Table 3.

Summary of randomised controlled trials of physical rehabilitation (mobility) interventions on muscle mass, strength or function

Author, year, country	Population	Timing	Intervention	Comparator	Muscle mass, strength or functional outcome	Results
Cui, 2020, China [65]	178 off-pump CABG patients aged 60 years or above	<48 h	Precision early ambulation duration and intensity determined by age-predicted maximal heart rate and V02Max. Day 1: 10 min sitting Day 2: SOOB >10 min, standing 3–5 min; walking 20m Day 3: SOOB >10 min, standing 5 min and walk minimum of 30 m. Exercises repeated up to 5 times per day	Routine ambulation – patients engaged in ambulation on day 2 or 3 after surgery	Ambulation outcome reported (but not a pre-specified primary or secondary endpoint)	Significant difference between groups for ambulation distance on day 3 (75 m vs 56 m, p < 0.001)
Dantas, 2012, Brazil [66]	59 ICU MV patients	Unclear (however, patients excluded if MV >7 d)	2× day, 7 times per week at a moderate intensity level in ICU	Conventional physical therapy – passive mobility of UL/LL 5× week and active assisted exercises depending on the capability	MRC-SS	Significant improvement in muscle strength over the duration of the intervention (p = 0.00) – however, higher baseline MRC-SS scores compared to control
Denehy, 2013, Australia [67]	150 mixed ICU patients ICU LOS >5 d	Late >5 d	Functional mobility and strengthening exercises, aerobic training beginning in ICU and continuing for 8 weeks post-hospital discharge (up to an hour) at moderate intensity	Usual care (respiratory and mobility in hospital), no outpatient service	Primary: 6MWD Secondary: TUG test SF-36 AQOL	No significant difference for 6MWD between groups at 6 months, exploratory analyses demonstrated the rate of change over time and mean between group differences in 6MWD from the first assessment greater in the intervention group NB: did not reach enrolment target of 200 Secondary: no difference between groups for secondary outcomes
Dong, 2014, China [68]	60 ICU patients with tracheal intubation or tracheostomy 48–72 h with predicted MV >7 d	48–72 h	2× day daily until hospital discharge, functional mobility tasks	Control group (unspecified)	Time to first sit out of bed in days	Faster to sit out of bed in the intervention (mean of 3.8 vs 7.3 days; p = 0.00)
Hickmann, 2018, Belgium [69]	19 ICU patients with septic shock <72 h	<48 h	2× 30 min session/daily for one week with 1 session of functional mobility and 1×30 min passive/active cycling	Usual care (5× week, functional mobility)	Primary: regulation of protein degradation/synthesis pathways during the first week Secondary: muscle fibre CSA Exercise-induced muscle inflammation	Primary: reduced protein degradation in the intervention group but no significant difference between groups over the first week Secondary: muscle fibre CSA preserved by exercise between days 1 and 7 (−26% in control vs 12.4% in intervention, p = 0.005); no significant difference between groups for exercise-induced inflammation
Hodgson, 2016, Australia Pilot RCT [70]	50 mixed ICU patients MV >48 h	<72 h	Active exercises for 1 hour per day, early goal-directed mobility focused on functional mobility	Usual care	Primary: higher maximal level and duration of activity measured using IMS Scale Secondary: PFIT-s FSS-ICU MRC-SS IADL	Higher levels of activity (mean IMS 7.3 vs 5.9; p = 0.05) and duration of activity in intervention (median 20 vs 7 min; p = 0.002) Secondary: no significant differences between groups for secondary measures
Hodgson, 2020, Australia Pilot RCT [71]	20 ICU ECMO patients	<72 h	Early goal-directed mobility	Usual care	Primary: higher maximal level and duration of activity measured using the IMS scale Secondary: Katz ADL functional independence	Primary: higher duration of mobility in the intervention (median 133 vs 27.5 min) but no difference between groups for IMS maximal score (2.67 vs 1.5 points) Secondary: between group difference in favour of early goal-directed mobility group for Katz ADL (functional independence at hospital discharge)
Kayambu, 2015, Australia Pilot RCT [72]	50 mixed CU patients with sepsis syndromes, MV >48 h	<48 h of sepsis diagnosis	1–2 × 30 min sessions/day until ICU discharge involving EMS, functional mobility and cycling	Usual care (respiratory and functional mobility)	Acute Care Index of Function at ICU discharge	No difference between groups in ACIF scores at ICU discharge
Maffei, 2017, France [73]	40 ICU liver transplant recipients	48–72 h	2× day early progressive rehabilitation involving P/AROM, functional mobility until ICU discharge	Usual care (referral to physiotherapy with 1 session per day)	Time to first mobility milestones (sitting on the edge of the bed, sitting in the chair and walking)	Patients sat on the edge of the bed sooner in the intervention group (2.6 vs 9.7 days, p = 0.048) No significant difference between groups for time to first sit in a chair or walking
McWilliams, 2018, UK Pilot RCT [74]	103 ICU patients MV ≥5 d	>5 d	Enhanced rehabilitation	Usual care	Manchester Mobility Score	Median time to the first mobilisation was significantly shorter in the intervention group (8 vs 10 days, p = 0.035) and a higher level of mobility on Manchester Mobility Score at ICU discharge (MMS 7 vs 5, p = 0.016)
Morris, 2016, USA [75]	300 MICU patients requiring noninvasive or invasive MV	<48 h	Standardised rehabilitation therapy involving PROM, PT and progressive resistance training, 3× sessions per day, seven days per week until hospital discharge	Usual care	Primary: hospital LOS Secondary: SPPB SF-36 (PF domain) FPI Handgrip strength HHD strength	Primary: no significant difference between groups for hospital LOS Secondary: no difference between groups for secondary outcomes except SPPB, where there was a significantly higher score for SPPB, SF-36 (PF domain) and FPI score at 6 months within the intervention group
Moss, 2016, USA [76]	120 MV (≥4 d) MICU patients	Median 8 d	Intensive rehab for 28 days (7× week in hospital and× week outpatient/home) 30 min in ICU, 60 min in ward/outpatient Programme included breathing, ROM, strength, functional mobility	Usual care (3× week focused on ROM, positioning and functional mobility) up to 28 days, no formal outpatient programme	Primary: Continuous Scale Physical Functional Performance Test Secondary: 5 times sit to stand TUG test Berg Balance Scale SF-36	Primary: no significant difference between groups for Continuous Scale Physical Performance Test scores 1-month post enrolment Secondary: no significant differences between groups for any secondary measures
Nava, 1998, Italy [77]	80 RICU COPD patients	Unspecified commenced in RICU	2× 30–45 min sessions daily of comprehensive rehab involving Steps 1 and 2: P/AROM, respiratory Rx, mobility training; step 3: respiratory muscle training 2× 10 min, cycling 1× 20 min at a workload of 15 watts and flight of 25 stairs 5×; step IV: 3 weeks 2× 30 min treadmill walking at 70% pre-exercise test score	Control group (steps 1 and 2 only)	6MWD	Significant improvement in 6MWD in intervention group at hospital discharge (p < 0.0001)
Nydahl, 2020, Germany [78] Cluster randomised pilot study	274 ICU patients in ICUs with no protocol for early mobility present	Median 3 d	Intervention period: goal-directed mobility plan based on ICU Mobility Scale and interprofessional rounds daily	Control period: usual care	Primary: percentage of patients with ICU Mobility Score of 3 or more	Primary: non statistically significant increase in out-of-bed mobility by 9.6%
Schaller, 2016, Germany [79••]	200 SICU patients MV <48 h and expected further MV >24 h	<48 h	Early goal-directed mobility involving daily morning ward round to set mobility goal and second goal implementation cross shifts with interprofessional communication follow-up	Usual care	Primary: SOMS level Secondary: modified FIM MRC-SS SF-36	Primary: significant differences between groups in favour of intervention for mean SOMS score Secondary: significant differences between groups for modified FIM at hospital discharge in favour of intervention; no difference between groups for MRC-SS or SF-36.
Schweickert, 2009, USA [80•]	104 pts	<48 h	Passive ROM for all limbs (10 repetitions), transitioned to active assisted and active ROM exercises, bed mobility and sitting and ADL/exercise, walking, daily basis until returned to the previous level of function or discharged from hospital	Usual care	Primary: functional independence Secondary: Barthel Index Number of functionally independent ADLs Distance walked without assistance MRC-SS Handgrip strength	Primary: greater functional independence at hospital discharge in the intervention group (59 vs 35 %, p = 0.02) with the faster achievement of mobility milestones (i.e. sitting, standing, marching and walking) in favour of the intervention group (p > 0.0001), a greater walking distance at hospital discharge Secondary: Higher Barthel Scores, a higher number of independent ADLs and greater unassisted walking distance in the intervention group at hospital discharge; non-significant difference between groups for MRC-SS and handgrip strength at hospital discharge
Seo, 2019, Korea [81]	16 ICU patients in ICU ≥5d	>5 d	Exercise group included P/AROM, resistance training, functional mobility	Cycle ergometry 5× week for 30 min until ICU discharge	MRC-SS FSS-ICU SF-36	There was a significant difference between groups for MRC-SS, FSS-ICU and SF-36 (PF domain) at ICU discharge
Schujmann, 2020, Brazil [82]	99 ICU patients scoring 100 or above on Barthel Index 2 weeks prior to ICU admission	<48 h	Combined therapy consisting of a combination of conventional therapy and a programme of early and progressive mobility. 2× day 5× week, duration ~40 min	Conventional therapy involving active assists and active mobilisation as well as bed positioning, bedside and armchair transfers and ambulation. 2× day, 5× week	Primary: Barthel Index Secondary: handgrip strength EMG of anterior tibial, medial gastroc and VL muscles TUG test Sit to stand test 2-min walk test Physical activity levels ICU Mobility Score	Higher Barthel Scores for intervention at ICU discharge (97 vs 76, p < 0.001) No differences between groups for handgrip strength, EMG or TUG test. Difference between groups observed for sit to stand (8 vs 5 repetitions, p < 0.01), 2-min walk test (p < 0.001) and ICU Mobility Score at ICU discharge (9.8 vs 7, p < 0.001). Higher levels of physical activity in the intervention (1539 steps/day vs 591 in control, p < 0.001).
Wright, 2017, UK [83•]	308 ICU MV ≥48 h	<72 h	90 min rehab 5× week until ICU discharge split across 2 sessions until ICU discharge	30 min rehab 5× week	Primary: SF-36 (PF domain) Secondary: modified Rivermead Mobility Index 6MWT FIM Handgrip strength	Primary: no significant difference between groups for SF-36 (PF) Secondary: no significant difference between groups for secondary measures except FIM at 3 months
Yosef Brauner, 2015, Israel [84]	18 ICU MV ≥48h and expected to remain ventilated for further 48 h		Conventional physiotherapy (more intensive 2× day) involving respiratory and functional elements – respiratory, P/AROM, functional mobility	Conventional physiotherapy	MRC-SS Handgrip strength Sitting balance	There was a significant difference in the intensive treatment group over time compared to usual care for MRC-SS (p = 0.029) and non-significant for handgrip and sitting balance.

ADL, activities of daily living; AQOL, Assessment of Quality of Life Questionnaire; AROM, active range of motion; CSA, cross-sectional area; ECMO, extra corporeal membrane oxygenation; EMS, electrical muscle stimulation; FIM, Functional Independence Measure; FPI, Functional Performance Inventory; HHD, handheld dynamometry; IADL, instrumented activities of daily living; ICU, intensive care unit; IMS, ICU Mobility Scale; LOS, length of stay; LL, lower limb; MICU, medical ICU; min, minutes; MRC-SS, Medical Research Council sum score; MV, mechanical ventilation; PFIT-s, Physical Function in ICU test scored; PROM, passive range of motion; PT, physiotherapy; Rx, treatment; SF-36, Short Form 36 Questionnaire; SOM, Surgical Optimal Mobility Scale; SPPB, short physical performance battery; TUG test, timed up and go test; UL, upper limb; 6MWD, six-minute walk distance; %, percentage