The low oxygen levels found at high altitudes can cause problems for travelers who are going to destinations higher than 8,000 feet above sea level.

Ascend Gradually

If you plan to travel to a higher altitude and sleep there, you can get sick if you don’t ascend gradually:

• Do not go from a low altitude to sleeping at higher than 9,000 feet above sea level in one day. Instead, spend a few days at 8,000–9,000 feet before proceeding to a higher altitude to give your body time to adjust to the low oxygen levels.
• Once you are above 9,000 feet, increase your sleeping altitude by no more than 1,600 feet per day. For every 3,300 feet you ascend, try to spend a day without ascending further.
• Do not drink alcohol or do heavy exercise for at least the first 48 hours after you arrive at an altitude above 8,000 feet.
• As an alternative, consider taking a day trip to a higher altitude and then returning to a lower altitude to sleep.

Sometimes your itinerary may not allow gradual ascent. If this is the case, talk to your doctor about prescribing a medicine to prevent altitude illness. You should also be familiar with the symptoms of altitude illness so that you can take steps to prevent it from becoming more severe. Many high-altitude destinations are remote and lack access to medical care, so preventing altitude illness is better than getting sick and needing emergency treatment.

Altitude Illness

The symptoms of altitude illness are similar to those of a hangover: headache, tiredness, lack of appetite, nausea, and vomiting. Children who cannot yet talk may just seem fussy. Mild cases can be treated by alleviating symptoms (such as with painkillers for a headache) and should go away on their own within a few days. Medicines are available to shorten the time it takes to get used to high altitude. However, people with altitude illness should not continue to ascend until they have gotten used to the altitude. A person whose symptoms are getting worse while resting at the same altitude must descend or risk serious illness or death.

One severe consequence of altitude illness is swelling of the brain (high-altitude cerebral edema [HACE]). Symptoms include extreme fatigue, drowsiness, confusion, and loss of coordination. HACE is rare, but it can be fatal. If it develops, the person must immediately descend to a lower altitude.

Swelling of the lungs (high-altitude pulmonary edema [HAPE]) is another severe consequence of altitude illness. Symptoms include shortness of breath, weakness, and cough. A person with HAPE must also descend and will likely need oxygen.

Preexisting Medical Conditions

People with pre-existing medical conditions should talk with a doctor before traveling to high altitudes:

• People with heart or lung disease should talk to a doctor who is familiar with high-altitude medicine before their trip.
• People with diabetes need to be aware that their illness may be difficult to manage at high altitudes. Pregnant women can make brief trips to high altitudes, but they should talk with their doctor because they may be advised not to sleep at altitudes above 12,000 feet.

The high-altitude environment exposes travelers to cold, low humidity, increased ultraviolet radiation, and decreased air pressure, all of which can cause problems. The biggest concern, however, is hypoxia. At 10,000 ft (3,000 m), for example, the inspired PO2 is only 69% of sea-level value. The magnitude of hypoxic stress depends on altitude, rate of ascent, and duration of exposure. Sleeping at high altitude produces the most hypoxemia; day trips to high altitude with return to low altitude are much less stressful on the body. Typical high-altitude destinations include Cusco (11,000 ft; 3,300 m), La Paz (12,000 ft; 3,640 m), Lhasa (12,100 ft; 3,650 m), Everest Base Camp (17,700 ft; 5,400 m), and Kilimanjaro (19,341 ft; 5,895 m).

The human body adjusts very well to moderate hypoxia, but requires time to do so. The process of acute acclimatization to high altitude takes 3–5 days; therefore, acclimatizing for a few days at 8,000–9,000 ft (2,500– 2,750 m) before proceeding to a 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.

Tips for acclimatization

• Ascend gradually, if possible. Avoid going directly from low altitude to more than 9,000 ft (2,750 m) sleeping altitude in 1 day. Once above 9,000 ft (2,750 m), move sleeping altitude no higher than 1,600 ft (500 m) per day, and plan an extra day for acclimatization every 3,300 ft (1,000 m).
• Consider using acetazolamide to speed acclimatization, if abrupt ascent is unavoidable.
• Avoid alcohol for the first 48 hours.
• Participate in only mild exercise for the first 48 hours.
• Having a high-altitude exposure at more than 9,000 ft (2,750 m) for 2 nights or more, within 30 days before the trip, is useful.

High Altitude Effects

An increase in altitude results in a decrease in atmospheric pressure. Although the proportion of oxygen relative to gases in the atmosphere remains at 21 percent, its partial pressure decreases (image). As a result, it is more difficult for a body to achieve the same level of oxygen saturation at high altitude than at low altitude, due to lower atmospheric pressure. In fact, hemoglobin saturation is lower at high altitudes compared to hemoglobin saturation at sea level. For example, hemoglobin saturation is about 67 percent at 19,000 feet above sea level, whereas it reaches about 98 percent at sea level.

As you recall, partial pressure is extremely important in determining how much gas can cross the respiratory membrane and enter the blood of the pulmonary capillaries. A lower partial pressure of oxygen means that there is a smaller difference in partial pressures between the alveoli and the blood, so less oxygen crosses the respiratory membrane. As a result, fewer oxygen molecules are bound by hemoglobin. Despite this, the tissues of the body still receive a sufficient amount of oxygen during rest at high altitudes. This is due to two major mechanisms. First, the number of oxygen molecules that enter the tissue from the blood is nearly equal between sea level and high altitudes. At sea level, hemoglobin saturation is higher, but only a quarter of the oxygen molecules are actually released into the tissue. At high altitudes, a greater proportion of molecules of oxygen are released into the tissues. Secondly, at high altitudes, a greater amount of BPG is produced by erythrocytes, which enhances the dissociation of oxygen from hemoglobin. Physical exertion, such as skiing or hiking, can lead to altitude sickness due to the low amount of oxygen reserves in the blood at high altitudes. At sea level, there is a large amount of oxygen reserve in venous blood (even though venous blood is thought of as “deoxygenated”) from which the muscles can draw during physical exertion. Because the oxygen saturation is much lower at higher altitudes, this venous reserve is small, resulting in pathological symptoms of low blood oxygen levels. You may have heard that it is important to drink more water when traveling at higher altitudes than you are accustomed to. This is because your body will increase micturition (urination) at high altitudes to counteract the effects of lower oxygen levels. By removing fluids, blood plasma levels drop but not the total number of erythrocytes. In this way, the overall concentration of erythrocytes in the blood increases, which helps tissues obtain the oxygen they need.

Acute mountain sickness (AMS), or altitude sickness, is a condition that results from acute exposure to high altitudes due to a low partial pressure of oxygen at high altitudes. AMS typically can occur at 2400 meters (8000 feet) above sea level. AMS is a result of low blood oxygen levels, as the body has acute difficulty adjusting to the low partial pressure of oxygen. In serious cases, AMS can cause pulmonary or cerebral edema. Symptoms of AMS include nausea, vomiting, fatigue, lightheadedness, drowsiness, feeling disoriented, increased pulse, and nosebleeds. The only treatment for AMS is descending to a lower altitude; however, pharmacologic treatments and supplemental oxygen can improve symptoms. AMS can be prevented by slowly ascending to the desired altitude, allowing the body to acclimate, as well as maintaining proper hydration.

Acclimatization

Especially in situations where the ascent occurs too quickly, traveling to areas of high altitude can cause AMS. Acclimatization is the process of adjustment that the respiratory system makes due to chronic exposure to a high altitude. Over a period of time, the body adjusts to accommodate the lower partial pressure of oxygen. The low partial pressure of oxygen at high altitudes results in a lower oxygen saturation level of hemoglobin in the blood. In turn, the tissue levels of oxygen are also lower. As a result, the kidneys are stimulated to produce the hormone erythropoietin (EPO), which stimulates the production of erythrocytes, resulting in a greater number of circulating erythrocytes in an individual at a high altitude over a long period. With more red blood cells, there is more hemoglobin to help transport the available oxygen. Even though there is low saturation of each hemoglobin molecule, there will be more hemoglobin present, and therefore more oxygen in the blood. Over time, this allows the person to partake in physical exertion without developing AMS.

Inadequate acclimatization may lead to altitude illness in any traveler going to 8,000 ft (2,500 m) or higher, and sometimes even at lower altitude. Susceptibility and resistance to altitude illness are genetic traits, and no simple screening tests are available to predict risk. Risk is not affected by training or physical fitness. Children are equally susceptible as adults; people aged >50 years have slightly lower risk. How a traveler has responded to high altitude previously is the most reliable guide for future trips if the altitude and rate of ascent are similar, but this is not infallible. Given certain baseline susceptibility, risk is largely influenced by the altitude, rate of ascent, and exertion (see table below). Creating 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. The goal for the traveler may not be to avoid all symptoms of altitude illness but to have no more than mild illness.

Some common destinations such as the ones mentioned above require rapid ascent by airplane to >3,400 meters and thus place travelers in the high-risk category (see table below). Chemoprophylaxis may be necessary for these travelers, in addition to 2–4 days of acclimatization before going higher. In some cases, such as Cuzco and La Paz, the traveler can descend to altitudes much lower than the airport to sleep.

Risk categories for acute mountain sickness

Preexisting Medical Problems

Travelers with medical conditions, such as heart failure, myocardial ischemia (angina), sickle cell disease, any form of pulmonary insufficiency or preexisting hypoxemia, or obstructive sleep apnea (OSA) should consult a physician familiar with high-altitude medical issues before undertaking high-altitude travel (see table below). The risk for new ischemic heart disease in previously healthy travelers does not appear to be increased at high altitudes. Patients with asthma, hypertension, atrial arrhythmia, and seizure disorders that are well controlled at low altitude generally do well at high altitude. All patients with OSA should receive acetazolamide; those with mild to moderate OSA may do well without their CPAP machines, while those with severe OSA should avoid altitude travel unless given supplemental oxygen in addition to their CPAP. People with diabetes can travel safely to high altitudes, 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 read accurately at high altitudes.

Most people do not have visual problems at high altitudes. However, at very high altitudes some people who have had radial keratotomy may develop acute farsightedness and be unable to care for 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 altitudes during pregnancy. However, it may be prudent to recommend that pregnant women do not stay at sleeping altitudes higher than 10,000 ft (3,048 m). In addition, the pregnancy should be verified as low risk and the mother in good health. The dangers of having a pregnancy complication in remote, mountainous terrain should also be discussed.

Ascent risk associated with various underlying medical conditions

Altitude illness is divided into 3 syndromes: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE).

Acute Mountain Sickness

AMS is the most common form of altitude illness, affecting, for example, 25% of all visitors sleeping above 8,000 ft (2,500 m) in Colorado. Symptoms are similar to 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 12–48 hours of acclimatization.

High-Altitude Cerebral Edema

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

High-Altitude Pulmonary Edema

HAPE can occur by itself or in conjunction with AMS and HACE; incidence is 1 per 10,000 skiers in Colorado and up to 1 per 100 climbers at more than 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 is life-saving. HAPE can be more rapidly fatal than HACE.

Acute Mountain Sickness/High-Altitude Cerebral Edema

The differential diagnosis of AMS/HACE includes dehydration, exhaustion, hypoglycemia, hypothermia, or hyponatremia. Focal neurologic symptoms, or seizures, are rare in HACE and should lead to suspicion of an intracranial lesion or seizure disorder. Patients with AMS can descend ≥300 m, and symptoms will rapidly abate. Alternatively, supplemental oxygen at 2 L per minute will relieve headache quickly and resolve AMS over hours, but it is rarely available. People with AMS can also safely remain at their current altitude and treat symptoms with nonopiate analgesics and antiemetics, such as ondansetron. They may also take acetazolamide, which speeds acclimatization and effectively treats AMS, but is better for prophylaxis than treatment. Dexamethasone is more effective than acetazolamide at rapidly relieving the symptoms of moderate to severe AMS. If symptoms are getting worse while the traveler is resting at the same altitude, or in spite of medication, he or she must descend.

HACE is an extension of AMS characterized by neurologic findings, particularly ataxia, confusion, or altered mental status. HACE may also occur in the presence of HAPE. People developing HACE in populated areas with access to medical care can be treated at altitude with supplemental oxygen and dexamethasone. In remote areas, descent should be initiated in any person suspected of having HACE. If descent is not feasible because of logistical issues, supplemental oxygen or a portable hyperbaric chamber in addition to dexamethasone can be lifesaving.

High-Altitude Pulmonary Edema

Although the progression of decreased exercise tolerance, increased breathlessness, and breathlessness at rest is almost always recognizable as HAPE, the differential diagnosis includes pneumonia, bronchospasm, myocardial infarction, or pulmonary embolism. Descent in this situation is urgent and mandatory, and should be accomplished with as little exertion as is feasible for the patient. If descent is not immediately possible, supplemental oxygen or a portable hyperbaric chamber is critical. Patients with mild HAPE who have access to oxygen (at a hospital or high-altitude medical clinic, for example) may not need to descend to lower elevation and can be treated with oxygen at the current elevation. In the field setting, where resources are limited and there is a lower margin for error, nifedipine can be used as an adjunct to descent, oxygen, or portable hyperbaric therapy. A phosphodiesterase inhibitor may be used if nifedipine is not available, but concurrent use of multiple pulmonary vasodilators is not recommended.

Medications

In addition to the discussion below, recommendations for the usage and dosing of medications to prevent and treat altitude illness are outlined below.

ACETAZOLAMIDE

Acetazolamide 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 arterial oxygenation 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. As a nonantimicrobial sulfonamide, it does not cross-react with antimicrobial sulfonamides. However, it is best avoided by people with history of anaphylaxis to any sulfa. People with history of severe penicillin allergy have occasionally had allergic reactions to acetazolamide. The pediatric dose is 5 mg/kg/day in divided doses, up to 125 mg twice a day.

DEXAMETHASONE

Dexamethasone is effective for preventing and treating AMS and HACE and prevents HAPE as well. Unlike acetazolamide, if the drug is discontinued at altitude before acclimatization, mild rebound can occur. Acetazolamide is preferable to prevent AMS while ascending, with dexamethasone reserved for treatment, as an adjunct to descent. The adult dose is 4 mg every 6 hours. An increasing trend is to use dexamethasone for “summit day” on high peaks such as Kilimanjaro and Aconcagua, in order to prevent abrupt altitude illness.

NIFEDIPINE

Nifedipine prevents HAPE and ameliorates it as well. For prevention, it is generally reserved for people who are particularly susceptible to the condition. The adult dose for prevention or treatment is 30 mg of extended release every 12 hours, or 20 mg every 8 hours.

OTHER MEDICATIONS

Phosphodiesterase-5 inhibitors can also selectively lower pulmonary artery pressure, with less effect on systemic blood pressure. Tadalafil, 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 a day, was shown to reduce AMS in adults in some trials, but it was not effective in others, probably due to variation in ingredients. Ibuprofen 600 mg every 8 hours was recently found to help prevent AMS, although it was not as effective as acetazolamide. However, it is over-the-counter, inexpensive, and well-tolerated.

Recommended medication doses to prevent and treat altitude illness

Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema; IM, intramuscular; IV, intravenous; SR, sustained release.
¹Acetazolamide can also be used at this dose as an adjunct to dexamethasone in HACE treatment, but dexamethasone remains the primary treatment for that disorder.
²Should not be used as monotherapy and should only be used in conjunction with oral medications.

The main point of instructing travelers about altitude illness is not to eliminate the possibility of mild illness but to prevent death or evacuation. Since the onset of symptoms and the clinical course are sufficiently slow and predictable, there is no reason for anyone to die from altitude illness, unless trapped by weather or geography in a situation in which descent is impossible. Three rules can prevent death or serious consequences from altitude illness:

• 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 be beneficial. A foot pump produces an increased pressure of 2 lb/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 about 14 lb (6.5 kg).