PROCESS has been backed up by ARISE in goal-directed therapy for sepsis. PROMISE is awaited (finished recruiting in July).
A large (1600), international, randomised, un-blinded, intention-to-treat trial with sensible exclusion criteria, conducted 2008-2014 of excellent quality. ARISE showed no benefit in using a protocolised 6 hour package for septic shock which involved continuous ScvO2 and CVP targetting
Their protocol included:
1. Supplemental oxygen if saturations <93 (No PaO2 limit)
2. Targets – using pressor (or dilator), red cells, dobutamine, mechanical ventilation to acheive:
- CVP >8 (or 12 in ventilated)
- MAP target range of 65 to 90 mmHg.
- Continuous ScvO2 >70%
The control group had conventional local management (usually guideline-driven) and weren’t aloud to peak at ScvO2. Both groups received around 2 litres over the 6 hours. Enrolment meant antibiotics had already been given (mean time around 70 mins for both groups).
This surely doesn’t damn EGDT but suggests that the ‘goals’ are now more (or less) clearly:
- Definitely
- early antimicrobials – within the first hour?
- Probably
- fluid repletion – at least some, but likely to vary with pathology?
- blood pressure control – 65 as a minimum, but maybe previous BP has an impact?
- cardiac output improvement when necessary, but not supra-normalising, and not using dopamine?
- hope to see some lactate reduction!
None of this detracts form sepsis being a ‘thing’ to take seriously and jump on (like MI & CVA). The surviving sepsis campaign quickly issued an update suggesting that ScvO2 and CVP may not be necessary targets. They also point out that whatever the weaknesses of individual elements of the SSC guidelines, if you adhere to them you can expect to do better than institutions that don’t, as demonstrated by their metrics published earlier in the month. Some have commented that a hospital that adheres to a guideline is more likely to be a hospital that has systems for recognition of critical illness, is introspective with its processes, educates internally, collects data and audits well – a better hospital.
It might be argued that perhaps there wasn’t comprehensive equipoise prior to these studies. EGDT has largely been embraced by a specialty short of breakthroughs. Perhaps a worldwide Hawthorne effect plays some part in these ‘non-positive’ studies.
Maybe more of our pre-conceptions about managing sepsis will be stripped away. Maybe in a few years we’ll be practising glycocalyx-protective bolus-less resuscitation, with permissive hypotension and permissive hypoxia. But we will still stay alert for the diagnosis, start the clock and give antimicrobials early. And for now, Rivers EGDT remains as good as any other!
