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.
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.
Himalayan Rescue Association and Nepal International Clinic, Kathmandu, Nepal.
Buddha
B
Basnyat
Jeffrey H
JH
Gertsch
Peter S
PS
Holck
E William
EW
Johnson
Andrew M
AM
Luks
Benjamin P
BP
Donham
Ross J
RJ
Fleischman
Daniel W
DW
Gowder
Jason S
JS
Hawksworth
Brett T
BT
Jensen
Richard J
RJ
Kleiman
Adam H
AH
Loveridge
Elizabeth B
EB
Lundeen
Sheri L
SL
Newman
Jesse A
JA
Noboa
Daniel P
DP
Miegs
Kenneth A
KA
O'Beirne
Kelly B
KB
Philpot
Miriam N
MN
Schultz
Matthew C
MC
Valente
Mandie R
MR
Wiebers
Erik R
ER
Swenson
D000086:Acetazolamide / Q000008:administration & dosage*; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000188:drug therapy* / Q000517:prevention & control*; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009051:Mountaineering; D009390:Nepal; D016017:Odds Ratio; D011446:Prospective Studies; D011654:Pulmonary Edema / Q000517:prevention & control; D016896:Treatment Outcome
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide