How Early Goal-Directed Therapy Changed Sepsis Care

On the Shoulders of Giants

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Even though early goal-directed therapy (EGDT) has subsequently been shown to be no more effective than usual care, this landmark trial put a spotlight on sepsis care, especially starting aggressive measures as early as possible in the ED.

Why does this matter?
Sepsis is associated with a high mortality rate.  EGDT was an early systematic approach to reduce this.  The lessons learned from this early iteration were helpful in finding out what works best for sepsis patients.  Also, if you are still practicing EGDT by the original protocol, you need to take into consideration subsequent studies that have shown certain aspects were not as helpful as previously thought.

Swept up in the Rivers
This was a single-center RCT of 263 patients with septic shock or severe sepsis who received usual care or EGDT.  They found markedly improved survival with EGDT, 30.5% vs 46.5% mortality.  There were a number of issues with this study.  EGDT was a complex composite of several treatments (click here for EGDT in a nutshell or for the free full text) including early recognition, early cultures, source control, antibiotics, vasopressors, mechanical ventilation, aggressive IV fluids, transfusions as needed, invasive monitoring, and inotropes as needed.  It was hard to know which intervention was most important.  Also, baseline mortality rates at this center were extraordinarily high.  There were also concerns about conflict of interest that seem to have been thoroughly debunked.  Subsequent studies have shown no advantage of EGDT compared to usual care (ARISE, ProCESS, ProMISe, and PRISM); more on this over the next 2 weekends.  These authors deserve credit for drawing attention to the need for early aggressive care for sepsis patients in the ED.  Sepsis is first an ED disease, not just an ICU disease.  EGDT was a clarion call that when you pay attention to and take meticulous care of sepsis patients in a timely manner, they do better.  The across-the-board improvements in sepsis mortality over the past 16 years may not have happened without this study as a wake up call.

Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77.

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