High-Altitude MedicineHigh-Altitude Medicine

Alicia Bond MDAlicia Bond MD

High altitudeHigh altitude

Moderate altitude Moderate altitude 5,000 – 10,000 feet above sea level5,000 – 10,000 feet above sea levelHighest U.S. ski resortsHighest U.S. ski resorts

High altitudeHigh altitude10,000 – 18,000 feet above sea level10,000 – 18,000 feet above sea levelHigh peaks in the lower 48, EuropeHigh peaks in the lower 48, Europe

Extreme altitudeExtreme altitudeGreater that 18,000 feet above sea levelGreater that 18,000 feet above sea levelDenali, Himalaya, Karakoram, AndesDenali, Himalaya, Karakoram, Andes

EpidemiologyEpidemiology

Most cases of high-altitude illness take place in Most cases of high-altitude illness take place in people rapidly ascending to altitudes between people rapidly ascending to altitudes between 8,000 and 12,000 feet8,000 and 12,000 feet

Can affect people who live at low altitude as well Can affect people who live at low altitude as well as people who live at high altitude and return as people who live at high altitude and return from travel to lower altitude (re-entry)from travel to lower altitude (re-entry)

Millions at risk each year – roughly 20-40% Millions at risk each year – roughly 20-40% affected by some type of altitude illnessaffected by some type of altitude illness 30 million Western states visitors30 million Western states visitors 12,000 Mt. Everest trekkers12,000 Mt. Everest trekkers 1,200 Denali climbers1,200 Denali climbers 1 million visitors to extreme high ranges worldwide1 million visitors to extreme high ranges worldwide

High-altitude environmentsHigh-altitude environments

Decreased barometric pressure = Decreased barometric pressure = logarithmically lower partial pressure of logarithmically lower partial pressure of oxygen (PO2) in inspired airoxygen (PO2) in inspired air

Higher latitudes have lower barometric Higher latitudes have lower barometric pressure at equivalent altitudespressure at equivalent altitudes

Weather systems can significantly lower Weather systems can significantly lower barometric pressure transientlybarometric pressure transiently

Cold, dry conditions may be contribute to Cold, dry conditions may be contribute to high-altitude illnesshigh-altitude illness

Factors affecting riskFactors affecting risk

Rate of ascentRate of ascentRecent high-altitude exposureRecent high-altitude exposureGenetic variabilityGenetic variabilitySleeping altitudeSleeping altitudeMaximum altitude reachedMaximum altitude reached

AcclimatizationAcclimatization

Series of physiologic adaptations to maintain Series of physiologic adaptations to maintain tissue oxygenationtissue oxygenation

Ability to acclimatize varies geneticallyAbility to acclimatize varies genetically Hours: Hypoxic ventilatory response (HVR), fluid Hours: Hypoxic ventilatory response (HVR), fluid

shift to increase hematocrit, increase in cardiac shift to increase hematocrit, increase in cardiac outputoutput

Days: Increased erythropoiesis, return of cardiac Days: Increased erythropoiesis, return of cardiac function to baseline, increase in 2,3-DPGfunction to baseline, increase in 2,3-DPG

Weeks: Increased plasma volume and red blood Weeks: Increased plasma volume and red blood cell masscell mass

Hypoxic ventilatory responseHypoxic ventilatory response

Most important component of acclimatizationMost important component of acclimatization Affected by genetics, ethanol, sleep Affected by genetics, ethanol, sleep

medications, caffeine, cocoa, progesteronemedications, caffeine, cocoa, progesterone PaO2 = PiO2 (PaCO2/R)PaO2 = PiO2 (PaCO2/R)

Hyperventilation decreases the partial pressure of CO2 in the alveoli, Hyperventilation decreases the partial pressure of CO2 in the alveoli, thereby increasing the partial pressure of oxygen in the alveoli to thereby increasing the partial pressure of oxygen in the alveoli to facilitate oxygenationfacilitate oxygenation

Resulting metabolic alkalosis slows HVR, and Resulting metabolic alkalosis slows HVR, and ventilation slowly increases over several days as ventilation slowly increases over several days as kidneys excrete bicarbkidneys excrete bicarb

Can be facilitated by acetazolamideCan be facilitated by acetazolamide People with low HVR at higher risk for illnessPeople with low HVR at higher risk for illness

CardiovascularCardiovascular

Initial increase in resting HR, which normalizes Initial increase in resting HR, which normalizes with acclimatizationwith acclimatization

Decrease in maximal heart rateDecrease in maximal heart rate Decrease in plasma volume -> lower stroke Decrease in plasma volume -> lower stroke

volume, increase in hematocritvolume, increase in hematocrit Shift to extracellular spaceShift to extracellular space Diuresis from bicarbonate excretionDiuresis from bicarbonate excretion

Decrease in max HR and SV are Decrease in max HR and SV are cardioprotective – myocardial ischemia is rarecardioprotective – myocardial ischemia is rare

Hematopoietic responseHematopoietic response

Initial increase in hematocrit due to fluid Initial increase in hematocrit due to fluid shift and diuresisshift and diuresis

Erythropoietin stimulated early, resulting in Erythropoietin stimulated early, resulting in new RBCs within 4-5 daysnew RBCs within 4-5 days

Over weeks to months, red cell and total Over weeks to months, red cell and total circulating volume expand to meet circulating volume expand to meet demanddemand

Oxygen-hemoglobin curveOxygen-hemoglobin curve Above 10,000 feet Above 10,000 feet

(PO2 ~ 60), small (PO2 ~ 60), small changes in PO2 cause changes in PO2 cause large changes in SaO2large changes in SaO2

Initial increase in 2,3-Initial increase in 2,3-diphosphoglycerate diphosphoglycerate (DPG) promotes O2 (DPG) promotes O2 release to tissuesrelease to tissues

Opposed by respiratory Opposed by respiratory alkalosis, which shifts alkalosis, which shifts curve left, favoring curve left, favoring oxygen uptake in the oxygen uptake in the lung and higher SaO2lung and higher SaO2

Sleep and periodic breathingSleep and periodic breathing

Disturbed sleep with less deep sleep and Disturbed sleep with less deep sleep and significant arousals commonsignificant arousals common

Periodic breathing commonPeriodic breathing common Hyperpnea and respiratory alkalosis cause apneaHyperpnea and respiratory alkalosis cause apnea CO2 builds during apnea, causing hyperpneaCO2 builds during apnea, causing hyperpnea Not usually associated with significant hypoxemia or Not usually associated with significant hypoxemia or

high-altitude illnesshigh-altitude illness Decreases with acclimatizationDecreases with acclimatization

People with low HVR may have overall regular People with low HVR may have overall regular breathing pattern with periods of more significant breathing pattern with periods of more significant apnea and hypoxemia, which are associated apnea and hypoxemia, which are associated with high-altitude illnesswith high-altitude illness

Acute high-altitude illnessAcute high-altitude illness

Spectrum of disease with intertwining Spectrum of disease with intertwining pathophysiologypathophysiology

Acute mountain sickness (AMS)Acute mountain sickness (AMS)High altitude cerebral edema (HACE)High altitude cerebral edema (HACE)High altitude pulmonary edema (HAPE)High altitude pulmonary edema (HAPE)All correct rapidly with descentAll correct rapidly with descent

Prevention of high-altitude illnessPrevention of high-altitude illness

Avoid ascent to greater than 8,000 feet in one Avoid ascent to greater than 8,000 feet in one dayday

Spend 2-3 nights at 8,000-9,000 feet before Spend 2-3 nights at 8,000-9,000 feet before further ascentfurther ascent

Don’t ascend sleeping altitude more than 1500 Don’t ascend sleeping altitude more than 1500 feet per dayfeet per day

Limit exertion, alcohol, and sedative-hypnotics Limit exertion, alcohol, and sedative-hypnotics during first days at altitudeduring first days at altitude

Day trips to higher altitude while maintaining Day trips to higher altitude while maintaining sleeping altitude can speed acclimatizationsleeping altitude can speed acclimatization

Acetazolamide 125-250 mg BIDAcetazolamide 125-250 mg BID

Acute mountain sicknessAcute mountain sickness

Most common with rapid ascent from below Most common with rapid ascent from below 3,000 feet to above 8,000 feet3,000 feet to above 8,000 feet

Develops within hours of ascentDevelops within hours of ascent Headache plus at least one of:Headache plus at least one of:

Gastrointestinal discomfortGastrointestinal discomfort Sleep disturbanceSleep disturbance Generalized weakness or fatigueGeneralized weakness or fatigue Dizziness or lightheadednessDizziness or lightheadedness

Headache is usually throbbing, bitemporal, Headache is usually throbbing, bitemporal, worse at night and with Valsalvaworse at night and with Valsalva

AMS: PathophysiologyAMS: Pathophysiology

Pathophysiology incompletely understoodPathophysiology incompletely understood Vasodilatory response to hypoxemia, fluid shift, Vasodilatory response to hypoxemia, fluid shift,

inflammatory mediators, and alterations in inflammatory mediators, and alterations in cerebrospinal fluid buffering capacity are all cerebrospinal fluid buffering capacity are all implicatedimplicated

No evidence of cerebral edema in AMS, but No evidence of cerebral edema in AMS, but some studies suggest transient ICP elevations some studies suggest transient ICP elevations with exertion and Valsalvawith exertion and Valsalva

At risk may be people with low HVR and people At risk may be people with low HVR and people with smaller CSF capacity (“tight fit”)with smaller CSF capacity (“tight fit”)

Hyperbaria contributes, but role unclear (AMS Hyperbaria contributes, but role unclear (AMS does not develop with hypoxia alone)does not develop with hypoxia alone)

AMS: ManagementAMS: Management

Usually resolves within 1-3 days if no Usually resolves within 1-3 days if no additional ascentadditional ascent

Mild: Stop ascent, symptomatic treatment, Mild: Stop ascent, symptomatic treatment, may consider acetazolamidemay consider acetazolamide

Moderate to severe: Low-flow oxygen, Moderate to severe: Low-flow oxygen, acetazolamide +/- dexamethasone 4 mg q acetazolamide +/- dexamethasone 4 mg q 6 hours, hyperbarics, or descend6 hours, hyperbarics, or descend

Immediate descent if s/sx HAPE or HACEImmediate descent if s/sx HAPE or HACE

AcetazolamideAcetazolamide

Carbonic anhydrase inhibitorCarbonic anhydrase inhibitorPromotes bicarbonate diuresis and Promotes bicarbonate diuresis and

metabolic acidosis, speeding metabolic acidosis, speeding acclimatizationacclimatization

Decreases CSF productionDecreases CSF productionMaintains oxygenation during sleepMaintains oxygenation during sleepSide effects: polyuria and paresthesiasSide effects: polyuria and paresthesias125-250 mg BID for treatment and 125-250 mg BID for treatment and

prevention of AMSprevention of AMS

High-altitude cerebral edemaHigh-altitude cerebral edema

Least common but most severe form of Least common but most severe form of high-altitude illnesshigh-altitude illness

Incidence 1-2% of ascentsIncidence 1-2% of ascentsUsually develops above 12,000 feetUsually develops above 12,000 feetUsually preceded by AMS and associated Usually preceded by AMS and associated

with HAPEwith HAPEMost commonly develops days 1-3 after Most commonly develops days 1-3 after

ascent, but can develop laterascent, but can develop later

HACE: PresentationHACE: Presentation

Ataxia and altered mentation are Ataxia and altered mentation are hallmarks – ataxia usually first symptomhallmarks – ataxia usually first symptom

Focal neuro deficits may be presentFocal neuro deficits may be presentSeizures uncommon but reportedSeizures uncommon but reportedUsually preceded by AMS symptomsUsually preceded by AMS symptomsAny ataxia or change in consciousness in Any ataxia or change in consciousness in

a person at altitude should elicit immediate a person at altitude should elicit immediate action!action!

HACE: PathophysiologyHACE: Pathophysiology

Vasogenic cerebral edema caused by Vasogenic cerebral edema caused by same group of mechanisms as AMS same group of mechanisms as AMS (vasodilation, leakage of fluid from (vasodilation, leakage of fluid from vessels) – reversiblevessels) – reversible

Increased ICP causes decreased cerebral Increased ICP causes decreased cerebral blood flow, resulting in cell deathblood flow, resulting in cell death

At advanced stages, cytotoxic edema and At advanced stages, cytotoxic edema and necrosis are present - not reversiblenecrosis are present - not reversible

HACE: ManagementHACE: Management

Immediate descent is keyImmediate descent is key High-flow oxygen and dexamethasone 8 mg (IV, High-flow oxygen and dexamethasone 8 mg (IV,

IM, PO) followed by 4 mg q 6 hours if available IM, PO) followed by 4 mg q 6 hours if available Hyperbarics may result in temporary Hyperbarics may result in temporary

improvement but may delay descentimprovement but may delay descent Intubation, hyperventilation if severely alteredIntubation, hyperventilation if severely altered Can try mannitol or furosemide but caution due Can try mannitol or furosemide but caution due

to dehydration common at altitudeto dehydration common at altitude

HACE: PrognosisHACE: Prognosis

If descent initiated early, may be If descent initiated early, may be completely reversible over days to weeks completely reversible over days to weeks without sequelaewithout sequelae

Reports of ataxia and other neuro deficits Reports of ataxia and other neuro deficits persisting months to yearspersisting months to years

Mortality rate greater than 60% if Mortality rate greater than 60% if progresses to comaprogresses to coma

High-altitude pulmonary edemaHigh-altitude pulmonary edema

Most common cause of altitude-related Most common cause of altitude-related deathdeath

Incidence up to 15% of ascentsIncidence up to 15% of ascentsUsually greater than 10,000 feet, or Usually greater than 10,000 feet, or

greater than 8,000 feet with heavy exertiongreater than 8,000 feet with heavy exertionDevelops within 2-4 days of ascent, Develops within 2-4 days of ascent,

classically on the second nightclassically on the second night

HAPE: PresentationHAPE: Presentation

Early signs are severe dyspnea on Early signs are severe dyspnea on exertion, fatigue with minimal activity, and exertion, fatigue with minimal activity, and dry coughdry cough

Dyspnea at rest and clear, watery sputum Dyspnea at rest and clear, watery sputum develop as illness progressesdevelop as illness progresses

Dyspnea at rest is red flag for HAPE and Dyspnea at rest is red flag for HAPE and should prompt immediate action!should prompt immediate action!

Patchy infiltrates on CXR, worst right Patchy infiltrates on CXR, worst right middle lobemiddle lobe

HAPE: PathophysiologyHAPE: Pathophysiology

Hypoxic vasoconstriction causes Hypoxic vasoconstriction causes pulmonary hypertensionpulmonary hypertension

Uneven vasoconstriction (areas of Uneven vasoconstriction (areas of extreme hypoxia or anatomic difference) extreme hypoxia or anatomic difference) causes hyperperfusion of some areas, causes hyperperfusion of some areas, leading to vascular leak and patchy edemaleading to vascular leak and patchy edema

Both hypoxia and pulmonary hypertension Both hypoxia and pulmonary hypertension are exacerbated by exertionare exacerbated by exertion

HAPE: ManagementHAPE: Management

Symptoms resolve quickly upon descent of Symptoms resolve quickly upon descent of 1500-3000 feet1500-3000 feet

Mild cases may be treated with bedrest and O2 Mild cases may be treated with bedrest and O2 to maintain SaO2 > 90to maintain SaO2 > 90

Descent for severe symptoms, minimizing Descent for severe symptoms, minimizing exertionexertion

High-flow oxygenHigh-flow oxygen Continuous positive airway pressure if availableContinuous positive airway pressure if available Air drops of O2 may be lifesaving if descent not Air drops of O2 may be lifesaving if descent not

possiblepossible Hyperbarics may help conserve O2 supplyHyperbarics may help conserve O2 supply

HyperbaricsHyperbarics

Portable, lightweight,Portable, lightweight,manually-pressurizedmanually-pressurizedhyperbaric bags hyperbaric bags

Raise atmospheric Raise atmospheric pressure 2 psi (103 mmHg)pressure 2 psi (103 mmHg)

Simulates descent of Simulates descent of 4,000-5,000 feet at moderate 4,000-5,000 feet at moderate altitudes, more at higher altitudesaltitudes, more at higher altitudes

Can be lifesaving in HAPE and HACE, relieving Can be lifesaving in HAPE and HACE, relieving symptoms so that patients can descend without symptoms so that patients can descend without evacuationevacuation

Photo: Rosen’s Emergency Medicine, Courtesy of Thomas Dietz, MD

Take-homeTake-home

Slow ascent and acetazolamide are Slow ascent and acetazolamide are effective in preventing illnesseffective in preventing illness

Ataxia, altered mentation, and dyspnea at Ataxia, altered mentation, and dyspnea at rest are red flags for serious illnessrest are red flags for serious illness

Early recognition of HAPE and HACE with Early recognition of HAPE and HACE with descent prevents morbidity and mortalitydescent prevents morbidity and mortality

Have fun up there!Have fun up there!

Key ReferencesKey References

Marx, JA, ed. Marx, JA, ed. Rosen’s Emergency Rosen’s Emergency Medicine, 7Medicine, 7thth Ed. Ed. Philadelphia: Mosby Philadelphia: Mosby Elsevier, 2010Elsevier, 2010

Auerbach, PS, ed. Auerbach, PS, ed. Wilderness Medicine, Wilderness Medicine, 66thth Ed. Ed. Philadelphia: Mosby Elsevier, 2012 Philadelphia: Mosby Elsevier, 2012