ProCESS

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

The ProCESS Investigators. N Engl J Med 2014; 370:1683-1693.

Clinical Question

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

Design

  • Randomised, controlled trial of 3 groups in 1:1:1 ratio
  • Non-blinded design

Setting

  • 31 academic hospitals in US
  • March 2008 to May 2013

Population

  • Inclusion: adults arriving in the emergency department (ED) with suspected sepsis (refractory hypotension or lactate > 4 mmol/l with two or more SIRS criteria)
  • Exclusion: if another primary diagnosis was present, such as acute myocardial infarction
  • 12,707 screened of which 1,351 randomised

Intervention

  • Early goal-directed therapy (EGDT) group: strict protocolised care (based on Rivers study) for 6 hours with dedicated doctor, nurse and research assistant that provided prompts
  • Protocol-based standard therapy group: relaxed protocolised care (based upon published expert opinions) for 6 hours with dedicated doctor, nurse and research assistant that provided prompts

Control

  • Usual care group: no extra staffing, with all care as directed by bedside physician for 6 hours. Research assistant collected data but provided no prompting.

Outcome

  • Primary outcome: there were no differences in 60-day mortality between groups
    • EGDT 21.0%; Protocol-based standard therapy 18.2%; Usual care 18.9%. (P values 0.31 – 0.89)
  • Secondary outcomes: there were no differences in 90-day or 1-year mortality between groups, or markers of significant morbidity.

Authors’ Conclusion

  • No significant advantage, with respect to mortality or morbidity, of protocol-based resuscitation over bedside care that was provided according to the treating physician’s judgement.

Strengths

  • Well designed, pragmatic method
  • Methods and statistical analysis defined and published a priori.
  • Recruited adequate numbers as planned for 80% power to detect 6–7% mortality reduction with 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.

The Bottom Line

  • Adults with sepsis in the ED have ~20% 60-day mortality and providing care by a dedicated team following either a strict or relaxed protocol makes no difference to this.

Links

Full text pdf not available without subscription / abstract / doi: 10.1056/NEJMoa1401602

Editorial, Commentaries or Blogs

Metadata

Summary author: @DuncanChambler
Summary date: May 2014
Peer-review editor: @stevemathieu75

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