The ProCESS Trial
“A Randomized Trial of Protocol-Based Care for Early Septic Shock” (The ProCESS Trial)
The Rivers paper in 2001 was the landmark paper on management of sepsis, establishing a protocol called “Early Goal Directed Therapy” that relied on Central Venous Pressure, Central Venous Oxygen Saturation, and MAP to guide the administration of fluid, pressors, inotropes, and blood transfusions. The Rivers paper found that this protocol reduced mortality from sepsis fro 46.5% to 30.5%, and became widely regarded as a breakthrough in the management of sepsis. However, the Rivers protocol is not always easily implemented, as it relies on invasive procedures that are resource-intensive from both a physician and nursing perspective. Subsequent trials have explored whether the interventions Rivers identified as therapeutic (fluid, pressors, inotropes, blood) could instead be administered based on a more simple protocol. The Process Trial compared the Rivers protocol, a more simple protocol, and “usual care”, to evaluate whether similar outcomes could be achieved with less invasive and resource-intensive means.
Three arms of Process:
Rivers EGDT (n = 439)
CVP > 8mmHg (if not, give fluids)
ScvO2 > 70% (if not, give blood until hematocrit is >30%, if still ScvO2 <70% – inotropes)
MAP = 65-90 (if not, give pressors)
Closely adhered to Rivers – amount & timing of fluid but not type, thresholds for pressor use but not type
Actions outside of these guidelines were at the discretion of the physician
Protocol Based Standard Therapy (n = 446)
Central venous line placement not necessary if peripheral lines adequate
Goals – systolic blood pressure, and shock index (HR/SBP).
Clinical assessment of fluid status, hypoperfusion
Hbg < 7.5 threshold for RBC transfusion
Usual care (n = 456)
No protocol. Clinical judgement of physician.
Baseline characteristics well matched between these groups – similar age, similar health status, source of infection similarly distributed.
Difference in treatments:
Volume of fluid – most in Protocol-Based Standard Therapy, second in EGDT, third in Usual Care
Vasopressors – EGDT 55, Protocol-Standard 52, Usual Care 44
Dobutamine use – EGDT 8.0%, Protocol-Standard 1.1%, and Usual Care 0.9%; P<0.001;
Packed Red-Blood Cell transfusions, EGDT 14.4%, Protocol-Standard 8.3%, and Usual Care 7.5%; P=0.001
Highlights from results:
New Organ failure in first week
Duration of Organ Support
Use of hospital resources
Discharge status at 60 days
Serious adverse events
The only difference was in rate of admission to ICUs — higher in the EGDT group. Also significant (p = .04) was higher rates of new renal failure in the protocol based standard therapy vs in the EDGT or the usual care.
These findings suggest that EGDT is not superior to Protocol-Standard Care; it may be possible to address sepsis with appropriate interventions guided on more simple parameters without sacrificing quality of care
Caveats/Criticisms of ProCESS
Process Paper itself identifies several potential criticisms/weaknesses:
“Rivers patients may have been a sicker population, more persistent shock”
“Furthermore, changes during the past decade in the care of critically ill patients, including the use of lower hemoglobin levels as a threshold for transfusion, the implementation of lung-protection strategies, and the use of tighter control of blood sugar, may have helped lower the overall mortality and may have reduced the marginal benefit of alternative resuscitation strategies”
This second point is particularly salient – comparing Rivers vs. Standard Protocol vs. Usual Care may have shown much bigger differences in the 90s or early 2000s, when the Rivers paper was originally published. However, much more is known now about the appropriate treatment of sepsis, potentially understating the differences between Rivers vs. the Standardized Protocol.