5/9/2016 What'snewinpulmonaryandcriticalcaremedicine

OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

What'snewinpulmonaryandcriticalcaremedicine

Authors
HelenHollingsworth,MD
AprilFEichler,MD,MPH
GeraldineFinlay,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Aug2016.|Thistopiclastupdated:Sep02,2016.
ThefollowingrepresentadditionstoUpToDatefromthepastsixmonthsthatwereconsideredbytheeditorsandauthors
tobeofparticularinterest.ThemostrecentWhat'sNewentriesareatthetopofeachsubsection.

ASTHMA

Farmanimals,asthma,andtheinnateimmuneresponse(September2016)

Exposuretofarmanimals,particularlyearlyinlife,isnegativelyassociatedwiththedevelopmentofallergicdisease.A
recentstudycompared60childrenfromAmishandHutteritecommunities,twogeneticallysimilar,reproductivelyisolated
farmingpopulationsintheUnitedStates[1].TheAmishhavetraditional,singlefamilyfarmswithexposuretohorsesand
dairycows,whereastheHutteritesliveandworkonlargefarmsthatarehighlyindustrialized.Amishchildrenhave
significantlylowerratesofasthmaandallergicsensitizationthantheirHutteritecounterparts.Endotoxinlevelswere
significantlyhigherintheAmishhomes,anddustextractsfromtheAmishhomes,butnottheHutteritehomes,
significantlyblockedairwayhyperresponsivenessandeosinophiliainamousemodel.Inaddition,invitrostudiesshowed
anenhancedinnateimmuneresponseinAmish,butnotHutterite,children.Thesefindingssuggestthattheclosercontact
withfarmanimalsintheAmishlifestylemayhelppreventthedevelopmentofasthmabyalteringtheinnateimmune
response.(See"Increasingprevalenceofasthmaandallergicrhinitisandtheroleofenvironmentalfactors",sectionon
'Farms,villages,worms,andotherparasites'.)

Acetaminophenuseandasthmainchildren(September2016)

Morefrequentuseofacetaminophenwasassociatedwithincreasedasthmarelatedcomplicationsinchildrenin
observationalstudies,leadingtotherecommendationbysomeforchildrenwithasthmatoavoidacetaminophen.However,
thesefindingswerenotreplicatedinaprospective,randomizedtrialcomparingacetaminophenandibuprofenuse[2].In
thistrial,300childrenwithmildpersistentasthmawererandomlyassignedtoasneededtreatmentwithacetaminophenor
ibuprofenforfeverorpainovera48weekperiod.Allchildrenreceivedstandardcontrollertherapyforasthma.Therewas
nosignificantdifferencebetweenthetwogroupsinthenumberofasthmaexacerbationsrequiringtreatmentwithsystemic
glucocorticoidsorinthenumberofasthmaexacerbations.Thus,wedonotadviserestrictingtheuseofacetaminophenin
childrenwithasthma.(See"Virusinducedwheezingandasthma:Anoverview",sectionon'Acetaminophenuseforfebrile
illnesses'.)

Omalizumabforallergicasthmainchildren6to11yearsofage(July2016)

Omalizumab,amonoclonalantibodytoimmunoglobulinE(IgE),isanoptionforpatientswithmoderatetosevere
persistentasthmaandsensitizationtoperennialaeroallergenswhoareinadequatelycontrolledoninhaledglucocorticoids.
TheUSFoodandDrugAdministration(FDA)hasnowloweredtheapprovedagerangefrom12to6yearsofage,
expandingthetherapeuticoptionsinstep5asthmamanagementinchildren[3].(See"Asthmainchildrenyoungerthan12
years:Treatmentofpersistentasthmawithcontrollermedications",sectionon'Stepuptherapy'and"Asthmainchildren
youngerthan12years:Treatmentofpersistentasthmawithcontrollermedications",sectionon'AntiIgEtherapy'and
"AntiIgEtherapy",sectionon'Omalizumabtherapyinasthma'.)

Housedustmitesublingualimmunotherapyforallergicasthma(May2016)

Injectionallergenimmunotherapywithhousedustmiteextracthasdemonstratedbenefitinpatientswithasthmaand
housedustmiteallergy,butisinconvenientandcarriesasmallriskofseriousallergicreactions.Sublingual
immunotherapytablets(SLITtablets)areasaferformofallergenimmunotherapywithprovenefficacyinallergic
rhinoconjunctivitis,butstudiesinpatientswithallergicasthmaarelimited.Inarandomizedtrialofover800housedust
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mitesensitiveadultswithasthmanotcontrolledbyinhaledbudesonideandshortactingbetaagonists,subjectswere
treatedwithhousedustmiteSLITtabletsorplacebofor7to12months,afterwhichinhaledbudesonidewasgradually
withdrawnandthenstopped[4].HousedustmiteSLITsignificantlyprolongedthetimetofirstmoderateorsevereasthma
exacerbation,reducingtheabsoluteriskofanexacerbationduringbudesonidewithdrawalfrom32to25percentwith
placeboandSLIT,respectively.However,clinicallymeaningfulimprovementsinothermeasuresofasthmasymptoms
werenotclearlydemonstrated.Thus,furtherstudyisneededtoassesstheeffectivenessofSLITtabletsinpatientswith
allergicasthma.HDMSLITtabletsarenotyetavailableintheUnitedStates,butareavailableinAustralia,Japan,and
partsofEurope.(See"Sublingualimmunotherapyforallergicrhinoconjunctivitisandasthma",sectionon'Moderate
persistentasthma'.)

Newguidelinesregardingtheendocrineeffectsoflongterminhaledglucocorticoidsinchildren(April2016)

ThePediatricEndocrineSocietyDrugsandTherapeuticsCommitteereleasedguidelinesregardingadrenalinsufficiencyin
childrenonlongterminhaledcorticosteroids(ICS)[5].Theguidelinesrecommendtestingforadrenalinsufficiencyin
childrenandadolescentswhoaretakinglongtermICS(eg,>6months)andhavesymptomssuggestingadrenal
insufficiency(hypoglycemia,alteredmentalstatus,fatigue,weakness,anorexia,Cushingoidfeatures,growthfailure,or
weightloss).Theguidelinesalsosuggestscreeningasymptomaticchildrenandadolescentswhoaretakinghighdose
ICS.However,becauseoftherarityofclinicallysignificantadrenalinsufficiency,weprefertofollowanindividualized
determinationoftheneedforscreening,basedonthepresenceofthefollowingriskfactors:>6months'useofICSat
dosesexceedingthoseconsidered"high,"combineduseofhighdoseICSandintranasalglucocorticoidsorintermittent
useofsystemicglucocorticoids,andlowbodymassindex(BMI)(eg,<15thpercentileforage).Thefirststepinscreening
foradrenalinsufficiencyismeasurementofan8AMserumcortisol,followedbyadditionaltestingbasedontheresult.
(See"Majorsideeffectsofinhaledglucocorticoids",sectionon'Childrenandadolescents'.)

Asecondmonoclonalantibodyagainstinterleukin5approvedforsevereeosinophilicasthma(April2016)

Reslizumab,amonoclonalantibodytointerleukin(IL)5,hasbeenapprovedbytheUSFoodandDrugAdministration
(FDA)foraddonmaintenancetherapyofsevereasthmainpatientswhoareage18orolderandhaveaneosinophilic
phenotype[6].Itissimilartomepolizumab,whichwasapprovedinlate2015.Inclinicaltrialsofreslizumab,an
eosinophilicphenotypewasdefinedasaperipheralbloodabsoluteeosinophilcount400/microL.Studiesinpatientswith
severeeosinophilicasthmahaveshownthatreslizumabreducestherateofexacerbationsbyapproximately50percent
comparedwithplacebo[7,8].Reslizumabisadministeredintravenouslyatfourweekintervals.TheUSFDAhasaddeda
boxedwarningbecauseanaphylaxisoccurredin0.3percentoftreatedpatients.(See"Treatmentofsevereasthmain
adolescentsandadults",sectionon'Reslizumab'.)

Safetyoffluticasonesalmeterolcombinationtherapyinasthma(March2016)

Inearlystudies,asmallincreaseinasthmarelateddeathsassociatedwithsalmeterolledtheUSFoodandDrug
Administrationtoplaceaboxedwarningontheuseofsalmeterolinasthma.Whileconcerning,thenumberofeventswas
small,andthemagnitudeoftheriskwasunclear.Inaddition,itcouldnotbedeterminedifthepotentialriskofsalmeterol
couldbemitigatedbycombiningitwithaninhaledglucocorticoid.Thesafetyofsalmeterolincombinationwithfluticasone
hasbeenassessedinamulticentertrial,inwhichalmost12,000adolescentsandadultswithpersistentasthmawere
randomlyassignedtotakeinhaledfluticasoneorthecombinationofinhaledfluticasonesalmeterol(inasingleinhaler)for
26weeks[9].Therateofseriousasthmarelatedadverseeventswassimilarinthetwogroups,andnodeathsoccurredin
eithergroup.Inaddition,nodifferencewasnotedintherateofasthmarelatedhospitalizations.Thus,forpatientsoverage
12whodonothaveahistoryoflifethreateningasthmaevents,dataarereassuringaboutthesafetyoffluticasone
salmeterolinafixeddoseinhaler.(See"Betaagonistsinasthma:Controversyregardingchronicuse",sectionon
'Potentialriskmitigation'.)

COPD

GlycopyrroniumindacaterolversusfluticasonesalmeterolformoderatetosevereCOPD(June2016)

Currentguidelinessuggestuseofaninhaledglucocorticoid(ICS)longactingbetaagonist(LABA)inpatientswith
moderatetoseverechronicobstructivepulmonarydisease(COPD)whoareatincreasedriskofexacerbations.Newdata
suggestthatlongactinganticholinergic(LAMA)LABAcombinations,whichimprovepulmonaryfunctionandvariably
reducesymptomsinpatientswithCOPDatlowriskofexacerbations,mayalsobenefitpatientsatincreasedriskof
exacerbation.Inamulticentertrial,glycopyrroniumindacateroloncedailywascomparedwithfluticasonesalmeteroltwice
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dailyinover3000patientswithmoderatetosevereCOPDandatleastonemoderatesevereexacerbationintheprevious
year[10].Overthe52weektrial,glycopyrroniumindacaterolreducedexacerbationsby11percentandwasassociated
withslightlyfewerepisodesofpneumoniacomparedwithfluticasonesalmeterol.TheuseofLAMALABAcombinationsin
thesepatients,inpreferencetoanICSLABAcombination,requiresfurtherstudytodeterminethegeneralizabilityand
durabilityofthesefindings.(See"Managementofstablechronicobstructivepulmonarydisease",sectionon'Comparison
withLAMALABA'.)

Combinationinhaledglucocorticoid/longactingbetaagonistsinpatientswithCOPDandcardiovascularrisk
factorsordisease(May2016)

Whiletheevidencehasbeengenerallyreassuringaboutthesafetyofcombinationinhaledglucocorticoidpluslongacting
betaagonist(ICSLABA)inhalersinpatientswithchronicobstructivepulmonarydisease(COPD),patientswithknown
cardiovasculardisease(CVD)wereexcludedfrompreviousclinicaltrials.Inthethreeyearrandomizedtrial,Studyto
UnderstandMortalityandMorbidITy(SUMMIT),theeffectofthefluticasonefuroatevilanterolcombinationinhalerwas
comparedwiththeindividualcomponentsandplaceboinalmost17,000patientswithmoderateCOPD(FEV1between50
and70percentofpredicted)andknownorincreasedriskofCVD[11].Relativetoplacebo,thecombinationinhalerdidnot
affectallcausemortalityorcompositecardiovascularevents.Thus,thepresenceofCVDshouldnotaffecttheroleof
ICSLABAinhalersinCOPD.(See"ManagementofthepatientwithsevereCOPDandcardiovasculardisease",section
on'Combinationinhaledbronchodilatorplusglucocorticoid'.)

CRITICALCARE

IDSA/ATSguidelinesforthemanagementofhospitalacquiredpneumoniaandventilatorassociatedpneumonia
(August2016)

TheInfectiousDiseasesSocietyofAmericaandtheAmericanThoracicSocietyreleasedupdatedguidelinesforthe
managementofhospitalacquiredpneumonia(HAP)andventilatorassociatedpneumonia(VAP)[12].Empirictherapyfor
HAPandVAPshouldincludeagentswithactivityagainstStaphylococcusaureus,Pseudomonasaeruginosa,andother
gramnegativebacilli.Choiceofaspecificregimenforempirictherapyshouldbebaseduponknowledgeoftheprevailing
pathogens(andsusceptibilitypatterns)withinthehealthcaresettingaswellasriskfactorsformultidrugresistanceinthe
individualpatient.Theguidelinesemphasizethatasevendaycourseofantimicrobialtherapyisappropriateformost
patientsratherthanalongerduration.(See"Treatmentofhospitalacquiredandventilatorassociatedpneumoniainadults",
sectionon'Treatment'.)

Palliativecareconsultationforfamiliesofpatientsintheintensivecareunit(August2016)

Postintensivecaresyndromefamily(PICSF)isatermgiventofamilymemberswhohavebeenaffectedphysicallyand
psychologicallyduringtheintensivecareunit(ICU)stayofcriticallyillpatients.TherapeuticmeasuresforPICSFare
poorlystudied.Onemulticenterrandomizedtrialexaminedtheimpactofapalliativecareledconsultationforsurrogate
decisionmakersofcriticallyillpatientsintheICUwhowereunlikelytoweanfrommechanicalventilation[13].Compared
withroutinefamilymeetingsconductedbytheICUteam,palliativecareledconsultationdidnotreducesymptomsof
anxietyordepressionoffamilymembersandmayhaveincreasedsymptomsofposttraumaticstressdisorder.However,
limitationsofthisstudyincludepossibleinadequate"dosing"oftheintervention(onaverage,1.4encountersperfamilyand
physicianpresenceatonly9percentofmeetings),leavingthepossibilitythatmoreaggressiveandsupportive
interventionsmayhavedifferentoutcomes.(See"Postintensivecaresyndrome(PICS)",sectionon'Postintensivecare
syndromefamily'.)

Interventionsforpostintensivecaresyndromelackbenefit(July2016)

Severalinterventions(eg,earlyandaggressivephysicaltherapyregimensandmultidisciplinarypostintensivecareunit
syndromeclinics)havebeenusedtopreventortreatlongtermmentalandphysicalsequelaeduringrecoveryfromcritical
illness,althoughtheireffectivenesshasbeenpoorlystudied.Tworecentrandomizedtrialsaddresssuchinterventions.

Asinglecentertrialof300criticallyillventilatedpatientsreportednobenefitforanintensivedailyphysical
rehabilitationregimeninitiatedintheintensivecareunit(ICU)andcontinueduntilhospitaldischarge,whencompared
withusualcare(ie,interventionasneededwhenrequestedbythehealthcareteam)[14].(See"Postintensivecare
syndrome(PICS)",sectionon'Prevention'.)

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Amulticenterrandomizedtrialof291survivorsofsepticshockreportedthatamultidisciplinaryteambased
interventionthatincludedprimarycarephysiciancontact,casemanagement,education,subspecialistreferral,and
medicationsdidnotimprovementalhealthparameterssixmonthsafterICUdischarge[15].(See"Postintensive
caresyndrome(PICS)",sectionon'PICSclinics'.)

Althoughdiscouraging,methodologicalflawstothesetrialsmayhavelimitedthedetectionofapotentialbenefitfromthe
treatmentstrategies,andfurtherstudiesarewarranted.

Aspirindoesnotpreventacuterespiratorydistresssyndromeinadults(July2016)

Preclinicalandclinicalobservationalstudieshavesuggestedapotentialroleforaspirininthepreventionofacute
respiratorydistresssyndrome(ARDS).TheabilityofaspirintopreventARDSwastestedinarandomizedtrialof390
patientswhowereassesseduponpresentationtoanemergencydepartmenttobeatriskofdevelopingARDS[16].
Aspirin,administeredat325mgorallyfollowedby81mgdailyforsevendays,hadnoeffectontheincidenceofARDSby
oneweek(approximately10percentineachgroup).However,thelowerthanexpectedrateofARDSinthisstudymay
havelimitedthepotentialtodetectastudydrugeffect.(See"Acuterespiratorydistresssyndrome:Noveltherapiesin
adults",sectionon'Aspirin'.)

OutbreakofBurkholderiacepaciainfectionassociatedwithcontaminatedoralliquiddocusate(June2016)

InJune2016,amultistateoutbreakofBurkholderiacepaciainfectionwasreportedintheUnitedStates[17].B.cepacia
typicallycauseslungcolonizationandinfectioninpatientswithcysticfibrosis(CF),butmostcasesinthisoutbreakhave
involvedmechanicallyventilatedintensivecareunitpatientswithoutCF.Thetypesofinfectionsinvolvedhavenotyet
beenreported.Becausecasesinonestatehavebeenassociatedwithcontaminatedoralliquiddocusate,theUnited
StatesCentersforDiseaseControlandPrevention(CDC)recommendsthatfacilitiesnotuseliquiddocusateproductsfor
anypatient.PharmaTechLLC,themanufacturerofthecontaminatedproduct,DioctoLiquid,hasvoluntarilyrecalledall
nonexpiredlots[18].UpdatedinformationabouttheoutbreakandpublichealthreportingcanbefoundontheCDCs
website.(See"Epidemiology,pathogenesis,microbiology,anddiagnosisofhospitalacquired,ventilatorassociated,and
healthcareassociatedpneumoniainadults",sectionon'OutbreakofBurkholderiacepaciainfection'.)

Apneicoxygenationinadultsundergoingrapidsequenceintubationintheemergencydepartment(June2016)

Anumberoftechniquesareusedtopreventoxygendesaturationduringrapidsequenceintubation(RSI).Onesuch
techniqueinvolvesgivingoxygenpassivelyvianasalcannuladuringtheapneicphaseofRSI.Theresultsofarecent
observationalstudyof635patientsbeingintubatedintheemergencydepartmentsuggestthatthistechniquemayhave
benefitsbeyondsimplypreventinghypoxia[19].Accordingtothisstudy,therateoffirstpasssuccessfulintubationwithout
hypoxiawasgreaterinpatientsmanagedwithapneicoxygenation(82percent)comparedwithpatientsmanagedwithout
thisintervention(69percent).Theimprovementwasduetobothanincreaseintherateoffirstpasssuccessfulintubation
andadecreaseintheincidenceofhypoxia.Whilefurtherstudiesareneededtoconfirmthisfinding,apneicoxygenationis
asimple,beneficialinterventionthatshouldbeusedwheneverRSIisperformedintheemergencydepartment.(See
"Rapidsequenceintubationforadultsoutsidetheoperatingroom",sectionon'Preoxygenation'.)

Dosingofdirectoralanticoagulantsinobesepatients(June2016)

Limiteddataareavailabletoguidedosingofdirectoralanticoagulants(DOACsdabigatran,apixaban,edoxaban,
rivaroxaban)inpatientswithobesity.TheInternationalSocietyofThrombosisandHemostasis(ISTH)hasissued
guidanceonthissubject[20].ThemajorrecommendationsincludeuseofDOACsatstandarddosesforthosewithabody
massindex(BMI)40kg/m2orweight<120kg,andavoidanceofDOACsinindividualswithaBMI>40kg/m2orweight
120kg.(See"Directoralanticoagulants:Dosingandadverseeffects".)

Earlyinitiationofrenalreplacementtherapy(June2016)

Itisuncleariftheearlyinitiationofrenalreplacementtherapy(RRT)(ie,withoutanobviousindicationsuchassevere
hyperkalemia,metabolicacidosis,pulmonaryedemaoradvanceduremicsymptoms)providesanybenefittocriticallyill
patientswithacutekidneyinjury(AKI)comparedwithlaterinitiationsofRRT.Twonewrandomizedtrialshaveevaluated
thisinsomewhatdifferentpatientpopulations.Inthelargertrial,620criticallyillpatientswithsevereAKIwererandomized
toearlyordelayedRRT[21].Therewasnodifferencein60daymortality,andnearlyonehalfofpatientsinthedelayed
RRTgrouprecoveredwithoutrequiringRRT.Incontrast,asecondtrialof231criticallyillpatientswithmoremoderateAKI
showedreduced90daymortalitywithearlierRRT[22].Inthedelayedinitiationgroup,only11patientsendedupnot
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requiringRRT,andearlyRRTreducedthedurationofAKIandlengthofstay.However,wehavelowerconfidenceinthe
resultsofthesmallertrial,becauseitispossiblethattherelativelysmallsizeofthetrialresultedinanoverestimateofthe
treatmentbenefit.Itisotherwisedifficulttounderstandhowminordifferencesintheprotocolsandpatientpopulations
couldachievesuchdramaticallydifferentoutcomes.Untilfurtherdataareavailable,UpToDatesuggeststhatRRTnotbe
initiatedintheabsenceofobviousclinicalindications.(See"Renalreplacementtherapy(dialysis)inacutekidneyinjuryin
adults:Indications,timing,anddialysisdose",sectionon'Timingofelectiveinitiation'.)

Helmetdeliverednoninvasiveventilationinacuterespiratorydistresssyndrome(May2016)

Inpatientswithacuterespiratorydistresssyndrome(ARDS),noninvasiveventilation(NIV)deliveredwithafacemaskis
oftennotsufficienttopreventintubation.Problemsincludepatientdiscomfortandairleaks.DeliveryofNIVusingahelmet
(ie,atransparenthoodthatcoverstheentirehead,sealedwitharubbercollarattheneck)maycircumventsomeofthese
issues.ApreliminarytrialcomparedthetwoapproachesbyrandomlyassigningpatientswithARDSwhorequiredNIVto
continuefacemaskNIVorswitchtohelmetdeliveredNIV[23].HelmetdeliveredNIVreducedtheneedforintubation(18
versus62percent)andincreasedventilatorfreedays.Italsoreducedlengthofstayand90daymortalitywithoutadditional
adverseeffects.Whileencouraging,earlytrialterminationmayhaveexaggeratedtheefficacy.Inaddition,general
concernsregardinglimitedphysicianexperienceandunclearguidelinesregardingpatientselection,optimalventilator
settings,andmonitoringneedtobeaddressedbeforehelmetdeliveredNIVcanbeappliedasatherapyforpatientswith
ARDS.(See"Mechanicalventilationofadultsinacuterespiratorydistresssyndrome",sectionon'Invasiveversus
noninvasive'.)

Simplifiedapproachtoacetylcysteineinfusionforacetaminophenpoisoning(April2016)

Thetreatmentofacetaminophenpoisoningwithacetylcysteineissometimescomplicatedbynonallergicanaphylactic
reactions(NAARs).Theresultsofalargeretrospectivestudy,inadditiontorecentclinicalexperience,suggestthatthese
reactionscanbereducedbyusingatwobagregimeninsteadofthetraditionalthreebagregimendescribedinthe
manufacturerspackageinsertandmostdosingreferences.Inthestudy,NAARsoccurredin10percentofthe389
patientstreatedwiththestandardregimenversus4.3percentofthe210patientstreatedwithamodifiedtwobagregimen
[24].Inbothregimens,acetylcysteinewasinfusedover20hours.Whilefurtherstudyisneededtoensurethesafetyand
effectivenessofthisregimen,webelievethisisareasonableapproachtotreatmentinadultsandolderadolescentswith
acetaminophenpoisoning.(See"Acetaminophen(paracetamol)poisoninginadults:Treatment",sectionon'Simplified20
hourIVprotocol'.)

Noninvasiveventilationforpostoperativerespiratoryfailure(April2016)

Patientselectioniscriticalforthesuccessofnoninvasiveventilation(NIV).TheindicationsforNIVinmedicalpatients
withrespiratoryfailurearewelldefined.However,theindicationsinpatientswithpostoperativerespiratoryfailureareless
clear.TheroleofNIVwasstudiedinatrialofnearly300spontaneouslybreathingpatientswhodevelopedacute
hypoxemicrespiratoryfailurefollowingabdominalsurgery[25].Comparedwithpatientstreatedwithoxygenonly,patients
whoreceivedNIVhadfewerreintubations,moreventilatorfreedays,andfewerhealthcareassociatedinfections.The
exclusionofpatientsrequiringimmediatereintubationandlowerthanexpectedratesofreintubationingenerallimits
interpretationofthisstudy.Althoughencouraging,theseresultsdonotsupporttheroutineadministrationofNIVforthe
treatmentofrespiratoryfailureinsurgicalpatients.CliniciansshouldcontinuetoindividualizeNIVandutilizeitonatrial
basisinthispopulation.(See"Overviewofthemanagementofpostoperativepulmonarycomplications",sectionon
'Postoperativerespiratoryfailure'.)

Highflowoxygenfollowingextubation(March2016)

Highflowoxygendeliveredvianasalcannula(HFNC)isbeingincreasinglyusedinintensivecareandhighdependency
unitssinceitcandeliverhighamountsofsupplementaloxygenandasmallamountofpositiveexpiratorypressure.The
efficacyofHFNCfollowingextubationwasstudiedinover500patients(mostlypostoperativeorneurologic)whohadbeen
mechanicallyventilatedforanaverageofonlyonetotwodaysandconsideredatlowriskofreintubation[26].Patients
wererandomlyassignedtoconventionallowflowoxygenorHFNCimmediatelyfollowingextubation.HFNCledtoa
reductionintherateofreintubationandrespiratoryfailureat72hours.ThesefindingssuggestthatHFNCmaybeusefulin
patientswhoareatlowriskforreintubation.However,theresultsmaynotapplytootherpatientpopulations,since
criticallyillmedicalpatientsandpatientsathighriskofreintubationwereexcludedfromthisstudy.(See"Extubation
management",sectionon'Oxygen'.)

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Dexmedetomidineforagitationinventilatedpatients(March2016)

Dexmedetomidine,acentrallyactivealpha2agonistwithanxiolytic,sedative,andanalgesiceffectsbutnodeleterious
effectonrespiratorydrive,isbeingincreasinglyusedfortreatmentofagitationinmechanicallyventilatedpatients.The
randomizedDahLIatrialevaluateduseofdexmedetomidineinweaningpatientswithdeliriumfrommechanicalventilation
[27].Inamixedpopulationof71intensivecareunit(ICU)patientsinwhomagitateddeliriumwasprohibitingextubation,
dexmedetomidineplusstandardsedation(mostlypropofol)resultedinanincreaseinventilatorfreehoursandreducedtime
toextubation,comparedwithplaceboplusstandardsedation.However,thetrialwasstoppedearlybeforethetarget
enrollmentneededforadequatepowerwasreached.Althoughencouraging,theseresultsarenotdefinitiveandfurther
studiesareneededpriortorecommendationsfortheroutineuseofdexmedetomidinetofacilitateextubationinpatients
withdelirium.(See"Sedativeanalgesicmedicationsincriticallyilladults:Properties,dosageregimens,andadverse
effects",sectionon'Dexmedetomidine'.)

Newdefinitionsofsepsisandsepticshock(March2016)

The2016guidelinesfromTheSocietyofCriticalCareMedicineandEuropeanSocietyofIntensiveCareMedicine
(SCCM/ESICM)proposeanewdefinitionforsepsisandsepticshock[2830].Comparedwitholderguidelines,amajor
changeisthefocusonusingamultiorgandysfunctionscore,theSequentialOrganFailureAssessment(SOFA)score,to
helpidentifythoseatriskofdyingfromsepsis.Sepsisisnowdefinedaslifethreateningorgandysfunctioncausedbya
dysregulatedhostresponsetoinfection,wherelifethreateningorgandysfunctionisidentifiedbyanincreaseof2pointsin
theSOFAscorepatientswhofulfillthesecriteriahaveapredictedmortalityof10percent.Patientswithsepticshockare
definedasasubsetofpatientswithsepsiswhohaveprofoundcirculatory,cellular,andmetabolicabnormalities(ie,
patientswho,despiteadequatefluidresuscitation,requirevasopressorstomaintainameanarterialpressure65mmHg
andhavealactate>2mmol/L[>18mg/dL])thesepatientshaveapredictedmortalityof40percent.Thesystemic
inflammatoryresponsesyndrome(SIRS)criteriaarenolongerincludedinthedefinition.Whilenotdiagnostic,these
definitionsshouldhelpcliniciansidentifypatientswhoareatincreasedriskofdyingfromsepsis.(See"Sepsissyndromes
inadults:Epidemiology,definitions,clinicalpresentation,diagnosis,andprognosis",sectionon'Sepsis'and"Predictive
scoringsystemsintheintensivecareunit",sectionon'Sequential(sepsisrelated)OrganFailureAssessment(SOFA)'.)

Identificationofearlysepsis(March2016)

Theidentificationofearlysepsisiscriticalforthepreventionofsepsisrelateddeath.Ataskforcefromthe2016Societyof
CriticalCareMedicineandEuropeanSocietyofIntensiveCareMedicine(SCCM/ESICM)hasdescribedanew
assessmentscoreforpatientsoutsidetheintensivecareunit(ICU)asawaytofacilitatetheidentificationofpatients
potentiallyatriskofdyingfromsepsis[2830].ThequickSequentialOrganFailureAssessmentscore(qSOFA)canbe
easilycalculatedatthebedsideitcomprisesonlythreecomponents,eachworth1point:respiratoryrate22/minute,
alteredmentation,andsystolicbloodpressure100mmHg.Althoughthistooldoesnotdetectearlysepsis,ascore2
wasassociatedwithpooroutcomesinpatientswithsuspectedinfection,andmaypromptthecliniciantoconsidersepsis
sothattheycanmonitorand/ororinvestigateaccordingly.Whilepromising,qSOFArequiresprospectivevalidationbefore
itcanberoutinelyusedtoidentifypatientswithearlysepsisoutsideoftheICU.(See"Sepsissyndromesinadults:
Epidemiology,definitions,clinicalpresentation,diagnosis,andprognosis",sectionon'Identificationofearlysepsis'and
"Predictivescoringsystemsintheintensivecareunit",sectionon'Sequential(sepsisrelated)OrganFailureAssessment
(SOFA)'.)

Nutritionguidelinesincriticallyilladults(March2016)

GuidelinesfornutritionalsupportincriticallyilladultpatientswerepublishedbytheSocietyofCriticalCareMedicineand
theAmericanSocietyforParenteralandEnteralNutrition[31].Comparedwithearlierversionsoftheguidelines,emphasis
isplaceduponappropriateassessmentofnutritionalstatusinallcriticallyillpatientsusingindirectcalorimetryorpublished
equations,aswellastheearly(within48hoursofadmission)administrationoftrophicenteralnutrition(EN)inadequately
nourishedpatientsusinghighproteinformulations.SupplementationofENwithglutamine,omega3fishoils,or
antioxidantsisdiscouraged.Parenteralnutritionisreservedforthosewhoareunabletobefedadequatelyenterallyand
canbedelayedforupto10daysinthosewhoareadequatelynourished.Furtherdetailedrecommendationsaremadefor
specializedpopulationsofcriticallyillpatientsincludingthosewhoareinadequatelynourished,postoperativepatients,
patientswhoareobese,aswellaspatientswithacutepancreatitis,renalfailure,liverfailure,andsepsis.Notably,these
guidelinesonlyconsideredstudiesthatwerepublishedupuntil2014,andtheoverallqualityoftheevidencewaslow.(See
"Nutritionsupportincriticallyillpatients:Anoverview",sectionon'Introduction'.)

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Detectionandoutcomesinacuterespiratorydistresssyndrome(March2016)

Littleisknownabouttheglobalincidenceofacuterespiratorydistresssyndrome(ARDS)inadultsandwhetherbest
practicesareadheredtowhentreatingpatientswithARDSintheintensivecareunit(ICU).Inamulticenter,international,
prospective,cohortstudyofnearly30,000ICUpatients,ARDSwasresponsiblefor10percentofadmissionsandfor23of
patientswhoweremechanicallyventilated[32].DespitepublisheddefinitionsofARDSandknownbenefitsoflowtidal
volumeventilation(6to8mL/kgidealbodyweightthestandardofcare),cliniciansdemonstratedpoorrecognitionofthe
disorder,particularlywhenitwasmild,andlessthantwothirdsofpatientsreceivedtherecommendedtidalvolume.
Mortalityremainedhigh,rangingfrom35(mildARDS)to46(severeARDS)percent.Thus,cliniciansappeartounder
recognizeandusesuboptimalventilatorystrategiesinpatientswithARDS,adiseasethatcontinuestobeassociatedwith
ahighdiseaseburdenintheICUandsignificantmortality.(See"Acuterespiratorydistresssyndrome:Epidemiology,
pathophysiology,pathology,andetiologyinadults",sectionon'Epidemiology'.)

INTERSTITIALLUNGDISEASE

Revisedcriteriaforacuteexacerbationsofidiopathicpulmonaryfibrosis(August2016)

Aninternationalworkinggrouphaspublishedacomprehensivereviewofacuteexacerbationsofidiopathicpulmonary
fibrosis(IPF)thatincludesareviseddefinitionanddiagnosticcriteria.ThereportdefinesanacuteexacerbationofIPFas,
"anacute,clinicallysignificantrespiratorydeteriorationcharacterizedbyevidenceofnewwidespreadalveolarabnormality"
[33].Thefollowingdiagnosticcriteriaaresuggested:apreviousorconcurrentdiagnosisofIPFacuteworseningor
developmentofdyspneatypicallywithinonemonthofpresentationhighresolutioncomputedtomographywithnew
bilateralgroundglassabnormalityand/orconsolidationsuperimposedonusualinterstitialpneumonia(eg,bibasilarreticular
opacitiesassociatedwithhoneycombchangesandtractionbronchiectasis)deteriorationnotfullyexplainedbycardiac
failureorfluidoverload.Previouscriteriarequiredexclusionofothercausesofacutedeterioration,suchasinfectionor
pulmonaryembolism.(See"Treatmentofidiopathicpulmonaryfibrosis",sectionon'Definition'.)

Screeningforbleomycininducedlungdisease(June2016)

Therehasbeennoconsensusastotheutilityofserialpulmonaryfunctiontests(PFTs,includingthediffusingcapacityfor
carbonmonoxide[DLCO])todetectearlysignsofbleomycininducedlungdisease,andpracticeisvariable.Datareported
fromthecontemporaryDanishTesticularCancerdatabasesuggestthatasystematicapproachtoassessingPFTsbefore
andduringtherapy,withearlydiscontinuationofbleomycinforthosewithadropintheDLCOof25percentormore,
resultedinverylowratesofbothacuteandchroniclungdisease,andnoadverseeffectononcologicoutcomes[34].We
suggestassessmentofPFTs,includingDLCO,atbaselinepriortotreatmentandatintervalsduringtherapyformost
adultsreceivingableomycincontainingchemotherapyregimenforanymalignancy.Theoptimalfrequencyoftestingisnot
established.WesuggestdiscontinuationofbleomycinifthereisadecreaseintheDLCOof25percentormore,evenif
asymptomatic.(See"Bleomycininducedlunginjury",sectionon'Screeningforlungtoxicity'.)

Danazolintelomeredisorders(May2016)

Telomeresareregionsattheendsofchromosomesthatmaintainchromosomalintegrity.Telomeresshortenwithnormal
aging,butinheriteddisordersofprematuretelomereshorteningcancauseaplasticanemia(AA),pulmonaryfibrosis,and
certainmalignancies.Todate,notherapieshavebeendevelopedtoreverseprematuretelomereshortening.Inthefirst
prospectivestudytoevaluateandrogentherapyfortelomeredisorders,theandrogendanazolwasadministeredto27
individualswithmutationsthataffecttelomerelength(mostwithAA)[35].Danazolwasassociatedwithimproved
hematologicparametersinthosewithcytopenias,stabilizationofpulmonarystatusinthosewithpulmonaryfibrosis,and
reducedtelomereshorteninginallevaluableparticipants.Androgensareanattractivecandidatefortreatingtelomere
disorders,althoughfurtherstudyisneeded.(See"Aplasticanemia:Pathogenesisclinicalmanifestationsanddiagnosis",
sectionon'Telomerasemutationsandtelomerelength'and"Pathogenesisofidiopathicpulmonaryfibrosis",sectionon
'Geneticpredisposition'.)

Possibledelayedresponsetopirfenidonetherapyinidiopathicpulmonaryfibrosis(May2016)

Inpatientswithidiopathicpulmonaryfibrosis(IPF),serialmeasurementofforcedvitalcapacity(FVC)demonstrates
substantialvariabilityovertime,makingitdifficulttoanalyzetreatmentresponsesandselectsubsequenttreatment.Ina
followuptotheoriginaltrialsofpirfenidoneinIPF,34subjectsonpirfenidoneand68subjectsonplacebowhoexperienced
a10percentdeclineinFVCinthefirstthreeorsixmonthswerereassessedsixmonthslater[36].Fewersubjectsinthe

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pirfenidonegroupexperiencedafurther10percentdeclineinFVCordeathinthefollowingsixmonthscomparedwiththe
placebogroup(2/34versus19/68,respectively).Whilethenumbersaresmall,thisstudysuggeststhatcontinuing
pirfenidonemaybeofbenefitdespiteinitialevidenceofdiseaseprogression.(See"Treatmentofidiopathicpulmonary
fibrosis",sectionon'Pirfenidone'.)

LUNGTRANSPLANTATION

Zikavirusandtissue/gametedonation(March2016)

Zikavirushasbeendetectedinanumberoftissuesandbodyfluids.ToavoidpossibletransmissionofZikavirus
infection,theUSFoodandDrugAdministration(FDA)hasissueddonordeferralrecommendationsforhematopoieticstem
cells,tissues,anddonorspermoreggstherecommendationsdonotapplytosolidorgans[37].LivingdonorswithZika
virusinfectionorrelevantepidemiologicexposure(residenceinortraveltoanareawheremosquitobornetransmissionof
Zikavirusinfectionhasbeenreported,orunprotectedsexualcontactwithapersonwhomeetsthesecriteria)shouldbe
consideredineligiblefordonationforsixmonths.DeceaseddonorswithZikavirusinfectionintheprecedingsixmonths
shouldalsobeconsideredineligible.ThedeferralperiodrecommendedbytheFDAforblooddonorswithriskfactorsfor
Zikavirusinfectionremainsatfourweeks.(See"Zikavirusinfection:Anoverview",sectionon'Blood/tissuedonation'.)

PULMONARYVASCULARDISEASE

Updatedguidelinesforthetreatmentofvenousthromboembolism(March2016)

TheAmericanCollegeofChestPhysicians(ACCP)haspublishednewguidelinesonantithrombotictherapyforvenous
thromboembolic(VTE)diseasethatincludeguidanceonchoiceofanticoagulant,indicationsforextendedanticoagulation,
andindicationsforthrombolytictherapyinpatientswithacutepulmonaryembolism(PE)[38].Inadditiontoapreference
fordirectoralanticoagulantsforthetreatmentofVTE,theACCPsuggestsextendinganticoagulationbeyondthreemonths
(ie,noscheduledstopdate)inpatientswithunprovokedVTEoractivecancer.Formostpatientswithsmallsubsegmental
pulmonaryembolism(SSPE),anticoagulationissuggestedhowever,clinicalsurveillancewithlowerextremityDoppler
ultrasoundmaybeappropriateforselectpatientswithalowburdenofSSPEwhohavenoevidenceofthrombus
elsewhereandinwhomtheriskofrecurrenceislow.Theguidelinessuggestadministrationofsystemicthrombolytic
therapy,ratherthancatheterdirectedthrombolysis(CDT),forpatientswithhemodynamicallysignificantPECDTmaybe
appropriateforthosewhofailsystemicthrombolysisorwhoareathighriskofbleeding.(See"Fibrinolytic(thrombolytic)
therapyinacutepulmonaryembolismandlowerextremitydeepveinthrombosis",sectionon'Indications'and"Venous
thromboembolism:Anticoagulationafterinitialmanagement",sectionon'Selectionofagent'and"Rationaleandindications
forindefiniteanticoagulationinpatientswithvenousthromboembolism",sectionon'Patientslikelytobenefit'and
"Overviewofthetreatment,prognosis,andfollowupofacutepulmonaryembolisminadults",sectionon'Patientswith
subsegmentalPE'.)

Agentselectionforanticoagulationinvenousthromboembolism(March2016)

Guidelinesforthetreatmentofacutevenousthromboembolism(VTE)wereissuedbyTheAmericanCollegeofChest
Physicians(ACCP)[38].Comparedwithearlierversionsoftheguidelines,thedirectoralanticoagulants(DOACs)
apixaban,edoxaban,rivaroxaban,ordabigatranarenowthepreferredagentsforlongtermanticoagulationinpatientswho
arenotpregnantanddonothaveactivecancerorsevererenalinsufficiency.Thispreferencewasbaseduponrandomized
trialsthatconsistentlyreportedsimilarefficacy,alowerbleedingrisk,andimprovedconveniencewhencomparedwith
warfarin.WeagreewiththispreferenceforDOACsinpatientswithacuteVTE,understandingthatchoosingamong
anticoagulantsfrequentlydependsuponavailabilityandcostaswellaspatientcomorbiditiesandpreferences.(See
"Venousthromboembolism:Anticoagulationafterinitialmanagement",sectionon'Selectionofagent'.)

Estimationofpulmonaryarterypressurebyechocardiography(February2016)

Theaccuracyofechocardiographicestimationofpulmonaryarterysystolicpressurehasbeenquestioned.Whilesome
studieshavereportedthatechocardiographicestimatesandrightheartcatheterizationresultscorrelatestrongly,other
studieshavefoundonlyweakcorrelations.Suboptimalechocardiogramqualityisalikelycauseofthesediscrepant
results.Inaretrospectivestudyof307echocardiogramsinpatientswithadvancedlungdiseaseorpulmonaryarterial
hypertension,only61percentofstudiesweredeemedsufficientforestimationofpulmonaryarterypressure[39].For
interpretablestudies,identificationofpulmonaryhypertensionbyexpertreaderswasexcellent(areaunderthecurve0.97).
Wesuggestadherencetospecificqualitymetricsforacquisitionandinterpretationofechocardiogramstooptimize

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pulmonaryarterypressureestimation,withconfirmationofpressuresbyinvasiverightheartcatheterizationasclinically
indicated.(See"Echocardiographicassessmentoftherightheart",sectionon'Estimationofpulmonaryarterysystolic
pressure'.)

SLEEPMEDICINE

Chronicsleepwakedisturbancesaftertraumaticbraininjury(July2016)

Sleepwakedisturbancesareverycommonintheweekstomonthsfollowingtraumaticbraininjury(TBI),andanewstudy
suggeststhatmanyofthesesymptomspersistlongterm.Inaprospectivecasecontrolstudyinwhich31patientswith
TBIofanyseveritywereevaluatedat18monthsafterinjury,67percentofpatientshadevidenceofexcessivedaytime
sleepinessonobjectivetesting,comparedwithonly19percentofhealthycontrols[40].Patientsalsohadpersistent
pleiosomnia(increasedneedforsleep),requiringanaverageofonemorehourofsleepper24hoursthancontrols.Asin
earlierstudies,patientstendedtounderestimatetheirsymptoms,emphasizingtheimportanceofbothsubjectiveand
objectivesleeptestinginpatientswithsleepwakecomplaintsafterTBI.(See"Sleepwakedisordersinpatientswith
traumaticbraininjury",sectionon'Naturalhistory'.)

Prevalenceofcentralsleepapneainthecommunity(July2016)

Centralsleepapnea(CSA)occurswithincreasedfrequencyinpatientswithheartfailureandothercomorbid
cardiovasculardiseases,buttheprevalenceinthegeneralpopulationhasnotbeenwellestablished.Inapopulationbased
studyofover5000communitydwellingadultsage40yearsandolderwhounderwentpolysomnography,theprevalenceof
CSAwas0.9percent[41].Bycomparison,obstructivesleepapneawaspresentin48percentofpatients.Risksfactors
forCSAincludedageolderthan65years,malegender,andselfreportedheartfailure.CheyneStokesbreathingwas
presentinapproximatelyhalfofpatientswithCSA.(See"Centralsleepapnea:Riskfactors,clinicalpresentation,and
diagnosis",sectionon'Epidemiology'.)

Clinicalpracticeguidelineforchronicinsomniainadults(May2016)

TheAmericanCollegeofPhysicianshasreleasedanewclinicalpracticeguidelineforthemanagementofchronic
insomniainadults[42].Theguidelinerecommendsthatallpatientsreceivecognitivebehavioraltherapyforinsomnia
(CBTI)astheinitialtreatmentforchronicinsomniadisorder.Theguidelinesuggeststhatcliniciansuseashareddecision
makingapproach,includingdiscussionofbenefits,harms,andcostsofshorttermuseofmedications,todecidewhether
toaddmedicationtoCBTIinpatientswithpersistentsymptoms.Thisapproachisconsistentwithourpreferencefor
behavioraltherapyovermedicationinmostpatientswithchronicinsomnia,particularlyinolderadultsandpatientswith
organdysfunction,whoareatincreasedriskforsideeffectsfromsedativehypnoticdrugs.(See"Treatmentofinsomnia",
sectionon'Generalapproach'.)

Racialandethnicdisparitiesinsleepdurationandquality(February2016)

SurveybasedstudieshaveconsistentlyfoundthatblackAmericansandotherracialandethnicminoritiesreporthigher
ratesofinsufficientsleepandpoorsleepqualitycomparedwithwhiteAmericans.Thesedisparitieswereconfirmedina
recentpopulationbasedstudyinwhichnearly500individualscompletedsevennightsofwristactigraphymonitoring[43].
BlackAmericanshadsignificantlyshortermeansleepdurationcomparedwithwhiteAmericans(6.7versus7.5hours),
independentofage,gender,education,workstatus,andmedicalcomorbidities.Multipleindicatorsofsleepqualitywere
alsoworseinblacksandotherracialandethnicminorities.Furtherstudiesareneededtobetterunderstandthecausesof
thesedisparities,asshortsleepdurationhasbeenassociatedwithawiderangeofadversehealthoutcomes,including
cardiovascularmorbidityandallcausemortality.(See"Insufficientsleep:Definition,epidemiology,andadverse
outcomes",sectionon'Epidemiology'.)

OTHERPULMONARYMEDICINE

IDSAguidelinesonthemanagementofaspergillosis(July2016)

TheInfectiousDiseasesSocietyofAmericareleasedupdatedguidelinesforthetreatmentofaspergillosis[44,45].
Voriconazoleremainsthemainstayoftherapyforinvasiveaspergillosis.Incontrastwiththepreviousversionofthe
guidelines,theupdatedversionsuggestsconsiderationofcombinationtherapywithvoriconazoleplusanechinocandinfor
initialtherapyofsevereinvasiveaspergillosis,particularlyinpatientswithhematologicmalignancyand/orinthosewith
profoundandpersistentneutropenia.Wegenerallyagreewiththeseguidelinesandsuggestcombinationtherapywith

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voriconazoleplusanechinocandinforpatientswithsevere,microbiologicallydocumentedinvasiveaspergillosis,butwe
alsoconsidercombinationtherapyforallpatientswithanimmunocompromisingconditionthatledtodisease.(See
"Treatmentandpreventionofinvasiveaspergillosis",sectionon'Guidelines'.)

Restrictionoffluoroquinoloneuseinuncomplicatedinfections(May2016)

TheUSFoodandDrugAdministration(FDA)hasstatedthattheseriousadverseeffectsassociatedwithfluoroquinolones
generallyoutweighthebenefitsforpatientswithuncomplicatedacutesinusitis,acutebronchitis,andurinarytract
infectionswhohaveothertreatmentoptions[46].Forpatientswiththeseinfections,fluoroquinolonesshouldbereserved
forthosewhohavenoalternativetreatmentoptions.ThisannouncementwasbasedonanFDAsafetyreviewshowing
thatsystemicfluoroquinoloneuseisassociatedwithdisablingandpotentiallypermanentserioussideeffects,including
thoseinvolvingthetendons,muscles,joints,nerves,andcentralnervoussystem.(See"Fluoroquinolones",sectionon
'Restrictionofuseforuncomplicatedinfections'.)

NewACCPguidelinesforthetreatmentofunexplainedchroniccough(March2016)

TheAmericanCollegeofChestPhysicianshaspublishednewguidelinesforthetreatmentofunexplainedchroniccough
(definedascough>8weeks'durationthatisunexplainedaftersystematicinvestigationandtreatment)[47].Theguidelines
newlyincludeasuggestionforatherapeutictrialofgabapentin(acentralinhibitorofneurotransmitterrelease).Duetothe
knownadverseeffectsofgabapentin(eg,somnolence,weakness,diarrhea,andnausea),theinitialdoseshouldbe300
mgdaily,whichcanbegraduallyincreasedastoleratedtoamaximumdoseof900mgtwicedaily.(See"Treatmentof
subacuteandchroniccoughinadults",sectionon'Gabapentinandpregabalin'.)

Treatmentofunexplainedchroniccoughwithpregabalin(March2016)

Likegabapentin,pregabalinisthoughttoactcentrallytoinhibitneurotransmitterrelease.Evidenceforitsuseinchronic
coughcomesfromarandomizedtrialinwhich40adultswithchronicrefractorycoughwereassignedtotakepregabalin
dailyorplacebocombinedwithspeechpathologytreatmentfor14weeks[48].Baselinecoughfrequencywas24
coughs/hourinbothgroupsspirometrywasnormal.Bothgroupsexperiencedareductionincoughseverityandcough
frequency,andimprovementsincoughrelatedqualityoflife(QOL).Thepregabalingroupexperiencedgreaterimprovement
incoughseverityandQOL.Adverseeffectsinthepregabalingroupincludeddizzinessin45percentandcognitive
changesin30percent,althoughthesedidnotleadtodiscontinuationofthestudydrug.Fourweeksafterwithdrawalof
studymedication,therewasnodeteriorationinsymptomcontrol.Tominimizesedationanddizziness,pregabalinis
initiatedatalowdoseandgraduallyincreasedastoleratedoveraweek.Ofnote,theAmericanCollegeofChest
Physicians(ACCP)guidelinesdonotincludepregabalinbecausethisstudywaspublishedaftertheguidelineswere
prepared.(See"Treatmentofsubacuteandchroniccoughinadults",sectionon'Gabapentinandpregabalin'.)

Nontuberculousmycobacteriainpatientswithcysticfibrosis(February2016)

Nontuberculousmycobacteria(NTM)areinthesputumofupto20percentofpatientswithcysticfibrosis(CF),andsome
ofthesepatientsdevelopprogressiveNTMpulmonarydisease(NTMPD).Newguidelinesproviderecommendationsfor
thescreening,diagnosis,andmanagementofNTMinCFpatients[49].Annualscreeningofsputumisrecommendedfor
allexpectoratingpatients.PatientswithpersistentlypositiveresultsorsymptomssuggestingNTMPDshouldhaveafull
evaluationincludinghighresolutioncomputedtomography(HRCT)andsometimesbronchoscopytodetermineiftheymeet
criteriaforNTMpulmonarydisease.ForanypatientonchronicazithromycintherapysuspectedofNTMinfection,
azithromycinshouldbestoppedtemporarilypendingfurtherdiagnosticevaluation,toreducetheriskofinducingresistance
becauseofmonotherapy.(See"Cysticfibrosis:Antibiotictherapyforlungdisease",sectionon'Nontuberculous
mycobacteria'.)

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HelenHollingsworth,MDNothingtodisclose.AprilFEichler,MD,MPHEquityOwnership/StockOptions:Johnson&
Johnson[Dementia(galantamine),Epilepsy(topiramate)].GeraldineFinlay,MDNothingtodisclose.

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