Sustained high serum malondialdehyde levels are associated with severity and mortality in septic patients

Abstract

IntroductionThere is a hyperoxidative state in sepsis. The objective of this study was to determine serum malondialdehyde (MDA) levels during the first week of follow up, whether such levels are associated with severity during the first week and whether non-surviving patients showed higher MDA levels than survivors during the first week.MethodsWe performed an observational, prospective, multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were measured in 328 patients (215 survivors and 113 non-survivors) with severe sepsis at days one, four and eight of diagnosis, and in 100 healthy controls. The primary endpoint was 30-day mortality and the secondary endpoint was six -month mortality. The association between continuous variables was carried out using Spearman’s rank correlation coefficient. Cox regression analysis was applied to determine the independent contribution of serum MDA levels on the prediction of 30-day and 6-month mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated as measures of the clinical impact of the predictor variables.ResultsWe found higher serum MDA in septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001) of diagnosis than in healthy controls. Serum MDA was lower in surviving than non-surviving septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001). Serum MDA levels were positively correlated with lactic acid and SOFA during the first week. Finally, serum MDA levels were associated with 30-day mortality (HR = 1.05; 95% CI = 1.02-1.09; p = 0.005) and six-month mortality (hazard ratio (HR) = 1.05; 95% CI = 1.02-1.09; p = 0.003) after controlling for lactic acid levels, acute physiology and chronic health evaluation (APACHE)-II, diabetes mellitus, bloodstream infection and chronic renal failure.ConclusionsTo our knowledge, this is the largest series providing data on the oxidative state in septic patients to date. The novel finding is that high serum MDA levels sustained throughout the first week of follow up were associated with severity and mortality in septic patients.

Red Blood Cell Distribution Width during the First Week Is Associated with Severity and Mortality in Septic Patients

“…In addition, an association between oxidative state and mortality has been found in septic patients [28]–[30]. We here report for the first time an association between RDW and serum MDA levels during the first week of ICU stay in septic patients.…”

Protective Effects of Antioxidant Peptide SS-31 Against Multiple Organ Dysfunctions During Endotoxemia

“…Oxidative stress induces peroxidation of membrane lipids, affecting the biological properties of the cellular membrane and impairing normal cellular function [5,6]. In support with this hypothesis, it has been suggested that non-surviving septic patients showed higher serum MDA levels, which serve as a marker of lipid oxidative damage than surviving ones [19], while N-acetylcysteine, vitamins, and statins exert antioxidant capacity to show beneficial effects in sepsis [20][21][22]. In the present study, the presence of high ROS, MDA levels, and inflammatory mediators support the notion that increased oxidative stress and inflammatory response contributes to sepsis-induced organ dysfunctions.…”

New Prognostic Biomarkers of Mitochondrial Oxidative Stress in Septic Patients

“…In another study by our team on 328 severely septic patients (to our knowledge, the largest series providing data on oxidative stress in septic patients), we reported novel findings as follows: (a) septic patients showed higher MDA serum levels than did healthy controls during the first week post diagnosis, (b) non-survivors exhibited persistently higher serum MDA levels than did survivors during the first week post diagnosis, and (c) there was an association between serum MDA levels and several indicators of severity in sepsis (including lactic acid and the SOFA score) during the first week post diagnosis (20). Previous studies have reported a positive correlation between MDA and severity in septic patients (16)(17)(18).…”