Am Fam Physician. 1998 Apr 15;57(8):1907-1914.
See related patient information handout on high-altitude illness, written by the authors of this article.
As more people enjoy the outdoors, high-altitude illness is increasingly becoming a problem that family physicians across the country must treat. High-altitude illness, which usually occurs at altitudes of over 1,500 m (4,921 ft), is caused primarily by hypoxia but is compounded by cold and exposure. It presents as one of three forms: acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). But high-altitude illness can have many other manifestations. Cardinal symptoms include dyspnea on exertion and at rest, cough, nausea, difficulty sleeping, headache and mental status changes. Treatment requires descent, and gradual acclimatization provides the most effective prevention. Acetazolimide is an effective preventive aid and can be used in certain conditions as treatment.
More than ever before, our patients are traveling to the ends of the earth and to the top of world in search of adventure. Every year, thousands go trekking in the Himalayas, climbing in the Rockies and skiing in the Alps. An estimated 34 million people traversed terrain above 2,285 m (7,500 ft) in 1984, and since then that number has grown dramatically.1 Nearly 25 percent of those who travel above an elevation of 2,590 m (8,500 ft) develop manifestations of high-altitude illness.1
How would you counsel a patient who is planning a trip to a high-altitude area? What would you do if one of your patients had a high-altitude illness? This article summarizes the pathophysiology, signs and symptoms, treatment and prevention of acute high-altitude illness.
M.H., a 26-year-old man, and R.M., a 28-year-old man, drive from Los Angeles (sea level) to the trailhead for the Mount Whitney Summit Trail, where the altitude is 2,440 m (8,000 ft). M.H. lives in El Paso, Tex., where the altitude is 1,145 m (3,762 ft), and exercises regularly, while R.M. lives in Los Angeles, is overweight and primarily sedentary.
The two men sleep in the car overnight at the trailhead and begin their ascent the next day. On the first day they hike to the base camp, at 3,660 m (12,000 ft) elevation. Later that day R.M. complains of dyspnea on exertion, lightheadedness, nausea, fatigue and headache. M.H. has fatigue and mild shortness of breath but no other complaints.
On the following morning, after a restless night for R.M., the two men discuss proceeding to the summit versus turning back. Both want to proceed. They begin at 8 a.m. and reach the summit (4,433 m [14,500 ft]) at 2 p.m. Throughout the climb, R.M. complains of worsening symptoms but does not have a cough or pink, frothy sputum, altered consciousness or ataxia. After reaching the summit, the men return to base camp, where R.M. has another restless night.
On the third morning, they return to the trailhead and depart. R.M. later visits his primary care physician, who retrospectively diagnoses acute mountain sickness (AMS) and recommends that R.M. avoid elevations above 3,050 m (10,000 ft).
Hypoxia is the main contributor to high-altitude illness. Atmospheric pressure and the partial pressure of oxygen decrease rapidly at increasing levels above the earth's surface (Table 1).2 The partial pressure of oxygen is also lower as one moves northward. The barometric pressure of Mount Everest (8,850 m [29,028 ft]) is 253 mm Hg at latitude 27 degrees north. However, if Mount Everest were at the same latitude as Mount McKinley (6,200 m [20,320 ft] elevation and 62 degrees north), the barometric pressure would be 222 mm Hg, probably too low for an ascent without oxygen.2 The barometric pressure also fluctuates with the season (it is lower in the winter), the weather and the temperature.
Atmospheric Pressure and PaO2 in Relation to Altitude
|Elevation||Atmospheric pressure (mm Hg)||PaO2 in a young, healthy person (mm Hg)|
90 to 95
2,800 m (9,200 ft)
6,100 m (20,140 ft)
Hypoxia, however, does not act alone. In one study,4 it was found that symptoms of AMS are worse with the combination of normal oxygen and hypobaria (to simulate altitude) than with hypoxia and normal pressure. Several other altitude-related changes contribute directly or indirectly to AMS. Environmental temperature decreases an average of 6.5°C per 1,000 m (3,280 ft) gain in elevation,2 which increases the amount of oxygen required to maintain body temperature. Ultraviolet (UV) light penetration increases 4 percent per 300 m (985 ft) gain in altitude, increasing the danger of snow blindness, sunburn and, in the long-term, skin cancer. UV light also reflects off snow and ice and can produce temperatures of 40°C to 42°C (104°F to 107.6°F) in enclosed spaces, such as mountaineering tents,3 so even heat exhaustion is a danger. Dehydration is often a problem, since insensible losses are increased as a result of hyperventilation and increased work, and since the only way to get water at high altitude is to melt snow or ice.5
During ascent to altitude, chemoreceptors in the carotid body detect the decreasing partial pressure of arterial oxygen (PaO2) and stimulate the hypoxic ventilatory response.6 This causes hyperventilation, which results in water loss, increased PaO2 and decreased partial pressure of arterial carbon dioxide (PaCO2). Fluctuations in PaO2 and PaCO2 cause nocturnal periodic breathing (Cheyne-Stokes respiration). Respiratory alkalosis results, but the pH is usually stabilized within 24 to 48 hours by bicarbonate excretion from the kidneys.
Since the PaO2 is low because of atmospheric hypoxia and the blood volume is low because of dehydration, circulating levels of catecholamines increase, causing increased heart rate, blood pressure and venous tone. Clinicians can use this tachycardic response to roughly estimate how well a person is acclimatizing. Initially at high altitude, a person's pulse on awakening in the morning rises 20 percent or more, but after a week at altitude, it should be declining toward normal levels.1
Hypoxia also increases the contractility of pulmonary vessels, thereby increasing pulmonary artery pressure and cerebral blood flow. Hypocapnea balances this change by decreasing the cerebral blood flow. To improve the blood's oxygen-carrying ability, hemoconcentration occurs immediately, resulting in increased erythropoietin levels within two hours and new red blood cells within four days.2 Increased 2,3-diphosphoglycerate (2,3-DPG) production shifts the oxygen–hemoglobin dissociation curve to the right, resulting in improved tissue release of oxygen and acting against the leftward shift caused by alkalosis and hypocarbia.7 Capillary density in skeletal muscle also increases.
These acute adaptations (they occur within hours) are remarkably effective: five of the 10 people reported from 1947 to 1993 to have stowed away without survival gear in the wheel wells of commercial airliners that flew as high as 11,900 m (39,000 ft) on transcontinental flights survived.8 Together, the acute and chronic adaptations allow humans both to ascend to high altitudes and to reside at such altitudes.
General Characteristics of High-Altitude Illness
High-altitude illness is a spectrum of disease related to hypobaric hypoxia and its consequences. It includes AMS, high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE). The diagnosis is based primarily on the history and physical examination. When available, chest radiographs may show multiple small patchy infiltrates,9 and the electrocardiogram may show a right strain pattern.
Acute Mountain Sickness
The first description of AMS, written in 37 to 32 b.c., is attributed to To Kan, a Chinese governmental official, who noted, “A man's face turns pale, his head aches and he begins to vomit” when crossing the Himalayan Kilak Pass.10 The occurrence of AMS depends primarily on the rate of ascent, the altitude attained and the individual person's susceptibility. AMS affects 15 to 30 percent of Colorado resort skiers, 50 percent of climbers on Mount McKinley, 70 percent of climbers on Mount Rainier, and 25 to 50 percent of climbers who trek to the base of Mount Everest.1
Symptoms include headache, fatigue, weakness, gastrointestinal upset, difficulty sleeping and lightheadedness (Table 2).11 According to the 1991 International Hypoxia Symposium at Lake Louise, Canada, AMS can be diagnosed when headache and one other symptom are present in the setting of a recent gain in altitude.3,11,12 The headache is probably caused by a mild increase in intracranial pressure and is typically throbbing, bitemporal or occipital, worse at night or in the early morning, and worse with the Valsalva maneuver or when bending forward. Dyspnea on exertion is common at altitude, but dyspnea at rest indicates more severe AMS or HAPE. Cough and ataxia may occur in severe AMS but are also symptoms of HAPE and HACE, respectively.3 Similar symptoms may occur as a result of viral illness, hangover, exhaustion or dehydration. Carbon monoxide poisoning, which may be caused by the use of cooking stoves in the small windproof tents used by mountaineers, may mimic AMS.
Consensus on the Definition of High-Altitude Illnesses*
Acute mountain sickness (AMS)
Headache, plus at least one of the following:
Fatigue or weakness
Gastrointestinal symptoms (nausea, vomiting or anorexia)
Dizziness or lightheadedness
High-altitude pulmonary edema (HAPE)
At least two of the following symptoms:
Dyspnea at rest
Weakness or decreased exercise performance
Chest tightness or congestion
At least two of the following signs:
Audible rales or wheezing in at least one lung field
High-altitude cerebral edema (HACE)
Either the presence of a change in mental status and/or ataxia in a person with AMS or the presence of both mental status changes and ataxia in a person without AMS
*—Symptoms and signs occur in the setting of a recent gain in altitude.
Information from reference 11.
The treatment of AMS consists of stopping the ascent and allowing acclimatization at the same altitude. In addition, therapy should be started with oral acetazolamide (Diamox), a carbonic anhydrase inhibitor with weak diuretic properties; the dosage is 125 to 250 mg twice daily (Table 3).1–3,9 Alternatively, the affected person can descend 460 m (1,500 ft) or more until symptoms resolve, depending on the severity of AMS. The ascent can usually be resumed once symptoms have resolved. Aspirin is useful to treat headache, and nonbarbiturate sedatives can improve sleep. There is no evidence to support counseling a patient to avoid high altitudes after an episode of AMS.
Treatment of High-Altitude Illness
Acute mountain sickness (AMS)
Stop ascent, acclimatize at the same altitude; give acetazolamide (Diamox), 125 to 250 mg orally two times a day. Or descend 460 m (1,500 ft) or more until symptoms have resolved.
High-altitude pulmonary edema (HAPE)
Descend at least 610 m (2,000 ft) and keep descending until the symptoms have resolved. If that is impossible, temporize with oxygen, 4 to 6 L per minute; give nifedipine (Adalat, Procardia),10 mg by mouth initially, then 30 mg by mouth twice daily; keep the person warm and minimize his or her exertion. Use a Gamow or Chamberlite bag for hyperbaric therapy if available.
High-altitude cerebral edema (HACE)
Descend at least 610 m (2,000 ft) and keep descending until symptoms have resolved. If that is impossible, temporize with oxygen, 4 L per minute; give dexamethasone, 4 mg orally every 6 hours, and hyperbaric therapy as above.
High-Altitude Pulmonary Edema
Up to 15 percent of travelers to altitudes over 2,500 m (8,202 ft) will develop HAPE, depending on the traveler's age and sex, and the rate of ascent.13 HAPE is a form of noncardiogenic pulmonary edema and is associated with marked pulmonary hypertension. It is more common in persons under 20 years of age.14
The Lake Louise symposium proposed diagnostic criteria for HAPE. In the setting of a recent gain in altitude, at least two of the following symptoms must be present: dyspnea at rest, cough, weakness or decreased exercise performance, chest tightness or congestion. In addition, at least two of the following signs must be present: rales or wheezing in at least one lung field (usually the right middle lobe), central cyanosis, tachycardia or tachypnea.11,14
HAPE usually occurs at night, one to three days after an ascent is begun. It is a medical emergency and the most common cause of death from high altitude.2
The treatment of choice is immediate descent of at least 610 m (2,000 ft) until the symptoms have resolved. A repeat ascent should not be attempted soon after the episode, because up to two weeks may be required for the person to regain full strength.2 If HAPE is severe and the person cannot descend, he or she should rest, keep warm, receive oxygen at a rate of 4 to 6 L per minute and be given oral nifedipine (Adalat, Procardia), 10 mg once and then 30 mg (sustained-release form) every 12 hours. If available, portable hyperbaric bags, such as the Gamow bag or the Chamberlite bag, can be used.15 These bags can provide temporary treatment for severe AMS, HACE and HAPE, before descent is achieved.
There is no definitive treatment for HAPE other than descent. If HAPE is diagnosed early and treated appropriately, patients usually recover completely. The mortality rate for untreated patients can be as high as 44 percent.1 In one study, 66 percent of HAPE patients had a recurrence of HAPE on subsequent climbs.1
High-Altitude Cerebral Edema
HACE constitutes the progression of severe AMS or HAPE to include involvement of the brain, causing encephalopathy. It is probably related to vasogenic cerebral edema, resulting in increased intracranial pressure. Patients often have severe lassitude and altered consciousness, but the most sensitive indicator for HACE may be ataxia.16 The tandem gait test is the best test for evaluating this; HACE does not affect finger-to-nose tests for ataxia.12 Focal neurologic signs are rare. While mild AMS may progress to HACE with unconsciousness within 12 hours, HACE usually requires one to three days to develop. The symptoms of HACE, like HAPE, are worse at night.
Treatment of HACE requires immediate descent of at least 610 m (2,000 ft) and if improvement does not occur, descent should continue until the symptoms have resolved. If immediate descent is impossible, oxygen should be administered at a rate of 2 to 4 L per minute, along with dexamethasone (Decadron), 4 mg orally or intramuscularly every six hours, and hyperbaric therapy (as mentioned in the treatment of HAPE) until descent is possible.
Sequelae from HACE can last weeks but, eventually, patients usually recover completely. Overall mortality in untreated patients is 13 percent, which rises to 60 percent if coma occurs.16
Other Altitude-Related Disease
Other Altitude-Related Disorders
Maintain good fluid intake to reduce hemoconcentration; spontaneously resolves
Treat with a diuretic in the absence of AMS, HACE or HAPE; condition spontaneously resolves on descent
Venous stasis and thrombotic complications
Stay active, keep well hydrated and descend if needed
High-altitude pharyngitis and bronchitis
Suck on hard candy, breathe through a face mask and drink plenty of fluids
Ultraviolet keratitis (snow blindness)
Remove contact lenses, patch affected eye, use oral analgesics to decrease pain; prevent by wearing sunglasses
High-altitude retinopathy is related to hypoxia17 and is manifested by cotton-wool exudates, tortuosity and dilation of retinal veins and scotomata. It commonly occurs at altitudes over 5,000 m (16,000 ft), is usually asymptomatic and usually resolves after one to two weeks, even if the patient remains at altitude.1
Peripheral edema may develop in the hands, face and ankles, and can be treated with diuretics, in the absence of AMS.2
Thrombotic events such as a pulmonary embolus, stroke and venous thrombosis are a greater danger at high altitudes than at sea level, probably because of the combination of dehydration, polycythemia, cold and constrictive clothing. Bad weather can force prolonged periods of inactivity, causing venous stasis, which may also contribute to thrombosis. To avoid venous stasis and a thrombotic event, patients should be advised to keep active and well hydrated, and to descend immediately if serious complications arise.
At high altitude, active immunity and B cell function remain normal, while T cell function is impaired.1 This effect is probably related to the release of adrenocorticotropic hormone (ACTH), cortisol and endorphins, and results in increased susceptibility to bacterial (but not viral) infections. People at altitude, especially those with AMS, show an increased incidence of infectious symptoms, such as coryza, cough, sore throat and diarrhea. But it is difficult to know if such symptoms represent a real increase in infection or just overlapping symptoms of high-altitude illness.12
High-altitude pharyngitis and bronchitis are almost universal in people who spend over two weeks at altitudes higher than approximately 5,500 m (18,000 ft). Pharyngitis and bronchitis are probably caused by the effect of cold dry air on the respiratory mucosa, especially with hyperventilation and mouth breathing. Vasomotor rhinitis is common and can be treated with a decongestant nasal spray. Bronchitis can cause coughing fits, which can be disabling. Note that these symptoms are similar to those of early HAPE. Patients should be advised to wear a face mask, suck on hard candy and drink plenty of fluids to decrease these problems.3
Ultraviolet keratitis (snow blindness) occurs when bright sun reflecting off snow causes corneal burns. Damage can occur in one hour, but symptoms may not develop for six to 12 hours. Patients have severe pain, a “gritty” sensation in the eyes, photophobia, tearing, chemosis, conjunctival erythema and eyelid swelling. The keratitis usually resolves spontaneously in 24 hours, but treatment includes patching of the affected eye, rest and oral nonsteroidal anti-inflammatory drugs to control pain. Snow blindness can be prevented by wearing sunglasses.
Effects of High Altitude on Chronic Illness
Contraindications and Cautions for High-Altitude Travel
Uncompensated congestive heart failure
Sickle cell anemia
Compensated congestive heart failure
Sickle cell trait
Seizure disorders (not controlled on medication)
Stable angina or coronary artery disease
Patients with sickle cell anemia should not ascend to high altitudes because they can have a sickle crisis at elevations as low as 1,500 m (4,900 ft). Splenic infarction syndrome is also more common at altitude. The incidence of problems in persons with sickle trait is low.3
Older patients with coronary artery disease do not appear to be at increased risk of AMS on ascent to 2,440 to 3,050 m (8,000 to 10,000 ft).18,19 In one study, active older travelers with preexisting asymptomatic cardiovascular and pulmonary disease traveled to moderate altitudes without exacerbation of their disorders.19 Exercise testing may be a consideration in patients who are at risk of or who have documented atherosclerotic heart disease. (Authorities in Argentina require the results of an exercise test for everyone applying to climb Mount Aconcagua.1) Patients with minimal symptoms of angina who are taking few medications and can exercise for over nine minutes on a Bruce protocol will probably tolerate high altitude from a cardiovascular standpoint. However, exercise tolerance at low altitude does not predict a patient's immunity from AMS at high altitude.1 Patients with essential hypertension are not at increased risk for altitude sickness.2
Many patients with asthma report improvement in breathing at high altitude, possibly because of the lack of allergens, but some have an increase in cold- or exercise-induced bronchospasm. Investigators in India found that forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) decline at high altitude, probably because of increased upper airway resistance.20 Patients with mild chronic obstructive pulmonary disease (COPD) will probably have no trouble without supplemental oxygen at high or very high altitudes. Patients with moderate COPD, however, should exercise caution, and high mountaineering is contraindicated in patients with marked arterial desaturation and carbon dioxide retention.1 [corrected] Few data from mountaineering literature are available to define mild, moderate and severe COPD, but the travel medicine literature uses room-air PaCO2 of greater than 50 mm Hg and PaO2 of less than 55 percent as contraindications to airline travel without supplemental oxygen (cabin altitude of 2,440 m [8,000 ft]). These figures may serve as guidelines for high-altitude travelers.21
With regard to pregnancy, exposure to moderate altitude does not seem to increase the incidence of spontaneous abortion, abruptio placenta or placenta previa.4 Some authorities advise against pregnant patients trekking in remote areas above 2,440 m (8,000 ft).22
Being physically fit does not affect the incidence of AMS,23 but physical fitness does improve exercise tolerance. It also may help to prevent HACE and HAPE by improving the hemodynamic response to exercise.9 People going to a high altitude should keep well hydrated by forcing fluids and avoiding alcohol and drugs.
On expeditions, mountaineers should use graded ascents to acclimatize. One recommendation is to begin below 2,440 m (8,000 ft), rest the first day and ascend 305 m (1,000 ft) per day.9 The altitude where each night is spent should be no more than 305 m (1,000 ft) above the altitude of the previous night, and two nights should be spent at the same altitude every three days.24 Descent should be undertaken if symptoms occur. Sleep at night should take place at least 460 m (1,500 ft) lower than the altitude climbed during the day (“climb high, sleep low”).
Another option is the staged ascent. This involves traveling to an intermediate altitude and camping for several nights before continuing the ascent to the target altitude. For example, if a person is planning a prolonged trek at 3,000 to 4,300 m (10,000 to 14,000 ft), he or she should acclimatize at 1,800 to 2,500 m (6,000 to 8,000 ft) two to four days beforehand.
Acetazolamide can reduce the severity of AMS symptoms. The dosage is 250 to 1,000 mg per day, starting 12 to 24 hours before the climb and continuing for three to four days. Dexamethasone is useful for preventing and treating AMS and for treating HACE, but because of its side effects, including euphoria and glucosuria, it is best used for the treatment of HACE and for prophylaxis in acetazolamideintolerant (and sulfa-allergic) persons.2
For more information on high-altitude medicine, visit the Himalayan Rescue Association Nepal home page at http://www.gorge.net/hamg/AMS-LakeLouise.html
1. Bezruchka S. High altitude medicine. Med Clin North Am. 1992;76:1481–97.
2. High-altitude medicine. In: Auerbach PS, ed. Wilderness medicine: management of wilderness and environmental emergencies. 3d ed. St Louis: Mosby, 1995:1–37.
3. Zafren K, Honigman B. High-altitude medicine. Emerg Med Clin North Am. 1997;15:191–222.
4. Roach RC, Loeppky JA, Icenogle MV. Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia. J Appl Physiol. 1996;81:1908–10.
5. Westerterp KR, Robach P, Wouters L, Richalet JP. Water balance and acute mountain sickness before and after arrival at high altitude of 4,350 m. J Appl Physiol. 1996;80:1968–72.
6. McMurray SJ. High altitude medicine for family physicians. Can Fam Physician. 1994;40:711–8.
7. Roberts MJ. Acute mountain sickness—experience on the roof of Africa expedition and military implications. J R Army Med Corps. 1994;140:49–51.
8. Veronneau SJ, Mohler SR, Pennybaker AL, Wilcox BC, Sahiar F. Survival at high altitudes: wheel-well passengers. Aviat Space Environ Med. 1996;67:784–6.
9. Hughes PJ. Altitude sickness. In: Rakel RE, ed. Saunders' Manual of medical practice. Philadephia: Saunders, 1996:1184–5.
10. Porcelli MJ, Gugelchuk GM. A trek to the top: a review of acute mountain sickness. J Am Osteopath Assoc. 1995;95:718–20.
11. Dietz T. The Lake Louise consensus on the definition of altitude illness. Himalayan Rescue Association, Nepal. http://www.gorge.net/hra/us/AMS-LakeLouise.html (Accessed November 11, 1997).
12. Murdoch DR. Symptoms of infection and altitude illness among hikers in the Mount Everest region of Nepal. Aviat Space Environ Med. 1995;66:148–51.
13. Staton GW Jr, Ingram RH Jr. Pulmonary edema. In: Rubenstein E, ed. Scientific American medicine. New York: Scientific American, 1993:14.
14. Hultgren HN. High-altitude pulmonary edema: current concepts. Annu Rev Med. 1996;47:267–84.
15. Shimada H, Morita T, Kunimoto F, Saito S. Immediate application of hyperbaric oxygen therapy using a newly devised transportable chamber. Am J Emerg Med. 1996;14:412–5.
16. Tom PA, Garmel GM, Auerbach PS. Environment-dependent sports emergencies. Med Clin North Am. 1994;78:305–25.
17. Lang GE, Kuba GB. High-altitude retinopathy. Am J Ophthalmol. 1997;123:418–20.
18. Alexander JK. Coronary problems associated with altitude and air travel. Cardiol Clin. 1995;13:271–8.
19. Roach RC, Houston CS, Honigman B, Nicholas RA, Yaron M, Grissom CK, et al. How well do older persons tolerate moderate altitude? West J Med. 1995;162:32–6.
20. Basu CK, Selvamurthy W, Bhaumick G, Gautam RK, Sawhney RC. Respiratory changes during initial days of acclimatization to increasing altitudes. Aviat Space Environ Med. 1996;67:40–5.
21. Bia FJ, Barry M. Special health considerations for travelers. Med Clin North Am. 1992;76:1295–312.
22. Rose SR. Pregnancy and travel. Emerg Med Clin North Am. 1997;15:93–111.
23. Honigman B, Read M, Lezotte D, Roach RC. Sealevel physical activity and acute mountain sickness at moderate altitude. West J Med. 1995;163:117–21.
24. A'Court CH, Stables RH, Travis S. Doctor on a mountaineering expedition. BMJ. 1995;310:1248–52.
Copyright © 1998 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact email@example.com for copyright questions and/or permission requests.