Brain functional connectivity differentiates dexmedetomidine from propofol and natural sleep

[en] Background We used functional connectivity measures from brain resting state functional magnetic resonance imaging to identify human neural correlates of sedation with dexmedetomidine or propofol and their similarities with natural sleep. Methods Connectivity within the resting state networks that are proposed to sustain consciousness generation was compared between deep non-rapid-eye-movement (N3) sleep, dexmedetomidine sedation, and propofol sedation in volunteers who became unresponsive to verbal command. A newly acquired dexmedetomidine dataset was compared with our previously published propofol and N3 sleep datasets. Results In all three unresponsive states (dexmedetomidine sedation, propofol sedation, and N3 sleep), within-network functional connectivity, including thalamic functional connectivity in the higher-order (default mode, executive control, and salience) networks, was significantly reduced as compared with the wake state. Thalamic functional connectivity was not reduced for unresponsive states within lower-order (auditory, sensorimotor, and visual) networks. Voxel-wise statistical comparisons between the different unresponsive states revealed that thalamic functional connectivity with the medial prefrontal/anterior cingulate cortex and with the mesopontine area was reduced least during dexmedetomidine-induced unresponsiveness and most during propofol-induced unresponsiveness. The reduction seen during N3 sleep was intermediate between those of dexmedetomidine and propofol. Conclusions Thalamic connectivity with key nodes of arousal and saliency detection networks was relatively preserved during N3 sleep and dexmedetomidine-induced unresponsiveness as compared to propofol. These network effects may explain the rapid recovery of oriented responsiveness to external stimulation seen under dexmedetomidine sedation. Trial registry number Committee number: 'Comité d'Ethique Hospitalo-Facultaire Universitaire de Liège' (707); EudraCT number: 2012-003562-40; internal reference: 20121/135; accepted on August 31, 2012; Chair: Prof G. Rorive. As it was considered a phase I clinical trial, this protocol does not appear on the EudraCT public website. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

Disciplines :

Anesthesia & intensive care

Author, co-author :

Guldenmund, Pieter ^✱

VANHAUDENHUYSE, Audrey ^✱; Centre Hospitalier Universitaire de Liège - CHU > Département d'Anesthésie et réanimation > Centre interdisciplinaire d'algologie

Sanders, R. D.; Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI, United States, Wellcome Department of Imaging Neuroscience, Department of Anaesthesia, Surgical Outcomes Research Centre, University College London Hospital, London, United Kingdom

Sleigh, J.; Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, New Zealand

Bruno, Marie-Aurélie ; GIGA-Consciousness, Coma Science Group, Pain and Hypnosis, Anesthesia and Intensive Care Laboratories, GIGA Research, University, CHU University Hospital of Liège, Liège, Belgium

Demertzi, Athina ; Université de Liège - ULiège > Centre de recherches du cyclotron

Bahri, Mohamed Ali ; Université de Liège - ULiège > Centre de recherches du cyclotron

JAQUET, Océane ; Centre Hospitalier Universitaire de Liège - CHU > Département d'Anesthésie et réanimation > Service d'anesthésie - réanimation

Sanfilippo, Julien ; Centre Hospitalier Universitaire de Liège - CHU > Département d'Anesthésie et réanimation > Service d'anesthésie - réanimation

Baquero Duarte, Katherine Andrea ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux

More authors (4 more)

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Brain functional connectivity differentiates dexmedetomidine from propofol and natural sleep

Publication date :

2017

Journal title :

British Journal of Anaesthesia

ISSN :

0007-0912

eISSN :

1471-6771

Publisher :

Oxford University Press

Volume :

119

Issue :

Pages :

674-684

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 June 2018

Statistics

Number of views

107 (16 by ULiège)

Number of downloads

5 (5 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

100

Bibliography

Huupponen E, Maksimow A, Lapinlampi P, et al. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand 2008; 52: 289-94
Purdon PL, Sampson A, Pavone KJ, Brown EN. Clinical electroencephalography for anesthesiologists: part I: background and basic signatures. Anesthesiology 2015; 123: 937-60
Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The a2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003; 98: 428-36
Sanders RD, Maze M. Contribution of sedative-hypnotic agents to delirium via modulation of the sleep pathway. Can J Anaesth 2011; 58: 149-56
Zecharia AY, Franks NP. General anesthesia and ascending arousal pathways. Anesthesiology 2009; 111: 695-6
Gomez F, Phillips C, Soddu A, et al. Changes in effective connectivity by propofol sedation. PLoS One 2013; 8: e71370
Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med 2010; 363: 2638-50
Djaiani G, Silverton N, Fedorko L, et al. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial. Anesthesiology 2016; 124: 362-8
Su X, Meng ZT, Wu XH, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 2016; 388: 1893-902
Ni J, Wei J, Yao Y, Jiang X, Luo L, Luo D. Effect of dexmedetomidine on preventing postoperative agitation in children: a meta-analysis. PLoS One 2015; 10: e0128450
Turunen H, Jakob SM, Ruokonen E, et al. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care 2015; 19: 67
Guldenmund P, Vanhaudenhuyse A, Boly M, Laureys S, Soddu A. A default mode of brain function in altered states of consciousness. Arch Ital Biol 2012; 150: 107-21
Boveroux P, Vanhaudenhuyse A, BrunoMA, et al. Breakdownof within-and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness. Anesthesiology 2010; 113: 1038-53
Horovitz SG, Braun AR, Carr WS, et al. Decoupling of the brain's default mode network during deep sleep. Proc Natl Acad Sci USA 2009; 106: 11376-81
Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJ, et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 2010; 133: 161-71
Vanhaudenhuyse A, Demertzi A, Schabus M, et al. Two distinct neuronal networks mediate the awareness of environment and of self. J Cogn Neurosci 2011; 23: 570-8
Heine L, Soddu A, Gomez F, et al. Resting state networks and consciousness: alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness States. Front Psychol 2012; 3: 295
Sanders RD, Tononi G, Laureys S, Sleigh JW. Unresponsiveness not equal unconsciousness. Anesthesiology 2012; 116: 946-59
Schrouff J, Perlbarg V, Boly M, et al. Brain functional integration decreases during propofol-induced loss of consciousness. Neuroimage 2011; 57: 198-205
Guldenmund P, Demertzi A, Boveroux P, et al. Thalamus, brainstem and salience network connectivity changes during mild propofol sedation and unconsciousness. Brain Connect 2013; 3: 273-85
Boly M, Perlbarg V, Marrelec G, et al. Hierarchical clustering of brain activity during human nonrapid eye movement sleep. Proc Natl Acad Sci USA 2012; 109: 5856-61
Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41-8
Dyck JB, Maze M, Haack C, Azarnoff DL, Vuorilehto L, Shafer SL. Computer-controlled infusion of intravenous dexmedetomidine hydrochloride in adult human volunteers. Anesthesiology 1993; 78: 821-8
Damoiseaux JS, Rombouts SA, Barkhof F, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 2006; 103: 13848-53
Seeley WW, Menon V, Schatzberg AF, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007; 27: 2349-56
Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA 2003; 100: 253-8
Reed SJ, Plourde G. Attenuation of high-frequency (50-200 Hz) thalamocortical EEG rhythms by propofol in rats is more pronounced for the thalamus than for the cortex. PLoS One 2015; 10: e0123287
Akeju O, LoggiaML, Catana C, et al. Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidineinduced unconsciousness. Elife 2014; 3: e04499
Abulafia R, Zalkind V, Devor M. Cerebral activity during the anesthesia-like state induced by mesopontine microinjection of pentobarbital. J Neurosci 2009; 29: 7053-64
Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 2010; 214: 655-67
Langsjo JW, Alkire MT, Kaskinoro K, et al. Returning from oblivion: imaging the neural core of consciousness. J Neurosci 2012; 32: 4935-43
Maquet P, Peters J, Aerts J, et al. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature 1996; 383: 163-6
Soddu A, Vanhaudenhuyse A, Bahri MA, et al. Identifying the default-mode component in spatial IC analyses of patients with disorders of consciousness. Hum BrainMapp 2012; 33: 778-96
Bonhomme V, Vanhaudenhuyse A, Demertzi A, et al. Resting-state network-specific breakdown of functional connectivity during ketamine alteration of consciousness in volunteers. Anesthesiology 2016; 125: 873-88
Margulies DS, Bottger J, Long X, et al. Resting developments: a review of fMRI post-processing methodologies for spontaneous brain activity. Magn Reson Mater Physics Biol Med 2010; 23: 289-307
Demertzi A, Gomez F, Crone JS, et al. Multiple fMRI systemlevel baseline connectivity is disrupted in patients with consciousness alterations. Cortex 2014; 52: 35-46
Corfield DR, Murphy K, Josephs O, Adams L, Turner R. Does hypercapnia-induced cerebral vasodilation modulate the hemodynamic response to neural activation? Neuroimage 2001; 13: 1207-11
Dagal A, Lam AM. Cerebral autoregulation and anesthesia. Curr Opin Anaesthesiol 2009; 22: 547-52
Veselis RA, Feshchenko VA, Reinsel RA, Beattie B, Akhurst TJ. Propofol and thiopental do not interfere with regional cerebral blood flow response at sedative concentrations. Anesthesiology 2005; 102: 26-34
Drummond JC, Dao AV, Roth DM, et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology 2008; 108: 225-32
Sarasso S, Boly M, Napolitani M, et al. Consciousness and complexity during unresponsiveness induced by propofol, xenon, and ketamine. Curr Biol 2015; 25: 3099-105
Siclari F, Larocque JJ, Postle BR, Tononi G. Assessing sleep consciousness within subjects using a serial awakening paradigm. Front Psychol 2013; 4: 542
Noreika V, Jylhankangas L, Moro L, et al. Consciousness lost and found: subjective experiences in an unresponsive state. Brain Cogn 2011; 77: 327-34
Thirion B, Pinel P, Meriaux S, Roche A, Dehaene S, Poline JB. Analysis of a large fMRI cohort: Statistical and methodological issues for group analyses. Neuroimage 2007; 35: 105-20