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Acetazolamide Improves Central Sleep Apnea in Heart Failure

A Double-Blind, Prospective Study

Pulmonary Service, Department of Veterans Affairs Medical Center, and Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio

Correspondence and requests for reprints should be addressed to S. Javaheri, M.D., Pulmonary Section (111F), VA Medical Center, 3200 Vine Street, Cincinnati, OH 45220. E-mail: shahrokh.javaheri{at}med.va.gov

Rationale: Acetazolamide is a mild diuretic and a respiratory stimulant. It is used to treat periodic breathing at high altitude.

Objectives: To determine the therapeutic efficacy of acetazolamide on central sleep apnea associated with heart failure.

Methods: Twelve male patients with stable systolic heart failure whose initial polysomnograms showed more than 15 episodes per hour of apnea and hypopnea participated in the study. The patients were randomized to a double-blind cross-over protocol with acetazolamide or placebo, taken 1 h before bedtime for six nights with 2 wk of washout.

Measurements: Polysomnography, pulmonary function tests, arterial blood gases, and left ventricular ejection fraction were obtained initially along with a sleep questionnaire, history, and physical examination. Baseline measurements were repeated at the end of each arm.

Main Results: There were no significant differences between parameters at baseline and placebo. In comparing placebo with acetazolamide, the hourly number of episodes of central apnea (49 ± 28 vs. 23 ± 21 [mean ± SD]; p = 0.004) and the percentage of total sleep time spent below an arterial oxyhemoglobin saturation of 90% (19 ± 32 vs. 6 ± 13%; p = 0.01) decreased significantly. Acetazolamide improved subjective perception of overall sleep quality (p = 0.003), feeling rested on awakening (p = 0.007), daytime fatigue (p = 0.02), and falling asleep unintentionally during daytime (p = 0.002).

Conclusions: In patients with heart failure, administration of a single dose of acetazolamide before sleep improves central sleep apnea and related daytime symptoms.

Key Words: Cheyne-Stokes breathing • heart failure • metabolic acidosis

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