Is early goal-directed therapy (EGDT) effective in the management of severe 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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There is significant controversy surrounding goal-directed therapy (EGDT) in the management of sepsis and septic shock. EGDT was previously evaluated in a small, single, randomized trial at a single institution. [68] Subsequently, three newer, large, multicenter randomized trials were performed in the United States (ProCESS [Protocolized Care for Early Septic Shock]), [57] Australia (ARISE [Australasian Resuscitation In Sepsis Evaluation]), [58] and the United Kingdom (ProMISe [Protocolised Management In Sepsis]). [59]

In the ProCESS trial, 1341 patients with septic shock in 31 academic hospital EDs received treatment based on one of three approaches: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or standard care. [69, 70] No significant differences between groups were found for 90-day mortality, 1-year mortality, or the need for organ support.

Similar findings were reported from both the ARISE and the ProMISe trials. Important to note, measuring lactate, targeting ScvO2 values, and insertion of a central venous catheter were not associated with improved outcomes. What was important was the direct and aggressive individualized care each patient received, including early bacteriologic cultures of appropriate sites (eg, blood, urine, sputum), early and correct institution of broad-spectrum antibiotics, restoration of blood pressure, and reversal of evidence of end-organ perfusion. These findings are reasonable when considered within the context of acute care medicine resuscitation principles. Namely, stabilize the patient, reverse the cause of shock, and do no additional harm.

Results from a small 2017 study suggested that in patients with septic shock who did not respond to high doses of conventional vasopressors, angiotensin II may be an emerging treatment to increase blood pressure. [71, 72] The study had limitations and further research is needed. Results are awaiting US Food and Drug Administration (FDA) consideration for approval.

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