The search for efficacious new therapies in sepsis needs to embrace heterogeneity

Abstract

Most new drug treatments fail because they lack efficacy. In sepsis research, new therapies must contend with an additional barrier: the intractable heterogeneity of the sepsis syndrome. Together, these challenges have so far proved insurmountable. Hundreds of clinical trials have been conducted, at a cost of hundreds of millions of dollars, to test new agents to modulate the host response to injury in sepsis. None have succeeded. The sepsis syndrome itself is simultaneously too broad and too narrow. Sepsis encompasses numerous different etiologies and pathophysiological processes, but—by definition—excludes sterile injuries that lead to the same pathophysiology and organ failures, such as trauma, burns, hemorrhage, and pancreatitis.