Does early goal-directed therapy improve outcomes when treating septic shock?

Early goal-directed therapy (EGDT)—a 6-hour resuscitation protocol using central venous monitoring to administer fluids, vasopressors, inotropes, and as-needed transfusions for early treatment of septic shock—does not improve mortality and can lead to longer intensive care unit stays and higher hospitalization costs. Even patients at the highest risk of mortality did not benefit from EGDT in this analysis. Notably, another study in the same journal of the timing of more basic care for septic shock in the emergency department, including drawing blood cultures, measuring lactate levels, and administering antibiotics within 3 hours, showed that longer times were associated with higher in-hospital mortality. (LOE = 1a)

The PRISM Investigators, Rowan KM, Angus DC, et al. Early, goal-directed therapy for septic shock—a patient-level meta-analysis. N Engl J Med 2017;376(23):2223-2234. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376(23):2235-2244.  [PMID:28320242]

Meta-analysis (randomized controlled trials)

Government

Concealed

Inpatient (any location)

The ProCESS, ARISE, and ProMISe trials were multi-center randomized controlled trials that compared EGDT with usual care for the management of septic shock. Each trial revealed a lack of mortality benefit with the use of EGDT. The investigators planned a prospective meta-analysis prior to the enrollment of the first patient into the first trial with the goal of pooling patient-level data from all 3 trials (N = 3723). Patients in the EGDT group and the usual care group were balanced at baseline. For the primary outcome of 90-day mortality, the 2 groups had similar mortality rates (24.9% in the EGDT group vs 25.4% in the usual care group). Additionally, the EGDT group had longer intensive care unit stays, higher costs, and required more cardiovascular support. Subgroup analyses showed no benefit of EGDT in patients with greater severity of illness or those with a higher intensity of underlying care. A separate restrospective study looked at New York's mandated emergency care for the treatment of severe sepsis and septic shock. In this study, a delay in timing of the delivery of a 3-hour bundle, consisting of obtaining blood cultures prior to starting antibiotics, measuring serum lactate, and administering broad-spectrum antibiotics, was associated with higher in-hospital mortality with each incremental hour until the completion of the 3-hour bundle (odds ratio of death until completion of 3-hour bundle: 1.04 per hour; 95% CI 1.02 - 1.05).