Wednesday, 21 May 2014

The ProCESS Trial and the official burial of EGDT


Not quite ten years ago I conducted a multidisciplinary journal club looking at the original Rivers study on Early Goal Directed Therapy for sepsis. Despite the EM community embracing this new concept, my critical care colleagues were certainly less impressed. Well to be fair, they absolutely lambasted the study and could not believe that any reasonable person would change their practice based on one small study conducted in a single institution showing an unbelievably large treatment effect. After all, they had been conducting their own studies of ICU goal directed therapy for years to no avail.

It has taken over a decade for another more definitive RCT looking at EGDT in the form of the much publicised ProCESS trial. The authors are to be congratulated for their efforts. In a nutshell, they conducted a large multicenter RCT at 31 emergency departments in the USA. Patients with septic shock were randomly assigned to one of three treatment arms; the Rivers EGDT, protocol based standard care (without mandates for central lines, pressors or blood transfusions), or usual care (whatever the doctor wanted to do). The primary outcome was in-hospital mortality at 60 days. I think we all know the results showed no difference with mortality around 20% in all three groups. More patients in the EGDT went to the ICU, got transfusions and dobutamine. EGDT is officially dead.

To be fair, EGDT has been dying a death of a thousand cuts since it was originally published in 2001. There has been a mammoth amount of research and emphasis on sepsis care since its release and modifications of the original protocol have been ongoing. There still are two more large RCT’s yet to come from the UK and Australia so perhaps we still have more to learn.

I have always concerned about the resource implications of EGDT. In particular the harms it might create especially in smaller ED’s by diverting attention away to perform far from proven tasks. In the end it looks like early recognition, aggressive fluids and early antibiotics are still the mainstay of care- surprise, surprise.

There is no doubt this study will change the guidelines as put out by the Surviving Sepsis Campaign. But I don’t think there is any reason to wait for their formal recommendations. After all this “campaign” was originally created and funded by a public relations firm hired by Eli Lily in order to promote their now defunct drug Xigris. Shame on us...

What is the take home message? Please, please, please be sceptical of small studies showing large treatment effects especially when they show the unbelievable. Now scoop some dirt on the coffin of EGDT... too good to be true.

Covering:

Yealy, DM, Kellum JA, Huang DT, et al. A Randomized Trial of Protocol-Based Care for Early Septic Shock. N Engl J Med 2014;370(18):1683-1693.
http://www.ncbi.nlm.nih.gov/pubmed/24635773

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