Critically ill septic patients have elevated oxidative stress biomarkers: lack of attenuation by parenteral vitamin C

Abstract

Patients with septic shock are under an intense inflammatory burden, which is closely associated with increased oxidative stress and depletion of antioxidants such as vitamin C. We hypothesized that patients with septic shock would present with elevated oxidative stress (assessed as F2-isoprostanes) and that administration of parenteral vitamin C to these patients would attenuate F2-isoprostane concentrations. We recruited 40 critically ill patients with septic shock into a randomized placebo-controlled trial and assessed the effect of short-term (4-day) parenteral vitamin C administration (100 mg/kg/d) on 8-isoprostane F2α concentrations, which were measured using enzyme-linked immunosorbent assays. Sources of sepsis and intensive care unit severity scores were recorded. Smokers (n = 20) and nonsmoking controls (n = 50) were assessed for comparison. The median baseline 8-isoprostane F2α concentration in the septic patients was 3.95 (interquartile range [Q1, Q3] 2.1, 6.63) ng/mg creatinine; this was higher than smokers 1.61 [1.25, 2.82] P = .007 ng/mg creatinine; P = .005) and nonsmoking controls 1.12 [0.76, 1.57] ng/mg creatinine; P < .0001). The 8-isoprostane F2α concentrations in the placebo group did not vary significantly over the duration of the study. Although parenteral vitamin C administration significantly increased the vitamin C status of the patients within 24 hours, this did not affect their 8-isoprostane F2α concentrations. In conclusion, patients with septic shock have elevated 8-isoprostane F2α excretion, which short-term parenteral vitamin C administration is unable to attenuate. If vitamin C is to work by antioxidant mechanisms, then early administration, before the development of shock, may be required.This trial was registered at anzctr.org.au (ACTRN12617001184369).