Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea. 2013

Bradley A Edwards, and James G Connolly, and Lisa M Campana, and Scott A Sands, and John A Trinder, and David P White, and Andrew Wellman, and Atul Malhotra
Division of Sleep Medicine, Brigham and Women's Hospital - Harvard Medical School, Boston, MA 02115, USA. baedwards@partners.org

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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D012143 Respiratory Physiological Phenomena Physiological processes and properties of the RESPIRATORY SYSTEM as a whole or of any of its parts. Respiratory Physiologic Processes,Respiratory Physiological Processes,Respiratory Physiology,Physiology, Respiratory,Pulmonary Physiological Phenomena,Pulmonary Physiological Phenomenon,Pulmonary Physiological Process,Pulmonary Physiological Processes,Respiratory Physiological Concepts,Respiratory Physiological Phenomenon,Respiratory Physiological Process,Concept, Respiratory Physiological,Concepts, Respiratory Physiological,Phenomena, Pulmonary Physiological,Phenomena, Respiratory Physiological,Phenomenas, Pulmonary Physiological,Phenomenas, Respiratory Physiological,Phenomenon, Pulmonary Physiological,Phenomenon, Respiratory Physiological,Phenomenons, Pulmonary Physiological,Phenomenons, Respiratory Physiological,Physiologic Processes, Respiratory,Physiological Concept, Respiratory,Physiological Concepts, Respiratory,Physiological Phenomena, Pulmonary,Physiological Phenomena, Respiratory,Physiological Phenomenas, Pulmonary,Physiological Phenomenas, Respiratory,Physiological Phenomenon, Pulmonary,Physiological Phenomenon, Respiratory,Physiological Phenomenons, Pulmonary,Physiological Phenomenons, Respiratory,Physiological Process, Pulmonary,Physiological Process, Respiratory,Physiological Processes, Pulmonary,Physiological Processes, Respiratory,Process, Pulmonary Physiological,Process, Respiratory Physiological,Processes, Pulmonary Physiological,Pulmonary Physiological Phenomenas,Pulmonary Physiological Phenomenons,Respiratory Physiological Concept,Respiratory Physiological Phenomenas,Respiratory Physiological Phenomenons
D002257 Carbonic Anhydrase Inhibitors A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES. Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000086 Acetazolamide One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337) Acetadiazol,Acetazolam,Acetazolamide Sodium, (Sterile),Acetazolamide, Monosodium Salt,Ak-Zol,Apo-Acetazolamide,Diacarb,Diamox,Diuramide,Défiltran,Edemox,Glauconox,Glaupax,Huma-Zolamide,Ak Zol,AkZol,Apo Acetazolamide,ApoAcetazolamide,Huma Zolamide,HumaZolamide
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D001143 Arousal Cortical vigilance or readiness of tone, presumed to be in response to sensory stimulation via the reticular activating system. Vigilance, Cortical,Arousals,Cortical Vigilance

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