1. A combined early cognitive and physical rehabilitation program for survivors of critical illness:
Feasibility Results of The Activity and Cognitive Therapy in the ICU (ACT-ICU) trial
Nathan E. Brummel, MD
Department Of Medicine
Division Of Allergy, Pulmonary, And Critical Care Medicine
Center For Health Services Research
Vanderbilt University School Of Medicine
Tennessee Valley VA GRECC
Nashville, Tennessee, USA

2. Disclosures: I am supported by NHLBI T32HL087738-05 (PI: Bernard)
I have no industry-related conflicts of interest regarding the content of this presentation.
The content is solely my responsibility and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute or the National Institutes of Health.

3. Critical Illness and Aging
350
300
250
Incident Cases of ARDS
Cases per
100,000
person years
200
150
100 50
(p<0.001 for trend)
15-19
20-24
25-34
35-44
45-54
55-59
60-64
65-74
75-84
≥ 85
Age (yr)
Rubenfeld NEJM 2005; 353:

4. 6 out of 10 ICU patients are ≥ 65
Angus Crit Care Med 2006; 34:
Angus JAMA 2000; 284:
Society of Critical Care Medicine, Critical Care Statistics in the United States, 2012

5. 1.4 Million Annually Seniors Survive a Critical Illness
Wunsch JAMA 2010; 303:
Society of Critical Care Medicine, Critical Care Statistics in the United States, 2012

6. 50-70% Cognitively Impaired © rustyrhodes via Flickr
Wolters Intensive Care Med 2013; 39: 376
Jackson AJRCCM 2010; 182: 183
Girard Crit Care Med 2010; 38: 1513

7. Functionally Impaired
60-80%
Functionally Impaired
Marcel Oosterwijk via Flickr
Latronico Lancet Neurol 2011; 10: 931

8. ICU Survivorship Family Hobbies Work
Iwashyna Annals of Int Med 2010; 153:204-5

9. Rehabilitation of ICU Patients
Ward
Home
Animation
Early Physical
Lancet 2009; 373:

10. Early physical rehabilitation
Early PT+OT (n=55) 80
Proportion of patients with functional independence at hospital discharge
(%) 60
p = 0.048 40
Usual Care (n=49) 20 7 14 21 28 50
100
Hospital Days
Schweickert, Lancet 2009; 373:

11. Rehabilitation of ICU Patients
Ward
Home
Animation
Early Physical
Lancet 2009; 373:
Physical
RETURN
Crit Care Med 2012;40:
Cognitive

12. In-home Cognitive Rehabilitation
Cognitive + Physical Rehab 20
Usual Care 16
Adjusted p<0.01 12
Tower Test Achievement Score 8 4
Enrollment
(Hospital Discharge)
3-Month Follow-Up
Jackson Crit Care Med 2012;40:

13. Rehabilitation of ICU Patients
Ward
Home
Animation
Early Physical
Lancet 2009; 373:
Physical
RETURN
Crit Care Med 2012;40:
Cognitive
Cognitive
ACT-ICU
Early Physical
Phys Ther 2012; 92:

14. Primary Hypothesis
Combined cognitive and physical rehabilitation, started in the ICU and continued cognitive rehabilitation in the home, is safe and feasible to perform.

15. Secondary Hypotheses
This combined intervention will improve cognitive, functional and health-related quality of life outcomes 3-months following hospital discharge.

16. Assessment of Pre-Hospital Functional Status
Randomize
Usual Care
(Group 1)
Physical Therapy
(Group 2)
Cognitive + Physical Therapy
(Group 3)
ABCD
ABCD
ABCD
AND
AND
Physical Therapy
Physical Therapy
In Hospital
AND
Cognitive Therapy
Hospital Discharge
Hospital Discharge
Hospital Discharge
Brummel, Phys Ther 2012; 92:

17. Cognitive + Physical Therapy (Group 3)
Return to Home
Usual Care
(Group 1)
Physical Therapy
(Group 2)
Cognitive + Physical Therapy
(Group 3)
12-Weeks of Goal Management Training
Outpatient Phase
3-month follow-up
assessment
3-month follow-up
assessment
3-month follow-up
assessment
Brummel, Phys Ther 2012; 92:

18. Physical Therapy Protocol Groups 2 & 3
Stupor/ Coma
Awakens to Voice
Alert/ Calm
RASS -5 / -4
RASS -3 / -2
RASS -1 / 0
Study Enrollment
Hospital Discharge
Passive ROM
Passive ROM
Active Exercises
Sit at Edge of Bed
Sit
Stand and Transfer
Walk
ADL Training
Brummel, Phys Ther 2012; 92:

19. Cognitive Therapy Protocol: Group 3 Only
Awakens to Voice
Stupor/ Coma
Alert/ Calm
RASS -5 / -4
RASS -3 / -2
RASS -1 / 0
Study Enrollment
Hospital Discharge
No Intervention
Orientation Exercise
Orientation Exercise
Digit Span Forward
Matrix Puzzles
“Real World” Exercises
Digit Span Reverse
List & Paragraph Recall
Letter-Number Sequences
Pattern Recognition
Brummel, Phys Ther 2012; 92:

20. Digit Spans
Brummel, Phys Ther 2012; 92:

21. Matrix Puzzles ?
Brummel, Phys Ther 2012; 92:

22. ‘Real World’ Exercises
You want to go to an 8:00 movie. Which bus should you take?
Bus Schedule
Leaves Home
6:32
7:14
7:56
8:38
Arrives at Theater
6:57
7:39
8:21
9:03
Brummel, Phys Ther 2012; 92:

23. Pattern Recognition 23 - 20 - 17 - 14 - __ - __ - __ - __
__ - __ - __ - __
Brummel, Phys Ther 2012; 92:

24. Goal-Management Training!
Awareness of Deficits
Compensatory Strategies
STOP
&
Complex Task
Simplified Sub-Tasks
Levine Front Hum Neurosci 2011; 5: 9
Levine, J Int Neuropsychol Soc 2000; 6:
Levine, J Int Neuropsychol Soc 2006; 13:143-52

25. Study Flow 931 Patients with respiratory failure/shock 87 randomized
844 Excluded
142 Substance Abuse/Psych Disorder
100 Critically Ill >72 hours
95 Patient, Surrogate or MD refusal
94 No surrogate available
93 Baseline Physical Disability
85 Baseline Cognitive Impairment
87 randomized
22 Usual
Care
22 Physical Therapy
43 Cognitive + Physical Therapy
9 died
7 died
17 died
6 W/D
12/13 assessed at 3-months
(92%)
14/15 Assessed at 3-months
(93%)
18/26 Assessed at 3-months
(69%)

26. Baseline Characteristics
Usual Care (n=22)
Physical Therapy
(n=22)
Cognitive + Physical
Therapy
(n=43)
Age (years)
60 [51-69]
62 [48-67]
62 [54-69]
Sex (% female)
64%
41%
35%
APACHE II
27 [18-31]
22 [20-29]
25 [20-30]
Mechanical Ventilated
100%
78%
77%
ICU Type (% Medical)
55%
86%
51%
Admission Diagnosis
Sepsis/ARDS/Pneumonia
50%
67%
Abdominal Surgery
23% 5%
16%
Airway Protection
15% 0%
IQCODE
3 [3-3]
Katz ADL
0 [0-0]

27. Early Cognitive Therapy Feasibility
Patients Receiving CT
n/tot (%)
Median Days of CT
% [IQR]
during Mechanical Ventilation
32/33
(97%)
100%
[ %]
during ICU Stay
39/41
(95%)
[85-100%]
during Hospitalization
41/43
[92-100%]
*Only patients in Group 3 received Cognitive Therapy

28. In-home Cognitive Therapy Feasibility
Patients receiving CT
n/total (%)*
Total CT Sessions
Med [IQR]**
In-home Cognitive Therapy
17/18
(94%) 6
[2-6]
*N=number alive and in the study for full 12-week follow-up
** A total of 6 in-home sessions were possible

29. Cognitive + Physical Therapy (n=18)
3-month Cognitive Outcomes
Usual Care (n=12)
Physical Therapy (n=14)
Cognitive + Physical Therapy (n=18) P
Primary Outcome
Tower Test
(Exec. Function) 10
[9-12] 11
[11-12]
[8-11]
.20
Secondary Outcomes
Dysexecutive Questionnaire 18
[9-29]
[5-17] 9
[2-18]
.08
Trails B 50
[30-56] 38
[27-39] 47
[39-53]
.45
MMSE
(Global Cognition) 28
[27-29] 29
[27-30]
[28-30]
.64
Trails A
(Attention) 46
[33-52] 42
[33-51]
[40-50]
.50
Data are median [IQR]

30. Cognitive + Physical Therapy (n=18)
3-month Functional and HRQOL Outcomes
Usual Care (n=12)
Physical Therapy (n=14)
Cognitive + Physical Therapy (n=18) P
Secondary Functional Outcomes
Timed Up and Go
(Functional Mobility) 8
[8-14] 10
[8-13] 11
[9-13]
.79
Katz ADL
(ADL)
[0-0]
[0-1]
[0-2]
.69
FAQ
(IADL) 3
[1-6] 2
[0-5] 1
[0-4]
.67
Secondary Health Related Quality of Life Outcome
EQ-5D Visual Analog Scale
(HRQOL) 75
[61-86] 80
[62-89]
[60-80]
.44
Data are median [IQR]

31. Summary
Nearly all patients were able to undergo cognitive therapy in the earliest stages of critical illness
Patients underwent cognitive therapy on a majority of all study days
Combined cognitive and physical therapy did not alter cognitive or functional outcomes at 3-month follow-up

32. Conclusions
Combined cognitive and physical therapy is feasible early in critical illness
Larger studies are needed to determine the optimal dose and timing of cognitive therapy that will optimize long-term outcomes

33. ICU Delirium and Cognitive Impairment Study Group: selected local members
Pratik Pandharipande
Jim Jackson
Tim Girard
Ed Vasilevskis
Chris Hughes
Paula Watson
Lorraine Ware
Gordon Bernard
Bob Dittus
Ted Speroff
Jack Schnelle
Sandra Simmons
Joanna Stollings
Sunil Geevarghese
Art Wheeler
Leanne Boehm
Joyce Okahashi
Cayce Strength
Aimee Hoskins
Brenda Pun
Hillary Warrington
Amy Kiehl
Lindsay Anderson
Carrie Jones
Rob Gould
Mayur Patel
Amy Graves
Sharon Gordon
Elena Murphy
Bill Pojedinec
Carla Sevin
Jin Han
John Gore
Alessandro Morandi
Cathy Fuchs
Heidi Smith
Wes Ely
Elizabeth Card
Jennifer Thompson
Ayumi Shintani
Stephanie Hamilton
Benjamin Ferrell
Brett Norman
Gillian Sills
Brittany Work