High-Altitude Travel & Altitude Illness
High-Altitude Travel & Altitude Illness
Environments significantly above sea level expose 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 an elevation of 10,000 ft (3,000 m) above sea level, for example, the inspired PO2 is a little more than two-thirds (69%) what it is at sea level. The magnitude of hypoxic stress depends on elevation, rate of ascent, and duration of exposure. Sleeping at high elevation produces the most hypoxemia; day trips to high elevations with return to low elevation are much less stressful on the body. Typical high-elevation 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; see Chapter 10, Tanzania: Kilimanjaro).
The human body adjusts very well to moderate hypoxia, but requires time to do so (Box 3-5). The process of acute acclimatization to high elevation 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 elevation is ideal. Acclimatization prevents altitude illness, improves sleep and cognition, and increases comfort and well-being, although exercise performance will always be reduced compared to what it would be at lower elevations. Increase in ventilation is the most important factor in acute acclimatization; therefore, respiratory depressants must be avoided. Expanded red-cell production does not play a role in acute acclimatization, although hemoglobin concentration is increased within 48 hours because of diuresis and decreased plasma volume.
Box 3-5. Tips for acclimatization
- Ascend gradually, if possible. Avoid going directly from low elevation to more than 9,000 ft (2,750 m) sleeping elevation in 1 day. Once above 9,000 ft (2,750 m), move sleeping elevation 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; continue caffeine if a regular user.
- Participate in only mild exercise for the first 48 hours.
- Having a high-elevation exposure (greater than 9,000 ft [2,750 m]) for 2 nights or more, within 30 days before the trip, is useful, but closer to the trip departure is better.
Risk for Travelers
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 elevations. Susceptibility and resistance to altitude illness are genetic traits, and no simple screening tests are available to predict risk. Training or physical fitness do not affect risk. Children are equally susceptible as adults; people aged >50 years slightly so. How a traveler has responded to high elevations previously is the most reliable guide for future trips if the elevation and rate of ascent are similar, although this is not an infallible predictor. Given a baseline susceptibility, 3 factors largely influence the risk of a traveler developing altitude illness: elevation at destination, rate of ascent, and exertion (Table 3-4). 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 may not be to avoid all symptoms of altitude illness but to have no more than mild illness.
Acetazolamide prophylaxis generally not indicated.
Acetazolamide prophylaxis would be beneficial and should be considered.
Acetazolamide prophylaxis strongly recommended.
Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema.
Some common destinations (such as the ones mentioned above) require rapid ascent by airplane to >3,400 meters, placing travelers in the high-risk category (Table 3-4). Chemoprophylaxis may be necessary for these travelers, in addition to 2–4 days of acclimatization before going higher. In some cases, such as Cusco and La Paz, the traveler can descend to elevations much lower than the airport to sleep.
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 elevation 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; if the person fails to descend, death can occur within 24 hours of developing ataxia.
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 lifesaving. HAPE can be more rapidly fatal than HACE.
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 such travel (Table 3-5).
Likely no Extra Risk
Caution Required 1
Children and adolescents
Coronary artery disease following revascularization
Mild chronic obstructive pulmonary disease
Mild–moderate obstructive sleep apnea
Controlled seizure disorder
Infants <6 weeks old
Compensated heart failure
Cystic fibrosis (FEV1 30%–50% predicted)
Poorly controlled arrhythmia
Poorly controlled asthma
Poorly controlled hypertension
Moderate chronic obstructive pulmonary disease
Severe obstructive sleep apnea
Nonrevascularized coronary artery disease
Sickle cell trait
Poorly controlled seizure disorder
Mild pulmonary hypertension
Radial keratotomy surgery
Sickle cell anemia
Severe chronic obstructive pulmonary disease
Pulmonary hypertension with pulmonary artery systolic pressure >60 mm Hg
Decompensated heart failure
Cystic fibrosis (FEV1 <30% predicted)
Recent myocardial infarction or stroke (<90 days)
Untreated cerebral vascular aneurysms or arteriovenous malformations
Cerebral space-occupying lesions
Abbreviations: FEV1, forced expiratory volume in 1 s.
1 Patients with these conditions most often require consultation with a physician experienced in high-altitude medicine and a comprehensive management plan.
Travel to high elevations does not appear to increase the risk for new events due to ischemic heart disease in previously healthy persons. Patients with well-controlled asthma, hypertension, atrial arrhythmia, and seizure disorders at low elevations generally do well at high elevations. 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 high elevation travel unless given supplemental oxygen in addition to their CPAP. People with diabetes can travel safely to high elevations, but they must be accustomed to exercise and carefully monitor their blood glucose. Altitude illness can trigger diabetic ketoacidosis, which may be more difficult to treat in those taking acetazolamide. Not all glucose meters read accurately at high elevations.
Most people do not have visual problems at high elevations. However, at very high elevations 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 elevations.
Travel to high elevations during pregnancy warrants confirmation of good maternal health and verification of a low-risk gestation. A discussion with the traveler of the dangers of having a pregnancy complication in remote, mountainous terrain is also appropriate. That said, there are no studies or case reports of harm to a fetus if the mother travels briefly to high elevations during her pregnancy. It may nevertheless be prudent to recommend that pregnant women do not stay at sleeping elevations above 10,000 ft (3,048 m).
Diagnosis and Treatment
Acute Mountain Sickness/ High-Altitude Cerebral Edema
The differential diagnosis of AMS/HACE is broad and includes dehydration, exhaustion, hypoglycemia, hypothermia, hyponatremia, carbon monoxide poisoning, infections, drug effects, and neurologic problems including migraine. Focal neurologic symptoms and seizures are rare in HACE and should lead to suspicion of an intracranial lesion or seizure disorder. Descending ≥300 m in elevation relieves HACE symptoms rapidly. Alternatively, supplemental oxygen at 2 L per minute relieves headache quickly and helps resolve AMS over hours, but it is rarely available. People with AMS can also safely remain at their current elevation 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 elevation, 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. Initiate descent 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, 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 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.
In addition to the discussion below, recommendations for the usage and dosing of medications to prevent and treat altitude illness are outlined in Table 3-6.
AMS, HACE prevention
125 mg twice a day; 250 mg twice a day if >100 kg
Pediatrics: 2.5 mg/kg every 12 h, up to 125 mg
AMS treatment 1
250 mg twice a day
AMS, HACE prevention
2 mg every 6 h or 4 mg every 12 hPediatrics: should not be used for prophylaxis
AMS, HACE treatment
Oral, IV, IM
AMS: 4 mg every 6 h
HACE: 8 mg once, then 4 mg every 6 h
Pediatrics: 0.15 mg/kg/dose every 6 h up to 4 mg
30 mg SR version every 12 h, or 20 mg SR version every 8 h
30 mg SR version every 12 h, or 20 mg SR version every 8 h
10 mg twice a day
50 mg every 8 h
Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema; IM, intramuscular; IV, intravenous; SR, sustained release.
1 Acetazolamide can also be used at this dose as an adjunct to dexamethasone in HACE treatment, but dexamethasone remains the primary treatment for that disorder.
Acetazolamide prevents AMS when taken before ascent; it can also help speed recovery if taken after symptoms have developed. The drug works by acidifying the blood and reducing the respiratory alkalosis associated with high elevations, thus increasing respiration and arterial oxygenation and speeding 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 elevation, 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 is effective for preventing and treating AMS and HACE and prevents 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, with dexamethasone reserved as an adjunct treatment for 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 both prevents and ameliorates HAPE. 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.
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; it may also have use as a treatment. Gingko biloba, 100–120 mg taken twice a day before ascent, reduced AMS in adults in some trials. It was not effective in other trials, though, possibly due to variation in ingredients (see Chapter 2, Complementary and Integrative Health Approaches). Recent studies have shown ibuprofen 600 mg every 8 hours to be noninferior to acetazolamide in preventing AMS, although ibuprofen does not improve acclimatization or reduce periodic breathing. It is, however, over-the-counter, inexpensive, and well tolerated.
Prevention of 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. 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. Travelers who adhere to 3 principles 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 elevation when experiencing symptoms of altitude illness, no matter how minor they 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 (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 elevation. The total packed weight of bag and pump is about 14 lb (6.5 kg). Oxygen is an excellent option for emergency use but is often impractical.
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Peter H. Hackett, David R. Shlim