Critical Illness, Muscle Atrophy
Conditions
Brief summary
Muscle wasting occurs rapidly in critically ill patients and impacts both short and long term outcomes. Altered protein metabolism drives muscle loss in ICU patients, with muscle protein breakdown exceeding muscle protein synthesis (MPS). Interventions aimed at attenuating muscle loss by stimulating MPS rates are hampered by a lack of knowledge on altered muscle protein turnover rates during critical illness. Only a few studies have specifically assessed muscle protein synthesis by using contemporary intravenous stable isotope infusions, which allows the assessment of MPS over a short (\<9 hours) period of time. Results from such acute studies can be difficult to extend or translate into long-term clinical practice and outcomes. Oral deuterated water (2H2O) dosing provides an alternative method that can be utilized to extend the measurement of muscle protein synthesis over a period of several days or weeks. It could therefore provide a valuable tool to study muscle protein synthesis during ICU admission and the impact of different anabolic interventions. Although multiple studies using the deuterated water methodology have been performed in both healthy volunteers and patients, it has not yet been performed in critically ill patients. In this prospective study the investigators aim to assess fractional rates of muscle protein synthesis over a period of (maximal) 7 days in critically ill patients admitted to the intensive care unit. Secondly, the investigators aim to assess mechanisms of acute muscle wasting on an microscopic, ultrastructural and molecular level. Furthermore, the investigators aim to investigate to what extent muscle fibre size is recovered 3 months after ICU discharge.
Interventions
None listed
Sponsors
Jessa Hospital
Frank Vandenabeele
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* age \>18y * admitted to ICU * enteral nutrition line in situ * arterial line (any location) in situ * expected stay ICU \>7d
Exclusion criteria
* spinal cord injury * chronic use of corticosteroids before hospital admission * Contraindication to enteral infusion (e.g. due to GI-tract perforation) * Kidney or liver failure * therapeutic anti coagulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| muscle protein synthesis rate (%/h) | 7 days of stay at the intensive care unit | obtained by using deuterated water, muscle biopsy sampling and blood sampling |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| skeletal muscle fiber characteristics 2 | 7 days of stay at the intensive care unit | amount and distribution of muscle fibers (distribution will be calculated as: amount of type X / total amount of fibres) |
| mRNA expression in skeletal muscle tissue 1 | 7 days of stay at the intensive care unit | mRNA expression in skeletal muscle tissue of MAFBx (atrophy marker) |
| mRNA expression in skeletal muscle tissue 2 | 7 days of stay at the intensive care unit | mRNA expression in skeletal muscle tissue of MurF1 (atrophy marker) |
| mRNA expression in skeletal muscle tissue 3 | 7 days of stay at the intensive care unit | mRNA expression in skeletal muscle tissue of FOXO (atrophy marker) |
| patient characteristic- age | 7 days of stay at the intensive care unit | age in years |
| patient characteristic- body weight | 7 days of stay at the intensive care unit | body weight in kg |
| patient characteristic- height | 7 days of stay at the intensive care unit | height in m |
| patient characteristic- sex | 7 days of stay at the intensive care unit | male or female |
| patient characteristics (medical1) | 7 days of stay at the intensive care unit | mechanical ventilation (duration in days) |
| patient characteristics (medical2) | 7 days of stay at the intensive care unit | comorbidities (list of comorbidities) |
| patient characteristics (medical3) | 7 days of stay at the intensive care unit | reason hospital admission |
| skeletal muscle fiber characteristics 1 | 7 days of stay at the intensive care unit | cross sectional area of muscle fibers |
| patient characteristic- food intake | 7 days of stay at the intensive care unit | food intake (energy in kcal and protein intake in g/kg/d) |
| patient characteristic- LOS | Stay at the intensive care unit and Hospital (up to 1 year) | Length of stay ICU and hospital (in days) |
| muscle hand grip strength | 3 months post-hospital discharge | hand grip strength using the JAMAR dynamometer in kg |
| leg muscle strength | 3 months post-hospital discharge | 1RM upper leg at follow up visit |
| muscle volume | 3 months post-hospital discharge | 3d ultrasound assessed at follow up visit |
| habitual food | 3 months post-hospital discharge | Assessed using questionnaires at follow up visit (higher score means better intake) |
| habitual activity | 3 months post-hospital discharge | Assessed using questionnaires at follow up visit (higher score means better intake) |
| Functional capacity 1 | 3 months post-hospital discharge | SPPB at follow up visit (short physical performance battery) |
| Functional capacity 2 | 3 months post-hospital discharge | 6min walking test at follow up visit |
| Quality of life questionnaire | 3 months post-hospital discharge | SF-36 at follow up visit (Short Form Health Survey 36 items) range score between 0-100, lower score represents great health related problems |
| Quality of life questionnaires | 3 months post-hospital discharge | Euro-QoL-5D-5-level at follow up visit (Euro quality of life 5 Dimension 5 level) Answers can be converted into EQ-5D index, an utility scores anchored at 0 for death and 1 for perfect health |
| patient characteristic- APACHE score II | 7 days of stay at the intensive care unit | APACHE II score = acute physiology score + age points + chronic health points. Minimum score = 0; maximum score = 71. |
Countries
Belgium
Contacts
Primary ContactMichelle Weijzen, Dr.
Backup ContactFrank Vandenabeele, Prof.
Outcome results
None listed