Association between protein dose in the early and late acute phases of critical illness and time-to-discharge-alive: A secondary analysis of a randomized clinical trial.

backgroundResearch has sought to identify optimal protein doses during acute phases of critical illness to optimize outcomes.

methodsA secondary analysis of the EFFORT Protein trial, which compared high vs usual protein (N = 1301). Only participants with 8 evaluable days of protein intake were included in our analysis. Mean protein intake was categorized as low (<0.8), medium (0.8-1.3), or high (>1.3 g/kg/day). Acute illness phases were define as early (days 1-4) and late (days 5-8). Participants were grouped by protein dose received in each phase. Based on prior evidence, early phase medium protein/late phase high protein served as the referent. The primary outcome was time-to-discharge-alive; secondary outcomes included 60-day mortality and discharge home.

resultsWe identified 819 participants (median [IQR] age 59.0 [46.0, 69.0] years; 60% male). Time-to-discharge-alive did not differ significantly across groups (P = 0.19). The early low/late high-protein and early high/late high-protein groups had hazard ratios of 0.63 (95% CI, 0.35-1.11) and 0.70 (95% CI, 0.46-1.06), respectively. Mortality and discharge-home rates did not differ significantly across protein dose/acute phase groups (P = 0.85 and 0.65, respectively).

conclusionWe hypothesized that early medium and late high protein would improve outcomes; however, no significant differences between were observed across protein dose/acute phase groups. These findings are hypothesis-generating and highlight the need for future research to identify biomarkers or scoring tools that better define phase transitions in critical illness, enabling more precise nutrition strategies. TRIAL REGISTRATION (PRIMARY): NCT03160547.