Basnyat Buddha, Jeffrey H. Gertsch, Peter S. Holck, E. William Johnson, Andrew M. Luks, Benjamin
P. Donham, Ross J. Fleischman, Daniel W. Gowder, Jason S. Hawksworth, Brett T. Jensen,
Richard J. Kleiman, Adam H. Loveridge, Elizabeth B. Lundeen, Sheri L. Newman, Jesse A. Noboa,
Daniel P. Miegs, Kenneth A. O'Beirne, Kelly B. Philpot, Miriam N. Schultz, Matthew C. Valente,
Mandie R. Wiebers, and Erik R. Swenson. 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. High Alt. Med. & Biol. 7(17–27), 2006.—
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 com-parisons, 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.
