By Betty Tran, MD, MSc
Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago
SYNOPSIS: Among adults requiring invasive mechanical ventilation, the TEAM study reported that increased early mobilization resulted in no significant difference in the number of days that patients were alive and out of the hospital at 180 days after randomization.
SOURCE: The TEAM Study Investigators and the ANZICS Clinical Trials Group; Hodgson CL, Bailey M, Bellomo R, et al. Early active mobilization during mechanical ventilation in the ICU. N Engl J Med 2022;387:1747-1758.
The Treatment of Mechanically Ventilated Adults with Early Activity and Mobilization (TEAM) study was an international, multicenter, randomized controlled trial aimed to evaluate the effects of an early mobilization program in adults requiring mechanical ventilation beyond the calendar day after randomization. The trial excluded patients who were dependent in any activity of daily living the month prior to hospitalization, had rest-in-bed orders, and had suspected/proven brain or spinal cord injury. The primary outcome was the number of days patients were alive and out of the hospital at day 180. Secondary outcomes were considered exploratory and included the number of ventilator-free days and days out of the intensive care unit (ICU) at day 28 and patient-reported quality of life and physical, cognitive, and psychological function at day 180. The intervention was an early mobilization program, which involved minimization of sedation as required and daily physiotherapy in one or more sessions tailored to achieve the highest possible level of mobilization for as long as possible before stepping down to lower levels if the patient became fatigued as measured on the ICU Mobility Scale. The usual care group received a level of mobilization normally provided in each participating ICU. Patients received the intervention while they were in the ICU up to 28 days. Pre-specified serious adverse events were recorded and included falls to the floor, cardiac arrest, atrial fibrillation with ventricular response of > 150 bpm, other dangerous arrhythmias, oxygen desaturation < 80% for > 3 minutes, and unplanned extubation or removal of an intravascular line requiring urgent replacement.
Overall, 372 patients were randomized to the early mobilization group and 378 were randomized to the usual care group. Mean (± standard deviation) daily duration of mobilization per patient was 20.8 ± 14.6 minutes in the early mobilization group and 8.8 ± 9.0 minutes in the usual care group. The primary outcome was not significantly different between the early mobilization vs. usual care groups (143 days vs. 145 days; absolute difference -2 days; 95% confidence interval [CI], -10 to 6; P = 0.62). All secondary outcomes also were similar between the groups. There were more adverse events reported in the early mobilization group (9.2%) compared to the usual care group (4.1%) (P = 0.005), with arrhythmias, altered blood pressure, and oxygen desaturation being the most common. Overall, seven serious adverse events requiring medical intervention occurred in the early mobilization group (including five arrhythmias, a desaturation episode, and a cerebrovascular event) compared to one serious event in the usual care group (desaturation episode).
COMMENTARY
The incidence of ICU-acquired weakness is approximately 40% in the adult intensive care population.1 Beyond atrophy related to disuse, multiple pathophysiologic mechanisms contribute to the combination of myopathy and neuropathy observed. It has been a focus of interventional trials given its high incidence and association with poor ICU outcomes, including prolonged mechanical ventilation, hospital stay, and even increased mortality.2 The Pain, Agitation-Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS) guidelines recommend rehabilitation/mobilization in critically ill adults as an intervention for ICU-acquired weakness and as a part of delirium management strategies.3
In light of this recommendation and our partiality to the axiom that “more is better,” the primary finding in the TEAM study that an early, rigorous, active mobilization regimen did not result in an increased number of days that ICU survivors were alive and out of the hospital at day 180 after randomization was, perhaps, unanticipated. Furthermore, not only was there no difference in the primary outcome, the intervention was associated with an increased number of adverse events.
How are we to interpret these findings given the pressing need to find a therapeutic strategy to address ICU-acquired weakness? There are a few points to consider. First, although there was a significant difference between the mean daily duration of active mobilization per patient between both groups (12 minutes/day), the usual care group had a similarly high number of days per patient in which a physiotherapist assessment was performed and still achieved substantial levels of mobilization based on the ICU mobility scale. Therefore, lack of a significant difference in the primary outcome may be due in part to a still highly effective “usual care” comparison group in the trial, which may not be reflective of other hospital settings.
Second, the study’s primary outcome may not be the best metric to evaluate the benefits of an early mobilization program. The accompanying editorial suggests that larger sample sizes may be needed to detect a meaningful difference, and this would certainly hold true for the secondary outcomes as well.4 In addition, the benefits of an early mobilization program may be related to other outcomes not explored, such as the rate of ICU delirium.
Finally, the approach and timing of the mobilization intervention studied here may be off. It is possible that aiming for the highest level of mobilization for the longest duration of time up front when patients are more vulnerable leads to more adverse events rather than benefit, and a more protracted, but consistent, approach to physical rehabilitation beyond the ICU ultimately may result in better outcomes.
This field remains ripe for research to determine not only the best intensity and timing of a mobilization/rehabilitation program, but also the most informative metric by which to gauge benefit for patients with ICU-acquired weakness.
REFERENCES
- Appleton RT, Kinsella J, Quasim T. The incidence of intensive care unit-acquired weakness syndromes: A systematic review. J Intensive Care Soc 2015;16:126-136.
- Fan E, Cheek F, Chlan L, 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;190:1437-1446.
- Devlin JW, Skrobik Y, Gelinas 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;46:e825-e873.
- Moss M. Early mobilization of critical care patients—still more to learn. N Engl J Med 2022;387:1807-1808.
