ProMISe Trial Adds Skepticism to Early Goal-Directed Therapy for Sepsis
Clinical question: Does EGDT for sepsis reduce mortality at 90 days compared with standard therapy?
Background: EGDT is recommended in international guidelines for the resuscitation of patients presenting with early septic shock; however, adoption has been limited, and uncertainty about its effectiveness remains.
Study design: Pragmatic, multicenter, randomized controlled trial (RCT) with intention to treat analysis.
Setting: Fifty-six National Health Service EDs in the United Kingdom.
Synopsis: ProMISe trial enrolled 1,251 patients with severe sepsis or septic shock and patients were randomized to usual-care group (as determined by the treating clinicians) or algorithm-driven EGDT, which included continuous central venous oxygen saturation (ScvO2) using the original EGDT protocol. The primary outcome of all-cause mortality at 90 days was not significantly different between the two groups: 29.5% in EGDT and 29.2% in the usual-care group (P=0.9). This translated into a relative risk of 1.01% (95% CI 0.85-1.20) in the EGDT group. There were no meaningful differences in secondary outcomes.
Both groups in this study were actually well matched for most interventions. The main difference was in the use of continuous ScvO2 measurement and central venous pressure to guide management. Perhaps we should not completely dismiss the term EGDT. Most of our “usual care” consists of early intervention and goal-directed therapy.
Bottom line: In patients identified early with septic shock, the use of EGDT vs. “usual” care did not result in a statistical difference in 90-day mortality.
Citation: Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301-1311.