The long-awaited results of the Protocolized Care for Early Septic Shock (ProCESS) multicenter, randomized clinical trial were released today in the March 2014 issue of the New England Journal of Medicine.
ProCESS compared mortality and other outcomes in 1341 patients with septic shock treated using three different approaches:
- Protocol-based early goal-directed therapy (EGDT): Protocol required placement of central line for pressure and ScvO2 monitoring, and administration of IV fluids, vasopressors, dobutamine or PRBCs, as directed by the EGDT protocol.
- Protocol-based standard therapy: Less aggressive protocol than EGDT requiring only adequate peripheral IV access using >2 large bore (18 gauge or larger) IVs, with central line placement only if peripheral access failed. Fluids and vasoactive agents were administered to reach SBP and shock index goals and address hypoperfusion and fluid status, which were assessed once an hour. PRBCs were administered only if hemoglobin dropped below 7.5 g/dl.
- Usual care: The bedside clinicians directed all care at their discretion with the study coordinator collecting data, but not prompting any actions.
The study’s primary outcome was in-hospital death from any cause at 60 days. Secondary mortality outcomes included death from any cause at 90 days, and cumulative mortality at 90 days and 1 year. Other outcomes included duration of acute CV failure (as determined by the need for vasopressor support), acute respiratory failure and acute renal failure, hospital and ICU length of stay, and discharge disposition.
The statistically significant differences in treatment approaches between the 3 groups during the resuscitation period (0-6 hours) are summarized in the table below:
|EGDT protocol (n=439)||Standard therapy protocol (n=446)||Usual care (n=456)||p-value|
|IVF in first 6 hrs (L)*||2.8||3.3||2.3||<0.001|
|Vasopressor use (%)||54.9%||52.2%||44.1%||0.003|
|Dobutamine use (%)||8.0%||1.1%||0.9%||<0.001|
|PRBC transfusion (%)||14.4%||8.3%||7.5%||0.001|
*Crystalloids were the predominant fluid used in all 3 groups (96% overall); patients in the EGDT group received fluids at the most consistent rate.
The use of antibiotics, glucocorticoids and activated protein C was similar across the groups. Use of IVF, vasopressors, dobutamine and blood transfusions in the ancillary care period (6-72 hours) did not differ significantly among the groups.
ProCESS Results Summary
Results showed no signiﬁcant difference in mortality between the three groups at 60 or 90 days. A higher incidence of renal failure at 1 week was observed in the standard therapy protocol group, but no statistically significant differences in CV or respiratory failure were observed between the groups.
The main outcomes of ProCESS are summarized in the table below:
|EGDT protocol||Standard therapy protocol||Usual care||p-value|
|In-hospital death by 60 days||21.0%||18.2%||18.9%||0.83|
|Death by 90 days||31.9%||30.8%||33.7%||0.66|
|New organ failure during 1st week|
ProCESS reinforces the need for early recognition of sepsis and early administration of antibiotics, and appropriate and timely maintenance of circulatory function using adequate IV fluids and vasoactive agents.
A significant insight and take-home message provided by ProCESS is the finding that central hemodynamic and O2 monitoring did not result in better outcomes than those achieved by clinical assessment of the circulation. This finding should prompt institutions and regulatory bodies to revisit their sepsis guidelines and possibly replace the need for central hemodynamic monitoring with other lower-risk, less expensive, and equally effective alternatives.
We will review and revise the guidelines presented in the Sepsis Clinical Guide app to account for the findings of ProCESS.
The ProCESS study and accompanying supplementary materials may be accessed on the NEJM website.
Daniel Nichita, MD