Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea.
OBJECTIVE
The magnitude of the post-apnea/hypopnea ventilatory overshoot following arousal may perpetuate subsequent respiratory events in obstructive sleep apnea (OSA) patients, potentially contributing to the disorder's severity. As acetazolamide can reduce apnea severity in some patients, we examined the effect of acetazolamide on the ventilatory response to spontaneous arousals in CPAP-treated OSA patients.


METHODS
We assessed the ventilatory response to arousal in OSA patients on therapeutic CPAP before and after administration of acetazolamide for 7 days.


METHODS
Sleep research laboratory.


METHODS
12 (7M/5F) CPAP-treated OSA patients.


METHODS
Sustained-release acetazolamide 500 mg by mouth twice daily for one week.


RESULTS
A blinded investigator identified spontaneous arousals (3-15 s) during NREM sleep. Breath-by-breath measurements of minute ventilation, end-tidal CO(2), tidal volume, expiratory/inspiratory-time, and total breath duration were determined (4-s intervals) 32 s prior and 60 s following each arousal. Acetazolamide significantly increased resting ventilation (7.3 ± 0.2 L/min versus 8.2 ± 0.4 L/min; P < 0.05) and attenuated the percent increase in ventilation following arousal by ~2.5 fold (122.0% ± 4.4% versus 108.7% ± 3.5% pre-arousal level; P < 0.05). There was a positive correlation between the mean increase in ventilatory response to arousal and mean AHI (r(2) = 0.44, P = 0.01). However, absolute peak levels of ventilation following arousal remained unchanged between conditions (8.8 ± 0.4 L/min versus 8.9 ± 0.1 L/min).


CONCLUSIONS
Acetazolamide substantially attenuates the increase in ventilation following spontaneous arousal from sleep in OSA patients. This study suggests an additional mechanism by which acetazolamide may contribute to the improvement in ventilatory instability and OSA severity. The data also provide support for reinforcing the importance of ventilatory control in OSA pathogenesis.
Division of Sleep Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA. baedwards@partners.org
Bradley A
BA
Edwards
James G
JG
Connolly
Lisa M
LM
Campana
Scott A
SA
Sands
John A
JA
Trinder
David P
DP
White
Andrew
A
Wellman
Atul
A
Malhotra
D000086:Acetazolamide / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D016037:Single-Blind Method; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy
D002257:Carbonic Anhydrase Inhibitors; D003692:Delayed-Action Preparations; D000086:Acetazolamide