The Association of Enteral Protein Intake with Outcomes in Trauma ICU Patients

Abstract

Background: Critically ill trauma patients have distinct nutritional requirements due to increased catabolism and metabolic stress. Existing nutrition guidelines provide limited and outdated recommendations on optimal protein intake for this population. Recent studies suggest a potential dose-dependent harm associated with high protein intake in critically ill patients. We conducted a secondary analysis of a randomized clinical trial to investigate the relationship between early protein intake and ventilator-free days (VFDs), and to assess whether blood urea nitrogen (BUN)—a known marker of poor outcomes in ICU patients—mediates this relationship. Methods: This analysis included 329 trauma patients from a single-center randomized trial conducted between 2016 and 2021 at a Level 1 trauma center. The primary exposure was mean protein intake (g/kg/day) over the first week of ICU admission. The primary clinical outcome was VFDs, defined as days alive and free from mechanical ventilation within the first 28 days. Competing risks regression was used to analyze VFDs to calculate the subdistribution hazard of extubation, accounting for death as a competing event. A causal mediation analysis evaluated whether BUN mediated the relationship between protein intake and VFDs. The association between protein intake and secondary outcomes including acute respiratory distress syndrome (ARDS), ventilator-associated pneumonia (VAP), and aspiration were analyzed using logistic regression. Sensitivity analyses were performed for a subgroup of patients receiving ≥8kcal/kg/day. Results: Median patient age was 46 years (IQR: 30–59), 78% were male, and median injury severity score (ISS) was 34 (IQR: 26–43). Median protein intake was 1.6 g/kg/day (IQR: 1.0–2.0). Median VFDs was 14 (IQR 0–20). Each 1 g/kg/day of protein intake in the first week of ICU stay was associated with a significantly lower hazard of extubation (SHR 0.66; 95% CI: 0.53 to 0.81; p<0.001). Secondary outcomes, including ARDS, VAP, and aspiration, showed no significant associations with protein intake. Causal mediation analysis indicated that each additional 1 g/kg/day protein intake resulted in 3.53 fewer VFDs (95% CI: –4.81 to –2.30; p<0.001), with approximately 26% (95% CI: 12.0% to 41.0%) mediated by elevated BUN levels. Conclusions: In critically ill trauma patients, higher enteral protein intake early in ICU admission was associated with a lower hazard of extubation and fewer VFDs, partly due to elevations in BUN. These findings challenge current recommendations advocating high protein supplementation in trauma patients and highlight the need for further trials to define optimal protein dosing strategies tailored specifically to this high-risk population.