The sound you hear is a sigh of relief from Emergency Physicians and intensivists regarding the outcomes of the Australasian Resuscitation in Sepsis Evaluation (ARISE).
As ProCESS suggested, and as many have suspected all along, it seemed the critical intervention from Early Goal-Directed Therapy was the early part – and less the SCO2 monitoring and active management of physiologic parameters using dobutamine and blood transfusion. Now, we have a second study, in addition to ProCESS, supporting the same general conclusions.
ARISE enrolled patients with confirmed or suspected sepsis, and either hypotension refractory to 1L crystalloid fluid challenge or a lactate level of 4.0 mmol/L or more. 31 centers randomized 1,600 patients to undergo either EGDT or “usual care”, which entailed routine local clinical practice, excepting measurement of SCVO2 was forbidden. EGDT, however, was provided by specially coordinated teams to ensure all patients received the intervention. The primary outcome was death from any cause within 90 days, powered to detect an absolute risk-reduction of 7.6%.
Baseline characteristics between the two groups were quite similar, few patients dropped out of each arm, and, finally, there was no difference in the primary outcome – 18.6% vs. 18.8% (does it matter which is which?) Indeed, of all the outcomes measured, only two differed in statistically significant fashion: the EGDT cohort departed the Emergency Department 30 minutes more quickly, and the EGDT cohort received greater vasopressor support – attributable entirely to the use of dobutamine in 15.4% of patients vs. 2.6% in the usual care arm.
As expected, resource utilization unique to EGDT, of course, was different – more and different types of central venous catheters, more arterial catheters, and more frequent use of blood products. And, as we’re seeing – all of this is unnecessary. As with ProCESS, “usual care” has become EGDT, excepting these elements. Both groups received substantial, early crystalloid resuscitation, early appropriate antibiotic coverage, and departed the Emergency Department to a critical care setting quite quickly.
EGDT receives credit for making us aware the impact early identification and intervention can have on mortality. However, it is time to leave EGDT behind and identify new resuscitation targets and sensible strategies for achieving them.
“Goal-Directed Resuscitation for Patients with Early Septic Shock”
http://www.nejm.org/doi/full/10.1056/NEJMoa1404380
The background history of EGDT is interesting.
A small single center study with large treatment effect (Rivers) completely changed the landscape of sepsis care around the world. A tidal wave of nonsense followed with guidelines being created and endorsements from specialty societies. All of this happened without thinking that the original study of EGDT was probably a type I error all along. When was the last time you saw a small study with a large treatment effect get debunked? How about ALL the time. We should be ashamed of ourselves for getting so blinded by the hype and not realizing the foundations of EGDT were based on pseudoscience.
Rivers' was controversial even when it came out – regarding, particularly, the large effect size seen and how poorly the control group did. However, the skeptics were drowned out by far by policy makers, and you can see the results. Were patients harmed by EGDT? Probably not. Overall, the focus on sepsis probably resulted in tremendous strides in awareness, giving rise to the ~20% mortality seen in "usual care" in modern trials. In the academic settings these trials were conducted, it's clear the physicians respect sepsis – and are giving prompt, appropriate antibiotics and aggressive fluid resuscitation. EGDT may end up just a short-term blip in the evidence stream, but its overall effect is positive.
It somewhat reminds me of NINDS, a 600-patient two-part trial that changed everything … because of its effect size, attributable mostly by how poorly the control group did compared to other trials. tPA for stroke probably helps – but not as much as we suppose it does, and certainly not so much we ought to build our healthcare system around it.
Maybe the "usual care" down under is quite excellent ?
The usual care is so close from the EGDT… I am waiting for the meta-analysis of ProCESS, ARISE and PROMisE