A critical comparison of the hematologic, cardiovascular, and pulmonary response to steroids and nonsteroidal anti-inflammatory drugs in a model of sepsis and adult respiratory distress syndrome

Improved survival of patients receiving high-dose steroid therapy in sepsis and adult respiratory distress syndrome (ARDS) has been reported, but such therapy and its benefits remain controversial. Recently research has been directed toward manipulation of the arachidonic acid cascade. Improved survival and hemodynamics with administration of nonsteroidal anti-inflammatory drugs (NSAID) have been reported in animal models of sepsis and ARDS. The purpose of this study was to compare the effects of steroids (methylprednisolone) and NSAID (ibuprofen) in a porcine model of septic ARDS induced by a continuous infusion of live Pseudomonas aeruginosa. Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250 ml tidal volume and 0.5 Fio2. Pigs were randomly assigned to one of five groups: groups I and II received respective doses of 12.5 mg/kg ibuprofen and 30 mg/kg methylprednisolone at 20 and 210 minutes after baseline; group III had P. aeruginosa only; groups IV and V received respective doses of ibuprofen and methylprednisolone at 20 and 210 minutes of sepsis. Significant pulmonary edema, increased intrapulmonary shunting, hypoxemia, hemoconcentration, and systemic hypotension occurred with P. aeruginosa infusion. In septic animals treated with ibuprofen normal systemic arterial pressure was maintained, hemoconcentration was decreased, and oxygenation was improved with a significant decrease in shunting and pulmonary edema. Administration of methylprednisolone improved hemoconcentration and cardiac index, but no significant effect on pulmonary edema, intrapulmonary shunting, or oxygenation was observed. The results of this study demonstrated a significant beneficial effect of ibuprofen and we would encourage controlled clinical trials of this drug in the management of sepsis and ARDS. On the other hand, methylprednisolone was found to be relatively ineffective in treatment of circulatory collapse and ARDS associated with sepsis.