The FEDOX trial is a prospective randomized clinical trial exploring oxidative stress as a mechanism of harm to explain the negative outcomes found in feeding trials that achieved caloric exposure commensurate with the nationally recommended guidelines. Due to its impact on energy metabolism, we will also explore low T3 syndrome's relationship to this mechanism. Finally, we will explore circadian patterns of diurnal/nocturnal TSH fluctuation as a potential biomarker to indicate this mechanism of harm has subsided.

This 7-day prospective randomized clinical trial is designed to address the following specific aims (SA) in ICU patients (n=40) with systemic inflammatory response syndrome.

SA1) Determine whether provision of enteral nutrition (EN) at 100% of levels in Nationally Recommended Guidelines NRG (25-30 kcals/kg, 100%NRG) early in critical illness increases reactive oxygen species (ROS) production compared to EN at 40% of NRG levels (10-12 kcals/kg, 40%NRG). Subjects will be fasted overnight and randomized to receive either 100% NRG or 40%NRG for 7 days. Plasma F2-isoprostanes will be measured daily and compared between groups through repeated measures analysis.

SA2) Determine if EN at 100%NRG interrupts the critical illness induced low T3 syndrome and subsequently further increases the ROS production compared to 40%NRG. Serum thyroid parameters (T3, T4, rT3, TSH) with be measured daily and compared between groups as above.

Mediation analysis will be used to determine the proportion of the effect of nutrition group on F2-isoprostane production explained by each thyroid parameter.

SA3) Determine if the return of diurnal/noctural fluctuations in TSH is associated with decreased nutrition-induced ROS production. Plasma TSH will be measured twice per day at 0300 and 1800hrs to determine TSH fluctuation. The interaction effect between TSH fluctuation and nutrition group on F2-isoprostane production will be assessed through repeated measures analysis. This study provides vital mechanistic insight into the impact of feeding on oxidative stress during the first week of critical illness, represents an important first step in determining the safest timing and dosage of nutrition support, and sets the foundation for future larger clinical trials on these topics.

Inclusion Criteria:

• Adult patients (>18 years) admitted to RUMC MICU who are able to receive EN, who have two consecutive white blood cell lab values above 12,000/mm^3 or below 4,000/mm^3 plus at least one of the following 3 criteria met for at the past 12 hours will be eligible for participation. Criteria: (1) a respiratory rate greater than 20 breaths per minute or PaCO2 less than 32mmHg, (2) a heart rate greater than 90 beats per minute, or (3) a temperature greater than 100.4F or less than 96.8F.

Exclusion Criteria: Patients will be excluded if the are pregnant, have documented neurologic disease prior to admission that interferes with the capacity to give informed consent or do not require EN for their nutritional care.

Only our lab technicians will be truly blinding to group allocation.