High-Altitude Pulmonary Edema 

Updated: Dec 31, 2015
Author: Rohit Goyal, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP 



High-altitude illness may result from short-term exposures to altitudes in excess of 2000 m (6560 ft). This illness comprises a spectrum of clinical entities that are probably the manifestations of the same disease process. High-altitude pulmonary edema (HAPE) and cerebral edema are the most ominous of these symptoms, while acute mountain sickness, retinal hemorrhages, and peripheral edema are the milder forms of the disease. The rate of ascent, the altitude attained, the amount of physical activity at high altitude, and individual susceptibility are contributing factors to the incidence and severity of high-altitude illness.

Also see Altitude Illness - Cerebral Syndromes and Altitude Illness - Pulmonary Syndromes.


The pathophysiology high-altitude pulmonary edema (HAPE) is not well understood.[1] HAPE is a noncardiogenic form of pulmonary edema resulting from a leak in the alveolar capillary membrane. The various mechanisms believed to be responsible are pulmonary arterial vasoconstriction resulting in circulatory shear forces and a consequent permeability leak and antidiuresis possibly mediated by increased antidiuretic hormones, which contribute to fluid retention. The inciting factor appears to be excessive hypoxia.[2]

A number of compensatory mechanisms improve oxygen delivery when its inspired concentration is reduced. The first adaptation to high altitude is an increase in minute ventilation. The ventilatory response to a relatively hypoxic stimulus can be divided into 4 phases: (1) initial increase on ascent, (2) subsequent course over hours and weeks, (3) deacclimatization on descent, and (4) long-term response of high-altitude natives.

The barometric pressure decreases with distance above the Earth's surface in an approximately exponential manner. The pressure at 5500 m (18,000 ft) is only half the normal 760 mm Hg, so that the partial pressure of oxygen (PO2) of moist inspired gas is (380-47) X 0.2093 = 70 (47 mm Hg is the partial pressure of water vapor at body temperature [ie, 37ºC]). At the summit of Mount Everest (altitude 8848 m or 29,028 ft), the inspired PO2 is only 43. In spite of hypoxia associated with high altitude, approximately 15 million people live at elevations over 3050 m, and some permanent residents live higher than 4900 m in the Andes. A remarkable degree of acclimatization occurs when humans ascend to these altitudes. Climbers have lived for several days at altitudes that would cause unconsciousness within a few seconds in the absence of acclimatization.

Spirometric studies have shown that with increasing altitude, both forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) are reduced by up to 25% (74.8% / 74.6% of baseline). In the same study, peak expiratory flow (PEF) initially increased up to 4451 m and returned to baseline values above 5000 m. After descent below 2000 m, all values normalized within one day. These findings were consistent with increasing pulmonary restriction at high altitudes (without a marked reduction of PEF). Portable spirometry may provide clinically relevant information (impending pulmonary edema) in high-altitude travelers.[3, 4, 5]

Bronchoalveolar lavage fluid (BALF) studies have shown that after heavy exercise, under all conditions, athletes develop a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. Exercise at altitude (3810 m) caused significantly greater leakage of RBCs (92,000 [SD 3.1] cells/mL) into the alveolar space than that seen with normoxic exercise (54,000 [SD 1.2] cells/mL). At altitude, the 26-hour postexercise BALF had significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.[6]

Autopsy studies performed on patients who died of HAPE have shown a proteinaceous exudate with hyaline membranes. The studies have shown areas of pneumonitis with neutrophil accumulation, although none was noted to contain bacteria. Pulmonary veins were not dilated. Most reports mention capillary and arteriolar thrombi with deposits of fibrin, hemorrhage, and infarcts. The findings suggest a protein-rich edema with a possibility that clotting abnormalities may be partially responsible for this illness.

Bronchoalveolar lavages performed on patients with HAPE have also shown the fluid to have a high protein content, higher than in patients with adult respiratory distress syndrome (ARDS). The fluid was also highly cellular. Unlike ARDS, which primarily has neutrophils in the lavage fluid, HAPE fluid contains a higher percentage of alveolar macrophages. Additionally, chemotactic (leukotriene B4) and vasoactive (thromboxane B2) mediators were present in the lavage.



United States

In one study on Colorado skiers, the incidence of acute mountain sickness was as high as 15-40%. The incidence of high-altitude pulmonary edema (HAPE) is much lower, at about 0.1-1%.


In a study on Mount Everest trekkers, the incidence of high-altitude pulmonary edema (HAPE) was about 1.6%. The incidence of mountain sickness appears to be unusually high in trekkers on Mount Rainier; however, the incidence of pulmonary edema is the same as in other places. One study reported that Everest region trekkers were more likely to be evacuated for altitude illness than trekkers in other regions.[7]


Men and women are equally susceptible to acute mountain sickness, but women may be less likely to develop high-altitude pulmonary edema (HAPE). In addition to individual differences in susceptibility, other factors, such as alcohol, respiratory depressants, and respiratory infections, may enhance vulnerability to altitude illness.


The typical patient with high-altitude pulmonary edema (HAPE) is a young person who is otherwise physically fit. HAPE is rare in infants and small children.


High-altitude pulmonary edema (HAPE) may be fatal within a few hours if left untreated. Patients who recover from HAPE have rapid clearing of edema fluid and do not develop long-term complications. One study has shown that the estimated incidence of altitude illness–related death was 7.7 deaths in 100,000 trekkers. The mortality has been increasing over the last decade.[7]

Patient Education

For patient education resources, visit the First Aid and Injuries Center. Also, see the patient education article Mountain Sickness.




High-altitude pulmonary edema (HAPE) generally occurs 1-4 days after rapid ascent to altitudes in excess of 2500 m (8000 ft). Young people and previously acclimatized people reascending to a high altitude following a short stay at low altitude seem more predisposed to HAPE. Cold weather and physical exertion at high altitude are other predisposing factors.

The earliest indications are decreased exercise tolerance and slow recovery from exercise.

The person usually notices fatigue, weakness, and dyspnea on exertion.

The condition typically worsens at night, and tachycardia and tachypnea occur at rest. Periodic breathing during sleep is almost universal in sojourners at high altitude.

Cough, frothy sputum, cyanosis, rales, and dyspnea progressing to severe respiratory distress are symptoms of the disease.

A low-grade fever, respiratory alkalosis, and leukocytosis are other common features.

In severe cases, an altered mental status, hypotension, and death may result.


In addition to the symptoms discussed, high-altitude pulmonary edema (HAPE) is diagnosed by the presence of at least two of the following signs:

  • Tachycardia

  • Tachypnea

  • Crackles on auscultation

  • Central cyanosis

  • Disproportionately low oxygen saturation relative to altitude


Causes are as follows:

  • Rapid ascent

  • Physical exertion at high altitude

  • Exposure to cold





Laboratory Studies

Findings on laboratory studies from high-altitude pulmonary edema (HAPE) patients are nonspecific.

Arterial blood gas measurement may show acute respiratory alkalosis. A mild leukocytosis also may be present.

Some studies have demonstrated increase in interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and cross-reacting protein (CRP) in response to high altitude. The systemic increase of these inflammatory markers may reflect considerable local inflammation.[8]

Imaging Studies

Chest radiography in high-altitude pulmonary edema (HAPE) patients reveals bilateral patchy infiltrates.

In one study, stress echocardiography was used to quantitate pulmonary artery systolic pressure responses to prolonged hypoxia and normoxic exercise.[9] The data from the study indicate that individuals who are susceptible to HAPE have abnormal vascular responses not only to hypoxia but also to supine bicycle exercise under normoxic conditions. Thus, this modality may be a useful noninvasive screening method to identify subjects susceptible to HAPE.

Chest ultrasonography was evaluated in one study and showed that the comet-tail technique, which has been shown in cardiogenic pulmonary edema, effectively recognizes and evaluates the degree of pulmonary edema in HAPE patients.[10]

Other Tests

ECG in high-altitude pulmonary edema (HAPE) patients may reveal a right-sided heart strain pattern suggestive of pulmonary hypertension.


Portable hyperbaric chambers (Gamow, CERTEC) are in wide use by trekkers. A physiologic (simulated) descent of approximately 2000 m may be achieved in a few minutes. Patients are typically treated in 1-hour increments. Patients should be closely observed for rebound symptoms after hyperbaric treatments.



Medical Care

The treatment of high-altitude pulmonary edema (HAPE) includes rest, administration of oxygen, and descent to a lower altitude. If diagnosed early, recovery is rapid with a descent of only 500-1000 m. A portable hyperbaric chamber or supplemental oxygen administration immediately increases oxygen saturation and reduces pulmonary artery pressure, heart rate, respiratory rate, and symptoms. In situations where descent is difficult, these treatments can be lifesaving.[11, 12]

In one study, 11 patients at 4240 m altitude in Pheriche, Nepal were treated for HAPE with bed rest, oxygen, nifedipine, and acetazolamide.[13] Sildenafil and salmeterol were used in most, but not all patients. Seven of these had serious-to-severe HAPE (Hultgren grades 3 or 4). Oxygen saturation was improved at discharge (84% ±1.7%) compared with admission (59% ±11%), as was the ultrasound comet-tail score (11 ±4 at discharge vs 33 +/- 8.6 at admission), a measure of pulmonary edema for which admission and discharge values were obtained in 7 patients.

A randomized, double-blinded, placebo-controlled study showed that adults with previous HAPE who received prophylactic tadalafil (10 mg) or dexamethasone (8 mg) had significantly less HAPE compared with those who received placebo twice daily. The medications were administered during ascent and at a stay at 4559 m altitude.[14]

Two participants who received tadalafil developed severe acute mountain sickness upon arrival at 4559 m and withdrew from the study; they did not have HAPE at that time. HAPE developed in 7 of 9 participants who received placebo and in 1 of the remaining 8 participants who received tadalafil, but it did not develop in any of the 10 participants who received dexamethasone (P = .007 for tadalafil vs placebo; P < .001 for dexamethasone vs placebo). Eight of 9 participants who received placebo, 7 of 10 who received tadalafil, and 3 of 10 who received dexamethasone had acute mountain sickness (P = 1.0 for tadalafil vs placebo; P = .020 for dexamethasone vs placebo).

At high altitude, systolic pulmonary artery pressure increased less in participants who received dexamethasone (16 mm Hg [95% confidence interval, 9-23 mm Hg]) and tadalafil (13 mm Hg [95% confidence interval, 6-20 mm Hg]) than in those who received placebo (28 mm Hg [95% confidence interval, 20-36 mm Hg]) (P = .005 for tadalafil vs placebo; P = .012 for dexamethasone vs placebo).

The conclusion was that both dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may reduce the incidence of HAPE in adults with a history of HAPE.[15] Dexamethasone prophylaxis may also reduce the incidence of acute mountain sickness in these adults.

Finally, the use of an expiratory positive airway pressure mask improves oxygenation and may be useful as a temporizing measure.

Admission to a hospital is warranted for significant arterial desaturation and clinical deterioration despite outpatient management of HAPE.


A diet rich in carbohydrates has shown to be helpful in prevention of high-altitude pulmonary edema. Alcohol and sedatives should be avoided.


The following measures may prevent further episodes of high-altitude pulmonary edema (HAPE) in patients with a history of altitude illness:

  • Avoiding heavy exertion at high altitude

  • Slow ascent

  • Avoiding abrupt ascent to sleeping elevations higher than 3000 m: If possible, spend 2 nights at altitudes of 2500-3000 m before further ascent.

  • Avoiding alcohol and sedatives



Guidelines Summary

Related clinical guideline summaries are as follows:

  • The practice of travel medicine: guidelines by the Infectious Diseases Society of America[16]

  • Medical conditions affecting sports participation (American Academy of Pediatrics)[17]



Medication Summary

Drugs are not as effective as descent from altitude and oxygen in the treatment of high-altitude pulmonary edema (HAPE). Nifedipine, by reducing pulmonary arterial pressure, may be effective in treating HAPE.[18] Experience with other vasodilators such as hydralazine is limited. Some studies have reported good results with furosemide. However, concerns about hypovolemia have constrained its use in the United States. Some studies have reported vascular collapse at doses of 40 mg bid. Acetazolamide may be useful in the earliest stages of the illness. The best management of this uncommon illness is early recognition and descent.

Prophylaxis is indicated for persons who have been identified (from past experience) as being susceptible to developing high-altitude illness or who must ascend rapidly to a high altitude. Acetazolamide and dexamethasone have been shown to be effective agents for prophylaxis against high-altitude illness. These agents must be started 24 hours before ascent and continued for 48-72 hours at altitude. Acetazolamide, which appears to hasten acclimatization, is considered the drug of choice because of a low incidence of significant adverse effects. Acetazolamide has also been shown to reduce the risk and severity of HAPE in high-risk individuals. One study showed that low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of HAPE.[19] Other preventive measures include avoiding overexertion and respiratory depressants (eg, alcohol, sedatives) and eating a high-carbohydrate diet.

Calcium channel blockers

Class Summary

Nifedipine is used for its pulmonary vasodilating effects.

Nifedipine (Procardia, Adalat)

Nifedipine is used in HAPE for pulmonary vasodilation. It often improves SaO2 modestly within a few minutes.

Carbonic anhydrase inhibitors

Class Summary

These agents are helpful in the prevention of HAPE.

Acetazolamide (Diamox)

Acetazolamide is used in the prevention of HAPE. It is not used in the treatment of this condition. Acetazolamide promotes renal excretion of bicarbonate, which stimulates respiration. For the prophylaxis of altitude illness, start 24-48 hours before ascent and continue for 48 hours after arrival at high altitude.


Class Summary

These agents have profound and varied metabolic effects. They suppress inflammation and the immune response.

Dexamethasone (Decadron)

Dexamethasone alleviates vasogenic cerebral edema and improves endothelial integrity.