DECREASED ANTIOXIDANT STATUS AND INCREASED LIPID-PEROXIDATION IN PATIENTS WITH SEPTIC SHOCK AND SECONDARY ORGAN DYSFUNCTION

Objective: To determine antioxidant vitamin concentrations, lipid peroxidation, and an index of nitric oxide production in patients in the intensive care unit (ICU) with septic shock and relate the findings to the presence of secondary organ failure. Design: A prospective, observational study. Setting: A nine-bed ICU in a University teaching hospital. Patients: Sixteen consecutive patients with septic shock, defined as: a) clinical evidence of acute infection; b) hypo- or hyperthermia (<35.6 degrees C or >38.3 degrees C); c) tachypnea (>20 breaths/min or being mechanically ventilated); d) tachycardia (>90 beats/min); e) shock (systolic pressure <90 mm Hg) or receiving inotropes. Fourteen patients also had secondary organ dysfunction, Interventions: None. Measurements and Main Results: Antioxidant vitamin concentrations were significantly lower in the patients than the reference range obtained from a comparable group of healthy controls, The mean plasma retinol (vitamin A) concentration was 26.5 +/- 19.3 mu g/dL compared with 73.5 +/- 18.3 mu g/dL in healthy subjects (p < .01). Additionally, 13 (81%) patients had retinol values below the lower limit of our reference range (<37.0 mu g/dL). Tocopherol (vitamin E) plasma concentrations were below the reference range in all patients (<9.0 mg/L), with a mean value of 3.6 +/- 2.0 mg/L compared with 11.5 +/- 1.3 mg/L in healthy subjects (p < .001), Plasma beta carotene and lycopene concentrations were undetectable (<15 mu g/L) in eight (50%) patients, and below our reference range (<101 mu g/L and <154 mu g/L, respectively) in the remaining patients. In the five patients with three or more dysfunctional secondary organs, plasma thiobarbituric acid-reactive substances were significantly increased (p < .05), suggesting increased lipid peroxidation. Concentrations of thiobarbituric acid-reactive substances correlated negatively with both plasma retinol and plasma tocopherol (r(2) = .42, p < .01 and r(2) = .48, p < .005, respectively). In the five patients from whom we were able to collect urine, nitrite excretion was increased similar to 400-fold (p < .001), Conclusions: These data indicate decreased antioxidant status in the face of enhanced free radical activity, and suggest potential therapeutic strategies involving antioxidant repletion.