Project Summary: Patients who have a length of stay four or more days in ICU and requiring mechanical ventilation assistance to breathe for more than 48 hours will be invited to participate. Participants will be randomised to either receive Functional Electrical Stimulation (eStimCycle) assisted cycling or standard care. As cycling in bed has previously been shown to improve physical function, patients who receive cycling as a treatment will have one leg that cycles and the other leg that cycles with assistance of electrical stimulation as we want to establish the effectiveness of the addition of electrical stimulation of muscle. Muscle bulk, strength and physical function outcome measures will be measured at baseline, weekly in ICU, ICU discharge and hospital discharge. Cognitive function will also be measured at hospital discharge, 6- and 12-month follow-up. A small group of patients in this study will be invited to provide samples of blood, urine and muscle at ICU admission and discharge to try and determine what happens to muscle in patients who are critically ill.

Significance of the Project: This is an important study because the development of ICU-acquired weakness (ICU-AW) can result in long term limitations in physical function. Early treatment to maintain strong muscles during an intensive care stay may help speed up recovery and enhance participation in other rehabilitation treatments and improve functional activities and cognition. These are important objectives for both patients and their families. In addition understanding why the muscles become so weak so quickly in patients in ICU will help to develop treatments that may help to maintain muscle strength.

Study Hypotheses:

Hypothesis 1: eStimCycle versus usual care rehabilitation will improve muscle strength at hospital discharge.

Hypothesis 2: eStimCycle versus usual care rehabilitation will improve cognitive function at 6 month follow up.

Hypothesis 3: Patients receiving eStimCycle will have improved activity of anabolic signalling pathways and less atrophy of skeletal muscle fibre size compared with usual care rehabilitation.

Inclusion Criteria:

1. ≥18 years,
2. expected mechanical ventilation or ECMO >48 h with evidence of systemic inflammation as defined by American College of Chest Physicians (ACCP) Consensus Conference Criteria and
3. predicted ICU length of stay ≥4 days.

Exclusion Criteria:

1. Known primary systemic neuromuscular disease or intracranial process on ICU admission
2. Lower limb amputation/s
3. Unable to perform study physical outcome measures pre morbidly due to condition impairing mobility
4. Assessed by medical staff as not-expected to survive ICU
5. Pregnancy
6. BMI > 40
7. Presence of external fixator or superficial metal in lower limb
8. Open wounds or skin abrasions at electrode application points
9. Presence of cardiac or diaphragmatic pacemaker or implanted defibrillator with no underlying rhythm, as confirmed by the treating physician
10. Transferred from another ICU after > 2 days of mechanical ventilation
11. Platelets < 40 000 and INR > 1.6 (for muscle biopsy)
12. Lower limb malignancy
13. Pre-existing intellectual disability or cognitive impairment limiting the ability to accurately follow instructions.
14. Non-English speaking background restricting the individuals ability to accurately and consistently follow instructions.

Exclusion criteria for the 6 and 12 month cognitive testing follow-up portion of the study:

1. Cognitive impairment (IQCODE >3.3) done by proxy after informed consent obtained
2. No fixed home address
3. Score >= 10 on Alcohol use disorders and identification test (AUDIT)