INTENS CRIT CARE NUR 80 (2024) 103573

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Intensive & Critical Care Nursing

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Review Article

Early mobilisation within 72 hours after admission of critically ill patients

in the intensive care unit: A systematic review with network meta-analysis
Nils Daum a, Nils Drewniok a, Annika Bald a, Bernhard Ulm b, c, Alyona Buyukli a,
Julius J. Grunow a, Stefan J. Schaller a, b, *
a
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Anaesthesiology and Intensive
Care Medicine (CCM/CVK), Germany
b
Technical University of Munich, School of Medicine and Health, Klinikum rechts der Isar, Department of Anaesthesiology and Intensive Care Medicine, Germany
c
Department of Anesthesiology and Intensive Care Medicine, University of Ulm, Faculty of Medicine, Ulm, Germany

A R T I C L E I N F O A B S T R A C T

Keywords: Introduction: Early mobilisation within 72 hours of intensive care unit admission counteracts complications
Critical care caused by critical illness. The effect of different interventions on intensive care unit length of stay and other
Critical illness outcomes is unclear. We aimed to investigate the effectiveness of various early mobilisation interventions within
Early ambulation
72 hours of admission to the intensive care unit on length of stay and other outcomes.
Physical therapy
Rehabilitation
Methods: A systematic review and (network) meta-analysis examining the effect of early mobilisation on length of
stay in the intensive care unit and other outcomes, conducting searches in four databases. Randomised controlled
trials were included from inception to 10/08/2022. Early mobilisation was defined as interventions that initiates
and/or supports passive/active range-of-motion exercises within 72 hours of admission. In multi-arm studies,
interventions used in other studies were declared as early intervention and were included in subgroup meta-
analysis. Risk-of-bias was assessed using RoB2.
Results: Of 29,680 studies screened, 18 studies with 1923 patients (three high, eleven some, four low risk-of-bias)
and seven discriminable interventions of early mobilisation met inclusion criteria. Early mobilisation alone
(WMD 0.78 days, 95 %CI [− 1.38;-0.18], 11 studies, n = 1124) and early mobilisation with early nutrition (WMD
− 1.19 days, 95 %CI [− 2.34;-0.03], 1 study, n = 100) were able to significantly shorten length of stay. Early
mobilisation alone could also substantially shorten hospital length of stay (WMD -1.05 days, 95 %CI [− 1.74;-
0.36], 8 studies, n = 977). This effect in hospital length of stay was furthermore seen in the early intervention
group compared with standard care (WMD − 1.71 days, 95 %CI [− 2.99;-0.43], 14 studies, n = 1587). Also,
functionality and quality of life could significantly be improved by an early start of mobilisation.
Conclusion: In the network meta-analysis, early mobilisation alone and early mobilisation with early nutrition
demonstrated a significant effect on intensive care length of stay. Early mobilisation could also reduce hospital
length of stay and positively influence functionality and quality of life.
Implication for clinical practice: Early mobilisation and early mobilisation with early nutrition seemed to be
beneficial compared to other interventions like cycling on intensive care length of stay.

Introduction care syndrome (PICS) (Pandharipande et al., 2014).

The acute physical manifestation is known as ICU acquired weakness
Critically ill patients can suffer from various complications due to the (ICUAW) and affects up to half of all critically ill patients (Lacomis,
critical illness and accompanying intensive care unit (ICU) stay. Espe­ 2011), leading to a delayed withdrawal of mechanical ventilation and
cially an extended stay in the ICU is associated with severe physical, extended hospitalisation (Wang et al., 2020). A therapeutic approach to
cognitive, or mental health complications (Herridge et al., 2016; Tejero- counteract ICUAW is early mobilisation (EM) (Schaller et al., 2016).
Aranguren et al., 2022). These can persist for years as a post-intensive Studies have shown that an early start of mobilisation of critically ill

* Corresponding author at: Charité – Universitätsmedizin Berlin, Department of Anesthesiology and Intensive Care Medicine (CCM/CVK), Charitéplatz 1, 10117
Berlin, Germany.
E-mail address: [Link]@[Link] (S.J. Schaller).

[Link]
Received 19 August 2023; Received in revised form 18 October 2023; Accepted 23 October 2023
Available online 8 November 2023
0964-3397/© 2023 Elsevier Ltd. All rights reserved.
N. Daum et al. Intensive & Critical Care Nursing 80 (2024) 103573

patients can reduce the risk of ICUAW and positively affect the func­ Studies were excluded that met the following exclusion criteria:
tionality and quality of life (Hodgson et al., 2016; Schaller et al., 2016).
Patients are more likely to be discharged directly home after their hos­ 1. Studies that were not in German or English language
pital stay and be mobile there without assistance when they reach a
higher level of mobilisation in the ICU (Anekwe et al., 2020; Castro- Information sources
Avila et al., 2015; Fuest et al., 2023; Tipping et al., 2017; Zhang et al.,
2019). The systematic search strategy was developed jointly by all authors,
To address complications like ICUAW and PICS, mobilisation should and after approval, the following databases were searched: MEDLINE
be initiated early, and the ICU stay should be kept as short as possible. via PubMed, Cochrane Library, Pedro, and CINAHL. The exact search
But it is still being determined what effect EM has on ICU LOS. strategy of the databases used is shown in Table A2 in the Appendix. The
Previous systematic reviews of Zang et al. and Liang et al. showed search extended from the inception of the respective database to
that an early mobilisation start may shorten ICU LOS (Liang et al., 2021; October 8th, 2022. We additionally searched the reference list of review
Zang et al., 2020). However, Zang et al. showed that many different articles for relevant studies and added them manually.
interventions (i.e., cycling, neuromuscular electrical stimulation,
active/passive physical therapy) were declared as EM (Zang et al., Selection of studies
2020). Liang et al. examined the effect of various interventions on
delirium-prevention, here, EM was only one of several non- Two reviewers independently screened all studies from the system­
pharmacological interventions (Liang et al., 2021). Nevertheless, the atic search by title and abstract for PICOS criteria. Each study received
question of which type of EM yields the most significant clinical two independent and blinded assessments. A third independent reviewer
advantage remains unanswered in both studies. Therefore, the onset resolved conflicts.
timing of EM and the impact of specific EM types on ICU LOS remains
ambiguous. Data retrieval process
Overall, the exact definition of EM regarding the time point of
initiation and included measures is very heterogeneous, ranging from The included full texts were analysed by one reviewer, and all rele­
≤24 h, <14 days after ICU admission or throughout the ICU stay vant information was extracted. A second reviewer checked all trans­
(Clarissa et al., 2019). Ding et al. investigated the optimal timing for the ferred data for accuracy. If the intervention’s start time assessment,
onset of EM, identifying definitions from ≤24 h to >7 days after ICU according to our definition, needed to be clarified, the respective au­
admission. They showed that initiating mobilisation within 48–72 h may thors were contacted directly.
be optimal for improving clinical outcomes (Ding et al., 2019).
Consequently, this systematic review aims to summarise the evi­ Data details
dence of different EM interventions, defined as any patient intervention
that initiates and/or supports passive or active range-of-motion exer­ All relevant PICOS criteria were extracted from the included studies.
cises, within the first 72 h after ICU admission compared to standard In addition, we extracted study- and patient-specific characteristics.
care on its effect on ICU LOS and other patient outcomes.
Risk of bias
Methods
The risk of bias for randomised controlled trials was verified using
Protocol and registration the Cochrane Risk of Bias Tool (RoB2) (Sterne et al., 2019). This was
done for each study by two independent raters. In case of conflicts, the
The protocol for this systematic review was registered on PROSPERO final overall bias was determined by a third rater.
(CRD42022363584). This study followed the Preferred Reporting Items
for Systematic Reviews and Meta-analyses (PRISMA) reporting guide­ Statistical analysis
lines (see Table A1 in the appendix).
Statistical analysis was performed with program R (version 4.1.2). A
network meta-analysis was performed to analyse the effect of different
Selection criteria
interventions on ICU LOS and hospital LOS. For other secondary out­
comes, the number of studies was too small; here, we performed only a
Before the start of the systematic search, inclusion criteria were
meta-analysis. The network meta-analysis used the netmeta package in
established by common consensus using the PICOS (participants, in­
R (Rücker et al., 2022). To calculate the weighted mean difference
terventions, comparisons, outcomes, and study design) criteria
(WMD), all median values were converted to mean values based on Wan
(Table 1).
et al. (2014). Outcomes were pooled using a random effects model.
Comparisons between different interventions were represented using
Table 1 netgraph plots, with the lines between dots representing direct com­
PICOS criteria for the inclusion criteria of the systematic literature review.
parisons and line thickness representing the quantity of comparisons
P Critically ill patients (≥18 years old) who were admitted to the ICU between two interventions. Meta-analyses were conducted for subgroup
I Early mobilisation within 72 h after admission in an ICU (early mobilisation was analysis. Here, we pooled the most established EM interventions
defined based on Bein et al. and Schaller et al. as „any patient intervention that
initiates and/or supports passive or active range-of-motion exercises“ (Bein et al.,
(cycling, electrically stimulated cycling, and EM alone (i.e., EM in the
2015, Schaller et al., 2023)) strict sense without cycling or neuromuscular electrical stimulation))
C Standard care and defined it as Early Intervention (EI)-group.
O ICU LOS, ICU AW (ICU acquired weakness), hospital LOS, mortality, duration of The metafor package was used for the meta-analyses (Viechtbauer,
mechanical ventilation, mechanical ventilation free days, functionality, Quality
2010). Outcomes were pooled using a random-effects model for studies
of Life, Incidence of delirium, delirium free days (Functionality included
outcomes that evaluated muscle strength, physical activity or performance with high heterogeneity; the fixed-effects model was used for studies
abilities using validated scores or tests; Quality of life included outcomes that with low heterogeneity. In all other statistical analyses, the risk ratio of
measured patient quality of life and satisfaction using validated measurement the individual studies was calculated and integrated into the meta-
tools) analysis. The confidence interval was within 95 % confidence interval
S Randomised controlled trials (RCT)
(95 % CI), and the significance level was set at p < 0.05.

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Between studies, heterogeneity was measured using I2 statistics et al., 2018; Hodgson et al., 2016; Machado et al., 2017; Morris et al.,
(values >75 % considerable high heterogeneity, values <25 % consid­ 2016; Nickels et al., 2020; Ribeiro et al., 2021; Schujmann et al., 2020;
erable low heterogeneity), the τ2 with the restricted maximum- Waldauf et al., 2021) and 6 were multicenter studies (Afxonidis et al.,
likelihood estimator, and P values using Cochran’s Q (Higgins and 2021; Berney et al., 2021; Kho et al., 2019; Schaller et al., 2016;
Thompson, 2002; Higgins et al., 2003). Schweickert et al., 2009; Zhou et al., 2022) (Table A3 in Appendix).
Publication bias was described by a funnel plot to visually check Fifteen studies had a two-arm (Afxonidis et al., 2021; Berney et al.,
left–right symmetry (Sterne and Egger, 2001). 2021; Eggmann et al., 2018; Gama Lordello et al., 2020; Hickmann et al.,
Additional pre-planned subgroup analyses compared the interven­ 2018; Hodgson et al., 2016; Kho et al., 2019; Machado et al., 2017;
tion with the standard of care divided into the following subgroups: Morris et al., 2016; Nickels et al., 2020; Schaller et al., 2016; Schujmann
initiation of mobilisation within the first 72 h in the standard of care et al., 2020; Schweickert et al., 2009; Waldauf et al., 2021; Windmöller
group, initiation after the first 72 h of ICU admission in the standard of et al., 2020), two studies had a three-arm (Ribeiro et al., 2021; Zhou
care group, and initiation was not specified in the studies in the standard et al., 2022), and one study had a four-arm study design (Dos Santos
of care group. et al., 2020) (Table 2). Further differentiation of the EM interventions
resulted in seven different interventions (electrically stimulated cycling,
Results cycling, EM alone (defined as actively or passively performed physio­
therapy interventions), virtual reality, neuromuscular electrical stimu­
Selection of studies lation, EM in combination with neuromuscular electrical stimulation,
and EM in combination with early nutrition), which were included in the
Of the 29,680 studies screened, 18 met the inclusion criteria and network meta-analysis. The most used EM interventions were EM alone,
were included in the statistical analysis (Fig. 1). cycling, and electrically stimulated cycling. These were pooled for the
meta-analysis and defined collectively as the EI group.
Characteristics of the studies Sixteen studies defined the start of the intervention within 72 h of
ICU admission (Afxonidis et al., 2021; Dos Santos et al., 2020; Eggmann
Of the 18 included studies, 12 were single-center studies (Dos Santos et al., 2018; Gama Lordello et al., 2020; Hickmann et al., 2018; Hodgson
et al., 2020; Eggmann et al., 2018; Gama Lordello et al., 2020; Hickmann et al., 2016; Kho et al., 2019; Machado et al., 2017; Morris et al., 2016;

Fig. 1. Flowchart of the systematic search (Page et al., 2021).

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Table 2
Study characteristics and included patients in the respective intervention and control groups.
Author and year Country Included Interventions Start of mobilisation Control Start of mobilisation
patients (n) (Intervention) after ICU (Control) after ICU
admission in hours… admission in hours…

Afxonidis (2021) Greece 78 Early mobilisation Within 24 Standard 24–48

care
Berney (2021) Australia and 162 Electrical stimulated cycling Median 72 [IQR (48–96)] Standard Median 96 [IQR
USA care (24–192)]
Dos-Santos (2020) Brazil 51 Early mobilisation / Neuromuscular Within 48–72 Standard n.s
electrical stimulation / Early care
mobilisation and neuromuscular
electrical stimulation
Eggmann (2018) Switzerland 130 Early mobilisation Median 46.8 [IQR Standard Median 51.6 [IQR
(33.8–67.2)] care (36.7–69.4)]
Gama-Lordello (2020) Brazil 234 Cycling 6–8 Standard 6–8
care
Hickmann (2018) Belgium 19 Early mobilisation Mean 28 [SD (9)] Standard Mean 46 [SD (25)]
care
Hodgson (2016) New Zealand 50 Early mobilisation Median 72 [IQR (48–96)] Standard n.s
care
Kho (2019) Canada 66 Cycling Median 72 [IQR Standard Median 72 [IQR
(48–120)] care (24–96)]
Machado (2017) Brazil 49 Cycling Median 72 [IQR Standard Median 48 [IQR
(48–120)] care (24–72)]
Morris (2016) USA 300 Early mobilisation Median 24 [IQR (0–48)] Standard Median 168 [IQR
care (96–240)]
Nickels (2020) Australia 74 Cycling Median 55.2 [IQR Standard n.s
(43.2–74.4)] care
Ribeiro (2021) Brazil 70 Early mobilisation / Virtual Reality Within 24 Standard n.s
Program care
Schaller (2016) Austria, 200 Early mobilisation Within 24 Standard n.s
Germany and care
USA
Schujmann (2019) Brazil 135 Early mobilisation Within 48 Standard n.s
care
Schweickert (2009) USA 104 Early mobilisation Median 36 [IQR Standard Median 177.6 [IQR
(24–50.4)] care (144–261.6)]
Waldauf (2021) Czech 150 Electrical stimulated cycling Median 63 [IQR (45–84)] Standard Median 68 [IQR
Republic care (48–95)]
Windmöller (2020) Brazil 42 Cycling At 48 Standard n.s
care
Zhou (2022) China 150 Early mobilisation / Early mobilisation Within 24 Standard n.s.
and early nutrition care
n.s.: not stated; IQR:
interquartile range;
SD: standard
deviation

Nickels et al., 2020; Ribeiro et al., 2021; Schaller et al., 2016; Schujmann On the patient level, the two most common reasons for ICU admis­
et al., 2020; Waldauf et al., 2021; Windmöller et al., 2020; Zhou et al., sions were a respiratory failure or cardiac surgery (Table A6 in appen­
2022) and two studies within 72 h of intubation (Berney et al., 2021; dix). Further, patient characteristics and disease severity are available in
Schweickert et al., 2009) (Table A4 in appendix). the appendix (Table A7 and A8, respectively).
In the respective control groups, standard care also started within the
first 72 h after admission in 5 studies (Eggmann et al., 2018; Hickmann
et al., 2018; Kho et al., 2019; Machado et al., 2017; Waldauf et al., 2021) Primary endpoint
and after 72 h in 4 studies (Berney et al., 2021; Morris et al., 2016;
Schaller et al., 2016; Schweickert et al., 2009). 9 studies did not specify The included 18 studies investigated 1923 patients on the impact of
the start of control treatment (Afxonidis et al., 2021; Dos Santos et al., EM on ICU LOS and were included in the network meta-analysis.
2020; Gama Lordello et al., 2020; Hodgson et al., 2016; Nickels et al., Network meta-analysis showed that EM alone and cycling had the
2020; Ribeiro et al., 2021; Schujmann et al., 2020; Windmöller et al., greatest weighting in ICU LOS compared with standard care (Fig. 2a).
2020; Zhou et al., 2022) (Table 2 and A6 in appendix). In 12 studies, EM alone (WMD − 0.78 days, 95 % CI [− 1.38; − 0.18]; 11 studies with
standard care consisted of active and/or passive mobilisation in the 1124 patients (Afxonidis et al., 2021; Dos Santos et al., 2020; Eggmann
control group (Afxonidis et al., 2021; Dos Santos et al., 2020; Eggmann et al., 2018; Hickmann et al., 2018; Hodgson et al., 2016; Morris et al.,
et al., 2018; Gama Lordello et al., 2020; Hodgson et al., 2016; Machado 2016; Ribeiro et al., 2021; Schaller et al., 2016; Schujmann et al., 2020;
et al., 2017; Morris et al., 2016; Nickels et al., 2020; Schujmann et al., Schweickert et al., 2009; Zhou et al., 2022)) and EM with early nutrition
2020; Waldauf et al., 2021; Windmöller et al., 2020; Zhou et al., 2022). (WMD − 1.19 days, 95 % CI [− 2.34; − 0.03]; 1 study with 100 patients
In other studies, there was no precise specification of standard care (Zhou et al., 2022)) were able to significantly shorten the ICU LOS
(Table A5 in appendix). (Fig. 2b). All other EM interventions showed no significant differences.
The daily and total mobilisation duration was very heterogeneous. Heterogeneity was moderate for I2 > 25 % and <75 %.
The characteristics of the different interventions are presented in In multi-arm studies, interventions used in other studies were
Table A4 and those of the control group in Table A5 in the appendix. declared as EI group and were included in the subgroup meta-analysis.
These referred to electrically stimulated cycling, cycling and EM alone

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Fig. 2. Netgraph (a) and Netplot (b) of different EM interventions within 72 h of ICU admission, compared to standard care on ICU LOS using a network meta-
analysis of the 18 included studies. Lines between the points represent the direct comparison of two interventions; the line thickness refers to the weighting of
the comparisons between the interventions in the network meta-analysis.

(Dos Santos et al., 2020; Ribeiro et al., 2021; Zhou et al., 2022). 1587 patients; Fig. 5a).
The subgroup analysis regarding the start of EIs after admission and The analysis for EI compared with standard care initiated within 72 h
the length of ICU stay showed no significant effect of EI compared to or after 72 h showed no significant difference in hospital LOS (Fig. 5b). A
standard care (WMD − 0.58 days, 95 % CI [− 1.19; 0.03]; all 18 studies significant difference was only seen in comparison to the groups that did
with 1833 patients; Fig. 3a). not specify a defined start of standard care (WMD − 2.23 days, 95 % CI
Similarly, there was no significant effect when comparing EI to [− 3.95; − 0.50]; 7 studies with 585 patients).
standard care initiated within the first 72 h (WMD 0.23 days, 95 % CI The overall heterogeneity of the studies was high, with I2 > 75 %.
[− 0.97; 1.43]; 5 studies with 354 patients) or after 72 h (WMD − 0.94 Regarding functionality, seven studies showed results at the same
days, 95 % CI [− 2.11; 0.23]; 4 studies with 766 patients) of admission time points and were included in the meta-analysis (Berney et al., 2021;
on ICU LOS (Fig. 3b). Nine studies did not specify a defined start of Eggmann et al., 2018; Hodgson et al., 2016; Nickels et al., 2020;
standard care. This did not influence the outcome. Schujmann et al., 2020; Waldauf et al., 2021; Zhou et al., 2022).
Regarding the ICU LOS and sensitivity analysis, the funnel plot The meta-analysis showed a positive effect for EI compared to
showed no particular publication bias (Fig. A1 in appendix). standard care on muscle strength as measured by the Medical Research
The overall heterogeneity of the studies was high with I2 > 75 %. Council sum score (MRC-SS) (WMD 1.50 points, 95 % CI [0.21, 2.79];
Fig. A2a in Appendix; 6 studies with 527 patients). In terms of patient
mobility during ICU stay, measured with the ICU Mobility Scale (IMS), a
Secondary endpoints mobility level almost two levels higher was achieved in the EI-group
compared to standard care (WMD: 1.89 points, 95 % CI [0.90; 2.89];
Fourteen studies investigated 1587 patients on the impact of EM 3 studies with 211 patients; Fig. A2b in Appendix).
concerning hospital LOS. Similar results were seen for physical function measured by the
The network meta-analysis showed that EM alone and cycling had Functional Status Score-ICU for EI compared to standard care (FSS-ICU)
the greatest weighting in hospital LOS compared with standard care (WMD: 1.92 points, 95 % CI [0.50; 3.35]; 3 studies with 240 patients;
(Fig. 4a). Only EM alone was able to significantly shorten hospital LOS Fig. A2c in Appendix). The Barthel Index also improved significantly in
(WMD − 1.05 days, 95 % CI [− 1.74; − 0.36]; 8 studies with 977 patients the EI group compared to standard care (WMD: 17.11 points, 95 % CI
(Afxonidis et al., 2021; Eggmann et al., 2018; Hodgson et al., 2016; [8.12, 26.10]; 2 studies with 199 patients; Fig. A2d in Appendix).
Morris et al., 2016; Ribeiro et al., 2021; Schaller et al., 2016; Schujmann Overall, the studies showed high heterogeneity in MRC-SS, IMS, and
et al., 2020; Schweickert et al., 2009)) (Fig. 4b). All other EM in­ Barthel index (I2 > 50 %), while heterogeneity in FSS-ICU score was low.
terventions showed no significant differences. Concerning quality of life, two studies were included in the meta-
In the meta-analysis of the most widely used EM interventions, there analysis that collected the SF36 score six months after ICU treatment
was a significant reduction in hospital LOS for EI compared with stan­ (Eggmann et al., 2018; Morris et al., 2016). There was a significant
dard care (WMD − 1.71 days, 95 % CI [− 2.99; − 0.43]; 14 studies with

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Fig. 3. Effect of EIs, regarding the start after admission compared to standard care (a) and EI compared to initiated standard care within or after 72 h of admission on
ICU LOS (b).

improvement for the SF36 mental health subscore of more than two passive physiotherapy, and EM with early nutrition significantly
points in the EI-group compared to standard care (WMD 2.47 points, 95 reduced ICU LOS compared to standard care. EM significantly reduced
% CI [1.31; 3.64]; 2 studies with 219 patients; see Fig. A3 in Appendix, the hospital LOS and showed positive effects on functionality and
respectively). quality of life compared to standard care.
Other endpoints showed non-significant differences (Table A9 in Although the results on ICU LOS were consistent with previous sys­
Appendix). tematic reviews, which showed that EM can positively influence the
outcomes of critically ill patients (Chen et al., 2021; Monsees et al.,
2022; Okada et al., 2019), our systematic review adds two important
Risk of bias
aspects. First, we have defined EM precisely and based on available
recommendations and evidence. Second, we have compared different
Three studies had a high risk of bias (Dos Santos et al., 2020; Ribeiro
mobilisation interventions using a network meta-analysis. In previous
et al., 2021; Zhou et al., 2022) (see Fig. A5 in Appendix). Eleven studies
systematic reviews of RCTs involving critically ill patients in the ICU,
were rated with some concerns (Berney et al., 2021; Gama Lordello
Chen et al., Okada et al., and Monsees et al. investigated the mean dif­
et al., 2020; Hickmann et al., 2018; Hodgson et al., 2016; Kho et al.,
ference in ICU LOS between EM and control interventions. All three
2019; Machado et al., 2017; Morris et al., 2016; Nickels et al., 2020;
studies could not show a significant effect of EM concerning ICU LOS
Schujmann et al., 2020; Waldauf et al., 2021; Windmöller et al., 2020),
(Chen et al., 2021; Monsees et al., 2022; Okada et al., 2019). Chen et al.
and four studies had a low risk of bias (Afxonidis et al., 2021; Eggmann
conducted a meta-analysis of RCTs to assess the impact of EM therapy
et al., 2018; Schaller et al., 2016; Schweickert et al., 2009). Since these
compared to standard care on cardiac surgery patients in the ICU (Chen
were interventional studies utilizing highly visible measures, the
et al., 2021). The cohort of cardiac surgery patients represented a very
blinding of patients and the blinding of the executing personnel is a
vulnerable patient group, reducing the comparability with our results.
problem, contributing to a particular risk of bias.
Okada et al. examined in their systematic review of RCTs the impact of
early versus delayed mobilisation. However, the authors defined EM as
Discussion starting within the first week after admission to the ICU (Okada et al.,
2019). Compared to Ding et al. who showed in their systematic review
Our systematic review showed that EM alone, declared as active or

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Fig. 4. Netgraph (a) and Netplot (b) of different EM interventions within 72 h of ICU admission, compared to standard care on hospital LOS using a network meta-
analysis of the 14 included studies. Lines between the points represent the direct comparison of two interventions, the line thickness refers to the weighting of the
comparisons between the interventions in the network meta-analysis.

that EM should best be initiated during the first 72 h after admission to nonpharmacological delirium-prevention interventions of critically ill
the ICU to improve the clinical outcome of patients, this definition of EM patients on different clinical outcomes (Liang et al., 2021). A limiting
no longer corresponded to universally accepted definitions (Ding et al., aspect was the inclusion of non-pharmacological interventions, among
2019). Ding’s findings aligned with the recommendation of the current which EM was just one of several. It remains to be seen what significance
German guideline: “Positioning therapy and early mobilisation for the EM alone will have. In their systematic review of RCTs, Zang et al.
prophylaxis or therapy of pulmonary dysfunction”, which recommends that assessed the effect of EM on critically ill patients in the ICU regarding
mobilisation should be started within the first 72 h after admission to the different clinical outcomes. They included any form of EM intervention
ICU (Bein et al., 2015; Schaller et al., 2023). Monsees et al. included only (Zang et al., 2020). Our review showed that various EM interventions
active EM interventions in their systematic review to investigate the affected the ICU LOS differently. It is, therefore, essential to define EM
effect of EM on ICU LOS, so passive-only interventions, e.g., passive interventions more precisely to provide the best form of EM for the
cycling, were not integrated (Monsees et al., 2022). However, the ad­ patient.
vantages of passive mobilisation of critically ill patients have been Our meta-analysis also revealed heterogeneity in terms of EM in­
demonstrated. For example, Vollenweider et al. demonstrated in their terventions. This heterogeneity was primarily evident in the varying
systematic review that passive movement was a cellular benefit in me­ durations and frequencies of individual interventions. The optimal
chanically ventilated patients (Vollenweider et al., 2022). Other studies dosage for mobilisation remains uncertain. Several studies suggested
indicated that passive mobilisation, like passive range of motion exercise that a higher mobilisation dose can lead to improved outcomes in crit­
in a structured program, might reduce oedema, increase range of mo­ ically ill patients (Chen et al., 2021; Okada et al., 2019; Zang et al.,
tion, improve upper extremity function and activities of daily living, 2020) while the recent TEAM trial implied caution of very high mobi­
promote muscle regeneration and might induce reorganisation of lisation dosage (Hodgson et al., 2022). Additionally, a first analysis on
sensorimotor representation (Carel et al., 2000; Kim et al., 2014; Relaix mobilisation dose optimisation suggests that tailoring the mobilisation
and Zammit, 2012). approach to individual patients or specific patient groups is necessary
Other studies also showed that the definition of the intervention in (Fuest et al., 2023). It is evident that further research is required to
relation to EM is very heterogeneous or imprecise. In the studies by Zang investigate various EM interventions, their durations, and frequencies to
et al. and Liang et al. it was found that early initiation of mobilisation achieve optimal short- and long-term outcomes for critically ill patients.
might reduce the length of stay in an ICU by 1.82 days and 1.24 days; Our study had strengths and limitations. Strengths included that we
however, in these studies, various interventions were collectively focused on studies that defined EM within the first 72 h after admission
considered under the term EM (Liang et al., 2021; Zang et al., 2020). to ICU, as recommended by Bein et al. and Schaller et al. (Bein et al.,
Liang et al. investigated in their systematic review the effects of 2015; Schaller et al., 2023). This was one of the most important

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N. Daum et al. Intensive & Critical Care Nursing 80 (2024) 103573

Fig. 5. Effect of EIs, regarding the start after admission compared to standard care (a) and EI compared to initiated standard care within or after 72 h of admission on
hospital LOS (b).

limitations of other systematic reviews, as EM was often not defined very Competing interests
precisely. We also conducted a network meta-analysis on different EM
interventions to analyse the respective effect on ICU LOS and hospital SJS received grants and non-financial support from Reactive Ro­
LOS. A limitation was that some studies did provide insufficient infor­ botics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany),
mation about their initiation of mobilisation, precluding their inclusion STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants,
in this review. Second, the aim of this systematic review was to inves­ personal fees, and non-financial support from Fresenius Kabi Deutsch­
tigate the initiation of early mobilisation only. However, the in­ land GmbH (Bad Homburg, Germany), grants from the Innovationsfond
terventions were always complex with different doses (frequency, level, of The Federal Joint Committee (G-BA), personal fees from Springer
and duration), i.e., no studies only examined this temporal component. Verlag GmbH (Vienna, Austria) for educational purposes and Advanz
Pharma GmbH (Bielefeld, Germany), non-financial support from na­
Conclusion tional and international societies (and their congress organisers) in the
field of anesthesiology and intensive care medicine, outside the sub­
EM could significantly reduce the ICU and hospital LOS and mitted work. Dr. Schaller holds stocks in small amounts from Alphabeth
improved functionality and quality of life if initiated within the first 72 h Inc., Bayer AG, and Siemens AG; these holdings have not affected any
of ICU admission. There was also a signal for an improved effect with a decisions regarding his research or this study.
combination of other forms of EIs, like early nutrition therapy. Addi­ All remaining authors declare that they have no conflict of interest.
tional research is necessary to gain a better understanding of the effec­
tiveness of various EM interventions and to identify which patients Support
benefit the most from each intervention. Furthermore, it remains un­
clear what duration and frequency of individual EM interventions most There were no sponsors or financial support for this systematic
effectively enhance the short- and long-term outcomes of critically ill review.
patients.

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Declaration of Competing Interest Liang, S., Chau, J.P.C., Lo, S.H.S., Zhao, J., Choi, K.C., 2021. Effects of
nonpharmacological delirium-prevention interventions on critically ill patients’
clinical, psychological, and family outcomes: A systematic review and meta-analysis.
The authors declare that they have no known competing financial Austr. Crit. Care 34, 378–387.
interests or personal relationships that could have appeared to influence Machado, A.D.S., Pires-Neto, R.C., Carvalho, M.T.X., Soares, J.C., Cardoso, D.M.,
the work reported in this paper. Albuquerque, I.M., 2017. Effects that passive cycling exercise have on muscle
strength, duration of mechanical ventilation, and length of hospital stay in critically
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