antioxidants Article Oxidative Stress in ICU Patients: ROS as Mortality Long-Term Predictor Juan Carlos Ayala 1, * , Adriana Grismaldo 2 , Luis Gonzalo Sequeda-Castañeda 3 , Andrés Felipe Aristizábal-Pachón 2 and Ludis Morales 2, *   Citation: Ayala, J.C.; Grismaldo, A.; Sequeda-Castañeda, L.G.; Aristizábal-Pachón, A.F.; Morales, L. Oxidative Stress in ICU Patients: ROS as Mortality Long-Term Predictor. Antioxidants 2021, 10, 1912. https:// doi.org/10.3390/antiox10121912 Academic Editor: Steven P. Gieseg Received: 5 October 2021 Accepted: 22 November 2021 Published: 29 November 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá 110231, Colombia 2 Department of Nutrition and Biochemistry, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá 110231, Colombia; mgrismaldo@javeriana.edu.co (A.G.); andres_aristizabal@javeriana.edu.co (A.F.A.-P.) 3 Department of Chemistry, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá 110231, Colombia; lsequeda@javeriana.edu.co * Correspondence: jayalaacosta@gmail.com (J.C.A.); ludis.morales@javeriana.edu.co (L.M.) Abstract: Lipid peroxidation, protein oxidation, and mutations in mitochondrial DNA generate reactive oxygen species (ROS) that are involved in cell death and inflammatory response syndrome. ROS can also act as a signal in the intracellular pathways involved in normal cell growth and homeostasis, as well as in response to metabolic adaptations, autophagy, immunity, differentiation and cell aging, the latter of which is an important characteristic in acute and chronic pathologies. Thus, the measurement of ROS levels of critically ill patients, upon admission, enables a prediction not only of the severity of the inflammatory response, but also of its subsequent potential outcome. The aim of this study was to measure the levels of mitochondrial ROS (superoxide anion) in the peripheral blood lymphocytes within 24 h of admission and correlate them with survival at one year after ICU and hospital discharge. We designed an observational prospective study in 51 critical care patients, in which clinical variables and ROS production were identified and correlated with mortality at 12 months post-ICU hospitalization. Oxidative stress levels, measured as DHE fluorescence, show a positive correlation with increased long-term mortality. In ICU patients the major determinant of survival is oxidative stress, which determines inflammation and outlines the cellular response to inflammatory stimuli. Keywords: reactive oxygen species; critically ill; sepsis; survival 1. Introduction Sepsis is well known as the leading cause of mortality in intensive care units (ICU) [1]. Sepsis is defined as a life-threatening condition associated with generalized organic damage due to the dysregulated immune response of the patient [2,3]. The pathogenesis is still not fully understood, however, there are two fundamental conditions within the inflammatory response: the inability of the cell to consume oxygen and the excessive production of oxidants [4], the latter being the cornerstone of the pathogenesis of the sepsis condition. ROS are a set of unstable molecules, produced by all cells, which include hydrogen peroxide (H 2 O 2 ), hydroxyl radical (•OH), singlet oxygen ( 1 O 2 ) and superoxide O − 2 . These molecules are involved in deoxyribonucleotide formation, prostaglandin production, and oxidation, carboxylation, and hydroxylation reactions that are essential for cell function [5]. ROS also participate in the defense of the host against microbial infections, in the regulation of vascular tone and cell adhesion reactions, and act as sensors for oxygen concentration [6]; in inflammation, ROS production is enhanced to act not only as inflammatory mediators but, more importantly, as regulators of cell signaling [7], promoting cell proliferation and cell survival or cell death. Oxidative stress is the imbalance between the effectiveness of antioxidant defense and the rate of ROS generation, which causes an excess of oxidants within cells to an extant Antioxidants 2021, 10, 1912. https://doi.org/10.3390/antiox10121912 https://www.mdpi.com/journal/antioxidants