Acetazolamide pre-treatment before ascending to high altitudes: when to start?

Hypoxia is the main responsible factor initiating the symptoms of acute mountain sickness (AMS) in susceptible individuals. Measures that improve oxygenation and/or hasten acclimatization like pre-treatment with acetazolamide will prevent the development of AMS. We hypothesized that pre-treatment with acetazolamide the day before arrival at high altitude would elicit improved oxygenation compared to placebo not until the second day of high-altitude exposure. Fifteen study participants were randomly assigned in a double blind fashion to receive placebo or acetazolamide (2 × 125 mg) before (10 hours and 1 hour) exposure to high altitude (Monte Rosa plateau, 3480 m). Beside AMS scoring, heart rate, minute ventilation, and blood gas analyses were performed during rest and submaximal exercise at low altitude and on day 1, 2 and 3 at high altitude. From low altitude to day 1 at high altitude changes of pH (7.41 ± 0.01 vs. 7.48 ± 0.04) and HCO3 (24.0 ± 0.46 vs. 24.6 ± 2.6 mmol/L) within the placebo group differed significantly from those within the acetazolamide group (7.41 ± 0.01 vs. 7.41 ± 0.02; 23.6 ± 0.38 vs. 20.7 ± 1.8 mmol/L) (P < 0.05). AMS incidence tended to be lower with acetazolamide (P < 0.1). From low altitude to day 2 at high altitude changes of paO2 within the placebo group (75.3 ± 5.4 vs. 40.5 ± 3.4 mmHg) differed significantly from those within the acetazolamide group (76.5 ± 4.5 vs. 48.2 ± 4.9 mmHg) (P < 0.05). In conclusion, pre-treatment with low-dose acetazolamide on the day before ascending to high altitude tended to reduce AMS incidence on the first day at high altitude but improved oxygen availability to tissues not until the second day of exposure. Therefore, it is suggested that the beginning of pre-treatment with low-dose acetazolamide at least two days before arrival at high altitude, in contrast to usual recommendations, would be of greater beneficial effect on AMS development.