113 PROTEIN PROVISION AND EXERCISE THERAPY TO IMPROVE OUTCOMES IN ICU-SURVIVORS 7 7.1 INTRODUCTION There is a growing number of patients who survive critical illness and suffer from post-intensive care syndrome (PICS).1,2 This syndrome is characterised by severe physical, mental, and cognitive problems. Critical illness-induced severe catabolism, muscle loss, weakness, and organ dysfunction, also defined as ICU-acquiredweakness (ICUAW),3-5 cannot be prevented. Although improvements are seen within the first year after ICU-discharge,6,7 physical functioning QoL do not fully reach the patient’s baseline status.7-9 The prevalence of malnutrition and frailty in patients admitted to the ICU is about 38-78%.10-12 In addition, loss of muscle mass can add up to 22.5% during the first two weeks of ICU-admission13 and is associated with a decline in physical functioning, reduced QoL, and increased mortality in ICU-patients.14-17 Therefore, muscle mass is an important clinical marker for nutrition and ICU-related syndromes. Sufficient protein intake and exercise therapy are very likely to reduce muscle loss and recover muscle health in critically ill patients, improving physical performance and QoL.18-21 However, robust evidence is lacking.3,22-30 Since ICU-survivors are a heterogeneous population, it is not always clear which patients benefit more from treatment than others, which remains unexposed when an overall effect between groups is analysed. Also, insufficient protein intake, reduced mobility, and metabolic alterations may inhibit the potential to benefit from nutritional and exercise interventions.31-33 It is most likely that these aspects play an important part in patients who survive critical illness but do not fully recover. Although it seems that outcomes can be improved by nutrition and exercise interventions, the current lack of evidence could be a result of limited high- quality randomised controlled trials (RCTs) or the absence of observational studies with the potential to assess long-term and patient-reported outcome measures (PROMs). Therefore, a comprehensive systematic review was performed including both RCTs and non-randomised controlled trials of intervention effects (NRSI).34 With this review it was aimed to identify appropriate protein interventions, preferably combined with exercise therapy, compared to a distinct (lower) protein strategy or standard care. In addition, we aimed to identify specific patient characteristics to determine which patients might benefit more or less
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