Real-Time Energy Exposure Is Associated With Increased Oxidative Stress Among Feeding-Tolerant Critically Ill Patients: Results From the FEDOX Trial

Background: Prospective randomized controlled trials (PRCTs) that found harm in patients receiving higher levels of energy exposure have been largely ignored, in part because of the lack of a known mechanism of harm.

Objective: The current 7-day pilot study is a PRCT and post hoc analysis designed to explore the relationship between energy exposure and oxidative stress (as plasma total F2-isoprostanes) in mechanically ventilated intensive care unit patients with systemic inflammatory response syndrome.

Methods: Thirty-five participants were randomized to receive either 100% or 40% of their estimated energy needs. Our intent-to-treat model found no differences in F2-isoprostanes between groups. A post hoc analysis revealed that on days when participants were in the highest tertile of daily kcal/kg, the real-time energy flow rate within 2 hours of the blood draw was predictive of increased oxidative stress. On these days, participants in the second or third vs the first tertile of real-time energy flow rate experienced a 41.8% (P = .006) or 26.5% (P = .001) increase in F2-isoprostane levels, respectively. This was confirmed through a within-group subanalysis restricted to participants with measurements on both sides of the median of real-time energy flow rate that found a 28.2% F2-isoprostane increase on days in the upper vs lower median of flow rate (P = .002).

Conclusion: The benefits of feeding may be more nuanced than previously suspected. Our findings imply a potential mechanism of harm in meeting the current recommendations for nutrition support in the critically ill that warrants further investigation.