Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry.

Autor:	Nummela A; Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.; Department of Internal Medicine, Turku University Hospital, Turku, Finland., Laaksonen L; Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, Finland., Scheinin A; Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, Finland., Kaisti K; Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, Finland., Vahlberg T; Department of Clinical Medicine, Biostatistics, Intensive Care and Pain Medicine, University of Turku and Turku University Hospital, Turku, Finland., Neuvonen M; Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Valli K; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, Finland.; Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turku, Finland.; Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde, Sweden., Revonsuo A; Department of Psychology and Speech-Language Pathology, and Turku Brain and Mind Center, University of Turku, Turku, Finland.; Department of Cognitive Neuroscience and Philosophy, School of Bioscience, University of Skövde, Skövde, Sweden., Perola M; Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Finnish Institute for Health and Welfare, Helsinki, Finland., Niemi M; Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Scheinin H; Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, Finland.; Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland., Laitio T; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, Finland.
Jazyk:	angličtina
Zdroj:	BJA open [BJA Open] 2022 Dec 12; Vol. 4, pp. 100114. Date of Electronic Publication: 2022 Dec 12 (Print Publication: 2022).
DOI:	10.1016/j.bjao.2022.100114
Abstrakt:	Background: This exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection. Methods: In this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects ( n =160) received equipotent doses (EC 50 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 =40), S-ketamine (0.75 μg ml -1 ; n =20), or placebo ( n =20). Blood samples for tandem mass spectrometry were obtained at baseline, after study drug administration at 60 and 130 min from baseline; 40 metabolites were analysed. Results: Statistically significant changes vs placebo were observed in 62.5%, 12.5%, 5.0%, and 2.5% of analytes in dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively. Data are presented as standard deviation score, 95% confidence interval, and P -value. Dexmedetomidine induced wide-ranging decreases in oxylipins and bile acids. Amongst others, 9,10-dihydroxyoctadecenoic acid (DiHOME) -1.19 (-1.6; -0.78), P <0.001 and 12,13-DiHOME -1.22 (-1.66; -0.77), P <0.001 were affected. Propofol elevated 9,10-DiHOME 2.29 (1.62; 2.96), P <0.001 and 12,13-DiHOME 2.13 (1.42; 2.84), P <0.001. Analytes were mostly unaffected by S-ketamine. Sevoflurane decreased tauroursodeoxycholic acid (TUDCA) -2.7 (-3.84; -1.55), P =0.015. Conclusions: Dexmedetomidine-induced oxylipin alterations may be connected to pathways associated with organ protection. In contrast to dexmedetomidine, propofol emulsion elevated DiHOMEs, oxylipins associated with acute respiratory distress syndrome, and mitochondrial dysfunction in high concentrations. Further research is needed to establish the behaviour of DIHOMEs during prolonged propofol/dexmedetomidine infusions and to verify the sevoflurane-induced reduction in TUDCA, a suggested neuroprotective agent. Clinical Trial Registration: NCT02624401. (© 2022 The Author(s).)
Databáze:	MEDLINE
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