Merck Manual

Please confirm that you are a health care professional

Loading

Altitude Illness

By

Andrew M. Luks

, MD, University of Washington

Last full review/revision Sep 2019| Content last modified Sep 2019
Click here for Patient Education
Topic Resources

Altitude illness is caused by the decreased availability of oxygen at high altitudes. Acute mountain sickness (AMS), the mildest form, is characterized by headache plus one or more systemic manifestations; it may occur in recreational hikers and skiers and others traveling to high altitude. High-altitude cerebral edema (HACE) is a form of global encephalopathy, while high-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema causing severe dyspnea and hypoxemia. Diagnosis of altitude illness is clinical. Treatment of mild AMS is with analgesics and acetazolamide or dexamethasone. Severe AMS may require descent and supplemental oxygen if available. Both HACE and HAPE are potentially life-threatening and require immediate descent. In addition, dexamethasone is useful for HACE, and nifedipine or phosphodiesterase inhibitors are useful for HAPE. Prevention of AMS is by gradual ascent and use of acetazolamide.

As altitude increases, atmospheric pressure decreases while the percentage of oxygen in air remains constant; thus, the partial pressure of oxygen decreases with altitude and, at 5800 m (19,000 ft), is about one half that at sea level, while on the summit of Mt. Everest (8852 m, or about 29,000 ft), it is roughly one third that of sea level.

Most people can ascend to 1500 to 2000 m (5000 to 6500 ft) in one day without problems, but about 20% of those who ascend to 2500 m (8000 ft) and 40% of those who ascend to 3000 m (10,000 ft) develop AMS. Rate of ascent, maximum altitude reached, and sleeping altitude influence the likelihood of developing these disorders.

Risk factors

Effects of high altitude vary greatly among individuals. But generally, risk is increased by the following:

  • History of previous altitude illness

  • Living near sea level

  • Going too high too fast

  • Overexertion

  • Sleeping at too high an altitude

Disorders such as asthma, hypertension, diabetes, coronary artery disease, and mild chronic obstructive pulmonary disease are not risk factors for altitude illness, but hypoxia may adversely affect these disorders. Physical fitness is not protective.

Pearls & Pitfalls

  • Physical fitness is not protective against altitude illness.

Pathophysiology

Whereas severe acute hypoxemia can cause altered central nervous system function within a matter of minutes, acute altitude illness develops anywhere from 1 to 5 days after ascent to a given elevation.

The pathogenesis of acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) remain unclear despite considerable research in this area. The diseases likely develop as a result of the same underlying pathophysiology and fall on a continuum of severity, with HACE representing the extreme of the spectrum. AMS may involve activation of the trigeminovascular system due to a variety of stimuli, while HACE involves blood-brain barrier leakage and increased intracranial pressure.

High-altitude pulmonary edema (HAPE) is caused by hypoxia-induced elevation of pulmonary artery pressure which causes interstitial and alveolar pulmonary edema, resulting in impaired oxygenation. Small-vessel hypoxic vasoconstriction is patchy, causing elevated pressure, capillary wall damage, and capillary leakage in less constricted areas. Other factors, such as sympathetic overactivity, may also be involved.

Long-time high-altitude residents can develop HAPE when they return after a brief stay at low altitude, a phenomenon referred to as reentry pulmonary edema. Recent reports suggest that long-term high-altitude residents can also develop noncardiogenic pulmonary edema—referred to as high-altitude resident HAPE—even if they do not descend to and then return from a lower elevation.

Acclimatization

Acclimatization is an integrated series of responses that allow the body to tolerate the hypoxia at high altitude. Most people acclimatize reasonably well to altitudes of up to 3000 m (10,000 ft) within a few days. The higher the altitude, the longer acclimatization takes. However, no one can fully acclimatize to long-term residence at altitudes > 5100 m (> 17,000 ft).

Features of acclimatization include sustained hyperventilation, which raises the alveolar and arterial PO2 but also causes respiratory alkalosis. Blood pH tends to normalize within days as bicarbonate is excreted in urine; as pH normalizes, ventilation can increase further. Cardiac output increases initially and returns to baseline values over time; red blood cell mass and tolerance for aerobic work also increase over a period of several weeks.

Symptoms and Signs

Acute mountain sickness is by far the most common form of altitude illness.

Acute mountain sickness (AMS)

AMS is unlikely unless altitude is above 2440 m (8000 ft), but it can develop at lower elevations in some highly susceptible people. It is characterized by headache plus at least one of the following: fatigue, gastrointestinal symptoms (anorexia, nausea, vomiting), and persistent dizziness. Poor sleep was previously considered a symptom of AMS but is no longer considered one of the diagnostic criteria. Symptoms typically develop 6 to 10 hours after ascent and, in most cases, subside in 24 to 48 hours. AMS is common at ski resorts, and some people affected by it mistakenly attribute it to excessive alcohol intake (hangover) or a viral illness.

High-altitude cerebral edema (HACE)

HACE occurs rarely. Marked cerebral edema manifests as headache and diffuse encephalopathy with confusion, drowsiness, stupor, and coma. Gait ataxia is a reliable early warning sign. Seizures, focal deficits (eg, cranial nerve palsy, hemiplegia), fever, and meningeal signs are uncommon and should prompt concern for other diagnoses. Papilledema and retinal hemorrhage may be present but are not necessary for diagnosis. Coma and death may occur within a few hours unless HACE is treated promptly.

High-altitude pulmonary edema (HAPE)

HAPE typically develops 24 to 96 hours after rapid ascent to > 2500 m (> 8000 ft) and is responsible for most deaths due to altitude illness. It may be preceded by AMS, but can also develop in isolation in people who were not manifesting other evidence of altitude illness.

Initially, patients have dyspnea on exertion, decreased exertion tolerance, and dry cough. Later, dyspnea is present with simple activities or at rest. Pink or bloody sputum and respiratory distress are late findings. On examination, cyanosis, tachycardia, tachypnea, and low-grade fever (< 38.5° C) are common. Focal or diffuse crackles (sometimes audible without a stethoscope) are usually present. HAPE may worsen rapidly; coma and death may occur within hours unless HAPE is treated promptly.

Other manifestations

Peripheral and facial edema is common at high altitude even in the absence of altitude illness.

Headache, without other symptoms of AMS, is also common.

Retinal hemorrhages can develop at altitudes as low as 2700 m (9000 ft) and are common at > 5000 m (> 16,000 ft). They are usually asymptomatic unless they occur in the macular region, in which case they typically present as painless vision loss; they resolve over weeks without sequelae. With symptomatic hemorrhages, descent is indicated and further ascent is contraindicated until hemorrhages have resolved.

People who have had radial keratotomy or LASIK may have significant visual disturbances at altitudes > 5000 m (> 16,000 ft). These symptoms disappear rapidly after descent.

Chronic mountain sickness (Monge disease) is a disease that affects long-time high-altitude residents; it is characterized by excessive polycythemia, fatigue, dyspnea, aches and pains, and cyanosis. The disorder often involves alveolar hypoventilation. Patients should descend to low altitude and remain there permanently if possible, but economic factors often prevent them from doing so. Repeated phlebotomy can help by reducing polycythemia. In some patients, long-term treatment with acetazolamide results in improvement.

Diagnosis

  • Clinical evaluation

Prompt diagnosis and initiation of treatment of high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) are essential to prevent coma and death.

Diagnosis of altitude illness is usually clinical; laboratory tests are usually unnecessary and may be unavailable. However, imaging, when available, may be useful for HAPE and sometimes HACE. In HAPE, hypoxemia is often severe, with pulse oximetry showing 40 to 70% saturation, depending on the elevation at which the individual becomes ill. Chest x-ray shows a normal-sized heart and patchy lung edema. HACE can usually be differentiated from other causes of headache and coma (eg, infection, brain hemorrhage, uncontrolled diabetes) by history and clinical findings; if not, CT or MRI imaging of the head may help rule out other causes. The Lake Louise acute mountain sickness score is a tool that can be used in diagnosis but is primarily designed for the purpose of research studies rather than clinical practice (1).

Diagnosis reference

Treatment

  • For mild or moderate acute mountain sickness (AMS), halting ascent and treatment with fluids, nonopioid analgesics, and sometimes acetazolamide or dexamethasone

  • For severe AMS, descent, fluids, nonopioid analgesics, and acetazolamide or dexamethasone

  • For high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE), immediate descent and treatment with oxygen, drugs, and pressurization

Acute mountain sickness (AMS)

Patients should halt ascent and reduce exertion until symptoms resolve (1, 2). Other treatment includes fluids and nonopioid analgesics for headache. For severe symptoms or symptoms that fail to resolve with appropriate conservative measures, descent of 500 to 1000 m (1650 to 3200 ft) is often rapidly effective. Acetazolamide 250 mg orally twice a day may relieve symptoms and improve sleep. Dexamethasone 2 to 4 mg orally, IM, or IV every 6 hours is also highly effective for treating symptoms of AMS.

High-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE)

Patients should descend to low altitude immediately. Helicopter evacuation may be life-saving (1). If descent is delayed, patients should rest and be given oxygen. If descent is impossible, oxygen (to raise the O2 saturation to > 90%), drugs, and pressurization in a portable hyperbaric bag help buy time but are not substitutes for and should not delay descent.

  • Dexamethasone

For HACE (and severe AMS)

Dexamethasone 8 mg initially, followed by 4 mg every 6 hours, may help. It should be given orally but if this is impossible, dexamethasone may be given IM or IV. Acetazolamide 250 mg orally twice a day may be added. Depending on the severity of illness, HACE can take anywhere from several hours to several weeks to fully resolve.

For HAPE

  • Nifedipine or a phosphodiesterase inhibitor

Nifedipine 30 mg slow-release orally every 12 hours lowers pulmonary artery pressure and is beneficial, although systemic hypotension is a possible complication. A phosphodiesterase inhibitor, such as sildenafil (50 mg orally every 12 hours) or tadalafil (10 mg orally every 12 hours), may be used instead of nifedipine. Diuretics (eg, furosemide) are contraindicated; they have no efficacy and many patients have concomitant volume depletion. The heart is normal in HAPE, and digoxin and afterload reduction with acetylcholinesterase (ACE) inhibitors are of no value. When promptly treated by descent, patients usually recover from HAPE within 24 to 48 hours. Exertion should be avoided during descent. People who have had one episode of HAPE are likely to have another and should be so warned.

Pearls & Pitfalls

  • Diuretics are contraindicated in high altitude pulmonary edema.

Treatment references

  • Luks AM, Auerbach PS, Freer L, et al: Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2019 Update. Wilderness Environ Med. doi.org/10.1016/j.wem.2019.04.006.

  • Bartsch P, Swenson ER: Acute high-altitude illnesses. N Engl J Med 368:2294-2302, 2013. doi: 10.1056/NEJMcp1214870.

Prevention

  • Slow ascent

  • Sometimes acetazolamide or dexamethasone

Although physical fitness enables greater exertion at altitude, it does not protect against any form of altitude illness. Maintaining adequate fluid intake does not prevent acute mountain sickness (AMS) but does protect against dehydration, the symptoms of which closely resemble AMS. Opioids and heavy alcohol consumption, particularly shortly before sleep, should be avoided.

Ascent

The most important measure is a slow ascent (1, 2). Graded ascent is essential for activity at > 2500 m (> 8000 ft). Above 3000 m (10,000 ft), climbers should not increase their sleeping altitude by more than 500 m (1600 ft) per day and should include a rest day (ie, sleep at the same altitude) every 3 to 4 days. If a single day's ascent must exceed 500 m (eg, due to logistics or terrain features), they should add in rest days to achieve an average rate of < 500 m (1600 ft) per day over the entire ascent. During rest days, climbers can engage in physical activity and ascend to higher altitudes but should return to the lower level for sleep. Climbers vary in ability to ascend without developing symptoms; a climbing party should be paced for its slowest member.

Acclimatization is gradually lost after a few days at low altitude, and climbers returning to high altitude after this duration should once more follow a graded ascent.

Drugs

Acetazolamide 125 to 250 mg orally every 12 hours reduces the incidence of altitude illness. Sustained-release capsules (500 mg once a day) are also available. A recent report suggests that doses as low as 62.5 mg orally every 12 hours may be effective, but further research is necessary before this practice is adopted. Acetazolamide can be started the night before ascent; it acts by inhibiting carbonic anhydrase and thus increasing ventilation. Acetazolamide 125 mg orally at bedtime reduces the amount of periodic breathing (almost universal during sleep at high altitude), thus limiting sharp falls in blood oxygen.

Patients allergic to sulfa drugs have a small risk of cross-reactivity to acetazolamide; a supervised trial of acetazolamide should be considered for these patients before they make a trip to altitudes remote from medical care. Acetazolamide should not be given to patients with a history of anaphylaxis to sulfa drugs. Acetazolamide may cause numbness and paresthesias of the fingers; these symptoms are benign but can be annoying. Carbonated drinks taste flat to people taking acetazolamide.

Dexamethasone 2 mg orally every 6 hours (or 4 mg orally every 12 hours) is an alternative to acetazolamide.

Low-flow oxygen during sleep at altitude is effective but inconvenient and may pose logistic difficulties.

In addition to slowing their rate of ascent, patients who have had a previous episode of high-altitude pulmonary edema should consider prophylaxis with sustained-release nifedipine 30 mg orally twice a day or tadalafil 10 mg orally twice a day (3).

Analgesics (eg, acetaminophen, ibuprofen) may prevent high-altitude headache.

Prevention references

  • Luks AM, Auerbach PS, Freer L, et al: Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2019 Update. Wilderness Environ Med. doi.org/10.1016/j.wem.2019.04.006.

  • Bartsch P, Swenson ER: Acute high-altitude illnesses. N Engl J Med 368:2294-2302, 2013. doi: 10.1056/NEJMcp1214870.

  • Maggiorini M, Brunner-La Rocca HP, Peth S, et al: Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: A randomized trial. Ann Intern Med 3;145(7):497-506, 2006.

Key Points

  • About 20% of people who ascend to 2500 m (8000 ft) and 40% of those who ascend to 3000 m (10,000 ft) in one day develop acute mountain sickness (AMS).

  • AMS causes headache plus fatigue, gastrointestinal symptoms (anorexia, nausea, vomiting), and persistent dizziness.

  • High-altitude cerebral edema (HACE) causes ataxia and encephalopathy.

  • High-altitude pulmonary edema (HAPE) causes dyspnea, decreased exertion tolerance, and dry cough initially which can progress to dyspnea with simple activities or at rest, profound fatigue, cyanosis and a cough productive of blood sputum in the more severe stages.

  • Diagnose altitude illness based on clinical findings.

  • Treat mild AMS with fluids, analgesics, sometimes acetazolamide or dexamethasone, and by stopping further ascent.

  • Arrange immediate descent for patients with HACE, HAPE, or very severe AMS.

  • Prevent altitude illness by gradual ascent and use of acetazolamide.

Drugs Mentioned In This Article

Drug Name Select Trade
OZURDEX
DIAMOX
TYLENOL
LASIX
ADALAT CC, PROCARDIA
VIAGRA
ADVIL, MOTRIN IB
CIALIS
LANOXIN
Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Professionals also read

Also of Interest

Videos

View All
Bridging
Video
Bridging
1. Lie on back with both knees bent and feet on floor/table. 2. Perform abdominal and gluteus...
3D Models
View All
Nerves, Arteries, and Ligaments of the Ankle and Foot
3D Model
Nerves, Arteries, and Ligaments of the Ankle and Foot

SOCIAL MEDIA

TOP