Effect of altitude and acetazolamide on sleep and nocturnal breathing in healthy lowlanders 40 y of age or older. Data from a randomized trial

Laura C Graf; Michael Furian; Konstantinos Bitos; Maamed Mademilov; Ainura Abdraeva; Jana Buenzli; Simone Buenzli; Shaira Aidaralieva; Ulan Sheraliev; Laura C Mayer; Simon R Schneider; Talant M Sooronbaev; Silvia Ulrich; Konrad E Bloch

doi:10.1093/sleep/zsac269

Effect of altitude and acetazolamide on sleep and nocturnal breathing in healthy lowlanders 40 y of age or older. Data from a randomized trial

Sleep. 2023 Apr 12;46(4):zsac269. doi: 10.1093/sleep/zsac269.

Authors

Laura C Graf^{1

2

3}, Michael Furian^{1

2

3}, Konstantinos Bitos^{1

2

3}, Maamed Mademilov^{4

2

3}, Ainura Abdraeva^{4

2

3}, Jana Buenzli^{1

2

3}, Simone Buenzli^{1

2

3}, Shaira Aidaralieva^{4

2

3}, Ulan Sheraliev^{4

2

3}, Laura C Mayer^{1

2

3}, Simon R Schneider^{1

2

3}, Talant M Sooronbaev^{4

2

3}, Silvia Ulrich^{1

2

3}, Konrad E Bloch^{1

2

3}

Affiliations

¹ Department of Respiratory Medicine, University Hospital of Zurich, Zurich, Switzerland.
² Swiss-Kyrgyz High Altitude Medicine and Research Initiative, Zurich, Switzerland.
³ Swiss-Kyrgyz High Altitude Medicine and Research Initiative, Bishek, Kyrgyz Republic.
⁴ Department of Respiratory Medicine, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan.

PMID: 36356042
DOI: 10.1093/sleep/zsac269

Abstract

Study objectives: To assess altitude-induced sleep and nocturnal breathing disturbances in healthy lowlanders 40 y of age or older and the effects of preventive acetazolamide treatment.

Methods: Clinical examinations and polysomnography were performed at 760 m and in the first night after ascent to 3100 m in a subsample of participants of a larger trial evaluating altitude illness. Participants were randomized 1:1 to treatment with acetazolamide (375 mg/day) or placebo, starting 24 h before and while staying at 3100 m. The main outcomes were indices of sleep structure, oxygenation, and apnea/hypopnea index (AHI).

Results: Per protocol analysis included 86 participants (mean ± SE 53 ± 7 y old, 66% female). In 43 individuals randomized to placebo, mean nocturnal pulse oximetry (SpO2) was 94.0 ± 0.4% at 760 m and 86.7 ± 0.4% at 3100 m, with mean change (95%CI) -7.3% (-8.0 to -6.5); oxygen desaturation index (ODI) was 5.0 ± 2.3 at 760 m and 29.2 ± 2.3 at 3100 m, change 24.2/h (18.8 to 24.5); AHI was 11.3 ± 2.4/h at 760 m and 23.5 ± 2.4/h at 3100 m, change 12.2/h (7.3 to 17.0). In 43 individuals randomized to acetazolamide, altitude-induced changes were mitigated. Mean differences (Δ, 95%CI) in altitude-induced changes were: ΔSpO2 2.3% (1.3 to 3.4), ΔODI -15.0/h (-22.6 to -7.4), ΔAHI -11.4/h (-18.3 to -4.6). Total sleep time, sleep efficiency, and N3-sleep fraction decreased with an ascent to 3100 m under placebo by 40 min (17 to 60), 5% (2 to 8), and 6% (2 to 11), respectively. Acetazolamide did not significantly change these outcomes.

Conclusions: During a night at 3100 m, healthy lowlanders aged 40 y or older revealed hypoxemia, sleep apnea, and disturbed sleep. Preventive acetazolamide treatment improved oxygenation and nocturnal breathing but had no effect on sleep duration and structure.

Trial registration: The trial is registered at Clinical Trials, https://clinicaltrials.gov, NCT03561675.

Keywords: acetazolamide; altitude; apnea; healthy; older; sleep.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acetazolamide* / therapeutic use
Altitude*
Female
Humans
Male
Respiration
Sleep

Substances

Acetazolamide
AT 760

Associated data

ClinicalTrials.gov/NCT03561675