Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock

Abstract

Background: Many investigators have reproduced the mortality reduction shown in the original trial of early goal directed therapy (EGDT) in patients with severe sepsis and/or septic shock. Three large randomized controlled trials (RCTs) found neutral results when compared to usual care and a modified form of EGDT. Some have interpreted these studies as a reason to question the efficacy of EGDT.

Objectives: The purpose of this study was to comprehensively examine the effect of EGDT in the treatment of severe sepsis and/or septic shock in the literature.

Methods: A systematic review and meta-analysis of RCTs and prospective studies were performed, which extracted studies from PubMed, Elsevier ScienceDirect, Cochrane, Clinicaltrials.gov, Google Scholar, China Knowledge Resource Integrated Database, and Wanfang Database. The mortality trend in the control group from included studies was analyzed.

Results: Seven RCTs and twelve prospective studies enrolling 3502 EGDT and 3791 usual care participants were included in the analysis. EGDT was found to reduce overall mortality compared to usual care groups. This reduction in mortality was apparent in prospective and randomized control trials conducted before 2010. Over this time period there was a reduction in mortality in patients receiving usual care.

Limitations: This conclusion was limited by the small size of some selected studies and complicated by the long range of time during the conduction of these studies. These studies were further biased because of the lack of blinding and the crossover of care between the EGDT and usual care groups.

Conclusions: EGDT significantly reduced mortality in patients with severe sepsis and/or septic shock over 15 years since its publication. Recent studies examining usual care with EGDT have similar mortality benefit because of the diminished treatment effect. This treatment effect is diminished for multiple reasons. With progress in the management of this disease the benefit of EGDT on overall mortality has become comparable with the usual care for sepsis patients. This is because many of the components of EGDT have been incorporated into usual care protocols. As a result, the conclusion that EGDT is ineffective cannot be made. A more rigorous RCT which adjusts for the factors that narrows the treatment effect between groups is required. Given the current state of sepsis care and equipoise that exist, this would be difficult.

Keywords:

• Early goal directed therapy (EGDT)
• Mortality
• Septic shock
• Severe sepsis

Transparency

Declaration of funding

This study was not funded.

Declaration of financial/other relationships

B.L., X.D. and J.Y. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.