Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats

• Published in: Journal of anesthesia 2008, Vol.22 (3), p.221-228
• Main Authors: Taniguchi, Takumi, Kurita, Akihide, Kobayashi, Kyoko, Yamamoto, Ken, Inaba, Hideo
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Anesthesiology; Animals; Blood Gas Analysis; Blood Pressure - drug effects; Critical Care Medicine; Dexmedetomidine - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Emergency Medicine; Heart Rate - drug effects; Inflammation - drug therapy; Intensive; Interleukin-6 - blood; Interleukin-6 - metabolism; Male; Medicine; Medicine & Public Health; Original Article; Pain Medicine; Random Allocation; Rats; Rats, Wistar; Shock, Septic - drug therapy; Shock, Septic - mortality; Survival Rate; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha - blood
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-008-0611-9

Purpose Our previous study demonstrated that dexmedetomidine drastically reduced mortality and inhibited the inflammatory response during endotoxemia in rats. The aim of this study was to clarify the dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxemia in rats. Methods Male Wistar rats ( n = 96) were anesthetized intraperitoneally with pentobarbital sodium and assigned to one of two protocols: one representing the dose-related effects of dexmedetomidine, and the other, the time-related effects of dexmedetomidine. To evaluate the dose-related effects, the animals were randomly assigned to one of four groups ( n = 15 each): endotoxemic group (group E), receiving intravenous Escherichia coli endotoxin (15 mg·kg −1 over 2 min); small-dose group (group S), treated with a small dose of dexmedetomidine (2.5 μg·kg −1 ·h −1 , IV); medium-dose group (group M), treated with a medium dose (5 μg·kg −1 ·h −1 , IV); and large-dose group (group L), treated with a large dose (10 μg·kg −1 ·h −1 , IV). To evaluate the time-related effects, the animals were randomly assigned to one of three groups ( n = 12 per group): endotoxemic group; early posttreatment group, treated with 10 μg·kg −1 ·h −1 dexmedetomidine at 1 h after endotoxin injection; and late posttreatment group, treated with 10 μg·kg −1 ·h −1 at 2 h after endotoxin injection. Hemodynamics and arterial blood gases were recorded and plasma cytokine concentrations were measured throughout the observation period. The mortality rate was assessed up to 8 h after endotoxin injection. Results In the dose-related study, the mortality rates at 8 h after endotoxin injection were 81%, 26%, 32%, and 20% for groups E, S, M, and L, respectively. Plasma tumor necrosis factor-alpha (TNF) concentrations were lower in groups M and L than in group E at 2 h after endotoxin injection. Plasma interleukin-6 (IL-6) concentrations were lower in groups M and L than in group E at 4 and 5 h after endotoxin injection. In the time-related study, the mortality rates at 8 h after the endotoxin injection were 83%, 33%, and 58% for the endotoxemic, early posttreatment, and late posttreatment groups, respectively. The TNF concentration was lower in the early posttreatment group than in the endotoxemic group at 2 h after endotoxin injection, and the IL-6 concentration was lower in the early posttreatment group than in the endotoxemic group at 5 h after endotoxin injection. Conclusion Dexmedetomidine d