Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats

Objectives: The aim of this study was to document the effects of a new sedative agent, dexmedetomidine, on the mortality rate and inflammatory responses to endotoxin-induced shock in rats. Design: Randomized laboratory study. Setting: University experimental laboratory. Subjects: Fifty-seven male rats. Interventions: The animals were randomly assigned to one of four groups. The endotoxemic group (n = 16) received intravenous Escherchia coli endotoxin (15 mg/kg over 2 mins). The saline control group (n = 10) was given saline alone. The dexmedetomidine alone group (n = 15) was treated identically to the control group but also received dexmedetomidine (infusion at 5 mug.kg(-1).hr(-1)) immediately after the injection of 0.9% saline. The dexmedetomidine-endotoxin group (n = 16) was treated identically to the endotoxemic group with the additional administration of dexmedetomidine (infusion at 5 mug.kg(-1).hr(-1)) immediately after endotoxin injection. Measurements and Main Results: Hemodynamics and arterial blood gases were recorded and plasma cytokine concentrations measured during the observation. The mortality rate was assessed up to 8 hrs after endotoxin or saline injection. In addition, microscopic findings of lung tissue for each group were obtained at necropsy. Mortality rates 8 hrs after endotoxin injection were 94%, 10%, 0%, and 44% for the endotoxemic, saline control, dexmedetomidine alone, and dexmedetomidine-endotoxin groups, respectively. Hypotension and increases in plasma cytokine (tumor necrosis factor-alpha and interieukin-6) concentrations and infiltration of neutrophils in the airspace or vessel walls of the lungs were less in the dexmedetomidine-endotoxin group than in the endotoxemic group. Conclusions: 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.