Methylprednisolone plus ibuprofen increases mortality in septic rats

Steroids and cyclooxygenase inhibitors have been advocated as adjunctive treatment for sepsis. We studied the influences of these treatments on the survival of 98 male Sprague-Dawley rats in which sepsis was induced by cecal ligation and puncture. Rats received one of four treatments: sodium chloride (NaCl); methylprednisolone, 30 mg/kg (MP); ibuprofen, 12.5 mg/kg (I); methylprednisolone, 30 mg/kg, plus ibuprofen, 12.5 mg/kg (MP + I). Cumulative survival statistics were determined daily for 14 days thereafter. Survival was not altered by either MP or I when compared to animals receiving NaCl only. However, the combination of MP + I increased mortality from day 2 through day 14. The authors conclude that (1) MP administration alone does not increase mortality in septic rats; therefore, the results do not support the contention that steroid treatment in the absence of antibiotic therapy may be detrimental; (2) the cyclooxygenase inhibitor I does not improve survival in septic rats; and (3) the combined administration of MP and I increases mortality in septic rats and the possibility that this combination might be harmful in septic patients should be considered also.