The effects of acetazolamide on physiological variables among adolescents at high altitude

Balasekaran, Govindasamy; Thompson, Sarah; Govindaswamy, Visvasuresh Victor; Ng, Yew Cheo

doi:10.22059/sshr.2023.326622.995

The effects of acetazolamide on physiological variables among adolescents at high altitude

Document Type : Research Paper

Authors

¹ National Institute of Education, Nanyang Technological University, Singapore

² University of Pittsburgh

³ Concordia University Chicago

10.22059/sshr.2023.326622.995

Abstract

Background: High altitude environments can cause a range of physiological changes in the body, and adolescents may be particularly vulnerable to the effects of altitude sickness. Acetazolamide has been shown to be an effective treatment for altitude sickness, but further research is needed to determine its impact on physiological variables among adolescents at high altitude.
Aim: The aim of this study was to investigate the effects of acetazolamide in adolescents over 17 days at high altitude.
Materials and Methods: Twenty-five healthy adolescents volunteered for this study and were randomly separated into control group (CG, n=12) and acetazolamide group (AG, n=13). AG took 250mg of acetazolamide. Resting Heart Rate (RHR) and Acute Mountain Sickness (AMS) using the Lake Louise questionnaire were measured each morning and afternoon during field testing; Resting Blood Pressure (RBP) was measured each afternoon. Pre- and post-blood samples (haemoglobin (Hb) and haematocrit (Hct)) were taken at sea level (SL) one week before departure and within 40 hours on return to SL.
Results: Significant differences between groups for RHR on days 2, 3 and 5; systolic blood pressures for day 4 and 13 (P<0.05). No significant difference between groups for diastolic blood pressure, pre- and post-altitude for Hb, Hct and PV. AMS scores did not differ from the two groups except on morning of day 12 (P<0.05).
Discussion and Conclusion: Results revealed that acetazolamide did not significantly induce changes to adolescents’ AMS scores and physiological changes. However, adolescents may consume acetazolamide to achieve lower RHR that may enable them to accommodate to HA, prolonging exercise in similar environments.

Keywords

References

[1] Hannon JP, Shields JL, Harris CW. “A comparative review of certain responses of men and women to high altitude”. Symp. Arctic Med. BioZ. Physiology of Work in Cold and Altitude. Arctic Aeromed. 1966; 6: 113-245.

[2] Lipman GS, Pomeranz D, Burns P, Phillips C, Cheffers M, Evans K, Jurkiewicz C, Juul N, Hackett P. “Budesonide versus acetazolamide for prevention of acute mountain sickness”. Am J Med. 2018; 131(2): 200.e9-200.e16. doi: 10.1016/j.amjmed.2017.05.034. PMID: 28668540.

[3] Kakunje A, Prabhu A, Priya Es S, Karkal R, Pookoth RK, Pd R. “Acetazolamide for antipsychotic-associated weight gain in schizophrenia”. J Clin Psychopharmacol. 2018; 38(6): 652-653. doi: 10.1097/JCP.0000000000000940. PMID: 30192255; PMCID: PMC6221403.

[4] Teppema LJ. “Multifaceted clinical effects of acetazolamide: will the underlying mechanisms please stand up?”. J Appl Physiol. 2014; 116(7): 713-4. doi: 10.1152/japplphysiol.00141.2014. Epub 2014 Feb 20. PMID: 24557795.

[5] Todd TJ. “Pediatric Injectable Drugs”. The Teddy Bear Book. Stephanie J, Phelps Tracy M, Hagemann Kelly, Lee R. Jill Thompson A. American Society of Health-System Pharmacists Publication. Bethesda, MD. 2018.

[6] Krasney JA. “A neurogenic basis for acute altitude illness”. Med Sci Sports Exerc. 1994; 26(2): 195-208. doi: 10.1249/00005768-199402000-00010. PMID: 8164537.

[7] Zafren K, Honigman B. “High-altitude medicine”. Emerg Med Clin North Am. 1997; 15(1): 191-222. doi: 10.1016/s0733-8627(05)70291-1. PMID: 9056576.

[8] Stager JM, Tucker A, Cordain L, Engebretsen BJ, Brechue WF, Matulich CC. “Normoxic and acute hypoxic exercise tolerance in man following acetazolamide”. Med Sci Sports Exerc. 1990; 22(2): 178-84. PMID: 2355814.

[9] Ward M, West JB, Milledge JS. “High altitude medicine and physiology”. Michael P, Ward JS, Milledge JB. West Chapman & Hall Medical London. 1995.

[10] Pollard AJ, Murdoch DR. The High Altitude Medicine Handbook. Radcliffe Medical Press, Inc. 1997.

[11] Logan RW, Crooks SM, Hutchison JH, Kerr MM. “Blood carbonic anhydrase activity in the newborn”. Arch Dis Child. 1973; 48(4): 256-8. doi: 10.1136/adc.48.4.256. PMID: 4196214; PMCID: PMC1648337.

[12] Berfenstam R. “Studies on carbonic anhydrase activity in children”. Acta Paediatr (Stockh). 1952; 41(1): 32-52. doi: 10.1111/j.1651-2227.1952.tb17839.x. PMID: 14933012.

[13] Ucrós S, Granados CM, Castro-Rodríguez JA, Hill CM. “Oxygen saturation in childhood at high altitude: A systematic review”. High Alt Med Biol. 2020; 21(2): 114-125. doi: 10.1089/ham.2019.0077. Epub 2020 Apr 2. PMID: 32239983.

[14] Eskandari D, Zou D, Grote L, Hoff E, Hedner J. “Acetazolamide reduces blood pressure and sleep-disordered breathing in patients with hypertension and obstructive sleep apnea: A randomized controlled trial”. J Clin Sleep Med. 2018; 14(3): 309-317. doi: 10.5664/jcsm.6968. PMID: 29510792; PMCID: PMC5837832.

[15] Grissom CK, Roach RC, Sarnquist FH, Hackett PH. “Acetazolamide in the treatment of acute mountain sickness: Clinical efficacy and effect on gas exchange”. Ann Intern Med. 1992; 116(6): 461-5. doi: 10.7326/0003-4819-116-6-461. PMID: 1739236.

[16] Van Berkel MA, Elefritz JL. “Evaluating off-label uses of acetazolamide”. Am J Health Syst Pharm. 2018; 75(8): 524-531. doi: 10.2146/ajhp170279. PMID: 29626002.

[17] Greene MK, Kerr AM, McIntosh IB, Prescott RJ. “Acetazolamide in prevention of acute mountain sickness: a double-blind controlled cross-over study”. Br Med J (Clin Res Ed). 1981; 283(6295): 811-3. doi: 10.1136/bmj.283.6295.811. PMID: 6794709; PMCID: PMC1507046.

[18] 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. PMID: 7045433.

[19] 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. doi: 10.1136/bmj.38043.501690.7C. Epub 2004 Mar 11. PMID: 15070635; PMCID: PMC383373.

[20] Leaf DE, Goldfarb DS. “Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness”. J Appl Physiol. 2007; 102(4): 1313-22. doi: 10.1152/japplphysiol.01572.2005. Epub 2006 Oct 5. PMID: 17023566.

[21] Chao CC, Chen LH, Lin YC, Wang SH, Wu SH, Li WC, Huang KF, Chiu TF, Kuo IC. “Impact of a 3-day high-altitude trek on Xue Mountain (3886 m), Taiwan, on the emotional states of children: A prospective observational study”. High Alt Med Biol. 2019; 20(1): 28-34. doi: 10.1089/ham.2018.0086. PMID: 30543474.

[22] Shlim DR. “The use of acetazolamide for the prevention of high-altitude illness”. J Travel Med. 2020; 27(6): taz106. doi: 10.1093/jtm/taz106. PMID: 31897486.

[23] Harris MD, Terrio J, Miser WF, Yetter JF 3rd. “High-altitude medicine”. Am Fam Physician. 1998; 57(8): 1907-14, 1924-6. PMID: 9575328.

[24] Sutton CG, Houston CS. “Hypoxia and mountain medicine”. 7th International Hypoxia Symposium. Lake Louise, Canada, February 1991.

[25] Dill DB, Costill DL. “Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration”. J Appl Physiol. 1974; 37(2): 247-8. doi: 10.1152/jappl.1974.37.2.247. PMID: 4850854.

[26] Malconian M, Rock P, Hultgren H, Donner H, Cymerman A, Groves B, Reeves J, Alexander J, Sutton J, Nitta M, et al. “The electrocardiogram at rest and exercise during a simulated ascent of Mt. Everest (Operation Everest II). Am J Cardiol. 1990; 65(22): 1475-80. doi: 10.1016/0002-9149(90)91358-d. PMID: 2353654.

[27] Reeves JT, Groves BM, Sutton JR, Wagner PD, Cymerman A, Malconian MK, Rock PB, Young PM, Houston CS. “Operation Everest II: Preservation of cardiac function at extreme altitude”. J Appl Physiol. 1987; 63(2): 531-9. doi: 10.1152/jappl.1987.63.2.531. PMID: 3654411.

[28] Karliner JS, Sarnquist FF, Graber DJ, Peters RM Jr, West JB. “The electrocardiogram at extreme altitude: Experience on Mt. Everest”. Am Heart J. 1985; 109(3 Pt 1): 505-13. doi: 10.1016/0002-8703(85)90555-1. PMID: 3976477.

[29] Nishihara F, Shimada H, Saito S. “Rate pressure product and oxygen saturation in tourists at approximately 3000 m above sea level”. Int Arch Occup Environ Health. 1998; 71(8): 520-4. doi: 10.1007/s004200050317. PMID: 9860159.

[30] Parati G, Revera M, Giuliano A, Faini A, Bilo G, Gregorini F, Lisi E, Salerno S, Lombardi C, Ramos Becerra CG, Mancia G, Salvi P. “Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure”. Eur Heart J. 2013; 34(10): 759-66. doi: 10.1093/eurheartj/ehs140. Epub 2012 Jun 17. PMID: 22711752.

[31] 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. doi: 10.1136/bmj.321.7256.267. PMID: 10915127; PMCID: PMC27441.

[32] Pickerodt PA, Francis RC, Höhne C, Neubert F, Telalbasic S, Boemke W, Swenson ER. “Pulmonary vasodilation by acetazolamide during hypoxia: impact of methyl-group substitutions and administration route in conscious, spontaneously breathing dogs”. J Appl Physiol. 2014; 116(7): 715-23. doi: 10.1152/japplphysiol.01235.2013. Epub 2014 Jan 30. PMID: 24481964; PMCID: PMC3972746.

[33] Salvi P, Revera M, Faini A, Giuliano A, Gregorini F, Agostoni P, Becerra CG, Bilo G, Lombardi C, O'Rourke MF, Mancia G, Parati G. “Changes in subendocardial viability ratio with acute high-altitude exposure and protective role of acetazolamide”. Hypertension. 2013; 61(4): 793-9. doi: 10.1161/HYPERTENSIONAHA.111.00707. PMID: 23438935.

[34] Wolfel EE, Selland MA, Mazzeo RS, Reeves JT. “Systemic hypertension at 4,300 m is related to sympathoadrenal activity”. J Appl Physiol. 1994; 76(4): 1643-50. doi: 10.1152/jappl.1994.76.4.1643. PMID: 8045844.

[35] Böning D. “Altitude and hypoxia training--a short review”. Int J Sports Med. 1997; 18(8): 565-70. doi: 10.1055/s-2007-972682. PMID: 9443586.

[36] “Acetazolamide in control of acute mountain sickness”. Lancet. 1981; 1(8213): 180-3. PMID: 6109857.

[37] Huicho L, Pawson IG, León-Velarde F, Rivera-Chira M, Pacheco A, Muro M, Silva J. “Oxygen saturation and heart rate in healthy school children and adolescents living at high altitude”. Am J Hum Biol. 2001; 13(6): 761-70. doi: 10.1002/ajhb.1122. PMID: 11748815.

[38] Stokke KT, Rootwelt K, Wergeland R, Vale JR. “Changes in plasma and red cell volumes during exposure to high altitude”. Scand J Clin Lab Invest Suppl. 1986; 184: 113-7. PMID: 3473608.

[39] Sawka MN, Convertino VA, Eichner ER, Schnieder SM, Young AJ. “Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness”. Med Sci Sports Exerc. 2000; 32(2): 332-48. doi: 10.1097/00005768-200002000-00012. PMID: 10694114.

[40] Robach P, Déchaux M, Jarrot S, Vaysse J, Schneider JC, Mason NP, Herry JP, Gardette B, Richalet JP. “Operation Everest III: role of plasma volume expansion on VO₂max during prolonged high-altitude exposure”. Journal of Applied Physiology. 2000; 89(1): 29-37. https://doi.org/10.1152/jappl.2000.89.1.29.

[41] Sawka MN, Young AJ, Rock PB, Lyons TP, Boushel R, Freund BJ, Muza SR, Cymerman A, Dennis RC, Pandolf KB, Valeri CR. “Altitude acclimatization and blood volume: effects of exogenous erythrocyte volume expansion”. J Appl Physiol. 1996; 81(2): 636-42. doi: 10.1152/jappl.1996.81.2.636. PMID: 8872628.

[42] Pearson DT, Naughton GA, Torode M. “Predictability of physiological testing and the role of maturation in talent identification for adolescent team sports”. J Sci Med Sport. 2006; 9(4): 277-87. doi: 10.1016/j.jsams.2006.05.020. Epub 2006 Jul 17. PMID: 16844415.

[43] West JB. “Oxygen conditioning: A new technique for improving living and working at high altitude”. Physiology (Bethesda). 2016; 31(3): 216-22. doi: 10.1152/physiol.00057.2015. PMID: 27053735.

[44] Dempsey JA, McKenzie DC, Haverkamp HC, Eldridge MW. “Update in the understanding of respiratory limitations to exercise performance in fit, active adults”. Chest. 2008; 134(3): 613-622. doi: 10.1378/chest.07-2730. PMID: 18779196.

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The effects of acetazolamide on physiological variables among adolescents at high altitude

References

[1] Hannon JP, Shields JL, Harris CW. “A comparative review of certain responses of men and women to high altitude”. Symp. Arctic Med. BioZ. Physiology of Work in Cold and Altitude. Arctic Aeromed. 1966; 6: 113-245.

[2] Lipman GS, Pomeranz D, Burns P, Phillips C, Cheffers M, Evans K, Jurkiewicz C, Juul N, Hackett P. “Budesonide versus acetazolamide for prevention of acute mountain sickness”. Am J Med. 2018; 131(2): 200.e9-200.e16. doi: 10.1016/j.amjmed.2017.05.034. PMID: 28668540.

[3] Kakunje A, Prabhu A, Priya Es S, Karkal R, Pookoth RK, Pd R. “Acetazolamide for antipsychotic-associated weight gain in schizophrenia”. J Clin Psychopharmacol. 2018; 38(6): 652-653. doi: 10.1097/JCP.0000000000000940. PMID: 30192255; PMCID: PMC6221403.

[4] Teppema LJ. “Multifaceted clinical effects of acetazolamide: will the underlying mechanisms please stand up?”. J Appl Physiol. 2014; 116(7): 713-4. doi: 10.1152/japplphysiol.00141.2014. Epub 2014 Feb 20. PMID: 24557795.

[5] Todd TJ. “Pediatric Injectable Drugs”. The Teddy Bear Book. Stephanie J, Phelps Tracy M, Hagemann Kelly, Lee R. Jill Thompson A. American Society of Health-System Pharmacists Publication. Bethesda, MD. 2018.

[6] Krasney JA. “A neurogenic basis for acute altitude illness”. Med Sci Sports Exerc. 1994; 26(2): 195-208. doi: 10.1249/00005768-199402000-00010. PMID: 8164537.

[7] Zafren K, Honigman B. “High-altitude medicine”. Emerg Med Clin North Am. 1997; 15(1): 191-222. doi: 10.1016/s0733-8627(05)70291-1. PMID: 9056576.

[8] Stager JM, Tucker A, Cordain L, Engebretsen BJ, Brechue WF, Matulich CC. “Normoxic and acute hypoxic exercise tolerance in man following acetazolamide”. Med Sci Sports Exerc. 1990; 22(2): 178-84. PMID: 2355814.

[9] Ward M, West JB, Milledge JS. “High altitude medicine and physiology”. Michael P, Ward JS, Milledge JB. West Chapman & Hall Medical London. 1995.

[10] Pollard AJ, Murdoch DR. The High Altitude Medicine Handbook. Radcliffe Medical Press, Inc. 1997.

[11] Logan RW, Crooks SM, Hutchison JH, Kerr MM. “Blood carbonic anhydrase activity in the newborn”. Arch Dis Child. 1973; 48(4): 256-8. doi: 10.1136/adc.48.4.256. PMID: 4196214; PMCID: PMC1648337.

[12] Berfenstam R. “Studies on carbonic anhydrase activity in children”. Acta Paediatr (Stockh). 1952; 41(1): 32-52. doi: 10.1111/j.1651-2227.1952.tb17839.x. PMID: 14933012.

[13] Ucrós S, Granados CM, Castro-Rodríguez JA, Hill CM. “Oxygen saturation in childhood at high altitude: A systematic review”. High Alt Med Biol. 2020; 21(2): 114-125. doi: 10.1089/ham.2019.0077. Epub 2020 Apr 2. PMID: 32239983.

[15] Grissom CK, Roach RC, Sarnquist FH, Hackett PH. “Acetazolamide in the treatment of acute mountain sickness: Clinical efficacy and effect on gas exchange”. Ann Intern Med. 1992; 116(6): 461-5. doi: 10.7326/0003-4819-116-6-461. PMID: 1739236.

[16] Van Berkel MA, Elefritz JL. “Evaluating off-label uses of acetazolamide”. Am J Health Syst Pharm. 2018; 75(8): 524-531. doi: 10.2146/ajhp170279. PMID: 29626002.

[17] Greene MK, Kerr AM, McIntosh IB, Prescott RJ. “Acetazolamide in prevention of acute mountain sickness: a double-blind controlled cross-over study”. Br Med J (Clin Res Ed). 1981; 283(6295): 811-3. doi: 10.1136/bmj.283.6295.811. PMID: 6794709; PMCID: PMC1507046.

[18] 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. PMID: 7045433.

[20] Leaf DE, Goldfarb DS. “Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness”. J Appl Physiol. 2007; 102(4): 1313-22. doi: 10.1152/japplphysiol.01572.2005. Epub 2006 Oct 5. PMID: 17023566.

[22] Shlim DR. “The use of acetazolamide for the prevention of high-altitude illness”. J Travel Med. 2020; 27(6): taz106. doi: 10.1093/jtm/taz106. PMID: 31897486.

[23] Harris MD, Terrio J, Miser WF, Yetter JF 3rd. “High-altitude medicine”. Am Fam Physician. 1998; 57(8): 1907-14, 1924-6. PMID: 9575328.

[24] Sutton CG, Houston CS. “Hypoxia and mountain medicine”. 7th International Hypoxia Symposium. Lake Louise, Canada, February 1991.

[25] Dill DB, Costill DL. “Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration”. J Appl Physiol. 1974; 37(2): 247-8. doi: 10.1152/jappl.1974.37.2.247. PMID: 4850854.

[27] Reeves JT, Groves BM, Sutton JR, Wagner PD, Cymerman A, Malconian MK, Rock PB, Young PM, Houston CS. “Operation Everest II: Preservation of cardiac function at extreme altitude”. J Appl Physiol. 1987; 63(2): 531-9. doi: 10.1152/jappl.1987.63.2.531. PMID: 3654411.

[28] Karliner JS, Sarnquist FF, Graber DJ, Peters RM Jr, West JB. “The electrocardiogram at extreme altitude: Experience on Mt. Everest”. Am Heart J. 1985; 109(3 Pt 1): 505-13. doi: 10.1016/0002-8703(85)90555-1. PMID: 3976477.

[29] Nishihara F, Shimada H, Saito S. “Rate pressure product and oxygen saturation in tourists at approximately 3000 m above sea level”. Int Arch Occup Environ Health. 1998; 71(8): 520-4. doi: 10.1007/s004200050317. PMID: 9860159.

[31] 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. doi: 10.1136/bmj.321.7256.267. PMID: 10915127; PMCID: PMC27441.

[34] Wolfel EE, Selland MA, Mazzeo RS, Reeves JT. “Systemic hypertension at 4,300 m is related to sympathoadrenal activity”. J Appl Physiol. 1994; 76(4): 1643-50. doi: 10.1152/jappl.1994.76.4.1643. PMID: 8045844.

[35] Böning D. “Altitude and hypoxia training--a short review”. Int J Sports Med. 1997; 18(8): 565-70. doi: 10.1055/s-2007-972682. PMID: 9443586.

[36] “Acetazolamide in control of acute mountain sickness”. Lancet. 1981; 1(8213): 180-3. PMID: 6109857.

[37] Huicho L, Pawson IG, León-Velarde F, Rivera-Chira M, Pacheco A, Muro M, Silva J. “Oxygen saturation and heart rate in healthy school children and adolescents living at high altitude”. Am J Hum Biol. 2001; 13(6): 761-70. doi: 10.1002/ajhb.1122. PMID: 11748815.

[38] Stokke KT, Rootwelt K, Wergeland R, Vale JR. “Changes in plasma and red cell volumes during exposure to high altitude”. Scand J Clin Lab Invest Suppl. 1986; 184: 113-7. PMID: 3473608.

[39] Sawka MN, Convertino VA, Eichner ER, Schnieder SM, Young AJ. “Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness”. Med Sci Sports Exerc. 2000; 32(2): 332-48. doi: 10.1097/00005768-200002000-00012. PMID: 10694114.

[42] Pearson DT, Naughton GA, Torode M. “Predictability of physiological testing and the role of maturation in talent identification for adolescent team sports”. J Sci Med Sport. 2006; 9(4): 277-87. doi: 10.1016/j.jsams.2006.05.020. Epub 2006 Jul 17. PMID: 16844415.

[43] West JB. “Oxygen conditioning: A new technique for improving living and working at high altitude”. Physiology (Bethesda). 2016; 31(3): 216-22. doi: 10.1152/physiol.00057.2015. PMID: 27053735.

[44] Dempsey JA, McKenzie DC, Haverkamp HC, Eldridge MW. “Update in the understanding of respiratory limitations to exercise performance in fit, active adults”. Chest. 2008; 134(3): 613-622. doi: 10.1378/chest.07-2730. PMID: 18779196.

Volume 14, Issue 1January 2022Pages 115-140

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Volume 14, Issue 1
January 2022
Pages 115-140