{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:41:01Z","timestamp":1784547661259,"version":"3.55.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019065","name":"Masimo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005075","name":"Universitair Medisch Centrum Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005075","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Multichannel EEG datasets from two different sources were used in this study: (1) sedation dataset consisting of 102 healthy volunteers receiving propofol (N = 36), sevoflurane (N = 36), or dexmedetomidine (N = 30), and (2) publicly available sleep EEG dataset (N = 994). Forty-four quantitative time, frequency and entropy features were extracted from EEG recordings and were used to train the machine learning algorithms on sleep dataset to predict sleep stages in the sedation dataset. The predicted sleep states were then compared with the Modified Observer\u2019s Assessment of Alertness\/ Sedation (MOAA\/S) scores.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The performance of the model was poor (AUC = 0.55\u20130.58) in differentiating sleep stages during propofol and sevoflurane sedation. In the case of dexmedetomidine, the AUC of the model increased in a sedation\u2014dependent manner with NREM stages 2 and 3 highly correlating with deep sedation state reaching an AUC of 0.80.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We addressed an important clinical question to identify biological sleep promoting sedatives using EEG signals. We demonstrate that propofol and sevoflurane do not promote EEG patterns resembling natural sleep while dexmedetomidine promotes states resembling NREM stages 2 and 3 sleep, based on current sleep staging standards.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0304413","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T18:59:35Z","timestamp":1719946775000},"page":"e0304413","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5179-7601","authenticated-orcid":true,"given":"Sowmya M.","family":"Ramaswamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel H.","family":"Kuizenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud A. S.","family":"Weerink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo E. M.","family":"Vereecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil B.","family":"Nagaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-536X","authenticated-orcid":true,"given":"Michel M. R. F.","family":"Struys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"pone.0304413.ref001","first-page":"804","article-title":"Sleep in the Intensive Care Unit measured by polysomnography","volume":"79","author":"JH Andersen","year":"2013","journal-title":"Minerva Anestesiol"},{"key":"pone.0304413.ref002","doi-asserted-by":"crossref","first-page":"e12959","DOI":"10.1111\/jsr.12959","article-title":"The importance of the intensive care unit environment in sleep-A study with healthy participants","volume":"29","author":"L Reinke","year":"2020","journal-title":"J Sleep Res"},{"key":"pone.0304413.ref003","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13054-019-2366-0","article-title":"Sleep and Circadian Rhythm in Critical Illness","volume":"23","author":"I Telias","year":"2019","journal-title":"Crit Care Lond Engl"},{"key":"pone.0304413.ref004","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1056\/NEJMra0808281","article-title":"General anesthesia, sleep, and coma","volume":"363","author":"EN Brown","year":"2010","journal-title":"N Engl J Med"},{"key":"pone.0304413.ref005","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.euroneuro.2015.06.005","article-title":"Effects of oral temazepam on sleep spindles during non-rapid eye movement sleep: A high-density EEG investigation","volume":"25","author":"DT Plante","year":"2015","journal-title":"Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol"},{"key":"pone.0304413.ref006","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/sleep\/34.3.283","article-title":"Propofol anesthesia and sleep: a high-density EEG study","volume":"34","author":"M Murphy","year":"2011","journal-title":"Sleep"},{"key":"pone.0304413.ref007","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/sleep\/28.2.187","article-title":"A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo","volume":"28","author":"I Hindmarch","year":"2005","journal-title":"Sleep"},{"key":"pone.0304413.ref008","doi-asserted-by":"crossref","first-page":"400","DOI":"10.4103\/1319-3767.164202","article-title":"Cardiac arrests in patients undergoing gastrointestinal endoscopy: A retrospective analysis of 73,029 procedures","volume":"21","author":"B Goudra","year":"2015","journal-title":"Saudi J Gastroenterol Off J Saudi Gastroenterol Assoc"},{"key":"pone.0304413.ref009","doi-asserted-by":"crossref","first-page":"e7081","DOI":"10.1097\/MD.0000000000007081","article-title":"Effects of dexmedetomidine on sleep quality of patients after surgery without mechanical ventilation in ICU","volume":"96","author":"W Lu","year":"2017","journal-title":"Medicine (Baltimore)"},{"key":"pone.0304413.ref010","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.clinph.2017.10.005","article-title":"Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study","volume":"129","author":"O Akeju","year":"2018","journal-title":"Clin Neurophysiol"},{"key":"pone.0304413.ref011","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1097\/ALN.0000000000000361","article-title":"Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study","volume":"121","author":"C Alexopoulou","year":"2014","journal-title":"Anesthesiology"},{"key":"pone.0304413.ref012","first-page":"597","article-title":"Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine","volume":"8","author":"RB Berry","year":"2012","journal-title":"J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med"},{"key":"pone.0304413.ref013","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1097\/CCM.0b013e31828a3f75","article-title":"Atypical sleep in ventilated patients: empirical electroencephalography findings and the path toward revised ICU sleep scoring criteria","volume":"41","author":"PL Watson","year":"2013","journal-title":"Crit Care Med"},{"key":"pone.0304413.ref014","doi-asserted-by":"crossref","unstructured":"Ghassemi MM, Moody BE, Lehman L-WH, Song C, Li Q, Sun H, et al. You snooze, you win: the physionet\/computing in cardiology challenge 2018. 2018 Computing in Cardiology Conference (CinC). IEEE; 2018. pp. 1\u20134.","DOI":"10.22489\/CinC.2018.049"},{"key":"pone.0304413.ref015","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.bja.2017.11.072","article-title":"Test of neural inertia in humans during general anaesthesia","volume":"120","author":"MH Kuizenga","year":"2018","journal-title":"Br J Anaesth"},{"key":"pone.0304413.ref016","first-page":"1","article-title":"Frontal electroencephalogram based drug, sex, and age independent sedation level prediction using non-linear machine learning algorithms","author":"SM Ramaswamy","year":"2020","journal-title":"J Clin Monit Comput"},{"key":"pone.0304413.ref017","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.bja.2019.06.004","article-title":"Novel drug-independent sedation level estimation based on machine learning of quantitative frontal electroencephalogram features in healthy volunteers","volume":"123","author":"SM Ramaswamy","year":"2019","journal-title":"Br J Anaesth"},{"key":"pone.0304413.ref018","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1097\/ALN.0000000000002882","article-title":"Pharmacodynamic Interaction of Remifentanil and Dexmedetomidine on Depth of Sedation and Tolerance of Laryngoscopy","volume":"131","author":"MAS Weerink","year":"2019","journal-title":"Anesthesiology"},{"key":"pone.0304413.ref019","first-page":"244","article-title":"Validity and Reliability of the Observer\u2019s: Assessment of Alertness\/Sedation Scale: Study with: Intravenous Midazolam","volume":"10","author":"DA Chernik","year":"1990","journal-title":"J Clin Psychopharmacol"},{"key":"pone.0304413.ref020","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1097\/00000542-199805000-00006","article-title":"The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers","volume":"88","author":"TW Schnider","year":"1998","journal-title":"Anesthesiology"},{"key":"pone.0304413.ref021","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/bja\/aex086","article-title":"Dexmedetomidine pharmacodynamics in healthy volunteers: 2. Haemodynamic profile","volume":"119","author":"PJ Colin","year":"2017","journal-title":"Br J Anaesth"},{"key":"pone.0304413.ref022","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s40262-017-0507-7","article-title":"Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine","volume":"56","author":"MA Weerink","year":"2017","journal-title":"Clin Pharmacokinet"},{"key":"pone.0304413.ref023","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/bja\/aex085","article-title":"Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation","volume":"119","author":"PJ Colin","year":"2017","journal-title":"Br J Anaesth"},{"key":"pone.0304413.ref024","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/0013-4694(70)90143-4","article-title":"EEG analysis based on time domain properties","volume":"29","author":"B. Hjorth","year":"1970","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"pone.0304413.ref025","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s10439-012-0710-5","article-title":"An automated system for grading EEG abnormality in term neonates with hypoxic-ischaemic encephalopathy","volume":"41","author":"N Stevenson","year":"2013","journal-title":"Ann Biomed Eng"},{"key":"pone.0304413.ref026","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jneumeth.2013.07.003","article-title":"Real-time segmentation of burst suppression patterns in critical care EEG monitoring","volume":"219","author":"M Brandon Westover","year":"2013","journal-title":"J Neurosci Methods"},{"key":"pone.0304413.ref027","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/BF02344866","article-title":"Analysis of postural sway using entropy measures of signal complexity","volume":"38","author":"AM Sabatini","year":"2000","journal-title":"Med Biol Eng Comput"},{"key":"pone.0304413.ref028","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1145\/584091.584093","article-title":"A mathematical theory of communication","volume":"5","author":"CE Shannon","year":"2001","journal-title":"ACM SIGMOBILE Mob Comput Commun Rev"},{"key":"pone.0304413.ref029","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fncom.2015.00016","article-title":"EEG entropy measures in anesthesia","volume":"9","author":"Z Liang","year":"2015","journal-title":"Front Comput Neurosci"},{"key":"pone.0304413.ref030","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1142\/S0218127491000403","article-title":"Nonlinear time sequence analysis","volume":"01","author":"P Grassberger","year":"1991","journal-title":"Int J Bifurc Chaos"},{"key":"pone.0304413.ref031","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cmpb.2005.06.012","article-title":"Entropies for detection of epilepsy in EEG","volume":"80","author":"N Kannathal","year":"2005","journal-title":"Comput Methods Programs Biomed"},{"key":"pone.0304413.ref032","doi-asserted-by":"crossref","first-page":"174102","DOI":"10.1103\/PhysRevLett.88.174102","article-title":"Permutation entropy: a natural complexity measure for time series","volume":"88","author":"C Bandt","year":"2002","journal-title":"Phys Rev Lett"},{"key":"pone.0304413.ref033","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0092-8240(88)80009-0","article-title":"The fractal dimension of EEG as a physical measure of conscious human brain activities","volume":"50","author":"X Nan","year":"1988","journal-title":"Bull Math Biol"},{"key":"pone.0304413.ref034","article-title":"Large-Scale Automated Sleep Staging","volume":"40","author":"H Sun","year":"2017","journal-title":"Sleep"},{"key":"pone.0304413.ref035","doi-asserted-by":"crossref","first-page":"zsaa167","DOI":"10.1093\/sleep\/zsaa167","article-title":"Dexmedetomidine-induced deep sedation mimics non-rapid eye movement stage 3 sleep: large-scale validation using machine learning","volume":"44","author":"SM Ramaswamy","year":"2021","journal-title":"Sleep"},{"key":"pone.0304413.ref036","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"H Zou","year":"2005","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"key":"pone.0304413.ref037","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/978-0-387-09823-4_45","volume-title":"Data mining and knowledge discovery handbook","author":"NV Chawla","year":"2009"},{"key":"pone.0304413.ref038","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1097\/ALN.0000000000000841","article-title":"Clinical Electroencephalography for AnesthesiologistsPart I: Background and Basic Signatures","volume":"123","author":"PL Purdon","year":"2015","journal-title":"J Am Soc Anesthesiol"},{"key":"pone.0304413.ref039","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nn913","article-title":"The sedative component of anesthesia is mediated by GABA A receptors in an endogenous sleep pathway","volume":"5","author":"LE Nelson","year":"2002","journal-title":"Nat Neurosci"},{"key":"pone.0304413.ref040","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/01.anes.0000270741.33766.24","article-title":"Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat","volume":"107","author":"MT Alkire","year":"2007","journal-title":"J Am Soc Anesthesiol"},{"key":"pone.0304413.ref041","volume-title":"Anesthetic pharmacology: Basic principles and clinical practice","author":"AS Evers","year":"2011"},{"key":"pone.0304413.ref042","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1213\/ANE.0000000000004651","article-title":"Predicting Deep Hypnotic State From Sleep Brain Rhythms Using Deep Learning: A Data-Repurposing Approach","volume":"130","author":"S Belur Nagaraj","year":"2020","journal-title":"Anesth Analg"},{"key":"pone.0304413.ref043","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.conb.2017.04.011","article-title":"Neural oscillations demonstrate that general anesthesia and sedative states are neurophysiologically distinct from sleep","volume":"44","author":"O Akeju","year":"2017","journal-title":"Curr Opin Neurobiol"},{"key":"pone.0304413.ref044","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1097\/ALN.0000000000000419","article-title":"A comparison of propofol- and dexmedetomidine-induced electroencephalogram dynamics using spectral and coherence analysis","volume":"121","author":"O Akeju","year":"2014","journal-title":"Anesthesiology"},{"key":"pone.0304413.ref045","doi-asserted-by":"crossref","first-page":"e0216456","DOI":"10.1371\/journal.pone.0216456","article-title":"SleepEEGNet: Automated sleep stage scoring with sequence to sequence deep learning approach","volume":"14","author":"S Mousavi","year":"2019","journal-title":"PloS One"},{"key":"pone.0304413.ref046","unstructured":"Biswal S, Kulas J, Sun H, Goparaju B, Westover MB, Bianchi MT, et al. SLEEPNET: automated sleep staging system via deep learning. ArXiv Prepr ArXiv170708262. 2017."},{"key":"pone.0304413.ref047","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1109\/TNSRE.2017.2721116","article-title":"DeepSleepNet: A Model for Automatic Sleep Stage Scoring Based on Raw Single-Channel EEG","volume":"25","author":"A Supratak","year":"2017","journal-title":"IEEE Trans Neural Syst Rehabil Eng Publ IEEE Eng Med Biol Soc"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0304413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T19:00:07Z","timestamp":1719946807000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0304413"}},"subtitle":[],"editor":[{"given":"Dragan","family":"Hrncic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,2]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0304413","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,2]]}}}