Dexmedetomidine reduced mortality rate and had an inhibitory effect on inflammatory response during endotoxemia. These findings suggest that dexmedetomidine administration may inhibit the inflammatory response.

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.

In our previous study, ketamine administration was found to inhibit hypotension, metabolic acidosis, and cytokine responses in endotoxemia. However, only a few studies have indicated whether ketamine has the dose-related beneficial effects after endotoxin injection. Our objective was to clarify the dose-related effects of ketamine on mortality and cytokine responses to endotoxemia in rats. Sixty-five rats were divided at random among five equal groups: Group C was given saline alone. Group E was given endotoxin alone (Escherichia coli endotoxin; 10 mg/kg, IV). Group L received a a low dose of ketamine (5 mg.kg(-1).h(-1), IV), Group M a medium dose of ketamine (10 mg.kg(-1).h(-1), IV), and Group H a high dose of ketamine (20 mg.kg(-1).h(-1), IV), all exposure to endotoxin. After endotoxin injection, hemodynamics, acid-base status, mortality rate, and plasma concentrations of tumor necrosis factor alpha and interleukin 6 were assessed for each of the five groups. Endotoxin injection produced progressive hypotension, metabolic acidosis, and a large increase in plasma cytokine concentrations. Mortality rates 8 h after endotoxin injection were 0% for group C, 92% for group E, 48% for group L, 0% for group M, and 32% for group H. Ketamine administration thus clearly had a beneficial effect on mortality rates, with that for group M lower than for groups L and H (P < 0.05). The cytokine responses to endotoxin were somewhat suppressed in group M but not in group L. Ketamine administration dose-independently inhibited hypotension, metabolic acidosis, and cytokine responses in rats injected with endotoxin.

Our previous study reported that the change in the ratio of interleukin (IL)-6 to IL-10 influences the severity of sepsis in patients with systemic inflammatory response syndrome. We evaluated the change in the ratio of IL-6 to IL-10 after administration of ketamine or propofol in endotoxin-exposed rats in order to evaluate the relationship of pro-inflammatory and anti-inflammatory cytokines following ketamine or propofol administration during endotoxemia. We randomly assigned 40 rats to one of four equal groups: endotoxin alone, receiving Escherichia coli endotoxin (15 mg/kg, i.v.); saline control; ketamine (10 mg x kg(-1) x h(-1), i.v.) before and during exposure to endotoxin; and propofol (10 mg x kg(-1) x h(-1), i.v.) before and during exposure to endotoxin. We measured the plasma concentrations of tumor necrosis factor (TNF)-alpha, IL-6, and IL-10 and calculated the ratio of IL-6 to IL-10 in each group. The current study showed that ketamine and propofol administration attenuated the increase in TNF-alpha, IL-6, and IL-10, and ketamine attenuated the increase in the ratio of IL-6 to IL-10, but propofol increased this ratio in rats receiving a single intravenous bolus of endotoxin. While the mechanisms responsible for the inhibitory effects require further investigation, our results suggest that proper use of ketamine as an anesthetic agent may offer certain advantages in the management of patients with endotoxemia.