Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry
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 t...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | BJA Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772609622001137 |
| _version_ | 1798004824937070592 |
|---|---|
| author | Aleksi Nummela Lauri Laaksonen Annalotta Scheinin Kaike Kaisti Tero Vahlberg Mikko Neuvonen Katja Valli Antti Revonsuo Markus Perola Mikko Niemi Harry Scheinin Timo Laitio |
| author_facet | Aleksi Nummela Lauri Laaksonen Annalotta Scheinin Kaike Kaisti Tero Vahlberg Mikko Neuvonen Katja Valli Antti Revonsuo Markus Perola Mikko Niemi Harry Scheinin Timo Laitio |
| author_sort | Aleksi Nummela |
| collection | DOAJ |
| description | 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 (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=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. |
| first_indexed | 2024-04-11T12:29:32Z |
| format | Article |
| id | doaj.art-d163803b1d2d4883a888baeba03238a1 |
| institution | Directory Open Access Journal |
| issn | 2772-6096 |
| language | English |
| last_indexed | 2024-04-11T12:29:32Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | BJA Open |
| spelling | doaj.art-d163803b1d2d4883a888baeba03238a12022-12-22T04:23:48ZengElsevierBJA Open2772-60962022-12-014100114Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometryAleksi Nummela0Lauri Laaksonen1Annalotta Scheinin2Kaike Kaisti3Tero Vahlberg4Mikko Neuvonen5Katja Valli6Antti Revonsuo7Markus Perola8Mikko Niemi9Harry Scheinin10Timo Laitio11Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Department of Internal Medicine, Turku University Hospital, Turku, Finland; Corresponding author. Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.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, FinlandTurku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, FinlandTurku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Department of Peri-operative Services, University of Turku and Turku University Hospital, Turku, FinlandDepartment of Clinical Medicine, Biostatistics, Intensive Care and Pain Medicine, University of Turku and Turku University Hospital, Turku, FinlandDepartment of Clinical Pharmacology, University of Helsinki, Helsinki, Finland; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandDepartment 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, SwedenDepartment 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, SwedenDepartment 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, FinlandDepartment 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, FinlandTurku 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, FinlandDepartment of Peri-operative Services, University of Turku and Turku University Hospital, Turku, FinlandBackground: 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 (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=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.http://www.sciencedirect.com/science/article/pii/S2772609622001137bile acidsdexmedetomidinelipidomicsoxylipinspropofolsevoflurane |
| spellingShingle | Aleksi Nummela Lauri Laaksonen Annalotta Scheinin Kaike Kaisti Tero Vahlberg Mikko Neuvonen Katja Valli Antti Revonsuo Markus Perola Mikko Niemi Harry Scheinin Timo Laitio Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry BJA Open bile acids dexmedetomidine lipidomics oxylipins propofol sevoflurane |
| title | Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry |
| title_full | Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry |
| title_fullStr | Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry |
| title_full_unstemmed | Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry |
| title_short | Circulating oxylipin and bile acid profiles of dexmedetomidine, propofol, sevoflurane, and S-ketamine: a randomised controlled trial using tandem mass spectrometry |
| title_sort | circulating oxylipin and bile acid profiles of dexmedetomidine propofol sevoflurane and s ketamine a randomised controlled trial using tandem mass spectrometry |
| topic | bile acids dexmedetomidine lipidomics oxylipins propofol sevoflurane |
| url | http://www.sciencedirect.com/science/article/pii/S2772609622001137 |
| work_keys_str_mv | AT aleksinummela circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT laurilaaksonen circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT annalottascheinin circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT kaikekaisti circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT terovahlberg circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT mikkoneuvonen circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT katjavalli circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT anttirevonsuo circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT markusperola circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT mikkoniemi circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT harryscheinin circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry AT timolaitio circulatingoxylipinandbileacidprofilesofdexmedetomidinepropofolsevofluraneandsketaminearandomisedcontrolledtrialusingtandemmassspectrometry |