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The author works in emergency medicine at the Eden Medical Center, Castro Valley, Calif. He has indicated no relationships to disclose relating to the content of this article.

High-altitude illness includes the pulmonary and cerebral syndromes that can develop in unacclimated persons after an ascent to high altitude. The three major types of high-altitude illness are acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE). Individual susceptibility to altitude illness varies considerably, and there are no screening tests to predict risk for altitude illness. Susceptibility appears to be inherent in some way and is not affected by training or physical fitness. How a traveler has responded in the past to exposure to high altitude is the most reliable guide for future trips, but even this is not infallible. PAs should be familiar with these illnesses, as they may be called upon to treat the acutely ill or may be asked to consult with patients before high-altitude travel.

ACUTE MOUNTAIN SICKNESS

AMS is the most common form of altitude illness. Among lowland-living people visiting high altitudes, the prevalence of AMS has been reported at 25% to 75%.^1-4 Onset of symptoms typically occurs 8 to 96 hours after arrival at altitudes greater than 8,000 feet, although symptoms of AMS can also occur at lower altitudes. In one study of more than 3,000 tourists visiting moderate altitude (6,300-9,700 feet) ski resorts in Colorado, 25% experienced manifestations of AMS, including at least three or more of the following: loss of appetite, vomiting, shortness of breath, dizziness or lightheadedness, unusual fatigue, sleep disturbance, and headache.¹ The majority of these symptoms occurred within the first 12 hours after arrival.

Clinical manifestations

The most common symptoms of AMS are a mild headache, anorexia, insomnia, fatigue, nausea, shortness of breath with exertion, and sensation of an alcohol hangover5 (see Table 1). The headache of AMS is typically described as throbbing, bitemporal or occipital, and worse with Valsalva’s maneuver or stooping over.⁵ There is no neurologic dysfunction or deficit. Differentiating AMS from other conditions is important. AMS is commonly misdiagnosed as a viral illness, but AMS does not cause fever or myalgia. An alcohol hangover can typically be excluded by the history.

Diagnosis

The diagnosis of AMS is based on setting, symptoms, physical findings, and exclusion of other illnesses.⁵ In 1991, the Lake Louise scoring system was developed. It serves primarily as a tool for research and academic purposes, although recent studies have cast doubt on its sensitivity.⁶ The most sensitive test for AMS is a decrease in activity level and a subjective sensation of feeling ill.⁷ Physical examination findings may be quite unremarkable. Increased respiratory and pulse rates may be observed, but the remainder of the physical examination is usually normal.⁸ Laboratory tests and radiographs are of little value when the history and examination are normal aside from findings suggesting AMS and when other illnesses have been excluded.

Prevention and treatment

Acclimation at altitude may take 12 hours to 4 days.⁵ Recognizing AMS early is crucial if prevention of further, more critical illness is to be avoided. Upon first recognizing symptoms, the person should stop any further ascent and should rest and acclimate until symptoms improve. Ideally, the person should receive supplemental oxygen and prepare for descent to a symptom-free altitude (typically, descending 1,500-3,000 feet provides relief).⁷ Descent is not always possible, however, in which case medical therapy is crucial.

For relief of mild symptoms, including nausea and headache without neurologic dysfunction, antiemetics, supplemental oxygen, and analgesics usually suffice. In addition, use of a portable hyperbaric chamber—now common on expeditions to popular high-altitude destinations in remote locations—may provide relief. Inflating the chamber to a pressure of 2 pounds per square inch provides an altitude equivalent that is roughly 6,000 feet lower than the actual surrounding altitude.⁹ For people requiring treatment, the safest agent is acetazolamide, which reduces periodic breathing and improves nocturnal oxygenation.⁹ Zolpidem does not depress ventilation at high altitude and may therefore be a safe treatment for insomnia in persons with AMS.¹⁰ After the AMS has resolved, any further ascent should be made with caution, perhaps with acetazolamide prophylaxis.⁹

Acetazolamide Mountaineers and other high-altitude travelers have used acetazolamide for prophylaxis and acute treatment of AMS for several years. A carbonic anhydrase inhibitor and mild diuretic, it forces bicarbonate excretion from the kidneys, which reacidifies the blood, balancing the effects of the expected hyperventilation that occurs at altitude in an attempt to get oxygen. This reacidification acts as a respiratory stimulant, particularly at night, reducing or eliminating the periodic breathing pattern common at altitude. The net effect is to accelerate acclimation.¹¹ Acetazolamide is not a magic bullet, and cure of AMS is not immediate. The effect of acetazolamide is to accelerate a process that would normally take 24 to 72 hours to a period of 12 to 24 hours. The most common adverse effect associated with acetazolamide is extremity paresthesias, which usually stop once the medication is ceased.

The ideal dosing of acetazolamide has been the subject of much research. Studies have shown excellent results in the prevention and treatment of AMS with daily dosages from as low as 250 mg to as high as 750 mg.^7,12 The optimal dosage is uncertain; more comparisons of dosing regimens are necessary. The 750-mg dosage clearly works, but patients may complain of unbearable paresthesias.⁷ Until further studies are performed, current recommendations of acetazolamide for otherwise healthy adults are 250 mg daily in two divided doses for acute treatment or started 3 to 4 days before ascent for prophylaxis.^11-12 Persons with a hypersensitivity to sulfonamides should avoid acetazolamide. Concomitant use of salicylates and acetazolamide should be avoided because it may cause CNS depression and metabolic acidosis.

Ginkgo biloba While some studies have found pretreatment with Ginkgo biloba to be effective,¹³ other research has not.¹⁴ Studies are inconclusive, in part because ginkgo is a complicated plant extract and preparations vary considerably. In addition, dosing, timing, and ascent profiles have differed.⁷ Although ginkgo is relatively safe, further studies are needed.

High-altitude pulmonary edema

HAPE is potentially fatal and causes most of the deaths due to high-altitude illness.¹⁵ HAPE is a noncardiogenic pulmonary edema associated with pulmonary hypertension and elevated capillary pressure.¹⁶

Clinical manifestations

The symptoms of HAPE may appear insidiously over the course of several hours or days but can also manifest explosively and occur without preceding AMS. HAPE generally affects healthy young persons, and children appear to be more susceptible than adults.¹⁷ In addition, those who have experienced HAPE in the past are at increased risk for recurrence.¹⁷

Early symptoms of HAPE include dry cough and dyspnea with exertion and at rest. These symptoms often progress to subjective and objective findings of elevated jugular venous pressure, diffuse crackles on lung auscultation, and development of frothy sputum, tachypnea, and cyanosis.⁹ Chest radiography typically reveals a normal-sized heart, full pulmonary arteries, and patchy infiltrates, which are generally confined to the right middle and lower lobes in mild cases and are found in both lungs in more severe cases9 (see Figure 1). ECG usually demonstrates sinus tachycardia and often shows right ventricular strain, right axis deviation, right bundle branch block, and P-wave abnormalities.⁹ Arterial blood gas measurements typically reveal severe hypoxemia and respiratory alkalosis but not respiratory acidosis.⁹

Prevention and treatment

Ascending slowly is the most effective means of preventing HAPE. People who have previously experienced HAPE may want to consider prophylaxis with nifedipine. In a study of mountaineers with a history of radiographically documented HAPE, 20 mg of nifedipine was given by mouth every 8 hours while subjects ascended from a low altitude and during the following 3 days at altitude. Compared to a placebo group, those taking nifedipine had a significantly decreased incidence of HAPE (10% in the nifedipine group versus 70% in the placebo group).¹⁸

Prophylactic inhalation of high doses of a beta-agonist is another way to decrease the risk of developing HAPE. In a double-blind, randomized controlled trial of inhaled salmeterol, a dosage of 125 mcg every 12 hours was associated with a 50% decrease in the incidence of HAPE.¹⁹

Oxygen The highest priority in patients with HAPE is to increase alveolar and arterial oxygenation. Breathing supplemental oxygen reduces pulmonary artery pressure 30% to 50%, which is sufficient to reverse the effects of HAPE early.^20-22 Portable hyperbaric oxygen therapy units, which are becoming increasingly popular on mountaineering expeditions, may provide dramatic temporary relief until a patient can be moved to a lower altitude. Hyperbaric oxygen units effectively “lower” a patient several thousand feet in a matter of minutes.

Nifedipine Well-controlled studies have been performed examining nifedipine use for HAPE prophylaxis. Nifedipine in the acute treatment of HAPE continues to be studied, but preliminary data support this use.^20,23 In patients experiencing HAPE, the sublingual administration of 10 mg of nifedipine resulted in clinical improvement, better oxygenation, reduction of pulmonary artery pressure, and progressive clearing of alveolar edema.23 Since hypotension is the most worrisome side effect of nifedipine, BP monitoring is important; however, nifedipine offers a potential emergency treatment for HAPE when descent or evacuation is impossible and oxygen is not available.

Sildenafil Preliminary research on the use of sildenafil for acute treatment of HAPE has shown promising results. In one study of healthy mountaineers, 50 mg of sildenafil taken orally reduced pulmonary artery pressure at rest and with exercise, allowing increased exercise capacity at high elevation.²⁴ Other studies have also shown sildenafil to significantly decrease pulmonary hypertension.^25-28 These investigations used varying dosages, and although results are promising, further research is needed.

High-altitude cerebral edema

HACE is another potentially life-threatening condition. The current hypothesis is that HACE involves decreased integrity in the blood-brain barrier coupled with an increase in cerebral blood flow induced by hypoxia.^9,29,30 MRI studies of people with HACE have shown reversible white-matter edema, most prominently in the splenium of the corpus callosum.³¹

Clinical manifestations

Symptoms of HACE may appear within hours or days of arrival at high altitude. Signs and symptoms include papilledema, loss of cerebellar control, confusion, decreased mental status, and coma.⁵ Typically, globally diminished neurologic function is observed, rather than focal neurologic deficits. A headache, commonly seen in AMS, typically precedes HACE symptoms. However, headaches seen in AMS lack any accompanying neurologic dysfunction.

Prevention and treatment

Slow ascent is the best way to prevent HACE, a potentially life-threatening emergency that requires immediate management. Upon recognizing HACE in an individual, make plans for immediate descent and administer supplemental oxygen and dexamethasone. The suggested dose of dexamethasone is 8 mg by mouth initially, followed by 4 mg by mouth every 6 hours.³² If descent to a lower altitude is not immediately possible, the patient may be placed in a portable hyperbaric chamber as a temporary measure.

Conclusion

Whether skiing the slopes of Colorado’s high country or wandering the streets of La Paz, Bolivia, travelers at high altitude find both exciting opportunities and the potential for serious illness. Those who do not live at high altitudes rarely want to spend 2 to 3 days of a 7-day vacation resting and acclimating. Whether treating patients in a high-altitude ski town or consulting with them before a high-altitude trip, PAs should encourage appropriate acclimation, slow ascension, and early recognition of symptoms.

REFERENCES

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