1. The Delirious ICU Patient
Timothy D. Girard, MD, MSCI
ICU Delirium and Cognitive Impairment Study Group
Division of Allergy, Pulmonary, & Critical Care Medicine
Center for Health Services Research
Vanderbilt University School of Medicine
VA Tennessee Valley GRECC
Nashville, Tennessee

2. Disclosure
• Hospira, Inc.
• Pfizer, Inc.

3. 1. What is delirium?
What’s 2. How can I diagnose it?
ahead
3. Why does it matter?
4. How should I treat it?

4. What is delirium?

5. Consciousness Cognition

6. di-'lir-E-&m
“a disturbance of consciousness that is
accompanied by a change in cognition that
cannot be better accounted for by a preexisting
or evolving dementia”
– American Psychiatric Association

7. Estimated delirium rates
Mechanically ventilated ICU patients
26%-50%
Non-ventilated ICU patients
10%-25%
Patel R, et al. Crit Care Med 2009;37:825-32

8. Riker, ‘09
Girard, ‘08
Pisani, ‘07
Thomason, ‘05 Medical
Micek, ‘05 ICUs
McNicoll, ‘05
Ely, ‘04
(40%-80%)
McNicoll, ‘03
Ely, ‘01
Guenther, ‘09
Lat, ‘09
Plaschke, ‘07 Mixed
Pandharipande, ‘07 ICUs
Ouimet, ‘07
Skrobik, ‘04
(10%-40%)
Bergeron, ‘01
0 20 40 60 80 100
Actual Prevalence of Delirium

9. Delirium Subtypes in the ICU
100
80
60
%
40
20
0
Hypoactive Mixed Hyperactive
Peterson JF, et al. J Am Geriatr Soc 2006;54:479-84

10. 1. Definition
1 2. Prevalence
3. Subtypes
Summary

11. How can I diagnose ICU delirium?

12. 1 2

13. Which diagnostic method?
41% - none
37% - clinical assessment
14% - Confusion Assessment Method-ICU
2% - Delirium Rating Scale
2% - Mini Mental State Examination
01% - Delirium Screening Checklist
1%
Patel R, et al. Crit Care Med 2009;37:825-32

14. Confusion Assessment Method-ICU
Acute onset of changes or
fluctuations in the course
Feature 1
of mental status
and
Feature 2
Inattention
and either
Altered level of
Feature 3
Disorganized thinking or Feature 4
consciousness
Ely EW, et al. JAMA 2001; 286:2703-10

15. Intensive Care
Delirium Screening Checklist (ICDSC)
Altered level of consciousness
Inattentiveness
Disorientation ≥4 = delirium
Hallucination-delusion-psychosis
Psychomotor agitation or retardation
Inappropriate speech or mood
Sleep/wake cycle disturbance
Symptom fluctuation
Bergeron N, et al. Intensive Care Med 2001; 27:1297-1304

16. Validity of ICU Delirium Assessment Tools
Sensitivity Specificity
100
80
60
%
40
20
0
CAM-ICU Nu-DESC DDS ICDSC*
*Van Eijk MM, et al. Crit Care Med 2009;37:1881-5
Luetz A, et al. Crit Care Med 2010;38: [ePub ahead of print]

17. 2 1. Challenges
2. Diagnostic instruments
Summary

18. Why is ICU delirium important?

20. 5X self-extubation
Dubois MJ, et al. Intensive Care Med 2001;27:1297-1304

21. ICU Cost
per patient = $9,000
$60,000
$48,666
$50,000
Median Cost
$40,000 $34,976
$34,007
$30,000
$21,289 $19,702
$20,000
$11,870
$10,000
Mild Moderate Severe
Delirium Severity Index
Milbrandt EB, et al. Crit Care Med 2005;32:955-62

22. Delirium and Mortality
100
Never Delirious (n=41)
80
Survival (%)
60 Ever Delirious (n=183)
40 3X death
HR, 3.2; 95% CI, 1.4-7.7; p=0.008
20 Persistently Comatose (n=51)
0
0 1 2 3 4 5 6
Months Ely EW, et al. JAMA 2004;291:1753-62

23. 49-yr-old women with sepsis/ARDS
>3 years later

24. Delirium and Post-ICU Cognition
60
50
(Predicted Mean T-Score)
Cognitive Performance
40
T
30
20
*Adjusted β -5.2, 95% CI -9.8 to -0.7
10 p=.02
0
0 5 10 15 20
Days of Delirium among ICU Survivors
Girard TD, et al. Unpublished data from the ABC Trial

25. 1. 5X self-extubation
2. 2X hospital stays
3 3. $9000 ICU costs
4. 3X 6-month mortality
Summary
5. More cognitive impairment

26. How should I treat ICU delirium?

28. Treat pain with opioids
Morrison RS, et al. J Geront A Biol Sci Med 2003;58:76-81

29. Is intervention needed?
yes – 92%
no – 1%
Patel R, et al. Crit Care Med 2009;37:825-32

31. Lorazepam and Delirium
100
Prevalence of Delirium (%)
90
80
70
60
50
No Drug 0-1 1-2 2-3 3-4 4+ Log scale
0-2.7 2.7-7.4 7.4-20 20-55 55+ Original scale
Lorazepam Dose (mg)
Pandharipande PP, et al. Anesthesiology 2006;104:21-6

32. ABC Trial - Benzodiazepines
70
Control
60
Protocol
Daily Dose of Benzodiazepines
50
40
30
20
10
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Study Day

33. Effect of Wake Up and Breathe on
Brain Function
p=.002 p=.50
16
14
12
10
Days 8
6
4
2
0
Control Protocol Control Protocol
Coma Delirium
Girard TD, et al. Lancet 2008;371:126-34

34. Effect of Wake Up and Breathe
100 on Coma
90
80
Protocol
Comatose Patients (n)
70
60 Control
50
40
30
20
10
0
1 2 3 4 5 6 7 8 9 10111213141516171819202122232425262728
Study Day
Girard TD, et al. Unpublished data from the ABC
Trial.

35. Effect of Wake Up and Breathe
60 on Delirium
50
Protocol
Delirious Patients (n)
(
40
Control
30
20
10
0
1 2 3 4 5 6 7 8 9 10111213141516171819202122232425262728
Study Day
Girard TD, et al. Unpublished data from the ABC
Trial.

36. Which drug for delirium?
86% - haloperidol
37% - atypical antipsychotics
35% - benzodiazepines
13% - propofol
8% - opiates
5% - dexmedetomidine
Patel R, et al. Crit Care Med 2009;37:825-32

37. Haloperidol
Initial: 2 mg iv
Double the dose q15-20 min until calm
Then: Continue q4-6 hrs for 2-3 days
Taper for 2-3 days
Warnings
QT prolongation
EPS/NMS
Esophageal dysmotility
Jacobi J, et al. Crit Care Med 2002;30:119-41

38. Trial of Antipsychotics for ICU Delirium
8
Haloperidol
7 Olanzapine
Delirium Index Score
6
5
4
3
1 2 3 4 5
Days
Skrobik YK, et al. Intensive Care Med 2004;30:444-9

39. Antipsychotics – Delirium and Coma
100
Patients without Delirium or Coma (%)
(
p=0.66
80
60
40
Haloperidol (n=35)
Ziprasidone (n=32)
20
Placebo (n=36)
0
1 5 10 15 20
Day
Girard TD, et al. Crit Care Med 2010;38:428-37

40. Quetiapine – Resolution of Delirium
100
80
Quetiapine (n=18)
Patients with Delirium (%)
Placebo (n=18)
(
60
p=0.001
40
20
0
0 2 4 6 8 10
Day
Devlin JW, et al. Crit Care Med 2009 Nov 18. [Epub ahead of print]

41. Which drug for delirium?
86% - haloperidol
37% - atypical antipsychotics
35% - benzodiazepines
13% - propofol
8% - opiates
5% - dexmedetomidine
Patel R, et al. Crit Care Med 2009;37:825-32

42. Dexmedetomidine vs. Lorazepam
p=0.01 p=0.09 p<0.001
12
10
8
6
4
2
Dexmedetomidine
Lorazepam
0
Delirium/Coma-Free Days Delirium-Free Days Coma-Free Days
Pandharipande PP, et al. JAMA 2007;298:2644-53

43. Daily Risk of Delirium in MENDS
Dexmedetomidine Lorazepam
90 p=0.02
80
70
Delirious Patients (%)
60
50
40
30
20
10
0
1 2 3 4 5 6
Study Day
Pandharipande PP, et al. Unpublished data from MENDS

44. Daily Risk of Delirium in SEDCOM
Dexmedetomidine Midazolam
80 p<0.001
70
Delirious Patients (%)
60
50
40
30
20
10
0
Baseline 1 2 3 4 5 6
Study Day
Riker RR, et al. JAMA 2009;301:489-499

45. Dexmedetomidine – Extubation
100
Patients Mechanically Ventilated (%)
p=.01
80
Midazolam
60
Dexmedetomidine
40
20
0
0 2 4 6 8
Days
Riker RR, et al. JAMA 2009;301:489-499

46. Reduce immobility
Promote consciousness
Photo by Chris Hartlove for The New York Times

47. Effect of Early Mobility on Outcomes
Outcome* Early PT/OT Control p
Independent functional status
at discharge, % 59% 35% 0.02
Barthel Index score at discharge 75 [7.5-95] 55 [0-85] 0.05
ICU-acquired paresis at discharge 31% 49% 0.09
Ventilator-free days 23.5 [7.4-25.6] 21.1 [0-23.8] 0.05
ICU delirium, days 2.0 [0-6.0] 4.0 [2.0-7.0] 0.03
ICU length of stay, days 5.9 [4.5-13.2] 7.9 [6.1-12.9] 0.08
Hospital length of stay, days 13.5 [8.0-23.1] 12.9 [8.9-19.8] 0.93
In-hospital mortality 18% 25% 0.53
*Median [IQR] or %
Schweickert WD, et al. Lancet 2009;373:1874-82

48. 1. Prevention
2. Diagnose etiology
3. Treat pain
4 4. Avoid benzodiazepines
5. Antipsychotics
Summary
6. Dexmedetomidine
7. Early mobility

49. 1. What is delirium?
Looking 2. How can I diagnose it?
back
3. Why does it matter?
4. How should I treat it?