The effect of early goal-directed therapy on mortality in patients with severe sepsis and septic shock: a meta-analysis

Background: The Surviving Sepsis Campaign has recommended early goal-directed therapy (EGDT) as an essential strategy to decrease mortality among patients with severe sepsis and septic shock. However, three latest multicenter trials failed to show its benefit in the patients with severe sepsis and septic shock. This article was to evaluate the effect of EGDT on the mortality of patients with severe sepsis and septic shock.

Methods: Relevant studies from PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were identified from January 1, 2001 to June 13, 2015. With both randomized controlled trials (RCTs) and non-RCTs selected, a meta-analysis on the effects of EGDT on all identified trials was performed. The primary outcome was the inhospital mortality. In subgroup, RCTs and non-RCTs were analyzed, respectively.

Results: A total of five RCTs and 10 non-RCTs involving 3285 patients in EGDT group and 3233 patients in the control group were identified. Pooled analyses of all studies showed significant difference in the inhospital mortality between the EGDT group and the control group (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.74-0.94; P = 0.003) with substantial heterogeneity (χ2 = 24.93, P = 0.04, I(2) = 44%). In subgroup analysis, there were no significant difference in inhospital mortality between the EGDT group and the control group (RR, 0.95; 95% CI, 0.83-1.10; P = 0.51) with no significant difference in heterogeneity (χ2 = 6.62, P = 0.16, I(2) = 40%) in RCTs. In non-RCTs, EGDT significantly reduced inhospital mortality (RR, 0.75; 95% CI, 0.65-0.88; P = 0.0003) with no significant difference in heterogeneity (χ2 = 11.96, P = 0.22, I(2) = 25%).

Conclusions: This meta-analysis suggests that EGDT can significantly reduce the mortality among patients with severe sepsis and septic shock.