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Muscle atrophy commences early, within hours of commencement of invasive mechanical ventilation [1]. Therefore, patients who receive prolonged mechanical ventilation are at high risk of muscle atrophy, severe weakness, long-term disability, and increased mortality [2,3,4]. To mitigate these risks, early mobilisation has been recommended in at least seven international guidelines [5]. It is a management strategy that has had widespread support from clinicians.
Early mobilisation will purportedly reduce duration of mechanical ventilation and delirium and improve functional recovery, although the evidence from individual trials has been inconsistent [6,7,8,9]. The evidence for the international guidelines has been pooled from pilot studies, phase II trials, observational studies, and expert consensus.
Clinical practice guidelines universally recommend implementation of early mobilisation activities in the intensive care unit (ICU) [5]. Each of the guidelines has made recommendations for operationalising early mobilisation differently, reflecting the heterogeneity across included studies. Almost all of the guidelines highlight the importance of considerations of the ABCDE (awakening, breathing, coordination, delirium monitoring and management, and early mobility) bundle of care [10]. As clinicians implement mobilisation, consideration for a patient’s level of sedation and delirium is crucial, as the main barrier reported to early mobilisation is sedation [6]. Other important factors for implementation include clinician expertise and the availability of specific mobilisation equipment. Daily evaluation of a patient’s physiological status for the suitability of mobility activities and a-priori considerations for terminating a mobility session should be discussed [5, 11]. However, clinical practice guidelines should be considered according to the comprehensiveness and recency of the systematic review informing the guidelines, given the recent increase in primary research evaluating early mobilisation.
Early mobilisation is defined by an exercise intervention based on a reproducible and physiological approach. The aim is to deliver early mobilisation as soon as it is safe to do so, when patients are physiologically stable [11]. There are several difficulties with interpreting the evidence for early mobilisation:
(1) There is no clear definition of “early”. Some randomised-controlled trials have defined early mobilisation as mobilisation that commenced within 2 days of invasive mechanical ventilation, whilst others have defined it as within 5 days of admission to ICU or any time in ICU (Table 1). In the largest randomised controlled trial (RCT) to date of early mobilisation published in 2022 (N = 750), the mean duration of time from ICU admission to randomisation was 2.5 days and assessment for early active mobilisation occurred on the day of randomisation in 86% of the intervention group [6]. This study did not measure or include passive mobilisation which may have started earlier. However, in the recent study published by Patel and colleagues in 2023 (N = 200), early mobilisation (passive or active) occurred within 1.1 days [7]
(2) The definition and dose of “mobilisation” may be different amongst trials, for example, starting with passive exercies versus active exercises, varied use of equipment such as cycle ergometers, tilt tables or electrical muscle stimulation, or any combinations of exercise and equipment. Evidence synthesis suggests that functional exercises, such as standing, sitting, and walking, may be the most effective [5, 12].
(3) There may be a heterogeneity of treatment effect with early mobilisation where some patients respond better than others.
International clinical practice is varied. Pragmatic trials that have used “usual care” as the comparator to the intervention group may differ between trials (Table 1). Usual care comprises over half of control groups in ICU rehabilitation trials, with varied terminology, such as usual care, standard care, conventional care, and routine care. For clinicians considering the applicability of trial results in their clinical context, it is crucial to carefully review the description of both the intervention and the control groups of the study, and compare it to their own practice (Table 1). It is clear that some trials have included a usual care arm that includes minimal mobilisation in ICU, whilst other trials have included a usual care arm that includes a substantial amount of mobilisation consistent with standard practice in their ICU.
Similar to other trials of early mobilisation, the recent phase III trial (the TEAM trial) randomised 750 critically ill patients from 49 hospitals across six countries and has questioned the safety of early mobilisation compared to standard care [6]. In this trial, participants were a mixed cohort, of whom 66% had sepsis, mean body mass index was 30, 62% received vasopressors, and 22% received renal replacement therapy. Adverse events were 2.5 times more likely to occur in the intervention group compared to usual care and were more likely to reoccur in the same patients. These resolved with cessation of the early mobilisation session. Following this trial, a systematic review of the effects of early mobilisation on 6-month functional recovery was completed [13]. It included a Bayesian analysis of the data using vague priors, and reported 75% probability that early mobilisation was associated with an increase in days alive and out of hospital at 6 months, and 95% probability that it was associated with improved physical function at 6 months. However, it was also associated with 66% chance of increased adverse events and 72% chance of increased mortality at 6 months.
Overall, usual care groups have been poorly reported in the ICU rehabilitation literature. Of the studies that have reported the activities included in usual care, the content varies considerably. Activities may include passive (no patient participation, e.g., passive range of motion), active-assisted (some participation, e.g., active-assisted range of motion), or active participation. In the TEAM trial, the usual care group reported active or active-assisted mobilisation (i.e., sitting at the edge of bed or higher) for a mean duration of 9 min per day for approximately 5 days per week, as compared to 21 min, for approximately 7 days a week, in the intervention group. Similar mobility milestones were achieved in the usual care group compared to the intervention group, but not as quickly (i.e., 1–2 days later for major mobility milestones in the usual care group) in 89% of patients, including during invasive mechanical ventilation [11]. On the other hand, the study by Patel and colleagues reported an improvement in cognitive function with early mobilisation compared to standard care. Standard care in this trial included only 6/99 (6%) patients who were mobilised during mechanical ventilation.
Whilst we do not have all of the answers about the type, timing, or dose of early mobilisation to optimise patient outcomes, the implementation of early mobilisation needs to be considered on an individual basis, using the best evidence applied to a clinicians’ own setting, optimising safety and functional recovery whilst minimising risks. Future trials of early mobilisation should provide an individualised approach, and evaluate cumulative exposure to mobilisation using novel trial designs.
Data availability
Data included in this manuscript was available from published manuscripts. Authors should be contacted directly for further information.
References
Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Padhke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE (2013) Acute skeletal muscle wasting in critical illness. JAMA 310:1591–1600
Kress JP, Hall JB (2014) ICU-acquired weakness and recovery from critical illness. NEJM 371:287–288
Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM (2011) Functional disability 5 years after acute respiratory distress syndrome. NEJM 364:1293–1304
Higgins AM, Neto AS, Bailey M, Barrett J, Bellomo R, Cooper DJ, Gabbe BJ, Linke N, Myles PS, Paton M, Philpot S, Shulman M, Young M, Hodgson CL, Investigators PS (2021) Predictors of death and new disability after critical illness: a multicentre prospective cohort study. Intensive Care Med 47:772–781
Lang JK, Paykel MS, Haines KJ, Hodgson CL (2020) Clinical practice guidelines for early mobilization in the ICU: a systematic review. Critical Care Med 48:e1121–e1128
TEAM Study Investigators and the ANZICS Clinical Trials Group (2022) early active mobilization during mechanical ventilation in the ICU. NEJM 387:1747–1758
Patel B, Wolfe KS, Patel S, Dugan K, Esbrook CL, Pawlik AJ, Stulberg M, Kemple C, Teele M, Zeleny E, Hedeker D, Pohlman A, Hall J, Kress JP (2023) Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial. Lancet Resp Med. https://doi.org/10.1016/S2213-2600(22)00489-1
Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis I, Heim M, Houle T, Kurth T, Latronico N, Lee J, Meyer MJ, Peponis T, Talmor D, Velmahos GC, Waak K, Walz JM, Zafonte R, Eikermann M (2016) Early, goal-directed mobilisation in the surgical intensive care unit: a RCT. Lancet 388:1377–1388
Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L, Miller M, Franczyk M, Deprizio D, Schmidt GA, Bowman A, Barr R, McCallister KE, Hall JB, Kress JP (2009) Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 373:1874–1882
Ely EW (2017) The ABCDEF bundle: science and philosophy of how ICU liberation serves patients and families. Crit Care Med 45:321–330
Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE, Bradley S, Berney S, Caruana LR, Elliott D, Green M, Haines K, Higgins AM, Kaukonen KM, Leditschke I, Nickels MR, Paratz J, Patman S, Skinner EH, Young PJ, Zanni JM, Denehy L, Webb SA (2014) Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care 18:658
Waldauf P, Jiroutkova K, Krajcova A, Puthucheary Z, Duska F (2020) Effects of rehabilitation interventions on clinical outcomes in critically ill patients: systematic review and meta-analysis of randomized controlled trials. Crit Care Med 48:1055–1065
Paton M, Chan S, Tipping CJ, Stratton A, Serpa Neto A, Lane R, Young P, Romero L, Broadley T, Hodgson CL (2023) The effect of mobilization at 6 months after critical illness meta-analysis. NEJM Evidence. 2(2):EVIDoa2200234. https://doi.org/10.1056/EVIDoa2200234
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CH was supported by an NHMRC Investigator grant and was the lead investigator on the TEAM trial published in the NEJM in 2022 and referenced in this manuscript. MK is supported by a Canada Research Chair in Critical Care Rehabilitation and Knowledge Translation. She is leading a randomised control trial of in-bed cycle ergometry with critically ill patients, and received a loan of 3 RT300 supine ergometers from Restorative Therapies (Baltimore, MD) for her research.
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Hodgson, C.L., Kho, M.E. & da Silva, V.M. To mobilise or not to mobilise: is that the right question?. Intensive Care Med 49, 1000–1004 (2023). https://doi.org/10.1007/s00134-023-07088-7
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DOI: https://doi.org/10.1007/s00134-023-07088-7