Long-term cognitive impairment after critical illness.

BACKGROUND Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS 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. RESULTS 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. CONCLUSIONS 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.).

[1]  K. Langa,et al.  Long-term cognitive impairment and functional disability among survivors of severe sepsis. , 2010, JAMA.

[2]  Karen J. Chan,et al.  Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. , 2005, American journal of respiratory and critical care medicine.

[3]  G. Bernard,et al.  Lorazepam Is an Independent Risk Factor for Transitioning to Delirium in Intensive Care Unit Patients , 2006, Anesthesiology.

[4]  P. Eikelenboom,et al.  Systemic infection and delirium: when cytokines and acetylcholine collide , 2010, The Lancet.

[5]  Timothy J. Brennan,et al.  Early physical and occupational therapy in mechanically ventilated , critically ill patients : A randomised controlled trial , 2009 .

[6]  Stanislav V Kasl,et al.  Days of delirium are associated with 1-year mortality in an older intensive care unit population. , 2009, American journal of respiratory and critical care medicine.

[7]  G. Bernard,et al.  Delirium as a predictor of long-term cognitive impairment in survivors of critical illness , 2010, Critical care medicine.

[8]  Colm Cunningham,et al.  Systemic inflammation and delirium: important co-factors in the progression of dementia. , 2011, Biochemical Society transactions.

[9]  C. Randolph,et al.  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. , 1998, Journal of clinical and experimental neuropsychology.

[10]  T. Peto,et al.  Asymptomatic Clostridium difficile Colonisation and Onward Transmission , 2013, PloS one.

[11]  Sunil J Rao,et al.  Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis , 2003 .

[12]  Frank E. Harrell,et al.  Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis , 2001 .

[13]  A. Sarah Walker,et al.  Characterisation of Clostridium difficile Hospital Ward–Based Transmission Using Extensive Epidemiological Data and Molecular Typing , 2012, PLoS medicine.

[14]  C. Sessler,et al.  The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. , 2002, American journal of respiratory and critical care medicine.

[15]  J. Takala,et al.  Effect of sedation level on the prevalence of delirium when assessed with CAM-ICU and ICDSC , 2013, Intensive Care Medicine.

[16]  R. Bellomo,et al.  Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. , 2012, American journal of respiratory and critical care medicine.

[17]  J. Fisk,et al.  Societal Costs of Vascular Cognitive Impairment in Older Adults , 2002, Stroke.

[18]  R. Riker,et al.  1092: RELATIONSHIP BETWEEN DELIRIUM INCIDENCE ASSESSED WITH CAM-ICU AND LEVEL OF SEDATION ASSESSED BY RASS IN ADULT ICU PATIENTS , 2012 .

[19]  G. Bernard,et al.  Long-term cognitive impairment after critical illness. , 2014, The New England journal of medicine.

[20]  G. Rubenfeld,et al.  Critical care and the global burden of critical illness in adults , 2010, The Lancet.

[21]  O. Vignaux,et al.  Pancreatic atrophy--a new late toxic effect of sorafenib. , 2013, The New England journal of medicine.

[22]  Jane W. Marsh,et al.  Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  S. O'Bryant,et al.  Identifying functional impairment with scores from the repeatable battery for the assessment of neuropsychological status (RBANS) , 2010, International journal of geriatric psychiatry.

[24]  G. Bernard,et al.  Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). , 2001, JAMA.

[25]  S. Zeger,et al.  Cognitive and neurologic outcomes after coronary-artery bypass surgery. , 2012, The New England journal of medicine.

[26]  Y. Skrobik,et al.  Delirium in an intensive care unit: a study of risk factors , 2001, Intensive Care Medicine.

[27]  Cherisse McKay,et al.  Reliability and validity of the RBANS in a traumatic brain injured sample. , 2007, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[28]  Anthony F Jorm The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): a review , 2004, International Psychogeriatrics.

[29]  J. Blass Association Between Acute Care and Critical Illness Hospitalization and Cognitive Function in Older Adults , 2010 .

[30]  Russell R. Miller,et al.  The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: The VISIONS cohort magnetic resonance imaging study* , 2012, Critical care medicine.

[31]  E. Bigler,et al.  Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. , 1999, American journal of respiratory and critical care medicine.

[32]  Mark F. Newman,et al.  Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. , 2001, The New England journal of medicine.

[33]  E. Ely,et al.  Six-month neuropsychological outcome of medical intensive care unit patients , 2003, Critical care medicine.

[34]  Theodore Speroff,et al.  Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. , 2004, JAMA.

[35]  D. Gusmao-Flores,et al.  Tools for diagnosing delirium in the critically ill: is calibration needed for the less sedated patient? , 2013, Intensive Care Medicine.

[36]  Jing Xie,et al.  Framingham Stroke Risk Profile and poor cognitive function: a population-based study , 2008, BMC neurology.

[37]  R. Jaeschke,et al.  Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit , 2013, Critical care medicine.

[38]  J. Barth,et al.  The Halstead-Reitan Neuropsychological Test Battery. , 2000 .

[39]  M. Roizen Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial , 2010 .

[40]  T. Peto,et al.  Relationship Between Bacterial Strain Type, Host Biomarkers, and Mortality in Clostridium difficile Infection , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  B. Winblad,et al.  Institutionalization in the elderly: the role of chronic diseases and dementia. Cross-sectional and longitudinal data from a population-based study. , 2001, Journal of clinical epidemiology.

[42]  R. Little,et al.  The prevention and treatment of missing data in clinical trials. , 2012, The New England journal of medicine.

[43]  Russell R. Miller,et al.  The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: The VISIONS prospective cohort magnetic resonance imaging study* , 2012, Critical care medicine.

[44]  E. Keeler,et al.  Cognitive Decline in High‐Functioning Older Persons Is Associated with an Increased Risk of Hospitalization , 2004, Journal of the American Geriatrics Society.

[45]  D. Rubin,et al.  Statistical Analysis with Missing Data. , 1989 .

[46]  Lauren M. King,et al.  The Effect of a Quality Improvement Intervention on Perceived Sleep Quality and Cognition in a Medical ICU* , 2013, Critical care medicine.

[47]  J. Kirk-Bayley,et al.  Functional Disability 5 Years after Acute Respiratory Distress Syndrome , 2011 .

[48]  Robert J. Willis,et al.  National estimates of the quantity and cost of informal caregiving for the elderly with dementia , 2001, Journal of General Internal Medicine.

[49]  C. Randolph,et al.  Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) , 2009 .

[50]  E. Dimagno,et al.  Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. , 1973, The New England journal of medicine.

[51]  J. Vincent,et al.  Serial evaluation of the SOFA score to predict outcome in critically ill patients. , 2001, JAMA.

[52]  Nicole A. Lazar,et al.  Statistical Analysis With Missing Data , 2003, Technometrics.

[53]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[54]  M. Sugishita,et al.  [Clinical Dementia Rating (CDR)]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.