Early Active Mobilization during Mechanical
Ventilation in the ICU

@chodgsonANZICRC @TEAMtrialICU. NEJM 2022; 387:1747-58 doi:10.1056/NEJMoa2209083

Clinical Question

  • In mechanically ventilated adult patients does the provision of early mobilisation when compared to standard care increase the number of days alive and out of hospital at 180 days?


  • ICU Acquired weakness (ICUAW) is common with one systematic review reporting a median prevalence of 43%, and is associated with increased morbidity and mortality
  • The pathophysiology of ICUAW is multifactorial, however there is some evidence that suggests a benefit to early mobilisation
  • Early mobilisation has been shown to improve short term outcomes (incidence of ICUAW and improved MRC score)
  • Another meta-analysis showed that it might improve days alive and out of hospital to 180 days
  • The PADIS guidelines suggest performing early rehabilitation and mobilisation in critically ill adults (low quality evidence, conditional recommendation)
  • However, early mobilisation is not without risk and most trials have been small, and often single centre


  • Multi-centre, prospective, parallel group trial
  • Randomisation 1:1 ratio
    • Web based interface
    • Stratified by trial centre with variable block sizes
  • Intervention lasted for 28 days
  • Provision of physiotherapy unblinded but those involved in patient reported outcomes and statistical analysis were blinded
  • Patients who died by day 180 defined as having 0 days alive and out of the hospital
  • Sample size calculation:
    • Based on pilot study data
    • 750 patients would provide 90% power to detect a 7-day between group difference with a two-sided alpha of 0.05
    • Sample size increased by 15% for non-parametric distribution and 5% loss to follow up
  • Analysis of primary outcome performed as intention to treat


  • 49 sites in 6 countries
  • February 2018 to November 2021


  • Inclusion:
    • > 18 years old
    • Intubated and expected to remain so the day following randomisation
    • Sufficient cardiorespiratory stability to make mobilisation possible
      • Parameters for what was defined as stable is provided in the supplementary appendix
      • Some of these criteria include ventricular rate < 150 bpm, combined noradrenaline / adrenaline rate < 0.2mcg/kg/min, FiO2 < 0.6, PEEP < 16 cm H20, RR < 45 bpm
  • Exclusion:
    • Dependent on ADL prior to ICU admission
    • Cognitive impairment
    • Proven or suspected acute primary brain or spinal cord / neuromuscular pathology likely to result in permanent or prolonged weakness
    • Rest in bed orders / bilateral non-weight bearing orders
    • Life expectancy < 180 days
    • ICU re-admission
    • > 72 hours from meeting inclusion criteria
  • 750 randomised
    • Early mobilisation = 372
    • Usual Care = 378
  • Comparing baseline characteristics of early mobilisation vs. usual care group:
    • Age: 61 vs 60
    • Female Sex: 35 vs 40%
    • Clinical Frailty Scale (CFS): 3 vs 3
      • CFS > 5: 11 vs 12%
    • BMI: 30 vs 30
    • Time from ICU admission to randomisation: 60 vs 61 hours
    • Unplanned ICU admission: 82 vs 84%
    • Sepsis: 66 vs 66%
    • Median RASS at randomisation: -3 vs -3
    • CAM-ICU positive: 4 vs 4%
    • PEEP: 9 vs 9 cm H20
    • P/F Ratio: 226 vs 230
    • Vasopressors: 62 vs 62%
    • RRT: 22 vs 21%
    • Corticosteroids: 46 vs 45%


  • Early mobilisation
    • Sedation minimised to determine IMS level which was used to individually tailor the physiotherapy session for the day (both activity and target duration)
      • IMS of 0 = no mobilisation, 10 = independent walking
    • The goal was the “highest level of activity possible for the longest time”
    • If fatigued, then mobilisation stepped down to lower levels
    • Mobilisation allowed to be split into different sessions
    • Each day was tailored based on strength assessment each day


  • Usual Care
    • If feasible delivered by physiotherapy staff not involved in delivering the intervention

Management common to both groups

  • All other care as per treating teams


  • Primary outcome:
    • Days alive and out of hospital at day 180 (median) – not significant
      • 143 vs 145 (Difference -2, 95% CI -10 to 6), p = 0.62
  • Subgroups:
    • No benefit in any subgroup (Age, CFS, APACHE II, Trauma, COVID-19, Sepsis) except country in which Brazil strongly favoured early mobilisation (however they only randomised 10 patients)
  • Secondary outcomes:
  • Comparing early mobilisation vs. usual care group
    • No significant difference in
      • Death at day 180: 22.5% vs 19.5%
      • Median ventilator free days at day 28: 21 vs 21
      • Median ICU free days at day 28: 16 vs 17
      • Functional outcome scores at day 180 (EQ-5D-5L, Barthel Index of ADL, WHODAS 2.0)
    • Significantly greater in early mobilisation group
      • Patients with ≥1 adverse event potentially due to mobilization: 9.2% vs 4.1%
        • OR 2.55 (95% CI 1.33 – 4.89), p = 0.005
        • Most common were cardiac arrythmia, altered BP, and desaturation

Authors’ Conclusions

  • Increased early active mobilisation did not affect the number of days that patients were alive and out of the hospital as compared with the usual level of mobilisation received in the ICU


  • Randomised, multi-centre trial
  • International increases external validity
  • Small numbers of protocol violations (Figure S4)
  • Minimal loss to follow up – primary outcome data available for 99.6% of patients
  • Achieved separation of physiotherapy delivered and levels of mobilisation achieved between groups
    • Early group received 21 compared to 9 minutes of active mobilisation per day
  • Excellent assessment and record of serious adverse events


  • Unblinded
  • Approximately 10% of those assessed were excluded or did not undergo randomisation for “other reasons”
  • There were significant numbers in the early group who did not undergo mobilisation (predominantly due to sedation) – these numbers decreased with time (Figure S4)
    • The frequency of which barriers to mobilisation occurred appears to be ~300 on day 1, ~250 on day 2, ~220 on day 3
  • Usual care group had an increased level of mobilisation that was higher than expected based on the pilot study (Table 2)
    • 41% of usual care group achieved IMS 7, compared to 47% in early group; with median peak IMS the same in both groups (6)
    • This might be a Hawthorne effect, but probably more likely that centres that agreed to participate in this study had well resourced, highly motivated and proactive physiotherapy departments
  • Post ICU care not protocolised

The Bottom Line

  • This study shows that when early mobilisation is compared to usual care there was no increase in days alive and out of hospital with greater number of adverse events in the early group
  • However, the usual care group appears to have also received a high frequency of early mobilisation so this trial does not mean that early physiotherapy input for critically ill patients should be limited and should remain to be an individualised decision based on patient stability, presence of barriers to mobilisation and resource availability

External Links


Summary author: George Walker @hgmwalker89
Summary date: 6th December 2022
Peer-review editor: David Slessor

Picture by: Pexels from Pixabay


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