Studies were identified by searching the MEDLINE, Embase, Cochrane Clinical Trials Register, and ClinicalTrials.gov databases.
Primary end point was difference in incidence of AMS between acetazolamide and placebo groups. Acetazolamide prophylaxis was associated with a 48% relative-risk signaling pathway reduction compared to placebo. There was no evidence of an association between efficacy and dose of acetazolamide. Adverse effects were often not systematically reported but appeared to be common but generally mild. One study found that adverse effects of acetazolamide were dose related. Acetazolamide is effective prophylaxis for the prevention of symptoms of AMS in those going to high altitude. A dose of 250 mg/day has similar efficacy to higher doses and may have a favorable side-effect profile. Acute mountain sickness (AMS), characterized by headache, light-headedness, fatigue, nausea, and insomnia, occurs primarily at altitudes above 2,500 m in those poorly acclimatized to such conditions. If untreated, this symptom complex can progress to the life-threatening conditions of high altitude cerebral edema and high altitude pulmonary edema. It has been suggested that the carbonic anhydrase inhibitor acetazolamide is effective in the prevention of AMS when begun prior to ascent
to altitude. Bleomycin in vitro However, for clinicians prescribing for those ascending to altitude, there has been a lack of clarity regarding the usefulness of acetazolamide, when and for whom it should be recommended, and the optimum dose. While guidelines published by the Wilderness Medical Society recommend acetazolamide for travelers under some circumstances, the Union Internationale des Associations d’Alpinisme does not make a similar suggestion. The side effect profile of acetazolamide includes paraesthesia, urinary frequency, and 4-Aminobutyrate aminotransferase dysgeusia (taste disorder). As such unpleasant symptoms could affect compliance with treatment, it is desirable to determine the lowest effective dose in order to potentially minimize the harmful effects of acetazolamide. Two systematic reviews of acetazolamide in the prevention of altitude-related symptoms have been
published. The first, published in 1994, included trials measuring a diverse range of outcomes not limited to classic symptoms of AMS. This review found evidence of a benefit associated with acetazolamide but the heterogeneity in measured outcomes limits interpretation in a clinical context. The second systematic review was published in 2000 and had more restrictive inclusion criteria—including only studies reporting the incidence of AMS as an end point. The authors concluded that 750 mg/d of acetazolamide was effective in the prophylaxis of AMS but that there was no evidence of benefit from 500 mg/d. However, this review was limited by the small number of patients in the pooled analysis which significantly limited its power.