Acute effects of transdermal nicotine on sleep architecture, snoring, and sleep-disordered breathing in nonsmokers

Previous research has suggested that nicotine may be therapeutically useful in the treatment of sleep-disordered breathing. The development of transdermal nicotine delivery systems has allowed us to test the overnight effectiveness of nicotine. Twenty nonsmoking subjects (10 men, 10 women) were recruited on the basis of a history of habitual snoring that was confirmed by overnight laboratory monitoring. Subjects were then randomized (double-blind crossover design) to receive either placebo or an active patch that delivers 11 mg of nicotine over a 24-h period. Patches were applied at 6 P.M. and removed at 6 A.M. the following morning, at which time venous blood was obtained for determination of serum nicotine concentrations. Polysomnography was performed using standard techniques to assess sleep architecture and sleep-disordered breathing. Snoring was monitored with a sound-level meter and quantitatively analyzed to determine the snoring index (SI) (number of snores per hour of sleep) and mean and maximum snoring intensities. The age of the subjects was 46.9 ± 11.4 yr (mean ± SD) and their mean body mass index (BMI) 33.3 ± 4.6 kg/m². A mean nicotine level was nondetectable with placebo and 7.8 ± 2.3 ng/ml with wearing of an active patch. Nicotine decreased total sleep time (TST) by 33 min (p ≤ 0.01), sleep efficiency from 89.7 to 83.5% (p ≤ 0.01), and percent rapid eye movement (REM) sleep from 18.8 to 15.1% (p ≤ 0.01), and prolonged initial sleep latency (ISL) from 6.7 to 18.2 min (p ≤ 0.01). No significant changes in non-rapid eye movement (NREM) sleep stages 1, 2, 3-4, or arousal index were detected. Although the SI was unchanged (602 ± 177 versus 607 ± 205/h), mean snoring intensity decreased by 1.1 dB, p ≤ 0.01, with nicotine. A 1.4-dB reduction in maximum snoring intensity with nicotine was not significant. Although the decrease in disordered-breathing-event (DBE) frequency from 13.6 ± 15.4 to 11.4 ± 12.5/h with nicotine was not significant, a highly significant negative correlation (r = -0.71, p ≤ 0.001) was detected between nicotine level and DBE duration during the active-patch night. In addition, lowest SpO₂ was positively correlated (r = 0.52, p ≤ 0.05) with serum nicotine level. Nausea and emesis were the predominant side effects and were experienced by 50 and 20% of the subjects, respectively. In conclusion, transdermal nicotine significantly disrupted sleep architecture and produced no clinically significant improvements in either snoring or sleep-disordered breathing in this group of 20 nonsmoking snorers with mild sleep-disordered breathing. Increasing levels of nicotine were associated with a shorter DBE duration and less severe reductions in lowest SpO₂.