Propofol (diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock

Purpose: Human septic shock can be replicated in the endotoxaemic pig. Endotoxaemia causes a multitude of events, including reduced PaO2 and increased lipid peroxidation. This study was designed to evaluate the possible effects of a commonly used anaesthetic drug with known antioxidant properties (propofol) during porcine endotoxaemia. Methods: Ten pigs were anaesthetised and given a 6 h E. coli endotoxin infusion. The animals received, randomly, a supplementary continuous infusion of propofol emulsion (containing 0.005%. EDTA) or the corresponding volume of vehicle (controls). Pathophysiologic responses were deter-mined. Non-enzymatic (by measuring plasma 8-iso-PGF(2 alpha) and enzymatic (by measuring plasma 15-keto-dihydro-PGF(2 alpha)) lipid peroxidations were evaluated. Plasma levels of the endogenous antioxidants alpha- and gamma -tocopherols, were also analysed. Results: Endotoxaemia increased plasma levels of 8-iso-PGF(2 alpha) (1st-4th h) and 15-keto-dihydro-PGF(2 alpha) (1st-4th h) significantly more in controls than in the propofol + endotoxin group. PaO2 was significantly less affected by endotoxin in the propofol treated animals (2nd-4th h). Mean arterial pressure (4th-6th h) and systemic vascular resistance (6th h) were reduced significantly more by endotoxin among the propofol-treated animals. Vitamin E (oc-tocopherol) increased in all animals, significantly more in the propofol + endotoxin group (1-6th h) than in the control group. Conclusions: Propofol reduced endotoxin-induced free radical mediated and cyclooxygenase catalysed lipid peroxidation significantly. The implication is that propofol Counteracts endotoxin-induced deterioration of PaO2 (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.