Dataset Information

Dexmedetomidine-induced deep sedation mimics non-rapid eye movement stage 3 sleep: large-scale validation using machine learning.

ABSTRACT:

Study objectives

Dexmedetomidine-induced electroencephalogram (EEG) patterns during deep sedation are comparable with natural sleep patterns. Using large-scale EEG recordings and machine learning techniques, we investigated whether dexmedetomidine-induced deep sedation indeed mimics natural sleep patterns.

Methods

We used EEG recordings from three sources in this study: 8,707 overnight sleep EEG and 30 dexmedetomidine clinical trial EEG. Dexmedetomidine-induced sedation levels were assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score. We extracted 22 spectral features from each EEG recording using a multitaper spectral estimation method. Elastic-net regularization method was used for feature selection. We compared the performance of several machine learning algorithms (logistic regression, support vector machine, and random forest), trained on individual sleep stages, to predict different levels of the MOAA/S sedation state.

Results

The random forest algorithm trained on non-rapid eye movement stage 3 (N3) predicted dexmedetomidine-induced deep sedation (MOAA/S = 0) with area under the receiver operator characteristics curve >0.8 outperforming other machine learning models. Power in the delta band (0-4 Hz) was selected as an important feature for prediction in addition to power in theta (4-8 Hz) and beta (16-30 Hz) bands.

Conclusions

Using a large-scale EEG data-driven approach and machine learning framework, we show that dexmedetomidine-induced deep sedation state mimics N3 sleep EEG patterns.

Clinical trials

Name-Pharmacodynamic Interaction of REMI and DMED (PIRAD), URL-https://clinicaltrials.gov/ct2/show/NCT03143972, and registration-NCT03143972.

SUBMITTER: Ramaswamy SM

PROVIDER: S-EPMC7879420 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dexmedetomidine-induced deep sedation mimics non-rapid eye movement stage 3 sleep: large-scale validation using machine learning.

Ramaswamy Sowmya M SM Weerink Maud A S MAS Struys Michel M R F MMRF Nagaraj Sunil B SB

Sleep 20210201 2

<h4>Study objectives</h4>Dexmedetomidine-induced electroencephalogram (EEG) patterns during deep sedation are comparable with natural sleep patterns. Using large-scale EEG recordings and machine learning techniques, we investigated whether dexmedetomidine-induced deep sedation indeed mimics natural sleep patterns.<h4>Methods</h4>We used EEG recordings from three sources in this study: 8,707 overnight sleep EEG and 30 dexmedetomidine clinical trial EEG. Dexmedetomidine-induced sedation levels wer ...[more]

PMID: 32860500

Similar Datasets

Project description:BackgroundThe administration of dexmedetomidine is limited to highly monitored care settings because it is only available for use in humans as intravenous medication. An oral formulation of dexmedetomidine may broaden its use to all care settings. The authors investigated the effect of a capsule-based solid oral dosage formulation of dexmedetomidine on sleep polysomnography.MethodsThe authors performed a single-site, placebo-controlled, randomized, crossover, double-blind phase II study of a solid oral dosage formulation of dexmedetomidine (700 mcg; n = 15). The primary outcome was polysomnography sleep quality. Secondary outcomes included performance on the motor sequence task and psychomotor vigilance task administered to each subject at night and in the morning to assess motor memory consolidation and psychomotor function, respectively. Sleep questionnaires were also administered.ResultsOral dexmedetomidine increased the duration of non-rapid eye movement (non-REM) stage 2 sleep by 63 (95% CI, 19 to 107) min (P = 0.010) and decreased the duration of rapid eye movement (REM) sleep by 42 (5 to 78) min (P = 0.031). Overnight motor sequence task performance improved after placebo sleep (7.9%; P = 0.003) but not after oral dexmedetomidine-induced sleep (-0.8%; P = 0.900). In exploratory analyses, we found a positive correlation between spindle density during non-REM stage 2 sleep and improvement in the overnight test performance (Spearman rho = 0.57; P = 0.028; n = 15) for placebo but not oral dexmedetomidine (Spearman rho = 0.04; P = 0.899; n = 15). Group differences in overnight motor sequence task performance, psychomotor vigilance task metrics, and sleep questionnaires did not meet the threshold for statistical significance.ConclusionsThese results demonstrate that the nighttime administration of a solid oral dosage formulation of dexmedetomidine is associated with increased non-REM 2 sleep and decreased REM sleep. Spindle density during dexmedetomidine sleep was not associated with overnight improvement in the motor sequence task.Editor’s perspective

Project description:Dexmedetomidine, a highly selective ?2-adrenergic agonist, is widely used in clinical anesthesia and ICU sedation. Recent studies have found that dexmedetomidine-induced sedation resembles the recovery sleep that follows sleep deprivation, but whether orally delivered dexmedetomidine can be a candidate for the treatment of insomnia remains unclear. In this study, we estimated the sedative effects of orally delivered dexmedetomidine by spontaneous locomotor activity (LMA), and then evaluated the hypnotic effects of dexmedetomidine on sleep–wake profiles during the dark and light phase using electroencephalography/electromyogram (EEG/EMG), respectively. Using c-Fos staining, we explored the effects of dexmedetomidine on the cerebral cortex and the sub-cortical sleep–wake regulation systems. The results showed that orally delivered dexmedetomidine at 2 h into the dark cycle reduced LMA and wakefulness in a dose-dependent manner, which was consistent with the increase in non-rapid eye movement sleep (NREM sleep). However, dexmedetomidine also induced a rebound in LMA, wake and rapid eye movement sleep (REM sleep) in the later stage. In addition, orally delivered dexmedetomidine 100 ?g/kg at 2 h into the light cycle shortened the latency to NREM sleep and increased the duration of NREM sleep for 6 h, while decreased REM sleep for 6 h. Sleep architecture analysis showed that dexmedetomidine stabilized the sleep structure during the light phase by decreasing sleep–wake transition and increasing long-term NREM sleep (durations of 1024–2024 s and >2024 s) while reducing short-term wakefulness (duration of 4–16 s). Unlike the classic hypnotic diazepam, dexmedetomidine also increased the delta power in the EEG spectra of NREM sleep, especially at the frequency of 1.75–3.25 Hz, while ranges of 0.5–1.0 Hz were decreased. Immunohistochemical analysis showed that orally delivered dexmedetomidine 100 ?g/kg at 2 h into the dark cycle decreased c-Fos expression in the cerebral cortex and sub-cortical arousal systems, while it increased c-Fos expression in the neurons of the ventrolateral preoptic nucleus. These results indicate that orally delivered dexmedetomidine can induce sedative and hypnotic effects by exciting the sleep-promoting nucleus and inhibiting the wake-promoting areas.

Project description:BackgroundAnaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level.MethodsWe compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings.ResultsMost subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state.ConclusionsAnaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content.Clinical trial registrationClinical trial registration. This study was part of a larger study registered at ClinicalTrials.gov (NCT01889004).

Dataset Information

Dexmedetomidine-induced deep sedation mimics non-rapid eye movement stage 3 sleep: large-scale validation using machine learning.

Study objectives

Methods

Results

Conclusions

Clinical trials

Publications

Dexmedetomidine-induced deep sedation mimics non-rapid eye movement stage 3 sleep: large-scale validation using machine learning.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets