Altitude Illness

Altitude Illness

Peter H. Hackett, David R. Shlim

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 (Box 2-03). 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.

Box 2-03. 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.

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 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 2-07). 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 2-07). 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.

CLINICAL PRESENTATION

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.

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 2-08). 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.

Table 2-07. Risk categories for acute mountain sickness

RISK CATEGORY	DESCRIPTION	PROPHYLAXIS RECOMMENDATIONS
Low	People with no prior history of altitude illness and ascending to less than 9,000 ft (2,750 m) People taking ≥2 days to arrive at 8,200–9,800 ft (2,500–3,000 m), with subsequent increases in sleeping elevation less than 1,600 ft (500 m) per day, and an extra day for acclimatization every 3,300 ft (1,000 m)	Acetazolamide prophylaxis generally not indicated.
Moderate	People with prior history of AMS and ascending to 8,200–9,200 ft (2,500–2,800 m) or higher in 1 day No history of AMS and ascending to more than 9,100 ft (2,800 m) in 1 day All people ascending more than 1,600 ft (500 m) per day (increase in sleeping elevation) at altitudes above 9,900 ft (3,000 m), but with an extra day for acclimatization every 3,300 ft (1,000 m)	Acetazolamide prophylaxis would be beneficial and should be considered.
High	History of AMS and ascending to more than 9,200 ft (2,800 m) in 1 day All people with a prior history of HAPE or HACE All people ascending to more than 11,400 ft (3,500 m) in 1 day All people ascending more than 1,600 ft (500 m) per day (increase in sleeping elevation) above 9,800 ft (3,000 m), without extra days for acclimatization Very rapid ascents (such as less than 7-day ascents of Mount Kilimanjaro)	Acetazolamide prophylaxis strongly recommended.

Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema.

Table 2-08. Ascent risk associated with various underlying medical conditions

LIKELY NO EXTRA RISK	CAUTION REQUIRED	ASCENT CONTRAINDICATED
Children and adolescents Elderly people Sedentary people Mild obesity Well-controlled asthma Diabetes mellitus Coronary artery disease following revascularization Mild chronic obstructive pulmonary disease Low-risk pregnancy Mild–moderate obstructive sleep apnea Controlled hypertension Controlled seizure disorder Psychiatric disorders Neoplastic diseases	Infants <6 weeks old Compensated heart failure Morbid obesity Cystic fibrosis (FEV1 30%–50% predicted) Poorly controlled arrhythmia Poorly controlled asthma Poorly controlled hypertension Moderate chronic obstructive pulmonary disease Severe obstructive sleep apnea Stable angina Nonrevascularized coronary artery disease Sickle cell trait Poorly controlled seizure disorder Cirrhosis Mild pulmonary hypertension Radial keratotomy surgery	Sickle cell anemia Severe–very severe chronic obstructive pulmonary disease Pulmonary hypertension with pulmonary artery systolic pressure >60 mm Hg Unstable angina Decompensated heart failure High-risk pregnancy 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.

 

DIAGNOSIS AND TREATMENT

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 in Table 2-09.

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.

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. 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).

Table 2-09. Recommended medication doses to prevent and treat altitude illness

MEDICATION	INDICATION	ROUTE	DOSE
Acetazolamide	AMS, HACE prevention	Oral	125 mg twice a day; 250 mg twice a day if >100 kg. Pediatrics: 2.5 mg/kg every 12 h
	AMS treatment1	Oral	250 mg twice a day Pediatrics: 2.5 mg/kg every 12 h
Dexamethasone	AMS, HACE prevention	Oral	2 mg every 6 h or 4 mg every 12 h Pediatrics: 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
Nifedipine	HAPE prevention	Oral	30 mg SR version every 12 h, or 20 mg SR version every 8 h
	HAPE treatment	Oral	30 mg SR version every 12 h, or 20 mg SR version every 8 h
Tadalafil	HAPE prevention	Oral	10 mg twice a day
Sildenafil	HAPE prevention	Oral	50 mg every 8 h
Salmeterol	HAPE prevention2	Inhaled	125 μg twice a day

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.

 

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