Patients With Obstructive Sleep Apnea Syndrome Benefit From Acetazolamide During an Altitude Sojourn: A Randomized, Placebo-Controlled, Double-Blind Trial

doi:10.1378/chest.11-0375

Chest

Volume 141, Issue 1, January 2012, Pages 131-138

https://doi.org/10.1378/chest.11-0375 Get rights and content

Background

Many patients with obstructive sleep apnea syndrome (OSA) are unable or unwilling to use continuous positive airway pressure (CPAP) therapy when traveling to the mountains for work or recreation even though they risk pronounced hypoxemia and exacerbation of sleep apnea. Because the treatment of OSA at altitude has not been established, we tested the hypothesis that acetazolamide improves hypoxemia, sleep, and breathing disturbances in otherwise untreated patients with OSA at altitude.

Methods

Forty-five patients with OSA on long-term CPAP, median age 64 years, living at < 600 m underwent a placebo-controlled, double-blind, crossover trial randomized for the sequence of drug and altitude exposure (490 m, 1,860 m, and 2,590 m). Patients spent two 3-day periods at altitude and a 2-week wash-out period at < 600 m. At altitude, patients discontinued CPAP and received acetazolamide 2 × 250 mg daily or placebo. Polysomnography, vigilance, and symptoms were evaluated.

Results

At 490 m, off CPAP, median nocturnal oxygen saturation was 93%, and the apnea/hypopnea index was 51.2/h. On placebo at 1,860 m and 2,590 m, the corresponding values were 89% and 85% and 63.6/h and 86.2/h, respectively (P < .01 vs 490 m, both instances). On acetazolamide at 1,860 m and 2,590 m, oxygen saturation was higher (91% and 88%) and apnea/hypopnea indices were lower (48.0/h and 61.4/h) than on placebo (P < .01 all instances). Acetazolamide reduced nocturnal transcutaneous Pco₂, improved sleep efficiency and subjective insomnia, and prevented excessive BP elevations at altitude.

Conclusions

In patients with OSA discontinuing CPAP during an altitude sojourn, acetazolamide improves oxygenation, breathing disturbances, and sleep quality by stimulating ventilation. Therefore, patients with OSA may benefit from acetazolamide at altitude if CPAP therapy is not feasible.

Trial registry

ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov

Section snippets

Design Overview

We performed a randomized, placebo-controlled, double-blind, crossover trial to evaluate the effect of acetazolamide on nocturnal breathing, sleep, and daytime performance in patients with untreated OSA at altitude. The trial comprised two altitude sojourns of 3 days each, separated by a 2-week washout period spent at < 600 m (Fig 1). In the 3 nights before and during the altitude sojourns, patients discontinued CPAP, but used it during washout. Patients were not allowed to drive a car or

Results

Of 75 patients who applied for study participation, 49 met the inclusion criteria and were randomized (Fig 2). One patient had to withdraw from the study after the first night at 2,590 m because of an acute peripheral vestibulopathy. Data from three patients had to be excluded after study completion according to the predefined criteria, because baseline polysomnography at Zurich revealed an obstructive AHI < 10/h in two patients and predominant central sleep apnea in one patient. Data from 45

Discussion

We evaluated the effect of acetazolamide on sleep and breathing disturbances in patients with OSA discontinuing CPAP therapy during a temporary stay at moderate altitude. Our randomized, double-blind, placebo-controlled trial revealed a significantly improved nocturnal Spo₂ related to an increase in ventilation and a decrease in the AHI by acetazolamide mainly because of a reduction of central events. Because the drug alleviated sleep-related breathing disturbances, improved subjective

Acknowledgments

Author contributions: Dr Nussbaumer-Ochsner takes full responsibility for the integrity of all data and the accuracy of the data analysis.

Dr Nussbaumer-Ochsner: contributed to designing the study, collecting the data, analyzing the data, and writing the manuscript.

Dr Latshang: contributed to designing the study, collecting the data, analyzing the data, and revising the manuscript.

Dr Ulrich: contributed to collecting the data, analyzing the data, and revising the manuscript.

Dr Kohler:

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Endorsement of “European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea” by World Sleep Society
2024, Sleep Medicine
Guidelines for management of sleep disorders from national or regional societies provide recommendations that may be regionally appropriate but may not always be practical or relevant in other parts of the world. A task force of experts from the World Sleep Society's (WSS) International Sleep Medicine Guidelines Committee and Sleep and Breathing Disorders Task Force reviewed the European Respiratory Society's guideline on non-CPAP therapies for obstructive sleep apnea (OSA) with respect to its relevance and applicability to the practice of sleep medicine by sleep specialists in various regions of the world. The task force and the WSS guidelines committee endorsed the European Respiratory Society's guideline with respect to the utilization of bariatric surgery, mandibular advancement devices, positioning devices, myofunctional therapy, hypoglossal neurostimulation, maxilo-mandibular surgery, and carbonic anhydrase inhibitors for the treatment of OSA. The task force and the WSS guidelines committee noted that there is substantial new evidence for the role of soft tissue, upper airway surgery, not included in the guidelines paper.
Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea
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The acute effect during positive pressure titration and long term efficacy of acetazolamide (AZT) in high loop gain sleep apnea (HLGSA) is inadequately assessed. We predicted that AZT may improve HLGSA in both conditions.
A retrospective analysis of polysomnograms from patients with presumed HLGSA and residual respiratory instability administered AZT (125 or 250 mg) about 3 h into an initially drug-free positive pressure titration. A responder was defined as ≥ 50% reduction of the apnea hypopnea index(AHI 3% or arousal) before and after AZT. A multivariable logistic regression model estimated responder predictors. Long term efficacy of AZT was assessed by comparing both auto-machine (aREI_FLOW) and manually scored respiratory events (sREI_FLOW) extracted from the ventilator, prior to and after 3 months of AZT, in a subset.
Of the 231 participants (median age of 61[51–68] years) and 184 (80%) males in the acute effect testing: 77 and 154 patients were given 125 mg and 250 mg AZT. Compared to PAP alone, PAP plus AZT was associated with a lower breathing related arousal index (8 [3-16] vs. 5 [2-10], p < 0.001), and AHI3% (19 [7-37] vs. 11 [5-21], p < 0.001); 98 patients were responders. The non-rapid eye movement sleep (NREM) AHI3% (OR 1.031, 95%CI [1.016–1.046], p < 0.001) was a strong predictor for responder status with AZT exposure. In the 109 participants with 3-month data, both aREI_FLOW and sREI_FLOWwere significantly reduced after AZT.
AZT acutely and chronically reduced residual sleep apnea in presumed HLGSA; NREM AHI3% is a response predictor. AZT was well tolerated and beneficial for at least 3 months.
Sleep at high altitudes
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
High altitude is associated with a unique set of physiological and pathological changes, many of which affect sleep in different ways. Common disorders seen at high altitude include acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema; and common sleep disturbances include insomnia and periodic breathing. In addition, preexisting obstructive sleep apnea can transform into central sleep apnea resulting in a higher apnea-hypopnea index. Recommended treatment for symptoms associated with high altitude illness include descent to lower elevations and supplemental oxygen. Other treatment modalities that have been explored include pharmacologic interventions, positive pressure ventilation, and increasing physiologic dead space.
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2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
Obstructive sleep apnea (OSA) treatment is primarily focused on the usage of positive airway pressure (PAP) to stent open the upper airway to prevent obstruction and subsequent oxyhemoglobin desaturation. Unfortunately, the success rate of individuals on PAP therapy is mixed. Given this challenge, adjunctive and alternative measures need to be understood and offered to patients to ensure adequate relief of their symptoms, such as daytime sleepiness, and to prevent long term complications. In this chapter, we aim to discuss a variety of adjunctive and alternative treatment options for the treatment of OSA and these will be discussed in two broad categories: non-surgical and surgical treatments.
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Effect of One Night of Nocturnal Oxygen Supplementation on Highland Patients With OSA: A Randomized, Crossover Trial
2021, Chest
The treatment of OSA in highland residents is not established.
Does nocturnal oxygen supplementation (NOS) improve sleep-related breathing disturbances, nocturnal oxygenation, and cognitive performance in patients with OSA living at 3,200 m?
Forty patients with OSA permanently living in Shangri-La, China at 3,200 m (median age [interquartile range], 47.0 [44.0-53.0] years; oxygen desaturation index, 38.4/h [34.2/h-52.3/h]), were randomly assigned to receive nasal NOS and sham oxygen (ambient air), for one night each, at 2 L/min, in a crossover design, separated by a washout period of 2 weeks. During treatment nights polysomnography was performed, and further outcomes were evaluated the next morning. The primary outcome was the difference in apnea-hypopnea index (AHI) between nights with NOS and nights with sham oxygen.
During nights with sham oxygen, the median (interquartile range) total AHI was 43.4/h (31.1/h-67.5/h), the obstructive AHI was 41.9/h (28.5/h-66.8/h), and the central AHI was 0.6/h (0.1/h-1.3/h); blood oxygenation as determined by pulse oximetry (Spo₂) was 87.0% (84.5%-89.0%). In intention-to-treat analysis, NOS decreased the total AHI by a median of 17.9/h (95% CI, 8.0/h-27.1/h; P < .001), through a reduction in obstructive AHI by 16.0/h (95% CI, 6.8/h-26.0/h; P < .001) and central AHI by 0.4/h (95% CI, 0.1/h-0.9/h; P < .001). NOS also increased Spo₂ by 7.0% (95% CI, 6.0%-8.0%; P < .001). Heart rate during sleep and pulse rate in the morning after NOS were significantly reduced, but subjective sleep quality and cognitive performance showed no changes.
In highland residents with OSA, NOS significantly improved sleep-related breathing disturbances and nocturnal oxygenation. NOS also reduced heart rate during sleep and morning pulse rate. If these beneficial effects are confirmed in longer term studies, NOS may be a treatment option for highland patients with OSA who cannot be treated by CPAP.
Chinese Clinical Trial Registry; No.: ChiCTR1800017715; URL: http://www.chictr.org.cn/showproj.aspx?proj=29768

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Funding/Support: This study was supported by the Swiss National Science Foundation [Grant 32003B-122081]; the Lung League of Zurich and Schaffhausen; the Center for Clinical Research, University Hospital of Zurich; and the University of Zurich, Switzerland.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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Chest

Original ResearchOccupational And Environmental Lung DiseasesPatients With Obstructive Sleep Apnea Syndrome Benefit From Acetazolamide During an Altitude Sojourn: A Randomized, Placebo-Controlled, Double-Blind Trial

Background

Methods

Results

Conclusions

Trial registry

Section snippets

Design Overview

Results

Discussion

Acknowledgments

Chest

Clin Neurophysiol

Chest

Respir Physiol

Respir Physiol Neurobiol

Lancet

Exacerbation of sleep apnoea by frequent central events in patients with the obstructive sleep apnoea syndrome at altitude: a randomised trial

Thorax

Efficacy of low-dose acetazolamide (125 mg BID) for the prophylaxis of acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial

High Alt Med Biol

Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude

Eur Respir J

Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study

Am J Respir Crit Care Med

Effects of short-term CPAP withdrawal on neurobehavioral performance in patients with obstructive sleep apnea

Sleep

Respiratory muscle activity measured with a noninvasive EMG technique: technical aspects and reproducibility

J Appl Physiol

Original Research
Occupational And Environmental Lung Diseases
Patients With Obstructive Sleep Apnea Syndrome Benefit From Acetazolamide During an Altitude Sojourn: A Randomized, Placebo-Controlled, Double-Blind Trial