Effects of posttreatment with propofol on mortality and cytokine responses to endotoxin-induced shock in rats

Objective: To clarify the effects of posttreatment with propofol administration on mortality rate and cytokine responses to endotoxin-induced shock in rats. Design: Randomized prospective laboratory study. Setting: University laboratory. Subjects. Thirty-three male rats. Interventions: Animals were randomly assigned to one of three groups (n = 11 per group): a) endotoxemic group, receiving intravenous Escherichia coli endotoxin (20 mg/kg over 2 mins); b) early posttreatment group, treated identically to the endotoxemic group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg(.)kg(-1.)hr(-1)) 1 hr after the injection of endotoxin; and c) late posttreatment group, treated identically to the endotoxemic group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg(.)kg(-1.)hr(-1)) 2 hrs after the injection of endotoxin. Measurements and Main Results. Hemodynamics and arterial blood gases were recorded, and mortality rate and plasma cytokine concentrations were calculated for the 5-hr observation. The mortality rate 5 hrs after endotoxin injection was 73% for the endotoxic, 9% for the early posttreatment, and 36% for the late posttreatment groups. The mortality rate for the early posttreatment group was significantly lower than that for the other groups. The increases in plasma cytokine (tumor necrosis factor-a and interleukin-6 and -10) concentrations were less for the early posttreatment group than the other two groups. Conclusions. The early posttreatment of propofol after endotoxin injection drastically reduced the mortality rate of rats and attenuated their cytokine responses. Moreover, propofol attenuated the production of tumor necrosis factor-alpha. These findings suggest that propofol administration may be beneficial during sepsis.