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      Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies

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          Abstract

          Segregation of published research Patients with an acute illness frequently acquire an acute, global disturbance in cognition variably referred to as delirium, encephalopathy, acute confusional state, acute brain dysfunction, acute brain failure, and altered mental status [1]. Although these different terms may have been perceived as distinct clinical entities [2], evidence to support such distinctions is lacking. Acute disturbances in cognition are particularly prevalent among individuals admitted to the intensive-care unit [3]. These disturbances have been linked to predisposing and triggering factors [4], and have been independently associated with adverse short- and long-term outcomes, including higher mortality and chronic cognitive impairment [5, 6]. While progress has been made in the detection of this problem, research is needed to identify effective interventions for prevention and treatment. A rational approach to nomenclature represents an important basis to enable such advances. A definition of delirium is provided in the 5th version of the Diagnostic and Statistical Manual (DSM-5) of the American Psychiatric Association [7] and in the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) [8]. Encephalopathy is a generic term that has been used to describe a global disturbance in brain function. However, the terms acute encephalopathy, acute confusional state, acute brain dysfunction, acute brain failure, and altered mental status lack uniform definitions and are not present in formal diagnostic systems. Our analysis focuses on delirium and acute encephalopathy, as these are the most frequently used terms. We hypothesized that published research on delirium and encephalopathy is highly segregated, and that this segregation would be linked to the clinical discipline of investigators. We conducted a systematic search (see details in the Supplementary Materials) which led to three findings. First, journals on clinical neurology, neurosciences, or general or internal medicine published significantly more articles with ‘encephalopathy’ in the title, whereas journals associated with geriatrics, gerontology, psychiatry, psychology, intensive-care medicine, or anaesthesiology published significantly more delirium-titled articles (P < 0.001). Second, articles with ‘encephalopathy’ in the title rarely (1%, n = 1 of 100 randomly selected articles) mentioned ‘delirium’ in the text, and conversely articles with ‘delirium’ in the title used the word ‘encephalopathy’ in not more than 2% of publications (n = 2 out of 100). Third, almost all citations in the delirium and encephalopathy literature (98.77%, n = 36,729) were between papers with matching terms in the titles (i.e., delirium-titled articles citing other delirium-titled articles and encephalopathy-titled articles citing other encephalopathy-titled articles). Only a small proportion (0.53%, n = 197) of citations were from encephalopathy-titled articles citing delirium-titled papers, or from delirium-titled articles referencing papers with the term ‘encephalopathy’ in the title (0.70%; n = 259). It should, however, be noted that almost all articles on ‘acute encephalopathy’ use the term ‘encephalopathy’ in isolation; therefore, it is possible that segregation of the literature could be driven, in part, by the inclusion of articles on chronic encephalopathy. These findings confirmed our hypothesis on the existence of segregated literatures, and suggest conceptual or semantic disparities across different medical disciplines. We believe that the lack of a uniform nomenclature represents a significant barrier to scientific progress and has implications for clinical management that might influence patient outcome. For example, use of the term ‘delirium’ may trigger specific management, whereas ‘septic encephalopathy’ may overlook mechanisms other than sepsis, such as metabolic alterations or drug side-effects. Additional factors, such as differences in billing and reimbursement between patients diagnosed with encephalopathy (versus delirium), may be a factor driving the selective use of terms in some countries, such as the USA. Consensus recommendations on nomenclature To generate expert consensus, we convened an international, interdisciplinary panel of leading experts with expertise in intensive-care medicine, neurology, geriatrics, rehabilitation medicine, pharmacy, anaesthesiology, and psychiatry. Panellists were tasked with generating recommendations on the nomenclature of delirium, acute encephalopathy, and related terms. The definitions were created, refined, and voted on using the modified Delphi method (see Supplementary Materials). The panel recommends the term acute encephalopathy to describe a rapidly developing (in less than 4 weeks) pathobiological brain process which is expressed clinically as either subsyndromal delirium, delirium or coma and may have additional features, such as seizures or extrapyramidal signs (Box). The term acute encephalopathy is not recommended as a descriptor of clinical features that can be observed at the bedside. Instead, the panel recommends the term subsyndromal delirium for acute cognitive changes that are compatible with delirium, but do not fulfil all DSM-5 delirium criteria, delirium for a clinical state defined according to the criteria of the DSM-5 [6], and coma for a state of severely depressed responsiveness defined using diagnostic systems such as the Glasgow Coma Score (GCS) or the Full Outline of UnResponsiveness (FOUR) score (Box) [9, 10]. The panel further recommends against use of the terms acute confusional state, acute brain dysfunction, acute brain failure, or altered mental status in clinical practice or research (Box). Although these terms might have relevance for educational purposes, the panel felt that they lacked face or construct validity. The recommendations in this manuscript have been endorsed by ten key professional societies (see Supplementary Materials), and this terminology is congruent with the recent recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery [11]. Delayed neurocognitive recovery after anaesthesia and surgery can be regarded as consequence of prolonged postoperative acute encephalopathy. In conclusion, current literature on delirium and acute encephalopathy is highly segregated, presenting an obstacle for clinical care and research. We recommend a consensus-based, pragmatic nomenclature which we expect will establish a foundation for advances in the field. Following dissemination of these recommendations, future research should evaluate the impact of this revised nomenclature on clinical practice and research. Box: Recommendations for the nomenclature of delirium, acute encephalopathy, and related terms 1. The term acute encephalopathy refers to a rapidly developing (over less than 4 weeks, but usually within hours to a few days) pathobiological process in the brain. This is a preferred term 2. Acute encephalopathy can lead to a clinical presentation of subsyndromal delirium, delirium, or in case of a severely decreased level of consciousness, coma; all representing a change from baseline cognitive status 3. The term delirium refers to a clinical state characterized by a combination of features defined by diagnostic systems such as the DSM-5. Delirium according to the DSM-5 is defined if criterium A-E are fulfilled: A. Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment). B. The disturbance develops over a short period of time (usually hours to a few days) represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of the day. C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception). D. The disturbances in criteria A and C are not explained by another pre-existing, established, or evolving neurocognitive disorder, and do not occur in the context of a severely reduced level of arousal, such as coma. E. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiologic consequence of another medical condition, substance intoxication or withdrawal (i.e. because of a drug of abuse medication), or exposure to a toxin, or is because of multiple etiologies. This is a preferred term 4. The term coma refers to a clinical state of severely depressed responsiveness defined by diagnostic systems such as the GCS or FOUR score. This is a preferred term 5. The term acute confusional state should not be used in addition to the terms delirium and acute encephalopathy 6. The term acute brain dysfunction should not be used in addition to the terms delirium and acute encephalopathy 7. The term acute brain failure should not be used in addition to the terms delirium and acute encephalopathy 8. The term altered mental status is not synonymous with delirium and should not be used DSM-5 means the Diagnostic and Statistical Manual (DSM-5) of the American Psychiatric Association. GCS refers to Glasgow Coma Score; the FOUR score means the Full Outline of UnResponsiveness score. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary file1 (TIF 129 kb) Supplementary file2 (TIF 471 kb) Supplementary file3 (DOCX 44 kb)

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          Most cited references 5

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          Delirium in Hospitalized Older Adults

          A 75-year-old man is admitted for scheduled major abdominal surgery. He is functionally independent, with mild forgetfulness. His intraoperative course is uneventful, but on postoperative day 2, severe confusion and agitation develop. What is going on? How would you manage this patient’s care? Could his condition have been prevented?
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            TEMPORARY REMOVAL: Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery—2018

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              Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.

              Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific "confusion" regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma, delirium, delirio, delirium tremens, délire, confusion mentale, delir, delier, Durchgangs-Syndrom, acute verwardheid, intensiv-psykose, IVA-psykos, IVA-syndrom, akutt konfusion/forvirring. Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers.
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                Author and article information

                Contributors
                a.slooter-3@umcutrecht.nl
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                13 February 2020
                13 February 2020
                2020
                : 46
                : 5
                : 1020-1022
                Affiliations
                [1 ]GRID grid.5477.1, ISNI 0000000120346234, Department of Intensive Care Medicine and UMC Utrecht Brain Center, University Medical Center Utrecht, , Utrecht University, ; Room F06.149, PO Box 85500, 3508 GA Utrecht, The Netherlands
                [2 ]GRID grid.5477.1, ISNI 0000000120346234, Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, Department of Pediatric Neurology, and UMC Utrecht Brain Center, University Medical Center Utrecht, , Utrecht University, ; Utrecht, The Netherlands
                [3 ]GRID grid.261112.7, ISNI 0000 0001 2173 3359, School of Pharmacy, , Northeastern University, ; Boston, MA USA
                [4 ]GRID grid.67033.31, ISNI 0000 0000 8934 4045, Division of Pulmonary, Critical Care and Sleep Medicine, , Tufts Medical Center, ; Boston, MA USA
                [5 ]GRID grid.21613.37, ISNI 0000 0004 1936 9609, Department of Surgery, Max Rady College of Medicine, , University of Manitoba, ; Winnipeg, MB Canada
                [6 ]GRID grid.416356.3, ISNI 0000 0000 8791 8068, Cardiac Sciences Program, , St. Boniface Hospital, ; Winnipeg, MB Canada
                [7 ]GRID grid.16753.36, ISNI 0000 0001 2299 3507, Department of Neurology, , Northwestern University Feinberg School of Medicine, ; Chicago, IL USA
                [8 ]GRID grid.239585.0, ISNI 0000 0001 2285 2675, Department of Neurology and Neurosurgery, , Columbia University Medical Center, ; New York City, NY USA
                [9 ]GRID grid.412807.8, ISNI 0000 0004 1936 9916, Division of Allergy, Pulmonary, and Critical Care Medicine, Center for Quality Aging, Center for Health Services Research, Department of Medicine, , Vanderbilt University Medical Center, ; Nashville, TN USA
                [10 ]GRID grid.412807.8, ISNI 0000 0004 1936 9916, Geriatric Research, Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, , Vanderbilt University Medical Center, ; Nashville, TN USA
                [11 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Neurology, , Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                [12 ]GRID grid.7637.5, ISNI 0000000417571846, Department of Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital, , University of Brescia, ; Brescia, Italy
                [13 ]Department of Rehabilitation, Ancelle Hospital, Cremona, Italy
                [14 ]GRID grid.418194.1, ISNI 0000 0004 1757 1678, Geriatric Research Group, ; Brescia, Italy
                [15 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Psychiatry and Behavioral Sciences, , Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                [16 ]GRID grid.10992.33, ISNI 0000 0001 2188 0914, Unité Neuropathologie Expérimentale, Département Infection Et Épidémiologie, Institut Pasteur, and Service D’Anesthésie-Réanimation, Hôpital Sainte-Anne, , Université Paris-Descartes, ; Paris, France
                [17 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Edinburgh Delirium Research Group, Geriatric Medicine, and Centre for Cognitive Ageing and Cognitive Epidemiology, , University of Edinburgh, ; Edinburgh, UK
                [18 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Departments of Anesthesiology, Critical Care Medicine, Neurology and Neurosurgery, , Johns Hopkins University School of Medicine, ; Baltimore, MD USA
                Article
                5907
                10.1007/s00134-019-05907-4
                7210231
                32055887
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

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                Emergency medicine & Trauma

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