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• The EPICC trial, is it possible to perform intensive rehabilitation in the current framework of intensive care?
  Anthony Fung, Ann-Marie Evans, Alice E. Myers and Theophilus L. Samuels
  Published on: 15 May 2018
• What does the EPICC trial really tell us?
  Stefan J Schaller, Peter Nydahl, Manfred Blobner, Nicola Latronico and Carol Hodgson
  Published on: 21 March 2018
• Intensive or longer?
  Rodrigo Santos Queiroz, Micheli Bernardone Saquetto, Bruno Prata Martinez and Mansueto Gomes Neto
  Published on: 9 October 2017

• Published on: 15 May 2018

  The EPICC trial, is it possible to perform intensive rehabilitation in the current framework of intensive care?

  • Anthony Fung, Core Medical Trainee Surrey and Sussex Healthcare NHS trust
  • Other Contributors:
    • Ann-Marie Evans, Physiotherapist
    • Alice E. Myers, Consultant in Anaesthesia and Intensive Care Medicine
    • Theophilus L. Samuels, Consultant in Anaesthesia and Intensive Care Medicine

  The EPICC trial addresses the rarely investigated topic of rehabilitation in the critical care setting [1]. We note with interest that no improvement was found in outcomes in the rehabilitation group compared to the standard treatment group. Some of the reasons are clearly highlighted by Schaller et al. in their response to the paper including the time to starting intervention, therapy times and also sample size. Only 41% of the participants in the intervention group and 35% of the standard treatment group contributed data throughout the study period. In addition to this, only 8% of the intervention group managed over half the target therapy time and the EPICC trial showed that ‘an extra 10 minutes of physical therapy per day does not make a difference [2]’
  This study triggered an audit within our own 16 bedded mixed surgical and medical intensive care department assessing the number of sessions carried out over a 2 week period compared to those attempted. We investigated the actual duration of sessions achieved as compared to a target of 45 minutes rehabilitation each day during the working week (Monday-Friday). On average, 23.3 (standard deviation 20.19 minutes) minutes of rehabilitation per day was achieved and only 35% of attempted physical therapy sessions were completed. These figures are similar to those cited within the EPICC trial and highlight some of the difficulties of achieving longer therapy times within a busy intensive care department. Some of the fac...

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  The EPICC trial addresses the rarely investigated topic of rehabilitation in the critical care setting [1]. We note with interest that no improvement was found in outcomes in the rehabilitation group compared to the standard treatment group. Some of the reasons are clearly highlighted by Schaller et al. in their response to the paper including the time to starting intervention, therapy times and also sample size. Only 41% of the participants in the intervention group and 35% of the standard treatment group contributed data throughout the study period. In addition to this, only 8% of the intervention group managed over half the target therapy time and the EPICC trial showed that ‘an extra 10 minutes of physical therapy per day does not make a difference [2]’
  This study triggered an audit within our own 16 bedded mixed surgical and medical intensive care department assessing the number of sessions carried out over a 2 week period compared to those attempted. We investigated the actual duration of sessions achieved as compared to a target of 45 minutes rehabilitation each day during the working week (Monday-Friday). On average, 23.3 (standard deviation 20.19 minutes) minutes of rehabilitation per day was achieved and only 35% of attempted physical therapy sessions were completed. These figures are similar to those cited within the EPICC trial and highlight some of the difficulties of achieving longer therapy times within a busy intensive care department. Some of the factors cited by our physiotherapists include patient fatigue, limitations on staff availability and also clinical appropriateness of the patients for rehabilitation. Of interest, Schaller et al. have also suggested some solutions to the problems encountered in our own audit and also within the EPICC trial. We agree that the combined effort of the multi-disciplinary team is extremely important in order to maximise opportunities for rehabilitation sessions but also the ability to then consider multiple short sessions each day.
  In summary, we applaud the attempts of Wright and colleagues for addressing this under-investigated area of rehabilitation. We have reservations about some of the conclusions of the paper due to limited differences between intervention and treatment and underpowering of the study. Our own unpublished data supports the finding that to consistently achieve 90 minutes of therapy per patient as stipulated for the intervention group in this study would be very difficult in the current framework but this is an area to improve with some solutions already suggested.

  References:
  1. Wright SE, Thomas K, Watson G, et al. Intensive versus standard physical rehabilitation therapy in the critically ill (EPICC): a multicentre, parallel-group, randomised controlled trial. Thorax 2017:thoraxjnl-2016-209858
  2. Schaller SJ, Nydahl P, Blobner M, et al. What does the EPICC trial really tell us? Thorax 2018

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  Conflict of Interest:
  None declared.

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• Published on: 21 March 2018

  What does the EPICC trial really tell us?

  • Stefan J Schaller, Anesthesiologist Intensivist Klinikum rechts der Isar der TUM, Munich, Germany
  • Other Contributors:
    • Peter Nydahl, Research Nurse
    • Manfred Blobner, Professor of Anesthesiology
    • Nicola Latronico, Professor of Anesthesia and Critical Care Medicine
    • Carol Hodgson, Associate Professor and Deputy Director, ANZIC-RC

  We have read with great interest the multi-centred EPICC trial that randomized over 300 patients [1]. While the delivery of a complex physical rehabilitation intervention in clinical trials is difficult, we believe that several aspects of the trial may have resulted in the inability to detect a difference between the control and intervention groups. These factors include the delayed time to start the intervention, inadequate delivery of the intervention and the large loss to follow-up for the primary outcome measure. In our opinion, these three factors limit the interpretation of the results of the study. While the authors have mentioned some of these concerns in their discussion, and Connolly et al. raised some of these points already [2], we hope to learn some important lessons from the authors to better understand these limitations and how they can be minimized in future studies.
  The number of randomized controlled trials evaluating early physical rehabilitation in ICUs is increasing [3]. Positive effects on primary outcomes were only found in studies in which physical rehabilitation was started within 72 hours of ICU admission [4-6]. Studies, which did not meet this criterion of early onset of physical rehabilitation, did not demonstrate benefit of the intervention [7]. Therefore, this time frame has been defined in rehabilitation guidelines [8]. Based on this evidence, we are not surprised that the authors of the EPICC trial were unable to demonstrate beneficial...

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  We have read with great interest the multi-centred EPICC trial that randomized over 300 patients [1]. While the delivery of a complex physical rehabilitation intervention in clinical trials is difficult, we believe that several aspects of the trial may have resulted in the inability to detect a difference between the control and intervention groups. These factors include the delayed time to start the intervention, inadequate delivery of the intervention and the large loss to follow-up for the primary outcome measure. In our opinion, these three factors limit the interpretation of the results of the study. While the authors have mentioned some of these concerns in their discussion, and Connolly et al. raised some of these points already [2], we hope to learn some important lessons from the authors to better understand these limitations and how they can be minimized in future studies.
  The number of randomized controlled trials evaluating early physical rehabilitation in ICUs is increasing [3]. Positive effects on primary outcomes were only found in studies in which physical rehabilitation was started within 72 hours of ICU admission [4-6]. Studies, which did not meet this criterion of early onset of physical rehabilitation, did not demonstrate benefit of the intervention [7]. Therefore, this time frame has been defined in rehabilitation guidelines [8]. Based on this evidence, we are not surprised that the authors of the EPICC trial were unable to demonstrate beneficial effects of their intervention, since it approximately started on day 8 (the median (IQR) duration of ventilation at randomisation was 4 (3–7) days with a further 3 (1–6) days until the first physical rehabilitation was received), which may be too late to confer benefit.
  The EPICC protocol aimed to compare 30 min vs. 90 min of physical rehabilitation, which was not achieved in either group. The authors report that the daily physical therapy was applied for 23 min in the intervention group (26% of the planned intervention) and for 13 min in standard of care group (43% of the planned standard care), respectively. Not only this amount of physical rehabilitation is hardly conceivable as an effective therapeutic strategy, but in terms of testing the hypothesis, it did not achieve the planned separation between the groups. In other words, the EPICC trial teaches us that an additional 10 minutes of physical rehabilitation per day does not make a difference.
  The authors describe two main reasons for not achieving their planned intervention: (a) sedation and (b) patient fatigue. We have difficulties understanding why these two factors could not be controlled. The authors do not report the sedation regime during the study. If there was no standardized sedation protocol with daily awakening trials, this is a further shortcoming of the protocol as well as another reason for inability to improve the patients’ outcome in the intervention group. Deep sedation not only inhibits effective physical rehabilitation but is associated with increased mortality and length of stay [8]. To better appreciate the study results, it would be important that the authors report the sedation protocols/regimes of the participating centres.
  Furthermore, how was the treatment plan of the intervention in “difficult” patients with low physical reserve or pre-existing frailty implemented? From our own experience patients with impaired functional reserves or frailty might only be trained for a short period of time. However, to achieve an intervention time of 90 minutes per day, such patients must be trained several times a day (e.g. for 15 minutes every hour). If 23 minutes are achieved in the intervention group, there might have been an additional “resource” limitations which is not presented, e.g. that a physical therapist would not be able to do more than a session every 4 hours or than four times a day. Would it be possible to elaborate on the available staff resources to deliver the intervention? If we assume that the lack of staff resources were an additional limitation not mentioned by the authors, it supports our belief that a successful early rehabilitation program has to be interprofessional, including both physical therapists and nursing staff to maximize physical rehabilitation opportunities throughout the day [5, 10].
  Finally, the authors chose a primary outcome (Physical Component Summary Score of the SF-36 version 2) that does take into account mortality. Approximately one third of patients enrolled died before the functional outcome could be assessed. This functional outcome “truncated due to death” creates challenges in the definition and statistical evaluation of the treatment effect, and deserves careful planning of statistical analyses [11].
  An additional 25% of enrolled patients were lost to follow-up. Therefore 57% of the enrolled patients did not contribute to the primary outcome measure, making the overall results of the study difficult to interpret.
  In summary, we think that the conclusion and key message do not entirely reflect the study results. Physical therapy interventions of 90 min vs. 30 minutes were not achieved in the study. Additionally, less than half of enrolled patients contributed data to the primary outcome measure and excluding patients who did not survive limits the interpretation of this complex intervention.

  References
  1. Wright, S.E., et al., Intensive versus standard physical rehabilitation therapy in the critically ill (EPICC): a multicentre, parallel-group, randomised controlled trial. Thorax, 2017.
  2. Connolly B and Denehy L Hindsight and moving the needle forwards on rehabilitation trial design. Thorax. 2018 Mar;73(3):203-205. doi: 10.1136/thoraxjnl-2017-210588. Epub 2017 Nov 14. http://thorax.bmj.com/content/73/3/203
  3. Fuest, K. and S.J. Schaller, Recent evidence on early mobilization in critical-Ill patients. Curr Opin Anaesthesiol, 2018.
  4. Schweickert, W.D., et al., Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet, 2009. 373(9678): p. 1874-82.
  5. Schaller, S.J., et al., Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet, 2016. 388(10052): p. 1377-1388.
  6. Investigators, T.S., et al., Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study. Crit Care, 2015. 19: p. 81.
  7. Moss, M., et al., A Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute Respiratory Failure. Am J Respir Crit Care Med, 2016. 193(10): p. 1101-10.
  8. Bein, T., et al., S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders : Revision 2015: S2e guideline of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI). Anaesthesist, 2015. 64 Suppl 1: p. 1-26.
  9. Stephens, R.J., et al., Practice Patterns and Outcomes Associated With Early Sedation Depth in Mechanically Ventilated Patients: A Systematic Review and Meta-Analysis. Crit Care Med, 2018. 46(3): p. 471-479.
  10. McWilliams, D., et al., Earlier and enhanced rehabilitation of mechanically ventilated patients in critical care: A feasibility randomised controlled trial. J Crit Care, 2018. 44: p. 407-412.
  11. Colantuoni, E., et al., Statistical methods to compare functional outcomes in randomized controlled trials with high mortality. BMJ, 2018. 360: p. j5748.

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  Conflict of Interest:
  None declared.

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• Published on: 9 October 2017

  Intensive or longer?

  • Rodrigo Santos Queiroz, college professor Department of Health of Southwestern State University of Bahia - Brazil
  • Other Contributors:
    • Micheli Bernardone Saquetto, college professor
    • Bruno Prata Martinez, college professor
    • Mansueto Gomes Neto, college professor

  We read with great interest the article by Wright et al (1) published recently on the Thorax. We congratulate the authors for the study that focused on an important issue, an optimal dose of mobilization in critically ill patients. This is a very well designed clinical trial that allows us to delve deeper into discussions about training load variables applied to critical patients.
  The authors named the main study training load variable of intensity. However we note that the duration of the program was the main difference between the groups and not the intensity. This is, because duration is the time period for a specific activity, while the intensity is relative to the rate of energy expenditure required to perform the activity (aerobic activity) or the magnitude of the force exerted during the resistance exercise (2).
  It was unclear how muscle strength training progressed and there was no measure of energy expenditure (even if indirectly with accelerometers or perceived exertion scales), so we can not clearly state that there was a difference in the intensity of the groups, even though they had a longer duration for the intervention group (3). It is well known that in healthy subjects, shorter duration and shorter intervals may have substantially higher energy expenditure and may affect the metabolic pathways differently (4). A reality that still deserves more attention in intensive care mobilization studies.

  References

  1. Wright SE, Thomas K, Wa...

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  We read with great interest the article by Wright et al (1) published recently on the Thorax. We congratulate the authors for the study that focused on an important issue, an optimal dose of mobilization in critically ill patients. This is a very well designed clinical trial that allows us to delve deeper into discussions about training load variables applied to critical patients.
  The authors named the main study training load variable of intensity. However we note that the duration of the program was the main difference between the groups and not the intensity. This is, because duration is the time period for a specific activity, while the intensity is relative to the rate of energy expenditure required to perform the activity (aerobic activity) or the magnitude of the force exerted during the resistance exercise (2).
  It was unclear how muscle strength training progressed and there was no measure of energy expenditure (even if indirectly with accelerometers or perceived exertion scales), so we can not clearly state that there was a difference in the intensity of the groups, even though they had a longer duration for the intervention group (3). It is well known that in healthy subjects, shorter duration and shorter intervals may have substantially higher energy expenditure and may affect the metabolic pathways differently (4). A reality that still deserves more attention in intensive care mobilization studies.

  References

  1. Wright SE, Thomas K, Watson G, et al. Intensive versus standard physical rehabilitation therapy in the critically ill (EPICC): a multicentre, parallel-group, randomised controlled trial. Thorax. 2017.
  2. American College of Sports Medicine. ACSM's guidelines for exercise testing and prescription. Lippincott Williams & Wilkins. 2013.
  3. Beach LJ, Fetterplace K, Edbrooke L, et al. Measurement of physical activity levels in the Intensive Care Unit and functional outcomes: An observational study. Journal of Critical Care. 2017;40: 89-196.
  4. Tabata I. et al. Effects of moderate-intensity endurance and high-intensity intermittent training on anaerobic capacity and VO2max. Medicine and science in sports and exercise. 1996;28:1327-1330.

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  Conflict of Interest:
  None declared.

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