High-dose methylprednisolone in a porcine model of ARDS induced by endotoxemia

Using a continuous i.v. infusion of E. coli endotoxin in spontaneously breathing pigs under ketamine anesthesia we have developed a lung injury model which closely mimics the pathophysiological and morphological changes of early ARDS induced by sepsis in man. Pretreatment with high doses of methylprednisolone largely prevented the pulmonary, cardiovascular and morphological features induced by the endotoxin. Methylprednisolone treatment initiated 2 h after starting the endotoxin abolished further derangements in pulmonary and cardiovascular functions and there was a restoration towards normal values. Both pretreatment and delayed treatment with methylprednisolone improved survival. Although one should be extremely cautious in extrapolating these data to the more complex clinical situation, the implications are that high doses of methylprednisolone, given early in the course of sepsis in man, may help to prevent both the pulmonary and cardiovascular derangements of this disease.