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

Background Pre-existing 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 body mass index. International critical care nutrition guidelines recommend high protein treatment to improve clinical outcomes in critically ill patients diagnosed with pre-existing malnutrition. However, this recommendation is based on expert opinion. Research Questions In critically ill patients, what is the association between pre-existing malnutrition and time to discharge alive (TTDA), and does high protein treatment modify this association? Study Design and Methods This was a multicenter randomized controlled trial involving 16 countries designed to investigate the effects of high vs. usual protein treatment in 1301 critically ill patients. The primary outcome was TTDA. Multivariable regression was used to identify if pre-existing malnutrition was associated with TTDA, and if protein delivery modified their association. Results The prevalence of pre-existing 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 pre-existing malnutrition, respectively. The average protein delivery in the high vs. usual treatment groups was 1.6 vs. 0.9 g/kg/day. Pre-existing malnutrition was independently associated with slower TTDA (Adj HR 0.81, 95% CI 0.67-0.98). However, high protein treatment in patients with and without pre-existing malnutrition was not associated with TTDA (Adj HR 0.84, 95% CI 0.63-1.11; and 0.97, 95% CI 0.77-1.21, respectively). Furthermore, no effect modification was observed (ratio of Adj HR 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.