Dr Mike Howlett and Dr Benoit Phelan

A Randomized Trial of Protocol-Based Care for Early Septic Shock. The ProCESS Investigators. published on March 18, 2014, at NEJM.org.

Take home message:

Following SSC Guidelines may be most important initial step: Identify sepsis early, give fluids and antibiotics.

Refractory Sepsis may not need interventions beyond standard resuscitation to be effectively treated.

e.g., don’t need SvO2 measurements.

Study used BP <90 and Lactate as markers for end organ dysfunction in sepsis.

See Full Appraisal Below…..

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CRITICAL REVIEW FORM – THERAPY

Guide		Comments
I.	Are the results valid?
A.	Did experimental and control groups begin the study with a similar prognosis (answer the questions posed below)?	EGDT protocol-based therapy vs. protocol-based standard therapy vs. usualcare, in Sepsis
1.	Were patients randomized?	Yes
2.	Was randomization concealed (blinded)?	No, different physicians depending on group allocation
3.	Were patients analyzed in the groups to which they were randomized?	yes
4.	Were patients in the treatment and control groups similar with respect to known prognostic factors?	Yes.
B.	Did experimental and control groups retain a similar prognosis after the study started (answer the questions posed below)?
1.	Were patients aware of group allocation?	No
2.	Were clinicians aware of group allocation?	Yes
3.	Were outcome assessors aware of group allocation?	Yes
4.	Was follow-up complete?	Yes
II.	What are the results (answer the questions posed below)?
1.	How large was the treatment effect?	See below: no significant difference
2.	How precise was the estimate of the treatment effect?	RR with protocol-based therapy vs. usual care, 1.04; 95% CI, 0.82 to 1.31; P = 0.83; RR with Protocol -based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to1.51; P = 0.31. NS differences in 90-day mortality, 1-year mortality, or need for organ support
III.	How can I apply the results to patient care (answer the questions posed below)?
1.	Were the study patients similar to my patient?	Yes. SIRS + (refractory hypotension or serum Lactate >4)
2.	Were all clinically important outcomes considered?	yes
3.	Are the likely treatment benefits worth the potential harm and costs?	Yes. Using less interventions e.g., SvO2, CVP line measurements is easier and cheaper with same outcome

 

Process trial: EGDT vs Protocol based standard therapy vs Usual Care

PICO:

P: patients with severe sepsis in ED

I: EGDT vs protocol based usual care

C: Usual Care

O: Mortality

 

Question; In patients with severe sepsis presenting to the ED, does protocol based resuscitation improve mortality?

 

Methods:

patients over 18

Screened via SIRS +

refractory to initial SSC (refractory BP<90 systolic to fluids, needing pressors or serum lactate > 4)

Multicenter EDs in USA, annual census > 40,000

1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care.

 

Results:

Mortality lower than estimated from Rivers et al.

By 60 days, there were 92 deaths in the protocol-based EGDTgroup (21.0%),

81 in the protocol-based standard-therapy group (18.2%), and

86 inthe usual-care group (18.9%)

RR with Protocol -based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P = 0.31.RR with protocol-based therapy vs. usual care, 1.04; 95% CI, 0.82 to 1.31; P = 0.83;

NS differences in 90-day mortality, 1-year mortality, or need for organ support

 

Discussion:

Protocols did not improve survival vs usual care

Vs Rivers data, ? improvement in use of SSC guideline across hospitals has generally ?improved overall care and reduced mortality. This trial was multicenter, with better enrollment

Limitations: data for all groups based on initial compliance with SSC Guidelines, i.e, is the most important care actually delivered before randomization?

Not powered for subgroup analysis

 

Take home message:

Following SSC Guidelines may be most important initial step: Identify sepsis early, give fluids and antibiotics.

Refractory Sepsis may not need interventions beyond standard resuscitation to be effectively treated.

e.g., don’t need SvO2 measurements.

Study used BP <90 and Lactate as markers for end organ dysfunction in sepsis.

 

Two further trials: ARISE and PROMISE have come out and/or just been presented at meetings, both of which appear to support the same conclusions. Awaiting revisions to SSC Guidelines. . .

 

Mike Howlett MD April 8, 2015