TY - JOUR
T1 - Human plasma biomarker responses to inhalational general anaesthesia without surgery
AU - Deiner, Stacie
AU - Baxter, Mark G.
AU - Mincer, Joshua S.
AU - Sano, Mary
AU - Hall, James
AU - Mohammed, Ismail
AU - O'Bryant, Sid
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Eckenhoff, Roderic
N1 - Funding Information:
The authors disclose the following relationships, none related to the work presented in this paper: KB has served as a consultant or at advisory boards for Alector, Biogen, Cognition Therapeutics (CogRx), Lilly, MagQu, Novartis, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg, Sweden, a GU Ventures-based platform company at the University of Gothenburg. HZ has served at scientific advisory boards for Roche Diagnostics, Wave, Samumed, and CogRx; has given lectures in symposia sponsored by Biogen and AlzeCure; and is a co-founder of Brain Biomarker Solutions. SO has received funding from the National Institute on Aging , Michael J. Fox Foundation , and Alzheimer's Association ; has multiple patents pending on precision medicine for neurodegenerative diseases; is the founding scientist for Cx Precision Medicine; and has served as a consultant to Roche Diagnostics. SD has served as a consultant for Merck and Covidien, received product support from Covidien, Medtronic, Boulder, CO, USA, R01AG046634 and CASMED (processed EEG and oximetry monitors and sensors), and is an expert witness for legal affairs. The other authors have no conflicts to declare.
Funding Information:
The authors disclose the following relationships, none related to the work presented in this paper: KB has served as a consultant or at advisory boards for Alector, Biogen, Cognition Therapeutics (CogRx), Lilly, MagQu, Novartis, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg, Sweden, a GU Ventures-based platform company at the University of Gothenburg. HZ has served at scientific advisory boards for Roche Diagnostics, Wave, Samumed, and CogRx; has given lectures in symposia sponsored by Biogen and AlzeCure; and is a co-founder of Brain Biomarker Solutions. SO has received funding from the National Institute on Aging, Michael J. Fox Foundation, and Alzheimer's Association; has multiple patents pending on precision medicine for neurodegenerative diseases; is the founding scientist for Cx Precision Medicine; and has served as a consultant to Roche Diagnostics. SD has served as a consultant for Merck and Covidien, received product support from Covidien, Medtronic, Boulder, CO, USA, R01AG046634 and CASMED (processed EEG and oximetry monitors and sensors), and is an expert witness for legal affairs. The other authors have no conflicts to declare.US National Institutes of Health (grant R01AG046634).
Publisher Copyright:
© 2020 British Journal of Anaesthesia
PY - 2020/9
Y1 - 2020/9
N2 - Background: Postoperative neurocognitive disorders may arise in part from adverse effects of general anaesthetics on the CNS, especially in older patients or individuals otherwise vulnerable to neurotoxicity because of systemic disease or the presence of pre-existing neuropathology. Previous studies have documented cytokine and injury biomarker responses to surgical procedures that included general anaesthesia, but it is not clear to what degree anaesthetics contribute to these responses. Methods: We performed a prospective cohort study of 59 healthy volunteers aged 40–80 yr who did not undergo surgery. Plasma markers of neurological injury and inflammation were measured immediately before and 5 h after induction of general anaesthesia with 1 minimum alveolar concentration of sevoflurane. Biomarkers included interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), C-reactive protein (CRP), and neural injury (tau, neurofilament light [NF-L], and glial fibrillary acidic protein [GFAP]). Results: Baseline biomarkers were in the normal range, although NF-L and GFAP were elevated as a function of age. At 5 h after induction of anaesthesia, plasma tau, NF-L, and GFAP were significantly decreased relative to baseline. Plasma IL-6 was significantly increased after anaesthesia, but by a biologically insignificant degree (<1 pg ml−1); plasma TNF-α and CRP were unchanged. Conclusions: Sevoflurane general anaesthesia without surgery, even in older adults, did not provoke an inflammatory state or neuronal injury at a concentration that is detectable by an acute elevation of measured plasma biomarkers in the early hours after exposure. Clinical trial registration: NCT02275026.
AB - Background: Postoperative neurocognitive disorders may arise in part from adverse effects of general anaesthetics on the CNS, especially in older patients or individuals otherwise vulnerable to neurotoxicity because of systemic disease or the presence of pre-existing neuropathology. Previous studies have documented cytokine and injury biomarker responses to surgical procedures that included general anaesthesia, but it is not clear to what degree anaesthetics contribute to these responses. Methods: We performed a prospective cohort study of 59 healthy volunteers aged 40–80 yr who did not undergo surgery. Plasma markers of neurological injury and inflammation were measured immediately before and 5 h after induction of general anaesthesia with 1 minimum alveolar concentration of sevoflurane. Biomarkers included interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), C-reactive protein (CRP), and neural injury (tau, neurofilament light [NF-L], and glial fibrillary acidic protein [GFAP]). Results: Baseline biomarkers were in the normal range, although NF-L and GFAP were elevated as a function of age. At 5 h after induction of anaesthesia, plasma tau, NF-L, and GFAP were significantly decreased relative to baseline. Plasma IL-6 was significantly increased after anaesthesia, but by a biologically insignificant degree (<1 pg ml−1); plasma TNF-α and CRP were unchanged. Conclusions: Sevoflurane general anaesthesia without surgery, even in older adults, did not provoke an inflammatory state or neuronal injury at a concentration that is detectable by an acute elevation of measured plasma biomarkers in the early hours after exposure. Clinical trial registration: NCT02275026.
KW - biomarkers
KW - cognitive decline
KW - cytokine
KW - general anaesthetic
KW - neurocognitive disorders
KW - neurofilament
KW - perioperative
KW - tumour necrosis factor alpha
UR - http://www.scopus.com/inward/record.url?scp=85086359191&partnerID=8YFLogxK
U2 - 10.1016/j.bja.2020.04.085
DO - 10.1016/j.bja.2020.04.085
M3 - Article
C2 - 32536445
AN - SCOPUS:85086359191
SN - 0007-0912
VL - 125
SP - 282
EP - 290
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 3
ER -