Shaun D. Carstairs
EPIDEMIOLOGY
The incidence of acute mountain sickness (AMS), as well as high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE), is influenced primarily by the rapidity of ascent and sleeping altitude.
The incidence of AMS is 17% and 40% at resorts with altitudes between 2200 and 2700 m (7200 and 9000 ft).
The incidence of HAPE is much lower than that of AMS. HAPE has been reported in less than 1 in 10,000 skiers in Colorado, and 2% to 3% of climbers on Mt. McKinley. The incidence of HACE is lower than that of HAPE.
PATHOPHYSIOLOGY
AMS is caused by hypobaric hypoxia, and HAPE and HACE can be viewed as extreme progressions of the same pathophysiology.
Hypobaric hypoxemia increases cerebral blood flow and cerebral capillary hydrostatic pressure, contributing to fluid shifts, and cerebral edema (mild in AMS, severe in HACE). In addition, increased permeability of capillaries as a result of inflammatory endothelial activation may also play a role, especially in the brain.
Hypoxemia elevates sympathetic nervous system activity, which promotes uneven pulmonary vasoconstriction and increases pulmonary capillary pressure.
Increased sympathetic nervous system activity is associated with decreased urine output, mediated by increased renin-angiotensin, aldosterone, and antidiu-retic hormone (ADH). This leads to fluid retention and results in elevated capillary hydrostatic pressure in lungs, brain, and peripheral tissues.
Susceptibility to AMS is linked to a low hypoxic ven-tilatory response and low vital capacity; susceptible individuals are prone to recurrence on return to high altitude.
Partially acclimatized individuals who live at intermediate altitudes of 1000 to 2000 m are less likely to develop AMS on ascent to higher altitude.
CLINICAL FEATURES
AMS is usually seen in unacclimated people making a rapid ascent to over 2000 m (6600 ft) above sea level. The earliest symptoms are light-headedness and mild breathlessness.
Symptoms similar to a hangover may develop within 6 hours after arrival at altitude, but may be delayed as long as 24 hours. Symptoms may include bifrontal headache, anorexia, nausea, weakness, and fatigue.
Worsening headache, vomiting, oliguria, dyspnea, and weakness can indicate progression of AMS.
There are few specific physical examination findings in AMS. Postural hypotension and peripheral and facial edema may occur. Localized rales are noted in 20% of cases. Funduscopy can reveal tortuous and dilated veins; retinal hemorrhages are common at altitudes over 5000 m.
HACE is an extreme progression of AMS and is usually associated with pulmonary edema. It presents with altered mental status, ataxia, stupor, and progression to coma. Focal neurologic signs such as third and sixth cranial nerve palsies may be present.
HAPE is the most lethal of the high-altitude syndromes. Risk factors include heavy exertion, rapid ascent, cold exposure, excessive salt intake, use of sleeping medications, and previous history of HAPE.
Individuals with pulmonary hypertension as well as children with acute respiratory infections may be more susceptible to HAPE.
Early findings of HAPE include a dry cough, impaired exercise capacity, and localized rales, usually in the right mid-lung field.
Progression of HAPE leads to tachycardia, tachypnea, resting dyspnea, severe weakness, productive cough, cyanosis, and generalized rales. Low-grade fever is common.
As hypoxemia worsens, consciousness is impaired, and without treatment, coma and death usually follow.
Other findings of HAPE may include signs of pulmonary hypertension such as a prominent P2 and right ventricular heave on cardiac examination, as well as right axis deviation and a right ventricular strain pattern on electrocardiogram (ECG).
Early recognition of HAPE, and descent and treatment are essential to prevent progression.
High altitude may adversely affect patients with chronic obstructive pulmonary disease (COPD), heart disease, sickle-cell disease, and pregnancy.
COPD patients may require supplemental O2 or an increase in their usual O2 flow rate.
Patients with atherosclerotic heart disease do surprisingly well at high altitude, but there may be a risk of earlier onset of angina and worsening of heart failure.
Ascent to 1500 to 2000 m may cause a vaso-occlusive crisis in individuals with sickle-cell disease or sickle thalassemia.
Individuals with sickle-cell trait usually do well at altitude, but splenic infarction has been reported during heavy exercise.
Pregnant long-term high-altitude residents have an increased risk of hypertension, low-birth-weight infants, and neonatal jaundice, but no increase in pregnancy complications has been reported in pregnant visitors to high altitude who engage in reasonable activities.
It is reasonable to advise pregnant women to avoid altitudes above which oxygen saturation falls below 85%; this corresponds to a sleeping altitude of approximately 10,000 ft.
DIAGNOSIS AND DIFFERENTIAL
The differential diagnosis of the high-altitude syndromes includes hypothermia, carbon monoxide poisoning, pulmonary or central nervous system infections, dehydration, and exhaustion.
HACE may be difficult to distinguish in the field from other high-altitude neurologic syndromes.
Strokes due to arterial or venous thrombosis or arterial hemorrhage have been reported at high altitude in individuals without classic risk factors.
Reversible focal neurologic signs or symptoms may occur and may be due to vasospasm, migraine headache, or transient ischemic attack. These syndromes typically have more focal findings than HACE.
Previously asymptomatic brain tumors may be unmasked by ascent to high altitude.
Underlying epilepsy may be worsened by hyperven-tilation, which is part of the normal acclimatization response.
HAPE must be distinguished from pulmonary embolus, cardiogenic pulmonary edema, and pneumonia. Low-grade fever is common in HAPE and may make it difficult to distinguish from pneumonia.
A key to diagnosis is the clinical response to treatment.
CARE AND DISPOSITION IN THE FIELD AND EMERGENCY DEPARTMENT
AMS can usually be avoided by gradual ascent. A reasonable recommendation for sea-level dwellers is to spend a night at 1500 to 2000 m before sleeping at altitudes above 2500 m.
High-altitude trekkers should allow two nights for each 1000-m gain in sleeping altitude starting at 3000 m.
Eating a high-carbohydrate diet and avoiding overex-ertion, alcohol, and respiratory depressants may also help prevent AMS.
Mild AMS usually improves or resolves in 12 to 36 hours if further ascent is delayed and acclimatization is allowed. A decrease in altitude of 500 to 1000 m may provide prompt relief of symptoms.
Oxygen relieves symptoms of mild AMS, and nocturnal low-flow O2 (0.5-1 L/min) is helpful.
Patients with mild AMS should not ascend to a higher sleeping elevation. Descent is indicated if symptoms persist or worsen.
Immediate descent and treatment is indicated if there is a change in the level of consciousness, or if there is ataxia or pulmonary edema.
Acetazolamide causes a bicarbonate diuresis, leading to a mild metabolic acidosis. This stimulates ventilation and pharmacologically produces an acclimatization response. It is effective for prophylaxis and treatment.
Specific indications for acetazolamide are (1) prior history of altitude illness; (2) abrupt ascent to over 3000 m (10,000 ft); (3) treatment of AMS; and (4) symptomatic periodic breathing during sleep at altitude.
The adult dose of acetazolamide is 125 to 250 milligrams PO twice daily; it is continued until symptoms resolve or is started 24 hours before ascent and continued for 2 days at altitude as prophylaxis.
Acetazolamide should be restarted if symptoms recur. Acetazolamide is contraindicated in sulfa-allergic patients.
Dexamethasone 4 milligrams PO, IM, or IV every 6 hours, is effective in moderate to severe AMS. Tapering of the dose over several days may be necessary to prevent rebound.
Aspirin or acetaminophen may improve headache in AMS. Ondansetron 4 milligrams PO (disintegrating tablet) every 6 hours may help with nausea and vomiting.
Diuretics may be useful for treating fluid retention, but should be used with caution to avoid intravascular volume depletion.
HACE mandates immediate descent or evacuation. Oxygen and dexamethasone, 8 milligrams PO, IM, or IV initially, then 4 milligrams every 6 hours, should be administered.
Intubation and hyperventilation may be necessary in severe cases of HACE. Careful monitoring of arterial blood gases is needed to prevent excessive lowering of Pco2 (below 30 mm Hg), which may cause cerebral ischemia. Mannitol should also be considered.
HAPE should also be treated with immediate descent. Oxygen may be life-saving if descent is delayed. The patient should be kept warm and exertion minimized.
For HAPE, drugs are second-line treatment after descent and oxygen. Nifedipine, 20 to 30 milligrams extended release PO every 12 hours, may be effective. Sildenafil, 50 milligrams PO three times daily, and tadalafil, 10 milligrams PO twice daily, both blunt hypoxic pulmonary vasoconstriction and may be considered. Inhaled albuterol 2 to 4 puffs every 6 hours may also be considered but is not well studied.
HAPE patients are usually volume depleted, and care should be taken to avoid precipitating drug-induced hypotension.
An expiratory positive airway pressure (EPAP) mask may be useful in the field, and without supplemental O2 can increase oxygen saturation by 10% to 20%.
Portable fabric inflatable hyperbaric chambers may be effective in the field when immediate descent is not possible.
In individuals with prior episodes of HAPE, nifedipine, 20 milligrams extended release PO every 12 hours, every 8 hours during ascent may be effective as prophylaxis.
MISCELLANEOUS HIGH-ALTITUDE SYNDROMES
Acute hypoxia may occur with decompression of an aircraft or failure of a mountaineer’s oxygen delivery system. Symptoms include dizziness, light-headedness, and dimming of vision progressing to loss of consciousness.
A sudden drop in oxygen saturation to 50% or 60% will usually result in unconsciousness. Deliberate hyperventilation may increase the period of useful consciousness in the setting of acute hypoxia.
High-altitude retinopathy includes retinal edema, tortuous and dilated retinal veins, disc hyperemia, retinal hemorrhages, and less frequently, cotton wool exudates.
Except for macular hemorrhages, retinal hemorrhages are usually asymptomatic and descent is not indicated unless visual changes occur; hemorrhages usually resolve in 10 to 14 days.
High-altitude pharyngitis and bronchitis are due to local irritation and drying of mucus membranes from breathing high volumes of cold, dry air. Severe coughing spasms and bronchospasm may be present. Symptomatic treatment as well as hydration, lozenges to encourage salivation, and breathing of steam or through a scarf to trap moisture and heat may provide some relief.
Chronic mountain polycythemia in long-term high-altitude residents may be attributed to underlying diseases (such as COPD or sleep apnea) that worsen hypoxia at altitude in half of patients, or may be linked to idiopathic hypoventilation due to a diminished respiratory drive.
Symptoms of chronic mountain polycythemia include impaired cognition, sleep, and peripheral circulation, as well as headache, drowsiness, and chest congestion, along with abnormally elevated hemoglobin levels, usually over 20 to 22 grams/dL.
Treatment options for chronic mountain polycythemia include moving to a lower altitude, phlebotomy, home oxygen, and respiratory stimulants such as acetazola-mide and medroxyprogesterone.
Ultraviolet keratitis (snow blindness) may affect unprotected eyes in as little as 1 hour at high altitude. Findings include severe pain, photophobia, tearing, conjunctival erythema, chemosis, and eyelid swelling.
Cold compresses, analgesics, and occasionally eye patching are generally adequate symptomatic treatment for ultraviolet keratitis; the keratitis usually heals in 24 hours. Prevention with adequate sunglasses that transmit less than 10% of UVB light is essential.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 216, “High Altitude Medical Problems,” by Peter H. Hackett and Jenny Hargrove.