Plasma-induced endothelial oxidative stress is related to the severity of septic shock

Objective: To estimate the capacity of plasma from septic shock patients to induce in vitro reactive oxygen species (ROS) production by endothelial cells and to analyze whether ROS production is related to the severity of the septic shock. Design. Prospective, observational study. Setting. Medical intensive care unit in a university hospital. Patients. Twenty-one patients with septic shock. Interventions. The in vitro capacity of plasma from septic shock patients to induce ROS production by naive human umbilical vein endothelial cells (HUVEC) was quantified by using a fluorescent probe (2',7'-dichlorodihydrofluorescein diacetate). Measurements and Main Results. Blood samples were collected on day 1, day 3, and day 5 from 21 consecutive septic shock adult patients and from ten healthy volunteers. Patients mean age was 58 yrs old, mean Sequential Organ Failure Assessment (SOFA) score at admission was 12, mean severity illness assessed by Simplified Acute Physiology Score (SAPS) II was 53, and the mortality rate was 47%. In addition to assessment of in vitro ROS generation by HUVEC, oxidative stress in blood was evaluated by measuring lipid peroxidation products and enzymatic and nonenzymatic antioxidants. Septic shock was associated with oxidative stress and an imbalance in antioxidant status. As compared with controls, plasma-induced ROS production by naive HUVEC was significantly higher in septic shock. Moreover ROS production was significantly correlated with SAPS II (p =.028) and SOFA values (p =.0012) and was higher in nonsurvivors than in survivors. In contrast, no correlation was found between the severity of the septic shock and any of the levels of lipid peroxidation products or enzymatic and nonenzymatic antioxidants. Conclusion: Plasma from septic shock patients induces ROS formation by naive HUVEC, and the extent of ROS formation correlates with mortality and with criteria of the severity of septic shock as SOFA score and SAPS II.