The effect of theophylline on sleep-disordered breathing in patients with stable chronic congestive heart failure

Ke Hu, Qingquan Li, Jiong Yang, Suping Hu, Xilan Chen
Chinese Medical Journal 2003, 116 (11): 1711-6

OBJECTIVE: To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients.

METHODS: Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment.

RESULTS: Patients were divided into two groups. Group I (n = 21) consisted of individuals with 15 episodes of apnea and hypopnea [as determined by the apnea-hypopnea index (AHI)] per hour or less; Group II (n = 15, 41.7%) individuals had an index of more than 15 episodes per hour. In group II, the AHI varied from 16.8 to 78.8 (42.6 +/- 15.5) in which the obstructive AHI was 11.1 +/- 8.4 and the central AHI was 31.5 +/- 9.6. Group II had significantly more arousals (36.8 +/- 21.3 compared with 19.4 +/- 11.2 in group I) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76.7% +/- 4.6% compared with 86.5% +/- 2.8%) and lower left ventricular ejection fraction (24.2% +/- 8.8% compared with 31.5% +/- 10.6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4.3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11.3 +/- 2.5) micro g/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20.8 +/- 13.2 vs. 42.6 +/- 15.5; P < 0.001) and the number of episodes of central apnea-hypopnea per hour (10.1 +/- 7.6 vs. 31.5 +/- 9.6; P < 0.001). Furthermore, the percentage of total sleep time during which arterial oxyhemoglobin saturation (SaO(2)) was less than 90 percent (8.8% +/- 8.6% vs. 23.4% +/- 24.1%; P < 0.05) and the arousals per hour (18.7 +/- 21.2 vs. 36.8 +/- 21.3; P < 0.05) were also lower. There were no significant differences in the characteristics of sleep or obstructive AHI before and after theophylline treatment.

CONCLUSIONS: The prevalence of sleep-disordered breathing (mainly periodic respiration or cheyne-stokes respiration with central sleep apnea) is high in patients with stable chronic congestive heart failure. The sleep-disordered breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. In these patients, oral theophylline therapy may reduce the number of episodes of central apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during nocturnal sleep.

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