Polymyxin B protects horses against induced endotoxaemia in vivo.
BACKGROUND
A safe, affordable and effective treatment for endotoxaemia in horses is needed in order to reduce the incidence of this potentially fatal condition.


OBJECTIVE
To evaluate the effect of polymyxin B (PMB) on signs of experimentally-induced endotoxaemia.


OBJECTIVE
PMB ameliorates the adverse effects of endotoxaemia without causing nephrotoxicity.


METHODS
Four groups of 6 healthy mature horses each received 20 ng endotoxin/kg bwt i.v. over 30 mins. Additionally, each group received one of the following i.v.; 5000 u PMB/kg bwt 30 mins before endotoxin infusion; 5000 u PMB/kg bwt 30 mins after endotoxin infusion; 1000 u PMB/kg bwt 30 mins prior to endotoxin infusion; or saline. Clinical response data and samples were collected to determine neutrophil count, serum tumour necrosis factor (TNF) activity, plasma thromboxane B2 concentration and urine gamma glutamyltranspeptidase (GGT) to creatinine ratio.


RESULTS
Treatment with PMB before or after administration of endotoxin significantly reduced fever, tachycardia and serum TNF, compared to horses receiving saline. The differences in response to endotoxin were greatest between horses that received saline vs. those that received 5000 u PMB/kg bwt prior to endotoxin. Urine GGT:creatinine did not change significantly.


CONCLUSIONS
This study indicates that PMB may be a safe and effective treatment of endotoxaemia, even when administered after onset. Although nephrotoxicity was not demonstrated with this model, caution should be exercised when using PMB in azotaemic patients.
Barton
M H
MH
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA.
Parviainen
A
A
Norton
N
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D004731:Endotoxins / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006734:Horse Diseases / Q000097:blood / Q000188:drug therapy*; D006736:Horses; D011112:Polymyxin B / Q000627:therapeutic use*; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B