The antiendotoxin effects of polymyxin B in a feline model of endotoxemia

Abstract

Introduction: Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. Materials and Methods: We investigated the anti-endotoxin effects of 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 (2ug/kg/hr IV x 4 hours). Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Results: Ex vivo, PMB significantly decreased LPS-induced TNF production from whole blood. In vivo, endotoxin infusion resulted in the development of fever, hypotension, leucopenia and increased TNF activity. Polymyxin B (1mg/kg over 30 minutes) treatment decreased peak plasma TNF activity (p<0.001) and increased white blood cell count (p=0.019), with no adverse effects. Conclusions: Polymyxin B administration resulted in decreased peak plasma TNF activity and increased white blood cell count in this feline model of endotoxemia, 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.