A Randomized Controlled Trial of the Lowest Effective Dose of Acetazolamide for Acute Mountain Sickness Prevention.


Journal

The American journal of medicine
ISSN: 1555-7162
Titre abrégé: Am J Med
Pays: United States
ID NLM: 0267200

Informations de publication

Date de publication:
12 2020
Historique:
received: 30 04 2020
revised: 06 05 2020
accepted: 06 05 2020
pubmed: 2 6 2020
medline: 7 1 2021
entrez: 2 6 2020
Statut: ppublish

Résumé

Acetazolamide is the most common medication used for acute mountain sickness prevention, with speculation that a reduced dose may be as efficacious as standard dosing with fewer side effects. This double-blind, randomized, controlled noninferiority trial compared acetazolamide 62.5 mg twice daily to the standard dose acetazolamide 125 mg twice daily starting the evening prior to ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (ie, headache, Lake Louise Questionnaire ≥3, and another symptom). A total of 106 participants were analyzed, with 51 (48%) randomized to 125 mg and 55 (52%) to 62.5 mg, with a combined acute mountain sickness incidence of 53 (50%) and mean severity of 3 (± 2.1). The 62.5-mg group failed to fall within the prespecified 26% noninferiority margin for acute mountain sickness incidence (62.5 mg = 30 [55%] vs 125 mg = 23 [45%], 95% confidence interval [CI] -11% to 30%). Participants in the 62.5-mg group had a higher risk of acute mountain sickness (odds ratio = 1.5, 95% CI 0.7-3.2) and moderate acute mountain sickness (odds ratio = 1.8, 95% CI 0.6-5.9), with a number needed to harm (NNH) of 9, with a number needed to treat (NNT) in the 125-mg group of 4.8. Increased acute mountain sickness incidence and symptom severity corresponded to lower weight-based and body mass index dosing, with similar side effects between groups. Acetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness. With increased risk and no demonstrable symptomatic or physiologic benefits, acetazolamide 62.5 mg twice daily should not be recommended for acute mountain sickness prevention.

Sections du résumé

BACKGROUND
Acetazolamide is the most common medication used for acute mountain sickness prevention, with speculation that a reduced dose may be as efficacious as standard dosing with fewer side effects.
METHODS
This double-blind, randomized, controlled noninferiority trial compared acetazolamide 62.5 mg twice daily to the standard dose acetazolamide 125 mg twice daily starting the evening prior to ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (ie, headache, Lake Louise Questionnaire ≥3, and another symptom).
RESULTS
A total of 106 participants were analyzed, with 51 (48%) randomized to 125 mg and 55 (52%) to 62.5 mg, with a combined acute mountain sickness incidence of 53 (50%) and mean severity of 3 (± 2.1). The 62.5-mg group failed to fall within the prespecified 26% noninferiority margin for acute mountain sickness incidence (62.5 mg = 30 [55%] vs 125 mg = 23 [45%], 95% confidence interval [CI] -11% to 30%). Participants in the 62.5-mg group had a higher risk of acute mountain sickness (odds ratio = 1.5, 95% CI 0.7-3.2) and moderate acute mountain sickness (odds ratio = 1.8, 95% CI 0.6-5.9), with a number needed to harm (NNH) of 9, with a number needed to treat (NNT) in the 125-mg group of 4.8. Increased acute mountain sickness incidence and symptom severity corresponded to lower weight-based and body mass index dosing, with similar side effects between groups.
CONCLUSION
Acetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness. With increased risk and no demonstrable symptomatic or physiologic benefits, acetazolamide 62.5 mg twice daily should not be recommended for acute mountain sickness prevention.

Identifiants

pubmed: 32479750
pii: S0002-9343(20)30439-3
doi: 10.1016/j.amjmed.2020.05.003
pii:
doi:

Substances chimiques

Carbonic Anhydrase Inhibitors 0
Acetazolamide O3FX965V0I

Banques de données

ClinicalTrials.gov
['NCT03828474']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e706-e715

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Auteurs

Grant S Lipman (GS)

Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, Calif. Electronic address: grantlip@hotmail.com.

Carrie Jurkiewicz (C)

Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, Calif.

Andre Burnier (A)

Stanford Emergency Medicine Residency, Stanford University School of Medicine, Palo Alto, Calif.

James Marvel (J)

Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, Calif.

Caleb Phillips (C)

Department of Computational Science, University of Colorado, Golden.

Cassie Lowry (C)

MountainView Regional Medical Center, Las Cruces, NM.

Jessica Hawkins (J)

Stanford University School of Medicine, Palo Alto, Calif.

Andrew Navlyt (A)

Stanford Emergency Medicine Residency, Stanford University School of Medicine, Palo Alto, Calif.

Erik R Swenson (ER)

Medical Service, VA Puget Sound Health Care System, and Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle.

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Classifications MeSH