The BRAIN Intensive Care Unit (ICU) Study: Bringing to Light the Risk Factors

NCT00392795 | Active Not Recruiting

• 2 other identifiers: AG072472 01A1R01AG027472
• Study Type: observational
• Target: 826
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purpose of this proposal will be to identify potentially modifiable risk factors of long-term cognitive impairment (i.e. development of delirium and exposure to sedative and analgesic medications) in ICU patients. The investigators will quantify the independent contribution of these risk factors to the incidence of long-term cognitive impairment, controlling for other established risk factors including age, pre-existing cognitive impairment, and apolipoprotein E (apoE) genotype. Quantifying the contributions of these modifiable risk factors will pave the way for the development of preventive and/or treatment strategies to reduce the incidence, severity and/or duration of long-term cognitive impairment and improve functional recovery for patients with critical illness.

Conditions

Delirium; Cognition Disorders; Dementia

Keywords

Critical Care; Delirium; Long-term cognitive impairment; mechanical ventilation; Critical illness; dementia; sedatives and analgesics; aging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Medical and Surgical ICUs

You may qualify if:

• Patients will be included if they are adult, patients in a medical and/or surgical ICU receiving treatment for any of the following: respiratory failure or cardiogenic or septic shock.

You may not qualify if:

• Cumulative ICU time \>5 days in the past 30 days, not including the current ICU stay, as this might create a state of flux regarding patients' cognitive baseline
• Severe cognitive or neurodegenerative diseases that prevent a patient from living independently at baseline, including mental illness requiring institutionalization, acquired or congenital mental retardation, known brain lesions, traumatic brain injury, cerebrovascular accidents with resultant moderate to severe cognitive deficits or ADL dependency, Parkinson's disease, Huntington's disease, severe Alzheimer's disease or dementia of any etiology
• ICU admission post cardiopulmonary resuscitation with suspected anoxic injury
• Blind, deaf, or unable to speak English, as these conditions would preclude our ability to perform the follow-up evaluation interviews.
• Overly moribund and not expected to survive for an additional 24 hours and / or withdrawing life support to focus on comfort measures only.
• Prisoners.
• Patients who live further than 200 miles from Nashville and who do not regularly visit the Nashville area.
• The onset of the current episode of respiratory failure, cardiogenic shock, or septic shock was \> 72 hours ago.
• Patients who have had cardiac bypass surgery within the past 3 months (including the current hospitalization)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Saint Thomas Hospital

Nashville, Tennessee, 37205, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (19)

• Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.

  PMID: 15082703 BACKGROUND

• Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91. doi: 10.1001/jama.289.22.2983.

  PMID: 12799407 BACKGROUND

• Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703.

  PMID: 11730446 BACKGROUND

• Jackson JC, Gordon SM, Ely EW, Burger C, Hopkins RO. Research issues in the evaluation of cognitive impairment in intensive care unit survivors. Intensive Care Med. 2004 Nov;30(11):2009-16. doi: 10.1007/s00134-004-2422-2. Epub 2004 Sep 15.

  PMID: 15372146 BACKGROUND

• Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev. 2004 Jun;14(2):87-98. doi: 10.1023/b:nerv.0000028080.39602.17.

  PMID: 15264710 BACKGROUND

• Ely EW, Wheeler AP, Thompson BT, Ancukiewicz M, Steinberg KP, Bernard GR. Recovery rate and prognosis in older persons who develop acute lung injury and the acute respiratory distress syndrome. Ann Intern Med. 2002 Jan 1;136(1):25-36.

  PMID: 11777361 BACKGROUND

• Ely EW, Evans GW, Haponik EF. Mechanical ventilation in a cohort of elderly patients admitted to an intensive care unit. Ann Intern Med. 1999 Jul 20;131(2):96-104. doi: 10.7326/0003-4819-131-2-199907200-00004.

  PMID: 10419447 BACKGROUND

• Hopkins RO, Weaver LK, Pope D, Orme JF, Bigler ED, Larson-LOHR V. Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999 Jul;160(1):50-6. doi: 10.1164/ajrccm.160.1.9708059.

  PMID: 10390379 BACKGROUND

• Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR, Inouye SK. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001 Jul;29(7):1370-9. doi: 10.1097/00003246-200107000-00012.

  PMID: 11445689 BACKGROUND

• Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8.

  PMID: 11797025 BACKGROUND

• Rengel KF, Wilson JE, Silver HJ, Hollingsworth E, Orun OM, Jackson JC, Mart MF, Hughes CG, Ely EW, Brummel NE. Associations Among Skeletal Muscle Health, Disability, and Self-Reported Physical Function in Survivors of Critical Illness: A Secondary Analysis of the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors Study. CHEST Crit Care. 2025 Jun;3(2):100115. doi: 10.1016/j.chstcc.2024.100115. Epub 2024 Nov 29.

  PMID: 40837197 DERIVED

• Hughes CG, Hayhurst CJ, Pandharipande PP, Shotwell MS, Feng X, Wilson JE, Brummel NE, Girard TD, Jackson JC, Ely EW, Patel MB. Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study. Anesth Analg. 2021 Nov 1;133(5):1152-1161. doi: 10.1213/ANE.0000000000005544.

  PMID: 33929361 DERIVED

• Duggan MC, Morrell ME, Chandrasekhar R, Marra A, Frimpong K, Nair DR, Girard TD, Pandharipande PP, Ely EW, Jackson JC. A Brief Informant Screening Instrument for Dementia in the ICU: The Diagnostic Accuracy of the AD8 in Critically Ill Adults Suspected of Having Pre-Existing Dementia. Dement Geriatr Cogn Disord. 2019;48(5-6):241-249. doi: 10.1159/000490379. Epub 2020 Apr 7.

  PMID: 32259825 DERIVED

• Hayhurst CJ, Patel MB, McNeil JB, Girard TD, Brummel NE, Thompson JL, Chandrasekhar R, Ware LB, Pandharipande PP, Ely EW, Hughes CG. Association of neuronal repair biomarkers with delirium among survivors of critical illness. J Crit Care. 2020 Apr;56:94-99. doi: 10.1016/j.jcrc.2019.12.010. Epub 2019 Dec 16.

  PMID: 31896448 DERIVED

• Wilson JE, Duggan MC, Chandrasekhar R, Brummel NE, Dittus RS, Ely EW, Patel MB, Jackson JC. Deficits in Self-Reported Initiation Are AssociatedWith Subsequent Disability in ICU Survivors. Psychosomatics. 2019 Jul-Aug;60(4):376-384. doi: 10.1016/j.psym.2018.09.004. Epub 2018 Sep 29.

  PMID: 30352696 DERIVED

• Hayhurst CJ, Jackson JC, Archer KR, Thompson JL, Chandrasekhar R, Hughes CG. Pain and Its Long-term Interference of Daily Life After Critical Illness. Anesth Analg. 2018 Sep;127(3):690-697. doi: 10.1213/ANE.0000000000003358.

  PMID: 29649027 DERIVED

• Brummel NE, Bell SP, Girard TD, Pandharipande PP, Jackson JC, Morandi A, Thompson JL, Chandrasekhar R, Bernard GR, Dittus RS, Gill TM, Ely EW. Frailty and Subsequent Disability and Mortality among Patients with Critical Illness. Am J Respir Crit Care Med. 2017 Jul 1;196(1):64-72. doi: 10.1164/rccm.201605-0939OC.

  PMID: 27922747 DERIVED

• Jackson JC, Pandharipande PP, Girard TD, Brummel NE, Thompson JL, Hughes CG, Pun BT, Vasilevskis EE, Morandi A, Shintani AK, Hopkins RO, Bernard GR, Dittus RS, Ely EW; Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors (BRAIN-ICU) study investigators. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med. 2014 May;2(5):369-79. doi: 10.1016/S2213-2600(14)70051-7. Epub 2014 Apr 7.

  PMID: 24815803 DERIVED

• Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.

  PMID: 24088092 DERIVED

Related Links

• ICU Delirium and Cognitive Impairment Study Group Website

Biospecimen

Retention: SAMPLES WITH DNA

blood

MeSH Terms

Conditions

Delirium; Cognition Disorders; Dementia; Critical Illness

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Disease Attributes; Pathologic Processes

Study Officials

• E Wesley Ely, MD, MPH

  Vanderbilt University/VA TN Valley GRECC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: January 1, 2007
• Primary Completion: December 1, 2010
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (2)