• Aleksi J Nummela, Lauri T Laaksonen, Timo T Laitio, Roosa E Kallionpää, Jaakko W Långsjö, Joonas M Scheinin, Tero J Vahlberg, Harri T Koskela, Viljami Aittomäki, Katja J Valli, Antti Revonsuo, Mikko Niemi, Markus Perola, and Harry Scheinin.
• From the Department of Peri-operative Services, Intensive Care and Pain Medicine, Turku University Hospital (AJN, LTL, TTL, REK, JMS, KJV, HS), Department of Internal Medicine, Turku University Hospital, Turku (AJN), Turku PET Centre, University of Turku and Turku University Hospital (LTL, HS), Department of Psychology and Speech-Language Pathology and Turku Brain and Mind Center, University of Turku, Turku (REK, KJV, AR), Department of Intensive Care, Tampere University Hospital, Tampere (JWL), Department of Clinical Medicine, Biostatistics, University of Turku and Turku University Hospital, Turku (TJV), Nightingale Health Ltd, Helsinki, Finland (HTK, VA), Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde, Sweden (KJV, AR), Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital (MN), Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki (MN), Finnish Institute for Health and Welfare (MP), Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki (MP), and Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland (HS).
• Eur J Anaesthesiol. 2022 Jun 1; 39 (6): 521-532.

BackgroundPharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown.ObjectiveWe aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile.DesignRandomised, open-label, controlled, parallel group, phase IV clinical drug trial.SettingThe study was conducted at Turku PET Centre, University of Turku, Finland, 2016 to 2017.ParticipantsOne hundred and sixty healthy male volunteers were recruited. The metabolomic data of 159 were evaluable.InterventionsVolunteers were randomised to receive a 1-h exposure to equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n  = 40), propofol (1.7 μg ml-1; n  = 40), sevoflurane (0.9% end-tidal; n  = 39), S-ketamine (0.75 μg ml-1; n  = 20) or placebo (n = 20).Main Outcome MeasuresMetabolite subgroups of apolipoproteins and lipoproteins, cholesterol, glycerides and phospholipids, fatty acids, glycolysis, amino acids, ketone bodies, creatinine and albumin and the inflammatory marker GlycA, were analysed with nuclear magnetic resonance spectroscopy from arterial blood samples collected at baseline, after anaesthetic administration and 70 min post-anaesthesia.ResultsAll metabolite subgroups were affected. Statistically significant changes vs. placebo were observed in 11.0, 41.3, 0.65 and 3.9% of the 155 analytes in the dexmedetomidine, propofol, sevoflurane and S-ketamine groups, respectively. Dexmedetomidine increased glucose, decreased ketone bodies and affected lipoproteins and apolipoproteins. Propofol altered lipoproteins, fatty acids, glycerides and phospholipids and slightly increased inflammatory marker glycoprotein acetylation. Sevoflurane was relatively inert. S-ketamine increased glucose and lactate, whereasbranched chain amino acids and tyrosine decreased.ConclusionA 1-h exposure to moderate doses of routinely used anaesthetics led to significant and characteristic alterations in the metabolic profile. Dexmedetomidine-induced alterations mirror a2-adrenoceptor agonism. Propofol emulsion altered the lipid profile. The inertness of sevoflurane might prove useful in vulnerable patients. S-ketamine induced amino acid alterations might be linked to its suggested antidepressive properties.Trial RegistrationClinicalTrials.gov identifier: NCT02624401.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology and Intensive Care.

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