EBQ:ProMISe Trial
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
PubMed Full text
Clinical Question
Is there a different between EGDT versus “usual care” in 90-day mortality?
Conclusion
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
Population
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
Interventions
- 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
Outcomes
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
Funding
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.