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Critical Care Medicine:
doi: 10.1097/01.CCM.0000128579.84228.2A
Laboratory Investigations

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

Taniguchi, Takumi MD; Kidani, Yoko MD; Kanakura, Hiroko MD; Takemoto, Yasuhiko MD; Yamamoto, Ken MD

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Abstract

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 Escherichia 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 μg·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 μg·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-α and interleukin-6) concentrations and infiltration of neutrophils in the airspace or vessel walls of the lungs were less in the dexme-detomidine-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.

© 2004 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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