Professional Documents
Culture Documents
Author information continues on Measurements. A battery of neurocognitive and functional outcomes will be
next page. measured 3 and 12 months after hospital discharge.
Post a Rapid Response to Conclusions. If feasible, these interventions will lay the groundwork for a larger,
this article at: multicenter trial to determine their efficacy.
ptjournal.apta.org
W
P.P. Pandharipande, MD, MSCI, Division of ith the aging of the Ameri- (ie, this article deals with injury in
Critical Care, Department of Anesthesiology, can population, it is esti- patients from general medical or
Vanderbilt University School of Medicine,
and Anesthesia Service, Department of Vet-
mated that 1 in 5 Americans surgical ICUs), describes emerging
erans Affairs Medical Center, Tennessee Val- will be over the age of 65 years by rehabilitation strategies for these
ley Healthcare System, Nashville, Tennessee. the year 2030.1 The incidence of impairments, and presents a novel
common critical illness syndromes, investigational protocol of early and
E. Schiro, PT, Acute Rehabilitation Services,
Vanderbilt University Medical Center. including sepsis and acute respira- sustained cognitive rehabilitation
tory distress syndrome (ARDS), paired with early physical rehabilita-
B. Work, OTR/L, Acute Rehabilitation Ser-
increases with age.2,3 Thus, there is tion of patients who are critically ill.
vices, Vanderbilt University Medical Center.
likely to be a large increase in the
B.T. Pun, RN, MSN, ACNP, Center for Health number of patients developing and Cognitive and
Services Research, Department of Medicine,
Vanderbilt University School of Medicine.
surviving an episode of critical care Physical Impairments
in the coming years. Over the last Following Critical Illness
L. Boehm, MSN, RN, ACNS-BC, Vanderbilt decade, advances in the manage-
University School of Nursing, Nashville, Cognitive Impairment
ment of critical illness with therapies Patients who are critically ill fre-
Tennessee.
such as early goal-directed sepsis quently have acute brain dysfunc-
T.M. Gill, MD, Department of Internal Med- resuscitation,4 low tidal volume ven-
icine, School of Medicine, Yale University, tion in the ICU, manifesting as
New Haven, Connecticut.
tilation for ARDS,5 sepsis treatment either delirium or coma.13,14 Delir-
bundles,6 and paired sedation and ium is characterized by an acute
E.W. Ely, MD, MPH, Division of Allergy, Pul- ventilator weaning strategies7 have
monary, Critical Care Medicine and Center change in mental status and a fluctu-
for Health Services Research, and Center for
improved survival rates among peo- ating course, inattention, and dis-
Quality of Aging, Department of Medicine, ple who are critically ill. Never- organized thinking.15 In the ICU,
Vanderbilt University School of Medicine, theless, these survivors, particularly it affects 60% to 80% of patients
and GRECC Service, Department of Veterans elderly people, frequently develop
Affairs Medical Center, Tennessee Valley
who are mechanically ventilated and
newly acquired physical and cogni- is associated with several adverse
Healthcare System, Nashville, Tennessee.
tive impairments (or experience an outcomes, including prolonged
[Brummel NE, Jackson JC, Girard TD, et al. A acceleration of existing difficulties)
combined early cognitive and physical reha-
mechanical ventilation, delayed hos-
that lead to significant reductions in pital discharge, an increased risk
bilitation program for people who are criti-
cally ill: the Activity and Cognitive Therapy in
quality of life.8 –11 of death, and long-term cognitive
the Intensive Care Unit (ACT-ICU) Trial. Phys impairment.16 –19
Ther. 2012;92:1580 –1592.] Long-term cognitive impairment
© 2012 American Physical Therapy Association
emerges in the majority (50% to 75% Long-term cognitive impairment
or more) of survivors of admission to (LTCI) refers to the syndrome of
Published Ahead of Print: May 10, 2012 an intensive care unit (ICU) as the
Accepted: April 27, 2012 significant, and often persistent, cog-
Submitted: November 16, 2011
enduring or residual injury after a nitive deficits following critical ill-
life-threatening illness that is man- ness that varies widely in severity
aged in the ICU setting. During and at its worst can be functionally
patients’ critical illness, this injury debilitating.20 This syndrome may be
first manifests as acute brain dysfunc- observed in one half to three fourths
tion (delirium and coma) accompa- or more of ICU survivors, depending
nying neuromuscular weakness or on the tests used to detect cognitive
ICU-acquired weakness (ICU-AW).12 deficits and how these deficits are
As knowledge of these short-term defined.21–23 These newly acquired
and long-term consequences of crit- deficits have been observed not
ical illness has come to light, the
development of interventions to pre-
vent and rehabilitate these devastat- Available With
ing consequences has been sought. This Article at
This article reviews short-term and ptjournal.apta.org
long-term cognitive and physical
• Listen to a special Craikcast
impairments surrounding critical ill- on the Special Series on
ness that are unrelated to an overt, Rehabilitation in Critical Care
gross, structural brain injury such as with editor Patricia Ohtake.
that related to stroke or trauma
only in investigations of ICU survi- the term “ICU-acquired weakness” ical illness, as they do for patients
vors but also among patients after to describe the clinical syndrome of surviving other diseases, such as car-
acute non-ICU hospitalizations24,25 neuromuscular weakness in patients diac disease, stroke, and traumatic
and after severe sepsis.26 Although who are critically ill, in whom there brain injury.41 As awareness of func-
specific risk factors have not been is no other plausible etiology other tional and cognitive impairments
firmly established, 2 studies have than the critical illness.12,33 after critical illness has grown, pre-
shown the duration of delirium in vention and rehabilitation strategies
the ICU to be an independent Intensive care unit–acquired weak- have been developed, but these strat-
predictor of LTCI among survi- ness presents as symmetric weak- egies focus mainly on rehabilitation
vors of critical illness.19,27 The exact ness that ranges from severe weak- of physical impairments, with little
mechanism or mechanisms that ness to paralysis, with or without a attention on cognitive rehabilitation
lead to these cognitive impairments reduction in deep tendon reflexes.34 of patients who are critically ill.
remain unproven, although hypox- Risk factors for the development of
emia, inflammation, and glucose ICU-AW include multiple organ fail- Cognitive Rehabilitation
dysregulation each have been ure, sepsis, immobility, hyperglyce- Cognitive rehabilitation, focusing
hypothesized to be involved.28 The mia, and corticosteroids.32 This dis- on interventions directed at specific
most frequently reported impair- order has been associated with cognitive impairments (eg, atten-
ments following critical illness poor short-term outcomes, including tion, memory, executive function),
involve the neurocognitive domains difficulty weaning from mechanical is commonplace in the treatment
of executive functioning, memory, ventilation and prolonged ICU and of patients with other acquired
and attention.20 Impairments in hospital stays.35 The most severe brain injuries, such as traumatic
executive functioning are particu- cases of ICU-AW are associated brain injury and stroke, and has been
larly life changing and may manifest with an 8-fold increase in the risk of shown to be effective with many
as difficulties with planning, prob- death.36 Newly acquired functional populations.42 The role of cognitive
lem solving, inhibition, and control impairment and physical disability rehabilitation for the prevention
of behavior in everyday life.29 In nor- related to neuromuscular weakness and treatment of acquired cognitive
mal aging, impaired executive func- are common following critical ill- dysfunction in patients who are
tion is associated with impaired func- ness, and recovery from ICU-AW critically ill is largely unknown. A
tional status.30 For survivors of often is incomplete.37,38 Despite sim- small feasibility trial evaluated cog-
critical illness, these newly acquired ilar levels of pre-illness impairment nitive rehabilitation for survivors of
impairments, particularly those per- in activities of daily living (ADL), critical illness.43 Over the 12-week
taining to executive functioning, elderly patients who are hospitalized study period, patients in the inter-
may have dramatic, life-altering and undergo mechanical ventilation vention group underwent 6 in-home
effects on the patients’ lives, such as develop more profound ADL dis- cognitive rehabilitation sessions and,
inability to return to work or to func- ability compared with those hospital- on alternating weeks, received indi-
tion autonomously.31 ized without mechanical ventilation vidualized physical rehabilitation
and those never hospitalized in the “visits” via tele-technology. In addi-
Physical Impairment year following hospitalization.39 Sur- tion, patients underwent 4 tele-visits
Physical impairment, frequently vivors of ARDS followed at least 5 with an occupational therapist to
manifested as profound weakness, years after their illness had a signifi- aid in functional recovery. After 3
may be accompanied by a combined cantly reduced 6-minute walk dis- months of this multicomponent
motor/sensory neuromyopathy, but tance compared with population intervention, the intervention group
also may exist in the absence of such norms despite return to near-normal demonstrated improved executive
findings, and affects between 25% pulmonary function, indicating long- function and less disability in instru-
and 60% of ICU survivors.12,32 Formal lasting physical impairment.31,40 mental ADL compared with controls.
electrophysiologic testing is not rou- Although encouraging, these results
tinely performed in these patients Rehabilitation of will require validation with a larger,
because treatment of these disorders Impairments in Patients multicenter trial to elucidate the
generally does not differ, testing is Who Are Critically Ill magnitude of this effect and to deter-
difficult in sedated or uncooperative Despite the high prevalence of mine whether these findings trans-
patients, and patients may have elec- impairments after critical illness, for- late into “real-world” improvements
trophysiologic abnormalities with- mal rehabilitation pathways do not in cognitive and physical functioning
out significant weakness. Therefore, commonly exist for survivors of crit- as well as quality of life.
many experts recommend the use of
To our knowledge, no prior study significantly sooner than those in duration and content of postdis-
has evaluated the feasibility and the control group. Patients treated charge physical rehabilitation and
potential benefits of providing early with this intervention were more potential benefits of these interven-
cognitive therapy to ICU patients likely to return to their baseline func- tions remain unknown.
and, indeed, few data exist on the tional status upon hospital dis-
benefits of early cognitive therapy in charge. These results suggest that Combined Early Cognitive
general among patients recovering the timing of early physical rehabili- and Physical Rehabilitation?
from acute illness of any kind. In tation is important in preventing and Whether patients who are critically
implementing in-hospital cognitive rehabilitating newly acquired func- ill can undergo early cognitive reha-
rehabilitation exercises, we relied tional impairments following critical bilitation in much the same way
on the theoretical principle referred illness. In addition, patients under- they can undergo early physical reha-
to in both the popular and scholarly going early physical and occupa- bilitation has not been previously
literature as “use it or lose it.”44,45 tional rehabilitation had fewer days explored. Thus, this study primarily
This principle, often applied to of delirium compared with those not seeks to determine whether early
exercises and muscle training, sug- undergoing early mobility. Thus, cognitive therapy in patients who
gests that brain exercise can have a early physical rehabilitation may are critically ill is feasible.
beneficial effect on cognitive slow- enhance attentional ability, although
ing and may stave off neuropsy- the exact mechanism of this effect is In addition, physical exercise may
chological decline.44 – 46 Stated more unclear. have positive effects on cognition.
mechanistically, this concept posits Indeed, the benefits of vigorous
that neuronal activation can improve Finally, the beneficial effects of early physical exercise on cognitive func-
neuronal function and result in mobility in the ICU may persist fol- tioning have been widely demon-
improved neuronal survival in the lowing discharge. Follow-up of one strated in the context of clinical trials
context of a brain injury. As ICU cohort of patients who underwent with diverse populations.56,57 Fur-
patients characteristically are cog- an early mobility protocol showed thermore, evidence suggests that the
nitively inactive during extended an association between early mobil- cognitive domains of executive func-
hospitalizations, the use of cogni- ity and reduced readmission rates or tion and memory can be improved
tive stimulating exercises may have death in the year following hospital- with exercise.58,59 Whether physical
an effect via the “use it or lose it” ization for critical illness.52 rehabilitation may have beneficial
paradigm of improving cognitive effects on post-ICU cognitive out-
outcomes. Randomized trials of physical reha- comes remains unknown.
bilitation beginning after hospital
Physical Rehabilitation discharge have largely failed to dem- Finally, the effects of a paired early
and Early Mobility onstrate improved patient-centered and sustained cognitive rehabilita-
Early physical rehabilitation of outcomes underscoring the impor- tion and early physical rehabilitation
patients who are critically ill was tance of early mobility.53,54 Patients program on cognitive and physical/
once thought to be an unsafe prac- undergoing an 8-week, in-home, functional status in ICU survivors
tice; however, there is a growing supervised physical rehabilitation have not been studied. To address
body of literature on the safety program did not demonstrate these gaps in knowledge, we pro-
and feasibility of mobilizing these improvements in quality of life or pose to study an interdisciplinary
patients in the ICU to prevent func- 6-minute walk distance.54 Similarly, rehabilitation program aimed at pro-
tional impairments.47–51 The largest post-ICU outpatient rehabilitation viding early and sustained cognitive
trial of early physical rehabilitation with a self-directed physical rehabil- rehabilitation paired with early phys-
to date demonstrated that patients itation manual did not improve ical rehabilitation/early mobility to
could safely begin physical therapy quality of life compared with usual a cohort of medical and surgical
and occupational therapy within the care.53 Conversely, an outpatient patients who are critically ill.
first 72 hours following intubation.51 rehabilitation manual addressing psy-
In this trial, patients in the interven- chological, psychosocial, and physi- Materials and Methods
tion group received physical therapy cal needs of ICU survivors, coupled Research Hypothesis and Aims
and occupational therapy a median with nurse telephone calls and We hypothesize first that early
of 6 days sooner and reached the follow-up clinic visits, improved and sustained cognitive rehabilita-
functional milestones of getting out physical components of quality of tion can be combined with physi-
of bed, standing, marching in place, life compared with patients receiv- cal rehabilitation/early mobility to
transferring to a chair, and walking ing usual care.55 Thus, the optimal create a feasible and safe Activity
• ⬎72 hours since development of respiration failure or shock At the time of study enrollment,
• Cardiac surgery during the current hospitalization demographic data and data on
• Moribund/comfort measures only comorbidities and severity of ill-
• ⬎5 ICU days in the previous 30 days
• IQCODE score ⬎3.3 or neurodegenerative diseases preventing ness (using the Acute Physiologic
independent living and Chronic Health Evaluation II)60
• Inability to perform independent ADL (Katz Activities of Daily Living will be obtained. Baseline cognitive
Scale score of ⬎3)
• Inability to ambulate independently, excluding use of cane or walker impairment will be evaluated using
Exclusion Criteria • Post-cardiac arrest, with suspected anoxic brain injury the Informant Questionnaire of
• Medical or surgical conditions necessitating immobility (eg, long-bone Cognitive Decline in the Elderly
fractures, open abdomen)
• Active substance abuse, psychotic disorder, or suicidal ideation (IQCODE),61 and a score of ⬎3.3 will
• Blind, deaf, or unable to speak English be used to determine the presence
• Prisoners of cognitive impairment. Functional
• Residence ⬎120 miles from Nashville
• Homeless status in the 1 to 2 months prior to
• Attending physician refusal the patient’s acute illness will be
• No surrogate available determined using the Katz Activities
a
ICU⫽intensive care unit, IQCODE⫽Informant Questionnaire of Cognitive Decline in the Elderly, of Daily Living Scale,62 and a cutoff
ADL⫽activities of daily living.
score of ⬎3 will be used to define
functional disability. In addition,
surrogate information regarding a
and Cognitive Therapy in the Inten- decrease the presence and severity patient’s prehospital functional sta-
sive Care Unit (ACT-ICU) protocol of cognitive and physical impairment tus will be obtained using the Dys-
for the management of patients compared with physical rehabili- executive Questionnaire,63 AD8,64
with critical illness. Second, we tation alone and with usual care and Functional Activities Question-
hypothesize that this protocol will through a variety of short-term and naire.65 Data on severity of illness
improve recovery of cognitive and long-term outcome measures. will be collected daily for all
physical functioning among ICU patients.
survivors as well as improve quality Study Protocols
of life. To test our first hypothesis, Participants in the ACT-ICU trial Patients will be randomized in a
we will assess the feasibility and will be recruited from adult patients 1:1:2 manner to 1 of 3 groups: group
safety of this intervention in a single- admitted to the medical and surgical 1 will receive usual care, group 2 will
center, pilot, randomized controlled ICUs at Vanderbilt University Medi- undergo treatment with a physical
trial of patients enrolled from medi- cal Center with respiratory failure, rehabilitation/early mobility proto-
cal and surgical ICUs at Vanderbilt cardiogenic shock, septic shock, or col, and group 3 will undergo treat-
University. Although the trial will not hemorrhagic shock. As pre-existing ment with a paired cognitive and
be powered to prove efficacy, we cognitive and physical impairments physical rehabilitation/early mobility
also will obtain preliminary data to may not be amenable to acute reha- protocol (Fig. 1). Following hospital
examine our second hypothesis. Spe- bilitation, we will screen patients for discharge, patients in group 3 with
cifically, we will evaluate whether pre-existing impairments using vali- evidence of cognitive or physical
these combined interventions can dated tools (described below) and impairment also will receive a
Consent
Randomized
Daily Awakening and Breathing Daily Awakening and Breathing Daily Awwkening ahd Breathing
Trials Trials Trials
AND AND
AND
Abnormal
Executive Function No Assessment Only
or
Functional Mobility? (No Need for GMT)
Yes
7 Days After Discharge Assessment 7 Days After Discharge Assessment 7 Days After Discharge Assessment
ADL, IADL, Physical Function, Executive ADL, IADL, Physical Function, Executive ADL, IADL, Physical Function, Executive
Function (Dysexecutive Questionnaire) Function (Dysexecutive Questionnaire) Function (Dysexecutive Questionnaire)
Outpatient
12 Weeks of GMT
3- and 12-Month Follow-up Assessments 3- and 12-Month Follow-up Assessments 3- and 12-Month Follow-up Assessments
Executive Function Executive Function Executive Function
Functional Mobility Functional Mobility Functional Mobility
Global Cognitive Function Global Cognitive Function Global Cognitive Function
Figure 1.
Flow diagram of the Activity and Cognitive Therapy in the ICU (ACT-ICU) Trial. Patients will be screened for pre-existing cognitive
or physical impairments and then randomized to 1 of 3 groups. Group 1 will receive usual care, group 2 will undergo treatment with a
physical rehabilitation/early mobility protocol, and group 3 will undergo treatment with a paired cognitive and physical
rehabilitation/early mobility protocol. If patients in group 3 demonstrate evidence of cognitive or physical impairments at hospital
discharge, they will undergo a 12-week in-home cognitive rehabilitation program (goal management training [GMT]). Short-term
and long-term outcomes will be assessed at 3 and 12 months following hospital discharge. Each day, all mechanically ventilated
patients will be managed with a protocol of paired spontaneous awakening and breathing trials. Tower Test⫽Delis-Kaplan Executive
Function System (D-KEFS) Tower Test, TUG⫽Timed “Up & Go” Test, MMSE⫽Mini-Mental State Examination, ADL⫽activities of daily
living, IADL⫽instrumental activities of daily living.
will use modified goal management • Systolic blood pressure ⬎180 mm Hg for ⱖ5 min
training (GMT).68 Goal management • Active gastrointestinal bleeding
training is a protocolized approach • Evidence of elevated intracranial pressure
to cognitive rehabilitation that has
• Evidence of myocardial ischemia in last 24 h
been modified and adapted slightly
• Inadequately secured airway
to be optimally tolerable for
our study patients and feasible for • Agitation (RASS ⫹2 to ⫹4)
our staff to deliver. This approach • Presence of a femoral vascular device (no exercises on affected side; no sit, stand, or walk)
has been used in cognitive rehabili- • Increase in the dose of vasopressors in the previous 2 h
tation of patients with traumatic • Need for mechanical ventilation, with FIO2 ⬎0.6 and/or PEEP ⬎10
brain injury,68 frontal lobe dysfunc-
B. Criteria for Cessation of Physical Rehabilitation Session
tion,69 and normal aging,70 and most
• Symptomatic drop in mean arterial pressure (eg, dizziness, light-headedness, syncope)
recently in survivors of critical illness
in a small pilot study by our group.43 • Heart rate ⬍40 or ⬎130 bpmc
Outcome Measures
To provide preliminary data on the
efficacy of the in-hospital interven-
tions, prior to hospital discharge,
we will measure executive function
using the Delis-Kaplan Executive
Function System (D-KEFS) Tower
Test,74 functional mobility with the
Timed “Up & Go” Test (TUG),75
and overall cognitive functioning
Figure 3. with the Mini-Mental State Exami-
Physical rehabilitation protocol. Patient’s level of consciousness using the Richmond
nation (MMSE).76 As not all func-
Agitation-Sedation Scale (RASS) will be determined prior to the daily physical rehabil-
itation session. A patient who is only arousable to physical stimuli (RASS ⫺5/⫺4) will tional and cognitive impairments
undergo passive range of motion (ROM) exercises. Once a patient is able to open his are evident while a patient is hos-
or her eyes to voice (RASS ⫺2/⫺3), passive ROM exercises will be performed, and the pitalized, approximately 1 week fol-
patient will be placed in the chair position in bed. Finally, once a patient is alert and lowing hospital discharge, patients
calm, he or she will progress from active ROM up through ambulation as he or she is
will be assessed via telephone using
able. Sessions will continue until hospital discharge or a patient meets certain functional
milestones. ICU⫽intensive care unit, ADL⫽activities of daily living. Figure modified from the Dysexecutive Questionnaire,63
Morris et al.49 the Functional Activities Question-
naire,65 the Katz Activities of Daily
Living (ADL) Scale,77 and the
Prior to each session, each patient gress through active range of motion Activities-specific Balance Confi-
will be assessed for the presence of exercises of all major joints, bed dence Scale.78
any safety criteria that would pre- mobility exercises (eg, lateral rolling,
clude safely performing the protocol supine to sit), dangling at the edge of The primary outcome of this
(Tab. 2, panel A).72 In addition, if the bed, postural retraining, balance study will be executive functioning
the patient develops any safety cri- exercises (eg, reaching in and out of at 3 months following hospital dis-
teria during the session, the ses- the base of support, challenges to charge, as measured using the
sion will be halted immediately, elicit “righting” reflexes), training in D-KEFS Tower Test (higher scores
and the patient will be placed in a ADL (eating or simulated eating, indicate better performance).74 In
resting position (eg, seated in a grooming, bathing, dressing, and toi- addition, to measure the efficacy of
chair, seated at the edge of the bed, leting), transfer from a seated to a the combined in-hospital and out-of-
lying supine in bed); the session then standing position and from bed to hospital interventions, we will assess
may proceed at the physical thera- chair or commode, standing exer- secondary outcomes of global cogni-
pists’ and occupational therapists’ cises such as reaching in and out of tive function, physical functioning,
discretion (Tab. 2, panel B).47,72 the base of support, mini-squats, and health-related quality of life at 3
Comatose patients (RASS ⫺5/⫺4) marching, and ambulation (with or and 12 months by assessing scores
will undergo passive range of motion without assistive devices) (Fig. 3). If on the following measures:
of all major joints (eg, extension and a patient becomes more alert during
flexion of fingers, wrists, elbows, passive range of motion exercises, • Dysexecutive Questionnaire (test
knees, and ankles; shoulder flexion; the session will immediately pro- of executive function, where
flexion, abduction, and adduction of gress to the appropriate level of higher scores indicate greater
hips). Patients who open their eyes exercises. impairment)63
to voice (RASS ⫺3/⫺2) will undergo • AD8 (assessment of change in cog-
passive range of motion and be Physical rehabilitation sessions will nitive abilities, scored as “Yes,”
placed in the chair position in be performed daily until a patient “No,” or “Don’t know”)64
the bed for up to 2 hours follow- is able to perform all ADL tasks • Short-Informant Questionnaire of
ing the session. Awake and calm with supervision (Functional Inde- Cognitive Decline in the Elderly
patients (RASS ⫺1/0/⫹1) will pro- pendence Measure score of 5 or (assessment of cognitive decline,
where higher scores indicate cally ill, participants will be enrolled ment throughout the study stages,
greater decline)61 in the study until 60 patients survive newly acquired physical weakness,
• TUG (timed test of functional until hospital discharge. This enroll- and lack of awareness of cognitive
mobility, where slower times indi- ment goal is based on our desire to deficits leading to diminished inter-
cate worse performance)75 gather data regarding both the inpa- est in the cognitive rehabilitation
• MMSE (test of overall cognitive tient and outpatient portions of our protocols.
function, where lower scores indi- intervention rather than a formal
cate worse performance)76 power calculation. Inattention and disorganized think-
• Katz ADL Scale (assessment of basic ing are hallmark features of delirium;
ADL, where higher scores indicate To assess success of randomization, therefore, we anticipate that some
greater dependence) the distribution of baseline factors, patients with delirium may struggle
• Activities-specific Balance Confi- such as age, sex, race, severity of with the cognitive rehabilitation
dence Scale (rating of a patient’s illness, and sepsis, will be assessed exercises. In particular, due to their
confidence of maintaining balance by comparing summary measures poor attentional capacity, patients
and remain steady while engaged in among patients randomized into with delirium may have trouble fol-
certain tasks, where higher scores the 3 groups to identify clinically lowing instructions. Cues will be
indicate greater confidence)78 meaningful differences rather than provided to the patients to assist
• Functional Activities Questionnaire relying on statistical testing. To with completion of the exercises,
(assessment of higher-level func- determine the effect of the interven- and engaging them in a stimulating
tional abilities, where higher scores tions on the primary outcome and cognitive task will be emphasized.
indicate greater dependence)65 other continuous outcomes, we
• Trials A & B Test (timed test of will utilize the Kruskal-Wallis test to With regard to extreme physical
executive function [Trials A] and compare D-KEFS Tower Test scores weakness, our protocol addresses
attention [Trials B]; T-scores among the 3 treatment groups. If the needs of individual patients.
adjusted for age, education, and the test is significant, we will use Each patient will progress along the
sex are generated)79 pair-wise Wilcoxon rank sum tests protocol, under the direction of
• A general employment question- to compare each of the active inter- occupational therapists and physical
naire (employment status before vention groups (groups 2 and 3) therapists, who may use any treat-
and after ICU hospitalization) directly with the control group ments (eg, massage therapy and ther-
• Hospital Anxiety and Depression (group 1). To determine the effect apeutic exercise) or rehabilitation
Scale (assessment of anxiety and of the interventions on ICU length tools (eg, tilt table) needed to aid
depression, where higher scores of stay, survival, and other time- individual patients. The goal is to
indicate more severe disease)80 to-event outcomes, the cumulative provide an earlier and increased
• EQ-5D (measure of health out- incidence probability of these out- “dose” of physical therapy and occu-
comes, where lower scores indi- comes will be estimated using the pational therapy than what is typi-
cate worse quality of life)81 Kaplan-Meier product limit method, cally done in many ICUs.
• Canadian Study of Health and and the log-rank test will be used
Aging Frailty Scale (global rating of to compare the 3 groups. With Newly developed cognitive impair-
frailty, where higher scores indi- properly implemented randomiza- ments (eg, thinking and memory
cate increased frailty)82 tion, which should result in bal- problems) are likely not as obvious
• Patient weight anced distribution of measured and to patients as physical impairments
• D-KEFS Tower Test74 at 12-month unmeasured covariates among the that are difficult not to notice (eg,
follow-up treatment groups, the unadjusted inability to ambulate) while in the
analyses will provide the most con- hospital. For example, patients will
We also will track readmission to the servative and unbiased estimate of likely recognize physical limitations
hospital and admission to a nursing the intervention effects. All data will when they are unable to get out of
home or skilled rehabilitation facility be analyzed using the intention-to- bed unassisted, but it may not be as
as secondary outcomes during the treat principle. apparent that they are unable to bal-
12-month follow-up period. ance a checkbook or follow a simple
Methodological Issues recipe. We will emphasize this point
Statistical Analysis Plan We anticipate several difficulties in to patients and attempt to individu-
Given the primary feasibility aim of implementing the rehabilitation pro- alize portions of the study protocol
our study and the high baseline mor- tocols, including delirium, varying to address their needs, specifically
tality rates in patients who are criti- manifestations of cognitive impair- with regard to the optional exer-
7 Girard TD, Kress JP, Fuchs BD, et al. Effi- 22 Jackson JC, Hart RP, Gordon SM, et al. Six- 38 van der Schaaf M, Beelen A, Dongelmans
cacy and safety of a paired sedation and month neuropsychological outcome of DA, et al. Functional status after intensive
ventilator weaning protocol for mechani- medical intensive care unit patients. Crit care: a challenge for rehabilitation profes-
cally ventilated patients in intensive care Care Med. 2003;31:1226 –1234. sionals to improve outcome. J Rehabil
(Awakening and Breathing Controlled tri- Med. 2009;41:360 –366.
23 Jackson JC, Girard TD, Gordon SM, et al.
al): a randomised controlled trial. Lancet. Long-term cognitive and psychological 39 Barnato AE, Albert SM, Angus DC, et al.
2008;371:126 –134. outcomes in the Awakening and Breathing Disability among elderly survivors of
8 Davidson TA, Caldwell ES, Curtis JR, et al. Controlled Trial. Am J Respir Crit Care mechanical ventilation. Am J Respir Crit
Reduced quality of life in survivors of Med. 2010;182:183–191. Care Med. 2012;183:1037–1042.
acute respiratory distress syndrome com- 24 Ehlenbach WJ, Hough CL, Crane PK, et al. 40 Herridge MS, Tansey CM, Matte A, et al.
pared with critically ill control patients. Association between acute care and criti- Functional disability 5 years after acute
JAMA. 1999;281:354 –360. cal illness hospitalization and cognitive respiratory distress syndrome. N Engl
9 Davydow DS, Desai SV, Needham DM, function in older adults. JAMA. 2010;303: J Med. 2011;364:1293–1304.
Bienvenu OJ. Psychiatric morbidity in sur- 763–770. 41 Centre for Clinical Practice. Rehabilita-
vivors of the acute respiratory distress syn- 25 Witlox J, Eurelings LS, de Jonghe JF, et al. tion After Critical Illness (Clinical Guide-
drome: a systematic review. Psychosom Delirium in elderly patients and the risk line No. 83). London, United Kingdom:
Med. 2008;70:512–519. of postdischarge mortality, institutionaliza- National Institute for Health and Clinical
10 Cuthbertson BH, Roughton S, Jenkinson tion, and dementia: a meta-analysis. JAMA. Excellence (NICE); 2009. Available at:
D, et al. Quality of life in the five years 2010;304:443– 451. http://www.nice.org.uk/nicemedia/live/
after intensive care: a cohort study. Crit 12137/43528/43528.pdf. Accessed Sep-
26 Iwashyna TJ, Ely EW, Smith DM, Langa
Care. 2010;14:R6. tember 27, 2011.
KM. Long-term cognitive impairment and
11 Dowdy DW, Eid MP, Sedrakyan A, et al. functional disability among survivors of 42 Cicerone KD, Langenbahn DM, Braden C,
Quality of life in adult survivors of critical severe sepsis. JAMA. 2010;304:1787–1794. et al. Evidence-based cognitive rehabilita-
illness: a systematic review of the litera- tion: updated review of the literature from
27 van den Boogaard M, Schoonhoven L,
ture. Intensive Care Med. 2005;31:611– 2003 through 2008. Arch Phys Med Reha-
Evers AW, et al. Delirium in critically ill
620. bil. 2011;92:519 –530.
patients: impact on long-term health-
12 Stevens RD, Marshall SA, Cornblath DR, related quality of life and cognitive func- 43 Jackson J, Ely EW, Morey MC, et al.
et al. A framework for diagnosing and clas- tioning. Crit Care Med. 2012;40:112–118. Cognitive and physical rehabilitation of
sifying intensive care unit-acquired weak- intensive care unit survivors: results of the
28 Jackson JC, Hopkins RO, Miller RR, et al.
ness. Crit Care Med. 2009;37(10 suppl): RETURN randomized controlled pilot
Acute respiratory distress syndrome, sep-
S299 –S308. investigation. Crit Care Med. 2012;40:
sis, and cognitive decline: a review and 1088 –1097.
13 Ely EW, Inouye SK, Bernard GR, et al. case study. South Med J. 2009;102:1150 –
Delirium in mechanically ventilated 1157. 44 Shors TJ, Anderson ML, Curlik DM Jr,
patients: validity and reliability of the con- Nokia MS. Use it or lose it: how neurogen-
29 Oddy M, Worthington A. The Rehabilita-
fusion assessment method for the inten- esis keeps the brain fit for learning. Behav
tion of Executive Disorders: A Guide to
sive care unit (CAM-ICU). JAMA. 2001; Brain Res. 2012;227:450 – 458.
Theory and Practice. New York, NY:
286:2703–2710. Oxford University Press; 2009. 45 Swaab DF, Dubelaar EJ, Hofman MA, et al.
14 Pandharipande P, Cotton BA, Shintani A, Brain aging and Alzheimer’s disease: use
30 Royall DR, Palmer R, Chiodo LK, Polk MJ.
et al. Prevalence and risk factors for devel- it or lose it. Prog Brain Res. 2002;138:
Declining executive control in normal
opment of delirium in surgical and trauma 343–373.
aging predicts change in functional status:
intensive care unit patients. J Trauma. the Freedom House Study. J Am Geriatr 46 Ball K, Berch DB, Helmers KF, et al. Effects
2008;65:34 – 41. Soc. 2004;52:346 –352. of cognitive training interventions with
15 Task Force on DSM-IV. Diagnostic and older adults: a randomized controlled trial.
31 Rothenhausler HB, Ehrentraut S, Stoll C,
Statistical Manual of Mental Disorders: JAMA. 2002;288:2271–2281.
et al. The relationship between cognitive
DSM-IV-TR. 4th ed. Washington, DC: performance and employment and health 47 Bailey P, Thomsen GE, Spuhler VJ, et al.
American Psychiatric Association; 2000. status in long-term survivors of the acute Early activity is feasible and safe in respi-
16 Ely EW, Shintani A, Truman B, et al. Delir- respiratory distress syndrome: results of an ratory failure patients. Crit Care Med.
ium as a predictor of mortality in mechan- exploratory study. Gen Hosp Psychiatry. 2007;35:139 –145.
ically ventilated patients in the intensive 2001;23:90 –96. 48 Burtin C, Clerckx B, Robbeets C, et al.
care unit. JAMA. 2004;291:1753–1762. 32 de Jonghe B, Lacherade JC, Sharshar T, Early exercise in critically ill patients
17 Shehabi Y, Riker RR, Bokesch PM, et al. Outin H. Intensive care unit-acquired weak- enhances short-term functional recovery.
Delirium duration and mortality in lightly ness: risk factors and prevention. Crit Care Crit Care Med. 2009;37:2499 –2505.
sedated, mechanically ventilated intensive Med. 2009;37(10 suppl):S309 –S315. 49 Morris PE, Goad A, Thompson C, et al.
care unit patients. Crit Care Med. 2010; 33 Griffiths RD, Hall JB. Intensive care unit- Early intensive care unit mobility therapy
38:2311–2318. acquired weakness. Crit Care Med. 2010; in the treatment of acute respiratory fail-
18 Pisani MA, Kong SY, Kasl SV, et al. Days of 38:779 –787. ure. Crit Care Med. 2008;36:2238 –2243.
delirium are associated with 1-year mortal- 34 Schweickert WD, Hall J. ICU-acquired 50 Needham DM. Mobilizing patients in the
ity in an older intensive care unit popula- weakness. Chest. 2007;131:1541–1549. intensive care unit: improving neuromus-
tion. Am J Respir Crit Care Med. 2009; cular weakness and physical function.
180:1092–1097. 35 de Jonghe B, Bastuji-Garin S, Sharshar T, JAMA. 2008;300:1685–1690.
et al. Does ICU-acquired paresis lengthen
19 Girard TD, Jackson JC, Pandharipande PP, weaning from mechanical ventilation? 51 Schweickert WD, Pohlman MC, Pohlman
et al. Delirium as a predictor of long-term Intensive Care Med. 2004;30:1117–1121. AS, et al. Early physical and occupational
cognitive impairment in survivors of criti- therapy in mechanically ventilated, criti-
cal illness. Crit Care Med. 2010;38:1513– 36 Ali NA, O’Brien JM Jr, Hoffmann SP, et al. cally ill patients: a randomised controlled
1520. Acquired weakness, handgrip strength, trial. Lancet. 2009;373:1874 –1882.
and mortality in critically ill patients. Am J
20 Hopkins RO, Jackson JC. Long-term neu- Respir Crit Care Med. 2008;178:261–268. 52 Morris PE, Griffin L, Berry M, et al. Receiv-
rocognitive function after critical illness. ing early mobility during an intensive care
Chest. 2006;130:869 – 878. 37 van der Schaaf M, Dettling DS, Beelen A, unit admission is a predictor of improved
et al. Poor functional status immediately
21 Hopkins RO, Weaver LK, Collingridge D, outcomes in acute respiratory failure.
after discharge from an intensive care unit.
et al. Two-year cognitive, emotional, and Am J Med Sci. 2011;341:373–377.
Disabil Rehabil. 2008;30:1812–1818.
quality-of-life outcomes in acute respira-
tory distress syndrome. Am J Respir Crit
Care Med. 2005;171:340 –347.
53 Cuthbertson BH, Rattray J, Campbell MK, 63 Bodenburg S, Dopslaff N. The Dysexecu- 73 Dodds TA, Martin DP, Stolov WC, Deyo
et al. The PRaCTICaL study of nurse led, tive Questionnaire advanced: item and RA. A validation of the functional indepen-
intensive care follow-up programmes for test score characteristics, 4-factor solu- dence measurement and its performance
improving long term outcomes from criti- tion, and severity classification. J Nerv among rehabilitation inpatients. Arch Phys
cal illness: a pragmatic randomised con- Ment Dis. 2008;196:75–78. Med Rehabil. 1993;74:531–536.
trolled trial. BMJ. 2009;339:b3723. 64 Galvin JE, Roe CM, Powlishta KK, et al. 74 Delis D, Kaplan E, Kramer J. Delis-Kaplan
54 Elliott D, McKinley S, Alison J, et al. The AD8: a brief informant interview to Executive Function System (D-KEFS):
Health-related quality of life and physical detect dementia. Neurology. 2005;65: Examiner’s Manual. San Antonio, TX:
recovery after a critical illness: a multi- 559 –564. Psychological Corporation; 2001.
centre randomised controlled trial of a 65 Pfeffer RI, Kurosaki TT, Harrah CH Jr, et al. 75 Podsiadlo D, Richardson S. The timed “Up
home-based physical rehabilitation pro- Measurement of functional activities in & Go”: a test of basic functional mobility
gram. Crit Care. 2011;15:R142. older adults in the community. J Gerontol. for frail elderly persons. J Am Geriatr Soc.
55 Jones C, Skirrow P, Griffiths RD, et al. 1982;37:323–329. 1991;39:142–148.
Rehabilitation after critical illness: a ran- 66 Ely EW, Truman B, Shintani A, et al. Mon- 76 Folstein MF, Folstein SE, McHugh PR.
domized, controlled trial. Crit Care Med. itoring sedation status over time in ICU “Mini-mental state:” a practical method
2003;31:2456 –2461. patients: reliability and validity of the Rich- for grading the cognitive state of patients
56 Baker LD, Frank LL, Foster-Schubert K, mond Agitation-Sedation Scale (RASS). for the clinician. J Psychiatr Res. 1975;12:
et al. Effects of aerobic exercise on mild JAMA. 2003;289:2983–2991. 189 –198.
cognitive impairment: a controlled trial. 67 Lezak MD. Neuropsychological Assess- 77 Katz S, Akpom CA. A measure of primary
Arch Neurol. 2010;67:71–79. ment. 4th ed. New York, NY: Oxford Uni- sociobiological functions. Int J Health
57 Mead GE, Greig CA, Cunningham I, et al. versity Press; 2004. Serv. 1976;6:493–508.
Stroke: a randomized trial of exercise or 68 Levine B, Robertson IH, Clare L, et al. 78 Powell LE, Myers AM. The Activities-
relaxation. J Am Geriatr Soc. 2007;55: Rehabilitation of executive functioning: an specific Balance Confidence (ABC) Scale.
892– 899. experimental-clinical validation of goal J Gerontol A Biol Sci Med Sci. 1995;50:
58 Colcombe S, Kramer AF. Fitness effects on management training. J Int Neuropsychol M28 –M34.
the cognitive function of older adults: a Soc. 2000;6:299 –312. 79 Corrigan JD, Hinkeldey NS. Relationships
meta-analytic study. Psychol Sci. 2003;14: 69 Levine B, Schweizer TA, O’Connor C, et al. between parts A and B of the Trail Making
125–130. Rehabilitation of executive functioning in Test. J Clin Psychol. 1987;43:402– 409.
59 Erickson KI, Voss MW, Prakash RS, et al. patients with frontal lobe brain damage 80 Zigmond AS, Snaith RP. The hospital anx-
Exercise training increases size of hip- with goal management training. Front iety and depression scale. Acta Psychiatr
pocampus and improves memory. Proc Hum Neurosci. 2011;5:9. Scand. 1983;67:361–370.
Natl Acad Sci U S A. 2011;108:3017–3022. 70 Levine B, Stuss DT, Winocur G, et al. Cog- 81 The EuroQol Group. EuroQol: a new facil-
60 Knaus WA, Draper EA, Wagner DP, Zim- nitive rehabilitation in the elderly: effects ity for the measurement of health-related
merman JE. APACHE II: a severity of dis- on strategic behavior in relation to goal quality of life. Health Policy. 1990;16:
ease classification system. Crit Care Med. management. J Int Neuropsychol Soc. 199 –208.
1985;13:818 – 829. 2007;13:143–152.
82 Rockwood K, Song X, MacKnight C, et al.
61 Jorm AF, Jacomb PA. The Informant 71 Thomsen GE, Snow GL, Rodriguez L, A global clinical measure of fitness and
Questionnaire on Cognitive Decline in Hopkins RO. Patients with respiratory fail- frailty in elderly people. CMAJ. 2005;173:
the Elderly (IQCODE): socio-demographic ure increase ambulation after transfer to 489 – 495.
correlates, reliability, validity and some an intensive care unit where early activity
norms. Psychol Med. 1989;19:1015–1022. is a priority. Crit Care Med. 2008;36:
1119 –1124.
62 Katz S, Ford AB, Moskowitz RW, et al.
Studies of illness in the aged. The Index of 72 Pohlman MC, Schweickert WD, Pohlman
ADL: a standardized measure of biological AS, et al. Feasibility of physical and occu-
and psychosocial function. JAMA. 1963; pational therapy beginning from initiation
185:914 –919. of mechanical ventilation. Crit Care Med.
2010;38:2089 –2094.
http://ptjournal.apta.org/content/92/12/1580#otherarticles
Subscription http://ptjournal.apta.org/subscriptions/
Information
Permissions and Reprints http://ptjournal.apta.org/site/misc/terms.xhtml
Information for Authors http://ptjournal.apta.org/site/misc/ifora.xhtml