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

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 F-isoprostanes) and that administration of parenteral vitamin C to these patients would attenuate F-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 F 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 F 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 F 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 F concentrations. In conclusion, patients with septic shock have elevated 8-isoprostane F 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).

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