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

Authors: Mouncey PR et al., N Engl J Med 2015 Apr 2; 372:1301

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.

Comment

We have convincing evidence that formalized EGDT does not benefit patients with septic shock and potentially results in more interventions with little value. In all three studies, patients were identified early and subsequently were given antibiotics and 1 to 2 L of intravenous fluids. The keys to treating sepsis patients probably are early recognition, early fluid resuscitation, and appropriate antibiotics.