Effect of Theophylline on Sleep-Disordered Breathing in Heart Failure

Javaheri, S.
Parker, T.J.
Wexler, L.
Liming, J.D.
Lindower, P.
Roselle, G.A.

From the Pulmonary Section (S.J., T.J.P., J.D.L.), the Cardiology Section (L.W., P.L.), and the Medical Service (G.A.R.), Veterans Affairs Medical Center and the University of Cincinnati College of Medicine -- both in Cincinnati. Address reprint requests to Dr. Javaheri at the Sleep Disorders Laboratory, Pulmonary Section (111F), VA Medical Center, 3200 Vine St., Cincinnati, OH 45220.

New England Journal of Medicine 335(8):p 562-567, August 22, 1996. | DOI: 10.1056/NEJM199608223350805

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 microg 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. (N Engl J Med 1996;335:562-7.)