What comes after the Early Goal Directed Therapy for sepsis era?

Abstract

The idea of sepsis was introduced in the literature in the 4 th century BCE by the ancient Greek Hippocrates when animal and plant decomposition (σηψις, rot) was reported. In the 11 th century, Avicenna described the process of acute inflammation and purulence formation, a "blood rot", and he included body temperature, heart rate, and the state of body fluids in his description (1). However, the word "sepsis" was not used until the 19 th century. Over the past 30 years, the need to understand the underlying pathophysiological process and to identify better clinical criteria for early detection of sepsis has rapidly evolved because of the increasing number of patients with sepsis receiving advanced organ support systems, including mechanical ventilation, renal replacement therapy, and extracorporeal membrane oxygenation, has taxed health care systems (2,3). Furthermore, our awareness of the morbidity, mortality, and cost associated with this condition has increased.Despite the fact that we adopt studies that have the best external and internal validity and we know that patients managed according to evidence-based medicine do better than patients treated according to physician judgment and expertise which can vary considerably, there is no doubt that not every positive outcome found in clinical studies on welldefined patient populations can be applied to "real world" situations with extremely heterogeneous patient populations with the expectation of similar results. In this editorial, I will address the conflicting results on the role of the early goal directed therapy (EGDT) in managing sepsis.In the1990s, there was no standardized protocol for the early identification and treatment of patients with sepsis. The observed mortality then was more than 50%, and this triggered systematic investigations on the early identification and risk stratification of patients with sepsis and septic shock. The well-known study by Rivers et al.on EGDT conducted over 3 years (1997)(1998)(1999)(2000) reported a significant 16% absolute decrease in mortality with an aggressive protocol for sepsis resuscitation in the first 6 hours after presentation to the emergency center (4). This study included 263 patients with severe sepsis and septic shock at a single urban Detroit emergency center and compared an EGDT protocol with standard "usual care" treatment. In the EGDT arm, patients received mandatory arterial catheters and central venous catheters with continuous central venous oxygen saturation (ScvO 2 ) measurements. Patients received crystalloid or colloid until prespecified central venous pressures (8-12 mmHg) and a prespecified mean arterial pressures (MAP ≥65 mmHg) were achieved. If their MAPs were below 65 mmHg, treatment with vasopressors was started. If their ScvO 2 saturations were less than 70%, patients were transfused until their hematocrits were greater than 30%, and if the ScvO 2 remained low, patients were started on dobutamine. Both groups had early cultures.Despite initial concerns regarding the external validity of t...