• Abiodun M Noah, Dalal Almghairbi, Rachel Evley, and Iain K Moppett.
• Anaesthesia and Critical Care, Academic Unit of Injury, Inflammation and Recovery Science, University of Nottingham, Nottingham, UK.
• Br J Anaesth. 2021 Sep 1; 127 (3): 424-434.

BackgroundPostoperative delirium has eluded attempts to define its complex aetiology and describe specific risk factors. The role of neuroinflammation as a risk factor, determined by measuring blood levels of preoperative 'innate' inflammatory mediator levels, has been investigated. However, results have been conflicting. We conducted a systematic review and meta-analysis of the evidence on associations between preoperative blood levels of inflammatory mediators and postoperative delirium in the older person. Influence of type of surgery was also assessed.MethodsOriginal, low risk of bias studies, published in peer-reviewed journals, which fulfilled the eligibility criteria were included. Seventeen articles fulfilled study criteria. Data extraction, synthesis, and risk of bias analysis were guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and quality in prognostic studies guidelines. Meta-analyses used a random-effects model. Inflammatory mediators included C-reactive protein, interleukin-6, -8, and -10, tumour necrosis factor-α, insulin-like growth factor-1, cortisol, and neopterin. Surgical groups were cardiac, noncardiac, and hip fracture.ResultsHigher preoperative interleukin-6 was associated with postoperative delirium with a standardised mean difference (95% confidence interval) of 0.33 (0.11-0.56) and P=0.003. Higher neopterin was also associated with postoperative delirium.ConclusionsThe association of preoperative blood levels of inflammatory mediators with postoperative delirium may be influenced by the type of surgery and the specific mediator. The potential modulating effect of type of surgery, intrinsic brain vulnerability, and the complex interactions between inflammatory mediators and binding proteins will need to be considered in future studies.Clinical Trial RegistrationCRD42019159471 (PROSPERO).Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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