Epidemiology

• Incidence (With Ascent to 4500 m in 4 Days): 0.2%
• Incidence (With Ascent to 5500 m in 7 Days): 2%
• Incidence (With Ascent to 4500 m in 1-2 Days): 6%
• Incidence (With Ascent to 5500 m in 1-2 Days): 15%

Risk Factors

• History of High-Altitude Pulmonary Edema (HAPE)
  • Risk of Recurrence in Patients with History of HAPE and Ascent to 4500 m in 2 Days: 60%

Factors Not Associated with Increased Risk of High-Altitude Pulmonary Edema (HAPE)

• Physical Fitness

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Physiology

• Non-Cardiogenic Pulmonary Edema Due to Exaggerated Hypoxic Pulmonary Vasoconstriction and Abnormally High Pulmonary Artery Pressure and Pulmonary Capillary Pressure: results in non-inflammatory and hemorrhagic alveolar capillary leak, which secondarily may evoke an inflammatory response
  • Risk Increases with Increased Altitude and Faster Ascent

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Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

• Hypoxemia (see Hypoxemia, [[Hypoxemia]])

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Clinical Manifestations

General Comments

• Onset: develops 2 or more days after exposure to altitudes >3000 m
  • Rarely occurs at altitudes <2500-3000 m

Cardiovascular Manifestations

• Hypotension (see Hypotension, [[Hypotension]])

Neurologic Manifestations

• Lethargy/Drowsiness (see Obtundation-Coma, [[Obtundation-Coma]]): occurs late in course
• Signs of High-Altitude Cerebral Edema (HACE) (see High-Altitude Cerebral Edema, [[High-Altitude Cerebral Edema]]): occurs late in course

Pulmonary Manifestations

• Crackles
• Cyanosis (see Cyanosis, [[Cyanosis]]): occurs late in course
• Decreased Exercise Performance: occurs early in course
• Dyspnea (see Dyspnea, [[Dyspnea]])
• Dry Cough (see Cough, [[Cough]])
• Hemoptysis (see Hemoptysis, [[Hemoptysis]])
• Pink, Frothy Sputum: occurs late in course

Other Manifestations

• Low-Grade Fever (see Fever, [[Fever]])

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Prevention of High-Altitude Pulmonary Edema (HAPE)

General Measures

• Avoid Ethanol and Respiratory Depressants (see Ethanol, [[Ethanol]])
• Avoid Extreme Cold
• Maintain Hydration
• Graded Ascent (For Planned Final Altitude >3000 m): ascent rate of 300-500 m/day with rest q3-4 days
  • An ascent made after 1 wk at an altitude of at least 2000 m (as compared with an ascent from near sea level) reduces both the incidence and severity of acute mountain sickness at 4300 m by 50% [MEDLINE]

Risk Assessment [MEDLINE]

• Low Risk
  • Slow Ascent <500 m/day above 2500 m)
  • No History of Acute Mountain Sickness/High-Altitude Cerebral Edema/High-Altitude Pulmonary Edema
  • Rapid Ascent (>500 m/day in Person Partially Acclimatized (At Altitude <3000 m in Preceding Weeks)
• Medium Risk
  • Unknown History of Acute Mountain Sickness/High-Altitude Cerebral Edema/High-Altitude Pulmonary Edema and Fast Ascent (>500 m/day Above 3000 m)
  • Unknown History of Acute Mountain Sickness/High-Altitude Cerebral Edema/High-Altitude Pulmonary Edema and Rapid Ascent (Ascent to >3000 m in 1 Day)
• High Risk
  • Unknown History of Acute Mountain Sickness/High-Altitude Cerebral Edema/High-Altitude Pulmonary Edema Very Rapid Ascent (Considerably >500 m/day), and High Final Altitude (>4000 m)
  • History of Acute Mountain Sickness/High-Altitude Cerebral Edema/High-Altitude Pulmonary Edema with Previous Exposure to High Altitude That is Similar to Planned Final Altitude

Nifedipine (Adalat, Procardia) (see Nifedipine, [[Nifedipine]])

• First-Line Agent
• Administration: 30 mg nifedipine sustained release PO BID
• Pharmacology: calcium channel blocker (see Calcium Channel Blockers, [[Calcium Channel Blockers]])
• Clinical Efficacy: nifedipine/tadalafil/dexmethasone appear to be similarly effective in lowering pulmonary artery pressures and decreasing the incidence of high-altitude pulmonary edema from approximately 70% to approximately 10% or less

Tadalafil (Adcirca, Cialis) (see Tadalafil, [[Tadalafil]])

• Second-Line Agent
• Pharmacology: phosphodiesterase type 5 inhibitor (see Phosphodiesterase Type 5 Inhibitors, [[Phosphodiesterase Type 5 Inhibitors]])
• Clinical Efficacy: nifedipine/tadalafil/dexmethasone appear to be similarly effective in lowering pulmonary artery pressures and decreasing the incidence of high-altitude pulmonary edema from approximately 70% to approximately 10% or less
• Administration: 10 mg PO BID

Dexamethasone (Decadron) (see Dexamethasone, [[Dexamethasone]])

• Second-Line Agent
• Administration: 8 mg PO BID
• Clinical Efficacy: nifedipine/tadalafil/dexmethasone appear to be similarly effective in lowering pulmonary artery pressures and decreasing the incidence of high-altitude pulmonary edema from approximately 70% to approximately 10% or less

Salmeterol (Serevent) (see Salmeterol, [[Salmeterol]])

• Third-Line Agent: less effective than other options
• Administration: 125 ug inhaled BID

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Treatment of High-Altitude Pulmonary Edema (HAPE)

• Descent: as soon as possible
• Oxygen (see Oxygen, [[Oxygen]]): may be used with Gamow bag
• Hyperbaric/Gamow Bag: indicated if descent is not possible
• Nifedipine (see Nifedipine, [[Nifedipine]])
  • Administration: 60–80 mg sustained release nifedipine per day in divided doses
  • Clinical Efficacy: effective trials
• Tadalafil (Adcirca, Cialis) (see Tadalafil, [[Tadalafil]])
  • Clinical Efficacy: anecdotally effective
• Dexamethasone (Decadron) (see Dexamethasone, [[Dexamethasone]]): not effective
• Diuretics: not effective
• Re-Ascent: possible when symptoms have resolved and oxygenation at rest and during exercise is normal for altitude without supplemental oxygen
  • Continue nifedipine 60 mg of slow-release formulation/day

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Prognosis

• Mortality in Untreated HAPE: 50%

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References

• Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response. Eur Respir J 1991;4:1000-1003 [MEDLINE]
• Acute mountain sickness: influence of susceptibility, pre-exposure and ascent rate. Med Sci Sports Exerc 2002;34:1886-1891 [MEDLINE]
• Effect of six days of staging on physiologic adjustments and acute mountain sickness during ascent to 4300 meters. High Alt Med Biol 2009;10:253-60 [MEDLINE]
• Physiologic risk factors of severe high altitude illness: a prospective cohort study. Am J Respir Crit Care Med 2012;185:192-198 [MEDLINE]
• Acute high-altitude illnesses. N Engl J Med 2013;368:2294-2302 [MEDLINE]