Javaheri S, Parker T J, Wexler L, Liming J D, Lindower P, Roselle G A
Pulmonary Services, Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.
N Engl J Med. 1996 Aug 22;335(8):562-7. doi: 10.1056/NEJM199608223350805.
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.
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.
After five days of treatment, the mean (+/-SD) plasma theophylline concentration was 11 +/- 2 microgram 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.
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.
茶碱已被用于治疗与潮式呼吸（周期性呼吸）相关的中枢性呼吸暂停。我们研究了短期口服茶碱治疗对因收缩功能障碍导致的稳定型心力衰竭相关周期性呼吸的影响。
15名代偿性心力衰竭男性患者（左心室射血分数为45%或更低）参与了该研究。他们的基线多导睡眠图显示有周期性呼吸，每小时呼吸暂停和呼吸不足发作超过10次。在一项双盲交叉研究中，患者每天口服两次茶碱或安慰剂，持续五天，两个阶段之间有一周的洗脱期。
治疗五天后，血浆茶碱平均（±标准差）浓度为11±2微克/毫升。茶碱治疗使每小时呼吸暂停和呼吸不足发作次数显著减少（分别为18±17次，安慰剂组为37±23次，基线时为47±21次；P<0.001），每小时中枢性呼吸暂停发作次数显著减少（分别为6±14次，安慰剂组为26±21次，基线时为26±20次；P<0.001），以及动脉血氧血红蛋白饱和度低于90%的总睡眠时间百分比显著降低（分别为6±11%，安慰剂组为23±37%，基线时为14±14%；P<0.04）。在研究的基线、安慰剂和茶碱阶段，睡眠特征、室性心律失常频率、日间动脉血气值或左心室射血分数均无显著差异。
在稳定型心力衰竭患者中，口服茶碱治疗可减少睡眠期间呼吸暂停和呼吸不足发作次数以及动脉血氧血红蛋白去饱和持续时间。
