FOAM Eye-Catchers 9: Early Goal Directed Therapy is Dead

Apologies for the recent hiatus in FOAM Eye-Catchers – have had my head down in fellowship exam study.

The big news of late is that the 3rd episode in the trilogy of multi-centre trials evaluating Early Goal Directed Therapy (EGDT) for septic shock has been released.

First we had PROCESS from the US, then came ARISE from Australia/NZ and now we have PROMISE from the UK.

A closer review of PROMISE has been provided by emlitofnote and St Emlyn’s, but in a nutshell it has joined ARISE and PROCESS in demonstrating no benefit of EGDT. We now have over 4000 patients in a large number of centres across 4 countries showing no benefit of EGDT.

This is in contrast to the original single centre Rivers et al trial of only 263 patients which originally found a benefit of this package of care. While there were many criticisms of the external generalisablity of this study’s findings, the most concerning were later accusations in the Wall Street Journal that 25 patients were excluded from the study analysis post randomisation without proper transparent justification and if these patient’s had been included, no significant benefit would have been demonstrated. Notably all of this occurred under a cloud of financial conflicts of interest.

So what do we know now about septic shock management:

– central venous pressure monitoring is not useful and has been previously shown to have no value in predicting fluid responsiveness

-expensive SCVO2 monitors are not useful and should not be a trigger for blood transfusion. If you do wish to consider blood transfusions based on Hb (which was rarely used in the control groups in the above studies – between 3%-8% of patients) then note that a lower Hb trigger of 70 g/L uses less blood with equivalent outcomes to a trigger of 90 g/L.

Given the above and the relative safety of peripheral vasopressor infusions, certainly from an ED perspective, central lines are no longer urgently required in septic shock management. Low dose vasopressors infusions can be started peripherally in an emergent fashion and when all other essential urgent management steps have been completed (e.g. obtaining micro specimens, early antibiotics etc), and time permits in the ED or ICU, a central line can be placed with full surgical aseptic non touch technique, for longer term/higher dose vasopressor infusions as required.

It should be noted, that while Early Goal Directed Therapy is dead, “Early Therapy” is still very much alive and remains of utmost importance in septic shock management:

1. Early recognition: send off lots of lactates and don’t ignore falling blood pressures. Given 1 in 5 septic shock patients will die with best practice care, it is far better to overcall “septic shock” and act decisively early, then blame the BP drop on something else like hypovolaemia and realise you were wrong far too late.

2. Early antibiotics: treat early and as broad spectrum as required, narrowing the spectrum later when more definitive source/bugs are determined. Arguably the goal of antibiotics within the first hour is too generous – we should get them in as early as we can.

3. Early haemodynamic resuscitation: although the jury is out on whether this should take the form of the traditional fluid-heavy, late vasopressor approach compared with a “fluid-lite”, early vasopressor regime. I personally favour the latter.

While some of the resource intensive and expensive aspects of EGDT are dead, we should remember the positive influence that Dr Rivers’ team and the Surviving Sepsis Guidelines have had, in putting septic shock on the map of truly emergent medical conditions and at least focussing our efforts on early therapy.