EBQ:ProMISe Trial

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Complete Journal Club Article
Mouncey PR, Osborn TM, Power GS, et al. "Trial of Early, Goal-Directed Resuscitation for Septic Shock". NEJM. 2015. 14(372):1301-1311.
PubMed Full text

Clinical Question

Is there a different between EGDT versus “usual care” in 90-day mortality?


Using EGDT did not lead to an improved outcomes.

Major Points

  • Mortality was no different at 90-days 29.5% vs 29.2%
  • Slight increase is SOFA score at the first 6 hours in the EGDT group (assessment of organ dysfuction)
  • Slight increase in length of stay in the ICU

Study Design

Pragmatic, open, multicenter, parallel-group, randomized, controlled trial


56 hospitals in the UK from Feb 2, 2011 to Jul 24, 2014 (29% teaching hospitals)

Patient Demographics

  • Highlights
    • Only significant difference was age (66.4 vs 64.3)
    • ~58% male
    • ~55% had refractory hypotension
    • ~64% had hyperlactatemia

Inclusion Criteria

  • ≥18 years of age
  • Within 6 hours of presenting to ED
  • Known or presumed infection
  • 2 or more SIRS criteria
  • Refractory hypotension (<90 SBP or <65 MAP after 1L IVF trial) or hyperlactatemia (≥4.0)

Exclusion Criteria

  • Age <18yrs
  • Known pregnancy
  • Primary diagnosis of:
    • CVA, Acute pulmonary edema, Status asthmaticus, Major cardiac arrhythmia, Seizure, Drug overdose, Burn or trauma
  • GI bleeding
  • Known AIDS
  • Requirement for immediate surgery
  • DNR or advanced directives restricting the protocol
  • Contraindication to central line or blood transfusion
  • Transfer


  • Radomization within 2 hours after meeting criteria

Group 1 – EGDT (n=623)

  • Airway/breathing
  • Central line with oximetric port
  • Sedation, analgesia, and/or paralysis
  • IVF per CVP
  • Vasoactive agents per MAPs
  • Transfusion and inotrope agents per ScvO2
  • Reassess

Group 2 – Usual Care (n=620)

  • Typical care provided at clinician's discretion
  • Restricted usag of ScvO2 monitoring


Primary Outcome

  • All-cause mortality at 90 days
    • 29.5% vs 29.2% (p=0.90)

Secondary Outcomes

Findings with Significant Differences

  • SOFA score at 6hr
    • 6.4 vs 5.6 (p<0.001)
  • Receipt of advanced cardiac support
    • 37.0 vs 30.9 (p=0.026)
  • LOS in ICU
    • 2.6 vs 2.2 (p=0.005)

Findings with Non Significant Differences

  • SOFA score at 72hrs
  • Receipt of advanced respiratory, or renal support and when it started
  • Days free of the above advance support
  • LOS in ED and hospital
  • Duration of survival
  • All-cause mortality at 28 days, hospital discharge, and 1yr
  • Health related quality of life, resource use, and cost at 90d and 1yr

Criticisms & Further Discussion

  • There was a trend towards being more cost effective with usual-care ($17,647 vs $16,239, p=0.26).
  • The usual-care group still had a large portion of arterial lines and central lines. If we eliminate ScvO2 monitoring, the protocol becomes essentially guidelines for care.
  • Expected mortality in this group 40% while actual mortality was 29%. This matches closely with the 30.5% found in the Rivers 2001 EGDT Trial. This is the first time these numbers have been replicated as the US ProCESS Trial had a mortality rate of 18.9% at 60 days (compared to 30-46% as expected) and the Australia/New Zealand ARISE Trial had mortality 18.8% at 90 days (compared to 38% anticipated).

External Links


The NIHR Health Technology Assessment (HTA) Programme (07/37/47) is supported the central coordination of the trial through the ICNARC CTU, and the local site start up costs. This includes dedicated local research nurses and the economic evaluation.

See Also