Description

• A spectrum of cerebral and pulmonary syndromes ranging from mild discomfort to fatal illness that occur on ascent to higher altitudes as a direct result of inadequate acclimatization
• Categories of altitude: high, 1,500 to 3,500 m; very high, 3,500 to 5,500 m; and extreme, 5,500 to 8,850 m (1).
• Altitude illness can affect anyone, including experienced and fit individuals. For most, it is an unpleasant (self-limited) syndrome that does not require medical intervention (2).
• Acute mountain sickness (AMS): symptoms associated with a physiologic response to a hypobaric, hypoxic environment; onset usually occurs within 6 to 12 hours after ascending >2,500 m. Neurologic symptoms predominate, ranging from mild/moderate headache and malaise to severe impairment.
• High-altitude pulmonary edema (HAPE): noncardiogenic pulmonary edema; typically after ≥2 days at altitudes >3,000 m, rare between 2,500 and 3,000 m
• High-altitude cerebral edema (HACE): a potentially fatal neurologic syndrome considered to be the end stage of AMS; onset after at least 2 days at altitudes >4,000 m
• System(s) affected: nervous/pulmonary
• Synonym(s): mountain sickness

Geriatric Considerations

• Risk does not increase with age.
• Age alone should not preclude travel to high altitude; allow extra time to acclimate.
• Worsening of preexisting medical problems referred to as altitude-exacerbated conditions

Pediatric Considerations

• Altitude illness seems to have the same incidence in children as in adults; diagnosis may be delayed in younger children.
• Any child who experiences behavioral symptoms after recent ascent should be presumed to have an altitude-related illness.

Pregnancy Considerations

• The risk during pregnancy is unknown.
• No evidence suggests that exposure to high altitudes (1,500 to 3,500 m) poses a risk to a normal pregnancy.

Epidemiology

Most epidemiologic studies are limited to relatively homogeneous male populations.

Incidence

• Incidence and severity increase with altitude and rate of ascent.
• AMS effects >25% of people who ascend to 3,500 m (11,500 ft) and >50% of those who ascend above 6,000 m (19,700 ft)
• HACE: in general population at 2,500 m (8,202 ft) is <0.01%, but increases to 1–2% in trekkers, climbers, and soldiers near a 4,000-m altitude
• HAPE: 0.01–0.1% in the general population at 2,500 m (8,202 ft) to 2–6% in trekkers and mountaineers at 4,000 m (13,123 ft)

Etiology and Pathophysiology

• Hypobaric hypoxia and hypoxemia are the pathophysiologic precursors to altitude illness.
• The conditions of AMS and HACE represent a pathophysiologic continuum (1).
• Symptoms of AMS may be the result of cerebral swelling, either through vasodilatation induced by hypoxia or through cerebral edema.
• Other mechanisms include impaired cerebral autoregulation, release of vasogenic mediators, and alteration of the blood–brain barrier.
• HAPE is a noncardiogenic pulmonary edema characterized by exaggerated pulmonary hypertension leading to vascular leakage through overperfusion, stress failure, or both.

Genetics
Genetic factors involved in predisposition to developing AMS are poorly understood.

Risk Factors

• Individuals with a prior history of AMS, HACE, or HAPE
• Failure to properly acclimatize at a lower altitude
• Ascent rate (sleeping elevation) >500 m/day (3)
• Trips to extreme altitude
• Increased duration at high altitude
• Higher altitude during sleep cycle
• Cardiac congenital abnormalities
• Younger age (<50 years) (1)

General Prevention

• The Richalet hypoxia sensitivity test (indicated for those who have never been at a high altitude and who face a journey to a high altitude without the possibility of acclimatization) helps predict altitude illness (positive predictive value of 79%) (1).
• General guidelines
  • Preacclimatization (exposure of hypoxia prior to ascent) protects against altitude illness.
  • Staged ascent (spending 6 to 7 days) at 2,200 to 3,000 m can also prevent altitude illness (3).
  • Ascending no >500 m/day.
  • Lower sleeping elevation: “Climb high and sleep low” for anyone going >3,500 m.
  • Avoid heavy exertion for the first 1 to 3 days at altitude.
  • Avoid respiratory depressants (alcohol and sedatives).
  • Preascent physical conditioning is not preventive.
• Pharmacologic prophylaxis
  • Acetazolamide, dexamethasone, and ibuprofen (see “Treatment”)
  • For prevention of HAPE only (if at risk):
    • Consider nifedipine, dexamethasone, and tadalafil (see “Treatment”).