Castro-Avila, 2015

SR and meta-analysis of  RCTs

Literature search up to April, 2014

A: Schweickert, 2009

B: Routsi, 2010

C: Hanekom, 2012

D: Denehy, 2013

E: Brummel, 2014

Study design: RCT

Setting and Country: University of Queensland, Autralia

Source of funding and conflicts of interest:

The authors have no support or funding to report.

The authors have declared that no competing interests exist

Inclusion criteria SR:

Eligible studies were randomised or controlled clinical trials comparing rehabilitation to usual care in ICU/HDU patients. Adult patients had to be admitted to ICU/HDU for at least

48 hours and be followed for outcomes until ICU discharge.

Exclusion criteria SR:

compared passive therapies (i.e., not involving conscious muscle activation) to usual care; started rehabilitation after ICU/HDU discharge; evaluated interventions in the same patient (e.g., electrical stimulation is applied in one limb and the other serves as control); enrolled more than 20% of patients under 18 years; or had patients admitted to an ICU/HDU due to neurological conditions (e.g., stroke, acquired or traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, brain tumour, spinal cord injury, neuromuscular diseases), or trauma that could limit rehabilitation (e.g., major trauma, fractures, joint replacement).

5 studies included

Groups comparable at baseline? Yes

A: PT + OT + interruption of sedation. Sessions started with passive range of motion and when patient was able to interact, it progressed to active assisted and active range of motion exercises in supine and sitting in the bed.

B: Usual care+ electrical muscle stimulation in vastus lateralis, vastus medialis and peroneous longus of both lower limbs. They used biphasic, symmetric impulses of 45 Hz, 400 μsec pulse duration, 12 seconds on (0.8 second rise time and 0.8 second fall time) and 6 seconds off.

C: Protocol-based intervention, including one algorithm for each of the following conditions: Upper abdominal surgery, rehabilitation for chronic ventilated patients, thoracic injuries, acute lung injury, pulmonary dysfunction.

D: Exercise sessions based in baseline PFIT, including sitting out of bed, sit to stand, marching on the spot and shoulder elevation. Rehabilitation continued in the general ward, but the intensity was adjusted according to 6MWT results

E: Early PT + Cognitive therapy (CT): it also included exercises to improve orientation, attention and memory

A: Standard medical and nurse care. Physical and occupational therapy as ordered by primary care team

B: Standard medical and nurse care. Physiotherapy care included passive range of motion, sitting out of bed, transferring from bed to chair and sitting on a chair.

C: Decisions related to activities and intervention frequency were based on clinical decision of the therapist responsible for patient care.

D: Usual care.

E: ordered by treating clinician.

End-point of follow-up:

A: hospital discharge

B: n.r.

C: n.r.

D: hospital discharge

E: 3 months after hospital discharge

For how many participants were no complete outcome data available?

(intervention/control)

n.r.

Functional outcome

Defined as walking without assistance at hospital discharge

Effect measure: risk ratio [95% CI]:

A: 1.58 [1.07 – 2.33]

C: n.r.

D: n.r.

E: n.r.
F: n.r.

Author’s conclusion:

Early rehabilitation during ICU stay was not associated with improvements in functional status, muscle strength, quality of life or healthcare utilisation outcomes, although it seems to improve walking ability compared to usual care. Results from ongoing studies may provide more data on the potential benefits of early rehabilitation in critically ill patients.

Risk of bias (total score PEDro)

A: 8/10

B: 4/10

C: 7/10

D: 6/10

E: 7/10

Klem, 2021

SR and meta-analysis of  RCTs

Literature search up to April, 2020

A: Schweickert, 2009

B: Dong, 2016

C: Santos, 2018

D: Eggman, 2018

E: Hodgson, 2016

F: Kho, 2019

G: Morris, 2016

H: Schaller, 2016

I: Wright, 2018

Study design: RCT

Setting and Country: Section or Orthopaedic Rehabilitation, Department of Orthopaedics, Oslo University Hospital.

Source of funding and conflicts of interest:

The author has completed the ICMJE form and declares no conflicts of interest.

Inclusion criteria SR:

Design

Randomised controlled trials

Participants

Patients aged over 18 years

Patients who received mechanical ventilation in an ICU, with oral intubation or tracheostomy

Interventions

Respiratory muscle training

Active or active-assisted exercises for the extremities

Mobilisation to the edge of the bed, to sitting in a chair, or to a standing or ambulatory position

In-bed cycle ergometry

Comparison

Control group receiving a different treatment or no treatment

Primary outcome measures

Duration of mechanical ventilation

Weaning time from ventilator

Mortality in the hospital, at 1–3 months, 1–6 months and after 1 year

Secondary outcome measures

ICU length of stay

Hospital length of stay

Patient safety, adverse events

Publication date and language

Publication date 1.1.2006–27.4.2020

English or Scandinavian language

Only published studies were included

Exclusion criteria SR:

Patients with injury- or disease-specific muscle wasting; Intervention was passive or almost exclusively passive

Studies with other outcome measures or publication years, or in other languages; Studies with high risk of bias

9 studies included

Groups comparable at baseline?

Yes

A: Early mobilization once a day

B: Pre-surgical information and early mobilisation

twice daily

C: Active exercises with resistance bands

D: Early progressive mobilisation with in-bed cycle ergometry up to three times daily on weekdays + standard treatment

E: Early mobilization according to standard protocol for one hour a day

F: In-bed cycle ergometry + standard treatment

G: Intensive early Mobilisation according to standard protocol three times a day

H: Early mobilization across five levels

I: Intensive early mobilisation for 90 minutes on weekdays

A: Standard treatment when prescribed

B: Rehabilitation with assistance from family following discharge from intensive care

C: Passive exercises and positioning

D: Standard treatment (early mobilisation, respiratory physiotherapy and passive/active exercises)

E: Unit’s standard interventions: passive movement

F: Standard treatment (passive/active exercises and early mobilisation)

G: Standard treatment on weekdays when prescribed

H: Mobilisation in accordance with departmental guidelines

I: Standard treatment for 30 minutes on weekdays

End-point of follow-up:

n.r.

For how many participants were no complete outcome data available?

(intervention/ control)

n.r.

Duration of mechanical ventilation

Effect measure: mean difference [95% CI]

A: 2.24 [0.69 – 3.79]
B: 5.80 [4.38 – 7.22]
C: EX 4.53 [-0.41 – 9.47]

EX+NMES 9.10 [5.31 – 12.89]
D: -0.37 [-2.86 – 2.12]
E: 1.70 [-1.31 – 4.71]
F: 0.50 [-4.44 – 5.44]
G: n.r.
H: n.r.
I: n.r.

Pooled effect (random effects model):

2.23 [95% CI -0.27 to 4.73] favoring early mobilisation

Heterogeneity (I²): 84%

Duration of ICU stay

Effect measure: mean difference [95% CI]

A: 1.10 [-1.21 – 3.41]
B: n.r.
C: n.r.
D: 1.16 [-1.41 – 3.73]
E: 2.00 [-2.87 – 6.87]
F: -1.17 [-7.34 – 5.00]
G: -0.17 [-1.78 – 1.44]
H: 2.33 [0.64 – 4.02]
I: 1.33 [-1.01 – 3.67]

Pooled effect (random effects model):

1.08 [95% CI 0.21 to 1.95] favoring early mobilisation

Heterogeneity (I²): 0%

Author’s conclusion

This systematic review and meta-analysis show that early mobilisation of mechanically

ventilated adult ICU patients probably shortens the duration of mechanical ventilation and the ICU length of stay. Early mobilisation and inspiratory muscle training probably have no effect on mortality. Inspiratory muscle training may have little or no effect on the duration of mechanical ventilation or weaning time. Relatively few studies have examined inspiratory muscle training to date, however, and further studies are required. Additional studies should be conducted on long-term patient-reported outcome measures, and studies will hopefully provide more information about the effects of in-bed cycle ergometry.

Risk of bias

A: Lack of blinding
B: Lack of blinding.
C: Incomplete outcome data and other bias.
D: Lack of blinding
E: Lack of blinding and other bias.
F: Lack of blinding and incomplete outcome data.
G: Lack of blinding.
H: Lack of blinding.
I: Lack of blinding.

Monsees, 2022

SR and meta-analysis of  RCTs

Literature search up to November 2020.

A: Schweickert, 2009

B: Hodgson, 2016

C: Morris, 2016

D: Schaller, 2016

E: Maffei, 2017

Study design: RCT

Setting and Country: British Association of Critical Care Nurses.

Source of funding and conflicts of interest:

Jonas Monsees received a research grant from Tallaght University. Hospital. No further funding was awarded for this work. Open access funding provided by IReL.

Inclusion criteria SR:

RCTs, early and active mobilisation on critically ill adult patients, published in English, report ICU length of stay.

Exclusion criteria SR:

Non-RCT studies, passive exercise only regimes, focus on post-ICU-discharge interventions, not reporting ICU length of stay, cycle ergometry only studies.

5 studies included

Groups comparable at baseline?

No

A: progressive mobilisation regime

B: progressive mobilisation regime
C: 3 physiotherapy sessions/day
D: Progressive mobilization regime
E: 2 physiotherapy

sessions/day

A: daily interruption of sedation with therapy as ordered by the primary care team
B: standard care
C: weekday physical therapy when ordered by the clinical team
D: standard care
E: one session of physiotherapy a day (based on physician prescirpiton)
only

End-point of follow-up:

n.r.

For how many participants were no complete outcome data available?

(intervention/control)

n.r.

Duration of ICU stay

Effect measure: mean difference [95% CI]

A: 1.10 [-1.21 – 3.41]
B: 2.00 [-2.87 – 6.87]
C: -0.17 [-1.78 – 1.44]
D: 2.33 [0.64 – 4.02]
E: n.r.

Pooled effect (random effects model):

1.13 [95% CI -0.21 to 2.46] favoring early mobilisation

Heterogeneity (I²): 34%

Duration of mechanical ventilation

Effect measure: mean difference [95% CI]

A: 2.24 [0.69 – 3.79]
B: 1.70 [-1.31 – 4.71]
C: n.r.
D: n.r.
E: 0.80 [-0.11 – 1.71]

Pooled effect (random effects model):

1.32 [95% CI 0.35 to 2.29] favoring early mobilisation

Heterogeneity (I²): 22%

Author’s conclusion

This review has applied stricter time limits than previous SRs for the commencement of EM protocols, as patients had to be enrolled within four days of ICU admission or intubation. The emerging results give a strong indication that the commencement of EM has a positive effect on ICU LOS. In addition, there is a trend towards improved outcomes for Hospital LOS, duration of MV, and increased functional independence, than was the case with previous SRs. EM remains a safe intervention and does not influence mortality rates. However, findings are limited by small sample sizes and sources of bias. Further research and large-scale trials are required to solidify findings. However, based on the evidence of this SR, the application of EM should be widely considered in ICU settings, as ongoing RCTs will likely require years to complete.

Risk of bias

A: Peformance bias
C: Peformance bias
D: Peformance bias
E: Peformance bias

Zhang, 2019

SR and meta-analysis of RCTs

Literature search up to March, 2019

A: Schweickert, 2009

B: Hodgson, 2016

C: Kho, 2019

D: Morris, 2016

E: Moss, 2016

F: Schaller, 2016

G: Fossat, 2018

Study design: RCT

Setting and Country: University of Notre Dame

Australia, AUSTRALIA

Source of funding and conflicts of interest:

This work was supported by the Science and Technology Planning Project of Yuzhong District of Chongqing (grant number 20180136 to JM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist.

Inclusion criteria SR:

Adult patients, RCT, intervention was early mobilisation (applied when patients were stable and was applied earlier than in control group), mobilisation was defined as range of motion, motion involving axial loading exercises, movements against gravity, active activities, activities that require energy expenditure, control group received standard or usual care, outcomes included muscle strength, functional mobility capacity, duration of mechanical ventilation, ventilator-free days, mortality, discharged-to-home rate and adverse events.

Exclusion criteria SR:

Patients with neurological conditions, inclusion of ineligible interventions, exercises performed after ICU discharge, reviews, abstracts, case reports and pediatric, animal or cell-based studies.

7 studies included

Groups comparable at baseline?

Yes

A: Physical therapy, occupational therapy and interruption of sedation
B: Early mobilisation according to standard protocol for one hour a day
C: In-bed cycle ergometry + standard treatment
D: Intensive early mobilisation according to standard protocol three times a day
E: Level-appropriate early mobilisation once a day
F: Early mobilisation across five levels
G: Early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation

A: Usual care and nurse care
B: Unit's standard interventions: passive movement
C: Standard treatment (passive/active exercises and early mobilisation)
D: Standard treatment on weekdays when prescribed
E: Standard treatment three times a week (passive exercises, positioning and functional rehabilitation)
F: Mobilisation in accordance with departmental guidelines
G: Standardized early rehabilitation alone (usual care)

End-point of follow-up:

n.r.

For how many participants were no complete outcome data available?

(intervention/ control)

n.r.

Delirium

Effect measure: risk ratio [95% CI]

A: n.r.
B: n.r.
C: n.r.
D: n.r.
E: n.r.
F: n.r.
G: 1.03 [0.70 – 1.51] favoring early mobilisation.

Author’s conclusion

Regardless of the different techniques and periods of mobilisation applied, early mobilisation may be initiated safely in the ICU setting and appears to decrease the incidence of ICU-AW, improve the functional capacity, and increase the number of patients who are able to stand, number of ventilator-free days and discharged-to-home rate without increasing the rate of adverse events. However, due to the substantial heterogeneity among the included studies, the evidence has a low quality and the results of this study should be interpreted with caution. Further large-scale and well-designed research studies are needed to provide more robust evidence to support the effectiveness and safety of the early mobilisation of critically ill patients in the ICU setting.

Risk of bias

A: Low risk
B: Performance bias
C: Performance bias
D: Low risk
E: Low risk
F: Low risk
Gdd: Performance bias and detection bias

Afxonidis, 2021

Type of study:

A double-blinded randomized clinical trial

Setting and country:

Single-centre, Greece.

Funding and conflicts of interest:

The authors declare no conflict of interest. This research received no external funding.

Inclusion criteria:

(1) a written informed consent to participate in the study, (2) a Glasgow Coma Scale score = 15, and (3) musculoskeletal and cardiopulmonary conditions suitable for the accomplishment of the proposed activities.

Exclusion criteria:

(1) emergency, non-elective cardiac surgery, (2) hemodynamic instability preventing protocol performance, (3) breathing discomfort or invasive ventilator support or oxygen saturation below 90%, (4) severe neurological sequelae or neurodegenerative disorders, and (5) any mobile disability that did not allow them to perform exercise according to our protocol.

N total at baseline:

Intervention: 39

Control: 39

Important prognostic factors²:

age (SD):

I: 63.5 (8.9)

C: 65.1 (8.9)

Sex:

I: 87.2% M

C: 79.5% M

BMI (SD)

I: 26.8 (4.2)
C: 27.9 (4.2)

Groups comparable at baseline? Yes

Patients were provided with an extra physiotherapy session during first three post-operative days or until ICU discharge (three sessions per day). Except for the aforementioned enhanced physiotherapy strategy, patients of the EEPC group also received an early physiotherapy session performed during zero post-operative day in the ICU.

Usual physiotherapy care was applied to participants of the CPC group twice a day commencing on the first post-operative day until their discharge.

Length of follow-up:

Post-intervention

Loss-to-follow-up:

Intervention: 0 (0%)

Control: 0 (0%)

Incomplete outcome data:

n.r.

Duration of ICU stay (days)

Effect measure: mean difference [95% CI]

0.09 [0.05 – 0.13] days favoring early mobilisation.

Author’s conclusion

In patients undergoing open heart surgery, early mobilisation and physical activity, along with enhanced respiratory physiotherapy, significantly decreased the length of both ICU and hospitalization stay. However, these outcomes were not reflected in significant differences in post-intervention hemodynamic and laboratory parameters, except for increased PO2 and decreased lactate levels. Larger randomized, controlled trials are warranted to establish certain physiotherapy strategies and a structured physiotherapy program, which might lead to better clinical outcomes and faster postoperative recovery, decreasing the length of hospitalization and the subsequent financial burden.

Hodgson, 2022

Type of study:

multicenter, randomized,

controlled trial

Setting and country:

Multicenter, Australia

Funding and conflicts of interest:

The trial was funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand. The management committee designed the trial, which was endorsed by the Australian and New Zealand Intensive Care Society and the Irish Critical Care Trials Group. The institutions that managed the trial and monitored data quality are listed in the Supplementary Appendix (available with the full text of this article at NEJM.org).

Inclusion criteria:

Eligible patients were adults (≥18 years of age) who were expected to undergo mechanical ventilation in the ICU beyond the calendar day after randomization and whose condition was sufficiently stable to make mobilisation potentially possible.

Exclusion criteria:

Dependency in any activity of daily living in the month before hospitalization, rest-in-bed orders, and proven or suspected acute primary brain or spinal injury.

N total at baseline:

Intervention: 372

Control: 378

Important prognostic factors²:

age (SD):

I: 60.5 (14.8)

C: 59.5 (15.2)

Sex:

I: 34.5% M

C: 39.5% M

Groups comparable at baseline? Yes

Our intervention, which included minimization of sedation as required, was hierarchical and began after randomization with daily physiotherapy, which could be provided in one or more sessions. The sessions were individually tailored to achieve the highest possible level of mobilisation that was deemed to be safe for the patient at the initiation of daily therapy. The highest level of mobilisation was provided for as long as possible before a step-down to lower levels of activity if the patient became fatigued, as measured on the ICU Mobility Scale. This validated scale rates the level of mobilisation from 0 to 10, with 0 indicating no mobilisation and 10 indicating independent walking.

Patients who were assigned to the usual-care group received a level of mobilisation that was normally provided at each site.

Length of follow-up:

28 days after randomisation and 180 days of follow-up.

Loss-to-follow-up:

Intervention: 3 (0.8%)

Control: 14 (3.7%)

Reasons: Withdrawal of consent (all data or 180 days of follow-up).

Incomplete outcome data (primary outcome):

Intervention: 3 (0.4%)

Control: 5 (1.5%)

Reasons: n.r.

Functional outcome

Defined as the number of patients with an IMS score ≥ 7.

Effect measure: risk ratio [95% CI]

1.17 [0.99 to 1.38] favoring early mobilisation.

Author’s conclusion

Thus, for adults undergoing mechanical ventilation in the ICU, increased early active mobilisation did not affect the number of days that they were alive and out of the hospital as compared with the usual level of mobilisation received in the ICU.

Nickels, 2020

Type of study:

parallel two-arm, RCT

Setting and country:

26-bed tertiary

mixed medical, surgical and trauma ICU in Brisbane, Australia.

Funding and conflicts of interest:

No funding body had a role in study design, collection, management, analysis and interpretation of data; writing of the report; and the decision to submit the report for publication. There were no declarations of competing interest declared.

Inclusion criteria:

Eligible patients were adults (≥18 years of age) who were expected to undergo mechanical ventilation in the ICU beyond the calendar day after randomization and whose condition was sufficiently stable to make mobilisation potentially possible.

Exclusion criteria:

Dependency in any activity of daily living in the month before hospitalization, rest-in-bed orders, and proven or suspected acute primary brain or spinal injury.

N total at baseline:

Intervention: 372

Control: 378

Important prognostic factors²:

age (SD):

I: 60.5 (14.8)

C: 59.5 (15.2)

Sex:

I: 34.5% M

C: 39.5% M

Groups comparable at baseline?

Yes

The cycling group received the same usual-care interventions; they also received once daily (up to six-days per week) in-bed leg cycling using aMOTOmed Letto2 (RECK-Technik GmbH & Co. KG, Betzenweiler, Germany) cycle ergometer either in the ICU or in an acute hospital ward. The intervention co-ordinator (MRN) set-up and delivered the cycling sessions. Safety guidelines adapted from previous exercise intervention studies and recommendations were used to guide these sessions. Cycling sessions were chosen as they could be delivered to participants passively and progressed to active or resisted exercise depending on participants' ability and level of consciousness. Alert participants were encouraged to exercise at a moderate to hard level of perceived exertion, with the cycle ergometer resistance added and adjusted during the cycling session to achieve an appropriate level of exertion. Cycling sessions were delivered for a maximum of 30 min. However, sessions could be ceased early on participant request or if safety concerns arose.

The usual-care group received routine physiotherapy interventions that included a daily assessment of physical and respiratory status and treatment. Physical treatments were directed to functional task achievement including; sitting, standing and mobilising. In-bed cycling was not a routine intervention at the site prior to the study. Consequently, usual care group participants were not scheduled to participate in the cycling

intervention.

Length of follow-up:

10 days after study enrolment, 3 months post-hospital admission and 6 months post-hospital admission.

Loss-to-follow-up:

Intervention: 6 (16.2%)

Control: 6 (16.2%)

Reasons: Withdrawal, ischaemic spinal cord injury, death prior to assessment, discharge prior to completing primary outcome assessment, death before follow-up, lost to follow-up, unable, decline further participation. 

Incomplete outcome data (primary outcome):

n.r.

Functional status

Defined by the functional status score for the intensive care unit.

Effect measure: median [IQR]

Intervention: 23 [18-31]

Control: 23 [15-29]

Delirium

Effect measure: risk ratio [95% CI]

0.69 [0.23 – 1.41] favoring usual care.

Author’s conclusion

In-bed cycling did not reduce acute muscle wasting in critically ill adults, but this study provides useful effect estimates and learnings for large-scale clinical trials.

Nydahl, 2022

Type of study:

pilot, multi-centre, randomized, controlled trial

Setting and country:

mixed ICUs within two university

hospitals in Germany.

Funding and conflicts of interest:

This work is funded by the Delirium Research Prize of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) and the Philips company. Both entities did not have any influence in designing, conducting, analysing, interpreting, or writing the study. No conflict of interests were reported.

Inclusion criteria:

Patients were included, irrespective of their status of being

on MV or not, who fulfilled all following conditions: (a) ≥18 years old, (b) Richmond Agitation Sedation Score (RASS) ≥ 3 and were responsive, (c) could be assessed for delirium, and (d) were able to being mobilized out of bed according to local policies, and (e) were expected to spend at least one night in the ICU.

Exclusion criteria:

(a) expectation of death

within the next 72 hours, (b) no informed consent for the study, (c) pre-existing immobility, (d) contraindication against mobilisation, (e) delirium already present before recruitment, (f) positive pregnancy test (routinely carried out in all patients of childbearing age upon admission to ICU), (g) delirium assessment not possible (coma, foreign language, aphasia, etc.), and (h) participation in a competitive study with the outcome of delirium.

N total at baseline:

Intervention: 26

Control: 20

Important prognostic factors:

age (SD):

I: 64.4 (11.9)

C: 60 (17.3)

Sex:

I: 73.1% M

C: 70% M

Groups comparable at baseline? Yes

The early mobilisation intervention was provided by an additional mobilisation team. Mobilisation teams have been successfully used in other studies.16,24 The teams were made up of two people recruited from the study centres and consisted of trained intensive care nurses and/or physiotherapists and could be complemented by medical professionals.

Patients in the control group received usual care and were mobilized during the day by physiotherapists and nurses.

Length of follow-up:

28 days after ICU admission.

Loss-to-follow-up:

Total: 7 (13.2%)

Reasons: Rejection of intervention and lost to follow-up.

Incomplete outcome data (primary outcome):

n.r.

Delirium

Effect measure: risk ratio [95% CI]

0.54 [0.25 – 1.16] favoring usual care.

Author’s conclusion

In mixed ICU patients, a study of mobilisation in the evening to prevent and treat delirium is feasible. The intervention can be delivered to three of four occasions, while exceptions happen in a few cases because of examinations, patients' refusal, or other reasons. The intervention appears to be safe. Mobilisation shows signs of beneficial

effects on preventing and treating delirium, but more research is needed to prove further hypotheses, such as a dose–response relationship

between mobilisation and delirium. We estimate that a trial reaching statistical significance would require three times the number

of patients, study duration, and costs, compared with this pilot study.

Schujmann, 2020

Type of study:

randomized and controlled trial

Setting and country:

Central Institute

of Hospital das Clínicas, University of São Paulo, Brazil.

Funding and conflicts of interest:

Supported, in part, by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Brazil. Ms. Schujmann, Ms. Teixeira Gomes, Mr. Zoccoler Lamano, Ms. Lunardi,

Ms. Pimentel, Ms. Peso, Ms. Araujo, and Dr. Fu’s institutions received funding from Fundação de Amparo a Pesquisa do Estado de São Paulo. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Inclusion criteria:

Patients were excluded if 1) they had been previously hospitalized at other hospitals; 2) they had neurologic alterations; 3) they stayed less than 4 days in the ICU; 4) they were amputees upon admission; 5) they had contraindications for mobilisation; or 6) they had cognitive impairment with an inability to understand commands and perform tests.

Exclusion criteria:

N total at baseline:

Intervention: 68

Control: 68

Important prognostic factors:

age (SD):

I: 48 (15)

C: 55 (12)

Sex:

I: 54% F

C: 46% F

Groups comparable at baseline? Yes

The intervention group (IG) underwent a combined therapy consisting of a combination of conventional physiotherapy and a program of early and progressive mobilisation at the appropriate level of activity for each patient.

The control group (CG) underwent the conventional treatment offered by the unit physiotherapists, with active assists and active mobilisation as well as bed positioning, bedside and armchair transfers, orthostatism, and ambulation. The physiotherapist defined the type of therapy and did not use a preestablished routine. No equipment was used for the CG.

Length of follow-up:

3 months after discharge.

Loss-to-follow-up:

Intervention: 7 (10.3%)

Control: 11 (16.4%)

Reasons: discharge before evaluation, discharge IC before 3 days, death. 

Incomplete outcome data (primary outcome):

n.r.

Functional status

Defined by the number of independent patients (defined by a barthel index score ≥ 85).

Effect measure: risk ratio [95% CI]

2.14 [1.56 – 2.93] favoring early mobilisation. 

Author’s conclusion

An early and progressive mobilisation program for ICU patients may improve functional outcomes upon discharge and 3 months following hospitalization. Participation in a rehabilitation program in the ICU, as well as an increase in the level of physical activity during this period, proved to protect against the loss of functional status and to reduce the duration of ICU stay.

Castro-Avila, 2015

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

Yes

Yes

Klem, 2021

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

Yes

Yes

Monsees, 2022

Yes

Yes

Yes

Yes

Not applicable

Yes

No

Yes

Yes

Zhang, 2019

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

Yes

Yes

Study reference

(first author, publication year)

Was the allocation sequence adequately generated? ^a

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?^b

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?^c

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?^d

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?^e

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?^f

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/ necessary, per outcome measure^g

LOW

Some concerns

HIGH

Afxonidis, 2021

Definitely yes;

Reason: Participants were allocated in each group through computer-generated

random numbers.

No information;

Reason: No information was provided about allocation concealment. 

Definitely yes;

Reason: The study was a double-blinded trial so that the participants were unaware of the

existence of the other group. The blinded researcher was also not aware whether the

patients were in the CPC group or in the EEPC group. After collecting the data, the blinded

researcher measured the defined outcomes of interest.

Definitely yes;

Reason: No patients were lost to follow-up

Definitely yes;

Reason: Results of predefined outcome measures were presented.

Definitely no;

Reason: The trial was single-centered, the protocol was not registered in a protocol database, pre-operative physiotherapy was not incorporated in the analysis, the results could have been attributed to enhanced physiotherapy sessions.

LOW

Hodgson, 2022

Definitely yes;

Reason: We randomly assigned patients in a 1:1 ratio to receive early mobilisation or usual care using a

centralized Web-based interface. The trial statistician

generated the assignment sequence using computer-generated random numbers stratified

according to the trial center with variable block sizes.

No information;

Reason: No information was provided about allocation concealment. 

Definitely no;

Reason: Blinding of mobilisation in the ICU was not possible; however, trained staff who were unaware of trial-group assignments ascertained patient-reported outcomes, and the statistical

analysis was performed in a blinded manner.

Definitely yes;

Reason: Losses to follow-up were infrequent (2,3%). 

Definitely yes;

Reason: Results of predefined outcome measures were presented.

Definitely no;

Reason: Some data related to patient-reported outcomes at day 180 were missing; patients in the usual care group received a higher level of mobilisation than those in other cohort studies and previous trials; changes in practice could have affected treatment in the usual care group; not all patients were actively mobilized in the ICU.

Moderate

Nickels, 2020

Definitely yes;

Reason: A computer-generated

randomisation sequence was created by an investigator

(SMM) not involved in the screening, consenting, allocation or assessment

processes.

Definitely yes;

Reason: The randomised sequence was uploaded onto a secure web-based computer application, the Research Electronic Data Capture

(REDCap) [24]. Group allocation was revealed to the intervention coordinating

investigator (MRN) after informed consent (from the patient

or surrogate decision-maker) was granted.

Probably no;

Reason: Blinded assessment of the primary outcome was completed with over

85% of participants enrolled. No information was provided about blinding of patients, healthcare providers and data analysts.

Probably yes:

Reason: We minimised random error with a large sample size and high follow-up (≥98% for the primary outcome). Finally, we had high adherence to study medication in both treatment groups: 89% at 6 months across both groups.

Definitely yes;

Reason: Results of predefined outcome measures were presented.

Definitely no;

Reason: The study was single-centre; for the secondary outcomes the study was underpowered; variability in primary measure was greater than expected; only one sonographer completed the ultrasound assessment,

Moderate

Nydahl, 2022

Definitely yes;

Reason: this study randomized patients in a 1:1 ratio to the intervention or

usual care group. Randomization was completed without blocks using

a pseudo-random number generator based on a query at www.

randomizer.org.

No information;

Reason: No information was provided about allocation concealment. 

Definitely no;

Reason: Because of the obvious character of

the intervention, blinding was not feasible (for everyone).

Probably yes;

Reason: Lost to follow-up was infrequent (7,5% in the intervention group)

Definitely no;

Reason: The primary outcome measure was changes after registration.

Probably no;

Reason: Results may not be generizable among other centres; patients were only mobilized on three consecutive evenings (too short). 

Some concerns

Schujmann, 2020

Definitely yes;

Reason: An independent statistician performed the randomization with a computerized random numbers table and numbered brown envelopes in sequence with the group assignment inside.

No information;

Reason: No information was provided about allocation concealment

Definitely no;

Reason:

The evaluator

was blind to group assignment and recorded the results in a specific worksheet. Unfortunately, the patients and physiotherapists who

performed the interventions could not be blinded due to the characteristics

of the intervention and physical space of the ICU.

Definitely no;

Reason:

Losses to follow-up were frequent (26,7%).

Definitely yes;

Reason: Results of predefined outcome measures were presented.

Definitely yes;

Reason: No other problems reported.

Moderate