FEW CRITICAL conditions in medicine are as paradoxical as the events occurring during sepsis. The response of the patient's body to an insult such as infection or severe injury may initially be appropriate, but such defenses can lose their usual balance and destroy the patient. If the defense forces could be down-regulated after they have responded to the initial insult but before they begin destroying the body itself, we could prevent sepsis from developing—or at least reduce the associated mortality.
Deceptively simple, a viable way to accomplish this downregulation has eluded intense clinical research scrutiny for more than 10 years. All the trials of new therapies for sepsis conducted to date have failed to show efficacy (Table). Conducted under the rigorous conditions of the double-blind, randomized, placebo-controlled trial, their uniformly negative results have provoked great disappointment.
I believe the trials have reached the correct conclusion. The problem has not been