Another important event that can occur is HAPE, a life-threatening noncardiogenic pulmonary edema that affects unacclimatized lowlanders with a genetic predisposition and typically occurs within 4 days of arriving at high altitude. High-altitude pulmonary edema is an important differential diagnosis to cardiogenic edema in cardiac patients at altitude.
The processes causing HAPE to occur are likely multifactorial, including increased intravascular pressure (pulmonary artery vasoconstriction) leading to pulmonary vascular endothelial cell failure. The resulting impaired pulmonary endothelial and epithelial nitric oxide synthesis/bioavailability, as well as increased levels of thromboxane B 2 and endothelin-1, may represent a central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and, in turn, capillary stress failure and alveolar fluid flooding.
The major preventive measure is a slow ascent and sufficient time for acclimatization. For ascent > 3,050 m (10,000 ft), the recommended ascent rate is = 305 m (1,000 ft) daily with a rest day for every 1,000 m (3,300 ft) climbed. When HAPE is suspected, immediate descent and administration of supplemental oxygen to maintain a saturation of > 90% is the treatment of choice. Medications that have been shown to effectively prevent and treat HAPE include the calcium-channel blocker nifedipine and the phosphodiesterase inhibitors tadalafil and sildenafil.
Nifedipine, a calcium-channel blocker, inhibits hypoxic pulmonary vasoconstriction and thus blunts rising pulmonary artery pressures responsible for HAPE and so can prevent and treat HAPE (same dose for both: orally at 20-30 mg sustained release version q6-12h). The phosphodiesterase type 5 inhibitors reduce pulmonary artery pressure by inhibiting the hypoxia-induced vasoconstriction and thus may be used in the prevention of HAPE (tadalafil 10 mg bid, sildenafil 50 mg q8h); however, treatment doses have not been established.
In summary, the early recognition and appropriate treatment of HAPE with supplemental oxygen, descent to lower altitude, nifedipine, and bed rest are recommended.