High altitude illness pathogenesis and treatment

Abstract

As more people travel to high altitudes for economic or recreational purposes, altitude medicine has become increasingly important. High altitude illness is a term used to describe a number of acute syndromes that may occur in unacclimatized individuals at high altitude including acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Major risk factors for developing high altitude illness include the rate of ascent, the altitude reached, the altitude at which the person sleeps, and individual susceptibility. In both the brain and the lungs, hypoxia elicits neurohumoral and hemodynamic responses that result in overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage, and consequent edema. Evidence is accumulating that cerebral swelling trough vasodilation or cerebral edema, or both, is responsible for the symptoms and signs of AMS and HACE. HAPE results from the conjunction of a defect in pulmonary endothelial (exaggerated altitude-induced pulmonary vasoconstriction) and epithelial (impaired transepithelial sodium and water transport) function. Inflammation reported in HAPE is most likely a nonspecific response to stress-induced failure of capillaries and alveolar flooding, rather than part of the initial pathophysiological process. The main principles of high-altitude illnesses treatment are to stop further ascent, to descend if symptoms do not improve over 24 hours or deteriorate, and to descend urgently if signs of HAPE or HACE occur. Acetazolamide and dexamethasone are the most effective drugs in the treatment and prevention of AMS and HACE while oxygen, if available, is the most effective treatment of HAPE. Oxygen not only reduces pulmonary artery pressure but it also reverses the extreme arterial hypoxemia of HAPE, thus protecting the brain and other organs. Nifedipine, a potent pulmonary vasodilator, is the drug of choice for the treatment of HAPE while nifedipine, salmeterol and possibly phosphodiesterase-5 inhibitors such as sildenafil represent an effective preventive drug therapy in susceptible individuals.