High Altitude Illness - Physiology, Risk Factors, and General Prevention - UpToDate

10/7/2016
Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Highaltitudeillness:Physiology,riskfactors,andgeneralprevention
Authors: ScottAGallagher,MD,PeterHackett,MD,JonathanMRosen,MD
SectionEditor: DanielFDanzl,MD
DeputyEditor: JonathanGrayzel,MD,FAAEM
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Sep2016.|Thistopiclastupdated:Apr15,2015.
INTRODUCTIONThebeautyandrecreationalopportunitiesofthemountainsattractmillionsofvisitorsfrom
lowlandelevationstohighaltitudedestinationsworldwide.ResorttownsintheWesternUnitedStatesalone
attractover30millionvisitorsannually,generallytosleepingelevationsinthe2000to3000m(6500to9800
feet)range.Manymillionsmorevisitcitiesattheseelevations,includingseverallargecitiesinSouthAmerica
andAsiasituatedabove3000m[1].Mostofthesedestinationscanbereachedwithinaday.
Inaddition,tensofthousandsofclimbers,trekkers,andskiersworldwideascendtoelevationsinthe3000to
5500m(9800to18,000feet)range,oftenataratethatexceedsanindividual'sabilitytoacclimatize.A
growingnumberofmountaineersseekthesummitsofpeaksover5500m.Military,rescue,andother
professionalpersonnelmayalsobecalledupontoascendtohighaltitudeswithlittleornotimefor
acclimatization.Suchrapidascentsplacetheunacclimatizedtraveleratriskfordevelopinghighaltitudeillness
(HAI).
Cliniciansworkinginornearmountainousareasmustfamiliarizethemselveswiththepresentationand
managementofHAI,whileallhealthcareworkerswhoadvisetravelersneedtounderstandthebest
preventionstrategiesandtreatmentoptions.ThedifferenttypesofHAI,theirpathophysiology,andgeneral
methodsforpreventionwillbereviewedhere.Thediagnosis,treatment,andpreventionofspecifictypesof
HAIarediscussedseparately.(See"Acutemountainsicknessandhighaltitudecerebraledema"and"High
altitudepulmonaryedema"and"Highaltitude,airtravel,andheartdisease".)
HIGHALTITUDEPHYSIOLOGY
HypobarichypoxiaThepartialpressureofoxygen(PO2)isthedrivingforceforthediffusionofoxygen
downtheoxygencascade.Oxygenmovesfrominspiredairtothealveolarspaceviatheairwaysandthen
diffusesacrossthealveoliintotheblood(figure1andfigure2),whereitiscarriedmainlyboundtohemoglobin
butalsoindissolvedform.Atthelevelofthecapillaries,oxygendiffusesacrossvesselwalls,throughthe
tissuesandintocells,andultimatelyintothemitochondria.(See"Oxygendeliveryandconsumption"and
"Oxygenationandmechanismsofhypoxemia".)
Thepartialpressureofoxygenofinspiredair(PIO2)isgivenbytheequation:PIO2=FIO2x(Pb47mmHg),
whereFIO2isthefractionofoxygenininspiredair,Pbisthebarometricpressure,and47mmHgisthevapor
pressureofH2Oat37C.Inspiredgasis100percenthumidifiedbythetimeitreachesthealveoliandwater
vaporpressureisaffectedbytemperaturebut,unlikeothergases,isnotdependentonaltitude.The
proportionofaircomprisedbyoxygen(FIO2,20.94percent)remainsconstantatthehighestterrestrial
elevationsandevenintotheuppertroposphere.Hence,thePIO2andtherefore,theoxygencascade,are
directlyaffectedbybarometricpressure.
Barometricpressurediminishesinacurvilinearfashionwithincreasingaltitude(table1andtable2andtable
3).Barometricpressurealsodecreaseswithlowertemperature,higherlatitude,inclementweather,andduring
winter.Althoughtheeffectofthesevariablesuponbarometricpressureisnotnearlyassignificantasaltitude,
itbecomesphysiologicallysignificantatelevationsoverapproximately2800m(9200feet)[2].
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Atsealevelthereisalargepressuregradientforoxygenbetweeninspiredairandtissue.However,as
barometricpressurefallssodoestheavailableoxygen.Athighaltitudes,especiallywhentissueoxygen
demandsarehighduringathleticorworkactivities,themarkedreductioninthepressuregradientand
availableoxygencanleadtotissuehypoxia.Thisformofhypoxiaistermedhypobarichypoxia,andit
representstheinitialcauseofhighaltitudeillness(HAI).
Acclimatization
OverviewAsPIO2decreaseswithascent,thenormaldrivingpressureofPO2downtheoxygen
cascadediminishes,resultinginprogressivetissuehypoxia(figure3)[1,3,4].Thenormalcompensatory
responsestoacutehypobarichypoxiaaretermedacclimatization,anincompletelyunderstood,complexseries
ofphysiologicchangesinvolvingmultipleorgansystemsthatoccursovervaryingperiods(fromminutesto
weeks).Acclimatizationimprovestissueoxygenationbyincreasingtheefficiencywithwhichoxygenmoves
downtheoxygencascadeandbyoptimizingtheutilizationofoxygenatthecellularlevel.
Acclimatizationdiffersfromadaptation,whichreferstophysiologicchangesthattakeplaceinresponseto
chronicexposuretohypobarichypoxiaovergenerationsandareobservedinsomepopulationspermanently
situatedathighaltitude.Thecapacitytoacclimatizevariesgreatlyamongindividualsandisdependentupon
manyfactors,includingthedegreeofhypoxicstress(rateofascent,altitudeattained),theintrinsiccapacityof
theindividualtocompensatefordiminishedPaO2(geneticandanatomicvariation,medicalconditions),and
extrinsicfactors,whichmayenhanceorinterferewithcompensatorymechanisms(eg,alcohol,medications,
temperature)[5].
Theprocessofacclimatizationbeginswithinminutesofascentbutrequiresseveralweekstocomplete.
Hypoxiainduciblefactor1alpha(HIF1a)isatranscriptionfactorresponsibleforactivatingmorethan350
genesinresponsetohypoxia,andplaysamajorroleinactivatingthecellularmechanismsresponsiblefor
acclimatization.Otherfactorsandgenesarelikelybeinvolvedaswell[6].
AlthoughthecomplexcompensatorychangesthatoccurcannotfullyrestoretissuePO2tosealevelvalues,
acclimatizationcansubstantiallyimproveoxygendeliveryandutilization.Infact,acclimatizationenablessome
climberstofunctionwithonlyminordifficultyonthepeakofMountEverest(8848mor29,029feet)without
supplementaloxygen[3].
At8848m,PIO2is43.1mmHg,equivalenttobreathing6percentoxygenatsealevel.Suddenexposureto
suchhighaltitude(eg,pilot'scockpitsuddenlydecompresses)resultsinlossofconsciousnessanddeath[1].
Adetaileddiscussionofacclimatizationisbeyondthescopeofthisreview,butcanbefoundinseveral
excellentsources[1,7].Abriefreviewofthebeneficialchangesthatoccurduringacclimatizationisprovided
below.Otheraspectsofrespiratoryphysiologyarediscussedseparately.(See"Controlofventilation"and
"Physiologyofdyspnea".)
VentilationandPaO2Thefirstandmostimportantstepinimprovingoxygendeliveryisanincreasein
ventilation.Withoutincreasedventilation,humanscouldnottoleratealtitudeshigherthan5000m(16,400
feet)[1,3,4].
Hypoxicstimulationoftheperipheralchemoreceptors(atthecarotidandaorticbodies)resultsinincreased
minuteventilationandistermedthehypoxicventilatoryresponse(HVR).HVRincreasesinsensitivityover
severaldaysspentataltitude.Overall,minuteventilationincreasesinanearlylinearfashionwithdiminishing
SpO2.TheincreaseinventilationalsolowersthealveolarCO2andcausesarespiratoryalkalosis.The
reductionofCO2inthealveolarspacereducesthedilutionaleffectofCO2inalveolarair[4].Simultaneously,
thePCO2levelatwhichventilationisstimulatedislowered(hypercapnicventilatoryresponse(HCVR)),further
increasingtheventilatoryresponsetohighaltitude.Ventilationreachesamaximumonlyafterfourtoseven
daysatthesamealtitude.(See"Controlofventilation",sectionon'Peripheralchemoreceptors'.)
HVRisgeneticallydeterminedandquitevariableamongindividuals.HVRisnotinfluencedbyathletictraining
butisaffectedbyextrinsicfactors,suchasrespiratorydepressants(eg,alcoholandsedative/hypnotics)and
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fragmentedsleep.Conversely,respiratorystimulants(eg,progesterone)andsympathomimetics(eg,coca,
caffeine)increaseHVR.
WhileonemightassumethatabriskHVRwouldreducethedegreeofhypoxiaandprotectagainstacute
mountainsickness(AMS),studieshavefailedtodemonstratethisfindingconsistently.Someeliteclimbers,
enduranceathletes,andhighaltituderesidents(SherpasandAndeanpeoples)havelowHVRandperform
wellataltitude.However,alowHVRisassociatedwithanincreasedriskofHAPE,perhapsbecauseit
augmentshypoxiainducedpulmonaryvasoconstriction,leadingtoanexaggeratedincreaseinpulmonary
artery(PA)pressure[1,7].
Asventilationrisesinresponsetohypoxia,PaCO2fallsandpHrises.Thecentralchemoreceptorsinthe
medullaofthebrainrespondtoalkalosisinthecerebralspinalfluid(CSF)byinhibitingventilation,suchthat
thefullhypoxicventilatoryresponseisattenuated.Whileperipheralchemoreceptorsaresensitivetochanges
inpH,centralchemoreceptorsplaythemajorroleinthisresponse.(See"Controlofventilation",sectionon
'Centralchemoreceptors'.)
Partialrenalcompensationforrespiratoryalkalosisoccurswithin24to48hoursofascentasthekidneys
excretebicarbonate,decreasingthepHtowardnormal,andallowingventilationtoagainincreaseasthe
alkalosisisreduced.Plasmabicarbonateconcentrationcontinuestodropandventilationtorisewithfurther
increasesinaltitude.(See"Simpleandmixedacidbasedisorders",sectionon'Compensatoryrespiratoryand
renalresponses'.)
CirculatorychangesCirculatorychangesfollowingascentinvolvethesystemic,cerebral,and
pulmonaryvasculatures.Followingarapidandsustainedincreaseinaltitude,increasedsympatheticactivity
transientlyincreasescardiacoutput,bloodpressure,heartrate,andvenoustone.Heartrateremainselevated
whilestrokevolumeisdiminishedduetodecreasedplasmavolume,whichcandropasmuchas12percent
overthefirst24hoursfrombicarbonatediuresis,fluidshiftfromtheintravascularspace,andsuppressionof
aldosterone[1].Theeffectsofaltitudeuponcardiacfunctionarediscussedindetailseparately.(See"High
altitude,airtravel,andheartdisease".)
ThecerebralvasculatureishighlyautoregulatedinresponsetochangesinbothoxygenandCO2.Inthe
brain,oxygendeliveryisdependentuponcerebralbloodflow(CBF),whichinturndependsuponabalanceof
vasodilation(inresponsetohypoxia),vasoconstriction(inresponsetohypocapnia),andchangesin
autoregulation.Whilethereisconsiderablevariationofcerebralautoregulationamonghypoxicindividuals,
CBFandoxygendeliveryisgenerallymaintaineddowntoSpO2levelsof70to80percentdespitemarked
hypocapnia.Individualvariationincerebralbloodflowislinkedtodifferencesinventilatoryresponsesto
hypoxiaandhypocapnia.Despitemildregionalbraintissuehypoxiarevealedbynearinfraredspectroscopy,
overallglobalcerebralmetabolismiswellmaintainedduringmoderatehypoxia[8].
Thepulmonaryvasculaturevasoconstrictsinresponsetohypoxia,resultinginpromptincreasesinpulmonary
vascularresistanceandpulmonaryartery(PA)pressure.Individualvariationinthemagnitudeofthisresponse
canvarywidely.Increasedflowtousuallyunderperfusedareasmayaugmentgasexchangebyimproving
ventilation/perfusionmatching.However,anexaggeratedincreaseinPApressureandpulmonaryvascular
resistance(PVR)isassociatedwithsusceptibilitytoHAPE,asismarkedlyinconsistentvasoconstrictionof
pulmonaryarterioles.(See"Highaltitudepulmonaryedema",sectionon'Pathophysiology'.)
Ataltitude,mildpulmonaryhypertensionatrestcanbemarkedlyincreasedbyvigorousexercise,with
pulmonarypressurereachingnearsystemiclevels,especiallyinpeoplewithahistoryofHAPE.Coldambient
temperaturesathighaltitudealsoincreasepulmonaryarterypressure.
HematologicchangesIncreasedhemoglobinconcentration([Hb])isawellknowncomponentofhigh
altitudeacclimatization.Amodestincreasein[Hb]isbeneficialbyincreasingtheoxygencarryingcapacityof
blood.
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Inthefirstfewdaysataltitude,[Hb]isincreasedduetoplasmavolumecontraction.Withinafewhours,
hypoxemiastimulatesincreasedproductionoferythropoietinfromspecializedrenalcells,whichincreasesthe
productionofredbloodcells(RBCs)over10to14days,resultinginanincreased[Hb].Uptoaltitudesof
approximately4000m,thisincreaseissufficienttobalancethereductioninoxygensaturationandrestorethe
oxygencontentofarterialbloodtosealevelvalues(thoughnowatalowerPO2).
Theoxyhemoglobindissociationcurve(ODC)playsacrucialroleinoxygentransport.Becauseofthesigmoid
shapeofthecurve,arterialoxygensaturation(SpO2)iswellmaintainedupto3000m,despiteasignificant
decreaseinarterialPO2(PaO2).Thiscorrelateswithanoxygensaturationofabout88to89percent.Above
thataltitude,smallchangesinPaO2resultinlargechangesinSpO2.(See"Structureandfunctionofnormal
hemoglobins".)
WhileSpO2determinestissueoxygenation,PaO2determinesdiffusionofoxygenfromthecapillarytothe
cell.IntraerythrocyticalkalosiscausesaleftwardshiftoftheODC,butalkalosisisamajorstimulusforthe
productionof2,3DPG,whichshiftstheODCrightward,backtowarditsnormalposition.Thisbalancebetween
alkalosis(leftshift)andincreased2,3DPG(rightshift)ismaintaineduntilsojournersreachveryhighaltitudes.
There,theeffectofthealkalosisfaroutstripsthecapacityoftheRBCtoproducemore2,3DPG,leadingtoa
leftwardshiftoftheODC.
Asanexample,inclimbersatthesummitofMountEverestthePaCO2is8to10mmHgandthepHrises
above7.6.TheresultingshiftoftheODCtotheleftfacilitatesoxygenhemoglobinbindinginthelung,which
resultsinanadvantageousriseinSpO2.Also,animalsadaptedtohighaltitude(eg,yaks,llamas,barheaded
geese)haveleftshiftedODCscomparedwiththeirlowaltitudecounterparts.
OxygendeliveryandutilizationDiffusionofoxygenfromthecapillariestothemitochondriaandits
subsequentusebytheseorganellesconstitutesthefinalstepoftheoxygencascade.Diffusiondistancefrom
capillarywalltomitochondriaisdecreasedathighaltitude,mainlybecauseofreductioninthediameterof
musclefibers,whichatrophyduringhighaltitudeexpeditions.Thisatrophyoccursduetoanetenergydeficit
anddeconditioningeffect[9].
Atthetissuelevel,HIF1astimulatesvascularendothelialgrowthfactor(VEGF),whichstimulates
angiogenesisandnitricoxidesynthesis.Thisresultsingreaterbloodflowandoxygendeliverytotissues.
Hypoxiainduciblefactor1alpha(HIF1a)isatranscriptionfactorresponsibleforactivatingmorethan350
genesinresponsetohypoxia,anditsactivationprobablyplaysanimportantroleinacclimatizationatacellular
level.Improvementsinoxidativemetabolismandtissuegasexchangealsooccur.
DEFINITIONS
HighaltitudeillnessHighaltitudeillness(HAI)isthecollectivetermfortheuniquecerebraland
pulmonarysyndromesthatcanoccurfollowinganinitialascenttohighaltitudeorfollowingafurtherascent
whilealreadyathighaltitude.HAIincludesacutemountainsickness(AMS)andhighaltitudecerebraledema
(HACE),whichafflictthebrain,andhighaltitudepulmonaryedema(HAPE),whichafflictsthelungs.Theyare
inducedbythehypoxicstressofhighaltitudeandarecharacterizedbyextravascularfluidaccumulationinthe
brain(AMS/HACE)andlungs(HAPE).Allrespondtodescentandoxygentherapy.
AcutemountainsicknessandhighaltitudecerebraledemaMostexpertsconsideracutemountain
sickness(AMS)andhighaltitudecerebraledema(HACE)torepresentdifferentpointsofseverityalongthe
samepathophysiologicprocessinthebrain.ThisprocessmaycollectivelybereferredtoasAMS/HACE.
AMSisthemostcommonformofhighaltitudeillnessandmayoccurfollowingrapidascent[1,5,7,10].Itis
characterizedbyheadacheincombinationwithothernonspecificsymptoms,suchasmalaiseandanorexia.
HACEistheleastcommonformofhighaltitudeillnessbutisrapidlyfatalwithoutpromptrecognitionand
treatment.AMS/HACEarediscussedindetailseparately.(See"Acutemountainsicknessandhighaltitude
cerebraledema".)
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HighaltitudepulmonaryedemaHighaltitudepulmonaryedema(HAPE)isanuncommon,life
threateningnoncardiogenicpulmonaryedemathatdevelopstwotofourdaysfollowingrapidascentabove
2500m(8000feet)[11].HAPE,whichmayaccompanyAMS/HACE,isthemostcommoncauseofdeath
amongthehighaltitudeillnesses.IndividualswhohavehadHAPEareathighriskforrecurrenceifthey
ascendtothesamealtitude,particularlyiftheydosoatthesamerateofascent.HAPEisdiscussedindetail
separately.(See"Highaltitudepulmonaryedema".)
OtheraltituderelatedillnessesAlteredbreathingwithnonREMsleep,aphenomenonknownas
periodicbreathingofaltitude,isencounteredataltitudesover2500mandbecomesverycommonathigher
altitudes[1214].ItisaformofCheyneStokesrespirationandreflectschangesinneuralsignalingdueto
hypoxia(respiratorystimulant)andalkalosis(respiratorydepressant)duringsleep.Periodicbreathingof
altitudemayoccurataltitudesaslowas1400mbutgenerallydoesnotdisruptsleepuntilvisitorsorclimbers
reachaltitudesabove3500m.(See"Disordersofventilatorycontrol".)
Highaltituderetinalhemorrhageoccurswhenthereisruptureofretinalarteriolesleadingtoextravasationof
bloodintotheretina[1517].Theretinalcirculationdevelopsmanyofthesamechangesseeninthecerebral
circulationataltitude.Itismostcommonatelevationsabove5000m(16,400feet),particularlyamongthose
engagedinstrenuousactivity.Symptomsrarelydevelopunlesshemorrhageextendstothemacula.
NumerousmedicalillnessesotherthanAMS/HACEandHAPEmaybecausedorexacerbatedbyhigh
altitude(table4).Examplesinclude:problemsresultingfromchronicaltitudeexposure,suchaschronic
mountainsicknessandhighaltitudepulmonaryhypertensionpreexistingmedicalconditionsexacerbatedby
hypoxia,suchasischemicheartdiseaseandconditionsarisingataltitudeunrelatedtohypoxia,suchas
frostbiteandphotokeratitis.Manyoftheseconditionsarediscussedseparately.(See"Highaltitude,airtravel,
andheartdisease"and"Photokeratitis"and"Frostbite"and"Accidentalhypothermiainadults".)
RISKFACTORS
IndividualIndividualsusceptibilitytohighaltitudeillness(HAI)varieswidelyforreasonsthatremainlargely
unexplained.Givenadequatetime,someindividualscanacclimatizesufficientlytotolerateseverehypoxia,
suchasthatfoundatthesummitofMountEverest(8848mor29,029feetapproximatePaO220to30
mmHg).OthersconsistentlydevelopdebilitatingAMSorHAPEduringrapidascenttoelevationsaslowat
2500m(approximatePaO260to70mmHg).
Noreliableandeasilyavailablegeneticorphysiologicmarkersareabletopredictanindividual'ssusceptibility
toHAI.IndividualfactorsassociatedwithanincreasedriskofdevelopingHAIinclude(table5)[1,18,19]:
PasthistoryofHAI(stronglypredictiveifconditionsaresimilar)
Rateofascent
Vigorousexertionpriortoacclimatization
Lackofacclimatization(see'Acclimatization'above)
Substances(eg,alcohol)orconditionsthatinterferewithacclimatization
Comorbiditiesthatinterferewithrespiration(eg,neuromusculardisease)orcirculation(eg,pulmonary
hypertension)
HAIcanbeinducedinanysubjectifthealtitudeissufficientlyhighortherateofascentissufficientlyrapid,
regardlessoftheperson'scapacitytoacclimatize.Thus,themostimportantvariablesdeterminingwhether
HAIdevelopsareanindividual'sgeneticsusceptibilityandthedegreeofhypoxicstress.Theelevationattained
(particularlythesleepingelevation)andtherateofascentisofgreatestimportancewhenconsideringhypoxic
stress.Conditionsthatfurthercontributetohypoxicstress,suchasvigorousexertionpriortoacclimatization,
alsoincreasetheriskofHAI.
Otherfactorsthatalterventilationandtheventilatoryresponsemayimpairacclimatization.Examplesinclude
sedativehypnoticmedications,alcohol,andsleepapnea.Comorbidconditionsthatimpairventilation,
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respiration,oroxygencarryingcapacityincreasetheriskforHAI.Examplesincludeneuromusculardisease,
chronicobstructivepulmonarydisease(COPD),restrictivelungdisease,cysticfibrosis,pneumonia,pulmonary
hypertension,andcongenitalcardiacanomaliesinvolvingrighttoleftshunts[2030].Ofnote,neitheranemia
norasthmaisassociatedwithanincreasedriskforHAI(infact,asthmagenerallyimprovesathighaltitude).
Sicklecelldiseaseisexacerbatedbyhypoxicenvironments.Sicklecelldiseaseanditscomplicationsare
discussedseparately.(See"Overviewoftheclinicalmanifestationsofsicklecelldisease".)
HAIafflictsallagesandbothgenders,regardlessofphysicalfitness.Infact,youngerathletes,particularly
males,maybeatgreaterriskofHAIforbehavioralreasons.Theyarelikelytoengageinstrenuousexertion
priortoacclimatizationortopursuecontinuedascent,despitethepresenceofsymptomssuggestiveofHAI.
SuchbehaviorsfeatureprominentlyinsevereandfatalcasesofHAI.
PediatricTheriskfactorsforHAIarethesameinhealthychildrenasinadults.Expertopinionisthat
infantslessthansixweeksofageshouldavoidovernightexposuretomorethan2500m[31].Sharedrisk
factorsamongchildrenandadultsincludetherateofascent,absolutealtitudeachieved,degreeofphysical
exertion,andcolderambienttemperatures.Riskfactorsofgreaterimportanceforthepediatricpopulation
relatetotheuniquephysiologyofhypoxiaininfantsandyoungchildren,aswellastheeffectsofconcurrent
acquiredorcongenitalconditionsthataremoreprevalentinthisagegroup(eg,upperrespiratoryinfection,
congenitalcardiopulmonarydisease,cysticfibrosis,Downsyndrome).Theseissuesarediscussedingreater
detailseparately.(See"Highaltitudedisease:Uniquepediatricconsiderations",sectionon'Highaltitude
physiology'.)
PregnancyThereisnoevidenceofarelationshipbetweenpregnancyandhighaltitudeillness.Infact,high
progesterone,apotentrespiratorystimulant,resultsinhigherSpo2inpregnantpersonsataltitude.Travelto
moderatealtitudes(upto2500m)duringnormalpregnanciesappearssafe.Thisissueisdiscussedingreater
detailseparately.(See"Initialprenatalassessmentandfirsttrimesterprenatalcare",sectionon'Travelto
moderateandhighaltitudes'.)
Womenresidingathighaltitudeshaveagreaterriskofpregnancyinducedhypertension,proteinuria,and
preeclampsia,andtheirnewbornshavelowerbirthweights[1].(See"Fetalgrowthrestriction:Evaluationand
management".)
EnvironmentalHighaltitudeiscommonlycategorizedaccordingtothephysiologicstressitproduces
(table2andtable3).Althoughthereisnoconsensusaboutsuchclassification,themainconceptisthat
progressiveascentresultsinincreasedhypoxicstress,requiringgreaterdegreesofphysiologicand
behavioraladaptationsinordertopreservefunction.
IntermsofHAI,symptomsgenerallydonotmanifestbelow1500m(5000feet).Fromabout1500to2500m
(5000to8200feet),symptomsaregenerallymild,ifexperiencedatall.At2500m,symptomsofmildto
moderateAMSbecomequitecommonamongunacclimatizedvisitorsafterrapidascent.AtthisaltitudeHAPE
mayalsooccur,butitismorecommonabove3000m(9800feet).Above3000to4000m(9800to13,100
feet),AMSiscommonamongpeoplewhohavenotproperlyacclimatized,andtheriskofsevereHAI,
includinglifethreateningHAPEandHACE,issubstantial.
RISKSTRATIFICATIONOFTHETRAVELERTOHIGHALTITUDE
DeterminingoverallriskDeterminingtheriskofanindividualtravelerfordevelopinghighaltitudeillness
(HAI)maybedifficultinsomecircumstances,butdependsprimarilyupontheascentprofile(ie,howhighand
howfast),whetherthereisahistoryofHAIduringprevioustripstoaltitude,andwhetherthepatienthas
comorbiditiesthatpredisposetoHAI.Ofnote,cliniciansassessingpatientriskmustdistinguishbetweenthe
riskfordevelopingHAI(mostnotablyhighaltitudecerebraledema[HACE]andhighaltitudepulmonary
edema[HAPE])andtheriskthattheconditionsofhighaltitude(eg,relativehypoxia)willexacerbateaspecific
comorbidity(eg,coronaryheartdisease,sicklecellanemia).Thisdiscussionwilladdressonlytheformerrisks
associatedwiththeexacerbationofcomorbiditiesarereviewedseparately.(See"Highaltitude,airtravel,and
heartdisease"and"Travelingwithoxygenaboardcommercialaircarriers".)
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DevelopingHAIduringaprevioustriptoaltitudeplacesapatientathighriskforrecurrenceduringsubsequent
trips.However,risksaredistinct:thepatientwithahistoryofHAPEisatriskforarecurrenceofHAPE,but
maynotbeatincreasedriskforAMS/HACE.Wheninquiringaboutapatientshistory,cliniciansmustbe
carefultoclarifywhatthepatientmeansbyaltituderelatedillness.Asanexample,somepatientsmayconfuse
acaseofinfectiousdiarrheacontractedathighaltitudewithHAI.
AssessingtheproposedtripTheitineraryofatripmustbeconsideredwhendeterminingtheriskfor
developingHAI.Rapidascentswithoutadequatetimeprovidedforacclimatizationandascentstoextremely
highaltitudesincreasetheriskforHAIinalltravelers.
AusefulexercisefordeterminingtheriskofHAIistomakeagraph,withthepatient,oftheproposedascent
profileforthetrip.Agraphicrepresentationshowingthedailygaininaltitudemakescleartoeveryonewhen
therateofascentistoofast,andthecorrespondingriskofdevelopingHAItoogreat.Therisksofdeveloping
HAIassociatedwithdifferentratesofascentaredescribedinthefollowingtable(table5).
Otherimportantfactorstoconsiderwhenplanningatripincludetheeasewithwhichthetravelercandescend
toloweraltitudeandtheavailabilityofmedicalcare.FortravelersatsignificantlyincreasedriskforHAI,
descentfromaresorthotelmaybereasonablewhereasdescentfromaremotemountainsidebyyakis
probablynot.Considerationsabouttheavailabilityofmedicalresourcesshouldincludenotonlynearbyclinics
butalsowhetherthetravelgroupwillincludesomeoneexperiencedintherecognitionandacutemanagement
ofHAI.
DiseasesandmedicalconditionsthatincreaseriskTherearerelativelyfewdiseasesthatpredispose
thetravelertodevelopingHAI.Suchconditionsincludethosethatimpairthebodysabilitytoincrease
ventilationandacclimatizetohighaltitude,suchastheabsenceofcarotidbodiesduetosurgicalresectionor
theeffectsofradiation,neuromusculardiseaseaffectingthethoraxanddiaphragm,andmoderatetosevere
chronicobstructivepulmonarydisease(COPD)[2030].Althoughtheevidenceislessclear,conditionsthat
exaggeratetheeffectsofhypoxemiaarelikelytoincreasetheriskforHAI.Suchdiseasesincludeobstructive
sleepapnea,interstitiallungdisease,cysticfibrosis,pneumonia,andcongenitalcardiacanomaliesinvolving
righttoleftshunts(notethatpatentforamenovaledoesnotincreaserisk).Pulmonaryhypertensionclearly
predisposespatientstoHAPEbutnottoAMS/HACE.DownssyndromeisadistinctriskfactorforHAPE[32
34].Whethersignificantobesityisassociatedwithincreasedriskremainsunclear.
DiseasesofthecentralnervoussystemthatincreasetheriskofdevelopingHAIincludeidiopathicintracranial
hypertension(ie,pseudotumorcerebri)andvirtuallyanyspaceoccupyinglesion.Inaddition,patientswith
chronicheadachesaremorelikelytodevelopheadachesandAMSataltitude.
Thereareseveralcommondiseasesandconditionsthatsomecliniciansmightintuitivelyexpecttoincrease
theriskforHAIbutinfactdonot.Asexamples,asthmaoftenimprovesataltitude,whileanemiaisnot
associatedwithincreasedrisk.PregnantpatientsarelesslikelytodevelopHAI.Inaddition,patientsoverthe
ageof50years,assumingtheydonothaveanyoftheconditionsdescribedimmediatelyabove,areatlower
riskofdevelopingHAI.Mostothercommonchronicdiseases,suchashypertensionordiabetes,donot
appeartobeassociatedwithincreasedrisk.
AssessingthepatientPatientassessmentbeginswithacarefulhistory,includingquestionsaboutany
problemsthatdevelopedduringprevioustripstoaltitudeandwhetherthepatienthasanymedicalconditions
thatpredisposetoHAI.(See'Diseasesandmedicalconditionsthatincreaserisk'above.)
Aspartofthehistory,itisimportanttoaskaboutexercise.Apatientwhoexercisesregularly,particularlyat
highintensity,ismorethanlikelytohavethephysicalcapacitynecessarytotravel,climb,orskiataltitude,and
isunlikelytohaveasignificantunderlyingmedicalconditionthatmightbeaggravatedbyaltitude.Itisworth
inquiringaboutmedicalconditionsthatcanbeexacerbatedbyconditionsataltitude,suchasischemicheart
disease,sleepapnea,andchroniclungdisease,andsymptomscommonlyassociatedwithsuchailments,
suchaschestdiscomfortordyspneawithmildexertion,wheezing,oranyotherbreathingdifficulty.Therisks
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associatedwiththeexacerbationofcomorbiditiesataltitudearereviewedingreaterdetailseparately.(See
"Highaltitude,airtravel,andheartdisease"and"Travelingwithoxygenaboardcommercialaircarriers".)
Weaskwhetherthereisafamilyhistoryofmigraine,asaltitudemayprecipitateafirstmigraineheadache.
Patientswithsystemicscleroderma,rheumatoidarthritis,orotherconnectivetissuediseasesassociatedwith
pulmonarymanifestationswarrantcarefulscreeningforpulmonarycomplicationsbeforetravelingtoaltitude.
(See"Clinicalmanifestations,evaluation,anddiagnosisofinterstitiallungdiseaseinsystemicsclerosis
(scleroderma)"and"Interstitiallungdiseaseinrheumatoidarthritis".)
Duringthephysicalexamination,specialattentionshouldbepaidtodetectingheartmurmursandabnormal
pulmonaryfindings.Suchfindingsmayreflectthepresenceofunderlyingcardiacorpulmonarydiseasethat
increasestheriskassociatedwithtraveltoaltitudeandthuswarrantfurtherevaluation.Thepresenceof
thoracicirregularities,suchaskyphoscoliosis,whichmayaffectpulmonaryfunction,andobesityshouldbe
noted.
Somepatientswhotraveloncommercialairlinesrequiresupplementaloxygen.Itisgenerallysafetoassume
thatpatientswhorequiresupplementaloxygenforairtravelareatincreasedriskfordevelopingproblemsat
altitude.Althoughinsomecasespotentialproblemsmaybeavoidedifthepatientisnottravelingtoextreme
altitudesandhassufficienttimetoacclimatize,commercialairlinetravelerswhorequiresupplementaloxygen
andliveatornearsealeveltypicallycannotacclimatizetotheconditionsofflight(cabinpressuresaretypically
theequivalentof1400to2500m,or4000to8000feet).Thebasicscreeningusedforthesepatients,
althoughnotideal,mayprovidesomeinsightintotheirriskataltitude,particularlyforthosepatientswith
underlyingpulmonarydisease.Asanexample,achronicobstructivepulmonarydisease(COPD)patientwho
requiressupplementaloxygenforairtravelwillcertainlyrequireitifheorsheascendstoacomparable
altitude.Screeningforthesepatientsbeginswithpulseoximetryandisdiscussedindetailseparately.(See
"Travelingwithoxygenaboardcommercialaircarriers".)
Prophylacticmedication:WhoneedsitandwhattogiveGradualascentremainstheprimarymethod
forpreventingallformsofHAI.However,insomecasesprophylacticmedicationmaybewarranted.We
recommendprophylactictreatmentforallpatientsathighriskofdevelopingHAIaccordingtothecriterialisted
intheattachedtable(table5).Forhealthypatientswithnohistoryofmedicalproblemsathighaltitude,therisk
ofHAIislowwithgradualascentandroutineprophylaxiswithmedicationisnotwarranted.However,gradual
ascentisnotalwayspossibleandsometimespatientsatincreasedriskwishtotraveltoaltitude.Insuchcases
andforothersdeemedtobeatmoderateriskfordevelopingHAI,prophylacticmedicationmaybehelpful.
However,nomedicationiscompletelywithoutriskandweprefertodiscusstheuseofprophylacticmedication
withpatientsatmoderateriskandreachadecisionwiththeirinput.Inallcases,rescuemedication(given
whensymptomsbeginbutnotbefore)isareasonablealternativetoprophylacticmedication.
Themedicationgivenforprophylaxisdependsupontheindividualriskofthepatient.TheriskforHAPEis
typicallylow,unlessthepatienthasahistoryofHAPEorissusceptibleduetospecificunderlyingpulmonary
disease(eg,pulmonaryhypertension).Therefore,outsidesuchcircumstances,wedonotroutinely
recommendmedicationprophylaxisforHAPE.Ifsuchriskfactorsarepresentandprophylaxisisindicated,the
preferredprophylacticmedicationisnifedipine.Dosingforthemedicationsusedforprophylaxisandtreatment
ofhighaltitudeillnessaredescribedinthefollowingtable(table6).PreventionofHAPE,includingthe
medicationsusedforprophylaxis,isdiscussedingreaterdetailseparately.(See"Highaltitudepulmonary
edema",sectionon'Prevention'.)
ForpatientsatmoderateriskofdevelopingAMS/HACEbasedonthecriterialistedintheattachedtable(table
5)whodecideafterappropriatediscussionthattheywishtouseprophylacticmedication,acetazolamideisthe
preferreddrug,butdexamethasoneisalsoareasonableoption(table6).PreventionofAMS/HACE,including
themedicationsusedforprophylaxis,isdiscussedingreaterdetailseparately.(See"Acutemountainsickness
andhighaltitudecerebraledema",sectionon'PharmacologicpreventionofAMS/HACE'.)
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IntherareinstancewhenmedicationprophylaxisagainstbothAMS/HACEandHAPEisneeded,itisbestto
seekinputfromaphysicianwithexperiencemanagingHAI.
PREVENTION
GeneralapproachMostindividualsascendtohighaltitudewithminimalornosymptomsbyallowing
sufficienttimetoacclimatize.Asubsetofpatientsbenefitsfrompharmacologicprophylaxis.Thisincludes
thosewithaknownpredilectionforhighaltitudeillness(HAI)despitegradualascent,andthosewhomust
ascendrapidlyforconvenience(eg,touriststravelingtomountainresort)orwork(eg,rescueandmilitary
personnel).Pharmacologicprophylaxisisdiscussedseparately.(See"Acutemountainsicknessandhigh
altitudecerebraledema",sectionon'PharmacologicpreventionofAMS/HACE'.)
Whendeterminingtheoptimalpreventivestrategy,factorstoconsiderincludethefollowing[35]:
Patientsusceptibility(historyofpreviousHAI)
Elevationoftheperson'susualresidence
Intendedascentprofile(ie,rapidorgradualascent)
Medicalhistory
Medicationsandallergies
Purposeofascent
Behavioralmethods
GradualascentGradualascentisthesurestandsafestmethodofpreventingoramelioratingHAI
[19,36,37].Asageneralguideline,individualswhonormallyresidebelow1500m(5000feet)elevationshould
avoidanabruptascenttosleepingaltitudesabove2800m(9200feet).Thisisbestaccomplishedbyspending
onenightatanintermediatealtitude(particularlywhentravelingtoanelevationthatcausedsymptoms
previously).
Iffurtherascentabove3000m(9800feet)isplanned,wesuggestnotspendingsubsequentnightsat
elevationsover500mhigherthanthepreviousnight,andincludingarestday(noascentandnovigorous
activity)forevery1000m(3280feet)climbed.Eventhisconservativeapproachmayprovetooaggressivefor
individualsparticularlysusceptibletoHAI[38].Forothers,itmaybeagonizinglyslow.
Acommonadageamongmountaineersis"climbhigh,sleeplow."Daytripstohigherelevationwithareturnto
aloweraltitudeforsleepmayaccelerateacclimatizationandhelptopreventHAI.
Iftimeisavailable,stagedascentisanotherapproachtoacclimatizationthatreducestheriskofdeveloping
HAI[39].Stagedascentinvolvesascendingtoaltitudeinstages.Fivetosevendaysisspentatan
intermediatealtitude(typically3000to4000m)beforeproceedingtohigherelevations.
PreacclimatizationPreacclimatizationinvolvingpreexposuretohigheraltitudes(hypobarichypoxia)or
environmentsthatsimulatehighaltitude(normobarichypoxia)isaneffectivestrategyforpreventingHAI.
Residingatasiteabove2500m(8200feet)orparticipatinginbriefclimbstoactualelevationsover2500to
3000m(8200to9840feet)intheweeksleadinguptoatriptohigherelevations(approximately4500m
[14,800feet],orhigher)providesadegreeofpreacclimatization,andmayallowforafasterrateofascent
withoutAMS[1,3941].However,evidenceislimitedaboutwhetherbriefexposurestohighaltitudeare
effectiveandtheoptimalstrategyforpreacclimatizationremainsunproven.Asageneralruleofthumb,the
altitudeofpreexposureclimbs,realorsimulated,shouldreachwithinapproximately2000morcloserofthe
ultimatealtitude.Ifextendedpreexposureisnotfeasible,areasonablealternativewouldbetotraveltosuch
altitudesfortwoorthreeweekendsduringthetwomonthspriortothetrip.
Whilehypobarichypoxiaappearstobemoreeffective,analternativeapproachtopreacclimatizationinvolves
usingnormobarichypoxiatosimulatetherelativehypoxiaofhighaltitudes[37,4244].Suchprogramsare
sometimescalledintermittentnormobarichypoxicexposure(INHE).INHEprogramsusecommercially
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availabledevicesinvolvingfacemasksorsealedtentsorchambersthatallowuserstodecreasethe
percentageofinhaledoxygenfrom21percent(sealevel)tobelow16percentduringsleeporwhileexercising
forvariableintervalsoftimeandduration.WhileINHEismoreconvenientthantravelingtoaltitudeandthe
physiologicbasisappearssound,thereislessevidencethatthisapproachiseffectiveatreducingtheriskfor
HAI,unlessexposureisformorethanseventoeighthoursperdayforatleastaweek.Asmallrandomized,
placebocontrolledtrialshowedthattwoweeksofsleepingatasimulatedaltitudeof2200to2600mwas
requiredtopreventAMSat4600m[41].Briefexposuresofminutesorhoursperday,atrestorduring
exercise,havenotbeeneffectiveinpreventingHAIinthefewstudiestodate.
EducationIndividualswithahistoryofHAIorsignificantcardiopulmonarydiseaseshouldbecounseled
regardingtheirincreasedriskandbeprovidedwithaconservativeascentplan(orprofile).Theclinicianand
patientshouldreviewthisprofileanddiscusstherelativerisksassociatedwitheachelevation,aswellasthe
risksoflimitedaccessibilitytomedicalcareandevacuation.
EducatingpatientsabouttheearlysymptomsandsignsofHAIandtheneedforpromptintervention,
particularlywithregardtoHAPEandHACE,canbelifesaving[5,7,45].Patientsshouldcommittomemory
themantrathatnoonewithsymptomsofHAIshouldcontinuetoascend,andthatdescentismandatoryif
symptomsdonotimprove.Aplanofactionintheeventthatimmediatedescentisnotpossibleshouldbe
discussed.
Healthcareworkerswhoadvisetravelersneedtounderstandthebestpreventionstrategiesandtreatment
optionsbaseduponvariables,suchasascentprofile(rateofascent,ultimateelevationattained,timespentat
variouselevations),previoushistoryofHAI,comorbidities,medicationallergies,severityofillnessHAPEor
AMS/HACE,treatmentsetting(eg,terrain,weather,remoteness),andavailabletreatmentoptions(eg,field,
clinic,hospital)(table3).Individualsshouldbeinformedthattheprocessofacclimatizationishinderedbythe
useofrespiratorydepressants(eg,sedatives)oralcoholandbyoverexertionduringthefirstfewdaysathigh
altitude.
AlcoholanddruguseSedativehypnoticsandmoderatetoheavyalcoholintakeshouldbeavoided
duringtheacclimatizationprocess,particularlyduringthefirsttwonightsatanewelevation.Bothtypesof
agentsdepressrespiratoryfunctionandinterferewithnormalsleeppatternsandphysiologicresponsesto
altitude,whicharenecessaryforacclimatization.
StudiesofalcoholseffectonacclimatizationandHAIriskaremethodologicallylimitedandshowmixedresults
[39,40,46].Whileabstinencefromalcoholearlyduringacclimatizationisthesafestcourse,traditional
proscriptionsmaybeoverstatedandasingledrinkisunlikelytocausesignificantproblems.
Mildsleepingaidssuchaszolpidem(Ambien),takeninappropriatedoses,donotdepressventilationoraffect
acclimatizationtohighaltitudeandaresafe.
DietandhydrationVariousdiets,includinghighcarbohydrate,havebeentoutedtoreducethe
incidenceofHAI,butdataareinconclusive[1].Similarly,vigoroushydration,beyondtheamountrequiredto
maintainadequatehydration,hasnotbeenshowntoreducetheincidenceofHAI[7,47,48].Climbersor
visitorstohighaltitudesitesshouldbeawareoftheriskofhyponatremiawhenfollowing"conventional
wisdom"aboutvigoroushydration.(See"Causesofhyponatremiainadults".)
ExertionVigorousexertionataltitudecontributestothedevelopmentofAMSaswellasHAPE,
althoughsedentarypersonsalsodeveloptheseillnesses[49].Modestexercisemayaidacclimatization
[1,7,49,50].PatientswithaprevioushistoryofHAIshouldbeparticularlywaryofvigorousexertionduringthe
firstfewdaysathighaltitude.
CocaAmongsomelocalAndeanpopulations,cocaisfelttoenhancephysicalperformanceataltitude,
butformalstudiesofthisclaimarelimited[51,52].Whenassessingtheeffectsofcoca,itisimportantto
distinguishbetweencocatea(matedecoca)andcocaleaves.Cocateatypicallycontainsonlyatinyamount
ofcocainealkaloidandisunlikelytohavemuchimpactonpreventingHAI,althoughitmayslightlyenhance
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exercisetoleranceandprovidesomehydration,dependingonhowmuchisconsumed.Theeffectofchewing
cocaleavesonpreventingortreatingHAIhasnotbeenwellstudied,butthereisnoconvincingevidenceof
benefit,whiletheharmsofcocaarewelldescribed[51,53].Wedonotrecommendchewingcocaleavesasa
meansforpreventingHAI.(See"Cocaineusedisorderinadults:Epidemiology,pharmacology,clinical
manifestations,medicalconsequences,anddiagnosis".)
PharmacologicprophylaxisCliniciansshouldreserveprophylacticmedicationsforindividualswitha
historyofaltitudeintoleranceandthosewhomustmakeaplannedrapidascenttohighaltitude.Evenin
individualswithaprevioushistoryofHAI,gradualascentshouldbeemphasizedoverpharmacologic
prophylaxis.Often,ascendingataslowerratethanthepreviousoffendingascentallowsindividualstoavoid
illness.
Patientswithcomorbidconditionsthatareexacerbatedbyhypoxicenvironments(eg,ischemicheartdisease,
COPD,sicklecelldisease,cysticfibrosis)whowishtotraveltomoderatealtitudesmaywarrantprophylactic
oxygentherapy.(See"Highaltitude,airtravel,andheartdisease"and"Travelingwithoxygenaboard
commercialaircarriers"and"Managementofstablechronicobstructivepulmonarydisease"and"Overviewof
theclinicalmanifestationsofsicklecelldisease".)
PharmacologicprophylaxisagainstHAIisdiscussedseparately.(See"Acutemountainsicknessandhigh
altitudecerebraledema",sectionon'PharmacologicpreventionofAMS/HACE'.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasics
andBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoread
materials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.
Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepth
informationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremail
thesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsby
searchingonpatientinfoandthekeyword(s)ofinterest.)
Basicstopic(see"Patienteducation:Altitudesickness(includingmountainsickness)(TheBasics)")
BeyondtheBasicstopic(see"Patienteducation:Highaltitudeillness(includingmountainsickness)
(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Thearterialpartialpressureofoxygen(PaO2)decreaseswithaltitude,resultinginprogressivetissue
hypoxia.Thenormalcompensatoryresponsetohypobarichypoxiaistermedacclimatization.The
capacitytoacclimatizevariesgreatlyamongindividualsandisdependentuponmanyfactors,including
thedegreeofhypoxicstress(rateofascent,altitudeattained),theintrinsiccapacityoftheindividualto
compensatefordiminishedPaO2,andextrinsicfactors.Theprocessbeginswithinminutesofascentbut
requiresseveralweekstocomplete.(See'Highaltitudephysiology'above.)
Highaltitudeillness(HAI)isthecollectivetermforthepathologicsyndromesthatcandevelopfollowingan
initialascenttohighaltitudeorfollowingafurtherascentwhilealreadyathighaltitude.HAIincludesacute
mountainsickness(AMS)andhighaltitudecerebraledema(HACE),whichafflictthebrain,andhigh
altitudepulmonaryedema(HAPE),whichafflictsthelungs.(See'Definitions'above.)
IndividualfactorsassociatedwithanincreasedriskforHAIinclude:
PasthistoryofHAI(stronglypredictiveifconditionsaresimilar)
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Rateofascent
Altitudeattained,especiallysleepingaltitude
Vigorousexertionpriortoacclimatization
Substances(eg,alcohol)orconditionsthatinterferewithacclimatization
Comorbiditiesthatinterferewithrespiration(eg,neuromusculardisease)orcirculation(eg,
pulmonaryhypertension)(see'Individual'above)
Progressiveascentresultsinincreasedhypoxicstress,requiringgreaterdegreesofphysiologicand
behavioraladaptationsinordertopreservefunction.Themorerapidtheascentandthehigherthe
altitude,thegreaterthestress.(See'Environmental'above.)
Mostindividualsascendtohighaltitudewithoutcomplicationsbyallowingsufficienttimetoacclimatize.
PatientswithaknownpredilectionforHAIdespitegradualascent,andotherswhomustascendrapidly
forconvenience(eg,touriststravelingtomountainresort)orwork(eg,rescuepersonnel)maybenefit
frompharmacologicprophylaxis,whichisdiscussedingreaterseparately.(See"Highaltitudepulmonary
edema",sectionon'Prophylacticmedications'and"Acutemountainsicknessandhighaltitudecerebral
edema",sectionon'PharmacologicpreventionofAMS/HACE'.)
GradualascentisthesurestandsafestmethodofpreventingoramelioratingHAI.Asageneralguideline,
individualswhonormallyresidebelow1500m(5000feet)elevationshouldavoidanabruptascentto
sleepingaltitudesabove2800m(9200feet).Sedativehypnoticsshouldbeavoidedduring
acclimatization.Abstinencefromalcoholissafest,butasingledrinkisunlikelytocauseproblems.
VigorousexertionataltitudecontributestothedevelopmentofbothAMSandHAPE,andshouldalsobe
avoidedduringacclimatization.Additionalpreventivestrategiesarediscussedinthetext.(See
'Prevention'above.)
StrategiesforassessingthetravelertoaltitudeanddeterminingtheirriskofdevelopingHAIarereviewed
inthetext.Duringsuchevaluations,itisimportanttodistinguishbetweentheriskofdevelopingHAIand
theriskthathighaltitudemayexacerbateaspecificcomorbidity(eg,coronaryheartdisease).Auseful
exercisefordeterminingtheriskofHAIistomakeagraph,withthepatient,oftheproposedascent
profileforthetrip.Otherimportantfactorstoconsiderwhenplanningatripincludetheeasewithwhich
thetravelercandescendtoloweraltitudeandtheavailabilityofmedicalcare.(See'Riskstratificationof
thetravelertohighaltitude'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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GRAPHICS
Howairisexchangedinthelungs
Thisfiguredepictshowoxygen(02)andcarbondioxide(CO2)passbetweenthe
alveloi(insidethelung)andthecapillaries(thebloodstream).
Reproducedwithpermissionfrom:AnatomicalChartCo.Copyright2008Lippincott
Williams&Wilkins.
Graphic58392Version1.0
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10/7/2016
Oxygencascadeatsealeveland4300meters
Reproducedwithpermissionfrom:McArdleWD,KatchFI,KatchVL.Exercise
Physiology:Nutrition,Energy,andHumanPerformance,8thed,LippincottWilliams&
Wilkins,Philadelphia2014.Copyright2014LippincottWilliams&Wilkins.
www.lww.com.
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Acuteeffectofaltitudeonoxygensaturationandarterialbloodgasvalues
Altitude
(meters)
Altitude
(feet)
P B (mm
Hg)
PaO 2
(mmHg)
SaO 2 (%)
Altitude
residents
1646
5400
630
73(6583)
95.1(9397)
35.6(30.7
41.8)
Acute
exposure
2810
9219
543
60(47.4
73.6)
91(86.6
95.2)
33.9(31.3
36.5)
3660
12,008
489
47.6(42.2
53)
84.5(80.5
89)
29.5(23.5
34.3)
4700
15,420
429
44.6(36.5
47.5)
78(70.885)
27.1(22.9
34)
5340
17,520
401
43.1(37.6
50.4)
76.2(65.4
81.6)
25.7(21.7
29.7)
6140
20,144
356
35(26.9
40.1)
65.6(55.5
73)
22(19.2
24.8)
6500
21,325
346
41.13.3
75.26
202.8
7000
22,966
324
8000
26,247
284
36.62.2
67.85
12.51.1
8400
27,559
272
24.65.3
54
13.3
8848
29,029
253
30.32.1
584.5
11.21.7
8848
29,029
253
30.61.4
11.91.4
Population
Subacute
exposure
PaCO 2
(mmHg)
P B :barometricpressurePaCO 2 :arterialpartialpressureofcarbondioxidePaO 2 :arterialpartialpressureofoxygen

SaO 2 :arterialoxygensaturation.
*Dataaremeanvaluesand(range)andwereobtainedinsubjects20to40yearsofageduringthefirstonetotwodays
ofarrivingataltitude(acuteexposure)andassociatedwithgoodacclimatization(subacuteexposure).
Datafrom:
1.LoeppkyJA,CaprihanA,LuftUC.VA/Qinequalityduringclinicalhypoxemiaanditsalterations.In:ShirakiK,
Yousef,MK(Eds).ManinStressfulEnvironments,CCThomas,Springfield,Il,1987,p.199.
2.McFarlandRA,DillDB.Acomparativestudyoftheeffectsofreducedoxygenpressureonmanduring
acclimatization.JAviatMed19389:18.
Reproducedfrom:HackettPH,RoachRC.Highaltitudemedicineandphysiology.In:AuerbachPS(Ed).Wilderness
Medicine,6thedition,ElsevierMosby,Philadelphia,2012.TableusedwiththepermissionofElsevierInc.Allrights
reserved.
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Physiologiceffectsofhighaltitude
Highaltitude:1500to3500m(492111,483ft)
Highaltitudeillnesscommonwithabruptascenttoabove2500m(8202ft)
Decreasedexerciseperformanceandincreasedventilation
MinorimpairmentinSpO 2 ,usuallyatleast90percentPaO 2 significantlydiminished55to75mmHg
Veryhighaltitude:3500to5500m(11,48318,045ft)
Mostcommonrangeforseverehighaltitudeillness
Abruptascentmaybedangerousrequiresaperiodofacclimatization
SpO 2 75to85percentPaO 2 40to60mmHg
Extremehypoxiamayoccurduringsleep,exerciseandhighaltitudeillness
Extremealtitude:5500to8850m(18,04529,035ft)
Progressivedeteriorationofphysiologicfunctioneventuallyoutstripsacclimatization
Abovethehighestpermanenthumanhabitation
Abruptascentalmostalwaysprecipitatesseverehighaltitudeillness
Aperiodofacclimatizationnecessarytoascendtoextremealtitude
SeverehypoxiaandhypocapniaSpO 2 58to75percent,PaO 2 28to40mmHg
SaO 2 :arterialoxygensaturationPaO 2 :arterialPO 2 PO 2 :partialpressureofoxygen.
Datafrom:Hackett,PH,Roach,RC.HighAltitudeMedicine.In:WildernessMedicine,5thed,Auerbach,PS(Ed),Mosby,
Philadelphia2007.
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Highaltitudecitiesandpeaks
City
Altitude
The10highestcitiesintheworld
Peak
Altitude
Location
TheSevenSummits
1.Lhasa,Tibet,China
12,002ft./3658m.
MountEverest
29,035ft./8850m.
Asia
2.LaPaz,Bolivia
11,910ft./3630m.
MountKilimanjaro
19,563ft./5963m.
Africa
3.Cuzco,Peru
11,152ft./3399m.
MountMcKinley
20,320ft./6194m.
NorthAmerica
4.Sucre,Bolivia
9331ft./2844m.
PuncakJaya
16,023ft./4884m.
Australia/Oceania
5.Quito,Ecuador
9249ft./2819m.
VinsonMassif
16,066ft./4897m.
Antarctica
6.Toluca,Mexico
8793ft./2680m.
MountElbrus
18,510ft./5642m.
Europe
7.Bogot,Colombia
8675ft./2644m.
Aconcagua
22,841ft./6962m.
SouthAmerica
8.Cochabamba,Bolivia
8390ft./2557m.
9.AddisAbaba,Ethiopia
7900ft./2408m.
Annapurna
26,545ft./8091m.
Nepal
10.Asmara,Ethiopia
7789ft./2374m.
Dhaulagiri
26,794ft./8167m.
Nepal
MountEverest
29,035ft./8850m.
Nepal
Somelargecitiesathighaltitude
8000mpeaks
MexicoCity
2240meters
K2
28,253ft./8612m.
Pakistan
Johannesburg
1750meters
Kangchenjunga
28,169ft./8586m.
Nepal
Nairobi
1660meters
Lhotse
27,940ft./8516m.
Nepal
Denver
1610meters
Makalu
27,765ft./8462m.
Nepal
GuatemalaCity
1530meters
Manaslu
26,758ft./8156m.
Nepal
NangaParbat
26,658ft./8125m.
Pakistan
BroadPeak
26,400ft./8047m.
Pakistan
GasherbrumII
26,360ft./8035m.
Pakistan
ShishaPangma
26,289ft./8013m.
Tibet
Gasherbrum
26,470ft./8068m.
Pakistan
ChoOyu
26,906ft./8201m.
Nepal
ft:feetm:meters.
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Oxygenationatdifferentaltitudes
Increasingaltituderesultsinadecreaseininspiredoxygen(PiO 2 ),arterial
oxygen 2 (PaO 2 ),andarterialoxygensaturation(SaO 2 ).Notethatthe
differencebetweenPiO 2 andPaO 2 narrowsathighaltitudesbecauseof
increasedventilation,andthatSaO 2 iswellmaintainedwhileawakeuntilover
3000meters.
Reproducedwithpermissionfrom:Hackett,PH,Roach,RC.HighAltitudeMedicine.
In:WildernessMedicine,5thed,Auerbach,PS(Ed),Mosby,Philadelphia2007.
IllustrationusedwiththepermissionofElsevierInc.Allrightsreserved.
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Medicalconditionscausedorexacerbatedbyhighaltitude
Highaltitudeillness
Acutemountainsickness/Highaltitudecerebraledema(AMS/HACE)
Highaltitudepulmonaryedema(HAPE)
Altituderelatedillness(partiallist)
Acute
Highaltitudeheadache
Highaltitudepharyngitisandbronchitis
Periodicbreathing
Highaltitudesyncope
Acutehypoxia
Cerebrovascularsyndromes
Organicbrainsyndrome
Peripheraledema
Sleepperiodicbreathing
Ultravioletkeratitis(snowblindness)
Highaltituderetinopathy
Hypothermiaandfrostbite
Highaltitudedeterioration
Chronic
Chronicmountainsickness(Monge'sdisease,chronicmountainpolycythemia)
Highaltitudepulmonaryhypertension,withorwithoutrightheartfailure
Reentrypulmonaryedema
Problemsofpregnancy:preeclampsia,hypertension,andlowbirthweightinfants
Problemsexacerbatedbyhighaltitude(partiallist)
Variouscongenitalandvalvularheartdiseases
Primaryandsecondarypulmonaryhypertension
Symptomaticcoronaryarterydisease
PoorlycompensatedADHFandCOPD
Sicklecelldiseaseandtrait
Obstructivesleepapnea
UrinaryretentionfromBPH
Highriskpregnancy
Radialkeratotomy
ADHF:AcutedecompensatedheartfailureBPH:BenignprostatichyperplasiaCOPD:Chronicobstructivepulmonary
disease
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Riskforhighaltitudeillness
Risk
ofHAI
Low
Description
Nopriorhistoryofaltitudeillnessandplanningascentto<2800m
Takingtwodaysormoretoarriveat2500to3000mfromlowaltitude
Ascendingnomorethan500m/day(sleepingaltitude)onceover2500mandtakingoneextradayto
acclimatizeforeveryadditional1000mofascent
Moderate
PriorhistoryofAMSandascendingto2500to2800minlessthantwodays
NohistoryofAMSandascendingto2800morhigherinlessthantwodays
Ascending>500m/day(increaseinsleepingelevation)ataltitudesabove3000mwithoneextraday
foracclimatizationforeveryadditional1000mofascent
High
Historyofseverealtitudeillness(HACE,HAPE)
HistoryofAMSandascendingto2800morhigherinlessthantwodays
Ascendingover3500minlessthantwodays
Ascending>500m/day(increaseinsleepingelevation)above3000mwithoutextradaysfor
acclimatizationrapidguidedascents(eg,Mt.Kilimanjaroin<7days)
Personswithmedicalconditionspredisposingtoaltitudeillness
Notes:
Altitudeslistedrefertothealtitudeatwhichthepersonsleeps.
Ascentisassumedtobeginatlowaltitude(<1200m).
Riskcategoriesareforunacclimatizedpersons.
AMS:acutemountainsicknessHACE:highaltitudecerebraledemaHAPE:highaltitudepulmonaryedemam:meters.
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Pharmacologictreatmentandpreventionofhighaltitudeillness(HAI)
Condition
AMS/HACE
Prevention*
Treatment
mildAMS
Treatment
moderate
tosevere
AMS
HACE
treatment
HAPE
HAPE
prevention*
Preferredagent
Alternatives
Acetazolamide:125mgorallyevery12
hours
Children:2.5mg/kg(maximumsingle
dose:125mg)orallyevery12hours
Dexamethasone:2mgorallyevery6
hoursor4mgorallyevery12hours
Children:Acetazolamidepreferred,donot
useforprophylaxis
Duration:startdaybeforeascentand
continue23daysatmaximumaltitude
mayuseonceatnightthereafterto
improvesleep
Duration:startdayofascentand
continue23daysatmaximumaltitude,
butfornomorethan7daystotal
Acetazolamide:125to250mgorally
every12hours
Dexamethasone:2to4mgorallyevery
6hours
Children:0.15mg/kgorallyevery6
hours(maximumsingledose:4mg)
Duration:continuefor24hoursafter
symptomsresolveordescent
accomplished
Duration:continueuntil24hoursafter
symptomsresolveordescentcompleted,
butnotlongerthan7daystotal
Dexamethasone: 4mgorallyevery6
hours
Children:0.15mg/kgorally(maximum
singledose:4mg)every6hours
every12hours
Duration:continuefor24hoursafter
accomplished
Dexamethasone: 8to10mgorally
/IM/IVonce,then4mgorally/IM/IV
every6hours
Children:0.15mg/kgevery6hours
(maximumsingledose:4mg)
Acetazolamide:250mgorallyevery12
hours,mayuseasadjunctwith
dexamethasoneNOTformonotherapy
accomplished
Nifedipine:60mgextendedrelease
orallydivideddaily(30mgorallyevery12
hrsor20mgorallyevery8hours).
dose:20mg)extendedreleaseorally
every8hours
Furtherresearchisneededbeforethe
medicationslistedbelowcanbe
recommendedforroutineuse:
Duration:startdaybeforeascentand
continuefor35daysatmaximum
altitude
Sildenafil:50mgorallyevery8hours
startdayofascentandcontinue35days
atmaximumaltitude
Tadalafil:10mgorallyevery12hours
startdayofascentandcontinue35days
atmaximumaltitude
Dexamethasone:8mgorallyevery12
hoursstartdayofascentandcontinue
4872hoursatmaximumaltitude
every12hoursstartdaybeforeascent
andcontinue4872hoursatmaximum
altitude
HAPE
treatment
Nifedipine:60mgextendedrelease
orallydivideddaily(30mgorallyevery12
hoursor20mgorallyevery8hours).
dose:20mg)extendedreleaseorally
every8hours
Duration:continueuntildescent
completed,symptomsresolvedandSpO2
normalforaltitude
Furtherresearchisneededbeforethe
medicationslistedbelowcanbe
recommendedforroutineuseinHAPE
treatment:
Tadalafil:10mgorallyevery12hours
Sildenafil:50mgorallyevery8hours
Duration:continueuntildescent
completed,symptomsresolvedandSpO2
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normalforaltitude
AMS:acutemountainsicknessHACE:highaltitudecerebraledemaHAPE:highaltitudepulmonaryedemaIM:
intramuscularNSAID:nonsteroidalantiinflammatorydrug
*Gradualascentprofileisprimarymethodofprevention.Reservepharmacologicprophylaxisforallpatientsathighrisk
andselectedpatientsatmoderateriskofdevelopingHAIaccordingtocriterialistedintheseparatetable.Provisionof
rescuemedicationsisareasonablealternative.Refertoaccompanyingtext.
Maynotrequirepharmacologictreatment.Rest,haltascent,andsymptomatictreatment(eg,acetaminophenorNSAID
forheadacheandondansetronfornausea/vomiting)maybesufficient.Refertoaccompanyingtext.
TreatmentwithdexamethasonealleviatessymptomsofAMS/HACEbutdoesnotimproveacclimatization.
DexamethasoneisnotasubstituteforimmediatedescentinHACE.
InUnitedStatestheloweststrengthextendedreleasenifedipineoralpreparationavailableis30mg.Insomeother
countries,10and20mgextendedreleasepreparationsareavailable.
Maynotrequireanypharmacologicintervention.Inpropersetting,restandsupplementaloxygenmaybesufficient.
Refertoaccompanyingtext.
CourtesyofScottGallagher,MDandPeterHackett,MDwithadditionaldatafrom:
1.LuksA,McIntoshS,GrissomCK,etal.WildernessMedicalSocietyConsensusGuidelinesforthePreventionand
TreatmentofAcuteAltitudeIllness.WildernessEnvironMed201021:146.
2.PollardA,NiermeyerS,BarryP,etal.ChildrenatHighAltitude:AnInternationalConsensus,StatementbyanAd
HocCommitteeoftheInternationalSocietyforMountainMedicine,March12,2001.HighAltitudeMedicine&
Biology.Volume2,Number3,2001.MaryAnnLiebert,Inc.Pages389403.
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ContributorDisclosures
ScottAGallagher,MD Nothingtodisclose PeterHackett,MD Nothingtodisclose JonathanMRosen,
MD Nothingtodisclose DanielFDanzl,MD Nothingtodisclose JonathanGrayzel,MD,FAAEM Nothingto
disclose
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconform
toUpToDatestandardsofevidence.
Conflictofinterestpolicy
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P B :barometricpressurePaCO 2 :arterialpartialpressureofcarbondioxidePaO 2 :arterialpartialpressureofoxygen

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