Skeletal Muscle Wasting in ICU Patients

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.