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

Written By Rachel F

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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).

ProCESS

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

PICO

  • 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

Conclusions

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.

Strengths

  • 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

Weaknesses

  • 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

Sources:

https://www.thebottomline.org.uk

Rachel F

Rachel is a physician assistant who has been holding down the ICU since 2016. She joined the Pulmcast podcast in 2017 and has been hooked on FOAMed ever since. Rachel has a passion for teaching using technology with a special focus on preserving dignity in the ICU. When she's not at work, you’ll find her playing with her golden retriever, hunting for thrift store treasures, and soaking up time with her husband and son.

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Early Goal Directed Therapy