• Daniel Villalobos, Melody Reese, WrightMary CooterMCDepartment of Anaesthesiology, Duke University Medical Centre, Durham, NC, USA., Megan Wong, Ayesha Syed, John Park, Ashley Hall, Jeffrey N Browndyke, Katherine T Martucci, Michael J Devinney, Leah Acker, Eugene W Moretti, Leonard Talbot, Brian Colin, Brian Ohlendorf, Teresa Waligorska, Leslie M Shaw, Heather E Whitson, Harvey J Cohen, Joseph P Mathew, and Miles Berger.
• Duke University School of Medicine, Durham, NC, USA.
• Br J Anaesth. 2023 Aug 1; 131 (2): 328337328-337.

BackgroundAnimal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans.MethodsThis was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively.ResultsThere were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aβ), tau, or phospho-tau181p levels, or on the tau/Aβ or p-tau181p/Aβ ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses.ConclusionsIntraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults.Clinical Trial RegistrationNCT01993836.Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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