High Altitude Pulmonary Edema

High altitude pulmonary edema is a noncardiogenic pulmonary edema that develops after rapid ascent to over 2500 m (usually over 3000 m) in unacclimatized people. It is the commonest cause of death from altitude illness.

Incidence is 0.2% in visitors going to 4500 m over 4 or more days, and up to 6% after rapid ascent to 5500 m.

The risk is greater with fast ascent, heavy exertion, cold, previous episodes (a 60% recurrence rate on repeated rapid ascent) and, in children, with respiratory infection. People living at altitude can develop it on returning from a low-altitude stay (re-entry edema).

Mechanism: alveolar hypoxia causes exaggerated and uneven hypoxic pulmonary vasoconstriction. Pulmonary artery pressure rises to over 40 mmHg, and areas of lung that are over-perfused develop high capillary pressure, leading to stress failure of the capillary wall with leakage of protein-rich fluid and red cells into alveoli. Impaired alveolar fluid clearance and a reduced hypoxic ventilatory response contribute. Pulmonary edema in these patients is patchy and inflammatory changes follow.

Symptoms start 2 to 4 days after arrival, often at night. Untreated mortality is up to 50%, and with early descent and oxygen it is under 5%. Complications: respiratory failure, high altitude cerebral edema (coexisting in about 14 to 50% of fatal cases), pulmonary infection and recurrence on reascent.

• Reduced exercise performance, then breathlessness out of proportion to effort, dry cough and chest tightness
• Dyspnea at rest, orthopnea, wet cough with pink frothy sputum, and a gurgling chest
• Resting tachycardia, tachypnea, central cyanosis, crackles (first in the right mid-axillary area), and low-grade fever
• Oxygen saturation markedly lower than expected for the altitude
• Headache and ataxia signal coexisting cerebral edema
• Red flags: dyspnea at rest, cyanosis, confusion, ataxia, a resting saturation under 80% at over 4000 m, and a deteriorating patient overnight

1. Clinical diagnosis in a recent ascent (at least two symptoms: dyspnea at rest, cough, weakness or reduced performance, chest tightness or congestion; and at least two signs: crackles or wheeze, central cyanosis, tachypnea, tachycardia).
2. Pulse oximetry: typically 10 to 20 points below the expected value for altitude (for example under 75 to 80% at 4000 m).
3. Chest radiograph: patchy, asymmetric alveolar infiltrates. Lung ultrasound: multiple B-lines.
4. ECG: sinus tachycardia and right heart strain. Echocardiography: raised pulmonary artery systolic pressure (over 40 mmHg) with normal left ventricular function.
5. Exclusion of other causes: pneumonia, pulmonary embolism, asthma, myocardial infarction and cardiac failure.

Differentials: pneumonia, pulmonary embolism, acute mountain sickness with cough, bronchospasm, heart failure and acute myocardial infarction.

1. Descent is the definitive treatment: descend at least 1000 m (even 300 to 500 m helps) as fast as safely possible, keeping the patient at rest and warm, with an escort and avoidance of exertion (carry or transport the patient).
2. Oxygen: 4 to 6 L/min by mask to keep saturation over 90% (then 1 to 2 L/min once stable).
3. Portable hyperbaric chamber when descent is impossible: inflation to 2 psi (about 13.8 kPa) for 2 to 4 hours, which simulates descent of 1500 to 2000 m.
4. Nifedipine: 30 mg modified-release orally every 12 hours (or 20 mg modified-release every 8 hours) until descent is complete and symptoms have resolved, as an adjunct to oxygen and descent, and as the main drug when neither is available. Avoid in hypotension. It causes headache, flushing and ankle edema.
5. Phosphodiesterase-5 inhibitors if nifedipine is unavailable (do not combine): sildenafil 50 mg orally every 8 hours, or tadalafil 10 mg orally every 12 hours. Contraindicated with nitrates.
6. Continuous positive airway pressure or expiratory positive airway pressure 10 to 15 cmH2O by mask if oxygen alone fails, and intubation for respiratory failure.
7. Adjunct: salmeterol 125 micrograms by inhaler every 12 hours may help clearing of alveolar fluid. Dexamethasone 8 mg orally, IV or IM once then 4 mg every 6 hours is added when cerebral edema coexists.
8. Avoid diuretics (they worsen volume depletion), morphine (respiratory depression) and sedatives.
9. Re-ascent only after full recovery, with a rest period of several days.

Prevention: gradual ascent (above 3000 m increase sleeping altitude by no more than 300 to 500 m a day, with a rest day every 3 to 4 days), avoidance of heavy exertion in the first days, and drug prophylaxis for people with a previous episode.

The prophylaxis is nifedipine 30 mg modified-release orally every 12 hours starting the day before ascent and continuing for 4 days at the maximum altitude (or until descent).

Tadalafil 10 mg orally every 12 hours is an alternative, and dexamethasone 8 mg orally every 12 hours may be combined. Follow-up at 4 to 6 weeks with echocardiography.