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Current sepsis trials have not shown a benefit from protocolized early goal-directed care, as opposed to usual care.
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Early recognition of sepsis, fluid resuscitation, appropriate antibiotic treatment, source control, and the application of multidiscipline evidence-based medicine are essential components of sepsis care.
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Central venous pressure and continuous central venous saturation measurements, placement of central venous catheters, and routine blood transfusions are not necessary for all
The New Usual Care
Section snippets
Key points
Mortality in the era before early goal-directed therapy
In the roughly 35 years leading up to the introduction of the SSC, the overall mortality for patients with sepsis was 49.7%.11 Most publications over that time reported mortalities between 40% and 80%.11 Although there had been some improvements in mortality, the trend was small.11 Although it is easy to assume that this was the result of outdated treatments, the therapies delivered then were similar to modern interventions. Despite this, recent studies have suggested dramatic improvements in
Early goal-directed therapy
In 2001, Rivers and colleagues2 published a landmark article that challenged contemporary sepsis care. The investigators theorized that if patients could be treated in a timely and targeted manner to correct the imbalance between oxygen delivery and demand, the progression to multiorgan failure and death could be halted. They did this by targeting specific central hemodynamic end points during the initial 6 hours of treatment of severe sepsis (defined by the presence of 2 systemic inflammatory
A shift in sepsis care
After publication of the Rivers and colleagues2 trial, EGDT was viewed as cornerstone to successful sepsis management.15 In 2002, EGDT was suggested as a guideline for care by an expert sepsis panel.16 In 2004, the SSC, a committee composed of critical care and infectious disease experts representing 11 international organizations, recommended the following EGDT hemodynamic targets with grade B evidence: CVP of 8 to 12 mm Hg, MAP greater than or equal to 65 mm Hg, central venous or mixed venous
The ProCESS, ARISE, and ProMISe trials
Given the criticisms, 3 multicenter, randomized, independent but collaborative trials were conducted in the United States (ProCESS), Australia (ARISE), and United Kingdom (ProMISe) to evaluate the benefits of EGDT.8, 9, 10 Each trial used the definitions of severe sepsis and septic shock used in the original EGDT trial. However, the definition of refractory hypotension was changed from unresponsive to 20 to 30 mL/kg over 30 minutes (as in the original EGDT trial) to unresponsive to a 1-L fluid
What makes a difference?
The results of these 3 large trials provide a wealth of evidence to further refine current sepsis management. Importantly, strict adherence to the original goals of the initial EGDT trial and the methods implemented to reach central hemodynamic end points does not seem to result in a significant difference in patient outcomes. However, the mortality data from these 3 studies indicate a clear overall improvement in mortality compared with previous data and the original EGDT trial, which suggests
The new usual care
The use of continuous Scvo2 has now failed to show mortality benefit in 3 multicenter, randomized controlled trials when implemented in the routine care of patients with sepsis.8, 9, 10 Similarly the transfusion of red blood cells to target a hematocrit of 30%, either alone or with inotropic support with the goal of increasing oxygen delivery, is also unlikely to provide any additional benefit.8, 9, 10 Therefore, as with the use of continuous Scvo2, this practice is anticipated to become less
Summary
UC before the major EGDT trials2, 8, 9, 10 was characterized by a delayed response in the treatment of sepsis and septic shock. EGDT has evolved over the past 2 decades. Therapeutic modalities such as CVP and continuous Scvo2 measurements, placement of central venous catheters, routine blood transfusions, and inotropic support are no longer viewed as prerequisites in the treatment of sepsis. Notwithstanding, the current sepsis trials have established a culture of early recognition of sepsis,
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Disclosures: The authors have nothing to disclose.