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.
Basnyat
Buddha
B
Himalayan Rescue Association and Nepal International Clinic, Kathmandu, Nepal.
Gertsch
Jeffrey H
JH
Holck
Peter S
PS
Johnson
E William
EW
Luks
Andrew M
AM
Donham
Benjamin P
BP
Fleischman
Ross J
RJ
Gowder
Daniel W
DW
Hawksworth
Jason S
JS
Jensen
Brett T
BT
Kleiman
Richard J
RJ
Loveridge
Adam H
AH
Lundeen
Elizabeth B
EB
Newman
Sheri L
SL
Noboa
Jesse A
JA
Miegs
Daniel P
DP
O'Beirne
Kenneth A
KA
Philpot
Kelly B
KB
Schultz
Miriam N
MN
Valente
Matthew C
MC
Wiebers
Mandie R
MR
Swenson
Erik R
ER
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