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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 and others traveling to high altitude. High-altitude cerebral edema (HACE) is encephalopathy in people with AMS. High-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema causing severe dyspnea and hypoxemia. Diagnosis is clinical. Treatment of mild AMS is with analgesics and acetazolamide. Severe AMS may require descent and supplemental O2 if available. Both HACE and HAPE are potentially life-threatening and require immediate descent. In addition, dexamethasone may be useful for HACE, and nifedipine or phosphodiesterase inhibitors 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 the following:
Young children and young adults are probably more susceptible. Disorders such as asthma, hypertension, 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.
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.
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.
AMS is by far the most common form of AD.
This disease is unlikely unless altitude is above 2440 m (8000 ft), but it can develop at lower elevations in some highly susceptible people. 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), persistent 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.
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.
HAPE typically develops 24 to 96 h after rapid ascent to > 2500 m (> 8000 ft) and is responsible for most deaths due to AD.
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.
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 over weeks without sequelae, but if they develop, descent is indicated and further ascent is contraindicated until hemorrhages have resolved.
People who have had radial keratotomy 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 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, depending on the elevation at which the individual becomes ill. 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; CT imaging of the head is not usually done.
Patients should halt ascent and reduce exertion until symptoms resolve (1, 2). Other treatment includes fluids and nonopioid 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. Dexamethasone 2 to 4 mg po, IM, or IV q 6 h is also highly effective for treating symptoms of AMS.
Patients should descend to low altitude immediately. Helicopter evacuation may be life-saving (1). If descent is delayed, patients should rest and be given O2. If descent is impossible, O2 (to raise the O2 saturation to > 90%), drugs, and pressurization in a portable hyperbaric bag help buy time but are not substitutes for descent.
For HACE (and severe AMS)
Dexamethasone 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.
Nifedipine 30 mg slow-release po q 12 h lowers pulmonary artery pressure and is beneficial, although systemic hypotension is a possible complication. A phosphodiesterase inhibitor, such as sildenafil (50 mg po q 12 h) or tadalafil (10 mg po q 12 h), 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 ACE inhibitors are of no value. When promptly treated by descent, patients usually recover from HAPE within 24 to 48 h. Exertion should be avoided during descent. People who have had one episode of HAPE are likely to have another and should be so warned.
Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med 25(4S): S4-S14, 2014.
Bartsch P, Swenson ER. Acute high-altitude illnesses. N Engl J Med 368:2294-2302, 2013. DOI: 10.1056/NEJMcp1214870.
Although physical fitness enables greater exertion at altitude, it does not protect against any form of AD. Maintaining adequate fluid intake does not prevent 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.
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 per day and should include a rest day (ie, sleep at the same altitude) every 3 to 4 days. 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.
Acetazolamide125 to 250 mg po q 12 h reduces the incidence of altitude illness. 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 (or 4 mg po q 12 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 in addition consider prophylaxis with sustained-release nifedipine 30 mg po bid or tadalafil 10 mg po bid (3). Salmeterol, 125 micrograms inhaled q 12 h can be added as an adjunct to a pulmonary vasodilator but should not be used as monotherapy for prevention.
Analgesics (eg, acetaminophen, ibuprofen) may prevent high-altitude headache.
Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med 25(4S):S4-S14, 2014.
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.
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 AMS.
AMS causes headache plus fatigue, GI symptoms (anorexia, nausea, vomiting), dizziness, and/or sleep disturbance.
HACE causes ataxia and encephalopathy.
HAPE causes dyspnea, decreased exertion tolerance, and dry cough initially which may become productive.
Diagnose AD based on clinical findings.
Treat mild AMS with fluids, analgesics, sometimes acetazolamide, and by stopping further ascent.
Arrange immediate descent for patients with HACE, HAPE, or very severe AMS.
Prevent AD by gradual ascent and use of acetazolamide.