Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in critical illness patients during entire hospitalisation: a four-arm multicentre randomised controlled trial

Abstract

Abstract Background: Intensive Care Unit Acquired Weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training (RT) and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether RT and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients. Methods: In this multicentre, four-arm, single-blind RCT, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the RT group received protocol-based multilevel resistance exercise, the HMB group received 3g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model (GLLM), adhering to the principles of intention-to-treat analysis. Results: RT and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group, and substantial improvements in 6WMD (99.768 and 88.577 metres, respectively) (all with P<0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the RT and combination groups (P<0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects. Conclusions: RT with or without HMB during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected. Trial registration: ChiCTR2200057685 was registered on March 15th, 2022.