Patients participating in occupational and sports-related activities requiring ascent to high elevations are at risk of developing a range of high-altitude illnesses. Prompt recognition and treatment are paramount to improving outcomes and preventing life-threatening sequelae. High-elevation locations are the setting of many recreational activities for outdoor enthusiasts. As such, illnesses associated with high altitude may be encountered by those summiting peaks, traveling by air, or working in flight medicine or as part of an emergency rescue team. The altitude syndromes discussed in this review are acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). While these conditions do not represent all altitude-related illnesses, they are the primary pathological processes for which physicians should be familiar when working with high-altitude populations.
Physiological Response to Altitude
The Lake Louise Criteria
Acute Mountain Sickness
Acute mountain sickness comprises a constellation of symptoms caused by the atmospheric changes at elevations above approximately 2,500 m. It is the most common form of high-altitude illness, affecting 25% of travelers at moderate altitude and 50% to 85% above 4,000 m.3
Symptoms
The onset of symptoms (eg, headache, anorexia, nausea, vomiting, weakness) may occur at 2,000 m in the setting of rapid ascent—most commonly at 6 to 12 hours, but onset can range from 1 hour to 2 days after ascent. If symptoms begin after 3 days, other diagnoses should be considered. Symptoms of AMS are generally worse after the first night of sleep at elevation. On physical examination, vital signs are usually normal, though postural hypotension and tachycardia are possible. Oxygen saturation may be markedly decreased after rapid ascent, and chest auscultation may reveal rales in 20% of patients.4 Peripheral and facial edema may also be present. Funduscopic examination may show venous tortuosity and dilation, and retinal hemorrhage is common in ascents over 4,800 m.
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Differential Diagnosis
The differential diagnosis for AMS is broad and includes hypothermia, dehydration, exhaustion, subarachnoid hemorrhage, intracranial mass, carbon monoxide poisoning, alcohol hangover, intoxication, central nervous system infection and migraine. Risk factors for developing AMS are a previous history of altitude illness, rapid ascent, and lack of previous acclimatization. Interestingly, physical fitness does not protect a person from developing AMS.5
Mechanism of AMS
The true mechanism of AMS is uncertain, but it is clear that a fall in barometric pressure results in hypobaric hypoxia. This is thought to lead to an increased blood volume in the brain and increased cerebral blood flow, possibly precipitating an enlarged brain. A mechanism related to vasogenic edema has been proposed due to patients’ clinical improvement with dexamethasone therapy.6 Acute mountain sickness does appear to be related to overall fluid balance, as an increase in reninangiotensin, aldosterone, and antidiuretic hormone has been observed in patients with the condition. Elevation of these hormones is contrary to the appropriate physiological response of diuresis.
Treatment
Treatment of AMS begins with descent from elevation as soon as possible. Descent should be at least 500 m from the aggravating elevation. Patients should remain at least 1 to 2 days at this lower elevation before attempting reascent. If descent is not feasible, any further ascent should be delayed until symptoms have resolved.
Dexamethasone. This glucocorticoid has been used clinically with good success, although the mechanism of action in unclear. The initial dose is 8 mg followed by 4 mg every 6 hours.3
Acetazolamide. A carbonic anhydrase inhibitor, acetazolamide acts to temper symptoms by causing an acidosis that increases ventilation and prevents periodic breathing and hypoxia during sleep. The standard dose is 250 mg twice daily.3
Oxygen. Supplemental oxygen provided at 1 to 2 L/min via nasal cannula for 12 to 24 hours may help to improve symptoms. A portable hyperbaric oxygen (HBO) bag (eg, a Gamow bag) can be used to create an effective altitude of approximately 1,500 to 2,000 m inside the bag. The patient is placed completely within the bag, the zipper is sealed shut, and the bag is inflated with a foot pump. Treatment in such a chamber can be provided in 1-hour increments and repeated as needed. However, if descent is possible, use of the HBO chamber should not prevent or delay descent.
Ibuprofen. Compared to placebo, studies have shown ibuprofen 600 mg three times a day reduces the severity of AMS.7
Prevention
Strategies to prevent AMS are similar to those used to treat the condition. These include gradual ascent and prophylactic drug therapy.
Gradual Ascent. Gradual ascent is the primary strategy to prevent AMS. At altitudes above 3,000 m, each subsequent night should not be spent at an elevation 300 m higher than the previous night.
Acetazolamide. Pretreatment with acetazolamide is indicated for patients with a history of altitude illness or who anticipate an abrupt ascent (eg, rescue workers). Acetazolamide has been shown in multiple studies to be effective in the prevention of AMS.8 Adverse side effects of acetazolamide include paresthesias and increased urinary frequency; the drug may also make carbonated beverages taste flat. The preventive dose is 125 mg twice daily, and should be started the day before ascent.
Dexamethasone. In addition to treating AMS, dexamethasone may be taken as a preventive in doses of 2 mg every 6 hours or 4 mg twice daily.3 However, unlike acetazolamide, which acts to facilitate acclimatization, dexamethasone only prevents symptoms. Thus, cessation of the drug can result in rebound AMS symptoms, and prolonged use can result in adrenal suppression.3 Therefore, it should not be used for more than 10 days.
Sumatriptan and Gabapentin. In recent studies, sumatriptan and gabapentin haven shown benefit in preventing AMS, 9,10 but further study is needed before either of these drugs can be recommended.
Ginkgo Biloba. While ginkgo biloba has been touted as an effective preventive treatment, studies have shown no benefit to its use.8
Ibuprofen. ibuprofen 600 mg three times daily can be initiated the day prior to ascent, and has been shown to decrease the incidence of AMS.7