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      Current Evidence Regarding Biomarkers Used to Aid Postoperative Delirium Diagnosis in the Field of Cardiac Surgery—Review

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          Abstract

          Postoperative cognitive disorders after cardiac surgery may manifest as postoperative delirium (POD) or later as postoperative cognitive dysfunction (POCD). The incidence of POD after cardiac surgery ranges from 16% to 73%. In contrast to POD, POCD is usually diagnosed after the discharge from hospital, with an incidence of 30 to 70% of cases, very often noticed only by close relative or friends, decreasing after six (20–30%) and twelve (15–25%) months after surgery. Perioperative cognitive disorders are associated with adverse short- and long-term effects, including increased morbidity and mortality. Due to the complexity of delirium pathomechanisms and the difficulties in the diagnosis, researchers have not yet found a clear answer to the question of which patient will be at a higher risk of developing delirium. The risk for POD and POCD in older patients with numerous comorbidities like hypertension, diabetes, and previous ischemic stroke is relatively high, and the predisposing cognitive profile for both conditions is important. The aim of this narrative review was to identify and describe biomarkers used in the diagnosis of delirium after cardiac surgery by presenting a search through studies regarding this subject, which have been published during the last ten years. The authors discussed brain-derived biomarkers, inflammation-related biomarkers, neurotransmitter-based biomarkers, and others. Work based on inflammation-related biomarkers, which are characterized by the low cost of implementation and the effectiveness of delirium diagnosis, seems to be the closest to the goal of discovering an inexpensive and effective marker. Currently, the use of a panel of tests, and not a single biomarker, brings us closer to the discovery of a test, or rather a set of tests ideal for the diagnosis of delirium after cardiac surgery.

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          Most cited references119

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          Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

          To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.
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            Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.

            Recognition that inflammation may represent a common mechanism of disease has been extended to include neuropsychiatric disorders including major depression. Patients with major depression have been found to exhibit increased peripheral blood inflammatory biomarkers, including inflammatory cytokines, which have been shown to access the brain and interact with virtually every pathophysiologic domain known to be involved in depression, including neurotransmitter metabolism, neuroendocrine function, and neural plasticity. Indeed, activation of inflammatory pathways within the brain is believed to contribute to a confluence of decreased neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity and loss of glial elements, consistent with neuropathologic findings that characterize depressive disorders. Further instantiating the link between inflammation and depression are data demonstrating that psychosocial stress, a well-known precipitant of mood disorders, is capable of stimulating inflammatory signaling molecules, including nuclear factor kappa B, in part, through activation of sympathetic nervous system outflow pathways. Interestingly, depressed patients with increased inflammatory biomarkers have been found to be more likely to exhibit treatment resistance, and in several studies, antidepressant therapy has been associated with decreased inflammatory responses. Finally, preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication. Translational implications of these findings include the unique opportunity to identify relevant patient populations, apply immune-targeted therapies, and monitor therapeutic efficacy at the level of the immune system in addition to behavior.
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              Predictors of cognitive dysfunction after major noncardiac surgery.

              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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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                24 September 2020
                October 2020
                : 56
                : 10
                : 493
                Affiliations
                [1 ]Department of Cardiac Surgery, Ceynowa Hospital, 84-200 Wejherowo, Poland; lek.majewski.pawel@ 123456gmail.com
                [2 ]Department of Anesthesiology and Intensive Therapy, Regional Specialist Hospital, 72-300 Gryfice, Poland
                [3 ]Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland; karolinakaim@ 123456hotmail.com (K.K.); zukowski@ 123456pum.edu.pl (M.Ż.); katarzyna.kotfis@ 123456pum.edu.pl (K.K.)
                [4 ]Student Science Club, Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland; igor.karolak@ 123456gmail.com
                Author notes
                [* ]Correspondence: malgorzata.zegan@ 123456pum.edu.pl ; Tel./Fax: +48-91-466-11-44
                Author information
                https://orcid.org/0000-0001-8430-1369
                Article
                medicina-56-00493
                10.3390/medicina56100493
                7598630
                32987655
                d1b0c356-31f5-463a-a295-2faf69b54fea
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 August 2020
                : 22 September 2020
                Categories
                Review

                postoperative delirium,cardiac surgery,biomarkers,perioperative cognitive disorders,neuroinflammation

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