High-altitude pulmonary edema (HAPE) is a life-threatening, noncardiogenic form of pulmonary edema afflicting certain individuals after a rapid ascent to high altitude above 2,500 m (approximately 8,200 ft). HAPE is the most common cause of death related to high altitude.
In high-altitude pulmonary edema (HAPE), it’s theorized that vessels in the lungs constrict, causing increased pressure. This causes fluid to leak from the blood vessels to the lung tissues and eventually into the air sacs. These include acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). The most common cause of death related to high altitude, HAPE is completely and easily reversed if recognized early and treated properly.
As with other forms of pulmonary edema, oxygen is the usually the first treatment. If supplemental oxygen isn’t available, you may use portable hyperbaric chambers, which imitate a descent for several hours until you are able to move to a lower elevation.
Other Names
- High Altitude Pulmonary Edema (HAPE)
- High Altitude Pulmonary Oedema (HAPO)
- “re-entry” HAPE
Pathophysiology
- General
- HAPE is a pulmonary presentation of acute high altitude illness
- Onset is usually 2–4 days after ascent; rare after 1 week at a constant altitude
- Most commonly seen above 2500 to 3000 m, less commonly between 1400 and 2400 m
- Types
- Most commonly, it occurs in rapid ascension in unacclimatized lowlanders
- “re-entry” HAPE: rarely, it can occur in inhabitants returning from a trip at a “low altitude”
Mechanism
- Non-cardiogenic Pulmonary edema
- Alveolar hypoxia causes pulmonary circulation vasoconstriction, subsequent pulmonary hypertension
- HAPE susceptible individuals have exaggerated pulmonary artery vasoconstriction and pressures with hypoxia or normoxic exercise at sea level
- Hypoxic pulmonary vasoconstriction
- Thought to be non-uniform, causing regional overperfusion
- Endothelial dysfunction may be provoked
- Impaired nitrous oxide synthesis may confer genetic susceptibility, the underlying mechanism
- Alveolar capillary leak
- Stress failure secondary to pulmonary artery hypertension
- This leads to leakage of large molecules into the alveolar space, subsequent high-permeability pulmonary edema
- Worse/ exacerbated by exercise
- Impaired clearance of alveolar fluid
- HAPE susceptible individuals have a defective transepithelial sodium transport in their alveoli
- Impairment is likely exacerbated at altitude
- Salmeterol, and dexamethasone may improve transepithelial sodium transport
- Acute Mountain Sickness
- 50% of patients with HAPE also have AMS
- High Altitude Cerebral Edema
- 14% of patients with HAPE also have HACE
- 50% of autopsies in patients with HAPE had cerebral edema
- Pneumonia
- Bronchitis
- Pulmonary Embolism
- Myocardial Infarction
- Heart Failure
Symptoms
- Headache, which may be the first symptom.
- Shortness of breath with activity, worsens to shortness of breath at rest.
- Decreased ability to exercise as you once could.
- Dry cough, at first.
- Later, a cough produces frothy, pink sputum.
Diagnosis
- History
- Early symptoms include exertional dyspnea, dry cough, and reduced exercise performance
- It May appear over hours or days, and can appear suddenly after a night’s sleep at an altitude
- Note that early symptoms are often minimized by individuals but may reflect early HAPE
- Classic symptoms
- Dyspnea at rest
- Cough
- Decreased exercise tolerance
- Chest tightness or congestion
- Other potential symptoms: fatigue, headache, elevated body temperature, generally not exceeding 38.5°C
- Note that AMS often will overlap
- Symptoms can worse over time as pulmonary edema progresses
- Aggravated cough, breathlessness even at rest
- Physical Exam
- Classic signs
- Wheeze on auscultation
- Central cyanosis
- Tachypnoea
- Tachycardia
- Severe findings include pink frothy sputum, gurgling sounds
- Classic signs
| Symptom | Clinical Signs |
| Dyspnea at rest | Crepitus or wheezing on auscultation |
| Cough | Central cyanosis |
| Decreased exercise tolerance | Tachypnea |
| Chest tightness | Tachycardia |
- Diagnosis is clinical
- Diagnosis is made by the presence of two clinical symptoms and two clinical signs[12]
Radiographs
- Chest Radiograph
- Not required to make a diagnosis
- Findings
- Peripheral patchy pulmonary edema in the lower zones, more often right-sided
- Normal cardiac size with prominent pulmonary arteries
Electrocardiogram
- Not required to make a diagnosis
- Findings[13]
- Sinus tachycardia
- Right axis deviation
- Right bundle branch block or right strain
Laboratory
- Labs are not required to make the diagnosis
- Can be useful to confirm, and exclude other pathology
- Blood gas
- Hypoxemia
- Respiratory alkalosis
- Currently, no classification system exists for HAPE
Treatment
- Summary of treatment
- Increase oxygenation using rapid descent
- Adjunct: o2 supplementation or portable hyperbaric chamber
- Adjunct: Nifedipine if oxygen is not available
- Descent
- Most effective treatment (as with all forms of AHAI)
- First-line treatment, especially in remote or austere settings
- Initial descent should be at least 1000 m or until symptoms resolve
- Ideally, with minimal exertion by the patient
- Hospital
- Supplementary oxygen
- Considering positive airway pressure, there are case reports supporting use[15]
- Consider inhaled nitric oxide
- Nifedipine
- Can be used when descent or oxygen is not possible
- Dose: 60 mg modified release divided into 2 or 3 doses (same as prophylaxis)
- Recommended as a first-line adjunct with WMS guidelines
- However, no benefit if oxygen and descent are available
- Phosphodiesterase inhibitors
- Not currently recommended due to an increase in AMS severity
