Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide

Abstract

Introduction: We evaluated whether exposure to high altitude impairs visuomotor learning in lowlanders with chronic obstructive pulmonary disease (COPD) and whether this can be prevented by acetazolamide treatment.Methods: 45 patients with COPD, living <800 m, FEV1 ≥40 to <80%predicted, were randomized to acetazolamide (375 mg/d) or placebo, administered 24h before and during a 2-day stay in a clinic at 3100 m. Visuomotor performance was evaluated with a validated, computer-assisted test (Motor-Task-Manager) at 760 m above sea level (baseline, before starting the study drug), within 4h after arrival at 3100 m and in the morning after one night at 3100 m. Main outcome was the directional error (DE) of cursor movements controlled by the participant via mouse on a computer screen during a target tracking task. Effects of high altitude and acetazolamide on DE during an adaptation phase, immediate recall and post-sleep recall were evaluated by regression analyses. www.ClinicalTrials.gov NCT03165890.Results: In 22 patients receiving placebo, DE at 3100 m increased during adaptation by mean 2.5°, 95%CI 2.2° to 2.7° (p < 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p < 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p < 0.001), vs. corresponding values at 760 m. In 23 participants receiving acetazolamide, corresponding DE were reduced by −0.3° (−0.6° to 0.1°, p = 0.120), −2.7° (−3.7° to −1.6°, p < 0.001) and −3.1° (−4.3° to −2.0°, p < 0.001), compared to placebo at 3100 m.Conclusion: Lowlanders with COPD travelling to 3100 m experienced altitude-induced impairments in immediate and post-sleep recall of a visuomotor task. Preventive acetazolamide treatment mitigated these undesirable effects.

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

“…A major strength of our trial is to provide robust evidence of altitude-related deterioration of postural control in a large group of older individuals and to show that AZA mitigates this adverse effect of hypobaric hypoxia. This study was part of a larger trial investigating the efficacy of preventive AZA treatment in reducing AMS (Furian et al, 2022) and participants underwent various assessments other than just the balance board measurements including exercise tests which may have affected performance in postural control due to muscular fatigue (Paillard, 2012). Since postural control was assessed before exercise tests and because the same tests were performed at both altitudes and in both groups, it is unlikely that the various assessments have affected the conclusions.…”

“…This study was part of a randomized, placebo-controlled, double-blinded trial evaluating the efficacy of preventive AZA treatment in reducing AMS in healthy lowlanders 40 years of age or older during a 2-day sojourn at 3,100 m (Too Ashu High Altitude Clinic, Kyrgyz Republic). Data on effects of altitude and AZA on AMS and physiologic outcomes have been reported elsewhere (Furian et al, 2022). Data on postural control, the focus of the current study, have not been published.…”

“…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).…”

“…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.…”

Effect of acetazolamide on visuomotor performance at high altitude in healthy people 40 years of age or older—RCT

“…The rise in ventilation induced by acetazolamide improves systemic and cerebral oxygenation [14,15] and may therefore partially reverse the altitude-induced hypobaric hypoxia of the neuromuscular system and its clinical manifestations. Consistently, in patients with chronic obstructive pulmonary disease (COPD) travelling to 3,100 m, we found that preventive treatment with acetazolamide improved oxygenation, visuomotor performance, learning and postural control compared to placebo [16,17]. In healthy individuals, the few studies on effects of acetazolamide on cognition at high altitude are inconclusive because of the small number of participants and methodological limitations [18,19].…”