What is the latest research on early goal-directed therapy for sepsis/septic shock?

Updated: Oct 07, 2020
  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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EGDT may be considered for sepsis and septic shock [68] ; however, this approach remains controversial, and further studies are under way. One of these studies was just completed and published in 2014, the ProCESS trial, [57] which was a randomized trial of protocol-based care for early septic shock. This trial enrolled 1341 patients and compared a protocol-based EGDT (N=439) to two other arms: protocol-based standard therapy (N=446) and usual care (N=456). The results showed no significant 60-day mortality differences among the three arms, 21%, 18.2%, and 18.9%, respectively. Because these mortality rates were lower than the original EGDT study, [68] the authors performed a subgroup analysis including the sickest third of patients based on lactate levels and APACHE II scores, which showed similar or higher mortality than that from the original study, [68] but no benefit from EGDT was detected in this high-disease-severity population.

Following ProCESS, two additional EGDT studies, one from Australia-New Zealand called ARISE [58] and the other from the United Kingdom called ProMISe, [59] both found the exact same results, suggesting that strict protocolized resuscitation from septic shock is not as important as close bedside titration of care based on sound physiologic principles, independent of measures of lactate or ScvO2.

Another study recently published, the OPTIMISE study, [87] was a pragmatic, randomized, observer-blinded trial that compared a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid/inotrope (dopexamine) (N=368) with usual care within 6 hours following major gastrointestinal surgery (N=366). The outcome measured was a composite of 30-day mortality plus moderate or major complications; no composite outcome differences were observed between the two groups. The authors also performed an updated meta-analysis with the addition of their new data and found a potential reduction in complication rates, but not in mortality.

However, at the same time, a French study showed that in previously nonhypertensive patients, targeting a mean arterial pressure of 65-75 mm Hg was as good, if not better, than targeting a mean arterial pressure 80-85 mm Hg. [81] In those patients with preexisting hypertension, there was less AKI and less need for hemodialysis but also more cardiovascular compilations, presumably because the higher mean arterial pressure group received higher doses of vasopressor agents.

Further, the large retrospective study of all of Australia and New Zealand ICU care from 2000-2012 demonstrated a clear progressive decline in septic shock mortality rates from 35% to 18% over this period, with equal trends across all age groups and treatment settings. [47]

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