Effect of Theophylline on Sleep and Sleep-disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease

Abstract

To investigate the effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease (COPD), we studied 12 male nonhypercapnic subjects with a mean +/- SEM age of 62.8 +/- 2.5 yr and a FEV1 of 1.36 +/- 0.11 L using a randomized double-blind crossover protocol. Sustained-action theophylline (250 mg three times or four times a day) or placebo was administered for 2 days, and the alternate drug was administered on the following 2 days. Sleep studies were performed on Nights 2 and 4 with spirometry at 9:00P.M. and 7:00A.M. Two puffs of metaproterenol or albuterol were administered at 10:00P.M. on both study nights. A theophylline level, drawn at bedtime (10:00 to 11:00P.M.), was 14.2 +/- 0.78 micrograms/ml on the theophylline nights and less than 2 on placebo nights. The morning FEV1 was significantly better during theophylline administration (1.27 +/- 0.12 versus 1.00 +/- 0.11 L, p less than 0.001). The mean arterial oxygen saturation (SaO2) and transcutaneous carbon dioxide pressure (PCO2) were also better during NREM sleep on theophylline nights. Neither the mean SaO2 and transcutaneous PCO2 during REM sleep nor the apnea plus hypopnea index (events per hour of sleep) differed between placebo and theophylline nights. Theophylline administration did not impair the amount or architecture of sleep as neither total sleep time nor the fraction of time spent in Stages 1, 2, and 3/4 and REM differed between the two regimens. The number of arousals per hour of sleep was slightly less on theophylline nights (19.9 +/- 1.7 versus 24.9 +/- 2.7, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep Abnormalities and Treatment in Emphysema

“…Veale and coworkers (38) noted no change in sleep quality in 14 patients with COPD treated with a sustained-release form of salbutamol. The effects of theophylline on sleep quality have been more variable, with some studies demonstrating an impairment in sleep quality (39), whereas others have noted no significant effect (40)(41)(42). Anticholinergics such as ipratropium may improve sleep quality (43).…”

“…As noted above, bronchodilator medications have shown mixed results regarding their effects on sleep quality, with some demonstrating improvement (43), no significant effect (40)(41)(42)44), or deterioration in sleep quality (39). However, despite their diverse effects on sleep quality, the majority have demonstrated an improvement in nocturnal oxygen saturation (39,41,43,44) and lung function (39)(40)(41)(42)(43)(44).…”

“…However, despite their diverse effects on sleep quality, the majority have demonstrated an improvement in nocturnal oxygen saturation (39,41,43,44) and lung function (39)(40)(41)(42)(43)(44). Regarding treatment of insomnia symptoms in patients with emphysema, benzodiazepines should be avoided, even in normocapnic patients, because of their effect on ventilatory drive and worsening nocturnal hypoxemia (55).…”

Chronic Obstructive Pulmonary Disease and Sleep Quality

“…Ipratropium bromide enhances sleep quality, abrogates nocturnal oxygen desaturation, improves perceived sleep quality, and increases REM sleep duration without any effects on other sleep phases or total sleep duration [66]. On the other hand, while some studies examining the effect of Theophylline on sleep quality reported that it caused deterioration of sleep quality [65], other studies revealed that it had no effect on sleep quality [67][68][69].…”

Perturbação respiratória durante o sono em doença pulmonar obstrutiva crônica

“…6. Theophylline: Berry et al demonstrated improvement in overnight oxygen saturation and transcutaneous CO 2 after oral ingestion of theophylline during non-REM sleep in non-hypercapnic patients with COPD (76) . The effects were not carried on during REM sleep.…”