Sepsis: EGDT Continues to Deliver

Last month, Dr. Kevin Klauer suggested that emergency physicians “unbundle the sepsis bundle.”
This month, Dr. Emanuel Rivers offers his rebuttal, explaining why EGDT greatly improves sepsis outcomes.

Last month, Dr. Kevin Klauer suggested that emergency physicians “unbundle the sepsis bundle.”

This month, Dr. Emanuel Rivers offers his rebuttal, explaining why EGDT greatly improves sepsis outcomes.

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The concept and components of early goal directed therapy (EGDT) for sepsis management has been part of the emergency medicine (EM) literature for over 40 years.1-3 Eleven years after the original publication of EGDT, the literature reflects the opposite position to that of Dr. Klauer, as put forth in last month’s Op/Ed. EGDT has been validated and proven effective in over 54 publications comprising over 23,000 patients (shown in the table at right).4 Because of these robust finding, the emergency department (ED) has had the most influential impact on sepsis outcomes in the last decade.5 EGDT remains one of the most important components of the Surviving Sepsis Campaign (SSC) recommendations.6 EGDT has not “failed to deliver,” as Dr. Klauer suggests.

In addition, large health care organizations such as Kaiser Health Care, Catholic Health Care West, Catholic Health Partners, HCA Healthcare have adopted EGDT. It has received the Joint Commission on Accreditation of Healthcare Organizations national quality award two years in a row and the results are not only improved outcomes but decreased hospital costs.7,8 This does not represent “premature” and “ill advised” treatment, as described by Dr. Klauer.

The conduction and results of the EGDT study are impeccable. After a decade of multiple confirmatory studies (single and multi-center), regurgitating inaccuracies to cast doubt on the EGDT study using a newspaper (which is under international investigation) is inappropriate. Furthermore, unilaterally relying on a source which did not publish a reply from the leadership of Henry Ford Health Systems is unacceptable. The EGDT study received no financial support from industry or extra-mural sources. This reply has been publically available on the Henry Ford Hospital Web site since 2008; www.henryfordem.com/egdt.
The sepsis bundle is not a “mixed bag of tricks that lacks focus,” as described by Dr. Klauer. Each of the EGDT components have been validated and the concept remains a strong level 1 recommendation from the SSC (68 international experts representing 29 international organizations).

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In addition to hemodynamic monitoring, the CVP catheter provides an avenue for vasopressor administration which is contraindicated through peripheral veins. The study Dr. Klauer referenced was a retrospective ICU based study examining the outcome benefit of vasopressin in patients in shock for over 12 hours duration and after volume resuscitation.10,11,12 This was not an early resuscitation study which prospectively evaluated the merits of CVP.

CVP is a pressure and must be interpreted in the context of other surrogate measures of flow such as ScvO2. CVP measurement is indicative of fluid responsiveness in the lower ranges.13,14 In higher ranges, CVP is taken in the context of ScvO2, a high value with a low ScvO2 indicates myocardial suppression, necessitating inotropic therapy. CVP as part of EGDT has been shown to have a significant association with 30-day mortality.15 Early, aggressive fluid therapy which is associated with improved outcomes must be distinguished from late aggressive fluid therapy.16 The administered volume in the EGDT group within the first 6 hours was significantly greater compared to standard therapy group, but over 72 hours there were no differences in the amount of fluid between the two groups. Paradoxically, this is associated with decreased mechanical ventilation, vasopressor and corticosteroid therapy.3,17-20 Thus, CVP is not the problem; it is the clinician’s interpretation as with any hemodynamic variable.

Multiple studies, including a meta-analysis, show that an ScvO2 >70% is independently and significantly associated with mortality reduction in the first 6 hours.21-25 ScvO2 significantly predicts outcome 47 hours after the onset of acute lung injury and up to 48 hours in the ICU phase of sepsis.15,26 One of the reasons why a high ScvO2 is seen is because emergency intubation and mechanical ventilation has a strong effect on ScvO2. In a prospective multicenter observational study, ScvO2 increased from 61.8 +/- 12.6% to 68.9 +/- 12.2%. ScvO2 increases significantly in response to emergency intubation in the majority of septic patients.27

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Vallet et al. found that mortality is optimized when an ScvO2 of 69.5% is used as a trigger for red blood cell (RBC) transfusion.28 RBC transfusion does not negatively alter the sublingual microcirculation in patients with altered capillary perfusion at baseline.29 Furthermore, there are no clinically significant adverse effects on global indexes of tissue oxygenation30, mortality rates in sepsis31 and acute lung injury.32

Recognition of myocardial dysfunction (low cardiac index) requiring inotropic (dobutamine) occurs in 12-15% of patients.33 A low ScvO2 is highly predictive of a low cardiac index26 and is independently associated with decreased risk of mortality.34 Patients with systolic dysfunction have a mortality rate of 36.3% without and 16.67% with EGDT.35 Patients who benefit from receiving RBC or dobutamine are patients with elevated lactate concentrations.36

Nguyen et al. found that the clearance of lactate over the first 6 hours after presentation was associated with significant decreases in sepsis biomarkers, organ function and mortality.37,38,42,43 Taking a page from these findings, Jones et al. declared that lactate clearance of at least 10% is equivalent to ScvO2 using the EGDT algorithm in a noninferiority study.39 This was concluded in spite of the low number of interventions (only 10% of the patient population), lower illness severity and lack of cardiopulmonary events compared to the original study. Using the same data set by Boyd quoted above, normal lactate levels were present in patients with high mortality, questioning the value of lactate clearance advocated by Dr. Klauer.40 Twenty to 50% of septic shock patients will never elevate lactate levels at presentation or during the clinical course, frequently develop multi-system organ failure and death.24,40-43 Thus lactate clearance, while helpful, is of limited clinical utility when used alone. ScvO2 and lactate are complimentary endpoints and not mutually exclusive.

Dr. Klauer asks: “For sepsis, does the evidence support the increased time it takes, the additional cost and the associated risk to the patient?” The mortality risk for a patient that qualifies for EGDT is from 30 to 47%.5 The urgency comes from understanding the illness severity, short-long term consequences of inaction and accountability (i.e. acute myocardial infarction (AMI), trauma, stroke or cardiac arrest). The components of EGDT are supported by evidence and it is not a menu. Do you pick and choose which parts of the recommended therapy for AMI, trauma, stroke or cardiac arrest?

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After the EGDT publication, a 10-12% drop in mortality has been seen nationally over the last decade.44 Sepsis is the most expensive diagnosis being treated in hospitals in the U.S., consuming over $54 billion per year. Compliance to EGDT results in a 20% reduction in hospital-related
costs and decreases hospital length of stay by 4-5 days.45,46 As the most expensive and lethal cause of hospitalization in the last 10 years, severe sepsis and septic shock is an EM disease. Our specialty is one that responds to crisis as well as change. Our patients expect and deserve nothing less.

Emanuel P. Rivers, MD, MPH, is the vice chairman and research director, department of emergency medicine at Henry Ford Hospital. Dr. Rivers is also a clinical professor at Wayne State University         

References

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