ProMISe: Trial of Early, Goal-Directed Resuscitation for 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).

EGDT.PNG

Mouncey P. et al. "Trial of Early, Goal-Directed Resuscitation for Septic Shock". The New England Journal of Medicine. 2015; 372:1301-1311

Link to Article: https://www.nejm.org/doi/full/10.1056/nejmoa1500896


Clinical Question

In adult patients with septic shock, does early goal-directed therapy (EGDT) compared with standard therapy reduce mortality at 90 days?

  • Type of Trial: RCT

  • Blinding: non-blinded design

  • Setting: 56 hospitals in Englad (29% teaching hospitals) from Feb 2011 - July 2014

PICO

  • Population:

    • 1,260 adults presented to ED with suspected or confirmed infection and 2+ SIRS criteria AND evidence of refractory hypotension (same as ARISE)

      • Refractory hypoperfusion/hypotension was defined as SBP<90 or MAP<65 after 1000cc IVF challange within 60 min OR lactic>4

    • Given 1st dose of IV abx prior to randomization

    • Excluded: ACS, acute cerebral vascular event, acute pulmonary edema, status asthmaticus, major arrythmia, DNR order, and more

  • Intervention:

    • EGDT w/a CVL capable of continuous SCVO2 measurement + arterial line

    • A treatment algorithm based on River’s original EGDT algorithm for 6 hours

    • Intervention was provided by at least one trained staff member but other personnel involved and treatment location was decided according to site

  • Control:

    • Usual care - arterial and CVL if clinically appropriate, NO SCVO2 measurement permitted during 6 hours; decisions made regarding care was at discretion of physician

  • Outcome:

    • Primary outcome: 90 day mortality

      • No difference (29.5% in intervention, 29.2% in usual care; P value-0.9)

    • Secondary outcomes:

      • The only statistically significant different outcomes were SOFA score at 6 hours and median length of stay in ICU. Both were lower in the usual care group. Comparison is EGDT vs usual care)

Conclusions

In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome


Strengths

  • Robust methodological approach. Consistent inclusion criteria and protocol with ARISE study

  • Important outcome measures

  • Cost analysis and quality-adjusted life years an important outcome measure

  • Study population representative of critically ill patients with septic shock (mean APACHE II score 18. ARISE was 15)

  • Trial statistical analysis plan was published prior to completion of the study

  • Adherence to EGDT ranged from 86-95%

Weaknesses

  • Only 1/3 of eligible patients were recruited. The authors acknowledge this and provide an explanation. As in all studies that enroll patients presenting to ED, recruitment is more challenging on weekends and during out of office hours

  • Non blinded

Sources:

https://www.thebottomline.org.uk

Rachel MulderComment