The dose-related effects of ketamine on mortality and cytokine responses to endotoxin-induced shock in rats.
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.
Taniguchi
Takumi
T
Departments of *Emergency and Critical Care Medicine and †Anesthesiology and Intensive Care Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Takemoto
Yasuhiro
Y
Kanakura
Hiroko
H
Kidani
Yoko
Y
Yamamoto
Ken
K
D000818:Animals; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine