Anda di halaman 1dari 26

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].
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

1/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

2/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

3/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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".)
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

4/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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,
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

5/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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".)
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

6/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

7/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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'.)

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

8/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alti

9/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

10/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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)

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20alt 11/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
REFERENCES
1.HackettPH,RoachRC.Highaltitudemedicine.In:WildernessMedicine,6th,AuerbachPS(Eds),
Elsevier,Philadelphia2012.p.2.
2.ScogginCH,HyersTM,ReevesJT,GroverRF.Highaltitudepulmonaryedemainthechildrenand
youngadultsofLeadville,Colorado.NEnglJMed1977297:1269.
3.WestJB,AmericanCollegeofPhysicians,AmericanPhysiologicalSociety.Thephysiologicbasisof
highaltitudediseases.AnnInternMed2004141:789.
4.GallagherSA,HackettPH.Highaltitudeillness.EmergMedClinNorthAm200422:329.
5.SchoeneRB.Illnessesathighaltitude.Chest2008134:402.
6.MacInnisMJ,WangP,KoehleMS,RupertJL.Thegeneticsofaltitudetolerance:theevidencefor
inheritedsusceptibilitytoacutemountainsickness.JOccupEnvironMed201153:159.
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

12/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

7.WestJB,SchoeneRB,MilledgeJS.HighAltitudeMedicineandPhysiology,HodderArnold,London
2007.
8.WolffCB,RichardsonN,KempO,etal.Nearinfraredspectroscopyandarterialoxygenextractionat
altitude.AdvExpMedBiol2007599:183.
9.CalbetJA,LundbyC.AirtomuscleO2deliveryduringexerciseataltitude.HighAltMedBiol2009
10:123.
10.BasnyatB,MurdochDR.Highaltitudeillness.Lancet2003361:1967.
11.StreamJO,GrissomCK.Updateonhighaltitudepulmonaryedema:pathogenesis,prevention,and
treatment.WildernessEnvironMed200819:293.
12.JohnsonPL,PopaDA,PriskGK,etal.Noninvasivepositivepressureventilationduringsleepat3800
m:Relationshiptoacutemountainsicknessandsleepingoxyhaemoglobinsaturation.Respirology2010
15:277.
13.BlochKE,LatshangTD,TurkAJ,etal.Nocturnalperiodicbreathingduringacclimatizationatveryhigh
altitudeatMountMuztaghAta(7,546m).AmJRespirCritCareMed2010182:562.
14.KpperT,SchfflV,NetzerN.Cheynestokesbreathingathighaltitude:ahelpfulresponseora
troublemaker?SleepBreath200812:123.
15.HackettPH,RennieD.Rales,peripheraledema,retinalhemorrhageandacutemountainsickness.AmJ
Med197967:214.
16.ButlerFK,HarrisDJJr,ReynoldsRD.AltituderetinopathyonMountEverest,1989.Ophthalmology
199299:739.
17.LangGE,KubaGB.Highaltituderetinopathy.AmJOphthalmol1997123:418.
18.HackettPH,RoachRC.Highaltitudeillness.NEnglJMed2001345:107.
19.BrtschP,SwensonER.Clinicalpractice:Acutehighaltitudeillnesses.NEnglJMed2013368:2294.
20.DusterMC,DerletMN.Highaltitudeillnessinchildren.PediatrAnn200938:218.
21.DurmowiczAG,NoordeweirE,NicholasR,ReevesJT.Inflammatoryprocessesmaypredisposechildren
tohighaltitudepulmonaryedema.JPediatr1997130:838.
22.ChoudhuriJA,OgdenLG,RuttenberAJ,etal.Effectofaltitudeonhospitalizationsforrespiratory
syncytialvirusinfection.Pediatrics2006117:349.
23.FasulesJW,WigginsJW,WolfeRR.IncreasedlungvasoreactivityinchildrenfromLeadville,Colorado,
afterrecoveryfromhighaltitudepulmonaryedema.Circulation198572:957.
24.LoveringAT,RomerLM,HaverkampHC,etal.Excessivegasexchangeimpairmentduringexerciseina
subjectwithahistoryofbronchopulmonarydysplasiaandhighaltitudepulmonaryedema.HighAltMed
Biol20078:62.
25.RiosB,DriscollDJ,McNamaraDG.Highaltitudepulmonaryedemawithabsentrightpulmonaryartery.
Pediatrics198575:314.
26.SebbaneM,WuyamB,PinI,etal.Unilateralagenesisofthepulmonaryarteryandhighaltitude
pulmonaryedema(HAPE)atmoderatealtitude.PediatrPulmonol199724:111.
27.OadesPJ,BuchdahlRM,BushA.Predictionofhypoxaemiaathighaltitudeinchildrenwithcystic
fibrosis.BMJ1994308:15.
28.PashankarFD,CarbonellaJ,BazzyAsaadA,FriedmanA.Prevalenceandriskfactorsofelevated
pulmonaryarterypressuresinchildrenwithsicklecelldisease.Pediatrics2008121:777.
29.HultgrenHN,HonigmanB,TheisK,NicholasD.Highaltitudepulmonaryedemaataskiresort.WestJ
Med1996164:222.
30.DasBB,WolfeRR,ChanKC,etal.Highaltitudepulmonaryedemainchildrenwithunderlying
cardiopulmonarydisordersandpulmonaryhypertensionlivingataltitude.ArchPediatrAdolescMed
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

13/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

2004158:1170.
31.NiermeyerS.Goingtohighaltitudewithanewborninfant.HighAltMedBiol20078:117.
32.RichaletJP,ChenivesseC,LarmignatP,MeilleL.Highaltitudepulmonaryedema,downsyndrome,and
obstructivesleepapneas.HighAltMedBiol20089:179.
33.RgglaG,MoserB.Highaltitudepulmonaryedemaatmoderatealtitudeasfirstmanifestationof
pulmonaryhypertensionina14yearoldboywithDownSyndrome.WildernessEnvironMed2006
17:207.
34.DurmowiczAG.Pulmonaryedemain6childrenwithDownsyndromeduringtraveltomoderatealtitudes.
Pediatrics2001108:443.
35.LuksAM,McIntoshSE,GrissomCK,etal.WildernessMedicalSocietyconsensusguidelinesforthe
preventionandtreatmentofacutealtitudeillness.WildernessEnvironMed201021:146.
36.BlochKE,TurkAJ,MaggioriniM,etal.Effectofascentprotocolonacutemountainsicknessand
successatMuztaghAta,7546m.HighAltMedBiol200910:25.
37.BeidlemanBA,FulcoCS,MuzaSR,etal.Effectofsixdaysofstagingonphysiologicadjustmentsand
acutemountainsicknessduringascentto4300meters.HighAltMedBiol200910:253.
38.PesceC,LealC,PintoH,etal.DeterminantsofacutemountainsicknessandsuccessonMount
Aconcagua(6962m).HighAltMedBiol20056:158.
39.SchneiderM,BernaschD,WeymannJ,etal.Acutemountainsickness:influenceofsusceptibility,
preexposure,andascentrate.MedSciSportsExerc200234:1886.
40.HonigmanB,TheisMK,KoziolMcLainJ,etal.Acutemountainsicknessinageneraltouristpopulation
atmoderatealtitudes.AnnInternMed1993118:587.
41.DehnertC,BhmA,GrigorievI,etal.Sleepinginmoderatehypoxiaathomeforpreventionofacute
mountainsickness(AMS):aplacebocontrolled,randomizeddoubleblindstudy.WildernessEnviron
Med201425:263.
42.BeidlemanBA,MuzaSR,FulcoCS,etal.Intermittentaltitudeexposuresreduceacutemountain
sicknessat4300m.ClinSci(Lond)2004106:321.
43.FulcoCS,BeidlemanBA,MuzaSR.Effectivenessofpreacclimatizationstrategiesforhighaltitude
exposure.ExercSportSciRev201341:55.
44.SchommerK,WiesegartN,MenoldE,etal.Traininginnormobarichypoxiaanditseffectsonacute
mountainsicknessafterrapidascentto4559m.HighAltMedBiol201011:19.
45.GrahamLE,BasnyatB.CerebraledemaintheHimalayas:toohigh,toofast!WildernessEnvironMed
200112:62.
46.RoegglaG,RoegglaH,RoegglaM,etal.Effectofalcoholonacuteventilatoryadaptationtomildhypoxia
atmoderatealtitude.AnnInternMed1995122:925.
47.BasnyatB,LemasterJ,LitchJA.Everestorbust:acrosssectional,epidemiologicalstudyofacute
mountainsicknessat4243metersintheHimalayas.AviatSpaceEnvironMed199970:867.
48.SwensonER,MacDonaldA,VatheuerM,etal.Acutemountainsicknessisnotalteredbyahigh
carbohydratedietnorassociatedwithelevatedcirculatingcytokines.AviatSpaceEnvironMed1997
68:499.
49.RoachRC,MaesD,SandovalD,etal.Exerciseexacerbatesacutemountainsicknessatsimulatedhigh
altitude.JApplPhysiol(1985)200088:581.
50.MENONND.HIGHALTITUDEPULMONARYEDEMA:ACLINICALSTUDY.NEnglJMed1965
273:66.
51.ConwayR,EvansI,WeeramanD.Assessingtravelers'knowledgeanduseofcocaforaltitudesickness.
WildernessEnvironMed201223:373.
https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

14/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

52.SpielvogelH,CaceresE,KoubiH,etal.Effectsofcocachewingonmetabolicandhormonalchanges
duringgradedincrementalexercisetomaximum.JApplPhysiol(1985)199680:643.
53.SalazarH,SwansonJ,MozoK,etal.AcutemountainsicknessimpactamongtravelerstoCusco,Peru.
JTravelMed201219:220.
Topic181Version20.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

15/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

GRAPHICS
Howairisexchangedinthelungs

Thisfiguredepictshowoxygen(02)andcarbondioxide(CO2)passbetweenthe
alveloi(insidethelung)andthecapillaries(thebloodstream).
Reproducedwithpermissionfrom:AnatomicalChartCo.Copyright2008Lippincott
Williams&Wilkins.
Graphic58392Version1.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

16/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

Oxygencascadeatsealeveland4300meters

Reproducedwithpermissionfrom:McArdleWD,KatchFI,KatchVL.Exercise
Physiology:Nutrition,Energy,andHumanPerformance,8thed,LippincottWilliams&
Wilkins,Philadelphia2014.Copyright2014LippincottWilliams&Wilkins.
www.lww.com.
Graphic97579Version3.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

17/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
Graphic98575Version2.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

18/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
Graphic63999Version3.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

19/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
Graphic50199Version1.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

20/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
Graphic56808Version2.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

21/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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
Graphic75758Version3.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

22/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
Graphic65647Version5.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

23/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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
Children:2.5mg/kg(maximumsingle
dose:250mg)orallyevery12hours

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

Acetazolamide:125to250mgorally
every12hours
Children:2.5mg/kg(maximumsingle
dose:250mg)orallyevery12hours

Duration:continueuntil24hoursafter
symptomsresolveordescentcompleted,
butnotlongerthan7daystotal

Duration:continuefor24hoursafter
symptomsresolveordescent
accomplished

Dexamethasone: 8to10mgorally
/IM/IVonce,then4mgorally/IM/IV
every6hours
Children:0.15mg/kgevery6hours
(maximumsingledose:4mg)

Acetazolamide:250mgorallyevery12
hours,mayuseasadjunctwith
dexamethasoneNOTformonotherapy
Children:2.5mg/kg(maximumsingle
dose:250mg)orallyevery12hours

Duration:continueuntil24hoursafter
symptomsresolveordescentcompleted,
butnotlongerthan7daystotal

Duration:continueuntil24hoursafter
symptomsresolveordescent
accomplished

Nifedipine:60mgextendedrelease
orallydivideddaily(30mgorallyevery12
hrsor20mgorallyevery8hours).
Children:0.5mg/kg(maximumsingle
dose:20mg)extendedreleaseorally
every8hours

Furtherresearchisneededbeforethe
medicationslistedbelowcanbe
recommendedforroutineuse:

Duration:startdaybeforeascentand
continuefor35daysatmaximum
altitude

Sildenafil:50mgorallyevery8hours
startdayofascentandcontinue35days
atmaximumaltitude

Tadalafil:10mgorallyevery12hours
startdayofascentandcontinue35days
atmaximumaltitude

Dexamethasone:8mgorallyevery12
hoursstartdayofascentandcontinue
4872hoursatmaximumaltitude
Acetazolamide:125to250mgorally
every12hoursstartdaybeforeascent
andcontinue4872hoursatmaximum
altitude
HAPE
treatment

Nifedipine:60mgextendedrelease
orallydivideddaily(30mgorallyevery12
hoursor20mgorallyevery8hours).
Children:0.5mg/kg(maximumsingle
dose:20mg)extendedreleaseorally
every8hours
Duration:continueuntildescent
completed,symptomsresolvedandSpO2
normalforaltitude

Furtherresearchisneededbeforethe
medicationslistedbelowcanbe
recommendedforroutineuseinHAPE
treatment:
Tadalafil:10mgorallyevery12hours
Sildenafil:50mgorallyevery8hours
Duration:continueuntildescent
completed,symptomsresolvedandSpO2

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

24/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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.
Graphic76719Version11.0

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

25/26

10/7/2016

Highaltitudeillness:Physiology,riskfactors,andgeneralpreventionUpToDate

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

Close

https://www.uptodate.com/contents/highaltitudeillnessphysiologyriskfactorsandgeneralprevention/print?source=search_result&search=high%20al

26/26