ProCESS: A Randomized Trial of Protocol-Based Care for Early Septic Shock

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This is part of the infamous triad of NEJM studies showing no benefit of EGDT compared to usual care. Take a look at the Rivers study and compare them to ProCESS (done in USA), ProMISe (done in England) and ARISE (done in Australia/New Zealand).


Clinical Question

In adult patients with sepsis, does protocol-based care compared to usual care reduce death within 60 days?

  • Type of Trial: RCT of three groups in 1:1:1 ratio

  • Blinding: non-blinded design

  • Setting: 31 academic hospitals in the US from March 2008 to May 2013


  • Population:

    • 1,351 adults arriving in the ED with suspected sepsis (refractory hypotension or LA>5 mmol/L with two or more SIRS criteria

    • Did not require abx prior to randomization

      • Excluded: If another primary dx was present such as acute MI

  • Two Intervention groups:

    • 1) EGDT for 6 hours: strict, protocol care (based on Rivers study) with dedicated doctor, nurse and research assistant that provided prompts, AND

    • 2) Protocol based standard therapy group: relaxed, protocolized care (based upon published expert opinions) for 6 hours with dedicated doctor, nurse, and research assistant that provided prompts

  • Control:

    • Usual care for 6 hours without protocol - no extra staffing, all care directed by bedside physician for 6 hours; research assistant collected data

  • Outcome:

    • Primary outcome: 60 day mortality

      • No difference (21% in EGDT , 18.2% in protocol-based standard therapy, 18.9% in usual care; P values 0.31-0.89)

    • Secondary outcomes:

      • 90 day or 1 year mortality; no difference between groups or markers of significant morbitity


In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.


  • Well designed, pragmatic methods

  • Methods/statistical analysis defined and published a priori (knowledge that is independent of all particular experiences, as opposed to a posteriori knowledge, which derives from experience)

  • Recruited adequate numbers as planned for 80% power to detect 6-7% mortality reduction w/alpha 0.05


  • Changed inclusion criteria during trial (reduced fluid bolus required before meeting “refractory hypotension” criteria), but mean volume used was within Rivers’ original definition of 20–30 ml/kg

  • Mortality ~20% but initial power calculation based on 30–46%, therefore interim adjustment made and recruitment target reduced

  • Adherence to protocol was 88.1% in EGDT group and 95.6% in protocol-based standard therapy group. Although pragmatic, this is not perfect and may reduce between group differences


Rachel MulderComment