First there was ProCESS. Then there was ARISE. Now there is ProMISe.
If the prior two trials hadn’t already been celebrated and dissected, there would be much more to write regarding this one. This, like the others, randomized patients to Early Goal-Directed Therapy for severe sepsis versus “usual care”. This, like the others, found the basic components of resuscitation – intravenous fluids and early antibiotics – are far more important than the specific targets and protocols enshrined by Rivers et al.
These authors screened 6,192 patients to randomize 1,260. Half had refractory hypotension, and the mean lactate levels were 7.0 and 6.8 in the EGDT and usual care arms. Patients were enrolled within 6 hours of presentation and randomized within 2 hours of meeting inclusion criteria, with the EGDT arm receiving catheter insertion capable of SCVO2 monitoring within ~1 hour. EGDT protocol was adhered to for 6 hours following enrollment.
As expected, randomization produced some divergence in treatment due to the EGDT protocol. The EGDT cohort received more frequent red cell transfusions during both the protocolized period and subsequent care. Likewise, dobutamine use in the EGDT arm exceeded usual care. However, some differences occurred outside of the protocol. EGDT arm patients were more likely to be admitted to an ICU setting, more likely to receive any sort of central line, more likely to receive invasive blood pressure monitoring, and more likely to be placed on vasopressors. The remaining treatment – crystalloid resuscitation, colloid resuscitation, and other transfusions were similar.
And, finally, 90-day mortality was similar: 29.5% EGDT vs. 29.2% usual care.
A financial analysis found EGDT was more costly, but the result did not reach statistical significance. However, the cost analysis was performed using different financial models that may not be generalizable to the billing structure in the United States. The difference in ICU admission and length-of-stay alone certainly has important ramification both from a cost and a resource utilization standpoint.
So, finally, we have the publication of the last of the triumvirate of EGDT trials. If there were any lingering doubts (hopes?) regarding the necessity of the most resource-intensive interventions, they ought to be laid to rest. However, as with each of these negative trials, it is important to acknowledge the role of Rivers’ work in aggressively seeking, recognizing, and treating severe sepsis. Even as we discard the components of his protocol, the main thrust of his work has saved many, many lives.
“Trial of Early, Goal-Directed Resuscitation for Septic Shock”
http://www.nejm.org/doi/full/10.1056/NEJMoa1500896
Hey Ryan,
As always great work and post. I did want to make sure something was clarified from your post…..Looking at the results, a significant portion of “usual” care patients still get arterial catheters (62.2%), CVCs (50.9%), and vasopressors (46.6%). What this tells me is that our “usual” care has components of the EGDT algorithm engrained in it. Sick patients need fluids, antibiotics, and supportive therapies (i.e. Early critical care and resuscitation), but they don’t need CVP and SCVO2 monitoring to dictate their care. So there are still components of EGDT that should continue to be used, it is the invasive monitoring that is not really needed. Hope all is well.
Salim
"Usual care" patients definitely received advanced interventions – but certainly at a lower rate than the EGDT arm. It wasn't long ago every patient was mandated to have a central line – and, I would expect, in a few years after all these trials, the rates of CVCs to decline even further to just the few patients who truly require them.