Author(s): Peter Hackett, David Shlim

Typical high-elevation travel destinations include Colorado ski resorts with lodgings at 8,000–10,000 ft (≈2,440–3,050 m); Cusco, Peru (11,000 ft; ≈3,350 m); La Paz, Bolivia (12,000 ft; ≈3,650 m); Lhasa, Tibet Autonomous Region (12,100 ft; ≈3,700 m); Everest base camp, Nepal (17,700 ft; ≈5,400 m); and Mount Kilimanjaro, Tanzania (19,341 ft; ≈5,900 m). High-elevation environments expose travelers to cold, low humidity, increased ultraviolet radiation, and decreased air pressure, all of which can cause health problems. The biggest concern, however, is hypoxia, due to the decreased partial pressure of oxygen (PO2). At 10,000 ft (≈3,050 m), for example, the inspired PO2 is only 69% of that at sea level; acute exposure to this reduced PO2 can lower arterial oxygen saturation to 88%–91%.

The magnitude and consequences of hypoxic stress depend on the elevation, rate of ascent, and duration of exposure; host genetic factors may also contribute. Hypoxemia is greatest during sleep; day trips to high-elevation destinations with an evening return to a lower elevation are much less stressful on the body. Because of the key role of ventilation, travelers must avoid taking respiratory depressants at high elevations.

Acclimatization

The human body can adjust to moderate hypoxia at elevations ≤17,000 ft (≈5,200 m) but requires time to do so. Some acclimatization to high elevation continues for weeks to months, but the acute process, which occurs over the first 3–5 days following ascent, is crucial for travelers. The acute phase is associated with a steady increase in ventilation, improved oxygenation, and changes in cerebral blood flow. Increased red cell production does not play a role in acute acclimatization, although a decrease in plasma volume over the first few days does increase hemoglobin concentration.

Altitude illness can develop before the acute acclimatization process is complete, but not afterwards. In addition to preventing altitude illness, acclimatization improves sleep, increases comfort and sense of well-being, and improves submaximal endurance; maximal exercise performance at high elevation will always be reduced compared to that at low elevation.

Travelers can optimize acclimatization by adjusting their itineraries to avoid going “too high too fast” (see Box 4-08). Gradually ascending to elevation or staging the ascent provides crucial time for the body to adjust. For example, acclimatizing for a minimum of 2–3 nights at 8,000–9,000 ft (≈2,450–≈2,750 m) before proceeding to a higher elevation is markedly protective against acute mountain sickness (AMS). The Wilderness Medical Society recommends avoiding ascent to a sleeping elevation of ≥9,000 ft (≈2,750 m) in a single day; ascending at a rate of no greater than 1,650 ft (≈500 m) per night in sleeping elevation once above 9,800 ft (≈3,000 m); and allowing an extra night to acclimatize for every 3,300 ft (≈1,000 m) of sleeping elevation gain. These reasonable recommendations can still be too fast for some travelers and annoyingly slow for others.

Altitude Illness

Risk to Travelers

Susceptibility and resistance to altitude illness are, in part, genetically determined traits, but there are no simple screening tests to predict risk. Training or physical fitness do not affect risk. A traveler’s sex plays a minimal role, if any, in determining predisposition. Children are as susceptible as adults; people aged >50 years have slightly less risk. Any unacclimatized traveler proceeding to a sleeping elevation of ≥8,000 ft (≈2,450 m)—and sometimes lower—is at risk for altitude illness. In addition, travelers who have successfully adjusted to one elevation are at risk when moving to higher sleeping elevations, especially if the elevation gain is >2,000–3,000 ft (600–900 m).

How a traveler previously responded to high elevations is the most reliable guide for future trips, but only if the elevation and rate of ascent are similar, and even then, this is not an infallible predictor. In addition to underlying, inherent baseline susceptibilities, a traveler’s risk for developing altitude illness is influenced by 3 main factors: elevation at destination, rate of ascent, and exertion (Table 4-04). Creating an itinerary to 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 might not be to avoid all symptoms of altitude illness but to have no more than mild illness, thereby avoiding itinerary changes or the need for medical assistance or evacuation.

Destinations of Risk

Some common high-elevation destinations require rapid ascent by a non-pressurized airplane to >11,000 ft (≈3,400 m), placing travelers in a high-risk category for AMS. A common travel medicine question is whether to recommend acetazolamide for travelers when gradual or staged acclimatization is not feasible. With rates of altitude illness approaching 30%–40% in these situations, a low threshold for chemoprophylaxis is advised. In some cases (e.g., Cusco and La Paz), travelers can descend to elevations much lower than the airport to sleep for 1–2 nights and then begin their ascent, perhaps obviating the need for medication.

Itineraries along some trekking routes in Nepal, particularly Everest base camps, push the limits of many people’s ability to acclimatize. Even on standard schedules, incidence of altitude illness can approach 30% at the higher elevations. Whenever possible, adding extra days to the trek can make for a more enjoyable and safer climb.

Altitude Illness Syndromes

Altitude illness is divided into 3 syndromes: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Some clinicians consider high-altitude headache a separate entity because isolated headache can occur without the combined symptoms that define AMS.

Acute Mountain Sickness

AMS is the most common form of altitude illness, affecting 25% of all visitors sleeping at elevations >8,000 ft (≈2,450 m) in Colorado.

Diagnosis

Diagnosis of AMS is based on a history of recent ascent to high elevation and the presence of subjective symptoms. AMS symptoms are like those of an alcohol hangover; headache is the cardinal symptom, usually accompanied by ≥1 of the following: anorexia, dizziness, fatigue, nausea, or, occasionally, vomiting. Uncommonly, AMS presents without headache. Symptom onset is usually 2–12 hours after initial arrival at a high elevation or after ascent to a higher elevation, and often during or after the first night. Preverbal children with AMS can develop loss of appetite, irritability, and pallor. AMS generally resolves within 12–48 hours if travelers do not ascend farther.

The condition is typically self-limited, developing and resolving over 1–3 days. Symptoms starting after 3 days of arrival to high elevation and without further ascent should not be attributed to AMS. AMS has no characteristic physical findings; pulse oximetry is usually within the normal range for the elevation, or slightly lower than normal.

The differential diagnosis of AMS is broad; common considerations include alcohol hangover, carbon monoxide poisoning, dehydration, drug intoxication, exhaustion, hyponatremia, and migraine. Travelers with AMS will improve rapidly with descent ≥1,000 ft (≈300 m), and this can be a useful indication of a diagnosis of AMS.

Treatment

Although rarely available, supplemental oxygen at 1–2 liters per minute will relieve headaches within about 30 minutes and resolve other AMS symptoms over hours. The popular small, handheld cans of compressed oxygen can provide brief relief, but contain too little oxygen (5 liters at most) for sustained improvement. Travelers with AMS but without HACE or HAPE (both described below) can remain safely at their current elevation and self-treat with non-opiate analgesics (e.g., ibuprofen 600 mg or acetaminophen 500 mg every 8 hours) and antiemetics (e.g., ondansetron 4 mg orally disintegrating tablets).

Acetazolamide speeds acclimatization and resolves AMS, but is more commonly used and better validated for use as prophylaxis. Dexamethasone is more effective than acetazolamide at rapidly relieving the symptoms of moderate to severe AMS. If symptoms worsen while the traveler is at the same elevation, or despite supplemental oxygen or medication, descent is mandatory.

High-Altitude Cerebral Edema

As an encephalopathy, HACE is considered “end stage” AMS. Fortunately, HACE is rare, especially at elevations <14,000 ft (≈4,300 m). HACE is often a secondary consequence of the severe hypoxemia that occurs with HAPE.

Diagnosis

Unlike AMS, HACE presents with neurological findings, particularly altered mental status, ataxia, confusion, and drowsiness, similar to alcohol intoxication. Focal neurologic findings and seizures are rare in HACE; their presence should lead to suspicion of an intracranial lesion, a seizure disorder, or hyponatremia. Other considerations for the differential diagnosis include carbon monoxide poisoning, drug intoxication, hypoglycemia, hypothermia, and stroke. Coma can ensue within 24 hours of onset.

Treatment

In populated areas with access to medical care, HACE can be treated with supplemental oxygen and dexamethasone. In remote areas, initiate descent for anyone suspected of having HACE, in conjunction with dexamethasone and oxygen, if available. If descent is not feasible, supplemental oxygen or a portable hyperbaric device, in addition to dexamethasone, can be lifesaving. Coma is likely to ensue within 12–24 hours of the onset of ataxia in the absence of treatment or descent.

High-Altitude Pulmonary Edema

HAPE can occur by itself or in conjunction with AMS and HACE; incidence is roughly 1 per 10,000 skiers in Colorado, and ≤1 per 100 climbers at >14,000 ft (≈4,300 m).

Diagnosis

Early diagnosis is key; HAPE can be more rapidly fatal than HACE. Initial symptoms include chest congestion, cough, exaggerated dyspnea on exertion, and decreased exercise performance. If unrecognized and untreated, HAPE progresses to dyspnea at rest and frank respiratory distress, often with bloody sputum. This typical progression over 1–2 days is easily recognizable as HAPE, but the condition sometimes presents only as central nervous system dysfunction, with confusion and drowsiness.

Rales are detectable in most victims. Pulse oximetry can aid in making the diagnosis; oxygen saturation levels will be at least 10 points lower in HAPE patients than in healthy people at the same elevation. Oxygen saturation values of 50%–70% are common. The differential diagnosis for HAPE includes bronchospasm, myocardial infarction, pneumonia, and pulmonary embolism.

Treatment

In most circumstances, descent is urgent and mandatory. Administer oxygen, if available, and exert the patient as little as possible. If immediate descent is not an option, use of supplemental oxygen or a portable hyperbaric chamber is critical.

Patients with mild HAPE who have access to oxygen (e.g., at a hospital or high-elevation medical clinic) might not need to descend to a lower elevation and can be treated with oxygen over 2–4 days at the current elevation. In field settings, 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 oxygen therapy. A phosphodiesterase inhibitor can be used if nifedipine is not available, but concurrent use of multiple pulmonary vasodilators is not recommended. Descent and oxygen are much more effective treatments than medication.

Medications

Recommendations for use and dosages of medications to prevent and treat altitude illness are outlined in Table 4-05.

Acetazolamide

Mechanism of Action

When taken preventively, acetazolamide hastens acclimatization to high-elevation hypoxia, thereby reducing occurrence and severity of AMS. It also enhances recovery if taken after symptoms have developed. The drug works primarily by inducing a bicarbonate diuresis and metabolic acidosis, which stimulates ventilation and increases alveolar and arterial oxygenation. By using acetazolamide, high-elevation ventilatory acclimatization that normally takes 3–5 days takes only 1 day. Acetazolamide also eliminates central sleep apnea, or periodic breathing, which is common at high elevations, even in those without a history of sleep disorder breathing.

Dose

An effective dose for prophylaxis that minimizes the common side effects of increased urination and paresthesia of the fingers and toes is 125 mg every 12 hours, beginning the day before ascent and continuing the first 2 days at elevation, and longer if ascent continues. Acetazolamide can also be taken episodically for symptoms of AMS, as needed. To date, the only dose studied for treatment is 250 mg (2 doses taken 8 hours apart), although the lower dosage used for prevention has anecdotally been successful. The pediatric dose is 5 mg/kg/day in divided doses, up to 125 mg, twice a day.

Adverse & Allergic Reactions

 Allergic reactions to acetazolamide are uncommon. Since acetazolamide is a sulfonamide derivative, cross-sensitivity between acetazolamide, sulfonamides, and other sulfonamide derivatives is possible.

Dexamethasone

Dexamethasone is effective for preventing and treating AMS and HACE and might prevent HAPE as well. Unlike acetazolamide, if the drug is discontinued at elevation before acclimatization, mild rebound can occur. Acetazolamide is preferable to prevent AMS while ascending, and dexamethasone generally should be reserved for treatment, usually as an adjunct to descent. The adult dose is 4 mg every 6 hours; rarely is it needed for more than 1–2 days. An increasing trend is to use dexamethasone for “summit day” on high peaks (e.g., Aconcagua and Kilimanjaro) to prevent abrupt altitude illness.

Ibuprofen

Recent studies have shown that taking ibuprofen 600 mg every 8 hours helps prevent AMS, although not quite as effectively as acetazolamide. Ibuprofen is, however, available over the counter, inexpensive, and well tolerated.

Nifedipine

Nifedipine both prevents and ameliorates HAPE. For prevention, nifedipine 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.

Phosphodiesterase-5 Inhibitors

Phosphodiesterase-5 inhibitors selectively lower pulmonary artery pressure, with less effect on systemic blood pressure than nifedipine. Tadalafil, 10 mg taken twice a day during ascent, can prevent HAPE. It is also being studied as a possible treatment.

Preventing Severe Altitude Illness or Death

The main point of instructing travelers about altitude illness is not to eliminate the possibility of mild illness but to prevent death or evacuation. Because 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 they are trapped by weather or geography in situations where descent is impossible. Travelers can adhere to 3 rules to help prevent death or serious consequences from altitude illness:

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

For trekking groups and expeditions going into remote high-elevation areas, where descent to a lower elevation could be problematic, a pressurization bag (e.g., 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 elevation. The total packed weight of bag and pump is about 14 lb (6.5 kg).

Preexisting Medical Conditions

Travelers with preexisting medical conditions must optimize their treatment and have their conditions stable before departure. In addition, these travelers should have plans for dealing with exacerbation of their conditions at high elevations. Travelers with underlying medical conditions (e.g., coronary artery disease, any form of chronic pulmonary disease or preexisting hypoxemia, obstructive sleep apnea [OSA], or sickle cell trait)—even if well controlled—should consult a physician familiar with high-elevation medical issues before undertaking such travel (Table 4-06).

Clinicians advising travelers should know that in most high-elevation resorts and cities, “home” oxygen is readily available. In North America, this requires a prescription that the traveler can carry, or oxygen can be arranged beforehand. Supplemental oxygen, whether continuous, episodic, or nocturnal, depending on the circumstances, is very effective at restoring oxygenation to low elevation values and eliminates the risk for altitude illness and exacerbation of preexisting medical conditions.

Diabetes Mellitus

Travelers with diabetes can travel safely to high elevations, but they must be accustomed to exercise if participating in strenuous activities at elevation and carefully monitor their blood glucose. Diabetic ketoacidosis can be triggered by altitude illness and can be more difficult to treat in people taking acetazolamide. Not all glucose meters read accurately at high elevations.

Obstructive Sleep Apnea

Travelers with sleep disordered breathing who are planning high-elevation travel should receive acetazolamide. Those with mild to moderate OSA who are not hypoxic at home might do well without a continuous positive airway pressure (CPAP) device, while those with severe OSA should be advised to avoid high-elevation travel unless they receive supplemental oxygen in addition to their CPAP. Oral appliances for OSA can be useful adjuncts when electrical power is unavailable.

Pregnancy

There are no studies or case reports describing fetal harm among people who briefly travel to high elevations during their pregnancy. Nevertheless, clinicians might be prudent to recommend that pregnant people do not stay at sleeping elevations >10,000 ft (≈3,050 m). Travel to high elevations during pregnancy warrants confirmation of good maternal health and verification of a low-risk gestation. Advise pregnant travelers of the dangers of having a pregnancy complication in remote, mountainous terrain.

Radial Keratotomy

Most people do not have visual problems at high elevations. At very high elevations, however, some people who have had radial keratotomy procedures might develop acute farsightedness and be unable to care for themselves. LASIK and other newer procedures may produce only minor visual disturbances at high elevations.