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Early Goal-Directed Therapy in Septic Shock Does Not Reduce Deaths (ProCESS)


Clinical question

Does use of protocol-based early goal-directed therapy with central venous monitoring decrease mortality in patients presenting with septic shock?

Bottom line

Protocol-based care for resuscitation in septic shock, with or without the use of central venous monitoring, does not confer a mortality advantage over care provided according to a physician’s bedside judgment. (LOE = 1b)


The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014 Mar 18. [Epub ahead of print]

Study design

Randomized controlled trial (nonblinded)

Funding source





Inpatient (any location)


Previous research suggested that a 6-hour protocol of early goal-directed therapy (EGDT) using central hemodynamic monitoring to guide the use of intravenous fluids, vasopressors, inotropes, and transfusions reduces mortality in patients who present with septic shock. In the current study, investigators randomized 1341 patients, using concealed allocation, to 1 of 3 groups: (1) protocol-based EGDT, (2) protocol-based standard therapy, or (3) usual care. Protocol-based standard therapy required peripheral venous access only with the administration of fluids and vasopressors to maintain blood pressure, optimize fluid status, and address hypoperfusion. In the usual care group, care was at the discretion of the bedside physicians. Both protocol-based groups had approximately 90% or greater adherence to the protocols. Notably, although central venous catheter placement was not required in the protocol-based standard therapy or usual care groups, the majority of patients in each had such catheters placed, though only 4% were used for actual central venous monitoring. Analysis was by intention to treat. During the first 6 hours of resuscitation, more patients in the 2 protocol-based groups received vasopressors than patients in the usual care group. Patients in the EGDT group were also more likely to receive dobutamine and red-cell transfusions. Between 6 hours and 72 hours, however, the 3 groups had similar use of intravenous fluids, vasopressors, and transfusions. For the primary outcome of 60-day in-hospital mortality, there were no significant differences among the 3 groups. Patients in the protocol-based standard therapy group were slightly more likely to require renal replacement therapy (6% vs 3% in the other 2 groups; P = .04), whereas patients in the EGDT group were more likely to require intensive care unit admission (90% vs 85% in the other 2 groups; P = .01). Serious adverse events were rare and did not differ among the groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

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