Effect of Acetazolamide on Postural Control in Patients with COPD Travelling to 3100 m Randomized Trial

Abstract

Patients with chronic obstructive pulmonary disease (COPD) may be susceptible to impairments in postural control (PC) when exposed to hypoxia at high altitude. This randomized, placebo-controlled, double-blind, parallel-design trial evaluated the effect of preventive acetazolamide treatment on PC in lowlanders with COPD traveling to 3100 m. 127 lowlanders (85 men, 42 women) with moderate to severe COPD, aged 57 ± 8 y, living below 800 m, were randomized to treatment with acetazolamide 375 mg/d starting 24 h before ascent from 760 m to 3100 m and during a 2-day sojourn in a clinic at 3100 m. PC was evaluated at both altitudes with a balance platform on which patients were standing during five tests of 30 s each. The primary outcome was the center of pressure path length (COPL). In the placebo group, COPL significantly increased from (mean ± SD) 28.8 ± 9.7 cm at 760 m to 30.0 ± 10.0 cm at 3100 m (p = 0.002). In the acetazolamide group, COPL at 760 m and 3100 m were similar with 27.6 ± 9.6 cm and 28.4 ± 9.7 cm (p = 0.069). The mean between-groups difference (acetazolamide-placebo) in altitude-induced change of COPL was −0.54 cm (95%CI −1.66 to 0.58, p = 0.289). Multivariable regression analysis confirmed an increase in COPL of 0.98 cm (0.39 to 1.58, p = 0.001) with ascent from 760 to 3100 m, but no significant effect of acetazolamide (0.66 cm, 95%CI −0.25 to 1.57, p = 0.156) when adjusting for several confounders. In lowlanders with moderate to severe COPD, an ascent to high altitude was associated with impaired postural control and this was not prevented by acetazolamide.

Effect of altitude and acetazolamide on postural control in healthy lowlanders 40 years of age or older. Randomized, placebo-controlled trial

“…In the current study, the altitude-induced alteration in postural control was mainly reflected in a longer COPL that was related to an increased AP sway velocity and amplitude. These observations are consistent with previous studies, which also showed that altitude exposure increased the sway in anterior-posterior direction (Muralt et al, 2018;Buergin et al, 2023). It has been suggested that this may be due to the anatomical alignment of the leg and feet joints that result in a greater flexibility in the antero-posterior compared to the medio-lateral direction and to the greater sensitivity of the visual corrective input to lateral vs. antero-posterior alterations (Nordahl et al, 1998).…”

“…Our data suggest that older age within this range had a negative effect on AP sway velocity while the COPL and mediolateral sway velocity were not associated with age (Tables 3, 4). A worse postural control of older compared to younger mountaineers has been reported previously (Bruyneel et al, 2017;Buergin et al, 2023). Moreover, a large-scale study has shown that postural control deteriorates with increasing age even at sea level (Era et al, 2006).…”

“…Participants received AZA or equally looking placebo capsules, 125 mg in the morning and 250 mg in the evening (total dose 375 mg daily). As in a similar study in patients with chronic obstructive pulmonary disease (Buergin et al, 2023), we choose to administer a higher dose of AZA in the evening to prevent sleep-related hypoventilation and a lower dose in the morning to avoid excessive stimulation of ventilation with dyspnea (Furian et al, 2022).…”

“…Baseline evaluation of postural control was performed at 760 m, before study drug intake, and at 760 m, after the third dose (i.e., after a total dose of 500 mg), approximately 24 h after the first study drug intake, to assess the effect of AZA in normobaric, normoxic conditions. Further evaluations were performed in the morning after one night at 3,100 m. A balance platform (Wii Balance Board, Nintendo, Kyoto, Japan), a validated tool for assessing standing balance (Clark et al, 2010), was employed as described previously and illustrated in Figure 1 (Stadelmann et al, 2015;Muralt et al, 2018;Buergin et al, 2023). Participants performed a series of five 30s trials of quiet standing with open eyes and both feet on the balance board with 2-3 min rest intervals.…”

“…Modern means of transportation allow rapid ascent to high altitudes even for untrained and older people, a growing proportion of mountain tourists. Exposure to hypobaric hypoxia at high altitude may cause adverse health effects including altitude illness (Furian et al, 2022), poor sleep (Latshang et al, 2013), psychomotor and learning impairment (Scheiwiller et al, 2022;Reiser et al, 2023) and deterioration of postural control (Stadelmann et al, 2015;Buergin et al, 2023). The latter is of particular concern as it may lead to potentially dangerous falls.…”