Physical Rehabilitation in the ICU:

A Systematic Review and Meta-Analysis*

Yi Tian Wang, BPhysio1,2
OBJECTIVES: Significant variability exists in physical rehabilitation modalities Jenna K. Lang, BPhysio (Hons)3
and dosage used in the ICU. Our objective was to investigate the effect of phys-
Kimberley J. Haines, PhD, BHSc
ical rehabilitation in ICU on patient outcomes, the impact of task-specific training,
(Physio)3,4
and the dose-response profile.
Elizabeth H. Skinner, PhD, MBBS
Downloaded from http://journals.lww.com/ccmjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 03/14/2022

DATA SOURCES: A systematic search of Ovid MEDLINE, Cochrane Library, (Hons), BPhysio (Hons)1,3
EMBASE, and CINAHL plus databases was undertaken on the May 28, 2020. Terry P. Haines, PhD, BPhysio1,5
STUDY SELECTION: Randomized controlled trials and controlled clinical tri-
als investigating physical rehabilitation commencing in the ICU in adults were
included. Outcomes included muscle strength, physical function, duration of me-
chanical ventilation, ICU and hospital length of stay, mortality, and health-related
quality of life. Two independent reviewers assessed titles, abstracts, and full texts
against eligibility criteria.
DATA EXTRACTION: Details on intervention for all groups were extracted using
the template for intervention description and replication checklist.
DATA SYNTHESIS: Sixty trials were included, with a total of 5,352 participants.
Random-effects pooled analysis showed that physical rehabilitation improved phys-
ical function at hospital discharge (standardized mean difference, 0.22; 95% CI,
0.00–0.44), reduced ICU length of stay by 0.8 days (mean difference, –0.80 d;
95% CI, –1.37 to –0.23 d), and hospital length of stay by 1.75 days (mean differ-
ence, –1.75 d; 95% CI, –3.03 to –0.48 d). Physical rehabilitation had no impact on
the other outcomes. The intervention was more effective in trials where the control
group received low-dose physical rehabilitation and in trials that investigated func-
tional exercises.
CONCLUSIONS: Physical rehabilitation in the ICU improves physical function
and reduces ICU and hospital length of stay. However, it does not appear to im-
pact other outcomes.
KEY WORDS: dose-response; healthcare utilization; physical function; physical
rehabilitation; task-specific training

U
p to 65% of critical illness survivors suffer clinically detectable weak-
ness from a combination of muscle mass loss, myopathy (1, 2), and
polyneuropathy (3). These changes occur early in ICU admission and
are associated with prolonged weaning from mechanical ventilation (MV)
(4–6) and increased ICU (6, 7) and hospital length of stay (LOS) (7). Clinical
weakness is also associated with increased mortality in ICU (8), in-hospital (8, 9),
and over the first year after ICU discharge (10).
Physical rehabilitation is a commonly adopted approach to manage the *See also p. 504.
physical sequelae of critical illness, following a signal in clinical trials (11–13). Copyright © 2021 by the Society of
Rehabilitation begins in the ICU, with the intent to reverse muscle catabolism, Critical Care Medicine and Wolters
mitigate neuropathy, and minimize the effects of immobility (14). Early system- Kluwer Health, Inc. All Rights
atic reviews have demonstrated the safety and feasibility of physical rehabili- Reserved.
tation in the ICU (15), as well as improvements in physical function (16, 17), DOI: 10.1097/CCM.0000000000005285

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Wang et al
health-related quality of life (HRQoL), muscle strength,
ventilator-free days, and ICU LOS (16). However, recent
systematic reviews with meta-analyses (18–21) have not
consistently supported these findings. Considerable het-
erogeneity in routine physical rehabilitation practices in
ICUs exist globally (22–24), and previous reviews have
not considered the amount of physical rehabilitation
available to the control group as a confounding factor
and source of heterogeneity. Furthermore, investigation
of the effectiveness of task-specific training in the ICU is
clinically important, as this involves more complex deci-
sion-making affecting sedation optimization, feasibility,
and safety. This review aimed to determine:
1) Does physical rehabilitation in ICU improve patient
outcomes?
2) Are functional exercise interventions more effective than
nonfunctional exercises?
3) How does the dose of control therapy impact the effective-
ness of experimental interventions?
MATERIALS AND METHODS
Study Design
This protocol was registered on the International
Prospective Register of Systematic Reviews
(PROSPERO) (CRD42017074228). Reporting con-
forms to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (25) guidelines and The
Cochrane Handbook (26).
Study Selection and Databases
Ovid MEDLINE, EMBASE, CINAHL plus, and the
Cochrane Library were electronically searched for ran-
domized controlled trials (RCTs) and controlled clin-
ical trials (CCTs) evaluating physical rehabilitation in
critically ill patients (e-Appendix 1—Search strategy,
http://links.lww.com/CCM/G656).
Publications available from January 1, 2000, to
May 28, 2020, were screened against eligibility crite-
ria (Table 1) by two independent reviewers (Y.T.W.,
J.K.L.). Full-text articles were obtained if titles and
abstracts were insufficient. Conflicts were discussed
between the two reviewers and adjudicated by a third
reviewer (T.P.H.) if required.
Data Extraction
Data extraction included study design, participant, in-
tervention delivered using the template for intervention
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description and replication (TIDieR) (27), and prede-
fined outcomes (details listed in e-Appendix 1, http://
links.lww.com/CCM/G656).
Risk of Bias
Two reviewers (Y.T.W., J.K.L.) independently assessed
the risk of bias at the outcome level. Conflicts were dis-
cussed between the two reviewers and adjudicated by a
third reviewer (T.P.H.) if required. The Cochrane risk-of-
bias tool for randomized trials (28) was used to assess the
RCTs. The Risk Of Bias In Nonrandomized Studies—of
Interventions assessment tool (29) was used to assess the
CCTs. The visualization tool for risk of bias assessments
in a systematic review (30) was used to present results.
Summary of Measures
Principal summary measures were the pooled standard-
ized mean difference, mean difference, or risk difference
with a 95% CI. For outcomes in which multiple hetero-
geneous outcome measures were reported across stud-
ies, results were summarized as a standardized mean
difference to facilitate their inclusion (a key limitation
in research synthesis) by standardizing the results of
the individual studies to a uniform scale. Standardized
mean difference expresses the size of the intervention
effect relative to the variability observed in each study
(26). Interpretation of the magnitude of standardized
mean difference is based on previous guidelines (31).
Where a single outcome measure was used, mean dif-
ference was used. Mortality outcomes were summarized
using risk difference.
Synthesis of Results
Random-effects meta-analysis was performed with
STATA/SE Version 13 (StataCorp LP, Austin, TX) to
quantify the effect of the intervention. Studies with
more than two groups were included. Studies that pre-
sented data in alternate methods than mean and sd
were attempted to be included (see e-Appendix 1, http://
links.lww.com/CCM/G656, for detailed methods).
Subgroup and Sensitivity Analyses
Subgroup analyses and meta-regression of studies in-
cluded in the primary pooled analysis were preplanned
according to PROSPERO registration.
Stratifications occurred post hoc because it was un-
known how much detail regarding intervention type
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 Feature Articles

TABLE 1.
Inclusion and Exclusion Criteria of Studies
Characteristics Inclusion Exclusion

Design Randomized controlled trials and controlled clinical trials Pre-post intervention trials, case report,
reviews, editorials, descriptive
commentary
Participants Adults admitted to an ICU Ages < 18
Participants with head injuries,
cerebrovascular accidents, burns,
and spinal injuries
Intervention Physical rehabilitation commenced in the intensive care, Physical rehabilitation delivered only
including but not limited to: Passive range of motions after discharge from ICU
exercises, active range of motion exercises, resistance Speech and swallowing rehabilitation
training, positioning, functional mobility and transfers,
respiratory muscle training, neuromuscular electrical Cognitive rehabilitation
stimulation, tilt tabling, cycle ergometry, or any combination
of above
Control Standard care
Outcome measures Muscle strength at awakening, ICU discharge, and hospital
discharge
Physical function at ICU discharge, hospital discharge and
at 6 mo
Mortality in ICU, in hospital and at 6 mo
Health-related quality of life at 6 mo
Duration of mechanical ventilation
Mechanical ventilation-free days at day 28
ICU LOS Hospital LOS
Publication status English only. Published after the year 2000 Studies published before the year 2000
LOS = length of stay.

and dosage would be available. Subgroup analyses by
individual intervention components were unable to be
performed due to insufficient reporting, and many tri-
als combined multiple interventions. Meta-regression
analysis by delivered dosage was also not possible due
to insufficient reporting of intervention delivery, for
both intervention and control groups.
Subgroup analyses were conducted to compare the
type of experimental intervention: functional exercise(s)
(defined as lifting head, rolling, sitting up, sitting balance,
standing, transferring, walking) versus nonfunctional ex-
ercise (defined as passive or active range of motion, neu-
romuscular electrical stimulation, and cycle ergometry).
These subgroups were based on evidence that task-spe-
cific exercises may be more effective than impairment-
based training in non-ICU patients (32–35).
Subgroup analyses were also conducted by stratify-
ing the amount of physical rehabilitation available to
control group participants as a part of routine care.
High-dose control therapy was defined as the control
group receiving or being assessed for physical rehabil-
itation greater than or equal to 5 days per week. Low-
dose control therapy was defined as the control group
receiving or being assessed for physical rehabilitation
less than 5 days per week. These subgroups were deter-
mined by surveys of mobilization practices in Canada
(36) and the United States (37), and the standard care
delivered by recent trials investigating the efficacy of
physical rehabilitation in the ICU. Standard practice has
likely evolved over time since the earliest trials found
benefits (11, 38, 39). For example, in the 23 trials pub-
lished since 2017 (40–62), 19 (40–50, 52, 53, 55, 57–60,
62) reported that physical rehabilitation was available
to the control group greater than or equal to 5 days per
week. In contrast, out of 19 trials published before 2015
(11, 38, 39, 63–78), only four (39, 69, 70, 74) reported

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Wang et al
that physical rehabilitation was available to the control
group greater than or equal to 5 days per week.
Meta-regression analysis examined the differences
between the subgroups on the effect of the intervention.
Post hoc analysis of RCTs only was performed. Post hoc
sensitivity analyses were performed to ensure any deci-
sions to exclude trials from the meta-analysis did not
change the results of the primary pooled analysis.
RESULTS
Flow of Studies
Database searches totaled 7,382 articles. After removal
of duplicates, screening by title, abstract, and full-text,
62 reports (11, 38–98) of 60 trials were included in this
review (e-Fig. 1, http://links.lww.com/CCM/G657;
legend, http://links.lww.com/CCM/G667).
Characteristics of Included Studies
A total of 5,352 participants were recruited across 60
trials, 2,699 intervention and 2,653 control (e-Table 1,
http://links.lww.com/CCM/G658). The cohort rep-
resented a mixture of medical and surgical patients
across 21 countries, predominantly middle-aged, with
a bias toward males. Most participants were recruited
from Europe, America, and South America. A sum-
mary of interventions and outcome measures are listed
in e-Table 1 (http://links.lww.com/CCM/G658).
Risk of Bias
The risk of bias of included studies was considerable,
with 31 of 57 RCTs classified as “high” risk of bias (e-
Fig. 2, http://links.lww.com/CCM/G659; and e-Fig. 3,
http://links.lww.com/CCM/G660 [legend, http://links.
lww.com/CCM/G667]), and four of five CCTs with a
“Serious or Critical” risk of bias (e-Fig. 4, http://links.
lww.com/CCM/G661; legend, http://links.lww.com/
CCM/G667). Major sources of bias for RCTs were due
to domain two, deviations from intended interventions;
domain five, bias in selection of the reported result.
Twenty-five RCTs rated “high” risk of bias for domain
two, due to poor reporting of interventions and lack of
an appropriate analysis to estimate the effect of inter-
vention adherence. Forty-nine RCTs were rated “some
concerns” for domain five by the two reviewers, due to
lack of a prespecified analysis plan before unblinded
outcome data were available.
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Pooled Analysis of Intervention Effect
Duration of Mechanical Ventilation. Forty-six stud-
ies (11, 38, 40, 41, 43, 44, 46–50, 52–55, 57, 59–64, 66,
67, 69–74, 77, 78, 80–85, 87–91, 93, 95, 98) reported
duration of MV (e-Appendix 2, http://links.lww.com/
CCM/G662).
A meta-analysis of pooled data showed no difference
in duration of MV between groups (mean difference,
–0.18; 95% CI, –0.37 to 0.02) (Fig. 1). In studies where
the control group received low-dose physical rehabilita-
tion (n = 15), the intervention resulted in a reduction of
MV duration by 1.6 days (mean difference, –1.6 d; 95%
CI, –2.49 to –0.71 d), but not in studies where the con-
trol group received high-dose physical rehabilitation
(n = 18) (mean difference, 0.21; 95% CI, 0.03–0.40)
(Fig. 1). Studies investigating functional experimental
intervention (n = 16) demonstrated the intervention
resulted in a reduction of MV duration (mean difference,
–1.15; 95% CI, –1.99 to –0.30), while nonfunctional ex-
perimental intervention (n = 18) increased duration of
MV (mean difference, 0.14; 95% CI, 0.00–0.27). Meta-
regression analysis of these study characteristics, sensi-
tivity analysis and subgroup analysis of RCTs are included
in e-Appendix 2 (http://links.lww.com/CCM/G662).
ICU Length of Stay. Forty-seven studies (11, 38–42,
44–50, 52, 53, 55, 57–63, 66, 67, 69–72, 74, 76–85, 87,
88, 90–94) reported ICU LOS (e-Appendix 2, http://
links.lww.com/CCM/G662).
Physical rehabilitation reduced ICU LOS by 0.8
days (mean difference, –0.80; 95% CI, –1.37 to –0.23)
(Fig. 2). This effect was magnified in studies where the
control group received low-dose physical rehabilita-
tion (n = 14), with a 1.87-days reduction in ICU LOS
compared with control (mean difference, –1.87; 95%
CI, –3.16 to –0.58). In contrast, in studies where the
control group received high-dose physical rehabilita-
tion (n = 27), the intervention did not change the ICU
LOS (mean difference, 0.23; 95% CI, –0.29 to 0.75).
Subgroup analysis of studies with functional exper-
imental intervention (n = 21) demonstrated the in-
tervention resulted in a reduction of ICU LOS (mean
difference, –1.31; 95% CI, –2.46 to –0.16), while non-
functional experimental intervention (n = 20) resulted
in no difference between groups (mean difference,
–0.26; 95% CI, –0.98 to 0.45) (Fig. 2). Meta-regression
analysis of these study characteristics, sensitivity anal-
ysis and subgroup analysis of RCTs are included in
e-Appendix 2 (http://links.lww.com/CCM/G662).
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Figure 1. Meta-analysis and pooled effect sizes (raw mean difference [d]) on the duration of mechanical ventilation for physical
rehabilitation and standard care with subgroup analysis according to the dosage of control intervention.

Hospital Length of Stay. Thirty-three studies (11,
38–41, 46–48, 50, 52, 53, 55, 60–63, 69–71, 74, 76,
78, 81, 83–85, 87, 88, 90–94) reported hospital LOS
(e-Appendix 2, http://links.lww.com/CCM/G662).
Physical rehabilitation reduced hospital LOS by 1.75
days (mean difference, –1.75 d; 95% CI, –3.03 to –0.48 d)
(Fig. 3). This effect was magnified in studies where the
control group received low-dose physical rehabilitation
(n = 11), with a 2.45 days reduction in hospital LOS
compared with control (mean difference, –2.45 d; 95%
CI, –4.05 to –0.84 d), but not in studies where the con-
trol group received high-dose physical rehabilitation
(n = 16) (mean difference, 0.16; 95% CI, –1.62 to 1.29)
(Fig. 3). Subgroup analysis of studies with functional

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Wang et al

Figure 2. Meta-analysis and pooled effect sizes (raw mean difference [d]) on the ICU length of stay for physical rehabilitation and
standard care with subgroup analysis according to the type of exercise used in the intervention group.

(n = 14) versus nonfunctional experimental interven- LOS compared with control (mean difference, –1.90;
tion (n = 13) demonstrated that the functional experi- 95% CI, –3.74 to –0.06), while nonfunctional experi-
mental intervention resulted in a reduction of hospital mental intervention resulted in no difference between

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 Feature Articles

Figure 3. Meta-analysis and pooled effect sizes (raw mean difference [d]) on the hospital length of stay for physical rehabilitation and
standard care with subgroup analysis according to the dosage of control intervention.

groups (mean difference, –1.39; 95% CI, –3.43 to 0.66).
Meta-regression analysis of these study characteris-
tics, sensitivity analysis and subgroup analysis of RCTs
are included in e-Appendix 2 (http://links.lww.com/
CCM/G662).
Mortality. Thirty-one trials (n = 2,945) (41, 43–45,
47–50, 53, 56, 58, 61, 62, 65, 66, 68, 70, 72–74, 76, 77,
82, 84, 85, 87, 88, 90, 93, 97) reported ICU mortality.
Twenty-seven trials (n = 3,336) (11, 38, 41, 43, 47, 48,
50, 52, 53, 56, 61, 62, 74, 76, 77, 80–85, 88, 92–95)
reported hospital mortality. Nine RCTs (n = 1,373)
(41, 43, 50, 74, 85, 87, 92, 93, 96) reported 6-month
mortality. Pooled analysis demonstrated no difference
between intervention and control groups at any of
the time points (e-Fig. 5, http://links.lww.com/CCM/
G663; legend, http://links.lww.com/CCM/G667).
Subgroup analysis and sensitivity analysis are included
in e-Appendix 2 (http://links.lww.com/CCM/G662).
Muscle Strength. Six trials (46, 53, 66, 86, 88, 90)
reported muscle strength on first awakening. Twenty-
one trials (39, 41, 43, 46–48, 50, 52, 53, 57, 62, 70,
72, 75, 84, 85, 87, 88, 90, 92, 97) reported at least one

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Wang et al
muscle strength outcome at ICU discharge. Eleven tri-
als (11, 39, 47, 48, 50, 52, 53, 84, 88, 92, 97) reported
at least one muscle strength outcome at hospital dis-
charge. See e-Appendix 2 (http://links.lww.com/CCM/
G662) for details on these studies.
Physical rehabilitation did not change the pooled
standardized mean difference for muscle strength at
any time point (e-Fig. 6, http://links.lww.com/CCM/
G664; legend, http://links.lww.com/CCM/G667).
Subgroup analysis and sensitivity analysis are included
in e-Appendix 2 (http://links.lww.com/CCM/G662).
Physical Function. Twenty-one (11, 39, 41, 43, 46,
47, 50, 52, 53, 57, 58, 62, 72, 74, 84, 85, 87, 88, 92, 94,
97) studies reported at least one physical function out-
come at ICU discharge. Fifteen trials (11, 39, 41, 47,
50, 52, 53, 55, 61, 74, 76, 84, 88, 92, 94) reported at
least one physical function outcome at hospital dis-
charge. Eight RCTs (n = 725) (43, 50, 52, 74, 85, 87,
92, 93) reported at least one physical function outcome
at 6 months. See e-Appendix 2 (http://links.lww.com/
CCM/G662) for details on these studies.
Physical rehabilitation resulted in a small improve-
ment of the physical function at hospital discharge
(standardized mean difference, 0.22; 95% CI, 0.00–
0.44), but there was no difference between groups at
ICU discharge and 6 months follow-up (Fig. 4). To aid
interpretation, this magnitude of effect is similar to the
trial by Wright et al (50), who found the Functional
Independence Measure was six points higher at ICU
discharge compared with control, given their reported
sd of 26 (a standardized mean difference of 0.23).
Subgroup and sensitivity analysis are included in
e-Appendix 2 (http://links.lww.com/CCM/G662).
MV-Free Days. Six RCTs (11, 43, 51, 56, 85, 92) re-
ported ventilator-free days at day 28 (e-Appendix 2,
http://links.lww.com/CCM/G662). There was no dif-
ference between the number of MV-free days interven-
tion and control groups at day 28 (e-Fig. 7, http://links.
lww.com/CCM/G665; legend, http://links.lww.com/
CCM/G667). Sensitivity analysis, including a study
with skewed data (11), did not change the pooled re-
sult. There were no differences between groups for any
of the subgroup analyses.
Health-Related Quality of Life. Ten RCTs (n = 843)
(41, 43, 50, 52, 62, 74, 85, 87, 92, 93) reported at least one
HRQoL outcome at 6 months. All were included in the
pooled analysis. There was no difference in the HRQoL
between intervention and control groups at 6 months
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(e-Fig. 8, http://links.lww.com/CCM/G666; legend,
http://links.lww.com/CCM/G667). There were no differ-
ences between groups for any of the subgroup analyses.
DISCUSSION
Key Findings and Clinical Implications
This meta-analysis found that physical rehabilitation
begun in the ICU improved physical function at hos-
pital discharge and reduced ICU and hospital LOS
compared with usual care.
It is highly plausible that physical rehabilitation
would have beneficial effects on the ICU LOS. Exercise
has been shown to positively affect cognition and res-
olution of delirium (11, 99). Sedation optimization is
a requirement for functional exercises, while sedation
break alone has been shown to decrease MV duration
and ICU LOS (100, 101). Hospital LOS can be influ-
enced by physical function, particularly if the discharge
destination is directly home. We found the hospital LOS
was shorter in the intervention group, with better phys-
ical function outcomes at hospital discharge.
In studies where the control group received low-
dose physical rehabilitation, the intervention resulted in
reductions in the duration of MV and ICU and hospital
LOS. In contrast, the intervention did not improve any
outcomes in studies where the control group received
high-dose physical rehabilitation. Our results sug-
gest the dose-response relationship of physical reha-
bilitation in the critically ill patient is not linear, with
a diminishing benefit at higher doses. Diminishing
returns is not a new concept in physical rehabilitation
(102). Earlier, more intensive and higher dosage exer-
cise does not always lead to better outcomes compared
with standard practice, as demonstrated in stroke (103),
pulmonary rehabilitation (104), and thoracic surgery
cohorts (105). A higher dosage of therapy delivered to
the control group makes it more difficult for the trial to
achieve separation between the intervention and con-
trol groups. The muscle fatigue threshold required for
a training response may be lower in critical illness. The
training response may also be limited by changes to
nerves and muscles from critical illness.
Subgroup analysis of studies with functional exper-
imental interventions resulted in reductions in the du-
ration of MV and ICU and hospital LOS, but not in
studies with nonfunctional experimental interventions.
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Figure 4. Meta-analysis and pooled effect sizes (standardized mean difference [SMD]) on physical function outcomes for physical
rehabilitation and standard care at ICU discharge, hospital discharge, and 6-mo follow-up.

Functional exercises produce better physical function
outcomes than nonfunctional exercises in non-ICU
patients (32–35). Functional exercises also have bene-
fits in other domains in the critically ill population, in-
cluding cognition and resolution of delirium (11, 99).
Thus, it is highly plausible that functional exercises are
superior to nonfunctional exercises in this population.
In summary, ICUs should have physical rehabilita-
tion services available up to 5 days per week, as this
dosage led to improved physical function and health

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Wang et al
service outcomes. Wherever possible, functional exer-
cises should be used. In ICUs that already provide
physical rehabilitation services at least 5 days per week,
a further increase in the dosage of rehabilitation is un-
likely to improve outcomes further.
Relationship With Existing Literature
No reviews before this current review have considered
the dose of physical rehabilitation available to control
group participants as part of routine care, nor investi-
gated the effectiveness of task-specific training in the
ICU. Therefore, our review had broad inclusion crite-
ria and sought to examine whether the inconsistency
in findings and conclusions in this field, along with the
statistical heterogeneity identified in some previous
reviews, could be explained through examination of
these factors as sources of heterogeneity.
Strength and Limitations
This systematic review and meta-analysis address two
major sources of heterogeneity not investigated in
previous reviews, the type of exercise and intensity of
control condition—essential in interpreting the body
of evidence. Our review benefits from novel data syn-
thesis and analytic approach, and many included stud-
ies. Our results have excellent representation from
across the globe, with the inclusion of 60 trials from 21
different countries. Numerous outcome measures and
different time points of assessment were included in
the pooled analysis.
There was considerable heterogeneity in the CIs of the
pooled results. Overall, the risk of bias in the included
studies was also high. Therefore, caution should be exer-
cised in the interpretation and application of the results.
Our review did not have the scope to investigate
the effect of sedation practices on the effectiveness of
physical rehabilitation. Sedation optimization facili-
tate physical rehabilitation, particularly task-specific
exercises. It may also decrease the time to initiation of
physical rehabilitation, which is also an important fac-
tor in the effectiveness of physical rehabilitation (19).
Sedation optimization associated with trial interven-
tions may have directly contributed to observed ben-
efits. Although in practice, it is highly recommended
that sedation optimization and physical rehabilitation
are both included in a bundle of care to optimize the
outcomes of critically ill patients (106–108).
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Included trials did not consistently report time-
related outcomes such as MV duration and ICU and
hospital LOS, with some reporting outcomes only in
survivors while others did not differentiate between
survivors and nonsurvivors. While there were no mor-
tality differences between groups, this was another
source of heterogeneity and bias.
Future Directions
We recommend better reporting of control and exper-
imental interventions that would allow analysis based
on the dosage of intervention delivered (i.e., using the
TIDieR checklist [27]). Future trials should use stan-
dardized outcome measures based on expert consensus,
such as European quality of life-five domains and
36-item Short Form Health Survey Version 2 for the
evaluation of HRQoL and pain; 6-minute walk test for
physical function, manual muscle test, and grip strength
for muscle strength (109). Reporting of time-related
outcomes such as MV duration and LOS in a critically
ill population should report survivors and nonsurvivors
separately and follow-up for 60 days (110).
CONCLUSIONS
Physical rehabilitation that commences in the ICU
improves physical function at hospital discharge and
reduces ICU and hospital LOS. However, it does not
appear to impact MV duration, muscle strength,
HRQoL, and mortality.
ACKNOWLEDGMENTS
We gratefully acknowledge Bernie Bissett for providing
further information on the timing of interventions in
Bissett et al (2016) and Tipping et al (2017), for the use of
6-month mortality data from Denehy et al (2013), which
was not published in the original report of the study.
1 School of Primary and Allied Health Care, Monash University,
Melbourne, VIC, Australia.
2 Department of Physiotherapy, Peninsula Health, Melbourne,
VIC, Australia.
3 Department of Physiotherapy, Western Health, Melbourne,
VIC, Australia.
4 Department of Critical Care, Melbourne Medical School,
The University of Melbourne, Melbourne, VIC, Australia.
5 National Centre for Healthy Ageing, Monash University,
Melbourne, VIC, Australia.
March 2022 • Volume 50 • Number 3

Supplemental digital content is available for this article. Direct
URL citations appear in the printed text and are provided in the
HTML and PDF versions of this article on the journal’s website
(http://journals.lww.com/ccmjournal).
Dr. Skinner and Prof. T. P. Haines should be considered as joint
senior authors.
Mr. Wang is the guarantor of this review; he conceived this review
and designed the first draft of its protocol; he screened records
for inclusion into the review, managed review data, performed
statistical inferences, and participated in drafting the final article;
and he takes full responsibility for the integrity of the data and
the accuracy of the data analysis. Ms. Lang screened records for
inclusion into the review, managed review data, and participated
in the drafting of the final article. Dr. Skinner conceived this re-
view and designed the first draft of its protocol; she participated
in the drafting of the final article. Dr. K. J. Haines participated in
the drafting of the final article. Prof. T. P. Haines conceived this
review and designed the first draft of its protocol; he performed
statistical inferences and participated in the drafting of the final
article. All authors read and approved the final article.
Mr. Wang received funding from the Australian Postgraduate
Award. Dr. Skinner’s institution (Western Health) received fund-
ing from the Australian Institute of Musculoskeletal Science. Prof.
T. P. Haines received funding from K&L Gates Law Firm and
Minter Ellison Law Firm. The remaining authors have disclosed
that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: mwang@phcn.vic.
gov.au
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