Early Mobilization During Mechanical Ventilation: Pain With No Gain

Early active mobilization has been shown to mitigate ICU-acquired weakness, reduce disability and, most importantly, reduce mortality. This Concise Critical Appraisal describes a recent article published in the New England Journal of Medicine from the Treatment of Invasively Ventilated Adults With Early Activity and Mobilisation (TEAM) Study Investigators and the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group on mobilization during mechanical ventilation that reevaluates the effects of sedation minimization and daily physiotherapy on serious adverse events and mortality at 180 days.¹
 
ICU-acquired weakness, or critical illness myopathy, occurs in approximately 25% to 50% of ICU patients and is associated with increased mortality, prolonged length of stay, and impaired recovery.^2-4 Previous data suggested that bedrest is an important risk factor for ICU-acquired muscle weakness and that early mobilization in the ICU can improve physical functioning, muscle strength, and quality of life while reducing delirium, length of stay, and mortality. Eleven randomized controlled trials (RCTs) have shown a 1.31-day reduction in mechanical ventilation days with early mobilization.⁵ The pain, agitation/sedation, delirium, immobility, and sleep disruption (PADIS) guidelines recommend mobilization, but do not offer guidance on how to mobilize patients.⁵ Early mobilization is often limited by numerous barriers including staff shortages, time constraints, sedation, agitation, physiologic instability, lack of training, and lack of resources.
 
The incidence of serious adverse events in 9 RCTs and 10 observation studies was very low.⁶ A serious adverse event is defined as a change in physiologic status or injury that requires intervention. Reported adverse events included increased oxygen requirement, unplanned extubation, falling, Achilles tendon rupture, polyarthralgia exacerbation, hypertensive urgency, and syncope. The PADIS guidelines do not preclude patients on vasoactive agents or mechanical ventilations from early rehabilitation and mobilization unless the patient was hemodynamically unstable or hypoxic.
 
The TEAM Study Investigators and the ANZICS Clinical Trials Group should be commended for their prospective, international, multicenter RCT evaluation of adult ICU patients. Eligible patients were older than 18 years, receiving mechanical ventilation, free of any suspected brain or spinal injuries, and independent in activities of daily living. Patients were separated into subgroups based on age, illness severity, diagnosis, disability level, and frailty before randomization.
 
Upon consent, 741 patients (372 in the early mobilization group and 378 in the usual care group) from 49 hospitals in 6 countries were randomized to early mobilization (sedation minimization and daily physiotherapy) by senior physiotherapists for up to 28 days versus usual ICU care to evaluate the effect on mortality, mechanical ventilation days, ICU length of stay, and discharge at 180 days. Process-of-care measures, including tracheostomy, neuromuscular blockades, glucocorticoids, renal replacement therapy, and vasopressor use were similar between the two groups.
 
Median daily duration of mobilization was 8.8 ± 9 minutes in the early care group versus 20.8 ± 14.6 minutes in the early mobilization group. Median number of days in which patients were alive and discharged was 143 days in the early mobilization group versus 145 days in the usual care group (P = 0.62). In both groups, 77% of patients were able to stand at 3 and 5 days. In the usual care group, 71 (19.5%) patients died by 180 days versus 83 (22.5%) patients in the early mobilization group. There was no significant difference in ventilator-free days or ICU-free days at 28 days, quality of life, activities of daily living, disability, cognitive function, or physiologic function.
 
There were 7 serious adverse events (5 arrhythmias, 1 desaturation, and 1 cerebrovascular accident) requiring medical intervention in the early mobilization group versus 1 serious adverse event (desaturation) in the usual care group. Adverse events potentially due to mobilization (arrhythmias, altered blood pressure, desaturation) were reported in 34 (9.2%) patients in the early mobilization group versus 15 (4.1%) patients in the usual care group. The authors concluded that early mobilization in mechanically ventilated patients does not reduce hospital or ICU length of stay, mechanical ventilation days, mortality, quality of life, or cognitive or physical function. Instead, early intervention is associated with increased adverse events.
 
This study is consistent with prior reports conducted in the past 6 years that also showed no differences among survivors with respect to physical function and length of stay. This study presents another barrier to early mobilization of ICU patients, especially mechanically ventilated patients. A limitation of this study is the vague and variable level of physiotherapy comprising usual care. While the variation in mobilization intensity and duration used in other studies makes it difficult to draw accurate comparisons, the present study overcomes some of the methodologic shortcomings by employing smaller sample sizes, monocentric designs, and historical controls. Mobilizing critically ill patients requires clinical stability, clinician training, proper resources, and time. This trial suggests increased risks without meaningful benefits of early mobilization in mechanically ventilated patients. Further studies are needed to reassess this risk-versus-benefit ratio.
 

References

1. TEAM Study Investigators and the ANZICS Clinical Trials Group, Hodgson CL, Bailey M, et al. Early active mobilization during mechanical ventilation in the ICU. N Engl J Med. 2022 Nov 10;387(19):1747-1758.
2. Appleton RT, Kinsella J, Quasim T. The incidence of intensive care unit-acquired weakness syndromes: a systematic review. J Intensive Care Soc. 2015 May;16(2):126-136.
3. Denehy L, Lanphere J, Needham DM. Ten reasons why ICU patients should be mobilized early. Intensive Care Med. 2017 Jan;43(1):86-90.
4. Fan E, Dowdy DW, Colantuoni E, et al. Physical complications in acute lung injury survivors: a two-year longitudinal prospective study. Crit Care Med. 2014 Apr;42(4):849-859.
5. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873.
6. Nydahl P, Sricharoenchai T, Chandra S, et al. Safety of patient mobilization and rehabilitation in the intensive care unit. Systematic review with meta-analysis. Ann Am Thorac Soc. 2017 May;14(5):766-777.