The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and Their Associations with the Incidence of Postoperative Delirium

Mijin Jung; Xiaobei Pan; Emma L. Cunningham; Anthony P. Passmore; Bernadette McGuinness; Daniel F. McAuley; David Beverland; Seamus O’brien; Tim Mawhinney; Jonathan M. Schott; Henrik Zetterberg; Brian D. Green

doi:10.3390/metabo12070616

The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and Their Associations with the Incidence of Postoperative Delirium

Mijin Jung, Xiaobei Pan, Emma L. Cunningham, Anthony P. Passmore, Bernadette McGuinness, Daniel F. McAuley, David Beverland, Seamus O’brien, Tim Mawhinney, Jonathan M. Schott, Henrik Zetterberg, Brian D. Green^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre-and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation.

Original language	English
Article number	616
Journal	Metabolites
Volume	12
Issue number	7
DOIs	https://doi.org/10.3390/metabo12070616
Publication status	Published - 01 Jul 2022

Bibliographical note

Funding Information:
Funding: This research was funded by an Alzheimer’s Research UK Network Centre Pump Priming Grant (2016) awarded to B.D.G, E.L.C., A.P.P., B.M and D.F.M. B.D.G. and E.L.C. are also in receipt of funding from the National Institutes of Health (NIH) under the program ‘Clarifying the Relationship between Delirium and Alzheimer’s Disease and Related Dementias (R21/R33)’ (R21AG067083-01). ELC is in receipt of a Fellowship from Alzheimer’s Research UK (ARUK-CRF2018C-001). The wider cohort study was funded by: Siew Keok Chin Scholarship (Philanthropic Funding). Belfast Arthroplasty Research Trust (now TORCNI) and Belfast Trust Charitable Funds.

Funding Information:
This research was funded by an Alzheimer’s Research UK Network Centre Pump Priming Grant (2016) awarded to B.D.G, E.L.C., A.P.P., B.M and D.F.M. B.D.G. and E.L.C. are also in receipt of funding from the National Institutes of Health (NIH) under the program ‘Clarifying the Relationship between Delirium and Alzheimer’s Disease and Related Dementias (R21/R33)’ (R21AG067083-01). ELC is in receipt of a Fellowship from Alzheimer’s Research UK (ARUK-CRF2018C-001). The wider cohort study was funded by: Siew Keok Chin Scholarship (Philanthropic Funding). Belfast Arthroplasty Research Trust (now TORCNI) and Belfast Trust Charitable Funds. Many people contributed to the successful completion of this study. In particular, we gratefully acknowledge the support of the anesthetists, surgeons, theater, and ward staff of Musgrave Park Hospital; John Conlon of the Centre for Experimental Medicine, QUB for technical laboratory support; Chris Patterson and Chris Cardwell of the Centre for Public Health for statistical support; Rebecca Cairns and Lauren Anderson for data inputting; Hazel Johnston and Eilish Armstrong for neuropsychology training. Belfast Arthroplasty Research Trust. Belfast Trust Charitable Funds.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

ornithine
orthopedic surgery
polyamine
postoperative delirium
spermine

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/metabo12070616Licence: CC BY

The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and their Associations with the Incidence of Postoperative Delirium
Copyright 2022 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.09 MBLicence: CC BY

Metabolomic studies of human plasma and cerebrospinal fluid from an observational cohort study of orthopaedic patients investigating post-operative delirium
Jung, M. (Author), Cunningham, E. (Supervisor) & Green, B. (Supervisor), Jul 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

Jung, M., Pan, X., Cunningham, E. L., Passmore, A. P., McGuinness, B., McAuley, D. F., Beverland, D., O’brien, S., Mawhinney, T., Schott, J. M., Zetterberg, H., & Green, B. D. (2022). The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and Their Associations with the Incidence of Postoperative Delirium. Metabolites, 12(7), Article 616. https://doi.org/10.3390/metabo12070616

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abstract = "The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre-and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation.",

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note = "Funding Information: Funding: This research was funded by an Alzheimer{\textquoteright}s Research UK Network Centre Pump Priming Grant (2016) awarded to B.D.G, E.L.C., A.P.P., B.M and D.F.M. B.D.G. and E.L.C. are also in receipt of funding from the National Institutes of Health (NIH) under the program {\textquoteleft}Clarifying the Relationship between Delirium and Alzheimer{\textquoteright}s Disease and Related Dementias (R21/R33){\textquoteright} (R21AG067083-01). ELC is in receipt of a Fellowship from Alzheimer{\textquoteright}s Research UK (ARUK-CRF2018C-001). The wider cohort study was funded by: Siew Keok Chin Scholarship (Philanthropic Funding). Belfast Arthroplasty Research Trust (now TORCNI) and Belfast Trust Charitable Funds. Funding Information: This research was funded by an Alzheimer{\textquoteright}s Research UK Network Centre Pump Priming Grant (2016) awarded to B.D.G, E.L.C., A.P.P., B.M and D.F.M. B.D.G. and E.L.C. are also in receipt of funding from the National Institutes of Health (NIH) under the program {\textquoteleft}Clarifying the Relationship between Delirium and Alzheimer{\textquoteright}s Disease and Related Dementias (R21/R33){\textquoteright} (R21AG067083-01). ELC is in receipt of a Fellowship from Alzheimer{\textquoteright}s Research UK (ARUK-CRF2018C-001). The wider cohort study was funded by: Siew Keok Chin Scholarship (Philanthropic Funding). Belfast Arthroplasty Research Trust (now TORCNI) and Belfast Trust Charitable Funds. Many people contributed to the successful completion of this study. In particular, we gratefully acknowledge the support of the anesthetists, surgeons, theater, and ward staff of Musgrave Park Hospital; John Conlon of the Centre for Experimental Medicine, QUB for technical laboratory support; Chris Patterson and Chris Cardwell of the Centre for Public Health for statistical support; Rebecca Cairns and Lauren Anderson for data inputting; Hazel Johnston and Eilish Armstrong for neuropsychology training. Belfast Arthroplasty Research Trust. Belfast Trust Charitable Funds. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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Jung, M, Pan, X , Cunningham, EL, Passmore, AP, McGuinness, B , McAuley, DF, Beverland, D, O’brien, S, Mawhinney, T, Schott, JM, Zetterberg, H & Green, BD 2022, 'The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and Their Associations with the Incidence of Postoperative Delirium', Metabolites, vol. 12, no. 7, 616. https://doi.org/10.3390/metabo12070616

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AU - Passmore, Anthony P.

AU - McGuinness, Bernadette

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AU - O’brien, Seamus

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AU - Schott, Jonathan M.

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N2 - The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre-and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation.

AB - The mechanisms underlying the occurrence of postoperative delirium development are unclear and measurement of plasma metabolites may improve understanding of its causes. Participants (n = 54) matched for age and gender were sampled from an observational cohort study investigating postoperative delirium. Participants were ≥65 years without a diagnosis of dementia and presented for primary elective hip or knee arthroplasty. Plasma samples collected pre-and postoperatively were grouped as either control (n = 26, aged: 75.8 ± 5.2) or delirium (n = 28, aged: 76.2 ± 5.7). Widespread changes in plasma metabolite levels occurred following surgery. The only metabolites significantly differing between corresponding control and delirium samples were ornithine and spermine. In delirium cases, ornithine was 17.6% higher preoperatively, and spermine was 12.0% higher postoperatively. Changes were not associated with various perioperative factors. In binary logistic regression modeling, these two metabolites did not confer a significantly increased risk of delirium. These findings support the hypothesis that disturbed polyamine metabolism is an underlying factor in delirium that warrants further investigation.

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The Influence of Orthopedic Surgery on Circulating Metabolite Levels, and Their Associations with the Incidence of Postoperative Delirium

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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Student theses

Metabolomic studies of human plasma and cerebrospinal fluid from an observational cohort study of orthopaedic patients investigating post-operative delirium

Cite this