Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial

Chest. 2012 Jan;141(1):131-138. doi: 10.1378/chest.11-0375. Epub 2011 Jun 9.

Abstract

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 Pco(2), 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / administration & dosage
  • Acetazolamide / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Altitude*
  • Blood Gas Monitoring, Transcutaneous
  • Carbonic Anhydrase Inhibitors / administration & dosage
  • Carbonic Anhydrase Inhibitors / therapeutic use
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoxia / blood
  • Hypoxia / etiology
  • Hypoxia / prevention & control
  • Male
  • Middle Aged
  • Oxygen Consumption
  • Polysomnography
  • Sleep / drug effects
  • Sleep / physiology*
  • Sleep Apnea, Obstructive / blood
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Apnea, Obstructive / physiopathology
  • Young Adult

Substances

  • Carbonic Anhydrase Inhibitors
  • Acetazolamide

Associated data

  • ClinicalTrials.gov/NCT00714740