Does Early Goal-Directed Therapy Reduce Mortality in Septic Shock?

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Duration of stay in the intensive care unit and receipt of cardiovascular support were greater in the EGDT group than in the usual-care group.
Duration of stay in the intensive care unit and receipt of cardiovascular support were greater in the EGDT group than in the usual-care group.

Early, goal-directed therapy (EGDT) did not result in better outcomes than usual care for patients undergoing septic shock and was associated with higher hospitalization costs, according to a study published in the New England Journal of Medicine.

Investigators from three multicenter trials (ProCESS, ARISE, and ProMISE) conducted a meta-analysis of individual patient data from each trial to determine the effect of EGDT vs usual care on 90-day mortality and secondary clinical end economic outcomes. They also sought to compare the effects of EGDT across prespecified patient and care-delivery subgroups. Core aspects of best care, including early recognition of sepsis and prompt delivery of intravenous fluids and antimicrobial agents, were promoted in the EGDT groups and the usual-care groups and reinforced through trial eligibility criteria.

The primary outcome measure was all-cause mortality at 90 days. Secondary outcome measures were in-hospital and 28-day mortality; duration stay in the emergency department, intensive care unit, and hospital; receipt and duration of invasive mechanical ventilation, vasopressors, and renal-replacement therapy; and costs and cost-effectiveness at 90 days.

From March 2008 through July 2014, the 3 trials enrolled 4211 patients at 138 hospitals in the US (ProCESS), Australia, New Zealand, Finland, Hong Kong, and the Republic of Ireland (ARISE), and England (ProMISE). A total of 3723 patients (98.9%) were included in the primary analysis, and 3511 (93.3%) were followed up to 1 year. Mortality at 90 days did not differ significantly between the two groups. Death occurred in 462 of 1852 patients (24.9%) in the EGDT group and in 475 of 1871 (25.4%) in the usual-care group.

Duration of stay in the intensive care unit and receipt of cardiovascular support were greater in the EGDT group than in the usual-care group. Duration of stay in the emergency department was shorter in the EGDT group than in the usual-care group in the ARISE trial but not in the ProCESS or ProMISE trials. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation.

“We found no evidence that EGDT resulted in lower mortality than usual care, a finding that is consistent with the results of our trial-level meta-analysis,” said the authors. “We also found that, although the three trials occurred in geographically distinct health care systems, there was no evidence of any trial-specific effect.”

Reference

PRISM Investigators. Early, goal-directed therapy for septic shock - A patient-level meta-analysis [published online March 21, 2017]. N Engl J Med. doi: 10.1056/NEJMoa1701380

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