Sepsis: a roadmap for future research

Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, induding administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.Brighton & Sussex Med Sch, Brighton, E Sussex, EnglandUniv Brussels, Erasme Univ Hosp, Brussels, BelgiumSunnybrook Hlth Sci Ctr, Dept Crit Care Med, Toronto, ON M4N 3M5, CanadaUniv Toronto, Toronto, ON, CanadaUniv Fed Sao Paulo, Dept Anesthesiol & Intens Care, Sao Paulo, BrazilUniv Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USACHU Vaudois, Infect Dis Serv, Lausanne, SwitzerlandCHU Vaudois, Dept Med, Inst Microbiol, Lausanne, SwitzerlandUniv Lausanne, Lausanne, SwitzerlandBrown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USAFeinstein Inst Med Res, Manhasset, NY USAUniv Amsterdam, Ctr Expt & Mol Med, Acad Med Ctr, NL-1012 WX Amsterdam, NetherlandsUniv Amsterdam, Div Infect Dis, Acad Med Ctr, NL-1012 WX Amsterdam, NetherlandsEuropean Med Agcy, Off Antiinfect & Vaccines, Human Med Evaluat Div, London, EnglandUniv Fed Sao Paulo, Dept Anesthesiol & Intens Care, Sao Paulo, BrazilWeb of Scienc