Altitude diseases (AD) are caused by the decreased availability of O2 at high altitudes. Acute mountain sickness (AMS), the mildest form of AD, is characterized by headache plus one or more systemic manifestations; it may occur in recreational hikers and skiers in mountains. High-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema causing severe dyspnea and hypoxemia. High-altitude cerebral edema (HACE) is encephalopathy in people with AMS. Diagnosis is clinical. Treatment of mild AMS is with analgesics and acetazolamide. Severe AMS may require descent and supplemental O2 if available. Both HAPE and HACE are potentially life-threatening and require immediate descent. In addition, dexamethasone may be useful for HACE, and nifedipine may be useful for HAPE. Prevention of AMS is by gradual ascent and use of acetazolamide.
As altitude increases, atmospheric pressure decreases while the percentage of O2 in air remains constant; thus, the partial pressure of O2 decreases with altitude and, at 5800 m (19,000 ft), is about one half that at 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 the disorder.
Effects of high altitude vary greatly among individuals. But generally, risk is increased by
Risk is greater in people who have had previous AD and in those who live near sea level. Young children and young adults are probably more susceptible. Disorders such as diabetes, coronary artery disease, and mild COPD are not risk factors for AD, but hypoxia may adversely affect these disorders. Physical fitness is not protective.
Acute hypoxia (eg, as occurs during rapid ascent to high altitude in an unpressurized aircraft) alters CNS function within minutes. However, AD results from the body's neurohumoral and hemodynamic responses to hypoxia and develops over hours to days. The primary manifestations involve the CNS and the lungs.
The pathogenesis of AMS and HACE is thought to be similar, with HACE representing the extreme of the spectrum. Although it is not certain, pathogenesis may involve mild cerebral edema, possibly related to the increased cerebral blood flow caused by hypoxia.
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.
Acclimatization is an integrated series of responses that gradually restores tissue oxygenation toward normal in people exposed to altitude. However, in spite of acclimatization, all people at high altitude have tissue hypoxia. 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 increases tissue oxygenation but also causes respiratory alkalosis. Blood pH tends to normalize within days as HCO3 is excreted in urine; as pH normalizes, ventilation can increase further. Cardiac output increases initially; RBC mass and tolerance for aerobic work also increase.
Symptoms and Signs
AMS is by far the most common form of AD.
Acute mountain sickness (AMS):
This disease may develop at altitudes as low as 2000 m (6500 ft). It may be due to mild cerebral edema and is characterized by headache plus at least one of the following: fatigue, GI symptoms (anorexia, nausea, vomiting), dizziness, and sleep disturbance. Exertion aggravates the symptoms. Symptoms typically develop 6 to 10 h after ascent and subside in 24 to 48 h. 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 pulmonary edema (HAPE):
HAPE typically develops 24 to 96 h after rapid ascent to > 2500 m (> 8000 ft) and is responsible for most deaths due to AD. HAPE is more common among young men. Long-time high-altitude residents can develop HAPE when they return after a brief stay at low altitude.
Initially, patients have dyspnea on exertion, decreased exertion tolerance, and dry cough. Later, dyspnea is present 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.
High-altitude cerebral edema (HACE):
Marked cerebral edema manifests as headache and diffuse encephalopathy with confusion, drowsiness, stupor, and coma. Gait ataxia is a reliable early warning sign. Seizures and focal deficits (eg, cranial nerve palsy, hemiplegia) are less common. Papilledema and retinal hemorrhage may be present but are not necessary for diagnosis. Coma and death may occur within a few hours.
Peripheral and facial edema is common at high altitude.
Headache, without other symptoms of AMS, is also common.
Retinal hemorrhages may 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; they resolve rapidly without sequelae.
People who have had radial keratotomy may have significant visual disturbances at altitudes > 5000 m (> 16,000 ft) or even as low as 3000 m (10,000 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 of most forms of AD is clinical; laboratory tests are usually unnecessary. In HAPE, hypoxemia is often severe, with pulse oximetry showing 40 to 70% saturation. If obtained, 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.
Patients should halt ascent and reduce exertion until symptoms resolve. Other treatment includes fluids and analgesics for headache. For severe symptoms, descent of 500 to 1000 m (1650 to 3200 ft) is often rapidly effective. Acetazolamide 250 mg po bid may relieve symptoms and improve sleep.
HAPE and HACE:
Patients should descend to low altitude immediately. Helicopter evacuation may be life-saving. If descent is delayed, patients should rest and be given O2. If descent is impossible, O2, drugs, and pressurization in a portable hyperbaric bag help buy time but are not substitutes for descent.
Nifedipine 30 mg slow-release po q 12 h lowers pulmonary artery pressure and is beneficial, although systemic hypotension is a possible complication. Diuretics (eg, furosemide) are contraindicated. The heart is normal in HAPE, and digitalis is of no value. When promptly treated by descent, patients usually recover from HAPE within 24 to 48 h. People who have had one episode of HAPE are likely to have another and should be so warned.
For HACE (and severe AMS)
Dexamethasone 4 to 8 mg initially, followed by 4 mg q 6 h, may help. It should be given po but if this is impossible, dexamethasone may be given IM or IV. Acetazolamide 250 mg po bid may be added.
The most important measure is a slow ascent.Maintaining hydration is important because breathing large volumes of dry air at altitude greatly increases water loss. Alcohol seems to worsen AMS and reduces nocturnal ventilation, thus accentuating sleep disturbance. Although physical fitness enables greater exertion at altitude, it does not protect against any form of AD.
Graded ascent is essential for activity at > 2500 m (> 8000 ft). Sleeping on the first night should be at < 2500 to 3000 m (< 8,000 to 10,000 ft), and climbers should ideally sleep at that altitude for 2 to 3 nights if subsequent higher sleeping altitudes are planned. Each day thereafter, sleeping altitude can be increased by about 300 m (1000 ft), although higher day hikes are acceptable with 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 at low altitude and climbers returning to high altitude should once more follow a graded ascent.
Acetazolamide125 to 250 mg po q 12 h reduces the incidence of AMS. Sustained-release capsules (500 mg once/day) are also available. Acetazolamide can be started on the day of the ascent; it acts by inhibiting carbonic anhydrase and thus increasing ventilation. Acetazolamide 125 mg po at bedtime reduces the amount of periodic breathing (almost universal during sleep at high altitude), thus limiting sharp falls in blood O2. Acetazolamide should not be given to patients allergic to sulfa drugs. Analogs of acetazolamide offer no advantage. 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 po q 6 h is an alternative to acetazolamide.
Low-flow O2 during sleep at altitude is effective but inconvenient and may pose logistic difficulties.
Patients who have had a previous episode of HAPE should consider prophylaxis with sustained-release nifedipine 20 to 30 mg po bid.
Analgesics may prevent high-altitude headache.
Last full review/revision September 2014 by John B. West, MD, PhD, DSc
Content last modified October 2014