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  • Kiely and Marcantonio paper showed that resolution of delirium seemed to be a prerequisite for resolution and stabilization of functional capacity
  • A joint Task Force of the Society of Critical Care Medicine (SCCM), American College Critical Care Medicine (ACCM), and the American Society of Health-System Pharmacists (ASHP) in alliance with the American College of Chest Physicians (ACCP) recommend daily delirium monitoring in the ICU.
  • Each additional day spent in delirium was associated with a 20% increased risk of remaining in hospital and a 10% increased risk of death (7).
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    1. 1. A New Frontier In Critical Care: Saving the Brain of Injured Elderly E. Wesley Ely, MD, MPH Professor of Medicine Pulmonary, Critical Care & Health Services Research Associate Director of Aging Research – VA GRECC Vanderbilt University, Nashville, TN
    2. 2. “Do you see what I see? The epistemology of interdisciplinary inquiry” H. G. Petrie. The Journal of Aesthetic Education 1976;10:29-43
    4. 4. Wall Street Journal THE INFORMED PATIENT By LAURA LANDRO Hospitals Combat an Insidious Complication Delirium in ICU Patients, October 17, 2007; Page D1 “Gravely ill with pneumonia and sepsis, SBM was heavily sedated on a ventilator for 10 days in 2002. She suffered several complications in the ICU -- including delirium, a state of temporary confusion and disorientation that frequently occurs in critically ill patients. But after she returned to work, Ms. Miller, now 54 years old, was unable to concentrate or organize her thoughts. She had to retire early...”
    5. 5. Anecdote: Sepsis Patient 64 y/o female executive: • Previously healthy • Community-acquired pneumonia, sepsis • ARDS and on vent for 10 days • Had ICU delirium • Lungs, heart, kidneys recovered without complications • Head CT and MRI normal, neuro exam non-focal • Debilitating “executive dysfunction” syndrome
    6. 6. Anecdote: Sepsis Patient 1 year follow-up letter Dear Doctor, you remember my sister, who is a 64 year old CEO with many employees. After she developed delirium, we couldn’t seem to get her mental clouding cleared for quite some time. She has tried to go back to work, and driving, and functioning although she can not seem to fully bounce back. I saw her for the first time about a month ago, when she came out for my daughter's Bat Mitzvah. She seems to have lost her "spark". She was such a personality pre-illness, so gregarious and really the life of the party. She is very flat now, and has memory problems. She doesn't remember anything about her illness or her hospitalization. Some long term, but mostly short term memory problems. She looks much older, and is walking very slowly, always holding onto railings, etc. She looks like a very elderly woman now. The illness really changed her. ref: Tremendous deterioration in cognitive and functional capacity (Kiely & Marcantonio, J Gerontol 2006;61:204-08)
    8. 8. Severe Sepsis Incidence by Age 0 20,000 40,000 60,000 80,000 100,000 120,000 <1 1 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85+ Age/Years 0 5 10 15 20 25 30 Number of cases Incidence rate Cases Incidence/1,000Population Angus, Crit Care Med 2001; 29:1303-10
    9. 9. Aging and Mechanical Ventilation • Incidence of acute respiratory failure requiring mechanical ventilation rises 10-fold from age 55 to 85 Behrendt, Chest 2000;118:1100-1105 • Greater numbers of older patients are being treated in our ICUs than ever before Jakob, Crit Care Med 1997;23:1165-70 • ~60% of all ICU days are incurred by patients >65 years old Angus et al., JAMA 2000;284:2762-70 These facts have altered the ICU landscape
    10. 10. “DIG THE BREAK”
    11. 11. BRAIN DYSFUCTION - a new frontier -
    12. 12. MeSH and Text for “Delirium in ICU” 1990-1999 0 5 10 15 20 25 30 35 40 45 50 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Delirium Articles (ICU)
    13. 13. MeSH and Text for “Delirium in ICU” Since Year 2000 0 5 10 15 20 25 30 35 40 45 1990 1992 1994 1996 1998 2000 2002 2004 2006 Delirium Articles (ICU)
    14. 14. Delirium Monitoring in ICU - 2007
    15. 15. Definition of Delirium • Delirium is (1) fluctuation/change in mental status (2) inattention either/or (3) disorganized thinking (4) altered level of consciousness DSM IV and CAM-ICU
    16. 16. Patient Comfort Pain Sedation Delirium • 0-10 Scale VAS Scale • Subjective/ Physiologic indicators Sedation Assessment Scale (e.g. RASS, SAS, MAAS) CAM-ICU IC-DSC Jacobi J et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30:119-141 Assessment of ICU Patients
    17. 17. Educational Delirium Website
    18. 18. DELIRIUM and SEDATION:DELIRIUM and SEDATION: OutcomesOutcomes Tools to UseTools to Use Vanderbilt RCTsVanderbilt RCTs
    19. 19. Delirium and Outcomes - Increased ICU Length of Stay (8 vs 5 days) - Increased Hosp Length of Stay (21 vs. 11days) - Increased time on the Ventilator (9 vs 4 days) - Higher costs ($22,000 vs $13, 000 in ICU costs) - Estimated $4 to $16 billion associated U.S. costs - 3-fold increased risk of death - Every delirium day increased by 35% ‘ICU accelerated dementia’ Ely EW, ICM2001; 27, 1892-1900 Thomason J, Crit Care 2005;9:375-381 Lin SM, CCM 2004; 32: 2254-2259 Ely EW, JAMA 2004; 291: 1753-1762 Milbrandt E,CCM 2004; 32:955-962 Jackson J, Neuropsych Rev 2004; 14: 87-98 Ouimet S, ICM 2007;33:66-73 Pisani M, Crit Care 2006;10:R121
    20. 20. Saving Lives Through NewSaving Lives Through New Treatment ApproachesTreatment Approaches
    21. 21. The Awakening and Breathing Controlled (ABC) Trial • To determine the efficacy and safety of a protocol combining daily (A) spontaneous Awakening trials and (B) spontaneous Breathing trials • Multicenter Investigation – Vanderbilt Hospital (Girard, Thomason, Ely) – University of Chicago Hospitals (Kress & Hall) – Saint Thomas Hospital, Nashville (Canonico) – Hospital of the Univ. of Pennsylvania (Fuchs) – Penn Presbyterian Medical Center (Taichman)
    22. 22. 1 day1 day 2 days2 days Fulminant Dz (33%) “Weaning” period (66%)Fulminant Dz (33%) “Weaning” period (66%) Esteban A, et al.Esteban A, et al. JAMAJAMA 2002;287:345-552002;287:345-55 Total time on ventilator – 2 to 7 daysTotal time on ventilator – 2 to 7 days
    23. 23. The ABC Trial O U T C O M E S d e lir iu m , L O S , 1 2 - m o N P S t e s t in g , Q O L S p o n t a n e o u s B r e a t h i n g T r i a l ( S B T ) v e n tila t o r o ff s a f e ly m o n it o r e d O U T C O M E S d e lir iu m , L O S , 1 2 - m o N P S t e s t in g , Q O L S p o n t a n e o u s B r e a t h i n g T r i a l ( S B T ) v e n tila t o r o ff s a f e ly m o n it o r e d S p o n t a n e o u s A w a k e n i n g T r i a l ( S A T ) t u r n s e d a t io n / n a rc o t ic s o ff m o n it o r s a f e ly M e d ic a l I C U o n V e n t ila t o r S u r ro g a t e I n f o r m e d C o n s e n t Control Intervention Girard T et al, Lancet 2008 in press
    24. 24. ABC Trial: Baseline Characteristics Characteristic* SBT (n=168) SAT+SBT (n=167) Age, mean years±SD 61±16 58±17 Female, n (%) 83 (49.4) 77 (46.1) APACHE II score 26.5 [21-31] 26 [21-33] ICU admission diagnosis, n (%) Sepsis and/or ARDS 89 (53) 79 (49) MI/CHF 29 (17) 22 (13) COPD/Asthma 12 (7) 17 (10) Other 38 (23) 45 (27) RASS on first study day -4 [-5 to -2] -4 [-5 to -2] *Median [interquartile range] except as noted*Median [interquartile range] except as noted
    25. 25. ABC Trial: Main Outcomes Outcome* SBT SAT+SBT p value† Ventilator-free days 12 15 0.02 Time to Event, days Successful extubation 7.0 5 0.05 ICU discharge 13 9 0.02 Hospital discharge 19 15 0.04 Death at 28 days, n (%) 58 (34.5) 47 (28) 0.21 Days of brain dysfunction Coma 3.0 2.0 0.002 Delirium 2.0 2.0 0.50 *Median [interquartile range] except as noted*Median [interquartile range] except as noted Girard T et al, Lancet 2008 in press
    26. 26. Improved one-year survival in ABC Trial PatientsAlive(%) 0 0 20 40 60 80 100 60 120 180 240 300 360 Days SBT (n=168) SAT+SBT (n=167) p=0.01 Girard T et al, Lancet 2008 in press
    27. 27. The MENDS Trial Vanderbilt University, Nashville TN Washington Hospital Center, Washington DC Maximizing Efficacy of targeted sedation and reducing Neurological Dysfunction
    28. 28. MENDS Study C o n t r o l L o r a z e p a m ( G A B A ) + / - F e n t a n y l I n t e r v e n t io n D e x m e d e t o m id in e ( α 2 ) + / - F e n t a n y l M I C U / S I C U V e n t ila t e d o n S e d a t iv e s I n f o r m e d C o n s e n t Pandharipande P et al, JAMA 2007;298:2644-2653
    29. 29. MENDS Trial: Baseline Characteristics Demographic Lorazepam (n=51) Dexmedetomidine (n=52) P value Age 59 (45, 67) 60 (49,65) 0.96 Males 45% 56% 0.42 APACHE II 27 (23,32) 28.5 (23, 32) 0.95 SOFA score 9 (7,11) 10 (8,12) 0.23 Sepsis diagnosis 39% 38% 0.95 Pandharipande P et al, JAMA 2007;298:2644-2653
    30. 30. 024681012 p = 0.011 Delirium/Coma-Free Days Delirium-Free Days p = 0.086 Dexmedetomidine Lorazepam p = 0.001 Coma-Free Days Days Lorazepam Dexmedetomidine JAMA 2007;298:2644-2653
    31. 31. MIND Study (Modifying the INcidence of Delirium) C o n t r o l P la c e b o I n t e r v e n t io n H a lo p e r id o l I n t e r v e n t io n Z ip r a s id o n e M I C U / S I C U V e n t ila t e d o n S e d a t iv e s I n f o r m e d C o n s e n t 6 sites: Vanderbilt TN, UNC-CH, U of Iowa, Baylor TX, St. Thomas TN, Moses Cone NC
    33. 33. Case History • 54 year old executive develops CAP/ARDS/Sepsis • Mechanical ventilation, MODS, delirium • Survived but “brain swimming in mollasses” • 2 years later not working but happy and active • “Doc, others don’t know” Anecdote: Young Sepsis Patient
    34. 34. Anecdote: Young Sepsis Patient Data on link between delirium and long-term CI growing; no proven link to sedation. This person retained a functional life, and though lost her profession, has stabilized.
    35. 35. The BRAIN ICU Project - Overview - Time Delirium Duration Drug Exposure Long Term Cognitive Impairment (LTCI) Battery Health-Related Quality of Life (HRQL) Battery Patient enrollment 12-month follow-up INDEPENDENT VARIABLES DEPENDENT VARIABLES Time Delirium Duration Drug Exposure Long Term Cognitive Impairment (LTCI) Battery Health-Related Quality of Life (HRQL) Battery Patient enrollment 12-month follow-up INDEPENDENT VARIABLES DEPENDENT VARIABLES
    36. 36. • Wes Ely, MD, MPH Critical Care and Aging Research • Robert Dittus, MD, MPH Division Chief GIM, GRECC Director • Gordon Bernard, MD Asst. Vice Chancellor for Research • Lorraine Ware, MD Biomarkers in Critical Care • Pratik Pandharipande, MD, MSCI Anesthesiology & Critical Care • Paula Watson, MD Sleep Medicine, Critical Care • Tim Girard, MD, MSCI Aging Critical Care • Russ Miller, MD, MPH & Rich Tyson, MD Pulm/Critical Care Fellows • Bryan Cotton, MD; Bill Obremskey MD Trauma and Orthopedic Surgery • Herbert Meltzer, MD; Stephan Heckars, MD Psychiatry • Sharon Gordon, PhD; Jim Jackson, PhD Geriatric Neuropsychology • Venice Anderson, MS Psychological Testing Expertise • Howard Kirshner, MD Behavioral Neurology • Mike Stein, PhD & Usha Nair PhD Clinical Pharmacology • Ayumi Shintani PhD, MPH, Frank Harrell, PhD Biostatisticians • Ted Speroff, PhD Psychometrics, Safety • Jennifer Thompson, BS, MA Database, Biostatistics • Renee Stiles, PhD; Steve Deppen, MS Resource Use / Cost • Brenda Pun, RN, MSN, ACNP Project and Nurse Coordinator • Joyce Okahashi and Kate VDH, RN, MSN Research Nurses (BRAIN) • Cayce Strength, BSN Research Nurse (SOMNUS) • Meredith Gambrell, BS Grants & Program Coordinator • Hope Campbell, PharmD and others Investigational Pharmacy • Vivek Agarwal, Rina Patel, Natalie Jacobowski, Eli Zimmerman Medical Students Our Research Engine: Over 30 Specialist Team Members
    37. 37. Contact Information • For information about this specific presentation please contact Stephanie Hamilton at • For any questions about the monthly GRECC Audio Conference Series please contact Tim Foley at or call (734) 222-4328 • For the link to the evaluation form for this conference that will confer CE credit please go to and click the “Handout: Registration and Evaluation” link