Title: Preventing muscle wasting in critically ill patients by repetitive occlusive stimulus (ROS): a feasibility study
Funder: Department of Health and Social Care

Abstract: A substantial loss of muscle mass and strength can occur during intensive care unit (ICU) stay irrespective of initial reason for admission. Intensive care unit-acquired weakness (ICU-AW) affects 40% of ICU patients and some are unable to move limbs nor breathe unsupported as a consequence. It is associated with prolonged need for mechanical ventilation and ICU stay, increased risk of death following hospital discharge, and long-term complications including increased need for assistance with activities of daily living. In order to prevent these consequences of ICU-AW early intervention is key. Repetitive Occlusion Stimulus (ROS) involves the repeated inflation (to above arterial pressure ~ 200 mmHg) of a cuff positioned around the thigh, to elicit brief bouts (~ 5 minutes) of limb ischaemia, followed by complete deflation to allow reperfusion. In immobilised patients, performing ROS daily can reduce the rate of muscle wasting and loss of strength. ROS applied to one area may have a systemic effect, benefiting areas remote to the site of its application. In this way, important muscle groups that could not receive localised ROS (such as respiratory muscles) will be protected from decline and patient outcomes will be maximally improved. ROS is a simple, non invasive and relatively inexpensive intervention that has potential to reduce muscle wasting and the development of ICU-AW. We aim to evaluate if the intervention is safe, tolerable and practical for ICU patients, and the feasibility of conducting a large trial. We will collect data specifically to inform a subsequent multicentre RCT to determine the clinical efficacy of ROS in the ICU setting. The proposed study is a small randomised controlled trial to assess the possible effects of ROS in this patient group, and to see if a larger study would be feasible. The study will recruit at least 30 critically ill patients at two sites (Royal Surrey Country Hospital and St Peters Hospital, Surrey) over 16 months. Patients will be randomized (1:1) to intervention and control groups. The intervention group will receive ROS (applied proximally on right leg) three times a day for 40 minutes, in addition to usual care. Patients randomized to the control group will not undergo ROS application or sham intervention, but will receive usual care delivered by specialist physiotherapists. We will monitor adverse safety and tolerance events, recruitment, retention, compliance and completeness of trial data. Properties of outcomes will be examined to determine a suitable primary outcome. Ultrasound measurement of rectus femoris cross sectional area (RFCSA) is a validated method of quantifying muscle wasting, and will be performed on day 1, 6 and 11 of ICU stay. As there is potential for ROS to benefit both localised and remote muscle, the intervention will be applied on one leg but assessments will be made in both (intervention group only). The ICU Mobility Scale will provide a subjective measure of physical function on day 1, 6 & 11 of ICU stay and at ICU and hospital discharge. Muscle strength (MRC sum score & handgrip strength) will be assessed at awakening, on day 11 of ICU stay and at ICU and hospital discharge. Objective measures of functional capacity (Sit-to-Stand and Timed Up & Go) will be performed at hospital discharge. Health related quality of life will be assessed at hospital discharge and 90 days post baseline. Acceptability of the trial experience for patients, consultees and clinicians will be investigated by questionnaire and semi structured interview at hospital discharge. The therapeutic effects of ROS could have clinical relevance in ICU patients, improving the rate of recovery and long-term prognosis. Dissemination will include peer-reviewed journal publications and presentations at national and international conferences.

Lay abstract: Hospital intensive care units (ICUs) can be dangerous places. A year after being discharged, 70% of patients remain reliant on assistance with daily activities due to their hospital stays. One reason for this is muscle wasting experienced in hospital. We want to test a treatment called Repetitive Occlusion Stimulus (ROS). A fabric cuff, similar to that used to measure blood pressure, is placed round one thigh and inflated and deflated repeatedly, causing a restriction and then release of blood flow. This is has been shown to effectively reduce muscle wasting in patients who are less ill but it has not been tried in ICU before. It is not painful and it should not cause any distress. Before we test ROS on a large number of patients we will test it on a small sample to check for any problems, either in the use of ROS or in the processes of the study. We will recruit 30 patients from two ICUs over 2 years and randomly allocate them (as if by chance) into two groups: one will have detailed observations, the other will have the same observations and also receive ROS treatment for 40 minutes, 3 times per day for 10 days. We will take ultrasound measurements during patients stay in ICU, and carry out strength tests in hospital and after discharge to see if ROS treatment reduces signs of muscle wasting more amongst the ROS patients. Previous ICU patients and family members have identified this area of research as a priority. The results will help us design a larger trial, with potential to definitively establish if ROS works. If it does, its impact could be substantial, at low cost. We will share the results of this study through presentations at conferences and publications.

Research activity codes: 6.7 PHYSICAL
Health categories: GENERIC HEALTH RELEVANCE