A New Frontier In Critical Care: Saving the Injured Brain · 2019-12-12 · A New Frontier In...
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A New Frontier In Critical Care: Saving the Injured Brain
E. Wesley Ely, MD, MPHCIBS Center, Aging Research, VA GRECC
Professor, Pulmonary & Critical Care MedicineVanderbilt Univ Medical Center, Nashville, TN
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Disclosures
• Physician-scientist, Vanderbilt University, Nashville TN, USA
• Honoraria from Pfizer, Orion for CME Activities• Consulting with Philips and Masimo• PI for MIND-USA and SCCM’s ICU Liberation• NIH and VA U.S. Federal Funding
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Over 20 Years of Research at Vanderbilt and VA
1998-2019…
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“Strange to say, he seemed immediately to have become perfectly calm; not a trace of
his recent delirium nor of the panic fear that had haunted him of late. It was the first moment of a strange sudden calm.”
In Crime and Punishment, Dostoyevsky used "delirium" 31 times.
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Pandharipande, NEJM 2013;369:1306-16
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The Picture of Dementia Following ICU Care
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Who gets this dementia?
NIH parlance: ADRD
Alz Dz, Vascular, Lewy Body, Mixed, Frontotemporal, Creutzfeldt-Jakob, NPH, Parkinson’s, Huntington’s, Wernicke-Korsakoff, and Post-Critical Illness ADRD (?)
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James et al, Neurology 2019;92:1-10
Hospitalization
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James et al, Neurology 2019;92:1-10
Elective vs Emergent Hospitalization
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Haloperidol Use for Delirium in the ICU became usual care
Fall 2018, Mastering Intensive Care podcastproducer Dr. Andrew Davies, Melbourne Australia
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131st Annual Meeting of the American Psych Assoc, Wash DC
1st Report of Haldol for ICU Delirium40 years ago…1978
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—2002 SCCM Guidelines
Haloperidol Use for Delirium in the ICU became usual care
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Morandi A. Crit Care Med 2017;45:e1111-22
Global use of Haloperidol for ICU Delirium
0%
20%
40%
60%
80%
100%
Africa Asia Europe NorthAmerican
Oceania SouthAmerica
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Schneider LS, JAMA 2005;294:1934-43
Wang PS, NEJM 2005;353:2335-41
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Girard TD, et al. NEJM 2018;379:2506-16
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D2 antagonism
α2
H1
D1
Ziprasidoneblocks 6 receptors, agonist at 1
D2
5-HT1D
5-HT2C
5-HT1A agonist
5-HT2A
α1
H1
Haloperidolmainly blocks DA
Traditional Teaching: “Dopamine blockade in the cerebral cortex improves cognition and reduces delirium.”
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MIND-USA: Baseline VariablesVariable Placebo
N=184Haloperidol
N=192 Ziprasidone
N=190 Age 59 [52-67] 61 [51-69] 61 [50-69]APACHE II 30 28.5 28
SOFA 11 11 10Mechanical Ventilation 175 (95%) 185 (96%) 185 (97%)Shock on Pressors 65 (35%) 58 (30%) 64 (34%)
Medical / Surgical ICU 72% / 28% 73% / 27% 71% / 29%Admission Diagnoses
ARDS or Sepsis 74 (40%) 87 (45%) 68 (36%)COPD, CHF, Cirrhosis 35 (19%) 29 (15%) 37 (19%)Other Diagnoses 75 (41%) 76 (40%) 85 (45%)
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MIND-USA: primary outcome
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MIND-USA: 90-Day Survival
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MIND-USA: Key 2° Outcomes
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MIND-USA: Hypoactive Delirium
Adj P=0.62
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MIND-USA: Hyperactive Delirium
Adj P=0.58
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A long habit of not thinking a thing wrong, gives it a superficial
appearance of being right…”
Common Sense, Thomas Paine, c. 1776
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Richard Harris, Senior NPR Science Reporter, Oct 8, 2018
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ABCDEF Bundle: Science & Philosophy(based on 40 Lancet, JAMA, NEJM papers + ~350 others)
• Analgesia: Assess, Prevent, Manage Pain• Both SATs and SBTs: Stop Drugs, Stop Vent• Choice of Analgesia and Sedation• Delirium: Assess, Prevent, Manage• Early Mobility and Exercise, Environment• Family Engagement and Empowerment
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A-E and A-F Bundle References
ABCDE Bundle1. Pandharipande P, Crit Care, 2010;14:157-592. Vasilevskis EE, Chest, 2010;138:1224-333. Morandi A, Curr Opin Crit Care, 2011;17:43-494. Balas MC, Crit Care Nurse, 2012;32:40-475. Carrothers KM, Crit Care Med, 2013;41:S128-356. Trogrlić Z, Crit Care, 2015;19:1577. Boehm LM, Am J Crit Care, 2017;26:e18-288. Boehm LM, Am J Crit Care, 2017;26:e38-47
ABCDEF Bundle9. Balas MC, Crit Care Med, 2014;42:1024-3610. Barnes-Daly MA, Crit Care Med, 2017;45:171-7811. Ely EW, Crit Care Med, 2017;45:321-3012. Marra A, Crit Care Clin, 2017;33:225-4313. Morandi A, Crit Care Med, 2017;45:e1111-2214. Barnes-Daly MA, World Evid Based Nurs,
2018;15:206-1615. Pun BT, Crit Care Med 2019;47:3-1416. Stollings, Crit Care Nurse 2019;39:36-45.17. Balas MC, Crit Care Nurse 2019;39:46-6018. Hsieh SJ, CCM 2019;47:885-93
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Liberated…?
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Liberated…
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ABCDEF…Early Mobility and Family in Poland:
Ventilated Patient and Her Husband with Shopping Cart
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Mr. D and Wanda
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Survival and Delirium-Coma FreedomImplementing ABCDEF Bundle in >6,000 patients
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0H
ospi
tal s
urvi
val,
prop
ortio
n
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0Partial compliance with the ABCDEF bundle, proportion
N = 6,064 subjectsOR = 1.15, p-value < 0.001
NOTE: Adjusted for age, APACHE III, and mechanical ventilation7 California Hospitals, Interprofessional QI Implementation project
Barnes-Daly MA, CCM 2017;45:171-8
Mortality Improvement Delirium and Coma Freedom
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Pun BT, et al. Crit Care Med. 2019;47:3-14Sponsored by the SCCM via The Moore Foundation
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ICU Liberation Hospitals and Regions
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ICU Liberation Collaborative
• Gordon Moore Foundation (Intel Billionaire)• SCCM (Sepsis, ICU Liberation, Thrive) • Aug 2015 to April 2017• 68 Adult American ICUs, 10 Pediatric • Medical, Surgical, Cardiac, Neuro ICUs• ABCDEF Bundle implementation• 15,226 patients • All regression models adjusted for 18
confounders chosen a priori
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ABCDEF bundle performance… improves ICU discharge
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ABCDEF bundle performance… improves hospital discharge
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Performance…reduces death
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Performance improves… coma, delirium, restraints
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Performance reduces… ICU readmission and NH transfers
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Future Directions
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Mobilizing the Brain with Sudoku & Scrabble
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Providing Lux to Restore Circadian Rhythm
VitalSky Basic VitalSky Advanced
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Circadian-effective white light
0
200
400
600
800
1000
1200
1400
1600
1800
2000Lu
x
6 hours Darkness
Bright light with 1900 lux
4 hours Darkness
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Clarifying the Relationship between Delirium and ADRD (NIA PAR-18-029)
Study Overview
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CIBS Collaborators
Surgery
Anesthesia
Medicine
Neurology
Psychiatry
Biostatistics
Epidemiology
Pharmacology
Radiology
Pediatrics
Biomedical Informatics
VU Engineering
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Health Policy