Description

• Altitude illness is a spectrum of medical problems ranging from mild discomfort to fatal illness that may occur on ascent to higher altitudes (elevations >1,500 m [4,921 feet]). It is divided into 3 categories: high, 1,500–3,500 m; very high, 3,500–5,500 m; and extreme, 5,500–8,850 m (1). Altitude illness can affect anyone, including the most experienced and fit individual (2). For most, it is an unpleasant but self-limiting syndrome that will not require physician intervention.
• Acute mountain sickness (AMS): Symptoms associated with a physiologic response to a hypobaric, hypoxic environment. Onset occurs within 24 hours of arrival at altitude, often within 1–4 hours. Neurologic symptoms are predominant and range from a mild to moderate headache and malaise to severe impairment.
• High-altitude pulmonary edema (HAPE): Noncardiogenic pulmonary edema. Onset 1–4 days at altitude. Rare <8,000 feet (2,438 m).
• High-altitude cerebral edema (HACE): A potentially fatal neurologic syndrome; considered the end stage of AMS. Onset within 3–5 days at elevations as low as 9,022 feet (2,750 m) but may be more abrupt at higher altitudes. Death results from brain herniation.
• System(s) affected: Nervous/Pulmonary
• Synonym(s): Mountain sickness

• Risk does not increase with age.
• Age alone should not preclude travel to high altitude; allow extra time to acclimate.
• Pre-existing medical problems are made worse; referred to as altitude-exacerbated conditions.

• Altitude illness seems to have the same incidence in children as in adults, but diagnosis may be delayed in younger children.
• Any child who experiences behavioral symptoms after recent ascent should be presumed to be suffering from altitude illness.

• The risk during pregnancy is unknown.
• There is no evidence that exposure to high altitudes (1,500–3,500 m) poses a risk to a pregnancy.
• It may be prudent to advise a low-altitude dwelling for any pregnant woman experiencing complications.

Epidemiology

Most epidemiologic studies are limited to relatively homogeneous populations of men.

• AMS: 10–90% of travelers ascending to higher altitudes may experience symptoms.
• HAPE/HACE: These conditions occur in 0.01–1% of sojourner ascents at typical mountain resorts, although incidence increases with rapid and higher ascents (3).

Risk Factors

• Rapid rate of ascent
• Maximum altitude attained
• Increased duration at high altitude
• Failure to acclimatize at lower altitude
• Higher altitude during sleep cycle
• Prior history of altitude illness
• Cardiac congenital abnormalities

General Prevention

• General guidelines:
  • Preacclimatization affords some protection against altitude illness.
  • A staged or graded ascent (rest every 600–1,200 m) and a slow ascent rate (maximum 600 m/d) should allow adequate time for acclimatization.
  • Sleeping elevation: “Climb high and sleep low” is a prudent practice for anyone going above 3,500 m.
  • Avoid heavy exertion for the first 1–3 days.
  • Avoid respiratory depressants such as alcohol and soporifics.
  • Preascent physical conditioning is not preventive.
• Drug prophylaxis:
  • Acetazolamide, dexamethasone, and ibuprofen (see below)
  • For HAPE only:
    • Consider nifedipine and beta agonists (see “Treatment” section).

Pathophysiology

• Not completely understood
• Hypobaric hypoxia and hypoxemia are the pathophysiologic precursors to altitude illness.
• 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.

Etiology

Individuals with a prior episode of HAPE have an increased risk of recurrence (4).

History

• AMS, mild to moderate symptoms:
  • Headache, plus at least 1 of the following:
    • Anorexia
    • Nausea or vomiting
    • Dizziness or lightheadedness
    • Insomnia
• AMS, severe symptoms:
  • Increased headache
  • Irritability
  • Marked fatigue
  • Dyspnea with exertion
  • Nausea and vomiting
  • HAPE (Lake Louise diagnostic criteria):
    • At least 2 of the following symptoms: Dyspnea at rest, cough, weakness, decreased exercise performance, chest tightness, congestion
    • AND at least 2 of the following signs: Crackles or wheezing in at least 1 lung field, central cyanosis, tachycardia, tachypnea. (Note: Fatigue may be pulmonary edema.)
  • HACE symptoms: Mental status changes (irrational behavior, lethargy, obtundation, coma)

Physical Exam

• HAPE:
  • Lung crackles or wheezing
  • Central cyanosis
  • Tachycardia
  • Tachypnea
• HACE:
  • Abnormal mental status exam (behavioral change, lethargy, obtundation, coma)
  • Truncal ataxia
  • Papilledema, retinal hemorrhage, cranial nerve palsies
  • Focal neurologic deficits (rare)

Diagnostic Tests and Interpretation

An ECG may show sinus tachycardia or right-sided heart strain.

• AMS: Laboratory studies are nonspecific and rarely required for diagnosis.
• HAPE: Severe hypoxemia demonstrated with oximetry or blood gas analysis.

Imaging
No radiographic feature is specific to HAPE.

Differential Diagnosis

• Onset of symptoms >3 days at a given altitude, the absence of headache, or the lack of rapid response to oxygen or descent suggest other diagnoses.

• AMS/HACE:
  • Subarachnoid hemorrhage, CNS mass, cerebrovascular accident
  • Migraine headache
  • Dehydration
  • Ingestion of toxins, drugs, or alcohol
  • Carbon monoxide exposure
  • CNS infection
  • Acute psychosis
• HAPE:
  • Pneumonia
  • Cardiogenic pulmonary edema
  • Spontaneous pneumothorax
  • Pulmonary embolism
  • Asthma
  • Bronchitis
  • Myocardial infarction
  • Hyperventilation syndrome

Medication (Drugs)

• Oxygen: 2–15 L/min to maintain SaO₂ >90% until symptoms improve
• Acetazolamide: If patient has a history of problems at altitude and/or plans to ascend >500 m/d. Dosage is usually 125–500 mg PO b.i.d. starting 2 days before ascent and continued for 3 days at maximum altitude. Patients with a drug allergy to sulfonamides should avoid acetazolamide (5)[C]:
  • Primary prevention of AMS: 125–500 mg PO b.i.d. starting 1 day before ascent and continued for 2 days at maximum altitude
  • Treatment of AMS: 125–500 mg PO b.i.d. until symptoms resolve
• Dexamethasone: May significantly reduce the incidence and severity of AMS. Dosage is 2–4 mg PO q6h, begun the day of ascent, continued for 3 days at the higher altitude, then tapered over 5 days. Adverse side effects are rare:
  • Prevention of AMS: 2 mg PO q6h or 4 mg PO q12h, starting 1 day before ascent and discontinued cautiously after 2 days at maximum altitude
  • Treatment of AMS: 4 mg PO/IV/IM q6h
  • Treatment of HACE: 8 mg PO/IV/IM initially, then 4 mg q6h
• Nifedipine (reduces pulmonary arterial pressure):
  • Prevention of HAPE: 20–30 mg extended-release PO b.i.d. starting 1 day prior to ascent and continued for 2 days at maximum altitude
  • Treatment of HAPE: 10 mg, then 20–30 mg extended-release PO b.i.d.
• Salmeterol:
  • Prevention and possible treatment of HAPE: 125 μg inhaled b.i.d. starting 1 day before ascent and continued for 2 days at maximum altitude
• NSAIDs:
  • Prevention and treatment of headache
  • Aspirin: 325 mg PO q4h for total 3 doses
  • Ibuprofen: 400–600 mg PO (6)
  • Prevention of AMS: Dose unknown. Begin 1–5 days before ascent.
• Antiemetics:
  • Prochlorperazine: 10 mg PO/IM q6–8h
  • Promethazine: 25–50 mg PO/IM/PR q6h

Second Line
Furosemide: Consider for treatment of AMS or HACE, 20–80 mg PO/IV q12h for a total of 2 doses. Currently out of favor; not recommended for prophylaxis; not established for use in HAPE.

Additional Treatment

• Therapy must be tailored to fit disease severity.
• Early recognition is critical.
• Stop ascent, acclimatize at the same altitude, and/or descend if symptoms do not improve over 24 hours. Definitive treatment is to descend to a lower altitude. Dramatic improvement accompanies even modest reductions in altitude.
• Oxygen helps relieve symptoms. Give continuously by cannula or mask initially, and then titrate to SaO₂ >90%.
• AMS:
  • Acetazolamide is effective in reducing mild to moderate symptoms of AMS, but the optimum dosage is unknown. Consider 125–500 mg PO b.i.d. until symptoms resolve.
  • Dexamethasone may also be effective in treating moderate AMS. Consider 4 mg PO/IM/IV q6h.
  • Analgesics and antiemetics as needed for symptomatic relief
• HAPE:
  • Oxygen therapy
  • Minimize exertion and keep patient warm.
  • Immediate descent or evacuation to a lower altitude
  • Portable hyperbaric therapy (2–15 psi), such as the Gamow bag or Chamberlite, is an effective and practical alternative when descent is not possible.
  • Consider nifedipine 10 mg PO, then 20–30 mg extended-release PO b.i.d.
• HACE:
  • Immediate descent
  • Supplemental oxygen (highest flow available; maintain SaO₂ >90%)
  • Dexamethasone: 8 mg IV/IM/PO initially, then 4 mg q6h
  • Hyperbaric therapy if unable to descend

In-Patient Considerations

Initial Stabilization
Outpatient treatment for mild cases

Follow-Up Recommendations

• For mild cases, no follow-up is needed.
• For more severe cases, follow until symptoms subside.

Patient Education

Patients should be counseled about the risks of high-altitude travel and how to recognize high-altitude illnesses.

Prognosis

Most cases of mild to moderate AMS are self-limiting and do not require physician intervention. Patients may resume ascent once the symptoms subside. HAPE and HACE respond well to descent, evacuation, and/or pharmacologic treatment if identified early.

Complications

A patient may experience a high-altitude retinal hemorrhage, which can cause visual changes, but this is usually asymptomatic.

ICD-9

• 514 Pulmonary congestion and hypostasis
• 993.2 Other and unspecified effects of high altitude

ICD-10

• T70.29XA Other effects of high altitude, initial encounter
• T70.20XA Unspecified effects of high altitude, initial encounter
• J81.0 Acute pulmonary edema

SNOMED

• 87284002 Effects of high altitude (disorder)
• 78590007 Acute mountain sickness (disorder)
• 233707008 High altitude pulmonary edema (disorder)