Markers of oxidative damage, antioxidant status and clinical outcome in critically ill patients

Abstract

Oxidative stress is a consequence of critical illness, and may have an impact on survival. We studied markers of oxidative damage and antioxidant (AO) protection and compared them with clinical scores and outcome. Blood sampling and clinical scoring was carried out on 60 consecutively admitted intensive therapy unit (ITU) patients within 24 h of admission and then every three days of ITU stay. The patients included 30 surgical and 30 medical patients, of whom 46 survived their stay in ITU. Clinical scoring was by Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ dysfunction (MOD) score and sepsis rating. Oxidative damage was assessed by measurement of plasma malondialdehyde (MDA) and F2 isoprostanes (F2 IsoPs). AO protection was assessed by measurement of plasma total AO status, AO gap, ascorbic acid and the enzymes glutathione peroxidase and superoxide dismutase. Both clinical markers, APACHE II and MOD, and oxidative damage markers MDA and F2 IsoPs were significantly higher in non-survivors (NS) than in survivors (S) at the time of admission. Median (interquartile ranges) were (APACHE II), 14[12--17] (S), 20.5[16.7--22.2] (NS),P<0.0001; (MOD), 3.0[2.0--5.0] (S), 8.0[4.7--9.2] (NS), P<0.0005; (MDA, mumol/L), 0.22[0.19--0.27] (S), 0.25[0.20--0.34] (NS), P=0.04 and (F2 IsoPs, pg/mL), 9.7[6.0--9.9] (S), 11.0[9.0--12.0] (NS), P=0.01. Oxidative damage markers reduced (improved) in the survivors but increased in the non-survivors. There was little difference between the groups in AO protection markers. There was a significant positive correlation between MOD and markers of oxidative damage at the time of admission (r=0.40, P=0.003, F2 IsoPs; r=0.28, P=0.035, MDA) and between the oxidative damage markers themselves (r=0.32, P=0.017). Increased oxidative stress is associated with poor outcome in critically ill patients, and may be a prognostic indicator. Oxidative damage markers are more useful than AO protection markers in predicting outcome.