefEditor
MichaelRPinsky,MD,CM,Dr(hc),FCCP,MCCMProfessorofCriticalCareMedicine,Bioengineering,
CardiovascularDisease,ClinicalandTranslationalScienceandAnesthesiology,ViceChairofAcademicAffairs,
DepartmentofCriticalCareMedicine,UniversityofPittsburghMedicalCenter,UniversityofPittsburghSchoolof
Medicine
MichaelRPinsky,MD,CM,Dr(hc),FCCP,MCCMisamemberofthefollowingmedicalsocieties:American
CollegeofChestPhysicians,AssociationofUniversityAnesthetists,EuropeanSocietyofIntensiveCare
Medicine,AmericanCollegeofCriticalCareMedicine,AmericanHeartAssociation,AmericanThoracicSociety,
ShockSociety,SocietyofCriticalCareMedicine
Disclosure:ReceivedhonorariafromLiDCOLtdforconsultingReceivedintellectualpropertyrightsfrom
iNTELOMEDforboardmembershipReceivedhonorariafromEdwardsLifesciencesforconsultingReceived
honorariafromMasimo,Incforboardmembership.
Acknowledgements
FranciscoTalavera,PharmD,PhD
AdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollegeofPharmacyEditorinChief,
MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment
RajatWalia,MD
AssistantProfessorofMedicine,DivisionofPulmonaryandCriticalCareMedicine,UniversityofFloridaCollege
ofMedicine
Disclosure:Nothingtodisclose.

http://emedicine.medscape.com/article/165139overview

3/6

6/12/2015

AcuteRespiratoryDistressSyndrome:Background,Pathophysiology,Etiology

References
1. AshbaughDG,BigelowDB,PettyTL.Acuterespiratorydistressinadults.Lancet.1967Aug12.
2(7511):31923.[Medline].
2. BernardGR,ArtigasA,BrighamKL.TheAmericanEuropeanConsensusConferenceonARDS.
Definitions,mechanisms,relevantoutcomes,andclinicaltrialcoordination.AmJRespirCritCareMed.
1994Mar.149(3Pt1):81824.[Medline].
3. ARDSDefinitionTaskForce,RanieriVM,RubenfeldGD,ThompsonBT,FergusonND,CaldwellE,etal.
Acuterespiratorydistresssyndrome:theBerlinDefinition.JAMA.2012Jun20.307(23):252633.
[Medline].
4. CalfeeCS,MatthayMA,EisnerMD,BenowitzN,CallM,PittetJF,etal.ActiveandPassiveCigarette
SmokingandAcuteLungInjuryFollowingSevereBluntTrauma.AmJRespirCritCareMed.2011Mar18.
[Medline].
5. GlavanBJ,HoldenTD,GossCH,BlackRA,NeffMJ,NathensAB,etal.GeneticvariationintheFAS
geneandassociationswithacutelunginjury.AmJRespirCritCareMed.2011Feb1.183(3):35663.
[Medline].[FullText].
6. RubenfeldGD,CaldwellE,PeabodyE,WeaverJ,MartinDP,NeffM.Incidenceandoutcomesofacute
lunginjury.NEnglJMed.2005Oct20.353(16):168593.[Medline].
7. LuhrOR,AntonsenK,KarlssonM.Incidenceandmortalityafteracuterespiratoryfailureandacute
respiratorydistresssyndromeinSweden,Denmark,andIceland.TheARFStudyGroup.AmJRespirCrit
CareMed.1999Jun.159(6):184961.[Medline].
8. DavidsonTA,CaldwellES,CurtisJR.Reducedqualityoflifeinsurvivorsofacuterespiratorydistress
syndromecomparedwithcriticallyillcontrolpatients.JAMA.1999Jan27.281(4):35460.[Medline].
9. DaveyQuinnA,GedneyJA,WhiteleySM.Extravascularlungwaterandacuterespiratorydistress
syndromeoxygenationandoutcome.AnaesthIntensiveCare.1999Aug.27(4):35762.[Medline].
10. ChenCY,YangKY,ChenMY,ChenHY,LinMT,LeeYC,etal.Decoyreceptor3levelsinperipheral
bloodpredictoutcomesofacuterespiratorydistresssyndrome.AmJRespirCritCareMed.2009Oct15.
180(8):75160.[Medline].
11. HerridgeMS,CheungAM,TanseyCM.Oneyearoutcomesinsurvivorsoftheacuterespiratorydistress
syndrome.NEnglJMed.2003Feb20.348(8):68393.[Medline].
12. HerridgeMS,TanseyCM,MattA,etal.Functionaldisability5yearsafteracuterespiratorydistress
syndrome.NEnglJMed.2011Apr7.364(14):1293304.[Medline].
13. MasclansJR,RocaO,MuozX,PallisaE,TorresF,RelloJ,etal.Qualityoflife,pulmonaryfunction,and
tomographicscanabnormalitiesafterARDS.Chest.2011Jun.139(6):13406.[Medline].
14. KressJP,PohlmanAS,O'ConnorMF,HallJB.Dailyinterruptionofsedativeinfusionsincriticallyill
patientsundergoingmechanicalventilation.NEnglJMed.2000May18.342(20):14717.[Medline].
15. LevittJE,VinayakAG,GehlbachBK,etal.DiagnosticutilityofBtypenatriureticpeptideincriticallyill
patientswithpulmonaryedema:aprospectivecohortstudy.CritCare.2008.12(1):R3.[Medline].[Full
Text].
16. MekontsoDessapA,BoissierF,LeonR,CarreiraS,CampoFR,LemaireF,etal.Prevalenceand
prognosisofshuntingacrosspatentforamenovaleduringacuterespiratorydistresssyndrome.CritCare
Med.2010Sep.38(9):178692.[Medline].
17. MekontsoDessapA,ProostO,BoissierF,LouisB,RocheCampoF,BrochardL.Transesophageal
echocardiographyinpronepositionduringsevereacuterespiratorydistresssyndrome.IntensiveCareMed.
2011Mar.37(3):4304.[Medline].
18. TheNHLBIARDSClinicalTrialsNetwork.Pulmonaryarteryversuscentralvenouscathetertoguide
treatmentofacutelunginjury.NEnglJMed.2006May25.354(21):221324.[Medline].
19. ConnorsAFJr,SperoffT,DawsonNV.Theeffectivenessofrightheartcatheterizationintheinitialcareof
criticallyillpatients.SUPPORTInvestigators.JAMA.1996Sep18.276(11):88997.[Medline].
20. WalmrathD,GntherA,GhofraniHA,SchermulyR,SchneiderT,GrimmingerF,etal.Bronchoscopic
surfactantadministrationinpatientswithsevereadultrespiratorydistresssyndromeandsepsis.AmJ
RespirCritCareMed.1996Jul.154(1):5762.[Medline].
21. MartinLoechesI,LisboaT,RhodesA,MorenoRP,SilvaE,SprungC,etal.Useofearlycorticosteroid
therapyonICUadmissioninpatientsaffectedbyseverepandemic(H1N1)vinfluenzaAinfection.Intensive
CareMed.2011Feb.37(2):27283.[Medline].
22. BrunBuissonC,RichardJC,MercatA,ThibautAC,BrochardL.EarlyCorticosteroidsinSevereInfluenza
A/H1N1PneumoniaandAcuteRespiratoryDistressSyndrome.AmJRespirCritCareMed.2011May1.
183(9):12001206.[Medline].
23. CepkovaM,MatthayMA.Pharmacotherapyofacutelunginjuryandtheacuterespiratorydistress
syndrome.JIntensiveCareMed.2006MayJun.21(3):11943.[Medline].
24. WalkeyAJ,SoylemezWienerR.Utilizationpatternsandpatientoutcomesassociatedwithuseofrescue
therapiesinacutelunginjury.CritCareMed.2011Feb17.[Medline].
25. DellingerRP,ZimmermanJL,TaylorRW.Effectsofinhalednitricoxideinpatientswithacuterespiratory
distresssyndrome:resultsofarandomizedphaseIItrial.InhaledNitricOxideinARDSStudyGroup.Crit
CareMed.1998Jan.26(1):1523.[Medline].
26. GriffithsMJ,EvansTW.Inhalednitricoxidetherapyinadults.NEnglJMed.2005Dec22.353(25):2683
95.
27. AfshariA,BrokJ,MllerAM,WetterslevJ.Inhalednitricoxideforacuterespiratorydistresssyndromeand
acutelunginjuryinadultsandchildren:asystematicreviewwithmetaanalysisandtrialsequential
analysis.AnesthAnalg.2011Jun.112(6):141121.[Medline].
28. TheNHLBIARDSClinicalTrialsNetwork.Comparisonoftwofluidmanagementstrategiesinacutelung
injury.NEnglJMed.2006Jun15.354(24):256475.[Medline].

http://emedicine.medscape.com/article/165139overview

4/6

6/12/2015

AcuteRespiratoryDistressSyndrome:Background,Pathophysiology,Etiology

29. MikkelsenME,ChristieJD,LankenPN,BiesterRC,ThompsonBT,BellamySL,etal.Theadult
respiratorydistresssyndromecognitiveoutcomesstudy:longtermneuropsychologicalfunctioninsurvivors
ofacutelunginjury.AmJRespirCritCareMed.2012Jun15.185(12):130715.[Medline].[FullText].
30. LakhalK,EhrmannS,BenzekriLefvreD,RungeI,LegrasA,DequinPF,etal.Respiratorypulse
pressurevariationfailstopredictfluidresponsivenessinacuterespiratorydistresssyndrome.CritCare.
2011Mar7.15(2):R85.[Medline].
31. FratJP,ThilleAW,MercatA,etal.Highflowoxygenthroughnasalcannulainacutehypoxemicrespiratory
failure.NEnglJMed.2015Jun4.372(23):218596.[Medline].
32. TheAcuteRespiratoryDistressSyndromeNetwork.Ventilationwithlowertidalvolumesascomparedwith
traditionaltidalvolumesforacutelunginjuryandtheacuterespiratorydistresssyndrome.NEnglJMed.
2000May4.342(18):13018.[Medline].
33. BrowerRG,LankenPN,MacIntyreN,MatthayMA,MorrisA,AncukiewiczM.Higherversuslowerpositive
endexpiratorypressuresinpatientswiththeacuterespiratorydistresssyndrome.NEnglJMed.2004Jul
22.351(4):32736.[Medline].
34. PapazianL,ForelJM,GacouinA,PenotRagonC,PerrinG,LoundouA,etal.Neuromuscularblockersin
earlyacuterespiratorydistresssyndrome.NEnglJMed.2010Sep16.363(12):110716.[Medline].
35. JaberS,PetrofBJ,JungB,ChanquesG,BerthetJP,RabuelC,etal.Rapidlyprogressivediaphragmatic
weaknessandinjuryduringmechanicalventilationinhumans.AmJRespirCritCareMed.2011Feb1.
183(3):36471.[Medline].
36. AmatoMB,BarbasCS,MedeirosDM.Effectofaprotectiveventilationstrategyonmortalityintheacute
respiratorydistresssyndrome.NEnglJMed.1998Feb5.338(6):34754.[Medline].
37. BrielM,MeadeM,MercatA,BrowerRG,TalmorD,WalterSD,etal.Highervslowerpositiveend
expiratorypressureinpatientswithacutelunginjuryandacuterespiratorydistresssyndrome:systematic
reviewandmetaanalysis.JAMA.2010Mar3.303(9):86573.[Medline].
38. BellaniG,GuerraL,MuschG,ZanellaA,PatronitiN,MauriT,etal.LungRegionalMetabolicActivityand
GasVolumeChangesInducedbyTidalVentilationinPatientswithAcuteLungInjury.AmJRespirCrit
CareMed.2011Jan21.[Medline].
39. EstebanA,AliaI,GordoF.Prospectiverandomizedtrialcomparingpressurecontrolledventilationand
volumecontrolledventilationinARDS.FortheSpanishLungFailureCollaborativeGroup.Chest.2000
Jun.117(6):16906.[Medline].
40. DerdakS,MehtaS,StewartTE.Highfrequencyoscillatoryventilationforacuterespiratorydistress
syndromeinadults:arandomized,controlledtrial.AmJRespirCritCareMed.2002Sep15.166(6):8018.
[Medline].
41. KacmarekRM,WiedemannHP,LavinPT.Partialliquidventilationinadultpatientswithacuterespiratory
distresssyndrome.AmJRespirCritCareMed.2006Apr15.173(8):8829.
42. GattinoniL,TognoniG,PesentiA.Effectofpronepositioningonthesurvivalofpatientswithacute
respiratoryfailure.NEnglJMed.2001Aug23.345(8):56873.[Medline].
43. GuerinC,GaillardS,LemassonS.Effectsofsystematicpronepositioninginhypoxemicacuterespiratory
failure:arandomizedcontrolledtrial.JAMA.2004Nov17.292(19):237987.
44. MorrisAH,WallaceCJ,MenloveRL,etal.Randomizedclinicaltrialofpressurecontrolledinverseratio
ventilationandextracorporealCO2removalforadultrespiratorydistresssyndrome.AmJRespirCritCare
Med.1994Feb.149(2Pt1):295305.[Medline].
45. BishopJF,MurnaneMP,OwenR.Australia'swinterwiththe2009pandemicinfluenzaA(H1N1)virus.N
EnglJMed.2009Dec31.361(27):25914.[Medline].
46. GadekJE,DeMicheleSJ,KarlstadMD.Effectofenteralfeedingwitheicosapentaenoicacid,gamma
linolenicacid,andantioxidantsinpatientswithacuterespiratorydistresssyndrome.EnteralNutritionin
ARDSStudyGroup.CritCareMed.1999Aug.27(8):140920.[Medline].
47. PontesArrudaA,AragoAM,AlbuquerqueJD.Effectsofenteralfeedingwitheicosapentaenoicacid,
gammalinolenicacid,andantioxidantsinmechanicallyventilatedpatientswithseveresepsisandseptic
shock.CritCareMed.2006Sep.34(9):232533.[Medline].
48. KrzakA,PlevaM,NapolitanoLM.NutritiontherapyforALIandARDS.CritCareClin.2011Jul.27(3):647
59.[Medline].
49. RiceTW,WheelerAP,ThompsonBT,SteingrubJ,HiteRD,MossM,etal.Initialtrophicvsfullenteral
feedinginpatientswithacutelunginjury:theEDENrandomizedtrial.JAMA.2012Feb22.307(8):795
803.[Medline].
50. GajicO,DaraSI,MendezJL,etal.Ventilatorassociatedlunginjuryinpatientswithoutacutelunginjuryat
theonsetofmechanicalventilation.CritCareMed.2004Sep.32(9):181724.[Medline].
51. CraigTR,DuffyMJ,ShyamsundarM,etal.Arandomizedclinicaltrialofhydroxymethylglutarylcoenzyme
areductaseinhibitionforacutelunginjury(TheHARPStudy).AmJRespirCritCareMed.2011Mar1.
183(5):6206.[Medline].
52. MeduriGU,ChinnAJ,LeeperKV.Corticosteroidrescuetreatmentofprogressivefibroproliferationinlate
ARDS.Patternsofresponseandpredictorsofoutcome.Chest.1994May.105(5):151627.[Medline].
53. SteinbergKP,HudsonLD,GoodmanRB,HoughCL,LankenPN,HyzyR.Efficacyandsafetyof
corticosteroidsforpersistentacuterespiratorydistresssyndrome.NEnglJMed.2006Apr20.
354(16):167184.[Medline].
54. MurrayJF,MatthayMA,LuceJM.Anexpandeddefinitionoftheadultrespiratorydistresssyndrome.Am
RevRespirDis.1988Sep.138(3):7203.[Medline].
55. CalfeeCS,WareLB,GliddenDV,EisnerMD,ParsonsPE,ThompsonBT,etal.Useofrisk
reclassificationwithmultiplebiomarkersimprovesmortalitypredictioninacutelunginjury.CritCareMed.
2011Jan28.[Medline].
56. GajicO,DabbaghO,ParkPK,etal.Earlyidentificationofpatientsatriskofacutelunginjury:evaluation
oflunginjurypredictionscoreinamulticentercohortstudy.AmJRespirCritCareMed.2011Feb15.
183(4):46270.[Medline].[FullText].

http://emedicine.medscape.com/article/165139overview

5/6

6/12/2015

AcuteRespiratoryDistressSyndrome:Background,Pathophysiology,Etiology

57. CraigTR,DuffyMJ,ShyamsundarM,McDowellC,O'KaneCM,ElbornJS,etal.ARandomizedClinical
TrialofHydroxymethylglutarylCoenzymeAReductaseInhibitionforAcuteLungInjury(TheHARPStudy).
AmJRespirCritCareMed.2011Mar1.183(5):6206.[Medline].
58. SprungCL,AnnaneD,KehD,MorenoR,SingerM,FreivogelK.Hydrocortisonetherapyforpatientswith
septicshock.NEnglJMed.2008Jan10.358(2):11124.[Medline].
59. MatthayMA,ZimmermanGA.Acutelunginjuryandtheacuterespiratorydistresssyndrome:fourdecades
ofinquiryintopathogenesisandrationalmanagement.AmJRespirCellMolBiol.2005Oct.33(4):31927.
[Medline].[FullText].
MedscapeReference2011WebMD,LLC

http://emedicine.medscape.com/article/165139overview

6/6