Muscle mass, muscle quality and protein provision during critical illness

Up to 50% of patients admitted to the Intensive Care Unit (ICU) develop ICU acquired weakness. ICU acquired weakness leads to impaired physical ablity and quality of life. Muscle atrophy is a major contributor to the development of ICU acquired weakness. Protein provision may attenuate loss of muscle mass during critical illness by enhancing muscle protein synthesis, but current guidelines remain expert opinion based. Our aim was to increase the knowledge on the assessment and the course of muscle mass and muscle quality during critical illness and how protein provision may affect outcomes in the critically ill. In chapter 2, an overview of recent literature on the monitoring of muscle mass using ultrasound in critically ill patients is provided. Interpretation and comparison between studies are complicated by lack of a uniform protocol leading to discrepancies between choice of measured muscle, landmarks used and compression level. Chapter 3 describes the changes in in vitro measured muscle mass and muscle strength during the first week of critical illness compared to a healthy control group. We did not observe a significant decrease in myofiber size as measured in vitro (cross-sectional area) during the first week of ICU stay. The absence of a significant decrease is likely due to the very small sample size. In chapter 4, skeletal muscle mass and quality were assessed by CT scan during the first 30 days of COVID-19 critical illness. Additionally, we assessed whether the administration of neuromuscular blocking agents (NMBA) or glucocorticoids affected muscle mass and quality. We did not detect a clear decrease in muscle mass, in which edema and differences between scanning protocols may have been confounding factors. For muscle quality, a more consistent decline was observed. Both short- and long-term NMBA use, as well as high-dose glucocorticoids, were associated with a decline in muscle quality. In the systematic review and meta-analysis presented in chapter 5, we found that a protein provision of >1.2 compared to ≤1.2 grams of protein/kg/day improved nitrogen balance and preservation of muscle mass. The results were rather controversial in light of newly published data. In response, chapter 6 discusses the importance of safe ranges of protein provision and protein requirements in subgroups of critically ill patients. Excessive protein provision may contribute to harm, especially in specific subgroups of patients with sepsis and/or higher disease severity. In chapter 7 of this thesis, we report the results of a retrospective cohort study in critically ill patients receiving early (day 4 of ICU stay) protein provision of more than 1.2 grams of protein/kg/day compared to patients receiving ≤1.2 grams of protein/kg/day. We confirmed previous findings of positive effects of higher protein provision in non-septic patients, but also that a lower protein provision may be preferred in septic patients. In chapter 8, we studied critically ill COVID-19 patients. We did not identify a clear relation between protein provision (≥1.2 versus <1.2 grams of protein/kg/day) and changes in skeletal muscle mass, diaphragm volume, skeletal muscle quality, or diaphragm muscle quality. This thesis identifies the following implications for guiding both clinical practice and future research in the critically ill: • Assessment of muscle beyond mass may provide valuable insights. Tools that measure muscle quality or strength, in this thesis by CT scan or in vitro strength, may provide earlier signals of muscle impairment than mass alone. • One nutritional strategy does not fit all. This thesis supports the ESPEN protein provision guideline of 1.3 grams of protein/kg/day for the general ICU population, but also emphasizes the need for more personalized protein provision recommendations.