The Association Between Malnutrition and High Protein Treatment on Outcomes in Critically Ill Patients: A Post Hoc Analysis of the EFFORT Protein Randomized Trial

Lew CCH 1 , Lee ZY 2 , Day AG 3 , Jiang X 3 , Bear D 4 , Jensen GL 5 Show all authors , Ng PY 6 , Tweel L 7 , Parillo A 8 , Heyland DK 3 , Compher C 9

Affiliations 

  • 1 Department of Dietetics & Nutrition, Ng Teng Fong General Hospital, Singapore, Singapore; Faculty of Health and Social Sciences, Singapore Institute of Technology, Singapore, Singapore
  • 2 Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Cardiac Anesthesiology & Intensive Care Medicine, Charité Berlin, Berlin, Germany
  • 3 Clinical Evaluation Research Unit, Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada
  • 4 Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; Department of Critical Care, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
  • 5 Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT
  • 6 Critical Care Medicine Unit, School of Clinical Medicine, The University of Hong Kong, Adult Intensive Care Unit, Queen Mary Hospital, Hong Kong
  • 7 Clinical and Preventive Nutrition Sciences, Rutgers University, School of Health Professions, New Brunswick, NJ; Foothills Medical Centre, Calgary, AB, Canada
  • 8 Department of Clinical Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH
  • 9 Department of Biobehavioral Health Science, University of Pennsylvania, School of Nursing, Philadelphia, PA. Electronic address: compherc@upenn.edu
Chest, 2024 Jun;165(6):1380-1391.
PMID: 38354904 DOI: 10.1016/j.chest.2024.02.008

Abstract

BACKGROUND: Preexisting malnutrition in critically ill patients is associated with adverse clinical outcomes. Malnutrition can be diagnosed with the Global Leadership Initiative on Malnutrition using parameters such as weight loss, muscle wasting, and BMI. International critical care nutrition guidelines recommend high protein treatment to improve clinical outcomes in critically ill patients diagnosed with preexisting malnutrition. However, this recommendation is based on expert opinion.

RESEARCH QUESTION: In critically ill patients, what is the association between preexisting malnutrition and time to discharge alive (TTDA), and does high protein treatment modify this association?

STUDY DESIGN AND METHODS: This multicenter randomized controlled trial involving 16 countries was designed to investigate the effects of high vs usual protein treatment in 1,301 critically ill patients. The primary outcome was TTDA. Multivariable regression was used to identify if preexisting malnutrition was associated with TTDA and if protein delivery modified their association.

RESULTS: The prevalence of preexisting malnutrition was 43.8%, and the cumulative incidence of live hospital discharge by day 60 was 41.2% vs 52.9% in the groups with and without preexisting malnutrition, respectively. The average protein delivery in the high vs usual treatment groups was 1.6 g/kg per day vs 0.9 g/kg per day. Preexisting malnutrition was independently associated with slower TTDA (adjusted hazard ratio, 0.81; 95% CI, 0.67-0.98). However, high protein treatment in patients with and without preexisting malnutrition was not associated with TTDA (adjusted hazard ratios of 0.84 [95% CI, 0.63-1.11] and 0.97 [95% CI, 0.77-1.21]). Furthermore, no effect modification was observed (ratio of adjusted hazard ratio, 0.84; 95% CI, 0.58-1.20).

INTERPRETATION: Malnutrition was associated with slower TTDA, but high protein treatment did not modify the association. These findings challenge current international critical care nutrition guidelines.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03160547; URL: www.

CLINICALTRIALS: gov.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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