Clinical trials in sepsis: an update

In this article, we place clinical sepsis trials from the past year in the context of similar sepsis trials run over the past three decades. These recent clinical sepsis trials include studies of agents administered to limit the effects of specific host proinflammatory mediators (tumor necrosis factor, platelet-activating factor and prostaglandins), studies of use of corticosteroids at low doses late in sepsis, and studies of administration of high doses of a nonspecific nitric oxide synthase inhibitor to decrease nitric oxide production in septic shock. The three trials of agents designed to limit host proinflammatory mediators showed minimal beneficial effects, results that are similar to those of the approximately 20 previous trials of similar agents. Low-dose corticosteroid therapy reversed shock and showed nonsignificant trends towards improvements in survival rates. In contrast, high doses of corticosteroids given early in sepsis have shown harmful effects in clinical sepsis trials. Finally, inhibition of nitric oxide production was lethal, indicating that high doses of nonspecific inhibitors of nitric oxide production are contraindicated in septic shock.