H. Bryant Nguyen et al. Critical Care 2016; 20:160 (Published: 1 July 2016)
DOI: 10.1186/s13054-016-1288-3
"Conclusions
EGDT has been shown to have internal and external validity in reducing mortality for the treatment of severe sepsis and septic shock. The various approaches examined by the trio of EGDT trials suggest that alternative strategies can provide an equal reduction in mortality. However, as a result of multiple methodological differences when compared to the original EGDT trial (including undefined usual care), the external validity of these alternative strategies remain to be determined. The combination of a diminishing treatment effect between these alternative strategies and EGDT, along with a global reduction in sepsis mortality over the last 15 years, can render even well-conducted control trials underpowered and inconclusive.
The trio of EGDT trials provides enormous insight into explaining the discrepancy in trials attempting to replicate a previously positive trial over a decade later. It has been shown that large prospective observational studies which have confirmed the external validity and reliability of the EGDT trial provide an equally reliable scientific alternative to randomized control trials.
In this era of global reductions in sepsis mortality, clinicians should view EGDT as a verb (series of actions) rather than a noun. Future research should focus on the precision for using invasive or non-invasive approaches at the initial presentation of high risk patients."