0025-7125/92 $0.00 + .20

TRAVEL MEDICINE

HIGH ALTITUDE MEDICINE Stephen Bezruchka, MD, FACEP

This article deals with problems of high altitude that affect increasing numbers of mountaineers and adventure travel tourists. Compared to climbers such as Hillary and Tenzing, today's mountain travelers, hikers, and skiers often have little relevant experience, yet yearn to reach substantial heights. Some may just want to fly to Lhasa, other trekkers aspire to go "one step beyond" to Everest Base Camp and can reach altitudes of 17,600 ft (5400 m) in Nepal and up to 21,000 ft (6400 m) in Tibet without requiring any technical climbing ability. Physicians are increasingly being asked to advise people with preexisting medical conditions who wish to venture to altitude." Because there is often no knowledgeable clinician at hand when problems occur, the travel medicine physician must inform the client on self-diagnosis and treatment of altitude illness.

EXPOSURE OF TRAVELERS TO HIGH ALTITUDES

In the mountain states of Utah, Colorado, Wyoming, and New Mexico, major roads reach 12,000 ft (3650 m) and some towns are located above 10,000 ft (3050 m) with resorts situated at 9000 ft (2750 m) or higher. Travelers can fly to a major airport and quickly drive to a high altitude destination. In these states, it is estimated that 34 million people traveled above 7500 ft (2285 m) in 1984, and 20% of those ascended to 8500 ft (2590 m) or higher. 48 About 25% of these travelers develop some manifestation of altitude illness. 47 High altitude produces euphoria in some sojourners but causes dysphoria and illness in others. The latter do not eat or drink as much and cannot enjoy their activities.J2 The revenue loss in Colorado from altitude illness in travelers is estimated at more than $35 million annually. Suits have been lodged against operators for failure to warn travelers of these possibilities. Besides the European Alps with their high huts and cable cars, Central From the Department of Family Medicine, School of Medicine; and Department of Health Services, School of Public Health, .University of Washington, Seattie, Washington MEDICAL CLINICS OF NORTH AMERICA VOLUME 76· NUMBER 6 • NOVEMBER 1992

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and South America and the Himalaya have roads to cities at altitudes above 10,000 ft (3050 m). Thirty thousand people a year now fly to Lhasa at 13,000 ft (3960 m) and can only descend by plane. On this immense Tibetan Plateau there is no established emergency rescue system. Helicopters are unavailable, and no radio communication system exists. Rapid descent to a lower altitude is usually not possible, and fatalities have resulted. Adventure travel, a growth industry, often persuades people with little emotional or physical preparation to undertake excursions far off the beaten path. Remote treks are featured destinations for most adventure travel companies. To cater to busy executives, itineraries are often brief. With an aging clientele yearning for new places to visit, tours are organized into ever more faraway areas making rescue operations very difficult or impossible. Tourists are often unaware of these potential problems. This article discusses relevant aspects of acclimatization and the syndromes of altitude illness and their diagnosis and treatment, and covers advice for travelers with preexisting diseases. Historical aspects have been reviewed elsewhere. 32 ACCLIMATIZATION

Acclimatization is a complex acute and chronic process, wherein the body adapts to hypoxia by optimizing oxygen delivery to cells. The following summarizes some of the adaptive mechanisms that have clinical implications. Specialized sources are available for details. 69 Figure 1 sketches many of the physiologic changes. Hyperventilation, initiated by the stimulation of the carotid body in response to hypoxemia, is the first and most important adaptation to hypoxia. It elevates alveolar P0 2 and produces a hypocapnic alkalosis that limits further increases in ventilation until renal compensation by bicarbonate excretion lowers the pH closer to normal (a period of days to weeks). Hyperventilation is sustained throughout the stay at altitude. The key to acute adaptation to altitude is a strong hypoxic ventilatory drive. Those with a brisk drive are more likely to be free of significant altitude illness. 50 Table 1 shows blood gases in acclimatized individuals at various altitudes. Nocturnal periodic breathing is almost universal above 10,000 to 12,000 ft (3050 to 3650 m) and common to newcomers as low as 8000 ft (2450 m), producing frequent awakenings and a decrease in quality of sleep. The marked oxygen de saturation caused by periodic breathing and by sleep improves with acclimatization. Tachycardia secondary to increased catecholamines, is the initial circulatory response to hypoxemia. Monitoring the resting pulse in the morning on awakening can be a valuable indicator of the state of acclimatization. Initially it will rise 20% or more. After a week or more at altitude with normal acclimatization, the resting pulse will decline toward normal sea level values. The cardiac output initially rises, to maintain oxygen delivery, then falls to normal for a given metabolic rate after a week. For a given work rate, the pulse will be higher than at sea level as the stroke volume is lower. The blood pressure response is not clearly understood at present. Studies looking at the coronary stress of activity at high altitude in healthy older men show no increase over comparable exercise at lower altitudes. 16 Hypoxia is one of the major causes of pulmonary hypertension. The pulmonary circulation undergoes an increase in vascular resistance secondary to vasoconstriction. This is thought to improve the ventilation perfusion mismatch

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HYPOXIA Acclimatization

Adaptation Life I Generationsl long

Chronic

Acute

.c--------=-

?

PH PR

C'-----...

Cap. Dens.

~ Hb

~

Hypoventilation

'\:::7'""

Hyperventilation

~

Heart rate

I 0.1

I 1.0

I I 10 100

I I I 10 100 1.0

I

3

I

30

I

I

I

300 3000 30K

L-...Minutes ~ L-Days~ L-Years--Log time Figure 1. Time courses of a number of acclimatization and adaptive changes plotted on a long time-scale, with the curve of each response denoting the rate of change, fast at first then tailing off. Included are heart rate, hyper- and hypoventilation, the carbon dioxide ventilatory response (C0 2 VR), hemoglobin concentration (Hb), changes in capillary density (Cap. Dens.), hypoxic ventilatory response (HVR), and the pulmonary hypoxic pressor response (PH PR). (From Ward MP, Milledge JS, West JB: High Altitude Medicine and Physiology. Philadelphia, University of Pennsylvania Press, 1989, p 68; with permission.)

Table 1. BLOOD GASES AT ALTITUDE* Altitude

Pa0 2

Sa0 2

Pac0 2

Sea Level 1524 m (5000 It) 2286 m (7500 It) 4572 m (15,000 It) 6096 m (20,000 It) 7620 m (25,000 It) 8848 m (29,029 It)

90--95 75-81

96 95

40 32-33

69-74

92-93

31-33

48-53

86

25

37-45

76

20

32-39

68

13

26-33

58

9.5-13.8

'All values are for subjects of age 20-40 years who were acclimatizing well. Data from Hackett PH, Roach RC, Sutton JR: High altitude medicine. In Auerbach PS, Geehr EC (eds): Management of Wilderness and Environmental Emergencies, ed 2. SI. Louis, CV Mosby, 1989; with permission.

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present at altitude although the pulmonary vasoconstriction may be a vestigial neonatal reflex. Cold and exercise are synergistic with altitude in producing pulmonary hypertension. This response varies considerably among individuals. Changes in the cerebral circulation at altitude are not clearly understood; hypoxia increases cerebral blood flow through vasodilatation, while hypocapnia decreases it. The response to hypoxia at high altitudes overrides that to hypocapnia. Those without a brisk hyperventilatory response to altitude may have a greater vasodilatation and vasogenic edema. Insufficient vasodilatati0n may contribute to cerebral ischemia. The hematocrit and hemoglobin rise in response to hypoxia. Initially, this is owing to plasma volume contraction via diuresis, with an erythropoietin induced erythrocytosis, appearing later. This improves oxygen carrying capacity, but when the hematocrit exceeds 60%, blood viscosity increases. Those who diurese acutely at altitude, resulting in a 2% loss in body weight, are relatively free of altitude illness. 21 , 22 ALTITUDE ILLNESS SYNDROMES

Problems with altitude adaptation are multifactorial and include leak of fluid from the vascular to the extravascular space and aberrant ventilatory control. Although individual entities are described here, they may all be facets of an as yet incompletely understood common pathophysiologic process. Acute Mountain Sickness

Acute mountain sickness (AMS), with symptoms mimicking a hangover, occurs a few hours to days after exposure. Severe enough to limit normal activities, it is found in 15% to 30% of Colorado resort skiers, 50% of climbers on Mount McKinley, 70% of climbers on Mount Rainier, and in 25% to 50% of trekkers to the base of Mount Everest.2 7 It occurs in those ascending to intermediate altitudes (6500 ft [2000 m]) and prompts many to self-medicate." It is more common among those who ascend quickly, who are younger, and who have a past history of AMS. Female gender is not an advantageY The role of physical fitness is questionable. AMS is more likely in those who retain fluid at altitude and relatively hypoventilate. 22 Those who diurese are unlikely to suffer. 4 It is thought to result from brain hypoxemia, fluid retention, and mild vasogenic brain edema. Intracranial pressure is elevated in severe AMS, which melds into cerebral edema. Mild AMS is characterized by headache, anorexia, insomnia, nausea, and malaise. In moderate forms, there is vomiting, unrelieved headache, and decreased urine output. Features of severe AMS are altered consciousness, localized rales, cyanosis, and ataxia, which may be the most sensitive early sign, and represents early high altitude cerebral edema (HACE). Peripheral edema of the hands, face, and ankles is common at altitude, especially in those with AMS and has a predilection for females over males. 18 Strenuous exercise at lower altitudes can also cause edema, so this can be an isolated finding at altitude. Mild AMS improves over a few days if the hypobaric stress is not increased by ascending. Severe AMS, which may also represent early HACE, or even high altitude pulmonary edema (HAPE), will usually progress unless treated aggressively.

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High Altitude Pulmonary Edema

HAPE, a noncardiogenic pulmonary edema, occurs in 5% to 10% of those with AMS, but can occur without previous symptoms. One to 2% of those traveling above 12,000 ft (3660 m) are affected, and males predominate. 28 It occurs at ski resorts situated at moderate altitudes. 65 There is a high mortality rate with 11 % reported in one study, and 44% if untreated in one retrospective analysisY HAPE often occurs on the second night after ascent to altitude. Relative hypoxemia and a low hypoxic ventilatory response are presenU4 It is characterized by a lung leak, not a lung injury, because people who recover have gone back up high on the same trip. HAPE victims have extremely high pulmonary artery pressures as compared with unaffected altitude controls. 5 There is marked ventilation-perfusion mismatch, with opening of the usually tight capillary endothelial junctions, and patchy edema is typically seen on chest roentgenograms. The edema fluid is very protein rich, as in adult respiratory distress syndrome. It contains large molecular weight proteins, indicating a permeability leak from the microvasculature, accompanied by alveolar macrophages and leukotrienes. 6o Features of early HAPE include decreased exercise performance (earliest symptom), dry cough, fatigue, tachycardia (above resting levels for that person at altitude), rales in the right middle lobe, and tachypnea. Later cyanosis, extreme weakness, productive cough, and dyspnea at rest may present. Mental obtundation, irrational behavior, and coma can be present. Atypical presentations include sudden death, ataxia only, or bronchospasm, possibly mixed with a respiratory infection. Fever less than 38.3°C may be present and by itself is not a helpful sign. Subclinical HAPE manifested as rales is probably very common at altitude. 2B A chest radiograph done at altitude can demonstrate HAPE before rales are heard. 6B Risk factors include rapid ascent, strenuous exertion on arrival, obesity, male gender, a previous history, and congenital absence of the right pulmonary artery or the proximal interruption of a pulmonary artery. 19, 41 The recurrence rate has been reported to be 66% in one study.68 Individuals who have lived at high altitude can develop HAPE on rea scent after going to low altitude. This has been widely reported in Peru,34 where rapid reascent is easy. It also occurs in the United States61 and probably in the Himalaya.

High Altitude Cerebral Edema

High altitude cerebral edema (HACE) is possibly an end stage of AMS, which usually presents several days after the onset of mild AMS. Death, however, has occurred 24 hours after AMS began. Intracranial pressure is increased, perhaps owing to increased brain cell volume, cytotoxic edema secondary to hypoxia, or vasogenic edema from a leaky blood-brain barrier. It is very uncommon below 10,000 ft (3050 m). Rapid ascent to significant altitudes strongly predisposes to development of HACE. Clinical presentation includes impaired judgment, inability to make decisions, irrational behavior, severe headache, nausea and vomiting, truncal ataxia, severe lassitude, and progression to coma. HAPE often can accompany HACE and vice versa. Hallucinations, hemiparesis, and other focal neurologic signs have been reported, but these may be owing to thrombosis. Chronic neurologic sequelae may exist.

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High Altitude Retinopathy

High altitude retinopathy (HAR) is common to those sleeping above 15,000 ft (4570 m). This condition usually presents with asymptomatic retinal hemorrhages that resolve spontaneously after a week or two whether at altitude or at sea level. There may also be dilatation of retinal veins, cotton-wool exudates, and disk hyperemia. 44 Vision is only affected if the macula is involved. Scotomata and even blindness can sometimes occur at altitude; the reasons 'lre poorly understood. DIAGNOSIS

Diagnosis of altitude illness in the clinical setting may be complicated by the diagnostician's judgment of the hypoxic state. 3!. 32 Diagnostic tools are often not available. Goal-driven adventurers, pressured by peers and on a tight schedule, have a tendency to ascribe altitude symptoms to other causes. An illness at altitude is altitude illness until proven otherwise. Physicians should advise travelers going to high altitudes to suspect significant altitude illness in themselves if they have: A headache and feel "hung over" Dyspnea and a respiratory rate above 20 at rest Anorexia Vomiting Ataxia Unusual fatigue while walking They should suspect significant altitude illness in their companions who are: Skipping meals Exhibiting antisocial behavior Stumbling Having the most difficulty with the activity Those going to altitude can be taught to test for ataxia by performing tandem walking on victims, using those unaffected as controls. Walking on a narrow piece of wood close to the ground is another useful test. The differential diagnosis is protean, and commonly includes dehydration, substance abuse, hypothermia, carbon monoxide poisoning (from a stove used in an enclosed tent"7), infection, exhaustion, and an exacerbation of a preexisting condition. Although it should be easy to exclude such conditions, mistakes are commonly made in the field. Observing the victim's response to oxygen or descent may help clarify the diagnosis in questionable circumstances. Groups carrying a portable hyperbaric chamber (Hyperbaric Mountain Technologies, Boulder, CO) might place the victim in the bag, pressurize it for an hour, and note the response. There may be a slight placebo response or sometimes a claustrophobic panic reaction, but clinical judgment should resolve the situation. PREVENTION

The key for those recognized as being at risk is to go slowly. These include groups traveling on tight schedules, having little flexibility to wait for members to acclimatize. Groups of goal-driven adventure travelers may be more prone

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to denial and appear to have a high incidence of problems with altitude, although confirmatory studies are lacking. Individual travelers going independently on a modest budget may suffer less serious altitude illness. Rapid ascent, especially by flying or driving to altitude is risky. Physicians themselves are at risk. l3 Physicians can advise a client going on a commercial tour to high destinations to inquire about the availability of oxygen or a hyperbaric bag, the flexibility of the itinerary, and the availability of rescue. Are the leaders knowledgeable about and equipped to treat altitude illness? What are the contingency plans if someone gets severe altitude illness? A lightweight source book on wilderness medicine can be helpful. 6 , 20, 72 Slow ascent is most important. The sleeping altitude should rise gradually. Climb high, but sleep low. Prudence suggests taking at least 2 days to get the sleeping altitude above 10,000 ft (3050 m). Thereafter, avoid raising the sleeping altitude more than 1000 feet a day. Because each person adapts differently to every exposure to altitude, rather than give a formula for how fast is slow enough, travelers should monitor each other, no matter what the ascent rate. Sedatives and tranquilizers result in hypoventilation and greater desaturation during sleep and must be avoided at altitudes above 8000 ft (2440 m). Mechanized or animal transport to a higher altitude, especially when an individual is having any difficulty coping with the physical activity, is risky. Enterprising people in one heavily trekked, high altitude area of Nepal rent ponies to help people ascend. The obtunded, ataxic trekker is then carried up even higher, where he may be found in coma! Drinking plenty of fluids is routinely recommended. A high carbohydrate diet increases the respiratory quotient and improves the use of oxygen at very high altitudes. It may also result in less altitude illness and superior performance! Liquid carbohydrate meals may be easier to eat at altitude then solid ones. 2 The diet should be low in fat and salt. Advise against strenuous overexertion for the first few days at altitude. Hypothermia is synergistic with the deleterious effects of altitude. Adequate clothing is necessary, because the temperature drops 3SF for every 1000 ft (O.65°C for 100 m) of ascent. Conscious effort to increase the depth and frequency of breathing at altitude is beneficial. There should be more breaths per step in the rhythm of the activity. Some advocates of specific breathing techniques have denied obvious symptoms of altitude illness and persisted in ascending. Although there are no studies to substantiate its efficacy, low-dose aspirin may be useful for thromboembolic prophylaxis above 12,000 ft (3660 m).75 Acetazolamide, by inhibiting carbonic anhydrase in the kidney and lung, promotes the excretion of bicarbonate and thus results in a slight metabolic acidosis. Acetazolamide reduces symptoms by speeding acclimatization and decreases susceptibility to AMS. It increases minute ventilation and oxygen saturation and decreases the periodic breathing at night. 23 It is thought to reduce the incidence of HAPE and HACE. Acetazolamide can be considered for those driving or flying to altitudes of 10,000 feet (3000 m) or more, but is also beneficial on slower ascent, especially for those who tend to get altitude illness. It is recommended for those who have had significant symptoms in the past and for rescue groups who must ascend quickly. Acetazolamide can be given when the sleeping altitude has to be raised abruptly. Acetazolamide should be carried by everyone going to altitude to treat possible symptoms and thereby accelerate the acclimatization process. The maximum dose is 5 mg/kg per day, in two or three doses, but 125 mg twice a day or once at bedtime may

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be adequate. Acetazolamide can be taken on the day of ascent and continued for 2 days on arrival at altitude. Acetazolamide may affect the taste of carbonated beverages because it decreases the hydration of carbon dioxide on the tongue. Common side effects of this sulfa drug include polyuria and paresthesias, and less commonly nausea, myopia, and impotence. It is the only Federal Drug Administration (FDA) approved pharmaceutical for prevention of AMS. It must be avoided by those with allergies to sulfanilamides. Dexamethasone is also effective as a prophylactic for AMS, but it is. not routinely recommended because of significant dysphoria and the'likelihood of rebound altitude illness when it is discontinued. 58, 76 It does not facilitate acclimatization; rather its mechanism of action is probably that of decreasing fluid leak from the microvasculature. Travelers can be advised to carry dexamethasone to treat cerebral symptoms, but it should not be routinely recommended for prophylaxis. Those who need to ascend rapidly for rescue purposes could take dexamethasone along with acetazolamide in doses of 4 mg orally every 6 hours. Smaller doses do not work,26 but dosing twice a day may be adequate. 57 Those who cannot take acetazolamide, have had a significant history of altitude illness, and must be exposed to the hypoxia of altitude, might also benefit. Dexamethasone should not be stopped at altitude until there has been a considerable descent. Tapering may be necessary after taking it for 3 days or more. Nifedipine, which decreases pulmonary artery pressures, appears to be an effective prophylactic for those who are susceptible to HAPE but is not FDA approved. 5 It may also ameliorate the symptoms of AMS. The dose is 20 mg (long acting preparation) three times a day. TREATMENT Acute Mountain Sickness

Mild forms of AMS can be treated by staying a day or two at the current altitude, then ascending cautiously. Modest exercise during the day may be encouraged. Symptomatic treatment includes mild analgesics, acetazolamide 125 or 250 mg bid to tid (begin with a dose at bedtime), and prochlorperazine for nausea and vomiting. Acetazolamide, taken before bed, is especially useful for treating sleep disturbance.23 Severe AMS calls for immediate descent, oxygen, and acetazolamide. Dexamethasone 4 mg PO every 6 hours should be given for severe AMS when descent is underway.4o Symptoms can recur with discontinuation of dexamethasone. 26 HA PE has also occurred after dexamethasone has been given for treatment of AMS.3 One or 2 hours of simulated descent in the hyperbaric bag may be as effective as oxygen therapy. 37, 56 Longer periods are necessary for serious illness. 38 , 66 Barotitis is a complication. High Altitude Pulmonary Edema

Treatment of HAPE relies on early recognition and must be expeditious to avoid death. HAPE is a medical emergency. The victim should be kept warm, given oxygen, and taken down. It is easier to descend an ambulatory rather than a moribund victim. Strenuous exertion, however, can worsen HAPE. A descent of 1500 to 3000 ft (500 to 1000 m) is often adequate. Experience with the hyperbaric bag is limited, but it has been considered

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life-saving. One problem with the currently available model is that the victim must lie down inside, which is difficult for the roughly 10% of HAPE victims who are orthopneic and find it difficult to lie flat. One study suggests that 4 hours of stay in the pressurized chamber is adequate. 66 Pulmonary vasodilators may have a useful role in improving gas exchange and the symptoms of HAPE. The most experience is with nifedipine 10 mg sublingually given acutely with 20 mg of the long acting preparation continued every 6 hours. 52 Postural symptoms and signs should be monitored if a sphygmomanometer is not available. This is not an FDA approved indication, but travelers can be advised to carry it for use in confirmed cases. Continuous positive airway pressure (CPAP), positive end expiratory pressure, and expiratory positive airway pressure have been advocated as temporizing measures to alleviate symptoms and increase oxygenation. 59 The CPAP mask has been successfully used with a 10-cm pressure valve, but pneumothorax can result and HACE has occurred after its use. 51 Delivery systems are usually unavailable in the clinical situation, but a lightweight portable CPAP mask is made (Downs CPAP Mask, Vital Signs Inc, Totowa, NJ).

In serious cases of HAPE, give dexamethasone (or another corticosteroid) if central nervous system (CNS) symptoms are present. Acetazolamide may be useful early on in HAPE, but it does not appear to be useful in severe cases. Diuretics and morphine were found useful by early investigators,64 but they are not believed to be effective today and are not currently used, although there are no recent studies. Intravenous loop diuretics can result in hypotenSion and shock. With the nondescent treatment modalities available today, there is a tendency to delay descent or cancel evacuation plans when some improvement occurs. HAPE has recurred fatally in such situations. Descent remains the mainstay of treatment and should be undertaken along with hyperbaric, oxygen, and drug therapies. After resolution of HAPE, some victims have reascended gradually without recurrence on that trip.52 Reascent should only be undertaken carefully, with responsible supervision. Slow release nifedipine, 20 mg orally three times a day, can be given. High Altitude Cerebral Edema

Key prinCiples in therapy include descent, oxygen, and dexamethasone 4 to 8 mg every 6 hours. Response to treatment may be slow. The hyperbaric bag has been used successfully with 6 hours or more being necessary for treatment. 38, 66 Mannitol, as well as endotracheal intubation and hyperventilation are presumed to be effective but have never been studied. Reascent in improved cases should not be considered. It should be recognized that coma can persist for long periods of time, especially if treatment is delayed. High Altitude Retinopathy

If vision is affected victims should descend. Oxygen (C0 2 or paper bag rebreathing) can be given for transient blindness (which is usually cortical blindness and not HAR).

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SUMMARY OF PHARMACOLOGIC ADVICE FOR THE TRAVELER TO ALTITUDE

Those on a travel itinerary that includes mechanized travel to altitude destinations such as La Paz, Bogota, Lhasa or Keystone, Colorado, should carry acetazolamide and use it to treat significant symptoms of AMS. Begin with a dose at bedtime. Those with a history of difficulties adapting to altitude could take it prophylactically, beginning on the day of travel and contin~ing for 1 to 2 days on arrival. Those venturing to remote altitude destinations such as the summit of Mt. McKinley (Denali), or Everest Base Camp also might carry dexamethasone and nifedipine and a hyperbaric chamber for treating presumptive severe AMS, HAPE, and HACE. PEOPLE WITH CHRONIC DISEASES GOING TO ALTITUDE

As our population ages and more recognition is given to the beneficial effects of exercise, more older people desire to travel to altitude for recreation. Some of these individuals undertaking an altitude adventure will have developed a chronic illness. Some published reports but no controlled studies of lowlanders with chronic diseases exposed to altitude exist. Not much is known about the effects of medicines during hypoxia, and advice to patients about their medication remains presumptive or speCUlative and should be cautious. 54 Rather than suffering the loss of self-esteem that may result from staying at home in a low-risk environment and nursing the chronic illness, in marginal clinical situations in which an individual has a strong will and motivation to reach a personal goal, a far greater benefit may be derived from the possible attainment of that goal. 55 Some who should not venture to altitude may wish to in spite of admonitions to the contrary. They should be urged to choose an itinerary with access to easy descent and have medical help readily available. Taking oxygen along is usually impractical. Those with chronic diseases that could cause problems at altitude should first undertake, near home, an activity similar to that planned. They should repeat the same activity at a moderate altitude (8000 ft, 2450 m), again, near home. If they perform well under both circumstances, then they can consider that activity at even higher altitudes. The following exercise guidelines for cardiac patients make sense for everyone. Cardiovascular Diseases

Death while exercising does not appear more common at altitude than at sea level. Deaths are more common in patients with known cardiac disease or with symptoms while exercising, but sudden death can occur in fit athletes as well. Exercise tests are useful in evaluating patients with known coronary disease, or who have symptoms suggestive of coronary disease. They are probably not useful in predicting coronary disease in asymptomatic individuals without a history of heart disease, because of a very high rate of false-positive results. 36 Preactivity exercise testing can be considered for those people 50 years of age or older who have significant risk factors for coronary disease, including family history, hypertension, chest pain, and ST depression on the resting

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electrocardiogram (ECG). It might also be indicated for the older asymptomatic risk-free individual who will be far from help on a trip. Those who test positive can undergo an exercise thallium reperfusion study. If that study is positive, they should probably undergo coronary angiography.36 Argentinean authorities have required the results of an exercise test on everyone applying to climb Mt. Aconcagua. The first 5 to 10 days at altitude is considered a dangerous period because of increased sympathetic outflow and circulating catecholamines.1l Catecholamine release is quite variable. Reports on the change in blood pressure at altitude are conflicting. Patients with minimal symptoms of angina who are taking few medicines and who can undergo the Bruce Protocol exercise test to more than 9 minutes will probably do well at altitude. Those with moderate symptoms, taking a number of medicines who have occasional angina at rest and exercise limitations may tolerate some exposure to altitude. Those with severe angina and limitation of effort at sea level should not go to altitude, as hypoxia will increase cardiac work and precipitate severe attacks. Those with angina who are going to altitude can be advised to ascend slowly, to increase antianginal medicines, and to rest for the first 2 to 3 days on arrival to altitude. If their blood pressures are elevated, labetalol or clonidine may be useful for treatment. Significant anginal symptoms are treated with oxygen, if available, and descent without exertion in addition to the usual modalities. Hypertensives may find their pressures elevated at altitude, although there are no data to support this claim. Because of increased sympathetic activity, beta blockers are probably not very effective. A low salt diet and increased rest during the first few days at altitude can be advised together with self-monitoring of pressures in selected individuals, as they may need to increase their antihypertensive drugs. Clonidine, which produces diffuse inhibition of CNS sympathetic neural outflow, and prazosin, which blocks alpha-adrenoceptors, can be given to control pressures. Calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors may also be useful, but there are no controlled trials of any agents at altitude. There are no data to suggest that post-myocardial infarction and postcoronary bypass surgery patients need to be treated any differently than those in the above categories. It is known that patients with coronary artery disease at altitude have decreased exercise tolerance and earlier appearance of angina and ST-segment changes. 7, 50, 77 Anecdotally, there are few reported cardiac events at high altitude ,43, 62 There are no controlled studies concerning the risk to people with known cardiac disease of venturing to altitude. Patients with coronary disease are probably not at a greater risk of having a coronary event at altitude as compared to performing the same exercise at sea level. The indirect evidence to support this view has been reviewed by Hultgren,36 but is controversial. 15, 35, 71 Individuals with marginally controlled congestive heart failure may decompensate at moderate altitude (6500 ft [2000 m]) or higher, and they are difficult to assess in situ because of tachypneic and tachycardic responses to altitude, AMS and other forms of fluid retention at altitude could aggravate congestive heart failure (CHF).25 Such individuals should avoid altitude. Advice to those with other forms of heart disease who wish to travel to altitude should be individualized on the basis of symptoms and exercise tolerance to exposure to lower altitudes near home. Exercise guidelines at altitude are helpful. Maximal body oxygen consumption and work capacity are decreased at altitude, irrespective of the presence

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of heart disease. Maximal heart rates decline. Target heart rates are a better end point for activity levels at altitude in those with coronary heart disease than an activity prescription. 49 Calculate 75% of the ischemic end point heart rate from a symptom-limited treadmill evaluation at home altitude as the target rate for cardiac patients at altitude. This may be a reasonable principle to follow in advising other individuals with chronic disease at altitude. Substitute a derived maximal heart rate (= 206 - 1.2[age - 20)) for the ischemia limited figure for those who have not had and do not need an exercise study . .The patient can test this with strenuous exercise.

Neurologic Diseases

Transient ischemic attacks and stroke have been reported at high altitude (above 16,000 ft [4900 m)) in young, healthy individuals. Dehydration may be a contributing factor. Those experiencing a transient ischemic attack (TlA) at altitude should increase hydration, take an aspirin tablet a day, and descend. 75 The seizure threshold at altitude may be lower, so those who have stopped taking their anti seizure medicines at sea level could have seizures after abrupt exposure to altitude. All epileptics with controlled seizures should be advised to continue their anticonvulsant medicines at altitude. There does not appear to be an increased incidence of breakthrough seizures in those who are medicated. The modest cerebral edema that develops at altitude may compromise neurologic function of people with brain tumors. Tumors and other CNS conditions may first become symptomatic at altitude. 63

Pulmonary Diseases

Many asthmatics report improvement in their condition at altitude, perhaps because there is less dust, a lower air density, and fewer inhaled allergens. Some have more cold or exercise-induced bronchospasm. Such individuals should use inhaled bronchodilators before cold or exercise exposure. Individuals with mild to moderate chronic lung disease may tolerate modest altitudes, but there is a higher incidence of AMS.15 Those on home oxygen should continue this and increase the flow rate by the ratio of the home to the new barometric pressure. Altitude exposure is contraindicated for those with marked arterial de saturation and CO 2 retention. Whether individuals with asymptomatic pulmonary hypertension, such as in some forms of congenital heart disease, or mitral stenosis will have difficulties at altitude is unknown. Most patients will tolerate modest altitudes. Those with primary pulmonary hypertension do not do well at altitude, but those who must visit a higher altitude might benefit from a calcium channel blocker such as diltiazem. They should be advised to avoid strenuous exercise, maintain body warmth through adequate clothing, and have oxygen available. To determine the advisability of going to altitude, consider testing these individuals to see if the calcium channel blocker or other pulmonary vasodilator has a significant effect at sea level. Those with sleep apnea syndrome do not do well at altitude. If it is necessary to go to altitude, oxygen and acetazolamide for sleep are advised.

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Hematologic and Endocrine Diseases

Diabetics may experience problems regulating the insulin dose because of the varying energy expenditure and food intake. More frequent insulin dosing and blood glucose de terminations should be advised than when undertaking normal work. 69 Use of shorter acting preparations is sensible. Glucagon should be carried. Insulin should not be allowed to freeze, and advise that an extra supply be carried in case of loss or breakage. Presence of sickle cell disease is considered a contraindication to ascend to altitude, at least for the African-American individual. Altitude exposures of only 6320 ft (1925 m) are associated with an almost 60% risk of crises. s Even air travel is associated with an increased risk. The splenic infarction syndrome, with left upper quadrant pain, is more common in the sickle cell trait rather than in the disease, as those with the latter probably have autoinfarcted their spleens early in life. 39 Those with intact spleens are advised to breathe supplemental oxygen during air travel (difficult on many airlines), and all should keep very well hydrated. Individuals with sickle cell trait and other hemoglobinopathies such as Se, Hb S, or (3+-thalassemia and normal lung function should limit exposure to 10,000 ft (3050 m), understanding that splenic infarction may occur.74 Those with impaired lung function may become symptomatic at lower altitudes. In Saudi Arabia some individuals with sickle cell disease tolerate residence at 10,000 ft (3050 m), but with twice the frequency of crises and complications. 1 There may be an increased risk of thromboembolic events at altitudes above 14,000 ft (4270 m).lO, 70 Dehydration, polycythemia, and immobility have been implicated. Those with a history of thromboembolic events could be anticoagulated before going to such altitudes. There are no data on the safety or efficacy of this potentially hazardous regimen. Prothrombin levels may be decreased at altitude because of hepatic hypoxia, 30 so frequent checks of prothrombin times may be necessary, although an impossibility in most such altitude environments. Gynecologic, Obstetric, and Pediatric Concerns

Women taking oral contraceptives have been advised by some to continue them at least to moderate altitudes «10,000 ft [3000 m]), as the risk of pregnancy may be greater than the increased risk of thrombosis. Others disagree and advise the use of other contraceptives at altitude. There are no data to support either argument. There are also no data regarding pregnant visitors to altitude. One lowlander is known to have climbed to an altitude of 24,600 ft (7500 m) while 4'/2 months pregnant and to later give birth to a normal child. 29 Studies on permanent residents at altitude show altitude-associated increase in fetal growth retardation, pregnancy-induced hypertension, and neonatal hyperbilirubinemia. 48 Physicians with a conservative point of view may advise against travel to altitude for the normal woman who is pregnant/° whereas other experts may advise limited exposure to moderate altitudes «13,125 ft or 4000 m).27 A reasonable compromise would be to limit exposure during the first trimester to 8000 ft (2450 m) for uncomplicated pregnancies. Infants and young children born at sea level are perhaps more at risk from altitude illness than adults. HAPE has been reported to be 16 times more prevalent among children in the Andes. 34 Diagnosis is more difficult in young

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children; however, children have been taken to altitudes over 15,000 ft (4571 m) by responsible adults without incident. Rapid descent if any questionable illness occurs is paramount, however. There are no data on the use of pharmaceuticals to prevent or treat mountain sickness in children. Miscellaneous Concerns

There is significant immune suppression in the normal human at altitudes of 10,000 ft (3050 m) or higher. Active immunization and B cell function is maintained, whereas T cell function is impaired following exposure to simulated altitude. 45 Anecdotally, bacterial infections at altitudes above 14,000 ft (4270 m) seem not to respond to appropriate treatment without descent. Those with significant trauma should descend expeditiously. There are no data on the exposure of HIV infected individuals to altitude, but infections of the gastrointestinal tract, among others, are likely to be more serious in the HIV-infected traveler to altitude.73 Easy descent should be a readily available option in their itinerary. Extended wear contact lenses have been worn to 26,000 ft (8000 m) without mishap, 53 although corneal hypoxia is a potential hazard. The use of disposable lenses obviates increased risks of infection from improper cleaning. SUMMARY

Altitude illness is common and may result in major disruption of travel plans. Visitors to altitude need to be aware of the various health problems they might encounter and how they may be prevented. Self-diagnosis and treatment is the norm in many remote locations. The hallmark of therapy remains descent, but with newer treatment modalities, this may be easily forgotten. People with preexisting health problems may desire to visit high altitude destinations. It is reasonable to support some strongly motivated people in undertaking such trips, providing they recognize the difficulties of coping with illness in remote locations. ACKNOWLEDGMENTS Special thanks to Elinor Graham, MD, and Yvonne Vaucher, MD, and to the following pioneers in this field, Peter Hackett, MD, Charles Houston, MD, Herbert Hultgren, MD, and Robert B Schoene, MD, for their constructive criticism. The staff at the Horton Health Sciences Library at Providence Hospital in Seattle have also been very helpful.

References 1. Addae S, Adzaku F, Mohammed S, et al: Sickle cell disease in permanent residents of mountain and low altitudes in Saudi Arabia. Trap Geogr Med 42:342, 1990 2. Askew EW: Carbohydrate supplementation for work at high altitude: Liquid versus solid food supplements. The First World Congress on Wilderness Medicine [abstract]. Whistler, British Columbia, Canada, July 1991, p 284 3. Bartsch P, Vock P, Franciolli M: High altitude pulmonary edema after successful treatment of acute mountain sickness with dexamethasone. J Wild Med 1:162, 1990

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4. Bartsch P, Pluger N, Audetat M, et al: Effects of slow ascent to 4559 m on fluid homeostasis. Aviat Space Environ Med 62:105, 1991

5. Bartsch P, Maggiorini M, Ritter M, et al: Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 325:1284, 1991 6. Bezruchka S: The Pocket Doctor: Your Ticket to Good Health While Traveling. Seattle, The Mountaineers, 1992 7. Brammell H, Morgan B, Niccoli S, et al: Exercise tolerance is reduced at high altitude in patients with coronary artery disease. Circulation 55 (suppl 2):371, 1988 8. Claster S, Godwin Ml, Embury SH: Risk of altitude exposure in sickle cell disease. West J Med 135:364, 1981 9. Consolazio CF, Matoush LO, Johnson HL, et al: Effects of high-carbohydrate diets on performance and clinical symptomatology after rapid ascent to high altitude. Fed Proc 28:937, 1969 10. Cucinell SA, Pitts CM: Thrombosis at mountain altitudes. Aviat Space Environ Med 58:1109, 1987 11. Cunningham WL, Becker El, Kreuser F: Catecholamines in plasma and urine at high altitude. J Appl Physiol 20:607, 1965 12. Dean AG, Yip R, Hoffmann RE: High incidence of mild acute mountain sickness in conference attendees at 10,000 foot altitude. J Wild Med 1:86, 1990 13. Dickinson l, Heath D, Gosney l, et al: Altitude-related deaths in seven trekkers in the Himalayas. Thorax 38:646, 1983 14. Froelicher, VF, West JB: Trekking in Nepal: Safety after coronary artery bypass. JAMA 259:3184, 1988 15. Graham WG, Houston CS: Short-term adaptation to moderate altitude-patients with chronic obstructive pulmonary disease. JAMA 240:1491, 1978 16. Grover RF, Tucker CE, McGroarty SR, et al: The coronary stress of skiing at high altitude. Arch Intern Med 150:1205, 1990 17. Hackett PH, Rennie ID, Levine HD: The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 2:1149, 1976 18. Hackett PH, Rennie ID: Rales, peripheral edema, retinal hemorrhage, and acute mountain sickness. Am J Med 67:214, 1979 19. Hackett PH, Creagh CE, Grover RF et al: High altitude pulmonary edema in persons without the right pulmonary artery. N Engl J Med 302:1070, 1980 20. Hackett PH: Mountain Sickness: Prevention, Recognition and Treatment. New York, American Alpine Club, 1980 21. Hackett PH, Rennie D, Grover RF, et al: Acute mountain sickness and the edemas of high altitude: A common pathogenesis? Respir Physiol 46:383, 1982 22. Hackett PH, Rennie D, Hofmeister SE, et al: Fluid retention and relative hypoventilation in acute mountain sickness. Respiration 43:321, 1982 23. Hackett PH, Roach RC, Harrison GL, et al: Respiratory stimulants and sleep periodic breathing at high altitude: Almitrine versus acetazolamide. Am Rev Respir Dis 135:896, 1987 24. Hackett PH, Roach RC, Schoene RB, et al: Abnormal control of ventilation in highaltitude pulmonary edema. J Appl Physiol 64:1268, 1988 25. Hackett PH, Hornbein TF: Disorders of high altitude. In Murray JF, Nadel JA (eds): Textbook of Respiratory Medicine. Philadelphia, WB Saunders, 1988, p 1659 26. Hackett PH, Roach RC, Wood RA, et al: Dexamethasone for prevention and treatment of acute mountain sickness. Aviat Space Environ Med 59:950, 1988 27. Hackett PH, Roach RC, Sutton JR: High altitude medicine. In Auerbach PS, Geehr EC (eds): Management of Wilderness and Environmental Emergencies, ed 2. St. Louis, CV Mosby, 1989, P 29 28. Hackett PH, Roach RC: High altitude pulmonary edema. J Wild Med 1:3, 1990 29. Harvard A, Thompson T: Mountain of Storms: The American Expeditions to Dhaulagiri. New York, New York University Press, 1974, p 50 30. Henriksson P, Varendh G, Lundstrom N-R: Haemostatic defects in cyanotic congenital heart disease. Br Heart J 41:23, 1979 31. Hornbein TF, Townes BD, Schoene RB, et al: The cost to the central nervous system of climbing to extremely high altitude. N Engl J Med 321:1714, 1989 32. Houston CS: Going Higher: The Story of Man and Altitude. Boston, Little, Brown & Co, 1987

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33. Hultgren HN, Grover RF: Circulatory Adaptation to High Altitude. Annu Rev Med 19:119, 1968 34. Hultgren HN: High Altitude Pulmonary Edema. Adv Cardiol 5:24, 1970 35. Hultgren HN: The safety of trekking at high altitude after coronary bypass surgery. JAMA 260:2218, 1988 36. Hultgren HN: Coronary heart disease and trekking. J Wild Med 1:154, 1990 37. Kasic JF, Yaron M, Nicholas RA, et al: Treatment of acute mountain sickness: Hyperbaric versus oxygen therapy. Ann Emerg Med 20:1109, 1991 38. King SI, Greenlee RR: Successful use of the Gamow hyperbaric bag in the treatment of altitude illness at Mount Everest. J Wild Med 1:193, 1990 39. Lane PA, Githens JH: Splenic syndrome at mountain altitudes in sickle cell trait: Its occurrence in non-black persons. JAMA 253:2251, 1985 40. Levine BD, Yoshimura K, Kobayashi T, et al: Dexamethasone in the treatment of acute mountain sickness. N Engl J Med 321:1707, 1989 41. Levine S, White DA, Fels AOS: An abnormal chest radiograph in a patient with recurring high altitude pulmonary edema. Chest 94:627, 1988 42. Lobenhoffer HP, Zink RA, Brendel W: High altitude pulmonary edema: Analysis of 166 cases. In Brendel W, Zink RA (eds): High Altitude Physiology and Medicine. New York, Springer, 1982, pp 219-231 43. Malhuber M, Humpeler E, Inama K, et al: Does altitude cause exhaustion of the heart and circulatory system? Med Sports Sci 19:192, 1985 44. McFadden OM, Houston CS, Sutton Jr, et al: High-altitude retinopathy. JAMA 245:581, 1981 45. Meehan RT: Immune suppression at high altitude. Ann Emerg Med 16:974, 1987 46. Milledge JS: The ventilatory response to hypoxia: How much is good for a mountaineer? Postgrad Med Jr 63:169, 1986 47. Montgomery AB, Mills I, Luce JM: Incidence of acute mountain sickness at intermediate altitude. JAMA 261:732, 1989 48. Moore, LG: Altitude-aggravated illness: Examples from pregnancy and prenatal life. Ann Emerg Med 19:965, 1987 49. Morgan BJ, Alexander JK, Nicoli SA, et al: The patient with coronary heart disease at altitude: Observations during acute exposure to 3100 meters. J Wild Med 1:147, 1990 50. Neill W, Hallenhauer M: Impairment of myocardial O 2 supply due to hyperventilation. Circulation 52:854, 1975 51. Oelz 0: High altitude cerebral oedema after positive airway pressure breathing at high altitude. Lancet 2:1148, 1983 52. Oelz 0, Maggiorini M, Ritter M, et al: Nifedipine for high altitude pulmonary oedema. Lancet 2:1241, 1989 53. Pizza CJ, Smith WE: Use of contact lenses on mountaineering expeditions. JAMA 252:2701, 1984 54. Rennie 0, Wilson R: Who should not go high. in Hypoxia: Man At Altitude. New York, Thieme-Stratton, 1982, pp 186-190 55. Rennie 0: Will mountain trekkers have heart attacks? JAMA 261:1045, 1989 56. Robertson JA, Shlim OR: Treatment of moderate acute mountain sickness with pressurization in a portable hyperbaric (Gamow"') bag. J Wild Med 2:268, 1991 57. Rock PB, Johnson TS, Larsen RF, et al: Dexamethasone as prophylaxis for acute mountain sickness: Effect of dose level. Chest 95:568, 1989 58. Rock PB, Johnson TS, Cymerman A, et al: Effect of dexamethasone on symptoms of acute mountain sickness at Pikes Peak, Colorado (4,300 m). Aviat Space Environ Med 58:668, 1987 59. Schoene RB, Roach RC, Hackett PH, et al: High altitude pulmonary edema and exercise at 4,400 meters on Mount McKinley: Effect of expiratory positive airway pressure. Chest 87:330, 1985 60. Schoene RB, Swenson EP, Pizzo CJ, et al: The lung at high altitude: Bronchoalveolar lavage in acute mountain sickness and pulmonary edema. J Appl Physiol 64:2605, 1988 61. Scoggin CH, Hyers TM, Reeves JT, et al: High altitude pulmonary edema in the children and young adults of Leadville, Colorado. N Engl J Med 297:1269, 1977

HIGH ALTITUDE MEDICINE

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62. Shlim D, Houston R: Helicopter rescues and deaths among trekkers in Nepal. JAMA 261:1017, 1989 63. Shlim DR, Meijer HJ: Suddenly symptomatic brain tumors at altitude. Ann Emerg Med 20:315, 1991 64. Singh I, Khanna PK, Srivastava MC, et al: Acute mountain sickness. N Engl J Med 280:175, 1969 65. Sophocies AM Jr: High-altitude pulmonary edema in Vail, Colorado, 1975-1982. West J Med 144:569, 1986 66. Taber RL: Protocols for the use of a portable hyperbaric chamber for the treatment of high altitude disorders. J Wild Med 1:181, 1990 67. Turner WA, Cohen MA, Moore S, et al: Carbon monoxide exposure in mountaineers on Denali. Alaska Med 30:85, 1988 68. Vock P, Fretz C, Franciolli M, et al: High-altitude pulmonary edema: Findings at high-altitude chest radiography and physical examination. Radiology 170:661, 1989 69. Ward MP, Milledge JS, West JB: High Altitude Medicine and Physiology. Philadelphia, University of Pennsylvania Press, 1989 70. Ward M: Mountain Medicine: A Clinical Study of Cold and High Altitude. London, Crosby Lockwood Staples, 1975 71. West JR: The safety of trekking at high altitude after coronary bypass surgery. JAM A 260:2218, 1988 72. Wilkerson JA: Medicine for Mountaineering. Seattle, The Mountaineers, 1992 73. Wilson ME, Fordham von Reyn C, Fineberg HV: Infections in HI V-infected travelers: Risks and prevention. Ann Intern Med 114:582, 1991 74. Winslow RM: Notes on Sickle Cell Disease. In Hypoxia: Man At Altitude. New York, Thieme-Stratton, 1982, pp 179-181 75. Wohns RNW: Transient ischemic attacks at high altitude. Crit Care Med 14:517, 1986 76. Zell SC, Goodman PH: Acetazolamide and dexamethasone in the prevention of acute mountain sickness. West J Med 148:541, 1988 77. Ziolkowski L, Wojcik-Ziolkowska E: Ischemic alternations in electrocardiogram and hemodynamic insufficiency during physical exercise in the mountain environment in patients after myocardial infarction. Przegl Lek 44:400, 1987

Address reprint requests to Stephen Bezruchka, MD, FACEP Department of International Health School of Hygiene and Public Health Johns Hopkins University 615 North Wolfe Street Baltimore, MD 21205