Feasibility challenges in protein supplementation research: Insights from the convalescence of functional outcomes after intensive care unit stay in a Randomised Controlled Trial

Abstract

Background & aims: Dietary protein supplementation may benefit physical outcomes in post-intensive care unit (ICU) patients suffering ICU-acquired weakness (ICU-AW). This study examines the impact of a six-week protein supplementation compared to an isocaloric carbohydrate on physical functioning outcomes in post-ICU patients with a follow-up of 12 weeks after ICU discharge. This paper presents descriptive data, feasibility outcomes, and the barriers faced while conducting this nutritional intervention study in post-ICU patients.

Methods: This two-arm, randomised, double-blind controlled intervention trial involved adult patients (≥18 y) who were admitted to the ICU for ≥72 h with moderate ICU-AW (Medical Research Council (MRC) score 24-48). Patients were randomly assigned to receive 22 g of collagen peptides supplementation or an isocaloric carbohydrate twice daily. The primary outcome was a composite score for physical functioning comprising handgrip strength, leg muscle strength, arm muscle strength, and exercise capacity, adjusted for age, sex, and body weight. Secondary endpoints included nutritional intake and biomarkers, scores in other post-intensive care syndrome (PICS) domains, and mortality rates. Descriptive data is presented, no between-intervention group analyses were conducted due to incomplete sample size.

Results: A total of 900 patients were screened for eligibility to participate in the study, of whom 59 met the requisite criteria between April 2022 and December 2023. The most common reasons for exclusion were treatment limitations, diabetes mellitus, or an MRC score <24 or above >48. Of the 59 patients deemed eligible, 15 patients were included to participate in the study. Due to the slow inclusion rate, the study was terminated early (at ∼20 % of anticipated sample size). At baseline (ICU discharge), patients initially had lower physical scores than reference values but showed improved (higher) scores at three months post-ICU discharge. Differences between the groups regarding the primary outcome (composite score of physical functioning) could not be identified due to early termination. Factors affecting the feasibility of nutrition research in post-ICU patients were identified, including slow patient recruitment rates, low adherence to the intervention, and the inability to complete outcome assessments.

Conclusions: Patients exhibited initial physical functioning scores below the reference values yet demonstrated substantial physical recuperation by the 12-week mark following their ICU discharge in both groups. Patients exhibited lower scores in all domains of PICS compared to reference values, emphasising the necessity for further investigation into the potential role of nutrition interventions in preventing and alleviating PICS symptoms. Furthermore, this study describes the factors affecting the feasibility of post-ICU intervention studies and provides recommendations for future studies on effective design and conduction of studies to address PICS (This study was supported by Rousselot; Confucius ClinicalTrials.gov number, NCT05405764).

Keywords: Critical care; ICU survivors; Nutrition; PICS; Post-ICU; Protein.