Effect of Theophylline on Sleep-Disordered Breathing in Heart Failure

Abstract

Background: Theophylline has been used to treat central apnea associated with Cheyne-Stokes respiration (periodic breathing). We studied the effect of short-term oral theophylline therapy on periodic breathing associated with stable heart failure due to systolic dysfunction. Methods: Fifteen men with compensated heart failure (left ventricular ejection fraction, 45 percent or less) participated in the study. Their base-line polysomnograms showed periodic breathing, with more than 10 episodes of apnea and hypopnea per hour. In a double-blind crossover study, the patients received theophylline or placebo orally twice daily for five days, with one week of washout between the two periods. Results: After five days of treatment, the mean (±SD) plasma theophylline concentration was 11±2 μg per milliliter. Theophylline therapy resulted in significant decreases in the number of episodes of apnea and hypopnea per hour (18±17, vs. 37±23 with placebo and 47±21 at base line; P < 0.001), the number of episodes of central apnea per hour (6±14, vs. 26±21 and 26±20, respectively; P < 0.001), and the percentage of total sleep time during which the arterial oxyhemoglobin saturation was less than 90 percent (6±11 percent, vs. 23±37 and 14±14 percent, respectively; P < 0.04). There were no significant differences in the characteristics of sleep, the frequency of ventricular arrhythmias, daytime arterial-blood gas values, or the left ventricular ejection fraction during the base-line, placebo, and theophylline phases of the study. Conclusions: In patients with stable heart failure, oral theophylline therapy reduced the number of episodes of apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during sleep.