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ICS 2013

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Rakesh Arora

on 8 September 2014

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Transcript of ICS 2013

So What is Delirium?
And why should I care??!!?
Different Questions
What was keeping patients in my ICU
Transition to translation
Why is this important?
Doesn't everyone "pump brain"
Bedside to the Bench
How can we answer this clinical conundrum
Where do we go from here?
What are the opportunities to intervene
A work in progress
Ensuring that patient not only survive but THRIVE after cardiac surgery
My Career So Far
University of Toronto
Medical School
"Maybe I'll just do ICU"
"I'm Going to be
Rehabilitation Specialist
Started my clerkship
Dalhousie University
Summer research project at
Lyndhurst Hospital
Dr. Robert Maggisano
Research - "Yuck"
"I'm going to do a
Critical Care Medicine
"I need a job!"
66% percent of patents have at least mild cognitive dysfunction
Determining the Impact of Frailty on Cardiac Surgery Patients
The delivery of high-quality critical care medicine is vital to the success of cardiac surgery
The Cardiac Critical Care Perspective Perspective
Statement of the Problem
Who is at risk following Cardiac Surgery?
Effectiveness of a systematic screening program

Impact of Depression following Cardiac Surgery
Jessup et al., N Engl J Med 2003;348:2007-18.
Heart failure (HF) affects over 350,000 Canadians
The medial survival after the onset of HF is 2 years in men and about 3 year in women, and worsens with advancing age
One-year mortality: 25% - 40%

Ho KK et al. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993;88: 107–15.
Canadian Epidemic
What are the issues that impact the the postoperative cardiac surgery patient?
What is unique about the CVICU?
No Financial Disclosures
But willing to entertain any
What is delirium to a patient?
Dementia is chronic and slowly progressive
a primary brain disease

Delirium is acute and rapidly progressive
the effect of systemic illness (sepsis, metabolic disturbance, medication toxicity, ACS, hypoxia) on a VULNERABLE BRAIN.
It is not DEMENTIA
Delirium is an acute confusional state characterized by fluctuating mental status, inattention, and either disorganized thinking or altered level of consciousness.
What does delirium look like?
Current Path
The Path of a Patient Through Cardiac Surgery
Patient is referred to
a Cardiologist
H+P (Cardiac risk factors)
Determine if a surgical lesion exists
Refer to a cardiac surgeon
Surgical Consultation
Patient is examined and medical chart/testing reviewed

Surgeon does the "eye ball" test

Determines risk of operative mortality

Consents patient for surgery
Now the wait begins
Wait around in fear
The miracle happens
Exposed to intraoperative "insult"
Back to the Ethos
Primary Care
Rate of Cardiac Surgery
1:1000 population
12-24 hours of potential hemodynamic instabilty
Standard Clinical Diagnosis

Based on STS’ definition of delirium: “a mental disturbance marked by illness, confusion, cerebral excitement and having a comparatively short course”.
Delirium Assessment
Higher Mortality

Longer Hospital Length of Stay

Higher Chance of Disposition to Assisted Living Facility

Higher Probability of Developing Dementia at 48 months
63% vs. 8%
It is important to exclude any medical conditions that may be causing the delirium.

“Delirium should be considered a medical emergency”
Delirium Assessment

Validated, standardized evidence-based tool

Designed for use by bedside clinicians

Takes less than 2 min to complete

Requires minimal training
Does the Environment Matter?

A retrospective analysis of consecutive patients
undergoing cardiac surgery during two time periods at a single hospital.

Exclusion Criteria:
off-pump non-CABG
in-hospital death
missing key data
Determine the prevalence rate of delirium after cardiac surgery as assessed by systematic screening.

Study how implementing a systematic screening program could influence the identification of delirium after cardiac surgery.

To identify independent perioperative risk factors associated with delirium after cardiac surgery in a cardiac population assessed by systematic screening.
Drugs that produce delirium are not benign
Conscious = arousal and brain content
Drugs may be neurotoxic

P. Pandharipande: Anesthesiology. 2006 Jan;104(1):21-6.
Keys Points in Implementing a Delirium Management Program
Risk factors associated with Delirium:
*Alpha level set at 0.05
Chi-square used for cohort delirium rate comparison

Risk Factors:
Cerejeira, J., Firmino, H., Vaz-Serra, A., & Mukaetova-Ladinska, E. B. (2010). The neuroinflammatory hypothesis of delirium. Acta Neuropathologica, 119(6), 737–754. doi:10.1007/s00401-010-0674-1
Why are cardiac patients at risk?
Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s)

Plaschke et al. Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s). Intensive Care Medicine (2008) vol. 34 (3) pp. 431-6
Which Scoring System Do I Use?
Intensive Care Delirium Screening Checklist

Society of Thoracic Surgery definition:

“mental disturbance marked by illness, confusion, cerebral excitement, and having a comparatively short course”

(Society of Thoracic Surgeons [http://www.sts.org]).
How frequent in the cardiac patient?
Patient’s pre-illness IQ was 140; following her sepsis and delirium,
her IQ was 110 at 6 months and 118 at 2 years
Loss of Brain on MRI:
49 y/o Patient 2 years after ICU stay for Sepsis
(had been normal at ICU discharge)
- Cohort 2
(CAM/CAM-ICU Assessment)
- Cohort 1
(Standard Clinical Diagnosis)
Delirium Prevalence Rates:
Delirium Assessment
Criteria used during the CAM screening process:
Feature 1 + Feature 2 + either Feature 3 or Feature 4
= CAM positive (Delirium Present)

Does the Environment Matter?
Arenson, B. G., Macdonald, L. A., Grocott, H. P., Hiebert, B. M., & Arora, R. C. (2013). Effect of intensive care unit environment on in-hospital delirium after cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery.
11 Bed Cardiac ICU and 28 bed surgical ward
1100 cardiac cases annually
In March 2010, the CAM and CAM-ICU was implemented in place of standard clinical diagnosis
At our centre
Intensive Care Delirium Screening Checklist (ICDSC), and the Confusion Assessment Method-ICU (CAM-ICU)
Dichotomous marker for delirium
i.e., they indicate that the patient either has delirium or does not

Bergeron N et al, (ICDSC) Intensive Care Med 27:859–864.
Ely EW et al , (CAM-ICU). JAMA 286:2703–2710.
Scoring Scales
Postoperative delirium developed in 46% of patients

Delirium lasted
1 to 2 days in 65%
3 or more days in 35%.

Saczynski, J. S., et al (2012). NEJM, 367(1), 30–39.
A cohort of 275 mechanically ventilated patients
an independent predictor of 6-month mortality
adjusted for relevant covariates including coma and sedative/analgesic medications.

Ely EW et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA (2004) 291:1753-1762.
ICU Delirium Increases Mortality
Source of distress for both family and patient

The importance of delirium is frequently dismissed
Seen as a transient entity
Clinical Impact of Delirium?
Cardiac surgery is increasingly being performed on older patients with limited physiologic reserve and multiple medical co-morbidities
Djaiani G et al. Sem Cardiothorac Vasc Anesth (2006);10:143-157.
Ferguson TB, et al. Ann Thorac Surg. 2002;73:480-489;

Type I: transient to permanent stroke
Type II: subtle cognitive dysfunction --> mild confusion --> frank delirium
Problem in the Cardiac Patient
- Cohort 2
(CAM/CAM-ICU Assessment)
- Cohort 1
(Standard Clinical Diagnosis)
P = 0.088
P <0.001
Delirium Prevalence Rates:
Delirium Rate as assessed by CAM/CAM-ICU:
- Cohort 2
(CAM/CAM-ICU Assessment)
- Cohort 1
(Standard Clinical Diagnosis)
Delirium Prevalence Rates:
Studied 5,034 consecutive patients undergoing isolated CABG surgery at a single institution from 1997 to 2007
3% < 65 years old
9% > 65 years old
The death rate
Delirium: 16.0 per 100 person-years,
No Delirium: 7.0 per 100 person-years
HR: 1.65 (1.38-1.97)

Gottesman RF et al, Ann Neurol 2010;67:338–344
Delirium in Cardiac Surgery
Post-operative delirium is very difficult to manage once it has occurred.
? efficacy strategies that have been published
Why is it a problem?

The prevalence of delirium after cardiac surgery is very variable ranging from 3-73%

Twice the rate observed in elective orthopedic or abdominal surgery
How frequent in the cardiac patient?
A neuroanatomical basis for cognitive impairment
Gunther et al. Crit Care Med. 2012 Jul;40(7):2022-32 2012
Higher severity and duration of delirium were associated with incrementally greater costs.
39% higher ICU costs
31% higher hospital costs
Milbrandt, EB et al. Crit. Care Med 2004;32:955-962
ICU Delirium and Cost
Delirium was the strongest independent determinant of length of stay in the hospital.

Ely EW et al. Care Med 2001; 27:1892-1900.
ICU Delirium Increases Hospital Length of Stay
Spectrum of Disease
Shehabi et al. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Critical Care Medicine (2010) vol. 38 (12) pp. 2311-8
Even one day likely has an effect
Martin, B.-J., Buth, K. J., Arora, R. C., & Baskett, R. J. F. (2011). Delirium: A Cause for Concern Beyond the Immediate Postoperative Period. The Annals of Thoracic Surgery.
Adjusted 5 year survival: 79.9% delirious, 85.6% non-delirious
No Delirium
Adjusted Hazard Ratio 1.52, 95% CI (1.29-1.78), p=0.0001
Number of cases remaining at risk
7978 6636 5074 3438 2141 912 No Delirium
496 349 224 124 43 10 Delirium
Freedom from All-Cause Mortality
Adjusted 5 year freedom: 93.1% delirious, 95.4% non-delirious
No Delirium
Adjusted Hazard Ratio 1.54, 95% CI (1.10-2.17), p=0.0116
Number of cases remaining at risk
7978 6519 4916 3290 2016 865 No Delirium
496 337 211 113 40 10 Delirium
Freedom from Hospital Admission for Stroke
Caspase-3 Activity
Both central and peripheral inflammation can exacerbate local brain inflammation and neuronal death.

A single acute systemic inflammatory event can induce neuronal death in the CNS
Cerejeira, J., Firmino, H., Vaz-Serra, A., & Mukaetova-Ladinska, E. B. (2010). The neuroinflammatory hypothesis of delirium. Acta Neuropathologica, 119(6), 737–754. doi:10.1007/s00401-010-0674-1
The effects of acute systemic inflammation in the brain: the influence of ageing
Cerejeira, J., Firmino, H., Vaz-Serra, A., & Mukaetova-Ladinska, E. B. (2010). The neuroinflammatory hypothesis of delirium. Acta Neuropathologica, 119(6), 737–754. doi:10.1007/s00401-010-0674-1
Interaction of circulating inflammatory mediators with the neurovascular unit
Random assignment to one of three postoperative
open label design
n = 90

sedation protocols:
dexmedetomidine (rate of delirium (RDD) = 10%)
propofol (RDD = 44%)
midazolam (RDD = 44%)

shorter duration of delirium if it did occur

less narcotic and benzo use

Maldonado, J. R., Wysong, A., van der Starre, P. J. A., Block, T., Miller, C., & Reitz, B. A. (2009).
Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery.
Psychosomatics, 50(3), 206–217.
Dexmedetomidine and the Reduction of Postoperative Delirium after Cardiac Surgery
Drug Therapies
Jalleh, R., Koh, K., Choi, B., Liu, E., Maddison, J., & Hutchinson, M. R. (2012). Role of microglia and toll-like receptor 4 in the pathophysiology of delirium. Medical Hypotheses, 1–5.
TLR4 signal transduction
First introduced as an anesthetic sparing agent
reduced isoflurane requirements by up to 90% when delivered as an infusion during general surgery.

Neuroprotective role
rat model of brain ischemia.

It may also have a useful role in managing the patient undergoing a drug or alcohol withdrawal proces
Dexetomidine background
Is there something we can measure?
Pathophysiology of Delirium
Inouye et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med (1999) vol. 340 (9) pp. 669-76
Can Delirium be Prevented in the
Post-operative Cardiac Surgery Patient
. Journal of Neuroscience, 25(40), 9275–9284.
IL-1β Beta
A container materials necessary to improve sensory input, cognitive stimulation, and promote sleep
Global brain disorder: endothelial dysfunction, increased blood–brain barrier permeability, and reduced blood flow.

blood–brain barrier disruption, neuronal apoptosis, and altered synaptic plasticity

Acetylcholine deficiency
Inouye SK et al. N Engl J Med. 2006;354: 1157-1165.
Pandharipande P 22:313-327.
Demeure MJ 203:752-757.
American Psychiatric Association. Am J Psychiatry. 1999;156(suppl 5): 1-20.
van der Cammen TJ et al.Int J Geriatr Psychiatry. 2006;21:838-84
Evil Humours Are Afoot
RCT of 457 patients > 65 years of age undergoing non-cardiac surgery admitted to an ICU following surgery

0.5mg bolus and 0.1mg/hr for 12 hours

Wang, W. et al. (2012). Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial*. Critical Care Medicine, 40(3), 731–739.
Prophylatic Haldol?
Cognitive and motor processes are far less dissimilar than previously thought
Juggling increases increases grey matter
Boyke J et al.J Neurosci. 2008 Jul 9;28(28):7031-5.
Wolfensteller U. Prog Brain Res. 2009;174:289-301.
Training-induced brain structure changes in the elderly.
Is there a “fingerprint” of neurocognitive testing

What happens to long-term survivors
Long Term Resetrictions to Activity
Barriers to Return to Work
Future Projects
> 36000 cardiac surgery cases are performed in Canada each year.

It would be a tragedy if a patient dies of a potentially preventable problem with a “normal” heart

At present there is a paucity information on the long-term HRQoL outcomes of ICU/Cardiac Surgery survivors
What is this important?
Inaugural Meeting - Ottawa, May 12, 2012
The Cancare Society Investigator Group
Arora VM et al. Quality indicators for hospitalization and surgery in vulnerable elders. Journal of the American Geriatrics Society (2007) vol. 55 Suppl 2 pp. S347-58.

Vasilevskis et al. Reducing iatrogenic risks: ICU-acquired delirium and weakness--crossing the quality chasm. Chest (2010) vol. 138 (5) pp. 1224-33
Delirium represents one of the most common preventable adverse events among older persons during hospitalization

Criteria for an indicator of the quality of health care:
frequently iatrogenic
integrally linked to processes of care
? Preventable
Is there an interaction with postoperative delirium and depression?

What is the impact at 1+ years
seeking help for mental illness/new MDE
new pharma Rx
sucidical ideation
loss of productivity/loss of employment
cognitive effects
Questions that remain
3rd Annual Meeting

American Delirium Society
Omni Hotel and Conference Center
Indianapolis, Indiana
June 2-4, 2013
American Delirium Society
You can fool some of the people all the time, and those are the ones you want to concentrate on.
- George W. Bush
The Duhamel Experience
MRP-CORE Investigators
Claudio Rigatto, Navdeep Tangri, Paul Komenda, Manish Sood
Funding Sources
MHRC, MMSF, U of M, Cardiac Sciences Program
Hilary Grocott

Brett Hiebert

Awesome students and research assistants
Ganghong Tian, Bo Xiang, Darren Freed
Heart Failure Partners
Newman MF et al. N Engl J Med 2001, 344(6):395-402.
Roach GW et al. N Engl J Med 1996, 335(25):1857-1864.
Nussmeier N et al. J Cardiothorac Vasc Anesth 1994, 8:13-18.
Sockalingam S et al. J Card Surg 2005;20:560–567. (*review article)
Full transcript