BACKGROUND: Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h of ICU admission may improve muscle function and long-term outcome. METHODS: An assessor-blinded, pragmatic, single-centre randomized controlled trial will be performed. Adults (n = 150) mechanically ventilated for < 48 h from four ICUs who are estimated to need > 7 days of critical care will be randomized (1:1) to receive either standard of care or FES-CE-based intensified rehabilitation, which will continue until ICU discharge. PRIMARY OUTCOME: quality of life measured by 36-Item Short Form Health Survey score at 6 months. SECONDARY OUTCOMES: functional performance at ICU discharge, muscle mass (vastus ultrasound, N-balance) and function (Medical Research Council score, insulin sensitivity). In a subgroup (n = 30) we will assess insulin sensitivity and perform skeletal muscle biopsies to look at mitochondrial function, fibre typing and regulatory protein expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02864745. Registered on 12 August 2016.

• Keywords
• Critically ill, Early rehabilitation, Functional electrical stimulation-assisted cycle ergometry, Intensive care unit, Mobility, Physical therapy,
• MeSH
• Time Factors MeSH
• Bicycling * MeSH
• Electric Stimulation Therapy * adverse effects   MeSH
• Ergometry * MeSH
• Intensive Care Units MeSH
• Muscle, Skeletal innervation   MeSH
• Critical Illness MeSH
• Quality of Life MeSH
• Humans MeSH
• Recovery of Function MeSH
• Pragmatic Clinical Trials as Topic MeSH
• Muscle Contraction * MeSH
• Muscle Strength * MeSH
• Muscle Weakness diagnosis   physiopathology   rehabilitation   MeSH
• Treatment Outcome MeSH
• Exercise Test MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Mitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. It has been hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. The aim of the present study was to determine whether mitochondrial dysfunction persists until protracted phase of critical illness. METHODS: In this single-centre controlled-cohort ex vivo proof-of-concept pilot study, we obtained vastus lateralis biopsies from ventilated patients with ICU-acquired weakness (n = 8) and from age and sex-matched metabolically healthy controls (n = 8). Mitochondrial functional indices were measured in cytosolic context by high-resolution respirometry in tissue homogenates, activities of respiratory complexes by spectrophotometry and individual functional capacities were correlated with concentrations of electron transport chain key subunits from respiratory complexes II, III, IV and V measured by western blot. RESULTS: The ability of aerobic ATP synthesis (OXPHOS) was reduced to ~54% in ICU patients (p<0.01), in correlation with the depletion of complexes III (~38% of control, p = 0.02) and IV (~26% of controls, p<0.01) and without signs of mitochondrial uncoupling. When mitochondrial functional indices were adjusted to citrate synthase activity, OXPHOS and the activity of complexes I and IV were not different, whilst the activities of complexes II and III were increased in ICU patients 3-fold (p<0.01) respectively 2-fold (p<0.01). CONCLUSIONS: Compared to healthy controls, in ICU patients we have demonstrated a ~50% reduction of the ability of skeletal muscle to synthetize ATP in mitochondria. We found a depletion of complex III and IV concentrations and relative increases in functional capacities of complex II and glycerol-3-phosphate dehydrogenase/complex III.

• MeSH
• Adenosine Triphosphate metabolism   physiology   MeSH
• Organelle Biogenesis MeSH
• Quadriceps Muscle metabolism   MeSH
• Energy Metabolism physiology   MeSH
• Glycerolphosphate Dehydrogenase metabolism   MeSH
• Intensive Care Units MeSH
• Cohort Studies MeSH
• Muscle, Skeletal metabolism   MeSH
• Critical Illness MeSH
• Middle Aged MeSH
• Humans MeSH
• Mitochondria metabolism   pathology   MeSH
• Oxidative Stress physiology   MeSH
• Pilot Projects MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Muscle Weakness etiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenosine Triphosphate MeSH
• Glycerolphosphate Dehydrogenase MeSH