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

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.

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: 1685-93

6 out of 10 ICU patients are ≥ 65 Angus Crit Care Med 2006; 34: 1016-1024 Angus JAMA 2000; 284: 2762-2770 Society of Critical Care Medicine, Critical Care Statistics in the United States, 2012

1.4 Million Annually Seniors Survive a Critical Illness Wunsch JAMA 2010; 303: 849-856 Society of Critical Care Medicine, Critical Care Statistics in the United States, 2012

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

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

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

Rehabilitation of ICU Patients Ward Home Animation Early Physical Lancet 2009; 373: 1874-82

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: 1874-82

Rehabilitation of ICU Patients Ward Home Animation Early Physical Lancet 2009; 373: 1874-82 Physical RETURN Crit Care Med 2012;40:1088-97 Cognitive

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;40:1088-97

Rehabilitation of ICU Patients Ward Home Animation Early Physical Lancet 2009; 373: 1874-82 Physical RETURN Crit Care Med 2012;40:1088-97 Cognitive Cognitive ACT-ICU Early Physical Phys Ther 2012; 92: 1580-92

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

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

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: 1580-92

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: 1580-92

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: 1580-92

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: 1580-92

Digit Spans Brummel, Phys Ther 2012; 92: 1580-92

Matrix Puzzles ? Brummel, Phys Ther 2012; 92: 1580-92

‘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: 1580-92

Pattern Recognition 23 - 20 - 17 - 14 - __ - __ - __ - __ 23 - 20 - 17 - 14 - __ - __ - __ - __ Brummel, Phys Ther 2012; 92: 1580-92

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; 6:299-312 Levine, J Int Neuropsychol Soc 2006; 13:143-52

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%)

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]

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

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

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]

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]

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

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

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