Acetazolamide reduces exercise capacity following a five-day ascent to 4559 m on Monte Rosa

Abstract

Acetazolamide (Az) is widely used to prevent and treat the symptoms of acute mountain sickness (AMS) but whether it alters exercise capacity at high altitude is unclear. Az (250 mg twice daily) or placebo were administered to 20 healthy adults (age range, 21-77 years) in a double-blind, randomized manner. Participants ascended over five days to 4559 m, before undertaking an incremental exercise test to exhaustion on a bicycle ergometer, with breathby-breath gas measurements recorded using a portable gas analysis system. Maximum power output (P max ) was reduced on Az compared with placebo (p=0.03), as was maximum O 2 uptake (VO 2max ) (20.7 vs 24.6 mL/kg/min; p=0.06) and maximum expired CO 2 (VCO 2max ) (23.4 vs 29.5 mL/kg/min; p=0.01).Comparing individuals matched for similar characteristics, Az-treated participants had smaller changes than placebo-treated participants in minute ventilation (88 vs 116 L/min: p=0.05), end tidal O 2 (6.6 vs 9.3 mm Hg: p=0.009), end-tidal CO 2 (-2.3 vs -4.2 mm Hg: p=0.005), VO 2max (9.8 vs 13.8 mL/kg/min; p=0.04) and VCO 2max (14.7 vs 20.8 mL/kg/min; p=0.009). There was a negative correlation between the mean ages of paired vs placebo-treated individuals and differences in P max reductions from base-line to altitude (r =-0.83: p<0.005) and HR max at altitude (r=-0.71; p=0.01). Glomerular filtration rate (measured at sea-level) declined with increasing age (r=-0.69; p=0.001). Thus, 250mg of Az twice daily reduced exercise performance, particularly in older individuals. The age-related effects of Az may reflect higher tissue concentrations due to reduced drug clearance in older people.Key words: acute mountain sickness, high altitude, acetazolamide, exercise, age not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/105726 doi: bioRxiv preprint first posted online Feb. 3, 2017; New and noteworthy:We have identified a reduction in exercise performance (maximum power output and VO 2max ) at high altitude in individuals given commonly prescribed doses of acetazolamide for acute mountain sickness. This reduction was greater in older people (>50 years) possibly due to reduced renal clearance of the drug. Results indicate that it may be appropriate for older people to use smaller doses of acetazolamide at altitude. Introduction:

Proceeding book

“…In some papers the acetazolamide was proven way to prevent or cure mountain sickness even though Bradwell and al. (2018) found in a randomized study that it reduces exercise capacity following a 5-day ascent to 4559 m. Even though the acetalazomid might reduce the symptoms of acute mountain sickness ( Hung et al, 2019, Gonzales et al, 2018 none of the subjects in this study used any drugs of that type in order to prevent or cure mountain sickness.…”