Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine.

Autor: Kantonen O; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland.; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland.; Department of Perioperative Services, Intensive Care and Pain Medicine, Satakunta Central Hospital, Pori FI-28500, Finland., Laaksonen L; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland.; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland., Alkire M; Department of Anesthesiology and Perioperative Medicine, University of California, Irvine, Irvine, California 92868., Scheinin A; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland.; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland., Långsjö J; Department of Intensive Care, Tampere University Hospital, Tampere FI-33521, Finland., Kallionpää RE; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland.; Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turun yliopisto FI-20014, Finland., Kaisti K; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland.; Department of Anesthesiology and Intensive Care, Oulu University Hospital, Oulu FI-90029, Finland., Radek L; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland., Johansson J; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland.; Department of Radiation Sciences, Umeå University, Umeå SE-901 87, Sweden., Laitio T; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland., Maksimow A; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland., Scheinin J; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland., Nyman M; Department of Radiology, Turku University Hospital, Turku FI-20521, Finland., Scheinin M; Institute of Biomedicine and Unit of Clinical Pharmacology, University of Turku and Turku University Hospital, Turun yliopisto FI-20014, Finland., Solin O; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland., Vahlberg T; Institute of Clinical Medicine, Biostatistics, University of Turku and Turku University Hospital, Turun yliopisto FI-20014, Finland., Revonsuo A; Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turun yliopisto FI-20014, Finland.; Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde SE-541 28, Sweden., Valli K; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland.; Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turun yliopisto FI-20014, Finland.; Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde SE-541 28, Sweden., Scheinin H; Turku PET Centre, University of Turku and Turku University Hospital, Turku FI-20521, Finland harry.scheinin@utu.fi.; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, University of Turku, Turku FI-20521, Finland.; Institute of Biomedicine and Unit of Clinical Pharmacology, University of Turku and Turku University Hospital, Turun yliopisto FI-20014, Finland.
Jazyk: angličtina
Zdroj: The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2023 Jun 28; Vol. 43 (26), pp. 4884-4895. Date of Electronic Publication: 2023 May 24.
DOI: 10.1523/JNEUROSCI.2339-22.2023
Abstrakt: Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 μg/ml; n = 40), dexmedetomidine (1.5 ng/ml; n = 40), sevoflurane (0.9% end-tidal; n = 40), S-ketamine (0.75 μg/ml; n = 20), or saline placebo ( n = 20) for 60 min using target-controlled infusions or vaporizer with end-tidal monitoring. Disconnectedness was defined as unresponsiveness to verbal commands probed at 2.5-min intervals and unawareness of external events in a postanesthesia interview. High-resolution positron emission tomography (PET) was used to quantify regional cerebral metabolic rates of glucose (CMR glu ) utilization. Contrasting scans where the subjects were classified as connected and responsive versus disconnected and unresponsive revealed that for all anesthetics, except S-ketamine, the level of thalamic activity differed between these states. A conjunction analysis across the propofol, dexmedetomidine and sevoflurane groups confirmed the thalamus as the primary structure where reduced metabolic activity was related to disconnectedness. Widespread cortical metabolic suppression was observed when these subjects, classified as either connected or disconnected, were compared with the placebo group, suggesting that these findings may represent necessary but alone insufficient mechanisms for the change in the state of consciousness. SIGNIFICANCE STATEMENT Experimental anesthesia is commonly used in the search for measures of brain function which could distinguish between global states of consciousness. However, most previous studies have not been designed to separate effects related to consciousness from other effects related to drug exposure. We employed a novel study design to disentangle these effects by exposing subjects to predefined EC 50 doses of four commonly used anesthetics or saline placebo. We demonstrate that state-related effects are remarkably limited compared with the widespread cortical effects related to drug exposure. In particular, decreased thalamic activity was associated with disconnectedness with all used anesthetics except for S-ketamine.
(Copyright © 2023 Kantonen et al.)
Databáze: MEDLINE
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