Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
Question: In sepsis, it is critical to recognize the “golden hours” at which point systemic oxygen delivery cannot meet tissue demand –> global tissue hypoxia. Instead of monitoring vital signs and hemodynamic stability, can monitoring factors associated with tissue hypoxia–and titrating treatment to meet certain goals–improve outcomes?
The Rivers trial, at least in my mind, coined “early goal-directed therapy” in the management of sepsis. It put tissue hypoxia front and center.
263 patients who had 2+ SIRS criteria AND either a systolic blood pressure <90 that was unresponsive to one fluid bolus OR lactate >4.0 were enrolled in this trial. They were randomized into two groups. The control group got whatever the providers deemed to be “best treatment.” The intervention group was treated according to a protocol aimed at optimizing tissue perfusion:
- Central venous oxygen saturation (ScvO2) <70%, or add dobutamine to optimize cardiac index
- Hct <30 were transfused RBCs until Hct was =30 or greater.
In-hospital mortality for the group receiving EGDT was 30.5% as compared with 46.5% in the group assigned to standard therapy (p=0.009). Furthermore, the EGDT group had higher ScvO2, lower lactate, and lower rates of organ failure. It should be noted that in addition to 99.2% of the EGDT patients meeting their hemodynamic goals, so did 86.1% of the control group, which speaks to the effectiveness of existing empiric therapy.
The authors made the interesting observation that the incidence of death due to sudden cardiovascular collapse was halved in the EDGT group, suggesting that an abrupt transition to severe disease is an important cause of early death. Early identification of patients proceeding down this route was important, as interventions that are started outside the “golden hours” may be too late.
There are a few controversies associated with the Rivers trial. One is that about one-third of the patients had CHF, so may have been in cardiogenic shock or mixed cardiogenic/septic shock, not pure septic shock. Thus, the use of dobutamine to increase the ScvO2 to > 70% in septic shock remains unclear. Additionally, the use of packed RBCs to a goal of Hct >30 to increase oxygen delivery remains controversial, since there are pros and cons (including cost, limited resources, transfusion reactions, and coagulation dysfunction) associated with using blood.