Seçkin ÖZKANLAR, Fatih AKÇAY, Zekai HALICI, Muhammet Hamidullah UYANIK

Antibiyotik, Steroid ve Vitamin K’nın Terapötik Etkilerinin Erken Dönem Sepsis Süresince Laboratuvar Hayvanlarında Karşılaştırılması

Sepsisin tedavisinde kortikosteroidlerin tek başına ya da antibiyotiklerle birlikte kullanımları halen anlaşılması güç bir konudur. Ayrıca, sepsiste kanamadan mikrovasküler tromboza kadar değişen koagülasyon anormalliklerinin Vitamin K (Vit K) bağımlılığı yönünden araştırılması gerekmektedir. Bu çalışmada antibiyotik, steroid ve Vit K’nın etkilerinin terapötik sonuçları şiddetli sepsiste araştırılmıştır. Sıçanlarda septik peritonitis oluşturmak için abdominal cerrahi ile çekal-bağlamadelme (CLP) yapıldı. Sıçanlar her grupta 12 sıçan olmak üzere 7 gruba ayrıldı. Gruplar Sham, CLP, CLP+IM (imipenem), CLP+MP (metilprednizolon), CLP+VK (vitamin K3, menadione), CLP+IM+MP ve CLP+IM+VK’dir. Her gruptan 6 hayvan 16’ncı saatte örneklerin elde edilmesi için sakrifiye edildi. Kalan hayvanlar yaşam sürelerinin kaydedilebilmesi için gözlemlendi. TNF-α, IL-1β ve IL-6 değerlerindeki en yüksek artış CLP ve CLP+VK gruplarında görüldü. Sitokinler CLP+IM+MP grubunda önemli derecede artmadı. Trombosit sayısı CLP ve CLP+MP gruplarında azaldı (P<0.05). İmipenem, metilprednizolon ve Vit K koagülasyon sürelerinde farklı tarzlarda değişikliklere neden oldu. CLP, CLP+MP ve CLP+VK gruplarında hiç hayvan yaşamazken CLP+IM ve CLP+IM+MP gruplarında hayvanların %66.7’si yaşadı. Metilprednizolon yaşam sürelerini uzattı. Antibiyotikler erken dönemde önemli koruyucu etkiye sahiptir ve steroidler bu etkiyi arttırmaktadır. İlginç olarak, Vit K’nın antibiyotiğe ya da steroid’e ilave edilmesi bu ilaçların koruyucu etkilerini kötüleştirmektedir. Bu bulgular, sepsis süresince koagülopati ile mücadelede törapötiklerin kullanılmasında dikkatli olunması gerektiğini göstermektedir.

Anahtar Kelimeler:

Imipenem, Menadion, Metilprednizolon, Sepsis, Sitokin

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

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 K3, menadione), CLP+IM+MP and CLP+IM+VK. Six animals from each group were sacrificed to obtain samples at the 16th 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.

Keywords:

Cytokine, Imipenem, Menadione, Methylprednisolone, Sepsis,

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