Depth of sedation with dexmedetomidine increases transcranial magnetic stimulation-evoked potential amplitude non-linearly

Paolo Cardone; Olivier Bodart; Murielle Kirsch; Julien Sanfilippo; Alessandra Virgillito; Charlotte Martial; Jessica Simon; Sarah Wannez; Robert D Sanders; Steven Laureys; Marcello Massimini; Gilles Vandewalle; Vincent Bonhomme; Olivia Gosseries

doi:10.1016/j.bja.2023.05.030

Depth of sedation with dexmedetomidine increases transcranial magnetic stimulation-evoked potential amplitude non-linearly

Br J Anaesth. 2023 Oct;131(4):715-725. doi: 10.1016/j.bja.2023.05.030. Epub 2023 Aug 16.

Authors

Affiliations

¹ Coma Science Group, GIGA-Consciousness, University of Liège, Liège, Belgium; Centre du Cerveau, University of Liège, Liège, Belgium.
² Coma Science Group, GIGA-Consciousness, University of Liège, Liège, Belgium; Centre du Cerveau, University of Liège, Liège, Belgium; Department of Neurology, University of Liège, Liège, Belgium.
³ Anesthesia and Perioperative Neuroscience Laboratory, GIGA-Consciousness, University of Liège, Liège, Belgium; Department of Anaesthesia and Intensive Care Medicine, University of Liège, Liège, Belgium.
⁴ Anesthesia and Perioperative Neuroscience Laboratory, GIGA-Consciousness, University of Liège, Liège, Belgium.
⁵ Department of Rehabilitation, ASL Toscana Nordovest, Livorno, Italy.
⁶ Psychology and Neuroscience of Cognition, University of Liège, Liège, Belgium.
⁷ Coma Science Group, GIGA-Consciousness, University of Liège, Liège, Belgium.
⁸ Specialty of Anaesthetics, University of Sydney, Camperdown, Australia; Department of Anaesthetics & Institute of Academic Surgery, Royal Prince Alfred Hospital, Camperdown, Australia.
⁹ Coma Science Group, GIGA-Consciousness, University of Liège, Liège, Belgium; Centre du Cerveau, University of Liège, Liège, Belgium; Joint International Research Unit on Consciousness, CERVO Brain Research Centre, CIUSS, University Laval, Québec City, QC, Canada.
¹⁰ Department of Biomedical and Clinical Sciences "L. Sacco", Università degli Studi di Milano, Milan, Italy; IRCCS Fondazione Don Gnocchi, Milan, Italy.
¹¹ Sleep and Chronobiology Lab, GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium.
¹² Anesthesia and Perioperative Neuroscience Laboratory, GIGA-Consciousness, University of Liège, Liège, Belgium; Department of Anaesthesia and Intensive Care Medicine, University of Liège, Liège, Belgium; University Department of Anaesthesia and Intensive Care Medicine, Centre Hospitalier Régional de la Citadelle (CHR Citadelle), Liège, Belgium. Electronic address: vincent.bonhomme@chuliege.be.
¹³ Coma Science Group, GIGA-Consciousness, University of Liège, Liège, Belgium; Centre du Cerveau, University of Liège, Liège, Belgium. Electronic address: ogosseries@uliege.be.

PMID: 37596183
DOI: 10.1016/j.bja.2023.05.030

Abstract

Background: Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known.

Methods: We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0-30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices.

Results: Compared with baseline, amplitude in the frontal cortex increased by 6.52 μV (P<0.001) in light sedation, 4.55 μV (P=0.003) in deep sedation, and 5.03 μV (P<0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P<0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 μV higher amplitude (P<0.001), 0.63 μV ms^-1 higher slope (P<0.001), and 2.2 ms shorter negative peak latency (P=0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P=0.004) and slope (P=0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline.

Conclusions: Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation.

Keywords: anaesthesia; consciousness; dexmedetomidine; responsiveness; sedation; transcranial magnetic stimulation-evoked potential.

MeSH terms

Anesthesia*
Dexmedetomidine* / pharmacology
Evoked Potentials
Frontal Lobe
Humans
Transcranial Magnetic Stimulation

Substances

Dexmedetomidine