Pharmacological prevention of altitude illness, so a few words about Acetazolamide
DOI:
https://doi.org/10.56782/pps.357Keywords:
acetazolamide, altitude illness, acute mountain sickness, HAPE, HACEAbstract
High-altitude illness is a condition occurring in individuals at high altitudes (above 2500 meters above sea level) resulting from inadequate acclimatization to the unique environment. Initially, the illness manifests as a set of nonspecific symptoms of acute mountain sickness (AMS). Rapid ascent to altitudes above 4000 meters can lead to severe complications, such as high-altitude cerebral edema (HACE) or high-altitude pulmonary edema (HAPE). With appropriate prevention measures, gradual ascent, and the use of medications such as acetazolamide, the risk of developing AMS can be significantly reduced. The mechanism of action of acetazolamide involves increased excretion of bicarbonates by the kidneys, leading to acidification of the blood (a decrease in blood pH). This process stimulates the respiratory center, increasing minute ventilation and improving oxygenation at high altitudes. Clinical studies have demonstrated that using acetazolamide at doses of 125 mg twice daily is effective in preventing AMS. Acetazolamide is well-tolerated, although it may cause side effects such as paresthesia, taste disturbances, or mild diuretic effects. Its use can significantly enhance the body's ability to adapt to high altitudes. In life-threatening conditions such as HAPE and HACE, the treatment primarily relies on other methods. Due to the increasing prevalence of travel to high-altitude regions, physicians and rescue workers are encountering this issue more frequently. The aim of this study is to compile current knowledge on the use of acetazolamide in altitude sickness.
Downloads
References
1. van Veelen, M.J.; Likar, R.; Tannheimer, M.; Bloch, K.E.; Ulrich, S.; Philadelphy, M.; Teuchner, B.; Hochholzer, T.; Pichler Hefti, J.; Hefti, U.; Paal, P.; Burtscher, M. Emergency Care for High-Altitude Trekking and Climbing. High Alt. Med. Biol. 2024, 26(1), 70-86. DOI: 10.1089/ham.2024.0065
2. Gatterer, H.; Villafuerte, F.C.; Ulrich, S; Bhandari, S.S.; Keyes, L.E.; Burtscher, M. Altitude illnesses. Nat. Rev. Dis. Primers 2024, 10(1), Art. No: 43. DOI: 10.1038/s41572-024-00526-w
3. Prince, T.S.; Thurman, J.; Huebner, K. Acute Mountain Sickness. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available online: https://www.ncbi.nlm.nih.gov/books/NBK557466/ (accessed on 13.01.2025)
4. Plewnia, B. W Tatrach padł turystyczny rekord. Polskie góry bardziej popularne od Wielkiego Kanionu. 2025. Available online: https://tvn24.pl/krakow/tatry-w-2024-roku-padl-rekord-liczby-turystow-ile-osob-odwiedzilo-najwyzsze-polskie-gory-st8260104 (accessed on 13.01.2025)
5. Axiom Alpha. Number of People Who Summited Mount Everest by Year (1983-2022). Available online: https://axiomalpha.com/number-of-people-who-summited-mount-everest-by-year/ (accessed on 13.01.2025)
6. Wright, A.D.; Fletcher, R.F. Acute mountain sickness. Postgrad. Med. J. 1987, 63(737), 163–164. DOI: 10.1136/pgmj.63.737.163
7. Imray, C.; Wright, A.; Subudhi, A.; Roach, R. Acute mountain sickness: pathophysiology, prevention, and treatment. Prog. Cardiovasc. Dis. 2010, 52(6), 467-84. DOI: 10.1016/j.pcad.2010.02.003
8. Luks, A.M.; Beidleman, B.A.; Freer, L.; Grissom, C.K.; Keyes, L.E.; McIntosh, S.E.; Rodway, G.W.; Schoene, R.B.; Zafren, K.; Hackett, P.H. Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update. Wilderness Environ. Med. 2024, 35(1_suppl), 2S-19S. DOI: 10.1016/j.wem.2023.05.013
9. Franek, E.; Kokot, F. Zasadowica oddechowa. 2018. Available online: https://www.mp.pl/interna/chapter/B16.II.19.2.4. (accessed on 13.01.2025)
10. Han, C.; Zheng, X.X.; Zhang, W.F. High altitude retinopathy: An overview and new insights. Travel Med. Infect. Dis. 2024, 58, Art. No: 102689. DOI: 10.1016/j.tmaid.2024.102689.
11. Clarke, A.K.; Cozzi, M.; Imray, C.H.E.; Wright, A.; Pagliarini, S. Birmingham Medical Research Expeditionary Society. Analysis of Retinal Segmentation Changes at High Altitude With and Without Acetazolamide. Invest. Ophthalmol. Vis. Sci. 2019, 60(1), 36-40. DOI: 10.1167/iovs.18-24966.
12. Totou, S.; Karmiris, E.; Kanakis, M.; Gartaganis, P.; Petrou, P.; Kalogeropoulos, C.; Kozobolis, V.; Stavrakas, P. Impact of flight and equivalent short-term high-altitude exposure on ocular structures and function. Med. Hypothesis. Discov. Innov. Ophthalmol. 2023, 12(3), 127-141. DOI: 10.51329/mehdiophthal1478.
13. Farzam, K.; Abdullah, M. Acetazolamide. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. Available online: https://www.ncbi.nlm.nih.gov/books/NBK532282/ (accessed on 13.01.2025)
14. Myers, W.R.; Bawcom, C.; Schraudenbach, C.; Bennett, B.L. Inappropriate Acetazolamide Use for a Hiker Who Developed Acute Kidney Injury. Wilderness Environ. Med. 2024, 35(3), 328-331. DOI: 10.1177/10806032241249452
15. Rothwell, A.; Anderson, O. Bilateral choroidal effusions after taking acetazolamide for altitude sickness. BMJ Case Rep. 2022, 15(1), e246145. DOI: 10.1136/bcr-2021-246145
16. Liu, M.; Jiao, X.; Li, R.; Li, J.; Wang, L.; Wang, L.; Wang, Y.; Lv, C.; Huang, D.; Wei, R.; Wang, L.; Ji X.; Guo, X. Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial. BMC Med. 2024, 22(1), 4. DOI: 10.1186/s12916-023-03209-7
17. Gao, D.; Wang, Y.; Zhang, R.; Zhang, Y. Efficacy of acetazolamide for the prophylaxis of acute mountain sickness: A systematic review, meta-analysis, and trial sequential analysis of randomized clinical trials. Ann. Thorac. Med. 2021, 16(4), 337-346. DOI: 10.4103/atm.atm_651_20
18. Shlim, D.R. The use of acetazolamide for the prevention of high-altitude illness. J. Travel Med. 2020, 27(6), taz106. DOI: 10.1093/jtm/taz106
19. Toussaint, C.M.; Kenefick, R.W.; Petrassi, F.A.; Muza, S.R.; Charkoudian, N. Altitude, Acute Mountain Sickness, and Acetazolamide: Recommendations for Rapid Ascent. High. Alt. Med. Biol. 2021, 22(1), 5-13. DOI: 10.1089/ham.2019.0123
20. Yang, H.L.; Deng, M.J.; Zhang, W.; Huang, S. [The preventive effect of four drugs on acute mountain sickness: a Bayesian network meta-analysis]. Zhonghua Jie He He Hu Xi Za Zhi. 2021, 44(11), 953-960. DOI: 10.3760/cma.j.cn112147-20210330-00211
21. Lipman, G.S.; Jurkiewicz, C.; Burnier, A.; Marvel, J.; Phillips, C.; Lowry, C.; Hawkins, J.; Navlyt, A.; Swenson, E.R. A Randomized Controlled Trial of the Lowest Effective Dose of Acetazolamide for Acute Mountain Sickness Prevention. Am. J. Med. 2020, 133(12), e706-e715. DOI: 10.1016/j.amjmed.2020.05.003
22. McIntosh, S.E.; Hemphill, M.; McDevitt, M.C.; Gurung, T.Y.; Ghale, M.; Knott, J.R.; Thapa, G.B.; Basnyat, B.; Dow, J.; Weber, D.C.; K Grissom, C. Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial). Wilderness Environ. Med. 2019, 30(1), 12-21. DOI: 10.1016/j.wem.2018.09.002
23. Burtscher, M.; Hefti, U.; Hefti, J.P. High-altitude illnesses: Old stories and new insights into the pathophysiology, treatment and prevention. Sports Med. Health Sci. 2021, 3(2), 59-69. DOI: 10.1016/j.smhs.2021.04.001
24. Graf, L.C.; Furian, M.; Bitos, K.; Mademilov, M.; Abdraeva, A.; Buenzli, J.; Buenzli, S.; Aidaralieva, S.; Sheraliev, U.; Mayer, L.C.; Schneider, S.R.; Sooronbaev, T.M.; Ulrich, S.; Bloch, K.E. Effect of altitude and acetazolamide on sleep and nocturnal breathing in healthy lowlanders 40 y of age or older. Data from a randomized trial. Sleep 2023, 46(4), zsac269. DOI: 10.1093/sleep/zsac269
25. Mutschler, T.; Furian, M.; Lichtblau, M.; Buergin, A.; Schneider, S.R.; Appenzeller, P.; Mayer, L.; Muralt, L.; Mademilov, M.; Abdyraeva, A.; Aidaralieva, S.; Muratbekova, A.; Akylbekov, A.; Shabykeeva, S.; Sooronbaev, T.M.; Ulrich, S.; Bloch, K.E. Effect of altitude and acetazolamide on postural control in healthy lowlanders 40 years of age or older. Randomized, placebo-controlled trial. Front. Physiol. 2024, 14, Art. No: 1274111. DOI: 10.3389/fphys.2023.1274111
26. Nimje, M.A.; Patir, H.; Tirpude, R.; Kumar, B. Elucidating the combined effect of intermittent hypoxia training and acetazolamide on hypoxia induced hematological and physiological changes. Curr. Res. Physiol. 2022, 5, 27-337. DOI: 10.1016/j.crphys.2022.07.004
27. Bhattachar, S.; Malhotra, V.K.; Yanamandra, U.; Singh, S.; Sikri, G.; Patrikar, S.; Kotwal, A. Ibuprofen Compared to Acetazolamide for the Prevention of Acute Mountain Sickness: A Randomized Placebo-Controlled Trial. Cureus 2024, 16(3), Art. No: e55998. DOI: 10.7759/cureus.55998
28. Pun, M. Rapid Ascent to High Altitude: Acetazolamide or Ibuprofen? Am. J. Med. 2021, 134(3), e230-e230. DOI: 10.1016/j.amjmed.2020.03.023
29. Schilling, M.; Irarrázaval, S. Ibuprofen versus acetazolamide for prevention of acute mountain sickness. Medwave 2020, 20(5), Art. No: e7733. DOI: 10.5867/medwave.2020.05.7732
30. Burns, P.; Lipman G.S.; Warner, K.; Jurkiewicz. C.; Phillips, C.; Sanders, L.; Soto, M.; Hackett, P. Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide. Am. J. Med. 2019, 132(2), 247-251. DOI: 10.1016/j.amjmed.2018.10.021
31. Kaeley, N.; Datta, S.S.; Sharma, A; Jithesh, G. Hiccups and Slurring of Speech: Atypical Presentation of High-Altitude Cerebral Edema. Cureus 2023, 15(2), Art. No: e34997. DOI: 10.7759/cureus.34997
32. Berger, M.M.; Sareban, M.; Schiefer, L.M.; Swenson, K.E.; Treff, F.; Schäfer, L.; Schmidt, P.; Schimke, M.; Paar, M.; Niebauer, J.; Cogo, A.; Kriemler, S.; Schwery, S.; Pickerodt, P.A; Mayer, B.; Bärtsch P.; Swenson, E.R. Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m. J. Appl. Physiol. 2022, 132(6), 1361-1369. DOI: 10.1152/japplphysiol.00806.2021
33. Park, A.; Brillhart, A.; Sethi, S.; Abramor, B.; Duplessis, R.; Pronce, R.; Seufferheld, J.;, Schlein, S. Characteristics of Climbers with High Altitude Pulmonary Edema on Mount Aconcagua. Wilderness Environ. Med. 2024, 36(1), 113-118. DOI: 10.1177/10806032241303438
34. Hundt, N.; Apel, C.; Bertsch, D.; Cerfontaine, C.; van der Giet, M.; van der Giet, S.; Graß, M.; Haunolder, M.; Heussen, N.M.; Jäger, J.; Kühn, C.; Morrison, A.; Museo, S.; Timmermann, L.; Wernitz, K.; Gieseler, U.; Küpper, T. Variables Influencing the Pressure and Volume of the Pulmonary Circulation as Risk Factors for Developing High Altitude Pulmonary Edema (HAPE). Int. J. Environ. Res. Public Health 2022, 19(21), Art. No: 13887. DOI: 10.3390/ijerph192113887
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Kinga Kocur, Oskar Fogiel, Dominika Mularska, Jan Machalica, Katarzyna Camlet
This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
How to Cite
