About 40 per cent of patients in intensive care units (ICU) develop ICU-acquired weakness—a musculoskeletal condition that results in generalised muscle weakness due to a combination of inflammation, protein catabolism, the effects of drugs given to ICU patients and prolonged bed rest. 

ICU-acquired weakness is linked to increased mortality, lengthy stays in hospital and a slow recovery.

In an effort to mitigate ICU-acquired weakness and speed the functional recovery of critically ill patients, mobilisation techniques are used by ICU physiotherapists. 

Current evidence suggests that early active mobilisation of patients at risk for ICU-acquired weakness might help. 

However, despite eight different published guidelines for early mobilisation of ICU patients, there is no clear indication what dose of early mobilisation is appropriate and when to start it.

Professor Carol Hodgson FACP, Specialist Cardiorespiratory Physiotherapist (as awarded by the Australian College of Physiotherapists in 2009), Head of the Division of Clinical Trials and Cohort Studies in the School of Public Health and Preventive Medicine and Deputy Director of the Australian and New Zealand Intensive Care Research Centre at Monash University, recently published the results (here) of a large international study examining early active mobilisation in critically patients at risk of ICU-acquired weakness: the Trial of Early Activity and Mobilisation (TEAM).

The study showed that a higher dose of early active mobilisation of critically ill patients resulted in more serious adverse events than the usual level of mobilisation provided to these patients and did not improve the number of days that patients were alive and out of the hospital or functional recovery.

Recently, the Australian Clinical Trials Alliance awarded the TEAM trial the 2023 Australian Clinical Trials Alliance Trial of the Year Award at the International Clinical Trials Symposium. 

The Australian Clinical Trials Alliance’s deputy chair noted that ‘the trial results directly and significantly affected patients’ outcomes and the financial burden on the healthcare system, and that its findings had the potential to be replicated in healthcare settings across the world.’

‘This is a significant win for physiotherapy and for multidisciplinary interventions. 

'We were up against some huge medical trials—other intensive care trials, international multicentre trials—including some orthopaedic and cardiothoracic trials,’ Carol says.

She explains that the TEAM trial was the first phase 3 trial of early active mobilisation in critically ill patients.

Previous studies were all on a much smaller scale. The trial included 750 ICU patients in 49 hospitals across Australia, New Zealand, the United Kingdom, Ireland, Germany and Brazil.

All patients were receiving mechanical ventilation in ICU at the time they were enrolled in the study. 

Patients were selected on the basis that they were expected to recover from their illness and were excluded from the trial if they had injuries that would impede recovery, such as a spinal cord or head injury.

‘We were trying to pick people who had been functionally independent prior to their critical illness and were expected to get back to that level of functional independence—that is, their prognosis was good despite their current illness,’ Carol says.

Eligible patients were randomised to receive either the usual level of mobilisation provided at that particular trial site or the intervention, which was a higher dose of mobilisation (commenced earlier and for a longer duration).

The patients in the intervention cohort were given daily physiotherapy individually tailored to achieve the highest possible level of mobilisation considered to be safe, delivered over one or more sessions during the day.

Using the ICU Mobility Scale, which had previously been developed by Carol and her team, each patient in the intervention group was assessed daily and their exercise program was adjusted accordingly.

‘If they could move their arms and legs against gravity, then we would immediately try to sit them over the edge of the bed or even stand them if they were able to do that,’ says Carol. 

‘If they could sit over the edge of the bed, we planned to give them 30 minutes of exercise. 

'And if they could stand, we tried to give them 45 minutes of exercise during the day.’ 

Because it’s very rare for a critically ill patient to be able to do 45 minutes of exercise in a row, the programs were often broken up into two or three shorter sessions over the day.

‘We moved them to the highest level possible but we really only had to achieve that once in the day and the rest of the time they could do exercises in the chair or bed. 

'The intervention in the TEAM trial had to be active exercise, so the patients had to be able to participate in exercises throughout to be recorded,’ says Carol.

The primary outcome for the trial was the number of days the patient was alive and out of hospital at day 180 after joining the trial.

‘We picked that outcome measure in part because our pilot study had shown a difference but also because it was patient-centred. 

'When patients are in ICU, they say they just want to go home.

'We felt that days alive and out of hospital, which is actually days alive and at home, was a very patient-centred outcome measure because that’s what patients want,’ Carol says.

Secondary outcomes included the number of deaths prior to 180 days, ventilator-free and ICU-free days, quality of life, functional outcomes and other clinical measures as well as adverse events.

The results of the trial, which took almost five years to complete, were a surprise to the research team.

‘When we finished the trial, we found that there was absolutely no difference in the primary outcome, which was days alive and out of hospital. 

'There was also no difference in most of our secondary outcomes, including functional outcomes at six months.

'So this higher dose of rehabilitation did not improve functional recovery in critically ill patients. 

'If anything, the point estimate actually favoured usual care,’ says Carol.

In fact, the only outcome measure that showed a difference between the two cohorts was the number of adverse events, which occurred at over double the rate in the intervention group versus the usual care group.

‘These adverse events were mostly cardiac arrhythmias and oxygen desaturations that were reversible when the intervention was stopped. They weren’t life-threatening,’ Carol says.

A key reason that the trial may not have shown a difference between active early mobilisation and usual care, she says, is that over the course of the five years it took to do the trial, 

ICUs started incorporating more early mobilisation into the usual care offered by physiotherapists. 

When the trial was initially planned, usual care typically did not include mobilisation out of bed and included very little active exercise.

‘What we found is that physios have increased the dose of rehabilitation in the past few years, and this new level of usual care is best. Adding additional rehabilitation on top of that appears to be harmful,’ she says.

Carol says it’s unfortunate that when the trial results were published, the messaging was skewed to suggest that rehabilitation of critically ill patients was bad, when in fact the study showed that physiotherapists are on the right track.

‘It is definitely not that “rest is best”, it’s that a high dose of rehabilitation is potentially harmful and we need to be really specific about the dose of rehab we’re delivering. 

'If you picture a U-shaped curve, one end is no rehabilitation and we know that’s bad for critically ill patients.

'And down the other end is very high dose rehabilitation and we know that’s bad too. 

'In the middle is the sweet spot around usual care,’ she explains.

Carol says her team plans to do more studies to determine when to start active mobilisation of patients in ICU and the optimal amount of rehabilitation for these patients.

An important consideration in delivering complex rehabilitation in the ICU is the financial burden of something like the early active intervention in the trial, which takes a lot of time and staff.

‘If, for every patient who was eligible for the Team trial, we doubled the amount of time spent delivering rehabilitation, the cost of that is actually over a hundred million dollars per annum in Australia,’ Carol says.

Continuing with usual care instead of increasing the amount of rehabilitation provided to ICU patients means that both money and time is saved, allowing physiotherapists to see more patients in a day, and providing more effective care.

‘We’re delivering a safer and improved service to patients, who are going to benefit more in terms of the dose we deliver, and we’re saving money because we’re not wasting extra time doing a longer duration of treatment.’ Carol says.

Right now, though, Carol and her team are focusing on extracting as much data from the trial results as they can. 

More papers are planned, including one that analyses the adverse events in depth to show what may have triggered them. A platform trial to compare different dosages of rehabilitation is also in the works.