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

Oluwaseun Akeju, Lauren E. Hobbs, Lei Gao, Sara M. Burns, Kara J. Pavone, George S. Plummer, Elisa C. Walsh, Tim T. Houle, Seong Eun Kim, Matt T. Bianchi, Jeffrey M. Ellenbogen, Emery N. Brown

Research output: Research - peer-reviewArticle

Abstract

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.

LanguageEnglish (US)
Pages69-78
Number of pages10
JournalClinical Neurophysiology
Volume129
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Dexmedetomidine
Biomimetics
Sleep Stages
Eye Movements
Sleep
zolpidem
Psychomotor Performance
Polysomnography
REM Sleep
Arousal
Pharmacology
Pharmaceutical Preparations
Adrenergic Agonists
Hypnotics and Sedatives
Cognition
Electroencephalography
Healthy Volunteers
Surveys and Questionnaires

Keywords

  • Biomimetic sleep
  • Dexmedetomidine
  • N3 sleep
  • Sedation
  • Zolpidem

ASJC Scopus subject areas

  • Sensory Systems
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

Akeju, O., Hobbs, L. E., Gao, L., Burns, S. M., Pavone, K. J., Plummer, G. S., ... Brown, E. N. (2018). Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study. Clinical Neurophysiology, 129(1), 69-78. DOI: 10.1016/j.clinph.2017.10.005

Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans : A pilot study. / Akeju, Oluwaseun; Hobbs, Lauren E.; Gao, Lei; Burns, Sara M.; Pavone, Kara J.; Plummer, George S.; Walsh, Elisa C.; Houle, Tim T.; Kim, Seong Eun; Bianchi, Matt T.; Ellenbogen, Jeffrey M.; Brown, Emery N.

In: Clinical Neurophysiology, Vol. 129, No. 1, 01.01.2018, p. 69-78.

Research output: Research - peer-reviewArticle

Akeju, O, Hobbs, LE, Gao, L, Burns, SM, Pavone, KJ, Plummer, GS, Walsh, EC, Houle, TT, Kim, SE, Bianchi, MT, Ellenbogen, JM & Brown, EN 2018, 'Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study' Clinical Neurophysiology, vol 129, no. 1, pp. 69-78. DOI: 10.1016/j.clinph.2017.10.005
Akeju O, Hobbs LE, Gao L, Burns SM, Pavone KJ, Plummer GS et al. Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study. Clinical Neurophysiology. 2018 Jan 1;129(1):69-78. Available from, DOI: 10.1016/j.clinph.2017.10.005
Akeju, Oluwaseun ; Hobbs, Lauren E. ; Gao, Lei ; Burns, Sara M. ; Pavone, Kara J. ; Plummer, George S. ; Walsh, Elisa C. ; Houle, Tim T. ; Kim, Seong Eun ; Bianchi, Matt T. ; Ellenbogen, Jeffrey M. ; Brown, Emery N./ Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans : A pilot study. In: Clinical Neurophysiology. 2018 ; Vol. 129, No. 1. pp. 69-78
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