Intensive versus standard physical rehabilitation therapy in the critically ill (EPICC): a multicentre, parallel-group, randomised controlled trial

Wright. 2017. Thorax 2017: 0:1–9. doi:10.1136/thoraxjnl-2016-209858

Clinical Question

  • Does an increased intensity of ICU based physical rehabilitation therapy improve improve long-term physical quality of life compared with a standard intensity of physical rehabilitation?


  • Physical and psychological recovery after a period of critical illness is slow and often incomplete
  • Current evidence informs us that patients report ongoing physical and psychological problems, and a decreased quality of life, for up to 5 years after their original illness
  • Whilst the aetiology of critical illness neuromyopathy is multifactorial, limiting the period of immobility and promoting movement and exercise are intuitively attractive strategies to prevent muscle weakness and enhance recovery


  • Randomised controlled trial
  • Patients were randomised to increased intensity or standard physiotherapy in a 1:1 ratio, stratified by admitting ICU, admission type and level of independence (Katz Index)
  • Allocation-concealed
  • Participants, research physiotherapists and the wider clinical team were not blinded to the treatment group
  • Participants were followed until hospital discharge and invited to attend a follow-up at their hospital 3 and 6months after randomisation. Follow-up questionnaires could be completed by telephone if participants were unable to attend in person
  • A sample size calculation based on a difference of five points in the primary outcome (mean Physical Component Summary (PCS) measure of the 36 item Short Form Survey (SF-36)), 80% power and a significance level of 0.05 required 77 patients to contribute primary outcome data at 6 months. Allowing for a mortality rate of 40% and a further 10% loss to follow-up required 154 in each group. At 6 months 116 patients (of 308 randomised) contributed primary outcome data (99 had died, 16 had withdrawn and 77 were lost to follow up)


  • 4 mixed medical-surgical ICUs in 4 UK hospitals
  • Jan 2012 – Dec 2014


  • Inclusion: 18 years or older and had received 48 hours or more of either invasive or non-invasive ventilation
  • Exclusion: End-of-life care; acute brain or spinal cord injury (or admitted following brain or spinal cord surgery); multiple trauma if mobilisation therapy was judged unlikely to be possible; burns; rapidly progressive neuromuscular disease; patients enrolled in another clinical trial without a co-enrolment agreement in place; and patients previously enrolled in this trial. Patients could be recruited following a cardiac arrest if the clinical team believed there was a possibility of recovery
  • 308 patients
  • Similar baseline characteristics in both study groups although the proportion of males in the intensive group (54%) was lower than in the standard group (63%). Most patients were emergency admissions with similar illness severity scores (mean APACHE II was 19) and high pre-hospital independence
    • Mean duration of ICU ventilation (days) was 4 in both groups
    • Almost all patients received invasive ventilation (>98%)
    • ICU length of stay was similar: mean 5-6 days


  • Intensive physical rehabilitation
  • Target delivery of 90 min of physical rehabilitation per day (Monday to Friday), split between at least two sessions


  • Standard care physical rehabilitation
  • Target of 30 min of physical rehabilitation per day (Monday to Friday)

Management common to both groups

  • All physical rehabilitation sessions were preceded by a sedation hold (or titration) with a target Richmond Agitation-Sedation Scale (RASS) of −1, 0 or +1
    • Patients were considered safe enough to undertake a sedation hold (or titration) in 88% (n= 4079) of the intensive group and 85% (n=2141) of the standard care group
    • 51% of the intensive group vs 53% of standard care group had a successful sedation hold (or titration) and passed the safety screen
  • The physical rehabilitation therapy included functional training and individually tailored exercise programmes and was delivered by experienced critical care physiotherapists
  • Following discharge from ICU, both groups received routine ward-based physiotherapy and an exercise diary to continue independently on discharge from hospital
  • Any participant readmitted to ICU received standard physical rehabilitation during their first and any subsequent readmissions


  • Primary outcome: Mean Physical Component Summary (PCS) measure of the 36 item Short Form Survey (SF-36) Quality of Life questionnaire at 6 months was similar in both groups
    • 37 (SD 12.2) in the intervention group vs 37 (SD 11.3) in the standard care group
  • Secondary outcome: all similar between groups (intervention vs standard care) across all follow-up time points apart from the Functional Independence Measure at 3 months
    • Mean Mental Health Component Summary (MCS) measure of the SF-36
      • 40 vs 39 at hospital discharge
      • 47 vs 45 at 3 months
      • 47 vs 48 at 6 months
    • Mean physical ability at ICU discharge (Modified Rivermead Mobility Index)
      • 19 vs 16 at ICU discharge
    • Median length of ICU stay (alive at ICU discharge)
      • 13 vs 15 days
    • Median hospital length of stay (alive at hospital discharge)
      • 28 vs 28 days
    • Exercise capacity based on median metres for 6 min walk test
      • 195 vs 173 at hospital discharge
      • 293 vs 255 at 3 months
      • 374 vs 321 at 6 months
    • Mean Functional status (Functional Independence Measure)
      • 70 vs 64 at ICU discharge
      • 113 vs 108 at hospital discharge
      • 116 vs 111 at 3 months
      • 118 vs 117 at 6 months
    • Mean hand grip strength
      • 14 vs 15 at ICU discharge
      • 19 vs 22 at hospital discharge
      • 25 vs 24 at 3 months
      • 29 vs 24 at 6 months
  • Other
    • Median (IQR) no of days from enrolment to the first day when physical rehabilitation was received was 3 (1-6 days) in both groups
    • Median time (IQR) receiving physical rehabilitation on ICU: intervention group 161 minutes (67-273) vs standard care group 86 (31-139)

Authors’ Conclusions

  • In this study, ICU based physical rehabilitation did not appear to improve physical outcomes at 6 months compared with standard physical rehabilitation


  • Registered with ISRCTN (20436833)
  • Protocol published a priori
  • Pretrial power calculation
  • Large range of general critical care patients included
  • Multi-centre study (although limited to 3 centres in the north of England)
  • Delivery of rehabilitation in the control group
  • Prolonged follow up of 6 months
  • Study outcomes at hospital discharge and at 3 and 6-month follow-up were assessed by research nurses who were blinded to the treatment group
  • Timings for characteristics of physical rehabilitation (functional retraining, strengthening and both) were recorded


  • Number of sites
  • Lack of 7-day rehabilitation interventions
  • Study outcomes at ICU discharge were assessed by the research physiotherapists who were unblinded to the treatment group
  • The original (and registered) version of the protocol listed 48–72 hours for the inclusion time but the upper limit was removed 2 months into recruitment as the time window proved too narrow and eligible patients were being missed, especially at weekends
  • The majority of treatment days in the standard care group included less than the target of 30 min physical rehabilitation, with 82% of treatment days including 20 min or less
  • The PCS measure of the SF-36 may not have been sensitive to change as it includes scoring coefficients from all 8 domains of the SF-36, including the negative scoring coefficients ‘role emotional’ and ’emotional well-being’, which may not have been affected by the intervention
  • 77 patients (25% of total participants) were lost to follow up
  • Over 2 years from follow up data being available to publication. Practice may have changed during this period

The Bottom Line

  • In this study, delivering more ICU-based physical rehabilitation did not appear to improve physical outcomes at 6 months
  • Patient tolerance, a non 7-day ICU rehabilitation service, poor compliance with the minimum time for sessions in the standard care group, and high loss of patients to follow up, are important confounders
  • Future work might concentrate on individualised, structured rehabilitation programme and optimising sedation protocols to facilitate these sessions. We also need a better understanding of the varying recovery trajectories after critical illness and the impact of psychological rehabilitation

External Links


Summary author: Steve Mathieu
Summary date: 15th August 2017
Peer-review editor: Adrian Wong

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