Body composition-guided protein dosing in critically ill patients: a before-and-after study (PROGRESS-ICU).

backgroundTo compare whether fat-free mass (FFM)-adjusted protein dosing is associated with different clinical and metabolic outcomes compared with total body weight (TBW)-based dosing in critically ill patients in the intensive care unit (ICU).

methodsAdult ICU patients (April 2020-October 2025) with serial bioelectrical impedance analysis were included in the PROGRESS-ICU observational cohort study. Patients received either TBW-based protein dosing (1.5 g/kg/day; April 2020-June 2023) or FFM-based dosing after protocol revision (1.85 g/kg/day dry FFM, corrected for fluid overload; July 2023 onward). The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, ICU and hospital length of stay, invasive mechanical ventilation (IMV) duration, and longitudinal changes in FFM and urea-to-creatinine ratio (UCR). Survival was analysed using multivariable Cox regression and inverse probability of treatment weighting; longitudinal outcomes were assessed using mixed-effects models.

resultsAmong 620 patients (310 per cohort), median age was 69 years, and ~ 60% were male. Notable baseline differences included a higher proportion of COVID-19 admissions in the TBW cohort (40% vs. 1%), which may have influenced outcomes. Ninety-day mortality did not differ significantly between groups (adjusted hazard ratio [HR] 0.78, 95% CI 0.56-1.09). FFM-based dosing was associated with shorter ICU stay (HR 0.79, 95% CI 0.69-0.91) and fewer IMV days (HR 0.79, 95% CI 0.65-0.96); hospital length of stay was similar (HR 0.86, 95% CI 0.67-1.10). TBW-based dosing was associated with higher UCR trajectories and greater FFM loss. These associations should be interpreted cautiously due to the observational design, substantial baseline imbalances, and potential residual confounding.

conclusionsIn this observational before-after study, FFM-based protein dosing was not associated with differences in mortality compared with TBW-based dosing. Associations with ICU stay, IMV duration, and metabolic markers were observed but may reflect residual confounding and temporal changes. The study was underpowered to detect modest differences in mortality, and confidence intervals include the possibility of clinically relevant benefit or harm. These findings are exploratory and require confirmation in adequately powered randomised controlled trials.

trial registrationThe study was approved by the local ethics committee (protocol number 2403-017; 11 April 2024) and registered prior to data analysis on ClinicalTrials.gov (NCT07312708; 5 December 2025), the Open Science Framework ( https://doi.org/10.17605/OSF.IO/3SU49 ; 4 December 2025), and the Dutch Central Committee on Research Involving Human Subjects (NL-010953; 26 October 2025). Patients admitted before ethics approval were retrospectively included under a waiver of informed consent, and from April 2024 an opt-out consent procedure was implemented for all new admissions. Data were collected as part of routine clinical care. The study protocol, including prespecified analyses, was finalised and registered before the research team accessed the data.