Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of endotoxemia
Journal of Feline Medicine & Surgery,
In Press, Corrected Proof
, Available online 13 February 2010

Claire R. Sharp, Amy E. DeClue, Carol E. Haak, Allison R. Honaker, Carol R. Reinero

Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. We investigated the anti-endotoxin effects of polymyxin B (PMB) in a blinded, placebo controlled fashion, both ex vivo in a feline whole blood culture system and in vivo, using a low-dose endotoxin infusion in cats. Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Ex vivo, PMB significantly decreased lipopolysaccharide-induced tumor necrosis factor (TNF) production from whole blood. PMB (1 mg/kg over 30 min) demonstrated anti-endotoxin effects in vivo, including decreased peak plasma TNF activity (P < 0.001) and increased white blood cell count (P = 0.019), with no adverse effects. Given the apparent safety and anti-endotoxin effects of PMB in this endotoxemia model, a carefully designed, randomized, blinded, placebo controlled clinical trial evaluating the use of PMB in naturally occurring Gram-negative feline sepsis should be considered.
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