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

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.

References