As ProMISe'd... the Trial is Complete!

As every child already knows by now the study by Rivers et al. in 2002 has raised the awareness about sepsis and led to the establishment of the surviving sepsis campaign. As we have posted on BIJC before, many elements of the early goal directed therapy (EGDT) have been discussed controversially since. In order to answer some of the questions of sepsis treatment three big trials have been started, involving different parts of this world. These efforts have led to a unique situation as we now have three high quality trials looking at the classical EGDT versus 'usual care'.

ARISE and ProCESS had been published before (read here) and both of them showed no difference between EGDT and 'usual care'.

ProMISe included 1251 patients with severe sepsis or septic shock that were admitted to a total 56 hospitals in the UK. Again classical EGDT with measurement of continuous central venous oxygenation was compared to so called 'usual treatment'. It's remarkable to notice that in the 'usual treatment' group about half of the patient didn't get a central line and central venous oxygenation wasn't even measured in the ones who got one. And here's the result:
There was no difference in 90-day mortality and no differences in secondary outcomes. In contrast EGDT actually increased costs.

It has become difficult to ignore these three trials!

Our conclusion: The classical EGDT therapy has ended here and now... but EGDT will keep its central role in the treatment of septic patients!

Early:
- Identify septic patient quickly, start screening for patients if indicated
- Administer antibiotics within the first our of recognition of sepsis
- Start IV-fluid therapy immediately
- Take (blood) cultures as quick as possible, but do not delay antibiotic treatment

Goal Directed:
- Aim for a reasonable mean arterial pressure (e.g. 65mmHg)
- Aim for a sufficient urinary output (0.5ml/h)
- Central venous pressure (CVP) certainly and most probably central venous oxygenation (ScvO2) are not parameters to measure fluid responsiveness
- Lactate remains an issue of debate

Therapy:
- Simple: Whatever the physician feels is best!


ProMISe Trial, Mouncey et al. N Engl J Med. 2015 Mar 17.

BIJC Review on ARISE and ProCESS


Picture displayed taken from the Ice Cream Trilogy by Wright, Pegg and Frost

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