Third strike for invasive EGDT, but still not inferior

ProMISe, the third of the trials examining goal-directed therapy in early septic shock (neatly compared by Bottom Line), was a large pragmatic parallel RCT at 56 hospitals in England published last month. Patients with SIRS and refractory hypotension OR hypoperfusion who had already had antibiotics were subjected either to the Rivers-style protocol below or to ‘standard care’.

The EGDT group recieved:

  • a similar number of arterial lines (70ish%)
  • more ICU admission (90 v 75%)
  • a similar median fluid delivery (enrolment to 6hr – 2 v 1.8L)
  • more CVCs (90 v 50%),
  • more dobutamine (18 v 4%)
  • similar vasopressor use.
  • twice as much blood (9 v 4%)

This resulted in:

  1. No difference in 90 day mortality (29%)
  2. SOFA at 6 hours: 6.4 vs. 5.6, and at 72 hours: 4.0 vs. 3.7 – significantly lower scores in the usual care group.
  3. No difference in days free from advanced respiratory, advanced cardiovascular support or renal support, length of stay, or resource use and costs at 90 days £12,414 ($17,647) vs £11,424 ($16,239) (p 0.25).


Screen Shot 2015-03-26 at 7.18.31 PM

Interestingly 25% of the usual patients with signs of septic shock were not admitted to the ICU; 13% in the intervention arm.

Of course, the control group was almost certainly largely ‘goal-directed’. None of these 3 studies was a repeatability assessment of Rivers’ original as the usual care is now contaminated with the knowledge that jumping on these patients early is a good thing (Sepsis 6 etc).



If you’d already dispensed with CVP measurement, had reservations about transfusing to a target haematocrit, and were dubious about using ScvO2 for mandating fluid delivery, you now have 3 good pieces of evidence to support your suspicions that these might not be necessary elements of the bundle.

If I’ve got septic shock, I want:

1. to be taken seriously and prioritised,

2. early antibiotics.

3. sufficient fluid resuscitation to be euvolaemic and hydrated (not ‘aggressive’ – most patients got around 4 litres in 8 hours.)

4. consideration of tissue perfusion optimisation.

Beyond that, you can stick some extra lines in me, transfuse if you must, boost me with some inodilators simply on the strength of a questionable number, but I think you’ll be wasting your time and money. Either way I’m glad your treating me now and not 15 years ago!

Early sepsis therapy management is becoming clearer. How about the next day or 2?


The EGDT ‘bottom line’ from The Bottom Line and other wise FOAM sites

WICS Bottom line

This is a landmark paper and completes the international triumvarate of sepsis studies. ProMISE, ARISE and ProCESS have shown no benefit (or harm) with EGDT over ‘usual care’, unlike the Rivers study.

Both groups in this study were actually well matched for most interventions. The main difference was in the use of continuous SCVO2 measurement and CVP to guide management. Perhaps we should not completely dismiss the term ‘EGDT’. Afterall,  our ‘usual care’ consists of early intervention and goal directed therapy. The goal… to continue to reduce mortality with high standard and consistent quality care.


There is no need to provide invasive expensive EGDT in the emergency department for septic shock patients.

St Emlyns

To my mind, this trial justifies our current approach. If your septic patient is sick, go for the EGDT approach. Insert a central line, insert an arterial line, fill the patient up, give vasopressors if they’re still hypoperfused. That’s what happened in this trial – it doesn’t knock that approach. It they’re not so sick, then don’t.

Maybe that’s all this trial is really telling us. And maybe that’s a limitation of the RCT to answer these questions.


As already confirmed by the ProCESS and ARISE trials, if patients are identified EARLY, given IVF EARLY, and antibiotics EARLY…the “ABCs” of resuscitation and critical care, then the pathway used afterwards (i.e EGDT, Protocolized, or “usual care”) the “DEF” after resuscitation is less important in the resuscitation of patients with severe sepsis and septic shock.


EGDT could be viewed as many of the on paper very strict standard operating procedures we have – they’re usually used as a guide. If you’re new and unfamiliar to it, you’ll often adhere strictly to it. But once you get lots of experience with that patient population and its management and procedures, you’ll start going more by clinical judgement and feel. Knowing when to adhere strictly to protocol, and when it’s better to make different calls. From that point of view, EGDT has been internalised, and is being tweaked and individualised by clinicians to suit each patient (and doctor).


What all the patients in all the trials had in common was early receipt of antibiotics, fluids and vasopressors, and a high survival rate from severe sepsis and septic shock.

Although well-intentioned, continuing to advise wasteful busywork simply to promote general conscientious care (after the crucial therapies have been provided) now seems a bit outdated, if not cynical. The consistent signal is, we must identify sepsis early and get antibiotics, fluids, and vasopressors started a.s.a.p. An algorithm for the next 6 hours is simply not needed to achieve that.


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.