Timothy D Girard1, Jennifer L Thompson2, Pratik P Pandharipande3, Nathan E Brummel4, James C Jackson5, Mayur B Patel6, Christopher G Hughes3, Rameela Chandrasekhar2, Brenda T Pun7, Leanne M Boehm8, Mark R Elstad9, Richard B Goodman10, Gordon R Bernard11, Robert S Dittus12, E W Ely13. 1. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Clinical Research, Investigation, and Systems Modeling of Acute illness (CRISMA) Center in the Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: timothy.girard@pitt.edu. 2. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA. 3. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Anesthesia Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. 4. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Quality Aging, Vanderbilt University School of Medicine, Nashville, TN, USA. 5. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA; Research Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. 6. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Trauma and Surgical Critical Care, Department of Surgery, Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, USA; Surgical Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. 7. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 8. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Vanderbilt University School of Nursing, Nashville, TN, USA. 9. Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine in the Department of Internal Medicine at the University of Utah School of Medicine, Salt Lake City, UT, USA; George E Wahlen Department of Veterans Affairs Medical Center, VA Salt Lake City Health Care System, Salt Lake City, UT, USA. 10. Division of Pulmonary, Critical Care, and Sleep Medicine in the Department of Internal Medicine at the University of Washington School of Medicine, Seattle, WA, USA; Department of Veterans Affairs Medical Center, Seattle Division, VA Puget Sound Health Care System, Seattle, WA, USA. 11. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA. 12. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of General Internal Medicine and Public Health in the Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Quality Aging, Vanderbilt University School of Medicine, Nashville, TN, USA; Geriatric Research, Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. 13. ICU Delirium and Cognitive Impairment Study Group at the Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Quality Aging, Vanderbilt University School of Medicine, Nashville, TN, USA; Geriatric Research, Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA.
Abstract
BACKGROUND: Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment. METHODS: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders. FINDINGS: Between March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01). INTERPRETATION: Our findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation. FUNDING: National Institutes of Health and the Department of Veterans Affairs.
BACKGROUND:Delirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment. METHODS: In this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders. FINDINGS: Between March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01). INTERPRETATION: Our findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation. FUNDING: National Institutes of Health and the Department of Veterans Affairs.
Authors: M Dietrich; C J Reuß; C Beynon; A Hecker; C Jungk; D Michalski; C Nusshag; K Schmidt; M A Weigand; M Bernhard; T Brenner Journal: Anaesthesist Date: 2020-01 Impact factor: 1.041
Authors: Stuti J Jaiswal; Anuja D Vyas; Andrew J Heisel; Haritha Ackula; Ashna Aggarwal; Nick H Kim; Kim M Kerr; Michael Madani; Victor Pretorius; William R Auger; Timothy M Fernandes; Atul Malhotra; Robert L Owens Journal: Crit Care Med Date: 2019-12 Impact factor: 7.598
Authors: Heidi Lindroth; Babar A Khan; Janet S Carpenter; Sujuan Gao; Anthony J Perkins; Sikandar H Khan; Sophia Wang; Richard N Jones; Malaz A Boustani Journal: Ann Am Thorac Soc Date: 2020-09
Authors: Hallie C Prescott; Theodore J Iwashyna; Bronagh Blackwood; Thierry Calandra; Linda L Chlan; Karen Choong; Bronwen Connolly; Paul Dark; Luigi Ferrucci; Simon Finfer; Timothy D Girard; Carol Hodgson; Ramona O Hopkins; Catherine L Hough; James C Jackson; Flavia R Machado; John C Marshall; Cheryl Misak; Dale M Needham; Pinaki Panigrahi; Konrad Reinhart; Sachin Yende; Ross Zafonte; Kathryn M Rowan; Derek C Angus Journal: Am J Respir Crit Care Med Date: 2019-10-15 Impact factor: 21.405
Authors: Christina S Boncyk; Kimberly F Rengel; Pratik P Pandharipande; Christopher G Hughes Journal: Curr Opin Crit Care Date: 2019-06 Impact factor: 3.687
Authors: Timothy D Girard; Matthew C Exline; Shannon S Carson; Catherine L Hough; Peter Rock; Michelle N Gong; Ivor S Douglas; Atul Malhotra; Robert L Owens; Daniel J Feinstein; Babar Khan; Margaret A Pisani; Robert C Hyzy; Gregory A Schmidt; William D Schweickert; R Duncan Hite; David L Bowton; Andrew L Masica; Jennifer L Thompson; Rameela Chandrasekhar; Brenda T Pun; Cayce Strength; Leanne M Boehm; James C Jackson; Pratik P Pandharipande; Nathan E Brummel; Christopher G Hughes; Mayur B Patel; Joanna L Stollings; Gordon R Bernard; Robert S Dittus; E Wesley Ely Journal: N Engl J Med Date: 2018-10-22 Impact factor: 91.245