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

Abstract

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

Methods: A 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.

Results: We 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).

Conclusion: We 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.

Keywords: acute phase; critically ill; enteral nutrition; mortality; nutrition support; protein.