Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta-analysis.

Objectives: To assess the efficacy of three different daily doses of acetazolamide in the prevention of acute mountain sickness and to determine the lowest effective dose.

Design: Systematic review and meta-analysis.

Data Sources: Medline and Embase along with a hand search of selected bibliographies. No language restrictions were applied.

Study Selection: Randomised controlled trials assessing the use of acetazolamide at 250 mg, 500 mg, or 750 mg daily versus placebo in adults as a drug intervention for the prophylaxis of acute mountain sickness. Included studies were required to state the administered dose of acetazolamide and to randomise participants before ascent to either acetazolamide or placebo. Two reviewers independently carried out the selection process.

Data Extraction: Two reviewers extracted data concerning study methods, pharmacological intervention with acetazolamide, method of assessment of acute mountain sickness, and event rates in both control and intervention groups, which were verified and analysed by the review team collaboratively.

Data Synthesis: 11 studies (with 12 interventions arms) were included in the review. Acetazolamide at doses of 250 mg, 500 mg, and 750 mg were all effective in preventing acute mountain sickness above 3000 m, with a combined odds ratio of 0.36 (95% confidence interval 0.28 to 0.46). At a dose of 250 mg daily the number needed to treat for acetazolamide to prevent acute mountain sickness was 6 (95% confidence interval 5 to 11). Heterogeneity ranged from I(2)=0% (500 mg subgroup) to I(2)=44% (750 mg subgroup).

Conclusions: Acetazolamide in doses of 250 mg, 500 mg, and 750 mg daily are all more effective than placebo for preventing acute mountain sickness. Acetazolamide 250 mg daily is the lowest effective dose to prevent acute mountain sickness for which evidence is available.