Acute mountain sickness: controversies and advances

This review discusses the impact of recent publications on pathophysiologic concepts and on practical aspects of acute mountain sickness (AMS). Magnetic resonance imaging studies do not provide evidence of total brain volume increase nor edema within the first 6 to 10 h of exposure to hypoxia despite symptoms of AMS. After 16 to 32 h at about 4500 m, brain volume increases by 0.8% to 2.7%, but morphological changes do not clearly correlate with symptoms of AMS, and lumbar cerebrospinal fluid pressure was unchanged from normoxic values in individuals with AMS. These data do not support the prevailing hypothesis that AMS is caused by cerebral edema and increased intracranial pressure. Direct measurement of increased oxygen radicals in hypoxia and a first study reducing AMS when lowering oxygen radicals by antioxidants suggest that oxidative stress is involved in the pathophysiology of AMS. Placebo-controlled trials demonstrate that theophylline significantly attenuates periodic breathing without improving arterial oxygen saturation during sleep. Its effects on AMS are marginal and clearly inferior to acetazolamide. A most recent large trial with Ginkgo biloba clearly showed that this drug does not prevent AMS in a low-risk setting in which acetazolamide in a low dose of 2 x 125 mg was effective. Therefore, acetazolamide remains the drug of choice for prevention and the recommended dose remains 2 x 250 mg daily until a lower dose has been tested in a high-risk setting and larger clinical trials with antioxidants have been performed.