Gram-negative bacteria are the most common cause of sepsis in dogs.1-4 During sepsis with gram-negative bacteria, LPS (ie, endotoxin), the glycolipid component of the cell wall of gram-negative bacteria, is released into the bloodstream. Endotoxin then binds to receptors on inflammatory cells, which leads to activation of NF-κB and results in formation of proinflammatory mediators, such as TNF-α.5 Ultimately, systemic manifestations of endotoxemia (such as fever, tachycardia, and hypotension) develop.
Ketamine is a dissociative anesthetic and competitive antagonist of the NMDA receptor.6 Ketamine has several advantageous qualities, compared with qualities of other anesthetic drugs, including unique cardiostimulatory, analgesic, and immunomodulatory effects. Because ketamine has a positive hemodynamic effect,7 it has been suggested8,9 as an ideal anesthetic for septic or critically ill dogs that require surgery. Additionally, subanesthetic doses of ketamine provide effective analgesia and have been recommended10,11 for the management of postoperative pain in dogs.
The immunomodulating effects of ketamine have been reported for several species.12-16 Ketamine ameliorates NF-κB activation and production of proinflammatory cytokines (such as TNF-α) in mice with experimentally induced endotoxemia.12,13 Furthermore, ketamine can prevent leukocyte-endothelial cell adhesion in rats,16 which may in turn decrease neutrophilic infiltration of tissues and thus decrease tissue damage. Ketamine also prevents endotoxin-induced hypotension and metabolic acidosis and, most importantly, decreases fatalities in rats.14,15
To the authors' knowledge, the potential hemodynamic and immunomodulatory protective effects of ketamine have not been evaluated in dogs. We hypothesized that subanesthetic doses of ketamine would ameliorate the hemodynamic and immunologic perturbations associated with low-grade endotoxemia in dogs. In the study reported here, healthy dogs were administered ketamine and a control solution prior to administration of low-dose endotoxin. Hemodynamic differences between the ketamine and control treatments were evaluated via changes in HR and SAP, whereas immunologic differences were evaluated by means of WBC counts and plasma TNF-α activity.
Nuclear factor-kappa B
Tumor necrosis factor
Systolic arterial blood pressure
Abbott Laboratories, Abbott Park, Ill.
Ketaset, Fort Dodge Animal Health, Fort Dodge, Iowa.
Sigma-Aldrich, St Louis, Mo.
Parks Medical Electronics, Las Vegas, Nev.
Coulter Electronics, Hialeah, Fla.
Fischer Scientific International, Pittsburgh, Pa.
SAS, version 9, SAS Institute Inc, Cary, NC.
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