Skip to main content
Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

What is the optimum time for initiation of early mobilization in mechanically ventilated patients? A network meta-analysis

  • Nannan Ding,

    Roles Conceptualization, Formal analysis, Software, Writing – original draft

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Zhigang Zhang ,

    Roles Conceptualization, Project administration, Supervision

    zzg3444@163.com (ZZ); 13893601236@163.com (CZ)

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Caiyun Zhang ,

    Roles Conceptualization, Project administration, Supervision

    zzg3444@163.com (ZZ); 13893601236@163.com (CZ)

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Department of Nursing, The First Hospital of Lanzhou University, Lanzhou, China

  • Li Yao,

    Roles Formal analysis, Software, Writing – review & editing

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Liping Yang,

    Roles Methodology, Writing – review & editing

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Biantong Jiang,

    Roles Data curation

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Yuchen Wu,

    Roles Data curation

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Lingjie Jiang,

    Roles Data curation

    Affiliations School of Nursing, Lanzhou University, Lanzhou, China, Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China

  • Jinhui Tian

    Roles Methodology, Software

    Affiliation Evidence-Based Medicine Center, Lanzhou University, Lanzhou, China

Abstract

Early mobilization has been proven to be an effective and safe intervention for preventing complications in mechanically ventilated patients; however, there is currently no unified definition of the optimal mobilization initiation time, hindering widespread clinical implementation. As clinicians are increasingly aware of the benefits of early mobilization, the definition of early mobilization is important. The purpose of this study was to evaluate the effects of different early mobilization initiation times on mechanically ventilated patients and rank these times for practical consideration. The Chinese Biomedical Literature Database, the Chinese Knowledge Infrastructure, Wanfang Data, PubMed, Cochrane Library, Web of Science, and Embase databases, along with grey literature and reference lists, were searched for randomized control trials (RCTs) that evaluated the effects of early mobilization for improving patient outcomes; databases were searched from inception to October 2018. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook (v5.1.0). Data were analyzed using Stata (v13.0) and Review Manager (v5.3.0). A total of 15 RCTs involving 1726 patients and seven mobilization initiation times (which were all compared to usual care) were included in our analysis. Network meta-analysis showed that mechanical ventilation for 48–72 h may be optimal to improve intensive care unit acquired weakness (ICU-AW) and reduce the duration of mechanical ventilation; however, there were no significant differences in length of ICU stay according to mobilization initiation time. The results of this study indicate that initiation of mobilization within 48–72 h of mechanical ventilation may be optimal for improving clinical outcomes for mechanically ventilated patients.

Introduction

Advances in medical technology and instrumentation in intensive care units (ICUs) have resulted in clear increases in patient survival rates; however, long-term immobility and bed rest can lead to physical dysfunction, such as ICU-acquired weakness (ICU-AW) and prolonged mechanical ventilation [12]. Further, complications of these conditions can persist for more than 5 years after hospital discharge, hindering the return of patients to normal social function [3].

Early mobilization can improve patient muscle strength, reduce the duration of mechanical ventilation, and improve patient quality of life, and is associated with low adverse event rates (<1%) [47]; however, to date, the time of early mobilization initiation has not been standardized. Harrold [8] conducted a systematic review of the time of early mobilization initiation in patients classified according to three criteria, which was ICU patients with or without mechanical ventilation or non-ICU patients. Clarissa et al. [9] conducted a systematic review of definitions of early mobilization for mechanically ventilated patients, which included 76 studies, and suggested that the time of initiation should be defined by mechanical ventilation duration, and demonstrated that an agreed standardized definition is a prerequisite to advance research into, and practice of early mobilization.

Initiation times range from ≤ 24 h after mechanical ventilation to ≥ 1 week after ICU admission. Morris et al. [10] produced the first report of early mobilization of ICU patients, with initiation within 48 h of mechanical ventilation. Further, one study [11] showed that mobilization started at ≥ 7 days after ICU admission cannot improve physical function or medical outcomes. The UK National Institute for Health and Clinical Excellence (NICE) recommends that mobilization should start as early as possible during an ICU stay [12]. At present, ICU medical staff are increasingly aware of the benefit of early mobilization for mechanically ventilated patients; however, when mobilization should be initiated remains unclear and controversial, which hinders the widespread implementation of this practice in the clinic. Therefore, exploration of the appropriate time to initiate mobilization is of great significance.

Traditional meta-analyses have demonstrated that early mobilization can improve physical function; however, there have been no studies regarding the effect of different initiation times or direct comparisons of different initiation times. Network meta-analysis (NMA) allows indirect comparisons of different interventions (without requiring direct comparisons), and selection of the optimal solution [13,14]. Therefore, this study aimed to evaluate the effects of different early mobilization initiation times in mechanically ventilated patients and to rank the different initiation times for practical application using an NMA approach. Our findings support the initiation of mobilization within 48–72 h of mechanical ventilation.

Materials and methods

This meta-analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) NMA Checklist [15] and the Cochrane Handbook for Systematic Reviews (v5.1.0) [16]. No ethics approval was required.

Inclusion/Exclusion criteria

The included population were aged > 18 years and had undergone mechanical ventilation. The intervention groups underwent early mobilization, initiated at various time points, as follows: within ≤ 24h, 24–48h, 48–72h, 72–96h, and > 96 h of mechanical ventilation, and > 5 and > 7 days after ICU admission. Control groups received usual nursing care. Outcomes included ICU-AW (according to Medical Research Council (MRC) diagnosis criteria [17]), duration of mechanical ventilation, and length of ICU stay. Studies were randomized control trials (RCTs) published in English and Chinese.

Exclusion criteria were as follows: (1) abstracts, letters, case reports, non-RCTs, expert opinions and reviews, and repeated literature; and (2) studies that did not specify the time of mobilization initiation or related outcomes.

Data sources and search strategies

The Chinese Biomedical Literature Database (CBM), Chinese Knowledge Infrastructure (CNKI), Chinese Wanfang Data, PubMed, Cochrane Library, Web of Science, and Embase databases were searched from inception to October 2018, along with grey literature and reference list searches. The search strategies were as follows: “early activit* OR accelerated ambulation* OR early action* OR early motion* OR early mobilisation* OR active* in early stage OR early-stage activit* OR early ambulant* OR early movement*” AND “artificial respiration OR mechanical ventilation” AND “randomized controlled trial* OR RCT*”. The search strategy are provided in Appendix 1–7.

Study selection

All studies retrieved were imported into literature management software (EndNote X8). To screen studies, two authors independently reviewed the titles and abstracts, and then reviewed the full-text of the included studies for quantitative analysis. A third reviewer resolved any discrepancies between the two authors. Also, two authors independently extracted the data, according to a predesigned form, which included study characteristics (first author, year, country, ICU type), patient characteristics (sample size, male/female, age, interventions, and controls), and outcomes (ICU-AW, duration of mechanical ventilation, and length of ICU stay).

Quality assessment

Two reviewers independently assessed the risk of bias using the Cochrane Handbook for Systematic Reviews (v5.1.0), which includes seven domains (random sequence generation, allocation concealment, participants/personnel blinding, outcome assessor blinding, incomplete outcome data, selective reporting, and other bias [16]).

Statistical analysis

NMA was performed using the mvmeta package in Stata (v13.0). Comparisons between different initiation times were represented using network plots, with the lines between dots representing direct comparisons and line thickness representing the quantity of comparisons between two interventions, i.e., the sample size involved in each comparison. Both comparisons of dichotomous variables and continuous variables are presented as mean with 95% confidence interval (95% CI); but dichotomous variables show the index number and continuous variables are logarithm. Ranking probabilities were estimated by determining the surface under the cumulative ranking (SUCRA) value, where higher SUCRA values indicate a higher probability of superior ranking. Funnel plots were constructed to represent publication bias, where symmetrical distribution indicates an absence of publication bias. The risks of bias of the included studies were analyzed using Review Manager (v5.3.0), where green, yellow, and red in the image represent low, unclear, and high risk of bias, respectively.

Literature search

A total of 808 studies were initially retrieved from electronic databases, including studies 625 in English and studies 183 in Chinese. There were 642 studies remaining after exclusion of duplicates using EndNote X8 and manual exclusion. There were 34 studies excluded by some reasons, for example, non-RCTs (n = 12), no mention the initiative time of mobilization (n = 11), no mention related outcomes (n = 8), incomplete data (n = 3). Finally, 15 studies were included in the analysis. The study flow diagram is shown in Fig 1.

Study and patient characteristics

A total of 15 studies were included, including seven published in Chinese and eight in English, with 1726 patients (868 and 858 in the intervention and control groups, respectively). There were seven initiation time categories (within ≤ 24h, 24–48h, 48–72h, 72–96h, and > 96 h of mechanical ventilation; and > 5 and > 7 days after ICU admission) along with usual care. All 15 studies provided data that allowed indirect comparisons of the initiation times, with no direct comparisons in any individual study. Basic study characteristics are presented in S1 Table

Results

Quality assessment

In Fig 2, green, yellow, and red represent low, unclear, and high risk of bias respectively. Eight studies [4,10,18,21,23,2729] were adequately randomized, five [4,10,18,27,29] reported allocation concealment, and four [4,10,19,22] reported blinding of outcome assessment. Four studies [4,10,20,27] did not report blinding of participants and personnel. All other risks of bias were low.

thumbnail
Fig 2.

Green: Low risk of bias; Yellow: Unclear risk of bias; Red: High risk of bias.

https://doi.org/10.1371/journal.pone.0223151.g002

Network plots of included studies

The control in all of the studies was usual care. ICU-AW data were included in six studies [4,19,23,2729]. Three of these studies [4,27,29] investigated mobilization within 48–72 h of mechanical ventilation and one study each investigated mobilization within ≤ 24h [28], 24–48h [19], and 72–96 h [23] of mechanical ventilation (Fig 3A). Data on the duration of mechanical ventilation were included for 13 studies [4,10,11,18,2022,2429]. Six of these studies [4,20,24,25,27,29] investigated mobilization within 48–72 h of mechanical ventilation, three studies [10,18,26] investigated mobilization within 24–48 h of mechanical ventilation, and one study each investigated mobilization within ≤ 24h [28] or > 96 h [11] of mechanical ventilation or > 5 [22] or > 7 days [21] after ICU admission (Fig 3B). Data on ICU length of stay were available for 13 studies [4,1011,1822,24,2629]. Four of these studies [4,20,24,29] investigated mobilization within 48–72 h of mechanical ventilation, four studies [10,1819,26] investigated mobilization within 24–48 h of mechanical ventilation, and one study each investigated mobilization within ≤ 24h [28] or > 96 h [11] of mechanical ventilation or > 5 [22] or > 7 days [21] after ICU admission (Fig 3C).

thumbnail
Fig 3. Network plot of included studies.

A: Network plot of ICU acquired weakness. B: Network plot of duration of mechanical ventilation. C: Network plot of ICU length of stay.

https://doi.org/10.1371/journal.pone.0223151.g003

Forest plots

NMA of data on the incidence of ICU-AW showed that there was a significant difference between mobilization within 72–96 h and 24–48 h of mechanical ventilation, with the former leading to a greater reduction in ICU-AW (Fig 4A). No significant differences were detected for the other comparisons. NMA of data on the duration of mechanical ventilation revealed significant differences between mobilization within ≤ 24 h, 48–72 h, > 96 h, and 24–48 h of mechanical ventilation, with shorter durations for patients mobilized at ≤ 24h, 48–72h, and > 96 h relative to 24–48 h. Further, there were significant differences between mobilization within ≤ 24 h or > 96 h of mechanical ventilation and > 5 days after ICU admission, with ≤ 24 h or > 96 h leading to shorter durations (Fig 4B). There were no significant differences in length of ICU stay among the seven initiation times (Fig 4C).

thumbnail
Fig 4. 95%CI: 95% Confidence Interval; (#): ICU admitted time.

https://doi.org/10.1371/journal.pone.0223151.g004

Ranking

Larger SUCRA values indicate that a specific early mobilization time is superior to another. The best initiation time for reducing ICU-AW after mechanical ventilation, was 72–96 h, followed by 48–72 h. To decrease the duration of mechanical ventilation, mobilization at 48–72 h, followed by ≤ 24 h, may be the best initiation times (S2 Table). Overall, based on the forest plots and SUCRA data, 48–72 h after mechanical ventilation may be the best time to initiate mobilization (Fig 5A and 5B; S2 Table).

thumbnail
Fig 5. SUCRA: Surface under the cumulative ranking; (#): ICU admitted time.

https://doi.org/10.1371/journal.pone.0223151.g005

Publication bias

A funnel plot was constructed to analyze the publication bias among the included studies. If the symmetrical distribution of studies around the red line indicates no publication bias or a small sample effect (Fig 6). However, there is one data point far away from other studies, which indicate there is publication bias or small sample effect of this study.

thumbnail
Fig 6.

A: mechanical ventilation ≤ 24h; B: mechanical ventilation with 24h-48h; C: mechanical ventilation with 48h-72h; D: mechanical ventilation > 96h; E: ICU admitted > 5days; F: ICU admitted > 7days; G: Usual care.

https://doi.org/10.1371/journal.pone.0223151.g006

Inconsistency between direct and indirect comparisons

There were no available loops formed by the study arms; therefore, loop-specific tests were not performed.

Discussion

The results of our NMA demonstrate that early mobilization, started within 72–96 h of mechanical ventilation, may be optimal for decreasing ICU-AW, while initiation within 48–72 h of mechanical ventilation may be superior for decreasing mechanical ventilation duration. Overall, based on our confidence interval and ranking results, we conclude that early mobilization initiated within 48–72 h of mechanical ventilation is likely optimal for improving the outcomes of mechanically ventilated patients. Of the 15 RCTs included in this study, five reported allocation concealment, four reported blinding of outcome assessment, and four studies did not report blinding of participants and personnel which showed that there were high risk bias of these four studies. The funnel plot of the studies was symmetrical, other than one study. Which may be of Hodgson et al [18], because of the small sample included; may be from Schaller et al [19], due to the patients included were surgical patients that wean from mechanical ventilation earlier; and it may because of Shao [26] which the study was from different country.

ICU-AW is defined as clinically detectable weakness, without possible cause other than critical illness in ICU patients [30]. ICU-AW is an independent predictor of prolonged mechanical ventilation [3132] and prevention of ICU-AW can reduce the duration of mechanical ventilation. Muscle strength drops by 3% to 11% for each additional day of immobility [33], and when it reaches a 40% reduction, the rate of patient mortality significantly increases. Further, rates of ICU-AW can be as high as 33–82% when mechanical ventilation continues for 4–7 days [3436].

The results of this NMA show that it may be optimal to mobilize patients within 48–72 h of mechanical ventilation. Another study [18] showed that earlier mobilization resulted in superior rehabilitation; however, the clinical implementation of early mobilization has been limited because of various factors, including respiratory and hemodynamic instability and patient safety concerns [3739]. Generally, the period within several hours of mechanical ventilation is the acute disease phase, where respiratory and hemodynamic parameters are unstable, meaning that the safety of patients cannot be guaranteed. Therefore, most clinicians choose to mobilize patients at a later time, which can prevent ICU-AW and reduce adverse events. Overall, mobilization initiation within 48–72 h of mechanical ventilation may be optimal.

Limitations of this study

This study had several limitations. First, despite a comprehensive search of Chinese and English databases, few RCTs met the inclusion criteria; therefore, the number of included studies was small, and the quality of the studies was not high, which may have influenced the results of our analyses. Second, some studies did not report blinding and allocation concealment, which may have led to exaggeration of clinical effects; meanwhile, the funnel plot analysis indicated publication bias or a small sample effect. Third, the designs of the included early mobilization studies were similar; however, the frequency, type, and intensity of early mobilization differed among them, which may have influenced the results of this study. Finally, the usual nursing practices applied for the control groups in the included studies may have differed, which could have introduced heterogeneity and influenced the results of this study.

Conclusion

We conclude that mobilization within 48–72 h of mechanical ventilation may be optimal for improvement of clinical outcomes. Based on our data, we suggest the following: 1) In clinical practice, clinical staff should choose an initiation time appropriate for their specific ICU; 2) In the future, researchers should conduct direct comparisons between different initiation times; for example, comparisons between mobilization within or after 48 h of mechanical ventilation, or at other times; 3) Research should be conducted to assess the long-term outcomes of different early mobilization initiation times; for example, investigation of mortality rates 1, 3, and 12 months after discharge.

Supporting information

S1 Table. Basic characteristics of included studies.

USA, United States of America; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; SICU, surgical intensive care unit; MICU, medical intensive care unit; A, < 24 h after mechanical ventilation; B, 24–48 h after mechanical ventilation; C, 48–72 h after mechanical ventilation; D, 72–96 h after mechanical ventilation; E, > 96 h after mechanical ventilation; F, > 5 days after ICU admission; G, > 7 days after ICU admission; H, usual care; MRC, Medical Research Council; 1, ICU acquired weakness; 2, duration of mechanical ventilation; 3, length of ICU stay.

https://doi.org/10.1371/journal.pone.0223151.s008

(DOCX)

S2 Table. SUCRA and Meanrank results.

SUCRA, surface under the cumulative ranking; ICU,Intensive care unit;—, not mentioned.

https://doi.org/10.1371/journal.pone.0223151.s009

(DOCX)

References

  1. 1. Castro-Avila AC, Serón P, Fan E, Gaete M, Mickan S. Effect of early rehabilitation during intensive care unit stay on functional status: systematic review and meta-analysis. PLoS ONE. 2015;10(7): e0130722. pmid:26132803.
  2. 2. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310(15): 1591. pmid:24108501.
  3. 3. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16): 1787. pmid:20978258.
  4. 4. Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet. 2009;373(9678): 1874–1882. pmid:19446324.
  5. 5. Yang LP, Zhang ZG, Zhang CY, Ma XJ, Tian JH, Zhang YH, et al. Effect of early mobilisation on the prevention of intensive care unit acquired weakness: A Meta-analysis. Nursing Journal of Chinese People's Liberation Army. 2018;35(05): 1–7.
  6. 6. Zhao GM, Jiao LL, Yang GH. The effects of early progressive exercise on ICU acquired weakness: a meta-analysis. Chinese Journal of Nursing. 2017;52(02): 177–181.
  7. 7. Bailey P, Thomsen GE, Spuhler VJ, Blair R, Jewkes J, Bezdjian L, et al. Early activity is feasible and safe in respiratory failure patients. Crit Care Med. 2007;35(1): 139–145. pmid:17133183.
  8. 8. Harrold ME. Early mobilisation of mechanically ventilated adults in intensive care: implementation of practice change and benchmarking of practice. Perth: Curtin University, 2013.
  9. 9. Clarissa C, Salisbury L, Rodgers S, Kean S. Early mobilisation in mechanically ventilated patients: a systematic review of definitions and activities. J Intensive Care. 2019;7: 3. pmid:30680218
  10. 10. Morris PE, Goad A, Thompson C, Taylor K, Harry B, Passmore L, et al. Early intensive care unit mobility therapy in the treatment of acute respiratory failure. Crit Care Med. 2008;36(8): 2238–2243. pmid:18596631.
  11. 11. Moss M, Nordon-Craft A, Malone D, Van Pelt D, Frankel SK, Warner ML, et al. A randomized trial of an intensive physical therapy program for acute respiratory failure patients. Am J Respir Crit Care Med. 2016;193(10): 1101. pmid:26651376.
  12. 12. Rehabilitation after critical illness in adults. National Institute for Health and Care Excellence (NICE). 2009. https://www.nice.org.uk/Guidance/CG832
  13. 13. Zeng XT, Cao SHY, Sun F, Tian GX. The sixth of meta analysis: Indirect comparison and network meta analysis. Chinese Journal of Evidence-Based Cardiovascular Medicine. 2012;4(05):309–402.
  14. 14. Rouse B, Chaimani A, Li T. Network meta-analysis: an introduction for clinicians[J]. Intern Emerg Med, 2017;12(1):103–111. pmid:27913917
  15. 15. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations. Ann Intern Med. 2015;162(11): 777–784. pmid:26030634.
  16. 16. Hu Y. Evidence-based nursing. Beijing: People's Medical Publishing House, 2012: 351.
  17. 17. Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS, et al. An official American Thoracic Society clinical practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med. 2014;190(12): 1437–1446. pmid:25496103
  18. 18. Hodgson CL, Bailey M, Bellomo R, Berney S, Buhr H, Denehy L, et al. A binational multicenter pilot feasibility randomized controlled trial of early goal-directed mobilization in the ICU. Crit Care Med. 2016;44(6): 1145–1152. pmid:26968024.
  19. 19. Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis , Heim M, et al. Early goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet. 2016;388(10052):1377–1388. pmid:27707496.
  20. 20. Dong ZH, Yu BX, Sun YB, Fang W, Li L. Effects of early rehabilitation therapy on patients with mechanical ventilation. World J Emerg Med. 2014;5(1): 48. pmid:25215147
  21. 21. Burtin C, Clerckx B, Robbeets C, Ferdinande P, Langer D, Troosters T, et al. Early exercise in critically ill patients enhances short-term functional recovery. Crit Care Med. 2009;37(9): 2499–2505. pmid:19623052.
  22. 22. Denehy L, Skinner EH, Edbrooke L, Haines K, Warrillow S, Hawthorne G, et al. Exercise rehabilitation for patients with critical illness: a randomized controlled trial with 12 months of follow-up. Crit Care. 2013;17(4): R156. pmid:23883525.
  23. 23. Zhang AM, ding AP, Lu YH. Effect of early mobilisation in preventing ICU acquired weakness in patients with COPD mechanical ventilation. Nursing Journal of Chinese People's Liberation Army. 2017;34(15): 44–46.
  24. 24. Yu P, Ren GQ, Lu XM, Yang ZY, Li YT. Application of early activity and rehabilitation program in ICU mechanical ventilation patients. J Nurs Train. 2016;31(02): 161–164.
  25. 25. Hu HJ, Wei HY, Xu J, Chen Q. Effect of early mobilisation on patients with ICU acquired weakness. Nurs Res. 2014,28(27): 3378–3379.
  26. 26. Shao X. The relationship between early activity and the incidence of delirium of patients with mechanical ventilation in ICU. Zunyi Medical University. 2015.
  27. 27. Ke H, Huang HY. Effect of four-stage early activity and rehabilitation exercise therapy on prevention of ICU acquired weakness. Nurs Res. 2016;30(18): 2202–2205.
  28. 28. Huang HY, Wang XF, Luo J, H L, Zhou XJ. Effect of early level 4 rehabilitation training for patients with mechanical ventilation in ICU. J Nurs Sci. 2016;31(15): 1–5.
  29. 29. Yu LN. Effect of early exercise in intensive care unit acquired weakness. Dalian Medical University, 2013.
  30. 30. Stevens RD, Marshall SA, Cornblath DR, Hoke A, Needham DM, De Jonghe B, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Crit Care Med. 2009;37(10Suppl): S299–S308. pmid:20046114.
  31. 31. De Jonghe B, Bastuji-Garin S, Sharshar T, Outin H, Brochard L. Does ICU-acquired paresis lengthen weaning from mechanical ventilation? Intensive Care Med. 2004;30(6): 1117–1121. pmid:14767593
  32. 32. Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness: a cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014;190(4): 410–420. pmid:24825371
  33. 33. Weinert CR, Calvin AD. Epidemiology of sedation and sedation adequacy for mechanically ventilated patients in a medical and surgical intensive care unit. Crit Care Med. 2007;35(2): 393–401. pmid:17205015.
  34. 34. Rodriguez PO, Setten M, Maskin LP, Bonelli I, Vidomlansky SR, Attie S, et al. Muscle weakness in septic patients requiring mechanical ventilation: Protective effect of transcutaneous neuromuscular electrical stimulation. J Crit Care. 2012;27(3): 319.e1-8. pmid:21715139.
  35. 35. Berek K, Margreiter J, Willeit J, Berek A, Schmutzhard E, Mutz NJ, et al. Polyneuropathies in critically ill patient: a prospective evaluation. Intensive Care Med. 1996;22(9): 849–855. pmid:8905416.
  36. 36. Leijten F S, De Weerd AW, Poortvliet DC, De Ridder VA, Ulrich C, Harink-De Weerd JE, et al. Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med. 1996;22(9): 856–861. pmid:8905417.
  37. 37. Castro E, Turcinovic M, Platz J, Law I. Early mobilization: Changing the mindset. Crit Care Nurse. 2015;35(4): e1–5. pmid:26232809.
  38. 38. Engel HJ, Needham DM, Morris PE, Gropper MA. ICU early mobilization: from recommendation to implementation at three medical centers. Crit Care Med. 2013;41(9 Suppl 1): 69–80. pmid:23989097.
  39. 39. Jolley SE, Regan-Baggs J, Dickson RP, Hough CL. Medical intensive care unit clinician attitudes and perceived barriers towards early mobilisation of critically ill patients: a cross-sectional survey study. BMC Anesthesiol. 2014: 14–84. pmid:25309124.