Acetazolamide 125 mg BD Is Not Significantly Different from 375 mg BD in the Prevention of Acute Mountain Sickness: The Prophylactic Acetazolamide Dosage Comparison for Efficacy (PACE) Trial

Abstract

750 mg per day of acetazolamide in the prevention of acute mountain sickness (AMS), as recommended in the meta-analysis published in 2000 in the British Medical Journal, may be excessive and is controversial. To determine if the efficacy of low-dose acetazolamide 125 mg bd (250 mg), as currently used in the Himalayas, is significantly different from 375 mg bd (750 mg) of acetazolamide in the prevention of AMS, we designed a prospective, double-blind, randomized, placebo-controlled trial. The participants were sampled from a diverse population of (non-Nepali) trekkers at Namche Bazaar (3440 m) in Nepal on the Everest trekking route as they ascended to study midpoints (4280 m/4358 m) and the endpoint, Lobuje (4928 m), where data were collected. Participants were randomly assigned to receive 375 mg bd of acetazolamide (82 participants), 125 mg bd of acetazolamide (74 participants), or a placebo (66 participants), beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd (24% vs. 21%, 95% confidence interval, -12.6%, 19.8%), in contrast to significantly greater AMS (51%) observed in the placebo group (95% confidence interval for differences: 8%, 46%; 12%, 49% for low and high comparisons, respectively). Both doses of acetazolamide improved oxygenation equally (82.9% for 250 mg daily and 82.8% for 750 mg daily), while placebo endpoint oxygen saturation was significantly less at 80.7% (95% confidence interval for differences: 0.5%, 3.9% and 0.4%, 3.7% for low and high comparisons, respectively). There was also more paresthesia in the 375-mg bd group (p < 0.02). We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 m.

Travel to high altitude with pre-existing lung disease

“…The disorder is best prevented by undertaking a slow ascent to high elevation. Acetazolamide and dexamethasone have both also been proven to be effective prophylactic options [43][44][45]. Adequate treatment requires cessation of ascent, symptomatic treatment with non-narcotic pain relievers and acetazolamide [46].…”

Pen Paper & A Pulse Oxymeter: Prospective Study of the Effect Acetazolamide Have in Quick Trans-Himalayan Acescent

“…Subjects on prophylaxis received one 125 mg acetazolamide tablet to be taken twice a day (35) .The dosage schedule was decided after consulting previous studies (33,34,35,3,4,5,6,19) . Tablets were administered by an appointed person who ensured the timely intake of tablets.…”

“…There is still varied opinion on its mechanism of action though (31) . There have been studies on effective dosage of Acetazolamides (25) and its role in Acute Mountain sickness has been recognized (19) . Hence an enquiry about role of acetazolamide in quick assent where altitude changes every other day was a novel idea for consideration.…”

Continuous Positive Airway Pressure Treatment for Acute Mountain Sickness at 4240 m in the Nepal Himalaya

“…The efficacy of acetazolamide for prevention of AMS has been demonstrated, and is widely used as a preventative in trekking areas of the Nepal Himalaya (Basnyat et al, 2006). Despite effective preventative measures being available, AMS continues to be a common illness during trekking, climbing, and working at altitudes above 2000 m. There is a risk of AMS progressing to the more serious, and sometimes fatal, illnesses high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE).…”