Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults
S. Kendall Smith,
MohammadMehdi Kafashan,
Rachel L. Rios,
Emery N. Brown,
Eric C. Landsness,
Christian S. Guay,
Ben Julian A. Palanca
Affiliations
S. Kendall Smith
Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Center on Biological Rhythms and Sleep, Washington University in St. Louis, St. Louis, MO, USA
MohammadMehdi Kafashan
Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Center on Biological Rhythms and Sleep, Washington University in St. Louis, St. Louis, MO, USA
Rachel L. Rios
Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Center on Biological Rhythms and Sleep, Washington University in St. Louis, St. Louis, MO, USA
Emery N. Brown
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Eric C. Landsness
Center on Biological Rhythms and Sleep, Washington University in St. Louis, St. Louis, MO, USA; Department of Neurology, Division of Sleep Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
Christian S. Guay
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Ben Julian A. Palanca
Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Center on Biological Rhythms and Sleep, Washington University in St. Louis, St. Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA; Corresponding author. Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Background: The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states. Methods: In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation. Results: Compared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of −17.1 min, 95% confidence interval −30.0 to −8.2, P=0.015). Dissipation of slow wave pressure was reduced (P=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (r=−0.61, P=0.03). Conclusions: Daytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults. Clinical trial registration: ClinicalTrials.gov NCT04206059.
