The first of three major trials assessing early goal directed therapy (EGDT) in sepsis – the American ProCESS Trial – has been published.
It showed what many of us thought – that the specific monitoring via a central line of central venous oxygen saturation – was not necessary for improved survival.
However the trial randomised 1341 patients to one of three arms:
(1) protocolised EGDT
(2) protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions
(3) ‘usual care’ which was not standardised.
There were no differences in any of the primary or secondary outcomes between the groups.
Interestingly, in the six hours of early care that the trial dictated, the volume of intravenous fluids administered differed significantly among the groups (2.8 litres in the protocol-based EGDT group, 3.3 litres in the protocol-based standard-therapy group, and 2.3 litres in the usual-care group).
There was also a difference in the amount of vasopressor given, with more patients in the two protocol-based groups receiving vasopressors (54.9% in the protocol-based EGDT group, 52.2% in the protocol-based standard-therapy group, 44.1% in the usual-care group).
The use of intravenous fluids, vasopressors, dobutamine, and blood transfusions between 6 and 72 hours did not differ significantly among the groups.
Overall 60 day mortality was in the region of 20% for all groups.
What are the take home points here? Firstly, overall sepsis outcomes have improved over recent years, and early recognition and antibiotic administration may be the most important components of care. In the early emergency department phase of care, protocolised fluid and vasopressor therapy may not be as important as we thought. Good clinical assessment and regular review seem to be as effective and perhaps more important than any specific monitoring modality or oxygen delivery-targeted drug and blood therapy.
We all await the ARISE and ProMISE studies which may shed more light on the most important components of early sepsis care.
A Randomized Trial of Protocol-Based Care for Early Septic Shock
NEJM Mar 18 2014 (Full Text Link)
Background: In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.
Methods: In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support.
Results: We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support.
Conclusions: In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes