Early Goal-Directed Therapy and Septic Shock — 15 Years after the Rivers’ Study, ARISE, ProCESS and ProMISe

Abstract

Septic shock is one of the main causes of admission in critically ill patients and its mortality rate remains high. Its prognosis is closely related to the earliness of both hemodynamic management and antibiotic therapy. The main goal of the initial hemodynamic management is to restore an adequate oxygen delivery to the tissues. The hemodynamic management, first described by Rivers in 2001 and called “early goal-directed therapy” (EGDT), aims to target a central venous oxygen saturation (ScvO₂) ≥ 70% within the first six hours of management. This is achieved by means of a therapeutic protocol including fluid administration, red blood cells transfusion, and infusion of vasoactive and/or inotropic agents. Compared to standard therapy, this aggressive management has been shown to significantly decrease in-hospital mortality. Thus, the Surviving Sepsis Campaign was inspired by the EGDT protocol when publishing the first international guidelines for management of severe sepsis and septic shock. These guidelines are summarized in bundles. Recently, the value of EGDT has been challenged by three multicenter randomized studies (ProCESS, ARISE, and ProMISe), which showed that EGDT using ScvO₂ did not reduce all-cause mortality, duration of organ support, or in-hospital length of stay. Nevertheless, in spite of these apparently negative results, one should not neglect the importance of low ScvO₂ values (lower than 65–70%) in patients with septic shock. A hemodynamic strategy aiming at increasing oxygen delivery and at targeting ScvO₂ > 70% in septic shock patients with ScvO₂ < 70% remains of utmost importance. The interpretation of these latter studies strongly incites to individualize the hemodynamic management rather to apply the same therapeutic algorithm in all septic shock patients.