Association between augmented enteral protein and muscle mass attenuation in critically ill patients: A sub‐study of a cluster randomized crossover trial

Background Critically ill patients experience muscle wasting, impacting recovery. The associations between augmented enteral protein and muscle mass, strength, physical function, and quality of life are uncertain. Methods We performed a sub‐study in adult TARGET Protein participants from two sites between 23/11/2022‐23/05/2023. Our exposure of interest was enteral formula with augmented protein (100 g protein/L) and comparator usual protein formula (63 g protein/L), which were isocaloric. Our primary outcome was the change in quadriceps muscle layer thickness from Days 1 to 7, determined by ultrasonography and compared between groups. Our secondary outcomes were group differences in handgrip strength, change in physical function, and quality of life. Data are numbers (%), mean (standard deviation), and differences with 95% confidence intervals (CI). Results Seventy‐two patients were included (augmented protein n = 46, 61 (16)y, 65% male; usual protein n = 26, 56 (16)y, 46% male), 56 had primary outcome data (augmented protein n = 35; usual protein n = 21). Delivered protein was higher with augmented protein (1.2 (0.4) vs 0.8 (0.3) g/kg/day). Quadriceps muscle layer thickness decreased in both groups, with change from Days 1 to 7 similar (0.01 cm; 95% CI, −0.27, 0.28; P = 0.970). Left handgrip strength at ICU discharge and quality of life at Day 90 were similar. Augmented protein was associated with greater right handgrip strength at ICU discharge (6.23; 95% CI, 0.67, 11.79) and was associated with greater decline in physical function at ICU discharge (−15.00; 95% CI, −19.75, −10.25), but not at Day 90. Conclusion No clear difference was detected in quadriceps muscle layer attenuation over 7 days between augmented enteral protein and usual protein. Trial Registration Australian New Zealand Clinical Trials Registry identifier: ACTRN12622001465741.