Peter H. Hackett, David R. Shlim

Occurrence

The stresses of the high-altitude environment include cold, low humidity, increased ultraviolet (UV) radiation, and decreased air pressure, all of which can cause problems for travelers. The greatest concern, however, is hypoxia. At 10,000 ft (3,000 m), for example, the inspired PO₂ is only 69% of sea-level value. The degree of hypoxic stress depends upon altitude, rate of ascent, and duration of exposure. Sleeping at high altitude produces the greatest hypoxia; day trips to high altitude with return to low altitude are much less stressful on the body.

Acclimatization

The human body adjusts very well to moderate hypoxia, but requires time to do so (Box 2-3). The process of acute acclimatization to high altitude takes 3–5 days; therefore, acclimatizing for a few days at 8,000–9,000 ft before proceeding to higher altitude is ideal. Acclimatization prevents altitude illness, improves sleep, and increases comfort and well-being, although exercise performance will always be reduced compared with low altitude. Increase in ventilation is the most important factor in acute acclimatization; therefore, respiratory depressants must be avoided. Increased red-cell production does not play a role in acute acclimatization.

Risk for Travelers

Inadequate acclimatization may lead to altitude illness in any traveler going to 8,000 ft (2,500 m) or higher. Susceptibility and resistance to altitude illness are genetic traits, and no screening tests are available to predict risk. Risk is not affected by training or physical fitness. Children are equally susceptible as adults; persons >50 years of age have slightly lower risk. How a traveler has responded to high altitude previously is the most reliable guide for future trips but is not infallible. However, given certain baseline susceptibility, risk is greatly influenced by rate of ascent and exertion.

Determining an itinerary that will avoid any occurrence of altitude illness is difficult because of variations in individual susceptibility, as well as in starting points and terrain. Itineraries with a high risk for altitude illness include flying directly to >9,000 ft or rapid hiking ascents, such as climbing Mt. Kilimanjaro. It is best to average no more than 1,000 ft (300 m) ft per day in altitude gain above 12,000 ft (3,660 m).

Examples of high-altitude cities with airports are Cuzco, Peru (11,000 ft; 3,326 m); La Paz, Bolivia (12,000 ft; 3,660 m); and Lhasa, Tibet (12,500 ft; 3,810 m). Travelers flying into these locations may require a period of acclimatization before proceeding higher, and drug prophylaxis may be indicated.

Clinical Presentation

Altitude illness is divided into three syndromes:

• Acute mountain sickness (AMS)
• High-altitude cerebral edema (HACE)
• High-altitude pulmonary edema (HAPE)

Acute Mountain Sickness (AMS)

AMS is the most common form of altitude illness, striking, for example, 25% of all visitors sleeping above 8,000 ft (2,500 m) in Colorado. Symptoms are those of an alcohol hangover: headache is the cardinal symptom, sometimes accompanied by fatigue, loss of appetite, nausea, and, occasionally, vomiting. Headache onset is usually 2–12 hours after arrival at a higher altitude, and often during or after the first night. Preverbal children may develop loss of appetite, irritability, and pallor. AMS generally resolves with 24–72 hours of acclimatization.

High-Altitude Cerebral Edema (HACE)

HACE is a severe progression of AMS and is rare; it is most often associated with pulmonary edema. In addition to AMS symptoms, lethargy becomes profound, with drowsiness, confusion, and ataxia on tandem gait test. A person with HACE requires immediate descent; death from HACE can ensue within 24 hours of developing ataxia if the person fails to descend.

High-Altitude Pulmonary Edema (HAPE)

HAPE can occur by itself or in conjunction with AMS and HACE; incidence is 1/10,000 skiers in Colorado and up to 1 of 100 climbers at >14,000 ft (4,270 m). Initial symptoms are increased breathlessness with exertion, and eventually increased breathlessness at rest, associated with weakness and cough. Oxygen or descent of 1,000 m or more is life-saving. HAPE can be more rapidly fatal than HACE.

Pre-Existing Medical Problems

• Travelers with medical conditions, such as heart failure, myocardial ischemia (angina), sickle cell disease, or any form of pulmonary insufficiency, should be advised to consult a physician familiar with high-altitude medical issues before undertaking high-altitude travel.
• The risk for new ischemic heart disease in previously healthy travelers does not appear to be increased at high altitudes.
• Diabetics can travel safely to high altitude, but they must be accustomed to exercise and carefully monitor their blood glucose. Diabetic ketoacidosis may be triggered by altitude illness and may be more difficult to treat in those on acetazolamide. Not all glucose meters may read accurately at high altitudes.
• Most people do not have visual problems at high altitude. However, at very high altitudes some persons who have had radial keratotomy may develop acute farsightedness and be unable to climb by themselves. LASIK and other newer procedures may produce only minor visual disturbances at high altitudes.
• There are no studies or case reports of harm to a fetus if the mother travels briefly to high altitude during pregnancy. However, it may be prudent to recommend that pregnant women stay at sleeping altitudes of 12,000 ft (3,658 m) if possible. The dangers of having a pregnancy complication in remote, mountainous terrain should also be discussed.

Treatment

Acetazolamide

Acetazolamide (Diamox) prevents AMS when taken before ascent and can speed recovery if taken after symptoms have developed. The drug works by acidifying the blood, which causes an increase in respiration and thus aids acclimatization. An effective dose that minimizes the common side effects of increased urination and paresthesias of the fingers and toes is 125 mg every 12 hours, beginning the day before ascent and continuing the first 2 days at altitude, or longer if ascent continues. Allergic reactions to acetazolamide are uncommon, but the drug is related to sulfonamides and should not be used by sulfa-allergic persons with history of anaphylaxis. A trial dose taken in a safe environment before travel may be useful for those with a more mild allergic history to sulfonamides. People with history of severe penicillin allergy have occasionally had allergic reactions to acetazolamide.

Dexamethasone

Dexamethasone is very effective for prevention and treatment of AMS and HACE, and perhaps HAPE as well. Unlike acetazolamide, rebound can occur if the drug is discontinued at altitude prior to acclimatization. Acetazolamide is preferable to prevent AMS while ascending, with dexamethasone reserved for treatment during descent. Adult dosage is 4 mg every 6 hours.

HAPE is always associated with increased pulmonary artery pressure, and pulmonary vasodilators are useful for preventing and treating HAPE.

Nifedipine

Nifedipine prevents and ameliorates HAPE in persons who are particularly susceptible to the condition. The adult dosage is 20 mg of extended release every 8–12 hours. PDE-5 inhibitors can also selectively lower pulmonary artery pressure, with less effect on systemic blood pressure.

Other Medications

Tadalafil (Cialis), 10 mg twice a day, during ascent can prevent HAPE and is being studied for treatment. When taken before ascent, gingko biloba, 100–120 mg twice daily, was shown to reduce AMS in adults in some trials, but it was not effective in others, probably due to variation in ingredients. Gingko biloba has not yet been compared directly with acetazolamide.

Preventive Measures for Travelers

The main point of instructing travelers about altitude illness is not to prevent any possibility of altitude illness, but to prevent death from altitude illness. The onset of symptoms and clinical course is sufficiently slow and predictable that there is no reason for someone to die from altitude illness unless trapped by weather or geography in a situation in which descent is impossible. The three rules that travelers should be made aware of to prevent death from altitude illness are—

• Know the early symptoms of altitude illness and be willing to acknowledge when they are present.
• Never ascend to sleep at a higher altitude when experiencing symptoms of altitude illness, no matter how minor they seem.
• Descend if the symptoms become worse while resting at the same altitude.

For trekking groups and expeditions going into remote high-altitude areas, where descent to a lower altitude could be problematic, a pressurization bag (such as the Gamow bag) can prove extremely beneficial. A foot pump produces an increased pressure of 2 lbs. per in², mimicking a descent of 5,000–6,000 ft (1,500–1,800 m), depending on the starting altitude. The total packed weight of bag and pump is 6.5 kg.

For most travelers, the best way to avoid altitude illness is by gradual ascent, with extra rest days at intermediate altitudes every 3,000 ft (900 m) or less. If ascent must be rapid, acetazolamide may be used prophylactically, and dexamethasone and pulmonary artery pressure-lowering drugs, such as nifedipine or sildenafil, may be carried for emergencies.

References

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