Difference between revisions of "EBQ:ProMISe Trial"

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| title= Trial of Early, Goal-Directed Resuscitation for Septic Shock
 
| title= Trial of Early, Goal-Directed Resuscitation for Septic Shock
 
| abbreviation= ProMISe Trial
 
| abbreviation= ProMISe Trial
 +
| expansion= Protocolised Management In Sepsis
 
| published= April 2, 2015
 
| published= April 2, 2015
 
| author= Mouncey PR, Osborn TM, Power GS, et al
 
| author= Mouncey PR, Osborn TM, Power GS, et al
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| fulltexturl= http://www.nejm.org/doi/full/10.1056/NEJMoa1500896
 
| fulltexturl= http://www.nejm.org/doi/full/10.1056/NEJMoa1500896
 
| pdfurl=
 
| pdfurl=
 +
| status=Complete
 
}}
 
}}
 
==Clinical Question==
 
==Clinical Question==
Line 17: Line 19:
  
 
==Conclusion==
 
==Conclusion==
Using EGDT did not lead to an improved outcome
+
Using EGDT did not lead to an improved outcomes.
  
 
==Major Points==  
 
==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==
 
==Study Design==
+
Pragmatic, open, multicenter, parallel-group, randomized, controlled trial
 +
 
 
==Population==
 
==Population==
56 hospitals in the UK
+
56 hospitals in the UK from Feb 2, 2011 to Jul 24, 2014 (29% teaching hospitals)
 
===Patient Demographics===
 
===Patient Demographics===
 +
*Highlights
 +
**Only significant difference was age (66.4 vs 64.3)
 +
**~58% male
 +
**~55% had refractory hypotension
 +
**~64% had hyperlactatemia
 +
 
===Inclusion Criteria===
 
===Inclusion Criteria===
 
*≥18 years of age
 
*≥18 years of age
Line 34: Line 46:
  
 
===Exclusion Criteria===
 
===Exclusion Criteria===
*CVA
+
*Age <18yrs
*ACS
+
*Known pregnancy
*Cardiac dysrhythmia
+
*Primary diagnosis of:
*Acute pulmonary edema
+
**CVA, Acute pulmonary edema, Status asthmaticus, Major cardiac arrhythmia, Seizure, Drug overdose, Burn or trauma
*GI bleed
+
*GI bleeding
*Seizure
+
*Known AIDS
*Drug overdose
+
*Requirement for immediate surgery
*Burn or trauma
+
*DNR or advanced directives restricting the protocol
*Immediate surgery needed
+
*Contraindication to central line or blood transfusion
*CD4 count <50
+
*Transfer  
*Advance directive that restricts either protocol
 
*Contraindication to interventions including refusal of blood transfusions
 
*Pregnant
 
*Transfer patient
 
  
 
==Interventions==
 
==Interventions==
Line 60: Line 68:
 
*Reassess
 
*Reassess
 
===Group 2 – Usual Care (n=620)===
 
===Group 2 – Usual Care (n=620)===
*Airway/Breathing
+
*Typical care provided at clinician's discretion
*2 large bore IVs (or central line if not achieved)
+
*Restricted usag of ScvO2 monitoring
*Sedation, analgesia, and/or paralysis
 
*Resuscitate with 2L IVF
 
*IVF and vasopressors per MAPs
 
*Reassess
 
  
 
==Outcomes==
 
==Outcomes==
 
 
 
===Primary Outcome===
 
===Primary Outcome===
+
*All-cause mortality at 90 days
 +
**29.5% vs 29.2% (p=0.90)
  
 
===Secondary Outcomes===  
 
===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)
  
===Subgroup analysis===
+
====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==
 
==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==
 
==External Links==
Line 87: Line 103:
  
 
==Funding==
 
==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.
 +
 
 +
==See Also==
 +
*[[Sepsis]]
  
==Sources==
+
==References==
 
<references/>
 
<references/>
  
[[Category:EBQ]]
+
[[Category:EBQ]][[Category:Critical Care]]

Latest revision as of 23:25, 26 February 2016

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.

See Also

References