Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

doi:10.5847/wjem.j.1920-8642.2018.01.009

Abstract

Abstract:

BACKGROUND: Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture (CLP) model in rats.
METHODS: After CLP, 48 Wistar rats were randomly allocated into four groups: (1) CLP group; (2) small-dose treatment group (2.5 μg·kg ^-1·h^-1); (3) medium-dose treatment group (5.0 μg·kg ^-1· h^-1); and (4) large-dose treatment group (10.0 μg·kg ^-1·h^-1). HLA-DR and plasma cytokine (IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure (MAP), heart rate (HR), arterial blood gases, lactate concentrations and mortality were also documented.
RESULTS: The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups (DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels (P_group=0.0202) and increased IL-6 production, which was increased at 3 h (P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR (P<0.001) while maintaining MAP (P_group=0.1238), and remarkably improving lactate (P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively.
CONCLUSION: Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dose-dependently.

Key words: Dexmedetomidine, Immunomodulation, Septic shock

Yan Ma, Xiang-you Yu, Yi Wang. Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats[J]. World Journal of Emergency Medicine, 2018, 9(1): 56-63.

Figures/Tables 5

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