Title: “The 52 in 52 Review: ProCESS”

Article Citation: ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. PMID: 24635773.

What we already know about the topic: Rivers shocked the world in 2001 with his revolutionary, if cumbersome, protocol for the care of septic patients. In the years since then, we’ve learned a lot, and many emergency physicians and intensivists have abandoned or significantly modified the care model developed by Rivers.

Why this study is important: Rivers called for a lot of invasive monitoring, therapies titrated to targets that were logistically challenging to follow, and (by modern standards) aggressive blood transfusion goals. The problem was, no one knew what subsets of this protocol actually were responsible for the observed mortality benefits, and as care relaxed around different aspects of the protocol, we needed to find out what, if anything we were losing.

Brief overview of the study: Septic patients with fluid refractory hypotension or lactate > 4 mmol/L, and without significant concurrent acute disease (ACS, CHF, GIB, trauma or similar) were identified in the emergency department. At this point they were randomized to one of three arms — Rivers Protocol, protocolized standard care (in which the blood transfusion, CVC, and inotrope rules were removed from Rivers), and usual care (in which an intensivist could make the plan as they saw fit). This was done in a multi-center, open label, random fashion.

Limitations: This trial was a pragmatic, intention to treat trial, and not everyone in the protocolized arms got the full protocol every time, possibly diminishing some effect size. Additionally, the researchers changed their definition of “fluid refractory hypotension” during the trial, though it remained within commonly established research parameters.

Take home points: This paper was the first of the triple threat of ProCESS, ProMISe, and ARISE which in some ways put EGDT to rest, once and for all. Specifically, ProCESS showed no difference in all cause mortality at 60 days in patients between the three arms. In some ways, this can be considered a good thing — we’re liberated of the cumbersome Rivers protocol. In another light, it’s humbling that in approximately one and a half decades all of medicine still can’t beat the results of one guy that thought really hard about this problem in the late 1990s.

June 2024