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Altitude sickness (AS) includes several related syndromes caused by decreased O2 availability at high altitudes. Acute mountain sickness (AMS), the mildest form, is headache plus one or more systemic manifestations. 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. AMS may occur in recreational hikers and skiers in mountains. Diagnosis is clinical. Treatment of mild AMS is with analgesics and acetazolamide. Severe syndromes require descent and supplemental O2 if available. In addition, dexamethasone may be useful for HACE, and nifedipine may be useful for HAPE.
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 ½ 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 some form of AS. Rate of ascent, maximum altitude reached, and sleeping altitude influence the likelihood of developing the disorder.
Risk factors:
Effects of high altitude vary greatly among individuals. But generally, risk is increased by
Risk is greater in people who have had previous AS and in those who live at low altitude (< 900 m [< 3000 ft]). Young children and young adults are probably more susceptible. Disorders such as diabetes, coronary artery disease, and mild COPD are not risk factors for AS, but hypoxia may adversely affect these disorders. Physical fitness is not protective.
Pathophysiology
Acute hypoxia (eg, as occurs during rapid ascent to high altitude in an unpressurized aircraft) alters CNS function within minutes. However, AS results from the body's neurohumoral and hemodynamic responses to hypoxia and develops over hours to days.
The CNS and lungs are primarily affected. In both, elevated capillary pressure, capillary leakage, and consequent edema formation probably occur.
In the lungs, hypoxia-induced elevation of pulmonary artery pressure causes interstitial and alveolar pulmonary edema, resulting in impaired oxygenation. Small-vessel hypoxic vasoconstriction is patchy, causing overperfusion with elevated pressure, capillary wall damage, and capillary leakage in less constricted areas. Various additional mechanisms have been proposed; they include sympathetic overactivity, endothelial dysfunction, decreased alveolar nitric oxide (perhaps due to decreased nitric oxide synthase), and a defect in the amiloride-sensitive Na channel. Some of these factors may have a genetic component.
Pathophysiology in the CNS is less clear but may involve a combination of hypoxia-induced cerebral vasodilation, alteration of the blood-brain barrier, and Na and water retention causing cerebral edema. One hypothesis is that patients with a low ratio of CSF to brain volume are less able to tolerate swelling (ie, by displacement of CSF) and thus are more likely to develop AS. The roles of atrial natriuretic peptide, aldosterone, renin, and angiotensin are unclear.
Acclimatization:
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 to altitudes of up to 3000 m (10,000 ft) in a few days. The higher the altitude, the longer full 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. After many generations at altitude, some ethnic groups have adapted in slightly different ways.
Symptoms and Signs
The clinical forms of AS are not separate entities but parts of a spectrum in which one or more forms may be present in different degrees.
Acute mountain sickness (AMS):
This form is by far the most common and 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, but they occasionally evolve into HAPE, HACE, or both. 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):
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.
High-altitude pulmonary edema (HAPE):
HAPE usually develops 24 to 96 h after rapid ascent to > 2500 m (> 8000 ft) and is responsible for most deaths due to AS. Respiratory infections, even minor ones, appear to increase risk. HAPE is more common among men (unlike other forms of AS). Long-time high-altitude residents can develop HAPE when they return after a brief stay at low altitude.
Initially, patients have dyspnea, decreased exertion tolerance, and dry cough. Pink or bloody sputum and respiratory distress are later findings. On examination, cyanosis, tachycardia, tachypnea, and low-grade fever (< 38.5° C) are common. Focal or diffuse rales (sometimes audible without a stethoscope) are usually present. HAPE may worsen rapidly; coma and death may occur within hours.
Other disorders:
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 alarming symptoms disappear rapidly after descent.
Chronic mountain sickness (Monge's disease) is a disorder that affects long-time high-altitude residents; it is characterized by fatigue, dyspnea, aches and pains, cyanosis, excessive polycythemia, and occasionally thromboembolism. The disorder often involves alveolar hypoventilation. Patients should descend to low altitude; recovery is slow, and return to high altitude may cause recurrence. Repeated phlebotomy can reduce polycythemia, but polycythemia may recur.
Diagnosis
Diagnosis of most forms of AS is clinical; laboratory tests are nonspecific and usually unnecessary. HACE can usually be differentiated from other causes of coma (eg, infection, ketoacidosis) by the history and by absence of fever and nuchal rigidity. If done, blood and CSF studies are normal. 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 (often middle or lower lobes), unlike what is seen in heart failure.
Treatment
AMS:
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 usually rapidly effective. Acetazolamide 250 mg po bid may relieve symptoms and improve sleep.
HAPE and HACE:
Patients should descend to low altitude immediately. 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.
For HAPE, nifedipine 10 mg sublingually followed by a 30-mg slow-release tablet lowers pulmonary artery pressure and is beneficial. 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 may be given po, sc, IM, or IV. Acetazolamide 250 mg po bid may be added.
Prevention
The most important measure is a slow ascent.Drinking extra water is important because breathing large volumes of dry air at altitude greatly increases water loss, and dehydration with some degree of hypovolemia aggravates symptoms. 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 AS.
Ascent:
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 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 reverses quickly. After descent to low levels for more than a few days, acclimatized climbers should once more follow a graded ascent.
Drugs:
Acetazolamide 125 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. Inhaled β-agonists may also be effective.
Analgesics may prevent high-altitude headache.
Last full review/revision April 2009 by John B. West, MD, PhD, DSc
Content last modified February 2012
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