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      Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study

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          Abstract

          Objective

          To assess factors associated with long-term neuropsychiatric outcomes, including biomarkers measured after discharge from the intensive care unit.

          Methods

          A prospective cohort study was performed with 65 intensive care unit survivors. The cognitive evaluation was performed through the Mini-Mental State Examination, the symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder was evaluated using the Impact of Event Scale-6. Plasma levels of amyloid-beta (1-42) [Aβ (1-42)], Aβ (1-40), interleukin (IL)-10, IL-6, IL-33, IL-4, IL-5, tumor necrosis factor alpha, C-reactive protein, and brain-derived neurotrophic factor were measured at intensive care unit discharge.

          Results

          Of the variables associated with intensive care, only delirium was independently related to the occurrence of long-term cognitive impairment. In addition, higher levels of IL-10 and IL-6 were associated with cognitive dysfunction. Only IL-6 was independently associated with depression. Mechanical ventilation, IL-33 levels, and C-reactive protein levels were independently associated with anxiety. No variables were independently associated with posttraumatic stress disorder.

          Conclusion

          Cognitive dysfunction, as well as symptoms of depression, anxiety, and posttraumatic stress disorder, are present in patients who survive a critical illness, and some of these outcomes are associated with the levels of inflammatory biomarkers measured at discharge from the intensive care unit.

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          Most cited references54

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          Long-term cognitive impairment after critical illness.

          Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).
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            Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference.

            Millions of patients are discharged from intensive care units annually. These intensive care survivors and their families frequently report a wide range of impairments in their health status which may last for months and years after hospital discharge. To report on a 2-day Society of Critical Care Medicine conference aimed at improving the long-term outcomes after critical illness for patients and their families. Thirty-one invited stakeholders participated in the conference. Stakeholders represented key professional organizations and groups, predominantly from North America, which are involved in the care of intensive care survivors after hospital discharge. Invited experts and Society of Critical Care Medicine members presented a summary of existing data regarding the potential long-term physical, cognitive and mental health problems after intensive care and the results from studies of postintensive care unit interventions to address these problems. Stakeholders provided reactions, perspectives, concerns and strategies aimed at improving care and mitigating these long-term health problems. Three major themes emerged from the conference regarding: (1) raising awareness and education, (2) understanding and addressing barriers to practice, and (3) identifying research gaps and resources. Postintensive care syndrome was agreed upon as the recommended term to describe new or worsening problems in physical, cognitive, or mental health status arising after a critical illness and persisting beyond acute care hospitalization. The term could be applied to either a survivor or family member. Improving care for intensive care survivors and their families requires collaboration between practitioners and researchers in both the inpatient and outpatient settings. Strategies were developed to address the major themes arising from the conference to improve outcomes for survivors and families.
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              Long-term cognitive impairment and functional disability among survivors of severe sepsis.

              Cognitive impairment and functional disability are major determinants of caregiving needs and societal health care costs. Although the incidence of severe sepsis is high and increasing, the magnitude of patients' long-term cognitive and functional limitations after sepsis is unknown. To determine the change in cognitive impairment and physical functioning among patients who survive severe sepsis, controlling for their presepsis functioning. A prospective cohort involving 1194 patients with 1520 hospitalizations for severe sepsis drawn from the Health and Retirement Study, a nationally representative survey of US residents (1998-2006). A total of 9223 respondents had a baseline cognitive and functional assessment and had linked Medicare claims; 516 survived severe sepsis and 4517 survived a nonsepsis hospitalization to at least 1 follow-up survey and are included in the analysis. Personal interviews were conducted with respondents or proxies using validated surveys to assess the presence of cognitive impairment and to determine the number of activities of daily living (ADLs) and instrumental ADLs (IADLs) for which patients needed assistance. Survivors' mean age at hospitalization was 76.9 years. The prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, an odds ratio (OR) of 3.34 (95% confidence interval [CI], 1.53-7.25) in multivariable regression. Likewise, a high rate of new functional limitations was seen following sepsis: in those with no limits before sepsis, a mean 1.57 new limitations (95% CI, 0.99-2.15); and for those with mild to moderate limitations before sepsis, a mean of 1.50 new limitations (95% CI, 0.87-2.12). In contrast, nonsepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment (OR, 1.15; 95% CI, 0.80-1.67; P for difference vs sepsis = .01) and with the development of fewer new limitations (mean among those with no limits before hospitalization, 0.48; 95% CI, 0.39-0.57; P for difference vs sepsis <.001 and mean among those with mild to moderate limits, 0.43; 95% CI, 0.23-0.63; P for difference = .001). The declines in cognitive and physical function persisted for at least 8 years. Severe sepsis in this older population was independently associated with substantial and persistent new cognitive impairment and functional disability among survivors. The magnitude of these new deficits was large, likely resulting in a pivotal downturn in patients' ability to live independently.
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                Author and article information

                Journal
                Crit Care Sci
                Crit Care Sci
                ccsci
                Critical Care Science
                Associação de Medicina Intensiva Brasileira - AMIB
                2965-2774
                Apr-Jun 2023
                Apr-Jun 2023
                : 35
                : 2
                : 147-155
                Affiliations
                [1 ] Laboratory of Translational Biomedicine, Postgraduate Program in Health Sciences, Universidade do Extremo Sul Catarinense - Criciúma (SC), Brazil
                [2 ] Laboratory of Experimental Pathophysiology, Postgraduate Program in Health Sciences, Health Sciences Unit, Universidade do Extremo Sul Catarinense - Criciúma (SC), Brazil
                [3 ] Research Centre, Hospital São José - Criciúma (SC), Brazil
                Author notes
                Corresponding author: Felipe Dal-Pizzol, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105, Zip code: 88801-460 - Criciúma (SC), Brazil, E-mail: fdpizzol@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-0409-2163
                http://orcid.org/0000-0002-7133-3596
                http://orcid.org/0000-0003-0328-753X
                http://orcid.org/0000-0002-7934-5348
                http://orcid.org/0000-0001-6607-5353
                http://orcid.org/0000-0001-8440-1976
                http://orcid.org/0000-0001-6124-2538
                http://orcid.org/0000-0002-1891-1561
                http://orcid.org/0000-0003-3003-8977
                Article
                10.5935/2965-2774.20230422-en
                10406403
                37712803
                e4cfe9fe-4c5f-43b8-a150-b7b3ca833513

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 December 2022
                : 16 March 2023
                Funding
                Funded by: FAPESC/MS-DECIT/CNPq/SES-SC - PPSUS
                Award ID: 2016TR2201
                Funded by: CNPq
                Award ID: 306383/2018-7
                Categories
                Original Article

                critical illness,critical care outcomes,cognitive dysfunction,anxiety,depression,delirium,patient discharge,biomarkers,intensive care units

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