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Getting patients moving as much as possible while on mechanical ventilation in the intensive care unit (ICU) didn't improve their chances of survival or getting home sooner, the TEAM trial showed.

An early strategy of sedation minimization and daily physiotherapy didn't improve number of days alive and out of the hospital at 180 days after randomization compared with usual care (143 vs 145 days, 95% CI for difference -10 to 6, P=0.62).

Nor were there "softer" benefits in quality of life, disability, or cognitive or psychological function, reported Carol L. Hodgson, PhD, of the Australian and New Zealand Intensive Care Research Centre in Melbourne, and colleagues.

Their findings were published in the in conjunction with presentation at the of the European Society of Intensive Care Medicine in Paris.

However, an accompanying by Marc Moss, MD, of the University of Colorado School of Medicine in Aurora, cautioned against over-interpreting the findings.

"The TEAM trial was designed to test different 'doses' of early mobilization and should not lead to the conclusion that early mobilization is ineffective in general," he wrote.

Also, the usual care group got an unusually good level of early mobilization, he noted.

A physiotherapist assessed patients on 81% of ICU days as compared with 94% for the intervention group. By comparison, a 2016 mobilization trial showed a median of only 1 day of therapy in the entire hospitalization for usual care, and a 2017 survey of dozens of ICUs indicated mobilization on 32% of ICU days.

"Therefore, the lack of separation in treatment exposure between the two groups may have contributed to the negative results," Moss wrote.

Another concern was that the hard endpoint used to measure success in the trial might have been "too rigorous" and would require larger sample sizes to detect meaningful differences, he added.

"The next stage of early-mobilization research in critically ill patients should focus on identifying which patients receive the most benefit from early mobilization, implementing the appropriate comparison group, examining outcomes that are attainable and inform clinical practice, and determining the appropriate type, timing, intensity, coordination, and duration of therapy," he urged.

ICU-acquired weakness affects some 40% of patients, due to rapid muscle wasting and other mechanisms, and is associated with an increased risk of death, prolonged hospitalization, and impaired recovery, the researchers noted. Prior studies on early mobilization have had mixed results, such that recommended mobilization without commenting on when to start or what regimen to use.

The TEAM trial included 750 adults on invasive mechanical ventilation in the ICU at 49 hospitals in six countries, a population that Moss noted would be fairly generalizable to patients in other high-income countries.

Patients were randomly assigned to mobilization by the ICU's usual approach or to receive early mobilization aiming for the highest level of mobilization deemed safe for the patient for as long as possible before stepping down in intensity according to patient fatigue. They averaged 20.8 minutes of active mobilization per day in the intervention group and 8.8 minutes with usual care. Sedation, agitation, and physiological instability were reported as the biggest barriers to more mobilization in the intervention group.

For the secondary endpoint, 180-day mortality was similar between the intervention and usual care groups (22.5% vs 19.5%, OR 1.15, 95% CI 0.81-1.65). Ventilator-free and ICU-free days came out similar as well, as did use of tracheostomy, neuromuscular blockers, glucocorticoids, new renal-replacement therapy, re-intubation, and vasopressor-free days. No subgroups stood out for outcome impact.

Early mobilization did lead to more adverse events potentially due to the intervention (9.2% vs 4.1%), particularly cardiac arrhythmia and oxygen desaturation, but Moss noted that the frequency of these events was as expected from prior studies and the researchers pointed out that surveillance bias could have been at play because assignment was unblinded. While there were seven serious adverse events in the intervention group (five arrhythmias, a desaturation episode, and a cerebrovascular accident) and one case of desaturation with usual care, there were no falls, cardiac arrest, unplanned extubation, or intravascular line removal resulting in urgent replacement.

The findings contrasted with those of a meta-analysis suggesting that early, active mobilization in the ICU significantly increased days alive and out of the hospital.

"However, in this meta-analysis, both the intensity and duration of mobilization in the control groups varied greatly, a factor that made it difficult to draw comparisons across the trials," Hodgson and colleagues wrote. "Our trial avoided some of the methodologic shortcomings of studies that were included in this meta-analysis, such as small sample sizes, single-center designs, and use of historical controls."

But the findings were in line with those of three more recent randomized controlled trials, which showed no advantage to intensive physiotherapy for physical function and no shorter hospital stay with standardized rehabilitation therapy in the ICU.

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