Septic Shock: Does Early, Goal-Directed Therapy Help?

Greg Martin, MD


September 29, 2017

Early, Goal-Directed Therapy for Septic Shock—A Patient-Level Meta-analysis

PRISM Investigators, Rowan KM, Angus DC, et al
N Engl J Med. 2017;376:2223-2234

Study Summary

The first study of early goal-directed therapy (EGDT) in sepsis was published in 2001,[1] and thereafter its use was integrated into clinical practice guidelines, such as the Surviving Sepsis Campaign. Because questions remained about the validity of the initial single-center study results, investigators from three parts of the world cooperatively designed trials to retest the EGDT hypothesis. Those trials were recently published,[2,3,4] and all failed to show benefit for EGDT over contemporary conventional care of sepsis patients. Those trials, however, were designed to be combined into a single patient-level meta-analysis—which is presented here—particularly to examine subgroups and provide greater power to examine the effect of EGDT in early sepsis.

Overall, the three studies included 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar between EGDT and usual care (24.9% vs 25.4%, P = .68). EGDT was associated with greater use of intensive care (5.3 vs 4.9 days, P = .04) and cardiovascular support (1.9 vs 1.6 days, P = .01), while other outcomes did not differ significantly. Average costs were higher to deliver EGDT. According to subgroup analyses, EGDT showed no benefit for patients with worse shock or for hospitals with less inclination to use vasopressors or fluids during usual resuscitation. The authors concluded that EGDT does not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics.


This well-conducted, preplanned, patient-level meta-analysis again demonstrates that use of EGDT in sepsis does not improve clinical outcomes compared with contemporary sepsis care where methods are in place to identify patients early and initiate care. One new finding is that use of EGDT is associated with greater healthcare expenses. This is not surprising and not a reason to abandon or narrow the delivery of critical sepsis care. It is, however, unfortunate that this combined analysis was unable to tease out any subgroups for whom EGDT may be more or less effective, such as those with more severe shock. This is particularly true because sepsis remains a common and difficult condition causing millions of deaths each year around the world.



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