Ketamine inhibits endotoxin-induced shock in rats.
BACKGROUND
Cytokines and nitric oxide are believed to participate importantly in the pathogenesis of endotoxin-induced shock. Several investigators have documented that ketamine attenuates production of cytokines and nitric oxide in endotoxemia, but little is known concerning hemodynamic effects of the drug in this state. The objective of the current study was to assess the potential modifying effects of ketamine in endotoxemia.


METHODS
The authors randomly assigned 40 rats to one of four equal groups: endotoxin alone, receiving Escherichia coli endotoxin (15 mg/kg, administered intravenously); saline control, receiving saline only; ketamine alone, receiving ketamine (10 mg x kg(-1) x h(-1), administered intravenously); pretreatment, with ketamine administration initiated before the endotoxin exposure; and posttreatment, with ketamine initiated 2 h after endotoxin. During the 5 h after endotoxin injection, hemodynamics, acid-base status, and plasma concentrations of tumor necrosis factor alpha and interleukin 6 were assessed in each group.


RESULTS
Endotoxin injection produced progressive hypotension, metabolic acidosis, and a large increase in the plasma cytokine concentrations. This hemodynamic and cytokine responses to endotoxin were completely abolished in the pretreatment group and modestly suppressed in the posttreatment group. in the absence of endotoxin, ketamine did not modify these responses.


CONCLUSIONS
Ketamine administration inhibited hypotension, metabolic acidosis, and cytokine responses in rats injected with endotoxin. The results suggest that judicious use of ketamine as an anesthetic agent may offer advantages in endotoxemia.
Taniguchi
T
T
Department of Emergency and Critical Care Medicine, School of Medicine, Kanazawa University, Japan. taniyan@med.kanazawa-u.ac.jp
Shibata
K
K
Yamamoto
K
K
D000818:Animals; D001784:Blood Gas Analysis; D004731:Endotoxins; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004731:Endotoxins; D018691:Excitatory Amino Acid Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D007649:Ketamine