The demise of early goal-directed therapy for severe sepsis and septic shock.

A protocol for the quantitative resuscitation of severe sepsis and septic shock known as early goal-directed therapy (EGDT) was published in 2001. Despite serious limitations, this study became widely adopted around the world and formed the basis of the Surviving Sepsis Campaign 6 h resuscitation bundle. Subsequently, a large number of observational before-and-after studies were published which demonstrated that EGDT reduced mortality. However, during this time period, there has been a substantial reduction in the mortality from sepsis in many Western nations that appears unrelated to EGDT. Recently, the Protocolized Care for Early Septic Shock (ProCESS) and The Australasian Resuscitation in Sepsis Evaluation (ARISE) trials failed to demonstrate any outcome benefit from EGDT. These two large, multicenter, randomized controlled studies raise serious questions regarding the validity of the original EGDT study and the scientific rigor of the uncontrolled, largely retrospective before-after clinical studies. Furthermore, accruing data suggest an association between the amount of fluid administered in the first 72 h and the mortality of patients with severe sepsis. Patients in all arms of the ProCESS and ARISE trials received substantial and nearly equivalent amounts of fluid. It is proposed that a more conservative fluid strategy and the earlier use of norepinephrine in patients with septic shock may be associated with further improvements in the outcome of patients with sepsis.