Evaluation of the anti-endotoxic effects of polymyxin-E (colistin) in dogs with naturally occurred endotoxic shock

• Published in: Journal of veterinary pharmacology and therapeutics 2005-02, Vol.28 (1), p.57-63
• Main Author: Senturk, S
• Format: Article
• Language: English
• Subjects: adverse effects; ampicillin; Ampicillin - administration & dosage; Ampicillin - therapeutic use; animal age; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; bacterial infections; Blood Chemical Analysis - veterinary; body temperature; breathing; colistin; Colistin - administration & dosage; Colistin - therapeutic use; combination drug therapy; dehydration (animal physiology); dog breeds; dog diseases; Dog Diseases - blood; Dog Diseases - drug therapy; Dogs; Double-Blind Method; Drug Combinations; drug evaluation; endotoxemia; Female; gender differences; Gram-negative bacteria; heart rate; hematologic tests; Injections, Intramuscular - veterinary; lipopolysaccharides; Male; polymyxin E; septic shock; Shock, Septic - drug therapy; Shock, Septic - veterinary; Treatment Outcome; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/j.1365-2885.2004.00634.x

Endotoxin is a potent stimulator of the inflammatory response and is believed to initiate the pathology in gram-negative sepsis. Agents are being searched for that bind and neutralize or block the effects of endotoxin. The aim was to study the anti-endotoxic effects of polymyxin-E (colistin) in endotoxaemic dogs. The study included a total of 30 endotoxaemic dogs, which were divided into two groups (control = 15; test = 15) of both sexes, different breeds and ages. Hetastarch colloid solution (Expahes,10 mL/kg, i.v.) with lactated Ringer's solution (20 mL/kg, i.v., Q12 h) was given to all dogs. While ampicillin was administered (Alfasilin, 10 mg/kg, i.m., Q12 h) as an antibacterial to the control group, colistin (12 500 IU/kg, i.m., Q12 h) + ampicillin were administered to the test group. The clinical examination (body temperature, pulse and respiration rates, capillary filling times, peripheral pulse qualities, dehydration degrees), hematological and biochemical examinations (WBC, RBC, HGB, HCT, thrombocyte, serum urea, creatinine and TNF-alpha) were performed both before the treatment, and 2, 4, 12 and 24 h after the treatment. In comparison with the control group, it was observed that test group had shorter capillary filling time at 24 h (P < 0.001). Moreover, the degree of dehydration in test group, was significantly improved at 24 h (P < 0.01). While the differences in peripheral pulse qualities significantly differed between 0 and 2 h in controls, at 2, 4, 24 h after treatment it was found to be significantly increased when compared with 0 h in the test group. Serum TNF-alpha concentrations were statistically decreased in the test group between 0 h and other times (P < 0.01). When compared with controls, serum TNF-alpha concentrations were lower at 2, 4, 12 and 24 h in test group (P < 0.05). Results of the study indicated that polymyxin-E (colistin) has an anti-endotoxic effect and is safe for the dogs with endotoxemia at the dosage used in this study.