Tuesday 11 November 2014

The wonderful ARISE trial

Journal club in 2014 would certainly not be complete without a mention of the fantastic ARISE trial. I think most practicing emergency doctors now are well aware of this study and how it concluded no benefit of early goal directed therapy (EGDT) vs. usual care in early septic shock. Therefore I will only focus on a few key points.

This was a huge undertaking involving 51 centres mostly in Australia and New Zealand and enrolled 1600 patients. The authors are to be absolutely congratulated for such great effort. However, I’ll bet they are kicking themselves for not being the first cab off the rank of the new large RCT’s. ProCESS just beat them by six months. The last of these trials is the ProMISe trial coming out of the UK. Therefore we will be seeing lots more data and meta-analysis coming in the future.

In the ARISE trial, both groups had a mortality just shy of 20%. This seems to be the new norm regarding mortality rates in studies of sepsis now days. Much has been made about the gradual reduction in mortality over the years but I would imagine that much of this is probably due to early recognition of milder sepsis and the creation of a lower risk cohort rather than any major breakthrough. (Although some might consider this a breakthrough.)

Both arms in the ARISE trial got just about the same amount of fluids. Two and a half litres were given before enrollment and almost two more litres in the six hours after. (To be fair, there actually was a statistical difference with a p value containing lots of pretty zeros but this most certainly was clinically meaningless). More patients in the EGDT group got red-cell transfusions, central lines, vasopressors, dobutamine and went to ICU. So many more resources were used to no benefit. Could this be thought of harm of EGDT? I think so.

So once again the original study of EGDT which claimed a 15% absolute mortality reduction has been debunked. ARISE has taught us again to be skeptical of small studies showing large treatment effect. Where else have we seen this recently? Think hypothermia after cardiac arrest? Could NINDS be next?

The basic summary for the early care of septic shock in the ED? Early recognition, aggressive fluids, and early antibiotics. Who would have figured?


Peake SL, Delaney A, Bailey M, et al. Goal-Directed Resuscitation for Patients with Early Septic Shock. N Engl J Med 2014 Oct 16;371(16):1496-506.

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