Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Jun 27;6(6):CD009761.
doi: 10.1002/14651858.CD009761.pub2.

Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs

Víctor H Nieto Estrada  1 , Daniel Molano Franco, Roger David Medina, Alejandro G Gonzalez Garay, Arturo J Martí-Carvajal, Ingrid Arevalo-Rodriguez
Affiliations
Meta-Analysis

Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs

Víctor H Nieto Estrada et al. Cochrane Database Syst Rev. .

Abstract

Background: High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions.

Objectives: To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search.

Selection criteria: We included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI.

Data collection and analysis: We used standard methodological procedures as expected by Cochrane.

Main results: We included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons: Acetazolamide versus placebo (28 parallel studies; 2345 participants)The risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I2 = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I2 = 60%; 5 studies, 789 participants; low quality of evidence). Budenoside versus placebo (2 parallel studies; 132 participants)Data on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I2 = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence). Dexamethasone versus placebo (7 parallel studies; 205 participants)For dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality.

Authors' conclusions: Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.

PubMed Disclaimer

Conflict of interest statement

Victor H Nieto Estrada: nothing to declare. Daniel Molano Franco: nothing to declare. Roger David Medina: nothing to declare. Alejandro Gonzalez Garay: nothing to declare. Arturo Marti Carvajal: nothing to declare. Ingrid Arevalo‐Rodriguez: nothing to declare.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, outcome: 1.1 Incidence of acute mountain sickness.
5
5
Funnel plot of comparison: 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, outcome: 1.1 Incidence of acute mountain sickness.
6
6
Trial sequential analysis on prevention of acute mountain illness in 16 oral acetazolamide at any dose vs placebo trials
1.1
1.1. Analysis
Comparison 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, Outcome 1 Incidence of acute mountain sickness.
1.2
1.2. Analysis
Comparison 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, Outcome 2 Incidence of high altitude pulmonary oedema.
1.3
1.3. Analysis
Comparison 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, Outcome 3 Incidence of high altitude cerebral oedema.
1.4
1.4. Analysis
Comparison 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, Outcome 4 Incidence of adverse events: Paraesthesia.
1.5
1.5. Analysis
Comparison 1 Carbonic anhydrase inhibitors: acetazolamide versus placebo, Outcome 5 Differences in HAI/AMS scores.
2.1
2.1. Analysis
Comparison 2 Steroids: budesonide vs. placebo, Outcome 1 Incidence of acute mountain sickness.
3.1
3.1. Analysis
Comparison 3 Steroids: dexamethasone vs. placebo, Outcome 1 Incidence of acute mountain sickness.
3.2
3.2. Analysis
Comparison 3 Steroids: dexamethasone vs. placebo, Outcome 2 Differences in HAI/AMS scores.
4.1
4.1. Analysis
Comparison 4 Calcium modulators: nifedipine vs. placebo, Outcome 1 Differences in HAI/AMS scores.
5.1
5.1. Analysis
Comparison 5 NSAIDs and other analgesic: aspirin vs. placebo, Outcome 1 Incidence of AMS.
6.1
6.1. Analysis
Comparison 6 NSAIDs and other analgesic: ibuprofen vs. placebo, Outcome 1 Incidence of acute mountain sickness.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Anonymous 1981 {published data only}
    1. Anonymous. Acetazolamide in control of acute mountain sickness. Lancet 1981;1(8213):180‐3. [PUBMED: 6109857] - PubMed
ASCENT 2012 {published data only}
    1. Gertsch JH, Corbett B, Holck PS, Mulcahy A, Watts M, Stillwagon NT, et al. Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): randomized, controlled trial of ibuprofen versus placebo for prevention of altitude illness. Wilderness and Environmental Medicine 2012;23(4):307‐15. - PubMed
Banderet 1977 {published data only}
    1. Banderet LE. Self‐rated moods of humans at 4300 m pretreated with placebo or acetazolamide plus staging. Aviation, Space, and Environmental Medicine 1977;48(1):19‐22. [PUBMED: 831706] - PubMed
Bartsch 1991 {published data only}
    1. Bartsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high‐altitude pulmonary edema by nifedipine. New England Journal of Medicine 1991;325(18):1284‐9. [PUBMED: 1922223] - PubMed
    1. Oelz O, Maggiorini M, Ritter M, Noti C, Waber U, Vock P, et al. Prevention and treatment of high altitude pulmonary edema by a calcium channel blocker. International Journal of Sports Medicine 1992;13(1):S65‐8. [PUBMED: 1483797] - PubMed
Basnyat 2003 {published data only}
    1. Basnyat B, Gertsch JH, Johnson EW, Castro‐Marin F, Inoue Y, Yeh C. Efficacy of low‐dose acetazolamide (125 mg BID) for the prophylaxis of acute mountain sickness: a prospective, double‐blind, randomized, placebo‐controlled trial. High Altitude Medicine & Biology 2003;4(1):45‐52. [PUBMED: 12713711] - PubMed
Basnyat 2008 {published data only}
    1. Basnyat B, Hargrove J, Holck PS, Srivastav S, Alekh K, Ghimire LV, et al. Acetazolamide fails to decrease pulmonary artery pressure at high altitude in partially acclimatized humans. High Altitude Medicine & Biology 2008;9(3):209‐16. [PUBMED: 18800957] - PubMed
Basu 2002a {published data only}
    1. Basu M, Sawhney RC, Kumar S, Pal K, Prasad R, Selvamurthy W. Glucocorticoids as prophylaxis against acute mountain sickness. Clinical Endocrinology 2002;57(6):761‐7. [PUBMED: 12460326] - PubMed
Basu 2002b {published data only}
    1. Basu M, Sawhney RC, Kumar S, Pal K, Prasad R, Selvamurthy W. Hypothalamic‐pituitary‐adrenal axis following glucocorticoid prophylaxis against acute mountain sickness. Hormone and Metabolic Research 2002;34(6):318‐24. [PUBMED: 12173072] - PubMed
Bates 2011 {published data only}
    1. Bates MG, Thompson AA, Baillie JK, Sutherland AI, Irving JB, Hirani N, et al. Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo‐controlled trial. High Altitude Medicine & Biology 2011;12(3):207‐14. [PUBMED: 21962063] - PubMed
Baumgartner 2003 {published data only}
    1. Baumgartner RW, Keller S, Regard M, Bartsch P. Flunarizine in prevention of headache, ataxia, and memory deficits during decompression to 4559 m. High Altitude Medicine & Biology 2003;4(3):333‐9. [PUBMED: 14561238] - PubMed
Bernhard 1994 {published data only}
    1. Bernhard WN, Miller SL, Gittelsohn A. Dexamethasone for prophylaxis against acute mountain sickness during rapid ascent to 5334 m. Journal of Wilderness Medicine 1994;5(3):331‐8.
Bernhard 1998 {published data only}
    1. Bernhard WN, Schalick LM, Delaney PA, Bernhard TM, Barnas GM. Acetazolamide plus low‐dose dexamethasone is better than acetazolamide alone to ameliorate symptoms of acute mountain sickness. Aviation, Space, and Environmental Medicine 1998;69(9):883‐6. [PUBMED: 9737760] - PubMed
Bradwell 1986 {published data only}
    1. Bradwell AR, Dykes PW, Coote JH, Forster PJ, Milles JJ, Chesner I, et al. Effect of acetazolamide on exercise performance and muscle mass at high altitude. Lancet 1986;1(8488):1001‐5. [PUBMED: 2871285] - PubMed
Burki 1992 {published data only}
    1. Burki NK, Khan SA, Hameed MA. The effects of acetazolamide on the ventilatory response to high altitude hypoxia. Chest 1992;101(3):736‐41. [PUBMED: 1541140] - PubMed
Burtscher 1998 {published data only}
    1. Burtscher M, Likar R, Nachbauer W, Philadelphy M. Aspirin for prophylaxis against headache at high altitudes: randomised, double blind, placebo controlled trial. BMJ 1998;316(7137):1057‐8. - PMC - PubMed
Burtscher 2001 {published data only}
    1. Burtscher M, Likar R, Nachbauer W, Philadelphy M, Pühringer R, Lämmle T. Effects of aspirin during exercise on the incidence of high‐altitude headache: a randomized, double‐blind, placebo‐controlled trial. Headache 2001;41(6):542‐5. - PubMed
Burtscher 2014 {published data only}
    1. Burtscher M, Gatterer H, Faulhaber M, Burtscher J. Acetazolamide pre‐treatment before ascending to high altitudes: When to start?. International Journal of Clinical and Experimental Medicine 2014;15(11):4378‐83. [PUBMED: 25550957] - PMC - PubMed
Carlsten 2004 {published data only}
    1. Carlsten C, Swenson ER, Ruoss S. A dose‐response study of acetazolamide for acute mountain sickness prophylaxis in vacationing tourists at 12,000 feet (3630 m). High Altitude Medicine & Biology 2004;5(1):33‐9. [PUBMED: 15072715] - PubMed
Chen 2015 {published data only}
    1. Chen GZ, Zheng CR, Qin J, Yu J, Wang H, Zhang JH, et al. Inhaled budesonide prevents acute mountain sickness in young Chinese men. Journal of Emergency Medicine 2015;48(2):197‐206. [PUBMED: 25294611] - PubMed
    1. Xiangjun L, Lan H. Inhaled budesonide for the prevention of acute mountain sickness in unacclimatization young men: A double‐blind randomized controlled trial. Journal of the American College of Cardiology 2014;16 Suppl 1(64):C69.
Chow 2005 {published data only}
    1. Chow T, Browne V, Heileson HL, Wallace D, Anholm J, Green SM. Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo‐controlled trial. Archives of Internal Medicine 2005;165(3):296‐301. [PUBMED: 15710792] - PubMed
Ellsworth 1991 {published data only}
    1. Ellsworth AJ, Meyer EF, Larson EB. Acetazolamide or dexamethasone use versus placebo to prevent acute mountain sickness on Mount Rainier. Western Journal of Medicine 1991;154(3):289‐93. [PUBMED: 2028586] - PMC - PubMed
Faull 2015 {published data only}
    1. Faull OK, Robertson J, Thomas O, Bradwell AR, Antoniades CA, Pattinson KTS, et al. The effect of acetazolamide on saccadic latency at 3459 meters. Wilderness and Environmental Medicine 2015;26(1):72‐7. - PubMed
Fischer 2000a {published data only}
    1. Fischer R, Hautmann H, Toepfer M, Tschoep M, Pongratz H, Huber RM. Oral slow release theophylline (oT) is effective in prevention of acute mountain sickness [abstract]. European Respiratory Journal. Supplement. 1998;12(Suppl 28):407S. [CN‐00382822]
    1. Fischer R, Lang SM, Steiner U, Toepfer M, Hautmann H, Pongratz H, et al. Theophylline improves acute mountain sickness. European Respiratory Journal 2000;15(1):123‐7. [PUBMED: 10678632] - PubMed
Fischer 2004 {published data only}
    1. Fischer R, Vollmar C, Thiere M, Born C, Leitl M, Pfluger T, et al. No evidence of cerebral oedema in severe acute mountain sickness. Cephalalgia 2004;24(1):66‐71. [PUBMED: 14687016] - PubMed
Fulco 2006 {published data only}
    1. Fulco CS, Muza SR, Ditzler D, Lammi E, Lewis SF, Cymerman A. Effect of acetazolamide on leg endurance exercise at sea level and simulated altitude. Clinical Science 2006;110(6):683‐92. [PUBMED: 16499476] - PubMed
Greene 1981 {published data only}
    1. Greene MK, Kerr AM, McIntosh IB, Prescott RJ. Acetazolamide in prevention of acute mountain sickness: a double‐blind controlled cross‐over study. BMJ 1981;283(6295):811‐3. [PUBMED: 6794709] - PMC - PubMed
Hackett 1976 {published data only}
    1. Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976;2(7996):1149‐55. [PUBMED: 62991] - PubMed
Hackett 1988 {published data only}
    1. Hackett PH, Roach RC, Wood RA, Foutch RG, Meehan RT, Rennie D, et al. Dexamethasone for prevention and treatment of acute mountain sickness. Aviation, Space, and Environmental Medicine 1988;59(10):950‐4. [PUBMED: 3190622] - PubMed
HEAT 2010 {published data only}
    1. Gertsch JH, Lipman GS, Holck PS, Merritt A, Mulcahy A, Fisher RS, et al. Prospective, double‐blind, randomized, placebo‐controlled comparison of acetazolamide versus ibuprofen for prophylaxis against high altitude headache: the Headache Evaluation at Altitude Trial (HEAT). Wilderness & Environmental Medicine 2010;21(3):236‐43. [PUBMED: 20832701] - PubMed
Hillenbrand 2006 {published data only}
    1. Hillenbrand P, Pahari AK, Soon Y, Subedi D, Bajracharya R, Gurung P, et al. Prevention of acute mountain sickness by acetazolamide in Nepali porters: a double‐blind controlled trial. Wilderness & Environmental Medicine 2006;17(2):87‐93. [PUBMED: 16805144] - PubMed
Hochapfel 1986 {published data only}
    1. Hochapfel G, Schlemmer W. Prophylaxis of acute mountain sickness. Experiences with acetazolamide in Nepal. Munchener Medizinische Wochenschrift 1986;128(8):137‐8.
Hohenhaus 1994 {published data only}
    1. Hohenhaus E, Goerre S, Niroomand F, Oelz O, Bartsch P. Nifedipine does not prevent acute mountain sickness [abstract]. European Respiratory Journal. Supplement. 1993; Vol. 7 Suppl 17:187S. [CN‐00393692] - PubMed
    1. Hohenhaus E, Niroomand F, Goerre S, Vock P, Oelz O, Bartsch P. Nifedipine does not prevent acute mountain sickness. American Journal of Respiratory and Critical Care Medicine 1994;150(3):857‐60. [PUBMED: 8087361] - PubMed
Hussain 2001 {published data only}
    1. Hussain MM, Aslam M, Khan Z. Acute mountain sickness score and hypoxemia. Journal of the Pakistan Medical Association 2001;5(5):173‐9. - PubMed
Jain 1986 {published data only}
    1. Jain SC, Singh MV, Sharma VM, Rawal SB, Tyagi AK. Amelioration of acute mountain sickness: comparative study of acetazolamide and spironolactone. International Journal of Biometeorology 1986;30(4):293‐300. [PUBMED: 3804482] - PubMed
Johnson 1984 {published data only}
    1. Johnson TS, Rock PB, Fulco CS, Trad LA, Spark RF, Maher JT. Prevention of acute mountain sickness by dexamethasone. New England Journal of Medicine 1984;310(11):683‐6. [PUBMED: 6700643] - PubMed
Kayser 2008 {published data only}
    1. Kayser B, Hulsebosch R, Bosch F. Low‐dose acetylsalicylic acid analog and acetazolamide for prevention of acute mountain sickness. High Altitude Medicine & Biology 2008;9(1):15‐23. [PUBMED: 18331216] - PubMed
Ke 2013 {published data only}
    1. Ke T, Wang J, Swenson ER, Zhang X, Hu Y, Chen Y, et al. Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent. High Altitude Medicine & Biology 2013;14(2):162‐7. [PUBMED: 23795737] - PMC - PubMed
Küpper 2008 {published data only}
    1. Küpper TE, Strohl KP, Hoefer M, Gieseler U, Netzer CM, Netzer NC. Low‐dose theophylline reduces symptoms of acute mountain sickness. Journal of Travel Medicine 2008;15(5):307‐14. [PUBMED: 19006503] - PubMed
Larson 1982a {published data only}
    1. Larson EB, Roach RC, Schoene RB, Hornbein TF. Acute mountain sickness and acetazolamide. Clinical efficacy and effect on ventilation. JAMA 1982;248(3):328‐32. [PUBMED: 7045433] - PubMed
Lipman 2012 {published data only}
    1. Lipman GS, Kanaan NC, Holck P, Gertsch JH, Constance BB, Corbett B, et al. Ibuprofen prevents altitude illness: A prospective, double‐blind, randomized controlled trial. Academic Emergency Medicine 2011;18(5 Suppl 1):S15. - PubMed
    1. Lipman GS, Kanaan NC, Holck PS, Constance BB, Gertsch JH, PAINS Group. Ibuprofen prevents altitude illness: a randomized controlled trial for prevention of altitude illness with nonsteroidal anti‐inflammatories. Annals of Emergency Medicine 2012;58(6):484‐90. [PUBMED: 22440488] - PubMed
Luks 2007 {published data only}
    1. Luks AM, Henderson WR, Swenson ER. Leukotriene receptor blockade does not prevent acute mountain sickness induced by normobaric hypoxia. High Altitude Medicine & Biology 2007;8(2):131‐8. [PUBMED: 17584007] - PubMed
Maggiorini 2006 {published data only}
    1. Bernheim AM, Kiencke S, Fischler M, Dorschner L, Debrunner J, Mairbaurl H, et al. Acute changes in pulmonary artery pressures due to exercise and exposure to high altitude do not cause left ventricular diastolic dysfunction. Chest 2007;132:380‐7. - PubMed
    1. Fischler M, Maggiorini M, Dorschner L, Debrunner J, Bernheim A, Kiencke S, et al. Dexamethasone but not tadalafil improves exercise capacity in adults prone to high‐altitude pulmonary edema. American Journal of Respiratory and Critical Care Medicine 2009;180(4):346‐52. [PUBMED: 19520908] - PubMed
    1. Maggiorini M, Brunner‐La Rocca HP, Peth S, Fischler M, Bohm T, Bernheim A, et al. Both tadalafil and dexamethasone may reduce the incidence of high‐altitude pulmonary edema: a randomized trial. Annals of Internal Medicine 2006;145(7):497‐506. [PUBMED: 17015867] - PubMed
    1. Mairbaurl H, Brunner‐La Rocca HP, Peth S, Dehnert C, Fischler M, Bohm T, et al. Phosphodiesterase‐5 inhibitors and glucocorticoids prevent a high‐altitude pulmonary oedema. Deutsche Zeitschrift für Sportmedizin 2005; Vol. 56, issue 7/8:218. [CN‐00727391]
Mirrakhlmov 1993 {published data only}
    1. Mirrakhimov M, Brimkulov N, Cielicki J, Tobiasz M, Kudaiberdiev Z, Moldotashev I, et al. Asthma treatment at high altitude effects of acetazolamide on overnight oximetry and prevention of acute mountain sickness [Abstract]. European Respiratory Journal 1992; Vol. 5, issue Suppl 15:366s. [CN‐00494881] - PubMed
    1. Mirrakhlmov M, Brimkulov N, Cieslicki J, Tobiasz M, Kudaiberdiev Z, Moldotashev I, et al. Effects of acetazolamide on overnight oxygenation and acute mountain sickness in patients with asthma. European Respiratory Journal 1993;6(4):536‐40. [PUBMED: 8491304] - PubMed
Montgomery 1989 {published data only}
    1. Montgomery AB, Luce JM, Michael P, Mills J. Effects of dexamethasone on the incidence of acute mountain sickness at two intermediate altitudes. JAMA 1989;261(5):734‐6. [PUBMED: 2911170] - PubMed
Moraga 2007 {published data only}
    1. Moraga FA, Flores A, Serra J, Esnaola C, Barriento C. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollague (3696 m) in northern Chile. Wilderness & Environmental Medicine 2007;18(4):251‐7. [PUBMED: 18076292] - PubMed
Muza 2004 {published data only}
    1. Muza SR, Kaminsky D, Fulco CS, Banderet LE, Cymerman A. Cysteinyl leukotriene blockade does not prevent acute mountain sickness. Aviation, Space, and Environmental Medicine 2004;75(5):413‐9. [PUBMED: 15152893] - PubMed
PACE 2006 {published data only}
    1. Basnyat B, Gertsch JH, Holck PS, Johnson EW, Luks AM, Donham BP, et al. 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 Altitude Medicine & Biology 2006;7(1):17‐27. [PUBMED: 16544963] - PubMed
Parati 2013 {published data only}
    1. Caravita S, Faini A, Lombardi C, Valentini M, Gregorini F, Rossi J, et al. Sex and acetazolamide effects on chemoreflex and periodic breathing during sleep at altitude. Chest 2015;147(1):120‐31. - PubMed
    1. Parati G, Revera M, Giuliano A, Faini A, Bilo G, Gregorini F, et al. Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure. European Heart Journal 2013;10(10):759‐66. - PubMed
    1. Salvi P, Revera M, Faini A, Giuliano A, Gregorini F, Agostoni, et al. Changes in subendocardial viability ratio with acute high‐altitude exposure and protective role of acetazolamide. Hypertension 2013;61(4):793‐9. - PubMed
PHAIT 2004 {published data only}
    1. Gertsch JH, Basnyat B, Johnson EW, Onopa J, Holck PS. Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT). BMJ 2004;328(7443):797. [PUBMED: 15070635] - PMC - PubMed
Rock 1987 {published data only}
    1. Rock PB, Johnson TS, Cymerman A, Burse RL, Falk LJ, Fulco CS. Effect of dexamethasone on symptoms of acute mountain sickness at Pikes Peak, Colorado (4,300 m). Aviation, Space,and Environmental Medicine 1987;58(7):668‐72. [PUBMED: 3619842] - PubMed
Rock 1989a {published data only}
    1. Rock PB, Johnson TS, Larsen RF, Fulco CS, Trad LA, Cymerman A. Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level. Chest 1989;95(3):568‐73. [PUBMED: 2920585] - PubMed
Sartori 2002 {published data only}
    1. Sartori C, Allemann Y, Duplain H, Lepori M, Egli M, Lipp E, et al. Salmeterol for the prevention of high‐altitude pulmonary edema. New England Journal of Medicine 2002;346(21):1631‐6. [PUBMED: 12023995] - PubMed
SPACE 2011 {published data only}
    1. Basnyat B, Holck PS, Pun M, Halverson S, Szawarski P, Gertsch J, et al. Spironolactone does not prevent acute mountain sickness: a prospective, double‐blind, randomized, placebo‐controlled trial by SPACE Trial Group (spironolactone and acetazolamide trial in the prevention of acute mountain sickness group). Wilderness & Environmental Medicine 2011;22(1):15‐22. [PUBMED: 21377114] - PubMed
Subudhi 2011 {published data only}
    1. Julian CG, Subudhi AW, Wilson MJ, Dimmen AC, Pecha T, Roach RC. Acute mountain sickness, inflammation, and permeability: New insights from a blood biomarker study. Journal of Applied Physiology 2011;111(2):392‐9. - PMC - PubMed
    1. Subudhi AW, Dimmen AC, Julian CG, Wilson MJ, Panerai RB, Roach RC. Effects of acetazolamide and dexamethasone on cerebral hemodynamics in hypoxia. Journal of Applied Physiology 2011;110(5):1219‐25. [PUBMED: 21393464] - PMC - PubMed
Van Patot 2008 {published data only}
    1. Patot MC, Leadbetter G 3rd, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic low‐dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Altitude Medicine & Biology 2008;9(4):289‐93. [PUBMED: 19115912] - PubMed
Wang 2013 {published data only}
    1. Wang J, Ke T, Zhang X, Chen Y, Liu M, Chen J, et al. Effects of acetazolamide on cognitive performance during high‐altitude exposure. Neurotoxicology and Teratology 2013;35:28‐33. [PUBMED: 23280141] - PubMed
Wright 1983 {published data only}
    1. Wright AD, Bradwell AR, Fletcher RF. Methazolamide and acetazolamide in acute mountain sickness. Aviation, Space, and Environmental Medicine 1983;54(7):619‐21. [PUBMED: 6349608] - PubMed
Wright 2004 {published data only}
    1. Wright AD, Beazley MF, Bradwell AR, Chesner IM, Clayton RN, Forster PJ, et al. Medroxyprogesterone at high altitude. The effects on blood gases, cerebral regional oxygenation, and acute mountain sickness. Wilderness & Environmental Medicine 2004;15(1):25‐31. [PUBMED: 15040503] - PubMed
Zell 1988 {published data only}
    1. Zell SC, Goodman PH. Acetazolamide and dexamethasone in the prevention of acute mountain sickness. Western Journal of Medicine 1988;148(5):541‐5. [PUBMED: 3051673] - PMC - PubMed
Zheng 2014 {published data only}
    1. Zheng CR, Chen GZ, Yu J, Qin J, Song P, Bian SZ, et al. Inhaled budesonide and oral dexamethasone prevent acute mountain sickness. American Journal of Medicine 2014;127(10):1001‐9.e2. [PUBMED: 24784698] - PubMed

References to studies excluded from this review

ACME‐1 2006 {published data only}
    1. Modesti PA, Vanni S, Morabito M, Modesti A, Marchetta M, Gamberi T, et al. Role of endothelin‐1 in exposure to high altitude: Acute Mountain Sickness and Endothelin‐1 (ACME‐1) study. Circulation 2006;114(13):1410‐6. [PUBMED: 16982943] - PubMed
Agostoni 2013 {published data only}
    1. Agostoni P, Swenson ER, Fumagalli R, Salvionia E, Cattadoria G, Farina S, et al. Acute high‐altitude exposure reduces lung diffusion: Data from the HIGHCARE Alps project. Respiratory Physiology & Neurobiology 2013;188(2):223‐8. - PubMed
Bartsch 1993 {published data only}
    1. Bärtsch P, Merki B, Hofstetter D, Maggiorini M, Kayser B, Oelz O. Treatment of acute mountain‐sickness by simulated descent ‐ a randomized controlled trial. BMJ 1993;306(6885):1098‐101. - PMC - PubMed
Bärtsch 1994 {published data only}
    1. Bartsch P, Maggi S, Kleger GR, Ballmer PE, Baumgartner RW. Sumatriptan for high‐altitude headache. Lancet 1994;344(8934):1445. [PUBMED: 7968111] - PubMed
Bilo 2015 {published data only}
    1. Bilo G, Lombardi C, Revera M, Diazzi E, Giuliano A, Faini A, et al. Acetazolamide counteracts ambulatory blood pressure increase under acute exposure to high altitude. High Blood Pressure and Cardiovascular Prevention 2011;18(3):118.
    1. Bilo G, Villafuerte FC, Faini A, Anza‐Ramírez C, Revera M, Giuliano A, et al. Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: The High Altitude Cardiovascular Research‐Andes study. Hypertension 2015;65(6):1266‐72. - PubMed
    1. Bilo, G, Villafuerte F, Anza C, Revera, Giuliano A, Faini A, et al. Combined antihypertensive treatment and blood pressure responses to acute high altitude exposure in patients with hypertension. HIGHCARE‐ANDES Lowlanders Study. European Heart Journal 2011;34(Suppl 1):269‐70.
Bloch 2009 {published data only}
    1. Bloch KE, Turk AJ, Maggiorini M, Hess T, Merz T, Bosch MM, et al. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. High Altitude Medicine & Biology 2009;10(1):25‐32. [PUBMED: 19326598] - PubMed
Broome 1994 {published data only}
    1. Broome JR, Stoneham MD, Beeley JM, Milledge JS, Hughes AS. High altitude headache: treatment with ibuprofen. Aviation, Space, and Environmental Medicine 1994;65(1):19‐20. [PUBMED: 8117220] - PubMed
Cain 1966 {published data only}
    1. Cain SM, Dunn JE 2nd. Low doses of acetazolamide to aid accommodation of men to altitude. Journal of Applied Physiology 1966;21(4):1195‐200. [PUBMED: 5916650] - PubMed
Debevec 2015 {published data only}
    1. Debevec T, Pialoux V, Saugy J, Schmitt L, Cejuela R, Mury P, et al. Prooxidant/Antioxidant balance in hypoxia: A cross‐over study on normobaric vs. hypobaric "live high‐train low". PLoS ONE 2015;10(9):e0137957. - PMC - PubMed
Dumont 1999 {published data only}
    1. Dumont L, Mardirosoff C, Soto‐Debeuf G, Tassonyi E. Magnesium and acute mountain sickness. Aviation, Space, and Environmental Medicine 1999;70(6):625. [PUBMED: 10373058] - PubMed
Forster 1982 {published data only}
    1. Forster P. Methazolamide in acute mountain sickness. Lancet 1982;1(8283):1254. [PUBMED: 6123014] - PubMed
Forwand 1968 {published data only}
    1. Forwand SA, Landowne M, Follansbee JN, Hansen JE. Effect of acetazolamide on acute mountain sickness. New England Journal of Medicine 1968;279(16):839‐45. [PUBMED: 4877992] - PubMed
Fulco 2011 {published data only}
    1. Fulco CS, Muza SR, Beidleman BA, Demes R, Staab JE, Jones JE, et al. Effect of repeated normobaric hypoxia exposures during sleep on acute mountain sickness, exercise performance, and sleep during exposure to terrestrial altitude. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 2011;300(2):R428‐36. [PUBMED: 21123763] - PubMed
Gertsch 2002 {published data only}
    1. Gertsch JH, Seto TB, Mor J, Onopa J. Ginkgo biloba for the prevention of severe acute mountain sickness (AMS) starting one day before rapid ascent. High Altitude Medicine & Biology 2002;3(1):29‐37. [PUBMED: 12006162] - PubMed
Gray 1971 {published data only}
    1. Gray GW, Bryan AC, Frayser R, Houston CS, Rennie ID. Control of acute mountain sickness. Aerospace Medicine 1971;42(1):81‐4. [PUBMED: 4925130] - PubMed
Harris 2003 {published data only}
    1. Harris NS, Wenzel RP, Thomas SH. High altitude headache: efficacy of acetaminophen vs. ibuprofen in a randomized, controlled trial. Journal of Emergency Medicine 2003;24(4):383‐7. [PUBMED: 12745039] - PubMed
Johnson 1988 {published data only}
    1. Johnson TS, Rock PB, Young JB, Fulco CS, Trad LA. Hemodynamic and sympathoadrenal responses to altitude in humans: effect of dexamethasone. Aviation, Space, and Environmental Medicine 1988;59(3):208‐12. [PUBMED: 3355474] - PubMed
Jonk 2007 {published data only}
    1. Jonk AM, Berg IP, Olfert IM, Wray DW, Arai T, Hopkins SR, et al. Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise. Journal of Physiology 2007;579(Pt 3):909‐21. [PUBMED: 17218362] - PMC - PubMed
Kotwal 2015 {published data only}
    1. Kotwal J, Kotwal A, Bhalla S, Singh PK, Nair V. Effectiveness of homocysteine lowering vitamins in prevention of thrombotic tendency at high altitude area: A randomized field trial. Thrombosis Research 2015;136(4):758‐62. - PubMed
Lalande 2009 {published data only}
    1. Lalande S, Snyder EM, Olson TP, Hulsebus ML, Orban M, Somers VK, et al. The effects of sildenafil and acetazolamide on breathing efficiency and ventilatory control during hypoxic exercise. European Journal of Applied Physiology 2009;106(4):509‐15. [PUBMED: 19337745] - PMC - PubMed
Lawley 2012 {published data only}
    1. Lawley JS, Oliver SJ, Mullins P, Morris D, Junglee NA, Jelleyman C, et al. Optic nerve sheath diameter is not related to high altitude headache: A randomized controlled trial. High Altitude Medicine and Biology 2012;3:193‐9. - PubMed
Levine 1989 {published data only}
    1. Levine BD, Yoshimura K, Kobayashi T, Fukushima M, Shibamoto T, Ueda G. Dexamethasone in the treatment of acute mountain sickness. New England Journal of Medicine 1989;321(25):1707‐13. [PUBMED: 2687688] - PubMed
Liu 2013 {published data only}
    1. Liu C, Croft QP, Kalidhar S, Brooks JT, Herigstad M, Smith TG, et al. Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin. Journal of Applied Physiology 2013;114(7):948‐56. [PUBMED: 23393065] - PMC - PubMed
Mairer 2012 {published data only}
    1. Mairer K, Gobel M, Defrancesco M, Wille M, Messner H, Loizides A, et al. MRI evidence: acute mountain sickness is not associated with cerebral edema formation during simulated high altitude. PloS One 2012;7(11):e50334. [PUBMED: 23226263] - PMC - PubMed
McIntosh 1986 {published data only}
    1. McIntosh IB, Prescott RJ. Acetazolamide in prevention of acute mountain sickness. Journal of International Medical Research 1986;14(5):285‐7. [PUBMED: 3533677] - PubMed
Purkayastha 1995 {published data only}
    1. Purkayastha SS, Ray US, Arora BS, Chhabra PC, Thakur L, Bandopadhyay P, et al. Acclimatization at high altitude in gradual and acute induction. Journal of Applied Physiology 1995;79(2):487‐92. [PUBMED: 7592207] - PubMed
Reinhart 1994 {published data only}
    1. Reinhart WH, Goerre S, Bartsch P. Acetazolamide reduces the erythropoietin response to hypoxia at high altitude in humans. Journal of Wilderness Medicine 1994;5(3):312‐7.
Sandoval 2000 {published data only}
    1. Sandoval M, Silva J, Parra M, Cifuentes F, Maluenda R, Escobar J. Effects of consumption of antioxidants in altitude exposure [Efectos del consumo de antioxidantes en exposición a altitud]. Boletin Cientifico de la Asociacion Chilena de Seguridad 2000;2(3):67‐73.
Scalzo 2015 {published data only}
    1. Scalzo RL, Binns SE, Klochak AL, Giordano GR, Paris HLR, Sevits KJ, et al. Methazolamide plus aminophylline abrogates hypoxia‐mediated endurance exercise impairment. High Altitude Medicine & Biology 2015;16:331‐42. - PubMed
Serra 2001 {published data only}
    1. Serra J. Chachacoma: An alternative treatment for the prevention of acute mountain sickness? [Chachacoma ¿un tratamiento alternativo para la prevención del mal agudo de montaña?]. Revista de Ciencias de la Salud 2001;5(1):36‐42.
Siebenmann 2011 {published data only}
    1. Siebenmann C, Bloch KE, Lundby C, Nussbamer‐Ochsner Y, Schoeb M, Maggiorini M. Dexamethasone improves maximal exercise capacity of individuals susceptible to high altitude pulmonary edema at 4559 m. High Altitude Medicine & Biology 2011;12(2):169‐77. [PUBMED: 21718165] - PubMed
Singh 1969 {published data only}
    1. Singh I, Khanna PK, Srivastava MC, Lal M, Roy SB, Subramanyam CS. Acute mountain sickness. New England Journal of Medicine 1969;280(4):175‐84. - PubMed
Solís 1984 {published data only}
    1. Solís JV. Acetazolamide: Effects on the "acute mountain sickness", aggravated by physical activity. Boletín de la Fundación Jiménez Díaz 1984;11(3):117‐20.
Suh 2015 {published data only}
    1. Suh KS, Kim T, Yi NJ, Hong G. Preparation for high altitude expedition and changes in cardiopulmonary and biochemical laboratory parameters with ascent to high altitude in transplant patients and live donors. Clinical Transplantation 2015;29(11):1013‐20. - PubMed
Teppema 2007 {published data only}
    1. Teppema LJ, Balanos GM, Steinback CD, Brown AD, Foster GE, Duff HJ, et al. Effects of acetazolamide on ventilatory, cerebrovascular, and pulmonary vascular responses to hypoxia. American Journal of Respiratory and Critical Care Medicine 2007;175(3):277‐81. [PUBMED: 17095745] - PubMed
Vuyk 2006 {published data only}
    1. Vuyk J, Bos J, Terhell K, Bos R, Vletter A, Valk P, et al. Acetazolamide improves cerebral oxygenation during exercise at high altitude. High Altitude Medicine & Biology 2006;7(4):290‐301. [PUBMED: 17173514] - PubMed
White 1984 {published data only}
    1. White AJ. Cognitive impairment of acute mountain sickness and acetazolamide. Aviation, Space, and Environmental Medicine 1984;55(7):598‐603. [PUBMED: 6466255] - PubMed
Wright 1988 {published data only}
    1. Wright AD, Bradwell AR, Jensen J, Lassen N. Cerebral blood flow in acute mountain sickness and treatment with acetazolamide. Clinical Science 1988;74 Suppl 18:1P.

References to studies awaiting assessment

Dugas 1995 {published data only}
    1. Dugas L, Dubray C, Herry JP, Olsen NV, Court‐Payen M, Hansen JM, et al. Cardiovascular effects of a calcium channel blocker in hypoxia caused by altitude [Effets cardiovasculaires d'un bloqueur calcique en hypoxie d'altitude]. Presse Medicale 1995;24(16):763‐8. [PUBMED: 7784415] - PubMed
Ellsworth 1987 {published data only}
    1. Ellsworth AJ, Larson EB, Strickland D. A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis. American Journal of Medicine 1987;83(6):1024‐30. [PUBMED: 3332564] - PubMed
Furian 2016 {published data only}
    1. Furian M, Lichtblau M, Aeschbacher SS, Bisang M, Hartmann SE, Poulin M, et al. Altitude related adverse health effects in lowlanders with COPD travelling to 3,200 m. randomized trial of preventive dexamethasone treatment. Respiration 2016;91(5):415.
Hefti 2014 {published data only}
    1. Hefti JP, Stutz M, Geiser T, Hefti U, Merz T, Huber A. Effect of antioxidant supplements on AMS and endothelial function during a high altitude expedition: A prospective randomized double‐blind trial. High Altitude Medicine & Biology 2014;15(2):A262.
Kasic 1991 {published data only}
    1. Kasic JF, Yaron M, Nicholas RA, Lickteig JA, Roach R. Treatment of acute mountain‐sickness ‐ hyperbaric versus oxygen‐therapy. Annals of Emergency Medicine 1991;20(10):1109‐12. - PubMed
Lee 2011 {published data only}
    1. Lee JH, Choi PC. Comparison of methazolamide and acetazolamide for prevention of acute mountain sickness in adolescents. Journal of the Korean Society of Emergency Medicine 2011;22(5):523‐30.
Pun 2014 {published data only}
    1. Pun M, Neupane M, Lohani A, Thapa GB, Yadav S, Holck PS, et al. Role of low‐dose acetazolamide (125 mg BID) in prevention of acute mountain sickness in pilgrims ascending rapidly: A prospective double‐blind placebocontrolled randomized trial. High Altitude Medicine & Biology 2014;15(2):A233.
Roncin 1996 {published data only}
    1. Roncin JP, Schwartz F, Darbigny P. EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure. Aviation, Space, and Environmental Medicine 1996;67(5):445‐52. - PubMed
Swenson 1997 {published data only}
    1. Swenson ER, Macdonald A, Vatheuer M, Maks C, Treadwell A, Allen R, et al. Acute mountain sickness is not altered by a high carbohydrate diet nor associated with elevated circulating cytokines. Aviation, Space, and Environmental Medicine 1997;68:499‐503. - PubMed
Utz 1970 {published data only}
    1. Utz G, Schlierf G, Barth P, Linhart P, Wollenweber J. Prevention of acute mountain sickness using acetazolamide [Prophylaxe der akuten hohenkrankheit mit acetazolamid]. Munchener Medizinische Wochenschrift 1970;112(23):1122‐4. [PUBMED: 5467747] - PubMed
Wang 1998 {published data only}
    1. Wang W, Zhang X, Ma Y. Low‐concentration nitrous oxide inhalation in the treatment of high‐altitude pulmonary edema. Chinese Journal of Tuberculosis and Respiratory Diseases 1998;21(4):212‐4. - PubMed
Xiangjun 2014 {published data only}
    1. Xiangjun L, Lan H. Inhaled budesonide for the prevention of acute mountain sickness in unacclimatization young men: a double‐blind randomized controlled trial. Journal of the American College of Cardiology 2014;64(16 Suppl 1):C69.

References to ongoing studies

ChiCTR‐TRC‐13003319 {published data only}
    1. ChiCTR‐TRC‐13003319. Oral zolpidem for improving sleep and then prevention of acute mountain sickness: a single centre, randomized, double‐blind, controlled, prospective trial. www.chictr.org.cn/hvshowproject.aspx?id=6053 (first received 28th June 2013).
ChiCTR‐TRC‐13003590 {published data only}
    1. ChiCTR‐TRC‐13003590. The Meaning of Intravenous Iron Supplementation In Acute Mountain Sickness: A Randomized, Double‐Blinded, Placebo‐Controlled Trail. http://www.chictr.org.cn/showproj.aspx?proj=5970 (first published 23 June 2013).
NCT00886912 {published data only}
    1. NCT00886912. Prevention of Acute Mountain Sickness (AMS) by Intermittent Hypoxic Training. http://clinicaltrials.gov/show/NCT00886912 Date of registration: April 21th 2009.
NCT01606527 {published data only}
    1. NCT01606527. Prospective, Double‐blind, Randomized, Placebo‐controlled Trial of Ibuprofen Versus Placebo for Prevention of Neurologic Forms of Altitude Sickness. http://clinicaltrials.gov/show/NCT01606527 April 13th 2012.
NCT01682551 {published data only}
    1. NCT01682551. Evaluation of the Prevention and Treatment Effects of Chinese Medicine on High Altitude Illness. http://clinicaltrials.gov/show/NCT01682551 September 5th 2012.
NCT01794078 {published data only}
    1. NCT01794078. A Randomized, 4‐Sequence, Double‐Blind Study to Test the Safety of Combined Dosing With Aminophylline and Ambrisentan in Exercising Healthy Human Volunteers at Simulated High Altitude. https://clinicaltrials.gov/show/NCT01794078 February 10th 2013.
NCT01993667 {published data only}
    1. NCT01993667. Acetazolamide for the Prevention of High Altitude Illness: a Comparison of Dosing. https://clinicaltrials.gov/show/NCT01993667 November 12th 2013.
NCT02244437 {published data only}
    1. NCT02244437. Ibuprofen vs Acetaminophen in the Prevention of Acute Mountain Sickness: A Double Blind, Randomized Controlled Trial. https://clinicaltrials.gov/show/NCT02244437 September 14th 2014.
NCT02450968 {published data only}
    1. NCT02450968. Dexamethasone for Prophylaxis of Acute Mountain Sickness in Patients With Chronic Obstructive Pulmonary Disease Travelling to Altitude. https://clinicaltrials.gov/show/NCT02450968 May 18th 2015.
NCT02604173 {published data only}
    1. NCT02604173. A Randomized Controlled Trial of Altitude Sickness Prevention and Efficacy of Comparative Treatments. https://clinicaltrials.gov/show/NCT02604173 November 6th 2015.
NCT02811016 {published data only}
    1. NCT02811016. Effect of Inhaled Budesonide on the Incidence and Severity of Acute Mountain Sickness at 4559 m. https://clinicaltrials.gov/show/NCT02811016 June 14th 2016.
NCT02941510 {published data only}
    1. NCT02941510. Inhaled Budesonide for Altitude Illness Prevention. https://clinicaltrials.gov/show/NCT02941510 October 19th 2016.

Additional references

Adams 2004
    1. Adams J. Ginkgo biloba and acetazolamide for acute mountain sickness: exclusion of high risk, low status groups perpetuates discrimination and inequalities. BMJ 2004;329(7458):171. [MEDLINE: ] - PMC - PubMed
Anonymous 1892
    1. Anonymous. Mountain sickness. British Medical Journal 1892;1(1633):829. - PMC - PubMed
Bailey 2009a
    1. Bailey DM, Bärtsch P, Knauth M, Baumgartner RW. Emerging concepts in acute mountain sickness and high‐altitude cerebral edema: from the molecular to the morphological. Cellular and Molecular Life Sciences 2009;66(22):3583‐94. [MEDLINE: ] - PMC - PubMed
Balshem 2011
    1. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011;64(4):401‐6. [PUBMED: 21208779] - PubMed
Bates 2007
    1. Bates MG, Thompson AA, Baillie JK. Phosphodiesterase type 5 inhibitors in the treatment and prevention of high altitude pulmonary edema. Current Opinion in Investigational Drugs 2007;8(3):226‐31. [MEDLINE: ] - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analyses may be inconclusive‐‐Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analyses. International Journal of Epidemiology 2009;38(1):287‐98. [PUBMED: 18824466] - PubMed
Bärtsch 1992
    1. Bärtsch P. Treatment of high altitude diseases without drugs. International Journal of Sports Medicine 1992;13 Suppl 1:71‐4. [MEDLINE: ] - PubMed
Bärtsch 2004
    1. Bärtsch P, Bailey DM, Berger MM, Knauth M, Baumgartner RW. Acute mountain sickness: controversies and advances. High Altitude Medicine & Biology 2004;5(2):110‐2. [MEDLINE: ] - PubMed
Bärtsch 2007
    1. Bärtsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation 2007;116(19):2191‐202. [MEDLINE: ] - PubMed
CATMAT 2007
    1. Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on high‐altitude illnesses. An Advisory Committee Statement (ACS). Canada Communicable Disease Report (Relevé des maladies transmissibles au Canada) 2007;33(ACS‐5):1‐20. [MEDLINE: ] - PubMed
Chandramoorthi 2008
    1. Chandramoorthi GD, Piramanayagam S, Marimuthu P. An insilico approach to high altitude pulmonary edema ‐ Molecular modeling of human beta2 adrenergic receptor and its interaction with salmeterol & nifedipine. Journal of Molecular Modeling 2008;14(9):849‐56. [MEDLINE: ] - PubMed
CTU 2011 [Computer program]
    1. Copenhagen Trial Unit. Trial Sequential Analysis Version. Copenhagen: Copenhagen Trial Unit, 2011.
DailyMed
    1. DailyMed. dailymed.nlm.nih.gov/dailymed/about.cfm 2011; Vol. (Accessed 25 May 2011).
Dehnert 2010
    1. Dehnert C, Bärtsch P. Can patients with coronary heart disease go to high altitude?. High Altitude Medicine & Biology 2010;11(3):183‐8. [PUBMED: 20919884] - PubMed
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88. - PubMed
Dumont 2000
    1. Dumont L, Mardirosoff C, Tramèr MR. Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systematic review. BMJ 2000;321(7256):267‐72. [MEDLINE: ] - PMC - PubMed
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. [PUBMED: 11914310] - PubMed
Elphick 2004
    1. Elphick HL, Elphick DA. Ginkgo biloba and acetazolamide for acute mountain sickness: bias in participants may underestimate effectiveness of agents. BMJ 2004;329(7458):172. [MEDLINE: ] - PMC - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck‐Ytter Y, Schunemann HJ. What is "quality of evidence"and why is it important to clinicians. BMJ 2008;336(7651):995‐8. [MEDLINE: ] - PMC - PubMed
Guyatt 2011a
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction‐GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. [PUBMED: 21195583] - PubMed
Guyatt 2011b
    1. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. Journal of Clinical Epidemiology 2011;64(4):395‐400. [PUBMED: 21194891] - PubMed
Guyatt 2011c
    1. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso‐Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence—imprecision. Journal of Clinical Epidemiology 2011;64(12):1283‐93. [PUBMED: 21839614] - PubMed
Guyatt 2011d
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence—indirectness. Journal of Clinical Epidemiology 2011;64(12):1303‐10. [PUBMED: 21802903] - PubMed
Guyatt 2011e
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence—inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294‐302. [PUBMED: 21803546] - PubMed
Guyatt 2011f
    1. Guyatt GH, Oxman AD, Montori V, Vist G, Kunz R, Brozek J, et al. GRADE guidelines: 5. Rating the quality of evidence—publication bias. Journal of Clinical Epidemiology 2011;64(12):1277‐82. [PUBMED: 21802904] - PubMed
Guyatt 2011g
    1. Guyatt GH, Oxman AD, Sultan S, Glasziou P, Akl EA, Alonso‐Coello P, et al. GRADE guidelines: 9. Rating up the quality of evidence. Journal of Clinical Epidemiology 2011;64(12):1311‐6. [PUBMED: 21802902] - PubMed
Guyatt 2011h
    1. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso‐Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias). Journal of Clinical Epidemiology 2011;64(4):407‐15. [PUBMED: 21247734] - PubMed
Hackett 1992
    1. Hackett PH, Roach RC, Hartig GS, Greene ER, Levine BD. The effect of vasodilators on pulmonary hemodynamics in high altitude pulmonary edema: a comparison. International Journal of Sports Medicine 1992;13 Suppl 1:68‐71. [MEDLINE: ] - PubMed
Hackett 1999
    1. Hackett PH. High altitude cerebral edema and acute mountain sickness. A pathophysiology update. Advances in Experimental Medicine and Biology 1999;474:23‐45. [PUBMED: 10634991] - PubMed
Hackett 2004
    1. Hackett PH, Roach RC. High altitude cerebral edema. High Altitude Medicine & Biology 2004;5(2):136‐46. [MEDLINE: ] - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [MEDLINE: ] - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. .Available from handbook.cochrane.org.
Higgins 2016
    1. Higgins JP, Lasserson T, Chandler J, Tovey D, Churchill R. Methodological Expectations of Cochrane Intervention Reviews. Cochrane: London, Version 1.05, 2016.
Hozo 2005
    1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology 2005;5:13. [PUBMED: 15840177] - PMC - PubMed
Hussain 2004
    1. Hussain MM, Aslam M. Hypoxia and pulmonary acclimatisation at 4578 m altitude: the role of acetazolamide and dexamethasone. Journal of the Pakistan Medical Association 2003;53(10):451‐8. [MEDLINE: ] - PubMed
Höhne 2007
    1. Höhne C, Pickerodt PA, Francis RC, Boemke W, Swenson ER. Pulmonary vasodilation by acetazolamide during hypoxia is unrelated to carbonic anhydrase inhibition. American Journal of Physiology. Lung Cellular and Molecular Physiology 2007;292(1):L178‐84. [PUBMED: 16936246] - PubMed
Imray 2010
    1. Imray C, Wright A, Subudhi A, Roach R. Acute mountain sickness: pathophysiology, prevention, and treatment. Progress in Cardiovascular Diseases 2010;52(6):467‐84. [MEDLINE: ] - PubMed
Kallenberg 2007
    1. Kallenberg K, Bailey DM, Christ S, Mohr A, Roukens R, Menold E, et al. Magnetic resonance imaging evidence of cytotoxic cerebral edema in acute mountain sickness. Journal of Cerebral Blood Flow and Metabolism 2007;27(5):1064‐71. [PUBMED: 17024110] - PubMed
Kayser 2012
    1. Kayser B, Dumont L, Lysakowski C, Combescure C, Haller G, Tramer MR. Reappraisal of acetazolamide for the prevention of acute mountain sickness: a systematic review and meta‐analysis. High Altitude Medicine & Biology 2012;13(2):82‐92. [PUBMED: 22724610] - PubMed
Kleinsasser 2002
    1. Kleinsasser A, Loeckinger A. Are sildenafil and theophylline effective in the prevention of high‐altitude pulmonary edema?. Medical Hypotheses 2002;59(2):223‐5. [MEDLINE: ] - PubMed
Lan 1983
    1. Lan KKG, Demets D. Discrete sequential boundaries for clinical trials. Biometrika 1983;70(3):659‐63.
Leaf 2007
    1. Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. Journal of Applied Physiology 2007;102(4):1313‐22. [MEDLINE: ] - PubMed
Leissner 2009
    1. Leissner KB, Mahmood FU. Physiology and pathophysiology at high altitude: considerations for the anesthesiologist. International Journal of Anesthesia 2009;23(4):543‐53. [MEDLINE: ] - PubMed
Low 2012
    1. Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott MP. Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta‐analysis. BMJ (Clinical research ed.) 2012;345:e6779. [PUBMED: 23081689] - PMC - PubMed
Luks 2008a
    1. Luks AM. Do we have a "best practice" for treating high altitude pulmonary edema?. High Altitude Medicine & Biology 2008;9(2):111‐4. [MEDLINE: ] - PubMed
Luks 2008b
    1. Luks AM, Swenson ER. Medication and dosage considerations in the prophylaxis and treatment of high‐altitude illness. Chest 2008;133(3):744‐55. [MEDLINE: ] - PubMed
Luks 2010
    1. Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Wilderness Medical Society. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness & Environmental Medicine 2010;21(2):146‐55. [MEDLINE: ] - PubMed
Luks 2014
    1. Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, et al. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness & Environmental Medicine 2014;25(4 Suppl):S4‐14. [PUBMED: 25498261] - PubMed
Maggiorini 1998
    1. Maggiorini M, Müller A, Hofstetter D, Bärtsch P, Oelz O. Assessment of acute mountain sickness by different score protocols in the Swiss Alps. Aviation, Space, and Environmental Medicine 1998;69(12):1186‐92. [PUBMED: 9856545] - PubMed
Maggiorini 2010
    1. Maggiorini M. Prevention and treatment of high‐altitude pulmonary edema. Progress in Cardiovascular Diseases 2010;52(6):500‐6. [MEDLINE: ] - PubMed
Monge 1942
    1. Monge C. Life in the Andes and chronic mountain sickness. Science 1942;95(2456):79‐84. [MEDLINE: ] - PubMed
Murata 2004
    1. Murata T, Hori M, Sakamoto K, Karaki H, Ozaki H. Dexamethasone blocks hypoxia‐induced endothelial dysfunction in organ‐cultured pulmonary arteries. American Journal of Respiratory and Critical Care Medicine 2004;170(6):647‐55. [MEDLINE: ] - PubMed
Murata 2005
    1. Murata T, Suzuki N, Yamawaki H, Sato K, Hori M, Karaki H, et al. Dexamethasone prevents impairment of endothelium‐dependent relaxation in arteries cultured with fetal bovine serum. European Journal of Pharmacology 2005;515(1‐3):134‐41. [MEDLINE: ] - PubMed
Naeije 2010
    1. Naeije R. Physiological adaptation of the cardiovascular system to high altitude. Progress in Cardiovascular Diseases 2010;52(6):456‐66. [MEDLINE: ] - PubMed
Ozaki 2001
    1. Ozaki M, Kawashima S, Yamashita T, Ohashi Y, Rikitake Y, Inoue N, et al. Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium. Hypertension 2001;37(2):322‐7. [MEDLINE: ] - PubMed
Palmer 2010
    1. Palmer BF. Physiology and pathophysiology with ascent to altitude. American Journal of the Medical Sciences 2010;340(1):69‐77. [MEDLINE: ] - PubMed
Pandit 2014
    1. Pandit A, Karmacharya P, Pathak R, Giri S, Aryal MR. Efficacy of NSAIDs for the prevention of acute mountain sickness: a systematic review and meta‐analysis. Journal of Community Hospital Internal Medicine Perspectives 2014;4(4):1‐7. [PUBMED: 25317267] - PMC - PubMed
Paralikar 2010
    1. Paralikar SJ, Paralikar JH. High‐altitude medicine. Indian Journal of Occupational and Environmental Medicine 2010;14(1):6‐12. [MEDLINE: ] - PMC - PubMed
Pasha 2010
    1. Pasha MA, Newman JH. High‐altitude disorders: pulmonary hypertension: pulmonary vascular disease: the global perspective. Chest 2010;137 Suppl(6):13‐9. [MEDLINE: ] - PubMed
RevMan 5.3 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3.. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Ri‐Li 2003
    1. Ri‐Li G, Chase PJ, Witkowski S, Wyrick BL, Stone JA, Levine BD, et al. Obesity: associations with acute mountain sickness. Annals of Internal Medicine 2003;139(4):253‐7. [PUBMED: 12965980] - PubMed
Richalet 2005
    1. Richalet JP, Gratadour P, Robach P, Pham I, Déchaux M, Joncquiert‐Latarjet A, et al. Sildenafil inhibits altitude‐induced hypoxemia and pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine 2005;171(3):275‐81. [MEDLINE: ] - PubMed
Ritchie 2012
    1. Ritchie ND, Baggott AV, Andrew Todd WT. Acetazolamide for the prevention of acute mountain sickness‐‐a systematic review and meta‐analysis. Journal of Travel Medicine 2012;19(5):298‐307. [PUBMED: 22943270] - PubMed
Rodríguez de Romo 2002
    1. Rodríguez de Romo AC. Daniel Vergara Lope and Carlos Monge Medrano: two pioneers of high altitude medicine. High Altitude Medicine & Biology 2002;3(3):299‐309. [MEDLINE: ] - PubMed
Scherrer 2010
    1. Scherrer U, Rexhaj E, Jayet PY, Allemann Y, Sartori C. New insights in the pathogenesis of high‐altitude pulmonary edema. Progress in Cardiovascular Diseases 2010;52(6):485‐92. [MEDLINE: ] - PubMed
Schneider 2002
    1. Schneider M, Bernasch D, Weymann J, Holle R, Bärtsch P. Acute mountain sickness: influence of susceptibility, preexposure, and ascent rate. Medicine and Science in Sports and Exercise 2002;34(12):1886‐91. [PUBMED: 12471292] - PubMed
Schoene 2004
    1. Schoene RB. Unraveling the mechanism of high altitude pulmonary edema. High Altitude Medicine & Biology 2004;5(2):125‐35. [MEDLINE: ] - PubMed
Schoene 2008
    1. Schoene RB. Illnesses at high altitude. Chest 2008;134(2):402‐16. [MEDLINE: ] - PubMed
Schoonman 2008
    1. Schoonman GG, Sandor PS, Nirkko AC, Lange T, Jaermann T, Dydak U, et al. Hypoxia‐induced acute mountain sickness is associated with intracellular cerebral edema: a 3 T magnetic resonance imaging study. Journal of Cerebral Blood Flow and Metabolism 2008;28(1):198‐206. [PUBMED: 17519973] - PubMed
Seupaul 2012
    1. Seupaul RA, Welch JL, Malka ST, Emmett TW. Pharmacologic prophylaxis for acute mountain sickness: a systematic shortcut review. Annals of Emergency Medicine 2012;59(4):307‐317.e1. [PUBMED: 22153998] - PubMed
Stedman 2011
    1. Stedman MR, Curtin F, Elbourne DR, Kesselheim AS, Brookhart MA. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2011;40(6):1732‐4. [PUBMED: 20026595] - PubMed
Stream 2008
    1. Stream JO, Grissom CK. Update on high‐altitude pulmonary edema: pathogenesis, prevention, and treatment. Wilderness & Environmental Medicine 2008;19(4):293‐303. [MEDLINE: ] - PubMed
Swenson 2006
    1. Swenson ER. Carbonic anhydrase inhibitors and hypoxic pulmonary vasoconstriction. Respiratory Physiology & Neurobiology 2006;151(2‐3):209‐16. [PUBMED: 16376158] - PubMed
Swenson 2007
    1. Swenson E, Teppema L. Prevention of acute mountain sickness by acetazolamide: as yet an unfinished story. Journal of Applied Physiology 2007;102(4):1305‐7. [MEDLINE: ] - PubMed
Tang 2014
    1. Tang E, Chen Y, Luo Y. Dexamethasone for the prevention of acute mountain sickness: systematic review and meta‐analysis. International Journal of Cardiology 2014;173(2):133‐8. [PUBMED: 24679688] - PubMed
Thorlund 2009
    1. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta‐analyses?. International Journal of Epidemiology 2009;38(1):276‐86. [PUBMED: 18824467] - PubMed
Tintinger 2010
    1. Tintinger GR, Feldman C, Theron AJ, Anderson R. Montelukast: more than a cysteinyl leukotriene receptor antagonist?. Scientific World Journal 2010;10:2403‐13. [PUBMED: 21170491] - PMC - PubMed
Wan 2014
    1. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Medical Research Methodology 2014;14:135. [PUBMED: 25524443] - PMC - PubMed
Wetterslev 2008
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta‐analysis. Journal of Clinical Epidemiology 2008;61(1):64‐75. [PUBMED: 18083463] - PubMed
Wilson 2009
    1. Wilson MH, Newman S, Imray CH. The cerebral effects of ascent to high altitudes. Lancet Neurology 2009;8(2):175‐91. [MEDLINE: ] - PubMed
Windsor 2009
    1. Windsor JS, Firth PG, Grocott MP, Rodway GW, Montgomery HE. Mountain mortality: a review of deaths that occur during recreational activities in the mountains. Postgraduate Medical Journal 2009;85(1004):316‐21. [PUBMED: 19528307] - PubMed
Wright 2008
    1. Wright A, Brearey S, Imray C. High hopes at high altitudes: pharmacotherapy for acute mountain sickness and high‐altitude cerebral and pulmonary oedema. Expert Opinion on Pharmacotherapy 2008;9(1):119‐27. [MEDLINE: ] - PubMed
Yang 2007
    1. Yang B, Wang GY, Chen B, Qin RB, Xi SL, Chen L. Anti‐hypoxia and anti‐oxidation effects of aminophylline on human with acute high‐altitude exposure. Chinese Medical Sciences Journal 2007;22(1):62‐5. [PUBMED: 17441321] - PubMed
Zafren 2014
    1. Zafren K. Prevention of high altitude illness. Travel Medicine and Infectious Disease 2014;12(1):29‐39. [PUBMED: 24393671] - PubMed
Zhao 2001
    1. Zhao L, Mason NA, Morrell N, Kojonazarov B, Sadykov A, Maripov A, et al. Sildenafil inhibits hypoxia‐induced pulmonary hypertension. Circulation 2001;104(4):424‐8. [MEDLINE: ] - PubMed

References to other published versions of this review

Martí‐Carvajal 2012
    1. Martí‐Carvajal Arturo J, Hidalgo R, Simancas‐Racines D. Interventions for preventing high altitude illness. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD009761] - DOI

Publication types

MeSH terms

Supplementary concepts