Comparison of the Therapeutic Effects of Antibiotic, Steroid, and Vitamin K during Early Sepsis in Laboratory Animals

Abstract

The use of corticosteroids alone or with antibiotics in the treatment of sepsis is still a subject of conflict. Besides, coagulation abnormalities in sepsis ranging from bleeding to microvascular thrombosis are needed to be evaluated with respect to Vitamin K (Vit K) dependence. The effects of antibiotic, steroid and Vit K on severe sepsis were investigated to compare therapeutic outcomes in this study. Cecal-ligation-puncture (CLP) was induced by abdominal surgery in rats to produce septic peritonitis. Rats were divided into 7 groups including 12 rats each. Groups were Sham, CLP, CLP+IM (imipenem), CLP+MP (methylprednisolone), CLP+VK (vitamin K 3 , menadione), CLP+IM+MP and CLP+IM+VK. Six animals from each group were sacrificed to obtain samples at the 16 th h. The remaining ones were observed to record survival times. The highest increases in serum TNF-α, IL-1β and IL-6 levels were observed in Group CLP and CLP+VK. Cytokines did not significantly increase in Group CLP+IM+MP. The platelet count decreased in Group CLP and CLP+MP (P<0.05). Imipenem, methylprednisolone and Vit K lead to change for coagulation times in a different manner. No animal survived in the groups CLP, CLP+MP and CLP+VK while 66.7% of them survived in the groups CLP+IM and CLP+IM+MP. Methylprednisolone increased the survival time. Antibiotics have a major protective effect in early stage and steroids may improve this effect. Interestingly, the adjunctive use of Vit K to antibiotic or to steroid deteriorated the protective effects of these drugs. These results suggest that therapeutics should be cautiously used to combat with coagulopathy during sepsis.