Keys to Treating Sepsis Are Early Recognition, Fluids, and Antibiotics

Patricia Kritek, MD reviewing Mouncey PR et al. N Engl J Med 2015 Apr 2.

A third trial shows no benefit for early goal-directed therapy for septic shock.

In 2001, a single-center randomized trial demonstrated a significant mortality benefit for early goal-directed therapy (EGDT) in patients with septic shock (NEJM JW Gen Med Dec 15 2001 and N Engl J Med 2001; 345;1368). EGDT has been incorporated into guidelines (e.g., Surviving Sepsis) despite persistent skepticism. Two randomized, controlled, multicenter trials — ProCESS (NEJM JW Gen Med Apr 15 2014 and N Engl J Med 2014 Mar 18 [e-pub]) and ARISE (NEJM JW Gen Med Nov 1 2014 and N Engl J Med 2014 Oct 1 [e-pub]), published in 2014 — demonstrated no benefit for EGDT over usual care for patients with septic shock.

In a third large study of EGDT, investigators randomized 1260 English patients with severe sepsis or septic shock to EGDT or usual care; in the EGDT arm, treatment decisions were based, in part, on measured central venous pressure and central venous oxygen saturation, according to a specific algorithm. Median intravenous fluids administered prior to randomization were similar in both groups (1600 mL and 1790 mL), and all patients received antibiotics before enrollment. During the initial 6 hours after randomization, EGDT patients received more fluids, vasopressors, blood transfusions, and dobutamine. Ninety-day mortality was about 29% in both groups; however, EGDT patients had a longer median intensive care unit length of stay (2.6 days vs. 2.2 days) and were significantly more likely to receive advanced cardiovascular support (37% vs. 31%). Costs were higher, although not significantly so, in the EGDT group.

CITATION(S):

Mouncey PR et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015 Apr 2; 372:1301.