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Feeding the Critically Ill During Phases of Altered Redox Status (FEDOX): a Prospective Randomized Trial
thesisposted on 01.02.2019 by William McKeever
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
Background: Increased oxidative stress through altered mitochondrial metabolism is a well-established phenomenon in critical illness. It is biologically feasible that nutrition support exacerbates this process in critically ill patients, contributing to increased systemic oxidative stress. The current study proposed that nutrition support provided at 100% of the National Recommended Guideline levels for energy (100%NRG) during these phases of altered redox status results in increased oxidative stress and may explain the negative outcomes reported in studies that achieved this level of energy exposure. We further proposed that feeding would attenuate low T3 Syndrome and that this may be protective against nutrition-induced oxidative stress. Finally, we explored mitochondrial antioxidant enzyme allele status as a possible modulator of nutrition-induced oxidative stress. We proposed that patients at least heterozygous for the risk alleles of both manganese-superoxide dismutase (MnSOD) and glutathione peroxidase 1(GPx1) would have increased nutrition-induced oxidative stress. Methods: We performed a single center prospective randomized controlled trial to assess the impact of energy intake at 100% NRG(25-30 Kcal/kg) versus 40%NRG(10-12Kcal/kg) on oxidative stress and thyroid parameters in mechanically ventilated patients with systemic inflammatory response syndrome(SIRS). The study was conducted in the Rush University Medical Center’s Neurosurgical and Medical ICUs. Blood was drawn twice daily. Total plasma F2-isoprostanes and Total T3 were obtained. Patient DNA was also sequenced to assess for allele status of GPx1 and MnSOD. Patients were followed for 7 days or until ICU discharge or death. Results: In all, 35 patients were successfully recruited. The primary findings of this study were that (1) critically ill SIRS patients with higher daily calorie exposure had increased oxidative stress at higher levels of real-time calorie exposure. (2) Daily calorie exposure caused elevation of total T3. (3) Patients with higher levels of T3 had increased oxidative stress in the higher but not the lower-fed group. (4) Being at least heterozygous for the risk alleles of MnSOD and GPx1 was associated with a significant increase in oxidative stress, but (5) was only the case for participants in the upper median of daily calorie exposure. Conclusion: Nutrition-induced oxidative stress represents a viable mechanism of harm in feeding the critically ill and causes elevations in total T3.