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

Objective: To determine antioxidant vitamin concentrations, lipid pero xidation, and an index of nitric oxide production in patients in the i ntensive care unit (ICU) with septic shock and relate the findings to the presence of secondary organ failure. Design: A prospective, observ ational study. Setting: A nine-bed ICU in a University teaching hospit al. 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) sh ock (systolic pressure <90 mm Hg) or receiving inotropes. Fourteen pat ients also had secondary organ dysfunction, Interventions: None. Measu rements and Main Results: Antioxidant vitamin concentrations were sign ificantly lower in the patients than the reference range obtained from a comparable group of healthy controls, The mean plasma retinol (vita min 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%) pat ients had retinol values below the lower limit of our reference range (<37.0 mu g/dL). Tocopherol (vitamin E) plasma concentrations were bel ow 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 subject s (p < .001), Plasma beta carotene and lycopene concentrations were un detectable (<15 mu g/L) in eight (50%) patients, and below our referen ce range (<101 mu g/L and <154 mu g/L, respectively) in the remaining patients. In the five patients with three or more dysfunctional second ary organs, plasma thiobarbituric acid-reactive substances were signif icantly increased (p < .05), suggesting increased lipid peroxidation. Concentrations of thiobarbituric acid-reactive substances correlated n egatively 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 increas ed similar to 400-fold (p < .001), Conclusions: These data indicate de creased antioxidant status in the face of enhanced free radical activi ty, and suggest potential therapeutic strategies involving antioxidant repletion.