Each year, 110,000 English/Welsh patients are admitted to Intensive Care Units (ICU). Many face prolonged disability as a result. Over two thirds have moderate-extreme limitation in their usual activity a year later, and one-third are severely affected, being unable to continue "most activities," or to live independently. Quite why known- but severe muscle wasting isn't may play an important role. We hope to find out, measuring the degree of wasting in patients, and seeking potential causes. We shall also address the mechanism of wasting, which may reflect an altered balance of activity in muscle growth pathways and those that break muscle down. We'll do this by collecting data, taking regular blood tests, scanning the leg muscles with an ultrasound machine, and analysing small muscle samples. In addition, we'll accurately and objectively measure how impaired these patients become, using specialist questionnaires, special monitoring equipment, simple walking tests and occasional special ('Cardio-Pulmonary') exercise tests. We'll try to see how badly activity is limited, and tease out whether muscle weakness plays a significant role in this. Finally, keeping muscles working (hard to do when unconscious/drowsy/bed-bound) may maintain muscle mass, so we'll see whether maintaining muscle activity using painless electrical stimulation will help.

Inclusion Criteria:

• Ventilated patients aged > 18 years likely to survive and remain ventilated for 48 hours and on ICU for 7 days will be recruited.

Exclusion Criteria:

• Those who are pregnant,
• Have active malignancy,
• Have primary muscle/bilateral lower limb disorders or
• Are unlikely to survive 48 hrs.

All admission to CRitical care who are ventilated, and are likely to remain so for 48hrs or more AND remain on ITU for 7 days