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      Dexmedetomidine May Reduce IL-6 Level and the Risk of Postoperative Cognitive Dysfunction in Patients After Surgery: A Meta-Analysis

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          Abstract

          Dexmedetomidine (DEX) was widely used in clinical work. However, the effectiveness of DEX on postoperative cognitive dysfunction (POCD) was still need to be confirmed. The aim of this meta-analysis was to explore whether DEX can reduce the incidence of POCD on the first day and seventh postoperative day. The results showed that lower incidence of POCD associated with DEX treatment on the first (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.31-0.54) or seventh postoperative day (OR: 0.53; 95% CI: 0.36-0.77). Mini-Mental State Examination scores on the first (mean difference [MD]: 4.67; 95% CI: 1.72-7.63) and seventh postoperative days (MD: 3.71; 95% CI: 2.51-4.90) were higher in DEX use group than that in physiological saline group. Meanwhile, neuron-specific enolase (NSE; MD: −3.99; 95% CI: −6.20 to −1.78) and interleukin 6 (IL-6) levels (MD: −17.53; 95% CI: −21.51 to −13.54) on the first postoperative day in DEX group were lower than that in the physiological saline group. This meta-analysis suggested that DEX use could reduce the risk of POCD and the reduction in levels of NSE and IL-6 can improve long-term cognitive dysfunction and anti-inflammation.

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          Predictors of cognitive dysfunction after major noncardiac surgery.

          Terri Monk, B Craig Weldon, Cyndi Garvan … (2008)
          The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery. One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18-39 yr), middle-aged (40-59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status. At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P = 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P = 0.02). Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery.
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            Long-term consequences of postoperative cognitive dysfunction.

            Jacob Steinmetz, Karl Christensen, Thomas Lund … (2009)
            Postoperative cognitive dysfunction (POCD) is common in elderly patients after noncardiac surgery, but the consequences are unknown. The authors' aim was to determine the effects of POCD on long-term prognosis. This was an observational study of Danish patients enrolled in two multicenter studies of POCD between November 1994 and October 2000. The cohort was followed up from the date of surgery until August 2007. Cognitive function was assessed by a neuropsychological test battery at three time points: before, at 1 week after, and at 3 months after noncardiac surgery. Data on survival, labor market attachment, and social transfer payments were obtained from administrative databases. The Cox proportional hazards regression model was used to compute relative risk estimates for mortality and disability, and the relative prevalence of time on social transfer payments was assessed by Poisson regression. A total of 701 patients were followed up for a median of 8.5 yr (interquartile range, 5.3-11.4 yr). POCD at 3 months, but not at 1 week, was associated with increased mortality (hazard ratio, 1.63 [95% confidence interval, 1.11-2.38]; P = 0.01, adjusted for sex, age, and cancer). The risk of leaving the labor market prematurely because of disability or voluntary early retirement was higher among patients with 1-week POCD (hazard ratio, 2.26 [1.24-4.12]; P = 0.01). Patients with POCD at 1 week received social transfer payments for a longer proportion of observation time (prevalence ratio, 1.45 [1.03-2.04]; P = 0.03). Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor market prematurely, and dependency on social transfer payments.
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              Resolving postoperative neuroinflammation and cognitive decline.

              Niccolò Terrando, Lars Eriksson, Jae Ryu … (2011)
              Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved. C57BL/6J, Ccr2(RFP/+)Cx3cr1(GFP/+), Ikk(F/F) mice and LysM-Cre/Ikk(F/F) mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood-brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied. Peripheral surgery disrupts the BBB via release of tumor necrosis factor-alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage-specific deletion of Ikappa B kinase (IKK)β, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation-resolving pathway, prevents TNFα-induced NF-κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery. These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline. Copyright © 2011 American Neurological Association.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Dose Response
                Journal ID (iso-abbrev): Dose Response
                Journal ID (publisher-id): DOS
                Journal ID (hwp): spdos
                Title: Dose-Response
                Publisher: SAGE Publications (Sage CA: Los Angeles, CA )
                ISSN (Electronic): 1559-3258
                Publication date (Electronic): 5 February 2020
                Publication date Collection: Jan-Mar 2020
                Volume: 18
                Issue: 1
                Electronic Location Identifier: 1559325820902345
                Affiliations
                [1 ]Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China
                [2 ]Nanjing Medical University, Jiangsu, China
                [3 ]Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, China
                Author notes
                [*]Chao Han, Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, Jiangsu, China. Email: staff940@ 123456yxph.com
                Author information
                https://orcid.org/0000-0001-9105-9021
                Article
                Publisher ID: 10.1177_1559325820902345
                DOI: 10.1177/1559325820902345
                PMC ID: 7003176
                PubMed ID: 32076394
                SO-VID: c9d50a14-e7af-47e3-abfb-9a8c511a4c4b
                Copyright © © The Author(s) 2020
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 20 October 2019
                Date revision received : 11 December 2019
                Date accepted : 19 December 2019
                Categories
                Subject: Review
                Custom metadata
                cover-date January-March 2020
                typesetter ts3

                Keywords: cognition disorders,dexmedetomidine,inflammation,postoperative
                Data availability:
                Keywords: cognition disorders, dexmedetomidine, inflammation, postoperative

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