Diagnosis and Treatment of Altitude Illness
By William H. Shoff, MD, DTMH and Stephanie B. Abbuhl, MD, FACEP
Altitude illness (AI) can be fatal if it is not diagnosed and treated early enough. Deaths have occurred as a result of unacclimatized travelers gaining rapid access to the high altitudes of the world through modern transportation. High altitude venues are listed in Table 1. Millions of people travel to intermediate altitude (5000-8000 feet) and high altitude (8000-14,000 feet) locations each year. A small subset ascend to very high altitude (14,000-18,000 feet) and extreme altitude (18,000-29,028 feet—the summit of Mt. Everest). Individual response to altitude varies greatly. While one person may develop AI at 8500 feet, another may be unaffected until reaching 16,000 feet. Everyone, however, is susceptible to AI every time he or she ascends.
|Altitudes at Various Geographic Locations|
(feet above sea level)
|Mt. Kilimanjaro, Tanzania||19,210 (summit readily ascended without technical equipment)|
|La Paz, Bolivia||12,730|
|Santa Fe, NM||10,283|
|Mexico City, Mexico||7347|
U.S. ski resorts
(above 8000 feet at base)
Barometric pressure decreases with increasing altitude, as does the partial pressure of oxygen, leading to hypoxia. The PaO2 is 94 mm Hg at sea level in a healthy person; 60 mm Hg at 8000 feet; 44 mm Hg at 15,000 feet; and 28 mm Hg at 29,028 feet.1 During sleep, hypoxemia is detectable in normal men at sea level.2 At increased altitude, it is accentuated and can exacerbate AI.3 Hypoxia initiates a series of events that may lead to acute mountain sickness (AMS), mild to moderate cerebral syndrome; high altitude cerebral edema (HACE), severe cerebral syndrome; and high altitude pulmonary edema (HAPE). Death may result in advanced cases. Although the precise sequence of biochemical events is not yet identified, the end stage pathophysiology involves overperfusion of the microvascular beds, increased capillary hydrostatic pressure, leakage, and edema formation.4
The major pathology is in the brain and lungs. In the brain, hypoxia leads to vasodilatation, increased cerebral blood flow/blood volume, impaired autoregulation, and overperfusion.4 Recent data suggest that all persons ascending to high altitude have brain swelling.4 In a case series with autopsy data from 11 AI patients,1 brain specimens demonstrated cerebral edema (9), petechial hemorrhages (7), venous thrombosis (2), focal tissue destruction, spongiosis, and brain herniation (2). In the lungs, hypoxia causes alveolar hypoxia, pulmonary hypertension, uneven pulmonary vasoconstriction, sympathetic discharge, increased pulmonary blood volume, and focal overperfusion.1 At autopsy, lung specimens demonstrated thrombosis (6), infarction (5), pneumonia (8), and edema (7).1
Clinical Definition and Diagnosis
The Lake Louise Consensus Definition of Altitude Illness delineates the diagnosis of AMS, HACE, and HAPE.5,6 The consensus definition does not include altitudes, but those listed below reflect the lowest altitudes generally associated with the AI syndromes, with few exceptions.1,4,7,8 Although the differential diagnosis is important, any illness at altitude is AI until proven otherwise.4
AMS diagnosis requires a recent gain in altitude (> 6,300 feet), and the presence of a headache coupled with one of the following:
- gastrointestinal distress (anorexia, nausea, vomiting),
- dizziness/lightheadedness, or
- difficulty sleeping.
HACE diagnosis requires a recent gain in altitude (> 8000 feet) coupled with one of the following:
- Mental status change or ataxia in the presence of AMS, or
- Mental status change and ataxia in the absence of AMS.
HAPE diagnosis requires a recent gain in altitude (> 8000 feet) coupled with both of the following:
- Two or more of the following symptoms: dyspnea at rest, cough, weakness/decreased exercise performance, and chest tightness/congestion; and
- Two or more of the following signs: crackles/wheezing in at least one lung field, central cyanosis, tachypnea, and tachycardia.
The higher the attained altitude, the greater the incidence of AI.1,7-11 (See Table 2.) Sleeping altitude defines the altitude attained, not the altitude reached for a brief period (minutes or hours). Several factors have been shown to affect the development of AI.1,8,12-15 (See Table 3.) Several other factors relative to AI deserve comment.1,4 AI susceptibility seems to be greater in young individuals (< age 30) and less in older individuals (> age 50). Women acclimatize better than men, and seem less susceptible to HAPE, but equally susceptible to AMS. Physical conditioning does not prevent AI. Conditions not associated with an increased risk for AI include asthma, mild chronic obstructive lung disease (normal blood gas), coronary artery disease, diabetes mellitus, hypertension, and pregnancy. Conditions associated with pulmonary hypertension, including primary pulmonary hypertension and certain types of congenital and valvular heart disease, increase the AI risk. Obesity also is a risk factor.
|Table 2 1,7-11|
|Attained Altitude and Incidence of Altitude Illness|
|Intermediate altitude (6300-8000 feet)||Incidence of AMI (%)|
|Lower high altitude (8000-9700 feet)|
|Higher high altitude (10,000-14,000 feet)|
|Very high altitude|
|* Rare below 9000 feet unless precipitated by HAPE|
|Table 3 1,8,12-15|
Factors Affecting Development of Altitude Illness
|• Sleep hypoxemia|
|• Rate of ascent|
|• Prior history of altitude illness|
|— 60% recurrence of HAPE with rapid ascent to 15,000 feet12|
|• Permanent residence below an altitude of 3000 feet|
|• Degree of exertion upon arrival at altitude|
|• Resting PO2 of 50 mmHg (saturation 88%)|
|— Relative contraindication for travel to high altitude1|
|• Duration at extreme altitude|
|— Prolonged stay at extreme altitude results in high altitude deterioration|
• Re-ascending after acclimatizing to high altitude and descending to a lower altitude
|— Adults lose adaptation in approximately 10-14 days|
|— Children lose adaptation in fewer than seven days|
AMS typically develops within 1-48 hours after arriving at altitude, usually within the first 6-12 hours.1,4,8 When it occurs in under six hours, it is because of rapid ascent to very high altitude or heavy exertion upon arrival. Symptoms progress on days two and three and subside by days 5-8. They are worse during the night secondary to sleep hypoxemia. Hultgren reviewed 10 studies conducted at altitudes between 10,000 and 17,500 feet.1 The most common symptoms were altered mentation/memory, dizziness, dyspnea, GI disturbance (anorexia, nausea, or vomiting), headache, insomnia, and lassitude/fatigue. Headache was the most predominant symptom, typically worse in the morning and exacerbated by exercise. Dyspnea occurred with some exertion but did not occur at rest. Signs included tachycardia, tachypnea, and peripheral edema (women more often than men). Blood gas analysis has demonstrated decreased oxygen content during AMS compared to controls. In one study at 14,430 feet, the PO2 was 34 mm in the presence of AMS symptoms and 40 mm in the control group.16 Unless there is progression to HAPE/HACE, AMS subsides over approximately seven days.
HACE begins 1-17 days after arrival at altitude (9000-20,000 feet). Symptoms (42 cases summarized)1 include unconscious/semiconscious (67%), ataxia (usually truncal) (59%), headache (40%), lethargy/weakness (36%), vomiting (33%), and irrational behavior (17%). Signs included decreased conscious level (74%), ataxia (64%), retinal hemorrhages (62%), papilledema (55%), bladder dysfunction (50%), positive Babinski (36%), and limb weakness (14%). HAPE occurred in conjunction with HACE in 31% of the cases. Spinal fluid cell counts, protein, and sugar are usually normal. The opening pressure may be normal or elevated. Early identification and treatment can be life saving. If death does not occur, recovery is complete, with rare exception.
HAPE typically begins within the first 2-4 days (rarely later) of ascent to 8000 feet or higher. It is usually associated with rapid ascent or heavy exertion, or both.1,4 Two reported series with a total of 286 cases included the following symptoms: dyspnea (particularly at rest) (74%), cough (69%), headache (44%), malaise (43%), nausea (29%), coma (24%), vomiting (17%), confusion (12%), insomnia (12%), and orthopnea (11%).1 Signs include cyanosis, lack of participation, decreasing effort, irrational behavior, tachypnea, gurgling respirations, tachycardia, fever, hemoptysis, rales, and cool/pale extremities. Fever may occur, but when it is greater than 101°F pneumonia or other bacterial infection should be suspected. Other associated conditions are HACE (the most commonly associated condition), pulmonary embolus, pulmonary infarction, aspiration pneumonia, and myocarditis.4 The WBC can be normal or elevated. In a series of 15 cases, the PO2 was 31.7 ± 5.5.16 The ECG demonstrates sinus tachycardia and may show right ventricular strain, right bundle branch block, and P-wave abnormalities.1,4 Chest x-ray reveals a normal-sized heart with a range of lung parenchymal findings seen in noncardiogenic pulmonary edema, including small infiltrates in the right mid-lung field, patchy infiltrates, diffuse bilateral infiltrates, or interstitial edema.1 Although patients may appear very ill, aggressive management often prevents death; however, death does occur unexpectedly in about 20% of cases.1
Acclimatization, Prevention, and Periodic Breathing
Acclimatization. When the human body is exposed to the reduced oxygen tension of altitude, it undergoes immediate adaptations and begins longer-term adjustments to maintain the oxygen gradient high enough at the cellular level to support oxidative processes. Immediate adaptations include increased depth and rate of respiration, shifts in the oxyhemoglobin dissociation curve at the alveolar and capillary level, and cellular adaptations, such as myoglobin facilitating oxygen diffusion.1 In addition, the hypoxic stimulation of the respiratory centers overrides the inhibitory effect of hypocapnea. Over time, normal respiratory stimulation by carbon dioxide returns, pulmonary diffusion capacity changes, and red cell mass increases. Athletic performance at intermediate and high altitude is initially decreased and requires 2-6 weeks to improve; however, sea level performance is not regained.1,17 Physical conditioning does not accelerate acclimatization. Acclimatization is sufficient after a few days so that most people can then proceed with their usual activity.
Prevention. Prevention involves slow ascent, avoiding heavy physical exertion upon arrival, and the use of acetazolamide or other medications. Recommendations on ascent adapted from Hultgren are shown in Table 4.1 The maximum recommended ascent rate is 2000 feet per 24 hours above 8000 feet, with an extra day of rest added for every additional 2000-4000 feet attained.4 Heavy physical exertion upon arrival exacerbates AI. (See section on Epidemiology.) Acetazolamide leads to a decrease in bicarbonate, pH, and alveolar PCO2; an increase in alveolar PO2; and has been shown to be efficacious in preventing AI by accelerating acclimatization.1 These effects are lost by the fifth day. The recommended dose is 125-250 mg twice a day beginning one day prior to ascending and continuing for two days upon arrival. If acetazolamide cannot be used, dexamethasone (which treats AMS) is an alternative, beginning the day of ascent with a dose of 2 mg tid on days one and two, 2 mg bid on day three, and 2 mg on day four. Other dexamethasone regimens have been published. Ginkgo biloba also has been reported to be effective.4
Periodic Breathing. Periodic breathing (several deep breaths followed by apnea [usually 8-12 seconds]), may or may not disturb sleep.1 When the apneic period is longer than 20-30 seconds, most people awaken. Periodic breathing is less common in women, although above 10,000 feet it occurs in most individuals. It is eliminated by inhaling oxygen and reduced by taking acetazolamide (62.5-125 mg per night).1
To maximize benefit and minimize the potential for progression to death, it is imperative that AI be recognized and treated as early as possible. Treatment is centered on descending 1500 feet to a lower altitude, evacuation, oxygen therapy, medications, and hyperbaric therapy. The following recommendations are adapted from Hackett and Roach:4
• Mild AMS—Initiate one or more of the following: descend or stop ascent and rest for at least 24 hours; take acetazolamide (125-250 mg bid); use analgesics as required.
• Moderate AMS—Initiate one or more of the following: follow mild AMS treatment guidelines; if unable to descend, use a portable hyperbaric chamber; administer nasal oxygen at 1-2 liters/minute; administer acetazolamide 250 mg bid, dexamethasone 4 mg PO/IM q 6h, or both until symptoms subside;
• HACE—Initiate immediate descent or evacuation; if descent not possible, use a portable hyperbaric chamber; administer nasal oxygen at 2-4 liters/minute; administer dexamethasone 8 mg PO/IM/IV immediately, then 4 mg q 6h; administer acetazolamide 250 mg bid;
• HAPE—Administer nasal oxygen immediately at 4-6 liters/minute followed by 2-4 liters/minute when symptoms improve to conserve oxygen; descend as soon as possible with minimal effort by patient; if descent not possible or oxygen unavailable, use a portable hyperbaric chamber; administer nifedipine 10 mg PO followed by 30 mg extended-release q 12-24h; administer dexamethasone as in HACE, if neurologic deterioration occurs.
|Recommendations for Altitude Ascent|
• When ascending to high altitude, sleep at an intermediate altitude for 1-3 nights
• When ascending to very high altitude with further rapid ascent anticipated, sleep at an altitude between 9000 and 12,000 feet for 4-5 nights
• When ascending above very high altitude and higher, ascend no faster than 1500 feet per day
1. Hultgren H. High Altitude Medicine. Stanford, CA: Hultgren Publications;1997.
2. Block B, et al. Sleep apnea, hypopnea, and oxygen saturation in normal subjects: A strong male predominance. N Engl J Med 1979;300:513-517.
3. Sutton J, et al. Effects of acclimatization on sleep hypoxemia at altitude. In: West J, Lahiri S, eds. High Altitude and Man. Bethesda, MD: American Physiology Society; 1984: 73-90.
4. Hackett PH, et al. High-altitude illness. N Engl J Med 2001;345:107-114.
5. Web: www.high-altitude-medicine.com/AMS-LakeLouise.html (accessed 9/10/2001).
6. Hypoxia and Mountain Medicine. Sutton JR, et al, eds. In: Adv Biosci. Oxford: Pergamon Press; 1992, Vol. 84.
7. Ward PM, et al. High Altitude Medicine and Physiology. 3rd ed. London: Arnold; 2000.
8. Honigman B, et al. Acute mountain sickness in a general tourist population at moderate altitudes. Ann Intern Med 1993;118:587-592.
9. Hackett PH, et al. High-Altitude Medicine. In: Auerbach PS, ed. Wilderness Medicine. 4th ed. St. Louis: Mosby; 2001:2-43.
10. Pollard AJ, et al. The High Altitude Medicine Handbook. 2nd ed. Abington, Oxon, Radcliffe Medical Press, 1997.
11. Singh I, et al. High altitude pulmonary edema. Lancet 1965;1:229-234.
12. Bartsch P, et al. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 1969;280:175-184.
13. Roach RC, et al. Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol 2000;88:581-585.
14. Dillard TA, et al. Hypoxemia during air travel in patients with chronic pulmonary disease. Ann Intern Med 1989;111:362-367.
15. Pugh L. Physiological and medical aspects of the Himalayan Scientific and Mountaineering Expedition, 1960-61. Brit Med J 1962;2:621-627.
16. Bartsch P, et al. Respiratory symptoms, radiographic, and physiologic correlations at high altitude. In: Sutton J, et al, eds. Hypoxia: The Adaptations. Toronto: BC Decker; 1990: 241-245.
17. Faulkner J, et al. Maximum aerobic capacity and running performance at altitude. J Appl Physiol 1968;24:685-691.