Early Goal-Directed Therapy for Sepsis: Show Me the Data!
A meta-analysis of randomized sepsis trials showed mortality benefit with early goal-directed therapy.
The validity of various aspects of early goal-directed therapy (EGDT) for patients with severe sepsis and septic shock has been challenged in non–peer-reviewed publications. Researchers conducted a meta-analysis of randomized controlled trials in adult patients with sepsis; eligible trials described the resuscitative protocol used to achieve predetermined hemodynamic endpoints and included control groups of patients who received standard care. The primary endpoint in the meta-analysis was mortality. Assessment of trial quality included evaluation of diagnostic criteria for patient selection and internal validity.
Of 903 reports identified in a comprehensive search, 29 were chosen for complete manuscript review, and 9 (involving a total of 1001 patients) were eligible for inclusion in the final analysis. Overall, mortality was significantly lower in patients who received resuscitation directed by quantitative endpoints than in those who received standard care (odds ratio, 0.64; 95% confidence interval, 0.43–0.96). Analysis of predefined subgroups of patients who received endpoint-directed resuscitation early (6 studies) demonstrated lower mortality with this procedure (OR, 0.50; 95% CI, 0.37–0.69). However, no mortality benefit resulted from late (>24 hours) resuscitation (OR, 1.16; 95% CI, 0.60–2.22). The results remained consistent in sensitivity analyses. Because the early endpoint-based resuscitation strategy had such a clear effect on mortality, the investigators performed a post hoc sensitivity analysis to determine whether any specific study had a disproportionate influence on the overall results; as each study was excluded and data from the remaining studies were reanalyzed, the significant mortality benefit of early goal-directed resuscitation remained consistent.
Comment: This meta-analysis showed a dramatic mortality benefit from early resuscitation that was targeted to achieve specified physiologic goals. The authors conclude that the data strongly support the Surviving Sepsis Campaign recommendations for EGDT in septic patients. Large multicenter studies evaluating the benefits of EGDT, including various individual components, currently are under way or nearing completion. Until those results are available, clinicians resuscitating patients with sepsis syndrome are well advised to embrace the principles of EGDT, which are supported by more than 14 peer-reviewed publications.
Published in Journal Watch Emergency Medicine October 3, 2008
Citation(s): Jones AE et al. The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis. Crit Care Med 2008 Oct; 36:2734