Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea

J Physiol. 2012 Mar 1;590(5):1199-211. doi: 10.1113/jphysiol.2011.223925. Epub 2012 Jan 4.


There is some evidence to suggest that acetazolamide may improve obstructive sleep apnoea (OSA).However, how acetazolamide affects the key traits causing OSA remains uncertain. We aimed to investigate the effect of acetazolamide on the traits contributing to OSA and its severity. Acetazolamide (500 mg twice daily) was administered for 1 week to 13 OSA subjects. Pharyngeal anatomy/collapsibility, loop gain (LG), upper-airway muscle responsiveness (gain) and the arousal threshold were determined using multiple 3 min 'CPAP pressure drops': pharyngeal anatomy/collapsibility was quantified as the ventilation at CPAP=0. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Upper-airway gain was taken as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was quantified as the level of ventilatory drive associated with arousal. The apnoea-hypopnoea index (AHI)was assessed on separate nights using standard polysomnography. Acetazolamide reduced the median [interquartile range] LG (3.4 [2.4-5.4] versus 2.0 [1.4-3.5]; P <0.05) and NREM AHI (50 [36-57] versus 24 [13-42] events h-1; P <0.05), but did not significantly alter pharyngeal anatomy/collapsibility, upper-airway gain, or arousal threshold. There was a modest correlation between the percentage reduction in LG and the percentage reduction in AHI (r =0.660, P =0.05). Our findings suggest that acetazolamide can improve OSA, probably due to reductions in the sensitivity of the ventilatory control system. Identification of patients who may benefit from reductions in LG alone or in combination with other therapies to alter the remaining traits may facilitate pharmacological resolution of OSA in the future.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / pharmacology
  • Acetazolamide / therapeutic use*
  • Arousal / drug effects
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrase Inhibitors / therapeutic use*
  • Continuous Positive Airway Pressure
  • Female
  • Humans
  • Middle Aged
  • Polysomnography
  • Pulmonary Ventilation / drug effects
  • Respiration / drug effects
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Apnea, Obstructive / physiopathology


  • Carbonic Anhydrase Inhibitors
  • Acetazolamide