Nursing in Critical Care - 2022 - Monsees - A systematic review of the effect of early mobilisation on length of stay for

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<p>L I T E R A T U R E R E V I EW</p><p>A systematic review of the effect of early mobilisation on</p><p>length of stay for adults in the intensive care unit</p><p>Jonas Monsees MSc, RGN, Clinical Nurse Manager1 |</p><p>Zena Moore PhD, RPN, Professor of Nursing2,3,4,5,6,7 |</p><p>Declan Patton PhD, RPN, Director of Nursing and Midwifery Research3,7,8,9 |</p><p>Chanel Watson, Lecturer10 | Linda Nugent PhD, FFNMRCSI, PG Dip Ed,</p><p>RGN, Lecturer and Programme Director, Adjunct Assistant Professor3,11 |</p><p>Pinar Avsar PhD, RGN, Senior Postdoctoral Fellow12 |</p><p>Tom O'Connor EdD, RGN, Director of Academic Affairs and Deputy Head of School3,5,7,11</p><p>1Post Anaesthetic Critical Care Unit, Tallaght University Hospital, Dublin, Ireland</p><p>2The Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, Dublin, Ireland</p><p>3Department of Nursing, Fakeeh College of Health Sciences, Jeddah, Saudi Arabia</p><p>4Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium</p><p>5School of Nursing & Health, Lida Institute, Shanghai, China</p><p>6School of Medicine, University of Wales, Cardiff, UK</p><p>7School Nursing and Midwifery, Griffith University, Queensland, Australia</p><p>8Wounds and Trauma Research Centre, School of Nursing and Midwifery, The Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health</p><p>Sciences, Dublin, Ireland</p><p>9Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia</p><p>10School of Nursing and Midwifery, The Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, Dublin, Ireland</p><p>11School of Nursing and Midwifery and Lead Researcher, Skin Wounds and Trauma Research Centre, The Royal College of Surgeons in Ireland (RCSI), University of</p><p>Medicine and Health Sciences, Dublin, Ireland</p><p>12Skin Wounds and Trauma Research Centre, The Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, Dublin, Ireland</p><p>Correspondence</p><p>Jonas Monsees, Post Anaesthetic Critical Care</p><p>Unit, Tallaght University Hospital, Tallaght,</p><p>Dublin.</p><p>Email: jonas.monsees@tuh.ie</p><p>Funding information</p><p>Tallaght University Hospital</p><p>Abstract</p><p>Background: EM has been hypothesized to help prevent the development of ICU</p><p>acquired weakness and may therefore result in positive outcomes for ICU patients.</p><p>Aim: To establish the impact of Early mobilisation (EM) on adult Intensive Care Unit</p><p>(ICU) patients in terms of ICU length of stay (LOS), as well as hospital LOS, duration</p><p>of mechanical ventilation, mortality, and functional independence.</p><p>Study design: A Systematic Review. EMBASE, MEDLINE, CINAHL, and the Cochrane</p><p>Library were searched on 24th November 2020. Included studies and other syste-</p><p>matic reviews were hand-searched for further includable studies. The primary</p><p>Received: 8 August 2021 Revised: 22 April 2022 Accepted: 6 May 2022</p><p>DOI: 10.1111/nicc.12785</p><p>This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any</p><p>medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</p><p>© 2022 The Authors. Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.</p><p>Nurs Crit Care. 2023;28:499–509. wileyonlinelibrary.com/journal/nicc 499</p><p>https://orcid.org/0000-0003-1681-5792</p><p>https://orcid.org/0000-0002-4692-9718</p><p>https://orcid.org/0000-0003-1018-2605</p><p>https://orcid.org/0000-0002-8548-1813</p><p>https://orcid.org/0000-0001-7480-8545</p><p>https://orcid.org/0000-0001-5948-0975</p><p>mailto:jonas.monsees@tuh.ie</p><p>http://creativecommons.org/licenses/by-nc-nd/4.0/</p><p>http://wileyonlinelibrary.com/journal/nicc</p><p>http://crossmark.crossref.org/dialog/?doi=10.1111%2Fnicc.12785&domain=pdf&date_stamp=2022-06-01</p><p>outcome was ICU LOS whilst secondary outcomes were duration of MV, mortality,</p><p>hospital LOS and functional independence. The PRISMA guidelines were utilized to</p><p>perform the review. Ten randomized controlled trials with a combined total of 1291</p><p>patients met inclusion criteria and were scrutinized using the Joanna Briggs Institute</p><p>(JBI) Checklist for Systematic Reviews. Revman 5.4.1 was used to conduct meta-anal-</p><p>ysis were possible.</p><p>Results: Results were limited by the evidence available for inclusion, in particular</p><p>small sample sizes. However, a trend towards a shorter duration of ICU LOS and</p><p>duration of mechanical ventilation emerged. There was also a trend towards</p><p>higher rates of functional independence for intervention groups. Mortality rates</p><p>appeared unaffected and results of meta-analysis were statistically non-significant</p><p>(p = 0.90).</p><p>Conclusion: By applying a stricter time limit than previous systematic reviews a trend</p><p>emerged that the commencement of EM has a positive effect on patient outcomes, in</p><p>particular ICU LOS.</p><p>Relevance to clinical practice: The evidence base surrounding EM remains poor;</p><p>however on the balance of the available evidence the application of EM should not</p><p>be delayed.</p><p>K E YWORD S</p><p>critical care, critical care nursing, early ambulation, physical therapy specialty, rehabilitation</p><p>1 | INTRODUCTION</p><p>Early mobilisation (EM) has not been universally defined.1 Hodgson</p><p>et al., (2013, p.1)12 defined it as: “the application of traditional modes</p><p>of physiotherapy at an earlier stage than and delivered more regularly</p><p>than conventional practice”.</p><p>EM has been hypothesized to prevent the development of Inten-</p><p>sive Care Unit (ICU) acquired weakness (ICU-AW), and may therefore</p><p>lead to improved patient outcomes both in terms of length of stay</p><p>(LOS) and functional independence.18 ICU-AW is common among ICU</p><p>survivors and many studies reported functional deficits, even five</p><p>years post discharge.6,8 In addition, a negative impact on family</p><p>income was reported by 33% of all patients at 6 months and 28% at</p><p>12 months.18 ICU-AW can develop within 24 h of ICU admission and</p><p>carries significant implications, both in terms of quality of life and</p><p>cost.6,8,29 Passive exercise has been standard care in most ICUs; how-</p><p>ever, the implementation of EM has shown promising results.26</p><p>Several systematic reviews (SR) have explored the effective-</p><p>ness of EM. Tipping et al. included 14 trials and concluded that</p><p>activity limitations decreased and muscle strength increased for</p><p>patients that received EM.31 However, a Cochrane review reported</p><p>that evidence was too weak to draw any conclusions, but only</p><p>included four randomized controlled trials (RCTs), due to their stri-</p><p>cter inclusion criteria.3 Zhang et al. reviewed 23 trials and con-</p><p>cluded that EM reduces the duration of mechanical ventilation</p><p>(MV) and incidence of ICU-AW, and leads to improvements in phys-</p><p>ical function.34 However, they advised caution when interpreting</p><p>results due to the mixed quality of the available evidence.34 Wang</p><p>et al. included 39 RCTs and showed that EM does not affect mor-</p><p>tality rates but significantly reduces rates of pressure sores and</p><p>deep vein thrombosis.33 They did not impose a language limit and</p><p>were able to include a large number of non-English publications,</p><p>particularly from China.33 Their results were limited by high levels</p><p>of heterogeneity.33</p><p>A SR of 48 publications and 7546 patients established that EM is safe,</p><p>even when patients are fully ventilated.22 Ding et al. conducted a SR on</p><p>the optimum time for enrolment to EM protocols and found that enrol-</p><p>ment within 48–72 h was likely to be most effective at reducing ICU-AW.2</p><p>What is known about the topic</p><p>• Evidence regarding the application of EM in ICU is mixed</p><p>What this paper adds</p><p>• The evidence base for the application of EM in ICU</p><p>remains poor; however trends towards improved out-</p><p>comes in terms of ICU LOS, Hospital LOS as well as dura-</p><p>tion of MV emerge from this review.</p><p>• Mortality rates are unaffected by EM.</p><p>• Disease severity may have an impact on the outcomes</p><p>of EM.</p><p>500 MONSEES ET AL.</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded</p><p>from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>The overall evidence, to date, is weak, due to the underpowered</p><p>nature of included trials, high heterogeneity and the fact that previous</p><p>SRs did not apply a time limit on enrolment time.31,33,34 A SR by Ding</p><p>et al. analysed the optimum time for initiation of EM and found that initi-</p><p>ation within 48–72 h was optimal.2 However previous SRs on EM</p><p>included studies with late interventions, for example, both Tipping et al.</p><p>and Zhang et al. included The trial by Moss et al., where patients did not</p><p>receive their first intervention until day eight of ICU admission.21,31,34</p><p>While this is likely worthwhile in its own right, it cannot be considered</p><p>“early” in the strictest sense of the word. The Inclusion of these studies</p><p>may have skewed results for Tipping et al. and Zhang et al.31,34 The pre-</p><p>sent review, therefore, aims to apply more stringent inclusion criteria and</p><p>different outcome measures to previous reviews, and will, therefore, con-</p><p>tribute to a deeper understanding of the effects of EM on adult ICU</p><p>patients, thereby informing future research and clinical practice. In partic-</p><p>ular, this review will use a strict limit on enrolment time.</p><p>2 | AIMS</p><p>This SR aims to establish the effect of EM in adult ICU patients on ICU</p><p>LOS. The primary outcome measure will be ICU LOS, followed by the</p><p>duration of MV, hospital LOS, mortality, and functional independence.</p><p>3 | METHODS</p><p>The question was formulated using the Population, Intervention,</p><p>Comparison, and Outcome (PICO) approach.5</p><p>• Population: Adult ICU patients.</p><p>• Intervention: Any form of EM that promotes active exercise</p><p>• Comparison: Normal care or no EM intervention</p><p>• Primary outcome measure: ICU LOS</p><p>• Secondary outcome measures:</p><p>� Duration of MV</p><p>� Mortality</p><p>� Hospital LOS</p><p>� Functional independence</p><p>Research Question:</p><p>What is the effect of early mobilisation on the length of stay of</p><p>adults in the ICU?</p><p>3.1 | Criteria for inclusion and exclusion</p><p>To be included in this SR, studies had to be RCTs and utilize early and</p><p>active mobilisation on critically ill adult patients. Studies had to be</p><p>published in English and report ICU LOS. Lastly, they had to enrol</p><p>their patients within 4 days of admission or intubation.</p><p>Non-RCT studies were excluded, as were passive exercise only</p><p>regimes, or studies that focused on post ICU-discharge interventions.</p><p>Studies that did not report on ICU LOS were also excluded. Further-</p><p>more, studies utilizing cycle ergometry as their only intervention were</p><p>also excluded. Tipping et al. excluded cycle ergometry while Zhang</p><p>et al. included it. For this work, the argument presented by Tipping</p><p>et al. was followed; cycle ergometry on its own cannot be considered</p><p>as EM, as it does not involve the same complexities as the active</p><p>mobilisation of ICU patients.31,34</p><p>3.2 | Search strategy</p><p>Searches were carried out on December 31, 2021. CINAHL,</p><p>MEDLINE, EMBASE, and the Cochrane Database were searched.</p><p>Searches were limited to human, adult and RCT studies published in</p><p>English. For CINAHL the following Medical Subject Heading (MeSH)</p><p>terms were used: rehabilitation, early ambulation, physical therapy</p><p>specialty, and critical care. For MEDLINE and EMBASE the following</p><p>Emtree terms were used: mobilisation, rehabilitation, intensive care,</p><p>and randomized controlled trial. For Cochrane, the terms early</p><p>mobilisation and ICU were utilized. Boolean operators were used in</p><p>conjunction with the selected search terms. Both search terms and</p><p>Boolean operators were verified with a second reviewer.</p><p>Reference lists of included studies and SRs on the topic were</p><p>hand-searched. Search Results were recorded in the Preferred</p><p>Reporting of Items for Systematic Reviews and Meta-Analyses</p><p>(PRISMA) flowchart.23 Please see Data S1 for details of searches and</p><p>results</p><p>3.3 | Data collection and extraction</p><p>A data extraction table was utilized to extract all necessary data to</p><p>complete the review. The Data extraction table contains summary</p><p>information for each article, patient characteristics, the nature of the</p><p>utilized EM protocol, and data as regards the primary and secondary</p><p>outcome measures. Electronic databases were searched to retrieve</p><p>studies in accordance with the eligibility criteria outlined above. Then</p><p>the data were extracted by one reviewer and validated by a second</p><p>reviewer.</p><p>3.4 | Quality appraisal</p><p>The Joanna Briggs Institute (JBI) Checklist for Randomized Controlled</p><p>Trials Tool was used to assess for bias in the included studies.14</p><p>3.5 | Data analysis</p><p>Meta-analysis was performed with the Review Manager 5.4.1.30</p><p>Continuous variables were presented as Standard Mean Difference,</p><p>while dichotomous variables were expressed as risk ratios. Results of</p><p>comparable trials were pooled using the fixed-effect or random</p><p>MONSEES ET AL. 501</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>effect model and 95% confidence intervals. Heterogeneity was</p><p>investigated by calculating the I2.9 A funnel plot to test for publica-</p><p>tion bias should only be used when there are at least 10 studies</p><p>included in the meta-analysis,10 therefore we did not assess the</p><p>publication bias.</p><p>Continuous data, not presented as a mean and standard devia-</p><p>tion (SD), were not mathematically converted due to correspondence</p><p>with authors and examination of articles, confirming that the data</p><p>were not normally distributed.7,16,19 Therefore, it was not suitable</p><p>for mathematical conversion to mean and SD.32 A narrative synthe-</p><p>sis was adopted for data that was unsuitable for meta-analysis. For</p><p>data reported as median and interquartile range (IQR), bar charts</p><p>were prepared to express the difference in median days between</p><p>intervention and control groups for ICU LOS, hospital LOS, and dura-</p><p>tion of MV.</p><p>4 | RESULTS</p><p>4.1 | Search results</p><p>The searches yielded 5172 articles. 5134 articles were excluded based</p><p>on title, or abstract. 34 full text articles were assesed, 10 of which</p><p>were suitable for inclusion, based on the inclusion and exclusion</p><p>criteria. See Figure 1 PRISMA flow diagram, summarizing the search</p><p>outcomes. The most common reason for exclusion on full-text review</p><p>was enrolment time after 4 days of ICU admission or intubation.</p><p>4.2 | Study characteristics</p><p>Ten RCTs enrolling a total of 1291 patients were included in this review.</p><p>Study sizes ranged from 4017 to 300.20 Four studies were set in general</p><p>mixed ICUs,4,11,25,27 three in medical ICUs,13,20,28 and the remaining three</p><p>in surgical ICUs.17,24,26 The three surgical RCTs varied considerably in their</p><p>settings. Maffei et al. performed their trial in a liver transplant unit, while</p><p>Schaller et al. included a wide variety of surgical specialties. Patman et al.</p><p>on the other hand included cardiac surgery patients only.17,24,26 The</p><p>included studies were set in nine different countries on four continents.</p><p>See Table 1 for the summary of characteristics.</p><p>4.3 | Nature of interventions</p><p>Seven of the included RCTs utilized progressive mobilisation regime</p><p>that generally involved a stepwise approach: gradually building up the</p><p>Records identified from*:</p><p>Databases (n = 5172:</p><p>Cinahl: 4105</p><p>Medline: 576</p><p>Embase: 240</p><p>Cochrane: 251)</p><p>Registers (n =0 )</p><p>Records removed before screening:</p><p>Duplicate records removed (n = 4)</p><p>Records marked as ineligible by</p><p>automation tools (n = 0)</p><p>Records removed for other reasons (n</p><p>= 0)</p><p>Records</p><p>screened</p><p>(n =5168 )</p><p>Records excluded**</p><p>(n = 5134)</p><p>Reports sought for retrieval</p><p>(n = 34)</p><p>Reports not retrieved</p><p>(n = 0)</p><p>Reports assessed for eligibility</p><p>(n = 34) Reports excluded:24</p><p>Conference abstracts: 1</p><p>Outside timelimit: 12</p><p>Wrong Design: 9</p><p>ICU LOS not reported: 2</p><p>Studies included in review</p><p>(n = 10)</p><p>Identification of studies via databases and registers</p><p>Id</p><p>en</p><p>tifi</p><p>cat</p><p>io</p><p>n</p><p>Sc</p><p>re</p><p>eni</p><p>ng</p><p>In</p><p>clu</p><p>de</p><p>d F IGURE 1 PRISMA 2020 flow</p><p>diagram for overall search results</p><p>502 MONSEES ET AL.</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>duration and level of the exercises.4,11,17,26–28 The remaining three</p><p>studies increased the amount of physiotherapy in comparison to the</p><p>control group, without following a stepwise mobilisation pro-</p><p>gram.20,24,25 Furthermore, Santos et al. divided their intervention</p><p>groups into an EM group called EX, and a group that received neuro-</p><p>muscular stimulation in addition to the EM protocol called NMES+-</p><p>EX.25 These subgroups have been listed separately for the purpose of</p><p>the meta-analysis. Neuromuscular stimulation was also part of the EM</p><p>interventions in Schujmann et al.27</p><p>5 | PRIMARY OUTCOMES</p><p>5.1 | ICU LOS</p><p>Four of the included studies reported their ICU LOS suitably for meta-</p><p>analysis.13,17,24,25 The results for Santos et al. were split into two</p><p>different subgroups of EM.25 The meta-analysis indicated a benefit</p><p>for intervention groups, but results were statistically non-significant</p><p>with high heterogeneity of I2 = 53% (Figure 2).</p><p>Patman et al. was the only trial to report an increase in ICU LOS,</p><p>although this was by 0.3 mean days and statistically not significant</p><p>(p = 0.56).24 Maffei et al. reported a reduction by 2.3 mean days</p><p>(p = 0.690), while Santos et al. reported a reduction by 2.8 mean days</p><p>for the NMES+EX group and 3.9 mean days for the EX group</p><p>(p = 0.03).17,25 Dong et al. also reported a reduction of ICU LOS by</p><p>2.5 mean days (p = 0.01).13</p><p>The remaining six studies reported results in median days with</p><p>IQR ranges. All studies reported a reduced ICU LOS for intervention</p><p>groups. Morris et al. (p = 0.68) and Eggmann et al. (p = 0.595) both</p><p>reported a reduction by 0.5 median days, Schweickert et al. (p = 0.08)</p><p>and Hodgson et al. (p = 0.28) reported a reduction by 2 median days,</p><p>and Schujmann et al. (p = 0.003) and Schaller et al. (p = 0.0054)</p><p>reported a reduction by 3 median days (Figure S1).4,11,20,26–28</p><p>TABLE 1 Study characteristics of included studies</p><p>Study</p><p>Patients main</p><p>diagnosis, if</p><p>specified</p><p>Sample</p><p>size</p><p>Mean</p><p>APACHE IIa Country Age</p><p>Percentage</p><p>female Type of intervention</p><p>Schujmann et al.27 General (mixed) 135 Brazil 51c 37% Progressive mobilisation</p><p>regime</p><p>Eggmann et al.4 General (mixed) 115 22 Switzerland 64c 41% Progressive mobilisation</p><p>regime</p><p>Santos et al.25 General (mixed) 51 15.9 Brazil 53c 32% 1 physiotherapy session/</p><p>day</p><p>Maffei et al.17 Liver transplant 40 France 53c 22.5% 2 physiotherapy</p><p>sessions/day</p><p>Morris et al.20 Respiratory 300 18b USA 56c 55% 3 physiotherapy</p><p>sessions/day</p><p>Hodgson et al.11 General (mixed) 50 18 Australia, New</p><p>Zealand</p><p>61c 40% Progressive mobilisation</p><p>regime</p><p>Schaller et al.26 Surgical (mixed) 200 20 Austria, Germany,</p><p>USA</p><p>65d 47% Progressive mobilisation</p><p>regime</p><p>Dong et al.13 Medical 60 15 China 55c 31% Progressive mobilisation</p><p>regime</p><p>Schweickert</p><p>et al.28</p><p>Medical 104 19 USA 56d 50% Progressive mobilisation</p><p>regime</p><p>Patman et al.24 Cardiac surgery 236 Australia 63c 22% 1 physiotherapy session/</p><p>day</p><p>aAcute Physiology and Chronic Health Evaluation II (APACHE II).</p><p>bproportionally converted from APACHE III.</p><p>cMean.</p><p>dMedian.</p><p>Study or Subgroup</p><p>Santos et al. 2018 NMES+EX</p><p>Santos et al. 2018 EX</p><p>Maffei et al. 2017</p><p>Dong et al. 2014</p><p>Patman et al. 2001</p><p>Total (95% CI)</p><p>Heterogeneity: Tau² = 0.08; Chi² = 8.52, df = 4 (P = 0.07); I² = 53%</p><p>Test for overall effect: Z = 0.99 (P = 0.32)</p><p>Mean</p><p>11.4</p><p>10.3</p><p>12</p><p>12.7</p><p>1.8</p><p>SD</p><p>9.8</p><p>8.7</p><p>15.7</p><p>4.1</p><p>1.8</p><p>Total</p><p>12</p><p>13</p><p>20</p><p>30</p><p>101</p><p>176</p><p>Mean</p><p>14.2</p><p>14.2</p><p>14.3</p><p>15.2</p><p>1.5</p><p>SD</p><p>9.7</p><p>9.7</p><p>20</p><p>4.5</p><p>1.1</p><p>Total</p><p>15</p><p>15</p><p>20</p><p>30</p><p>109</p><p>189</p><p>Weight</p><p>14.0%</p><p>14.3%</p><p>17.9%</p><p>21.5%</p><p>32.3%</p><p>100.0%</p><p>IV, Random, 95% CI</p><p>-0.28 [-1.04, 0.48]</p><p>-0.41 [-1.16, 0.34]</p><p>-0.13 [-0.75, 0.50]</p><p>-0.57 [-1.09, -0.06]</p><p>0.20 [-0.07, 0.47]</p><p>-0.18 [-0.53, 0.18]</p><p>Year</p><p>2018</p><p>2018</p><p>2017</p><p>2014</p><p>2001</p><p>ecnereffiD naeM .dtSecnereffiD naeM .dtSlortnoCnoitnevretnI</p><p>IV, Random, 95% CI</p><p>-1 -0.5 0 0.5 1</p><p>Favours Intervention Favours Control</p><p>F IGURE 2 Forest plot for early</p><p>mobilisation effect on ICU length of</p><p>stay in the included studies</p><p>MONSEES ET AL. 503</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>However, of the ten included studies only Dong et al., Schaller</p><p>et al. and Schujmann et al.'s results were statistically</p><p>significant.13,26,27</p><p>All trials, aside from Patman et al. reported reductions of ICU</p><p>LOS.24 In Dong et al., Schaller et al. and Schujmann et al. these reduc-</p><p>tions were statistically significant.13,26,27</p><p>6 | SECONDARY OUTCOMES</p><p>6.1 | Mortality</p><p>All included studies reported mortality rates; however, endpoints for</p><p>reporting varied from ICU mortality to 180 day mortality. In Figure 3,</p><p>mortality has been meta-analysed according to the specific endpoints.</p><p>Overall during the meta-analysis, a Risk Ratio of 1.01 (95% CI 0.82–</p><p>1.26) was calculated, indicating that EM does not affect mortality</p><p>rates. I2 of 0% indicates that there is no variability due to heterogene-</p><p>ity. However, results were not statistically significant for the overall</p><p>calculation, nor various endpoints.</p><p>6.2 | Hospital LOS</p><p>Hospital LOS was reported by eight studies. Only Patman et al. and</p><p>Maffei et al. reported their data suitably for meta-analysis</p><p>(Figure S2).17,24 Results favoured intervention treatment but were not</p><p>statistically significant (p= 0.53). There was no heterogeneity (I2= 0%).</p><p>Study or Subgroup</p><p>8.1.1 ICU Mortality</p><p>Santos et al. 2018</p><p>Hodgson et al. 2016</p><p>Subtotal (95% CI)</p><p>Total events</p><p>Heterogeneity: Tau² = 0.00; Chi² = 0.17, df = 1 (P = 0.68); I² = 0%</p><p>Test for overall effect: Z = 0.26 (P = 0.80)</p><p>8.1.2 Hospital Mortality</p><p>Schaller et al. 2016</p><p>Morris et al. 2016</p><p>Hodgson et al. 2016</p><p>Dong et al. 2014</p><p>Schweickert et al. 2009</p><p>Subtotal (95% CI)</p><p>Total events</p><p>Heterogeneity: Tau² = 0.00; Chi² = 3.74, df = 4 (P = 0.44); I² = 0%</p><p>Test for overall effect: Z = 0.31 (P = 0.75)</p><p>8.1.3 90 day mortality</p><p>Schujmann et al. 2019</p><p>Schaller et al. 2016</p><p>Subtotal (95% CI)</p><p>Total events</p><p>Heterogeneity: Tau² = 0.11; Chi² = 1.76, df = 1 (P = 0.19); I² = 43%</p><p>Test for overall effect: Z = 0.08 (P = 0.93)</p><p>8.1.4 180 day mortality</p><p>Eggmann et al. 2018</p><p>Morris et al. 2016</p><p>Subtotal (95% CI)</p><p>Total events</p><p>Heterogeneity: Tau² = 0.00; Chi² = 0.00, df = 1 (P = 0.96); I² = 0%</p><p>Test for overall effect: Z = 0.03 (P = 0.97)</p><p>Total (95% CI)</p><p>Total events</p><p>Heterogeneity: Tau² = 0.00; Chi² = 5.82, df = 10 (P = 0.83); I² = 0%</p><p>Test for overall effect: Z = 0.12 (P = 0.90)</p><p>Test for subgroup differences: Chi² = 0.17, df = 3 (P = 0.98), I² = 0%</p><p>Events</p><p>7</p><p>2</p><p>9</p><p>17</p><p>18</p><p>2</p><p>2</p><p>9</p><p>48</p><p>7</p><p>21</p><p>28</p><p>16</p><p>33</p><p>49</p><p>134</p><p>Total</p><p>15</p><p>29</p><p>44</p><p>104</p><p>150</p><p>29</p><p>30</p><p>49</p><p>362</p><p>68</p><p>104</p><p>172</p><p>58</p><p>150</p><p>208</p><p>786</p><p>Events</p><p>8</p><p>1</p><p>9</p><p>8</p><p>18</p><p>1</p><p>3</p><p>14</p><p>44</p><p>11</p><p>15</p><p>26</p><p>16</p><p>33</p><p>49</p><p>128</p><p>Total</p><p>15</p><p>21</p><p>36</p><p>96</p><p>150</p><p>21</p><p>30</p><p>55</p><p>352</p><p>67</p><p>96</p><p>163</p><p>57</p><p>150</p><p>207</p><p>758</p><p>Weight</p><p>9.2%</p><p>0.9%</p><p>10.0%</p><p>7.5%</p><p>12.6%</p><p>0.9%</p><p>1.6%</p><p>8.6%</p><p>31.2%</p><p>6.0%</p><p>13.1%</p><p>19.1%</p><p>13.7%</p><p>26.1%</p><p>39.7%</p><p>100.0%</p><p>M-H, Random, 95% CI</p><p>0.88 [0.43, 1.80]</p><p>1.45 [0.14, 14.94]</p><p>0.91 [0.46, 1.82]</p><p>1.96 [0.89, 4.34]</p><p>1.00 [0.54, 1.85]</p><p>1.45 [0.14, 14.94]</p><p>0.67 [0.12, 3.71]</p><p>0.72 [0.34, 1.52]</p><p>1.06 [0.72, 1.57]</p><p>0.63 [0.26, 1.52]</p><p>1.29 [0.71, 2.36]</p><p>0.97 [0.49, 1.94]</p><p>0.98 [0.55, 1.77]</p><p>1.00 [0.65, 1.53]</p><p>0.99 [0.70, 1.40]</p><p>1.01 [0.82, 1.26]</p><p>Year</p><p>2018</p><p>2016</p><p>2016</p><p>2016</p><p>2016</p><p>2014</p><p>2009</p><p>2019</p><p>2016</p><p>2018</p><p>2016</p><p>oitaR ksiRoitaR ksiRlortnoCnoitnevretnI</p><p>M-H, Random, 95% CI</p><p>0.05 0.2 1 5 20</p><p>Favours Intervention Favours Control</p><p>F IGURE 3 Forest plot of the effect of early mobilisation on mortality in the included studies. Since the line of no effect is crossed there is no</p><p>significant difference in mortality rates</p><p>504 MONSEES ET AL.</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>Of the remaining six trials, Eggmann et al. and Schweickert et al.</p><p>reported an increase of 3.9 (p = 0.723) and 0.6 (p = 0.93) median days</p><p>on Hospital LOS. Morris et al. reported no difference in terms of Hos-</p><p>pital LOS (p = 0.41).4,20,28 The other three trials all reported reduced</p><p>Hospital LOS for intervention groups. Schujmann et al. reported a</p><p>reduction of 3 median days (p = 0.1), Hodgson et al. reported a reduc-</p><p>tion by 10 median days (p = 0.33) and Schaller et al. reported a reduc-</p><p>tion of 6.5 median days (p = 0.011) (Figure S3).11,26,27</p><p>Overall, only Morris et al. showed no difference in Hospital LOS;</p><p>Eggmann et al. and Schweickert et al. reported an increase, while five</p><p>trials reported a reduced Hospital LOS.4,11,17,20,24,26–28</p><p>6.3 | Duration of mechanical ventilation</p><p>Seven trials reported duration of MV, of which four were suitable for</p><p>inclusion into meta-analysis. Santos et al.'s data for the two different</p><p>EM groups were included separately.25</p><p>Results of the meta-analysis show a statistically significant</p><p>reduction of duration of MV in intervention groups (p = 0.0002).</p><p>However heterogeneity among studies was very high (I2 = 82%)</p><p>(Figure S4).</p><p>Of the three studies not suitable for inclusion into the meta-anal-</p><p>ysis, Eggmann et al. was the only one to report a negative effect of</p><p>0.4 median days (p = 0.83).4 In contrast Hodgson et al. reported a</p><p>reduction of 1.6 median days (p = 0.18) and Schweickert et al.</p><p>reported a statistically significant reduction of 2.7 median days</p><p>(p = 0.02) (Figure S5).11,28</p><p>Of the studies reporting mean results, Patman et al. reported no</p><p>difference (p = 0.85), Dong et al. reported a shortened duration of</p><p>MV by 1.7 mean days which was statistically significant (p = 0.005),</p><p>and Maffei et al. reported an improvement of 0.8 mean days</p><p>(p = 0.104).13,17,24 Santos et al. reported a shortening of 4.7 mean</p><p>days for their EX group and a shortening of 9.1 mean days when com-</p><p>pared to the control group; the latter result was statistically significant</p><p>(p = 0.007).25</p><p>Overall, of the seven trials reporting on duration of MV, Eggmann</p><p>et al. reported a longer duration of MV, Patman et al. reported no dif-</p><p>ference and the remaining five trials reported shorter duration of</p><p>MV.4,11,13,17,24,25,28 Results for duration of MV found Santos et al.</p><p>results for NMES+EX group, Dong et al. and Schweickert et al. to be</p><p>statistically significant.13,25,28</p><p>6.4 | Effect on functional independence</p><p>Of the included studies, two did not report on physical function</p><p>outcomes.24,25</p><p>Maffei et al. reported a trend for walking earlier (p ≥ 0.99), but did</p><p>not report on performance at discharge.17 Similarly, Dong et al.</p><p>reported that the intervention group was earlier to mobilise out of</p><p>bed (p = 0.0), but reported no other functional outcomes.13</p><p>The effect of EM on functional independence was reported dif-</p><p>ferently among the various studies. Schujmann et al. reported that</p><p>at 3 months, 97.5% of the intervention group were functionally</p><p>independent, while only 74.4% of the control group had achieved</p><p>functional independence.27 This result was statistically significant</p><p>(p = 0.003).</p><p>Eggmann et al. reported no functional benefits for the interven-</p><p>tion group, but a trend towards better mental health was noted.4 Mor-</p><p>ris et al. initially reported no difference in terms of physical</p><p>function.20 However, at 6 months follow up, they reported a statisti-</p><p>cally significant improvement in their Short Form (36) Health Survey</p><p>(SF-36) score (p = 0.023).</p><p>Hodgson et al. reported that mobility milestones were achieved</p><p>earlier by members of the intervention group, however, at 6 months</p><p>there was no difference in terms of physical function between</p><p>groups.11</p><p>Schaller et al. reported that 51% of the intervention group and</p><p>25% of the control group were functionally independent at hospital</p><p>discharge, the difference between groups was statistically significant</p><p>(p = 0.009).26 Furthermore, 61% of the intervention group were able</p><p>TABLE 2 Effect on functional independence outcomes in the</p><p>included studies</p><p>Effect on physical function</p><p>Schujmann</p><p>et al.27</p><p>No difference in handgrip strength. In EM group</p><p>better performance for sit to stand and 2-minand</p><p>^# walk test. Also more likely to be physically</p><p>independent. At 3 months 97.5% versus 74.4%</p><p>functionally independent (p = 0.003).</p><p>Eggmann</p><p>et al.4</p><p>No functional benefits found. SF-36 at 6 months no</p><p>difference Trend towards better mental health for</p><p>intervention group noted.</p><p>Santos</p><p>et al.25</p><p>Not reported.</p><p>Maffei</p><p>et al.17</p><p>In EM group trend for walking earlier, but no report</p><p>on how performance compared at discharge.</p><p>Hodgson</p><p>et al.11</p><p>Mobility milestones achieved earlier for intervention</p><p>group, however at 6 months there was no</p><p>difference in terms of physical function between</p><p>groups.</p><p>Morris</p><p>et al.20</p><p>No difference in physical function initially, but at</p><p>6 months SF-36 significantly better for EM group</p><p>(p = 0.001).</p><p>Schaller</p><p>et al.26</p><p>Significant 51% EM versus 25% non-EM functionally</p><p>independent at hospital discharge (p = 0.009).</p><p>61% EM versus 30% non-EM discharged home</p><p>(p = 0.0007). No significant difference of SF-36.</p><p>Dong et al.13 Earlier to get out of bed, but nil else reported.</p><p>Schweickert</p><p>et al.28</p><p>59% versus 35% returned to functional normal</p><p>status at hospital discharge (p = 0.02).</p><p>Patman</p><p>et al.24</p><p>Not reported.</p><p>MONSEES ET AL. 505</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>to be discharged home directly, compared with 30% in the control</p><p>group.26 This was also statistically significant (p = 0.0007).26</p><p>Schweickert et al. reported that 59% of the intervention group</p><p>and 35% of the control group returned to their normal functional sta-</p><p>tus at hospital discharge, the difference between groups was statisti-</p><p>cally significant (p = 0.02).28</p><p>Overall, of the six studies that reported on functional indepen-</p><p>dence, Eggmann et al.'s was the only one that did not show any</p><p>improvements.4 Hodgson et al. showed earlier achievement of</p><p>mobility milestones, but this had balanced out again at six</p><p>months.11</p><p>The remaining four studies all showed statistically significant</p><p>improvements in physical independence at their individual end-</p><p>points.20,26–28</p><p>See Table 2 for a summary of the effects of EM on functional</p><p>independence.</p><p>6.5 | Results of quality appraisal</p><p>Quality appraisal results are presented in Figure 4. Findings were vali-</p><p>dated by a second reviewer. All studies suffered from performance</p><p>bias, as personnel were unable to be blinded due to the nature of the</p><p>intervention.4,11,17,20,24–28 Three of the included studies suffered from</p><p>four sources of bias.13,17,24 Two studies suffered from three sources</p><p>of bias,20,27 while the remaining trials suffered from</p><p>two or one source</p><p>of bias.4,11,25,26,28</p><p>The other sources of Bias highlighted in the diagram are the sta-</p><p>tistically significant differences between baseline characteristics of</p><p>intervention and control groups.11,27 Overall, while the analysis did</p><p>reveal moderate bias, with blinding being the main issue, it was</p><p>decided to include all studies.</p><p>7 | DISCUSSION</p><p>This review focused on EM in the strictest sense of the definition by</p><p>only including trials that enrolled their patients within 4 days of ICU</p><p>admission or intubation and by also excluding passive exercise</p><p>regimes. Therefore, the results from this review differ from</p><p>previous SRs.</p><p>From data analysed, a trend emerged towards reductions in ICU</p><p>LOS, with only Patman et al. reporting an increase in ICU LOS.24</p><p>Unfortunately, not all studies could be included in the meta-analysis</p><p>due to abnormal distribution of the data.</p><p>EM did not appear to have an effect on mortality, as the results</p><p>of the meta-analysis were statistically non-significant. Reporting on</p><p>functional independence was diverse, yet a majority of studies also</p><p>showed improved outcomes for intervention groups. Similarly, there</p><p>was a trend towards a reduction in duration of MV.</p><p>The data was less clear around Hospital LOS, but there was a</p><p>trend towards improved outcomes. Interestingly, two studies reported</p><p>a reduction of ICU LOS, but an increase in Hospital LOS.20,25</p><p>The level of baseline PT varied among studies. Schweickert et al.</p><p>and Patman et al. were the only ones without baseline PT.24,28 All</p><p>other trials included some level of PT at baseline.4,11,13,17,20,25–27</p><p>It is noteworthy that Eggmann et al. was the only study that</p><p>reported several disadvantageous results for their intervention</p><p>groups.4 There are likely a number of reasons for this. Firstly, the</p><p>mean APACHE II score of their participants was 22, which is the</p><p>highest of any included trial. The disease severity of included</p><p>patients was therefore higher. The level of baseline physiotherapy</p><p>(PT) was also high with the control group receiving EM as part of</p><p>the standard care. In the intervention group, resistance training was</p><p>introduced as well as motor-assisted, or active in bed cycling. Over-</p><p>all, PT time increased from once a day, mostly on weekdays to up</p><p>to three times a day, seven days a week. It is therefore likely that</p><p>the high level of baseline PT combined with the level of disease</p><p>severity led to fewer positive results when compared to other</p><p>included studies.</p><p>R</p><p>an</p><p>do</p><p>m</p><p>se</p><p>qu</p><p>en</p><p>ce</p><p>g</p><p>en</p><p>er</p><p>at</p><p>io</p><p>n</p><p>(s</p><p>el</p><p>ec</p><p>tio</p><p>n</p><p>bi</p><p>as</p><p>)</p><p>A</p><p>llo</p><p>ca</p><p>tio</p><p>n</p><p>co</p><p>nc</p><p>ea</p><p>lm</p><p>en</p><p>t (</p><p>se</p><p>le</p><p>ct</p><p>io</p><p>n</p><p>bi</p><p>as</p><p>)</p><p>Bl</p><p>in</p><p>di</p><p>ng</p><p>o</p><p>f p</p><p>ar</p><p>tic</p><p>ip</p><p>an</p><p>ts</p><p>a</p><p>nd</p><p>p</p><p>er</p><p>so</p><p>nn</p><p>el</p><p>(p</p><p>er</p><p>fo</p><p>rm</p><p>an</p><p>ce</p><p>bi</p><p>as</p><p>)</p><p>Bl</p><p>in</p><p>di</p><p>ng</p><p>o</p><p>f o</p><p>ut</p><p>co</p><p>m</p><p>e</p><p>as</p><p>se</p><p>ss</p><p>m</p><p>en</p><p>t (</p><p>de</p><p>te</p><p>ct</p><p>io</p><p>n</p><p>bi</p><p>as</p><p>)</p><p>In</p><p>co</p><p>m</p><p>pl</p><p>et</p><p>e</p><p>ou</p><p>tc</p><p>om</p><p>e</p><p>da</p><p>ta</p><p>(a</p><p>ttr</p><p>iti</p><p>on</p><p>b</p><p>ia</p><p>s)</p><p>Se</p><p>le</p><p>ct</p><p>iv</p><p>e</p><p>re</p><p>po</p><p>rt</p><p>in</p><p>g</p><p>(r</p><p>ep</p><p>or</p><p>tin</p><p>g</p><p>bi</p><p>as</p><p>)</p><p>O</p><p>th</p><p>er</p><p>b</p><p>ia</p><p>s</p><p>Schujmann et al. 2019</p><p>Eggmann et al. 2018</p><p>Santos et al. 2018</p><p>Maffei et al. 2017</p><p>Morris et al. 2016</p><p>Hodgson et al. 2016</p><p>Schaller et al. 2016</p><p>Dong et al. 2014</p><p>Schweickert et al. 2009</p><p>Patman et al. 2001</p><p>Green indicates no bias, red indicates presence of bias, yellow represents</p><p>that the presence of bias is unclear.</p><p>Other bias in Hodgson and Schujmann: Sta�s�cally significant differences</p><p>between baseline characteris�cs of interven�on and control group.</p><p>F IGURE 4 Quality appraisal for included studies performed with</p><p>JBI critical appraisal checklist. Green indicates no bias, red indicates</p><p>presence of bias, yellow represents that the presence of bias is</p><p>unclear. Other bias in Hodgson and Schujmann: Statistically significant</p><p>differences between baseline characteristics of intervention and</p><p>control group.</p><p>506 MONSEES ET AL.</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>Similar to this review, Tipping et al. found no difference in mortal-</p><p>ity, yet unlike this SR Tipping et al. showed no difference in functional</p><p>outcomes.31 They were unable to analyse LOS and duration of MV</p><p>due to the skewed nature of their data.</p><p>Wang et al. were able to show significance for their mortality</p><p>data, but their meta-analysis on ICU LOS, hospital LOS and duration</p><p>of MV suffered from high heterogeneity.33</p><p>Unlike this review, Zhang et al. reported that EM had no impact</p><p>on duration of MV.34 Similar to the findings of this review, they also</p><p>reported that EM improved rates of functional independence.</p><p>Doiron et al. did not draw any conclusions due to the poor quality</p><p>of the four included studies.3</p><p>In the discussion of their trial, Schaller et al. proposed that disease</p><p>severity may have an impact on outcomes.26 To explore this, out-</p><p>comes were plotted against the APACHE score. The APACHE II score</p><p>was thereby utilized to assess disease severity. The APACHE score</p><p>was designed to predict mortality and disease severity on ICU</p><p>admission.15</p><p>Six studies reported APACHE II scores.4,11,13,25,26,28 Morris et al.</p><p>reported APACHE III scores. Their APACHE III score was converted pro-</p><p>portionally into an APACHE II score. APACHE scores were plotted in a</p><p>graph against difference in ICU and Hospital LOS, as well as the differ-</p><p>ence in duration of MV in median days. Two RCTs could not be included</p><p>in this plot as they did not report their patient outcomes in median</p><p>values.13,25 Schaller et al. and Schweickert et al. reported their APACHE</p><p>score as median scores.26,28 Their scores were converted tomean values</p><p>using the method of Wan et al.32 Therefore, five studies encompassing</p><p>769 patients were included in the graphs.4,11,20,26,28 See Figures S6, S7</p><p>and S8 for results.</p><p>The trend lines strongly indicate more favourable outcomes for</p><p>patients with lower disease severity for Hospital LOS, ICU LOS as well</p><p>as duration of MV.</p><p>Overall, there appears to be a trend towards improved response</p><p>to EM from patients with lower diseases severity, the analysis was</p><p>limited as only 5 studies enrolling 769 patients were included. In</p><p>addition, it is likely that other factors including age profile, admis-</p><p>sion diagnosis and EM protocols have an effect on patient</p><p>outcomes.</p><p>However, it will be worthwhile to conduct further analysis on</p><p>the impact of disease severity, once larger trials have been</p><p>released.</p><p>7.1 | Limitations</p><p>This SR was limited by research available for inclusion. Numbers in</p><p>the individual trials were small and therefore results were mostly sta-</p><p>tistically non-significant.</p><p>Quality appraisal identified numerous sources of bias, thereby</p><p>limiting the quality of the included data. Blinding of personnel and</p><p>patients is impossible due to the nature of interventions; therefore</p><p>performance bias cannot be excluded. However, further sources of</p><p>bias were present in most studies.</p><p>The description of interventions was extremely brief in one</p><p>study.24 The remaining nine RCTs provided a reasonable level of</p><p>detail regarding their interventions; however, only three studies</p><p>provided enough detail to allow for the application of their study</p><p>protocol, based on the information provided within their</p><p>articles.4,11,27</p><p>7.2 | Future direction and Implications for clinical</p><p>practice</p><p>At least one large, well-designed RCT is required to gain certainty of</p><p>the effectiveness of EM. However, enrolling sufficient numbers for</p><p>EM trials is difficult. Therefore, it may be several years until strong</p><p>evidence will be available.</p><p>In their extensive review on the safety of EM, Nydahl et al. con-</p><p>cluded that EM is safe.22 Furthermore, this SR indicates that EM has</p><p>no effect on mortality. Other findings include a trend towards shorter</p><p>ICU and Hospital LOS for patients undergoing</p><p>EM, as well as a reduc-</p><p>tion of ventilator time for intervention groups. Further research is</p><p>required to solidify findings; however, this review shows that no evi-</p><p>dence of harm is assocated with EM and therefore the application of</p><p>EM in ICU settings should not be delayed.</p><p>8 | CONCLUSION</p><p>This review has applied stricter time limits than previous SRs for the</p><p>commencement of EM protocols, as patients had to be enrolled within</p><p>four days of ICU admission or intubation. The emerging results give a</p><p>strong indication that the commencement of EM has a positive effect</p><p>on ICU LOS. In addition, there is a trend towards improved outcomes</p><p>for Hospital LOS, duration of MV, and increased functional indepen-</p><p>dence, than was the case with previous SRs. EM remains a safe inter-</p><p>vention and does not influence mortality rates. However, findings are</p><p>limited by small sample sizes and sources of bias. Further research and</p><p>large-scale trials are required to solidify findings. However, based on</p><p>the evidence of this SR, the application of EM should be widely con-</p><p>sidered in ICU settings, as ongoing RCTs will likely require years to</p><p>complete.</p><p>AUTHOR CONTRIBUTIONS</p><p>Jonas Monsees: Conceptualization (lead), Formal Analysis, Investiga-</p><p>tion (lead), Methodology (lead), Writing – Original Draft Preparation</p><p>(lead), Writing – Review & Editing (lead); Zena Moore: Methodology</p><p>(equal), Writing – Original Draft Preparation (equal); Declan Patton:</p><p>Methodology (equal), Writing – Original Draft Preparation (equal);</p><p>Chanel Watson: Methodology (equal), Writing – Original Draft Prepa-</p><p>ration (equal); Linda Nugent: Methodology (equal), Writing – Original</p><p>MONSEES ET AL. 507</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>Draft Preparation (equal); Pinar Avsar: Writing – Review & Editing</p><p>(equal); Tom O'Connor: Conceptualization (equal), Formal Analysis</p><p>(equal), Methodology (equal), Writing – Original Draft Preparation</p><p>(equal), Writing – Review & Editing (equal).</p><p>ACKNOWLEDGEMENTS</p><p>Jonas Monsees received a research grant from Tallaght University</p><p>Hospital. No further funding was awarded for this work. Open access</p><p>funding provided by IReL.</p><p>ORCID</p><p>Jonas Monsees https://orcid.org/0000-0003-1681-5792</p><p>Zena Moore https://orcid.org/0000-0002-4692-9718</p><p>Declan Patton https://orcid.org/0000-0003-1018-2605</p><p>Chanel Watson https://orcid.org/0000-0002-8548-1813</p><p>Linda Nugent https://orcid.org/0000-0001-7480-8545</p><p>Tom O'Connor https://orcid.org/0000-0001-5948-0975</p><p>REFERENCES</p><p>1. Clarissa C, Salisbury L, Rodgers S, Kean S. Early mobilisation in</p><p>mechanically ventilated patients: a systematic integrative review of</p><p>definitions and activities. J Intensive Care. 2019;7(1):3.</p><p>2. Ding N, Zhang Z, Zhang C, et al. What is the optimum time for initia-</p><p>tion of early mobilisation in mechanically ventilated patients? A net-</p><p>work meta-analysis. PLoS ONE. 2019;14(10):e0223151.</p><p>3. Doiron KA, Hoffmann TC, Beller EM. 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Tipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL.</p><p>The effects of active mobilisation and rehabilitation in ICU on mortal-</p><p>ity and function: a systematic review. Intensive Care Med. 2017;43(2):</p><p>171-183.</p><p>32. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and stan-</p><p>dard deviation from the sample size, median, range and/or inter-</p><p>quartile range. BMC Med Res Methodol. 2014;14(1):135.</p><p>508 MONSEES ET AL.</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>https://orcid.org/0000-0003-1681-5792</p><p>https://orcid.org/0000-0003-1681-5792</p><p>https://orcid.org/0000-0002-4692-9718</p><p>https://orcid.org/0000-0002-4692-9718</p><p>https://orcid.org/0000-0003-1018-2605</p><p>https://orcid.org/0000-0003-1018-2605</p><p>https://orcid.org/0000-0002-8548-1813</p><p>https://orcid.org/0000-0002-8548-1813</p><p>https://orcid.org/0000-0001-7480-8545</p><p>https://orcid.org/0000-0001-7480-8545</p><p>https://orcid.org/0000-0001-5948-0975</p><p>https://orcid.org/0000-0001-5948-0975</p><p>https://joannabriggs.org/sites/default/files/2020-08/Checklist_for_RCTs.pdf</p><p>https://joannabriggs.org/sites/default/files/2020-08/Checklist_for_RCTs.pdf</p><p>33. Wang J, Ren D, Liu Y, Wang Y, Zhang B, Xiao Q. Effects of early</p><p>mobilisation on the prognosis of critically ill patients: a systematic</p><p>review and meta-analysis. Int J Nurs Stud. 2020;1(110):103708.</p><p>34. Zhang L, Hu W, Cai Z, et al. Early mobilisation of critically ill patients</p><p>in the intensive care unit: a systematic review and meta-analysis. PLoS</p><p>ONE. 2019;14(10):e0223185.</p><p>SUPPORTING INFORMATION</p><p>Additional supporting information may be found in the online version</p><p>of the article at the publisher's website.</p><p>How to cite this article: Monsees J, Moore Z, Patton D, et al.</p><p>A systematic review of the effect of early mobilisation on</p><p>length of stay for adults in the intensive care unit. Nurs Crit</p><p>Care. 2023;28(4):499‐509. doi:10.1111/nicc.12785</p><p>MONSEES ET AL. 509</p><p>14785153, 2023, 4, D</p><p>ow</p><p>nloaded from</p><p>https://onlinelibrary.w</p><p>iley.com</p><p>/doi/10.1111/nicc.12785 by C</p><p>A</p><p>PE</p><p>S, W</p><p>iley O</p><p>nline L</p><p>ibrary on [06/07/2024]. See the T</p><p>erm</p><p>s and C</p><p>onditions (https://onlinelibrary.w</p><p>iley.com</p><p>/term</p><p>s-and-conditions) on W</p><p>iley O</p><p>nline L</p><p>ibrary for rules of use; O</p><p>A</p><p>articles are governed by the applicable C</p><p>reative C</p><p>om</p><p>m</p><p>ons L</p><p>icense</p><p>info:doi/10.1111/nicc.12785</p><p>A systematic review of the effect of early mobilisation on length of stay for adults in the intensive care unit</p><p>1 INTRODUCTION</p><p>What is known about the topic</p><p>What this paper adds</p><p>2 AIMS</p><p>3 METHODS</p><p>3.1 Criteria for inclusion and exclusion</p><p>3.2 Search strategy</p><p>3.3 Data collection and extraction</p><p>3.4 Quality appraisal</p><p>3.5 Data analysis</p><p>4 RESULTS</p><p>4.1 Search results</p><p>4.2 Study characteristics</p><p>4.3 Nature of interventions</p><p>5 PRIMARY OUTCOMES</p><p>5.1 ICU LOS</p><p>6 SECONDARY OUTCOMES</p><p>6.1 Mortality</p><p>6.2 Hospital LOS</p><p>6.3 Duration of mechanical ventilation</p><p>6.4 Effect on functional independence</p><p>6.5 Results of quality appraisal</p><p>7 DISCUSSION</p><p>7.1 Limitations</p><p>7.2 Future direction and Implications for clinical practice</p><p>8 CONCLUSION</p><p>AUTHOR CONTRIBUTIONS</p><p>ACKNOWLEDGEMENTS</p><p>REFERENCES</p>