Discussion
muscle mass, ICU-AW, critically ill, muscle wasting
DISEASE, CRITICALLY ILL, MUSCLE WASTING
Our findings indicate that RT improved physical function, muscle strength, and physical activity in MICU patients to a comparable extent to the combined intervention group. However, neither RT, HMB intervention, nor the combined intervention demonstrated efficacy in reducing muscle wasting or enhancing patients’ self-reported quality of life at one month post-discharge. Our study is groundbreaking in that it is the first ever multicentre randomised controlled trial with four arms to demonstrate that RT with or without HMB intervention can effectively enhance physical function in MICU survivors. The intervention encompasses the timeframe from ICU admission to patient transfer and discharge. Its continuum throughout the hospitalisation process optimally meets the rehabilitation requirements of MICU patients, highlighting another aspect of its novelty.The utilisation of combined exercise and nutritional interventions in the ICU population remains limited, despite evidence from RCTs conducted in recent years. These trials have shown that integrating nutrition and exercise interventions can improve muscle mass, muscle strength, and physical function in critically ill patients [The lack of statistically significant differences in body composition (FFM, SMI, ASMM, and PhA) and physical function (SPPB/6MWD, MRC, grip strength, etc.) associated with HMB intervention may serve as an additional important factor explaining the absence of advantages in the combined intervention of this study. Our findings align with prior research by Viana et al. [In our study, we observed significant improvements in SPPB scores, 6MWD MRC score, and grip strength in both the RT group and the combined group. The effectiveness of these enhancements can be attributed to the meticulous specification of our research protocol. Notably, this is the first study to implement a stratified RT intervention for ICU patients, which includes supine, sitting, or standing positions based on individual functional capacity. Our interventions encompass physical functional training alongside muscle strength training, yielding more pronounced effects [This research has several limitations. Firstly, generalising our study findings to ICU patients with higher disease severity is limited due to potential selection bias in our sample. This is evident from the low proportion of mechanically ventilated patients (30.9% of participants) and low to intermediate disease severity, as indicated by a median SOFA score of 6.0, a median APACHE II score of 16.0 and a median length of ICU stays of 6.5 days. Insufficient sample size hindered meaningful subgroup analysis. As a result, the effectiveness of the intervention for patients with higher disease severity upon admission, who are at the highest risk for ICU-AW, remains inconclusive. Future research with larger samples and stratified analyses should determine the efficacy of this intervention protocol in different disease severities. Second, although the reasons why the combined intervention did not outperform the individual intervention are extensively discussed in this study, we observed lower survival and compliance rates in the combined intervention group during the intervention process. However, we did not conduct a comprehensive investigation to ascertain whether this was due to population heterogeneity, or substantial barriers associated with the combined intervention. Last, the study subjects had to simultaneously meet the requirements for resistance training (being awake, able to actively cooperate, and a muscle strength level of at least grade 3) and the conditions for HMB intervention (initiating enteral nutrition) to receive the intervention. This may have caused a delay in the intervention's scheduling, thereby influencing the outcomes.