Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study

Objectives Sleep, which comprises of rapid eye movement (REM) and non-REM stages 1–3 (N1–N3), is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function. The principal sedative drugs produce electroencephalogram beta oscillations, which have been associated with neurocognitive dysfunction. Pharmacological induction of altered arousal states that neurophysiologically approximate natural sleep, termed biomimetic sleep, may eliminate drug-induced neurocognitive dysfunction. Methods We performed a prospective, single-site, three-arm, randomized-controlled, crossover polysomnography pilot study (n = 10) comparing natural, intravenous dexmedetomidine- (1-μg/kg over 10 min [n = 7] or 0.5-μg/kg over 10 min [n = 3]), and zolpidem-induced sleep in healthy volunteers. Sleep quality and psychomotor performance were assessed with polysomnography and the psychomotor vigilance test, respectively. Sleep quality questionnaires were also administered. Results We found that dexmedetomidine promoted N3 sleep in a dose dependent manner, and did not impair performance on the psychomotor vigilance test. In contrast, zolpidem extended release was associated with decreased theta (∼5–8 Hz; N2 and N3) and increased beta oscillations (∼13–25 Hz; N2 and REM). Zolpidem extended release was also associated with increased lapses on the psychomotor vigilance test. No serious adverse events occurred. Conclusions Pharmacological induction of biomimetic N3 sleep with psychomotor sparing benefits is feasible. Significance These results suggest that α2a adrenergic agonists may be developed as a new class of sleep enhancing medications with neurocognitive sparing benefits.
National Institutes of Health (Grant TR01 GM104948)