The 2001 Early Goal-Directed Therapy (EGDT) study for severe sepsis and septic shock has been instrumental in shaping the current practices for sepsis management. This prospective, randomized study included 288 patients and looked for differences between standard therapy and EGDT. EGDT consists of fluid bolus therapy administration and subsequent administration of vasopressors, vasodilators, and dobutamine if venous oxygen saturation and venous pressure standards aren’t met. The 2001 study found that EGDT was effective when administered early to patients and that this success may be due to placing an emphasis on hemodynamic variables. Given this, the Surviving Sepsis Campaign, a sepsis coalition dedicated to improving patient outcomes, decided to implement components of EGDT into their guidelines and sepsis care bundle.
However, the efficacy of EGDT is now being called into question due to new evidence from recently completed randomized controlled trials. In a randomized controlled study (ProMISe) published in 2015, it was shown that EGDT didn’t improve outcomes. In this study 630 patients were assigned to EGDT and 630 patients assigned to standard care. All-cause mortality at 90 days was the primary outcome.Upon completion of the study, 29.5% of patients in the EGDT group died, while 29.2% in the standard group died. The absolute risk of reduction was -.3% and the odds ratio was .95. Overall, the study found that EGDT did not improve outcomes relative to standard care and that “on average, EGDT increased costs, and the probability that it was cost-effective was below 20%.”
Such findings were confirmed by a 2017 meta-analysis focused on EGDT RCTs. This study compared the differences in mortality outcomes between EGDT and standard sepsis treatment groups. Data was included from three multicenter trials: ProCESS, ARISE, and ProMISe. Overall, 3723 patients from 138 hospitals were included for data analysis. It was found that 90-day mortality, the primary outcome, was similar for both groups with a 24.9% mortality for the EGDT group and a 25.4% mortality for the standard sepsis treatment group. The difference was not statistically significant.
Such results may be explained by the fact that in the 2001 study, fluid resuscitation timing and volume was not consistent among all groups. Another possible explanation was that the patients in the 2001 study were sicker; however, in the 2017 study it was found that EGDT efficacy doesn’t depend on severity of illness. Differences between studies may also be due to the fact that over the years sepsis standard treatment has improved with current approaches focusing on early detection and treatment. These findings suggest that EGDT may not be the most effective treatment for sepsis, however early intervention, at least with antibiotics was still found to be a best practice.