PRO/CON Should Early Goal-Directed Therapy Be the Standard for Sepsis?

Manny Rivers, Brian Fuller and Kevin Klauer square off over the use of early goal-directed therapy for severe sepsis. 

Pro: Research Supports It  vs  Con: Too Many Assumptions

Educational Objectives:

After evaluating this article participants will be able to:

1. Incorporate into practice the critical components of early goal directed treatment for sepsis.
2. Identify the areas of controversy surrounding EGDT and rationally apply the principles to clinical practice.
3. Improve awareness, regarding the recognition and aggressive management of sepsis to improve patient outcomes



Pro: Research Supports It

by Brian M. Fuller, MD & Emanuel Rivers, MD, MPH

Ten years after the study was completed, Early Goal Directed Therapy (EGDT) for the treatment of severe sepsis and septic shock continues to generate much controversy and debate. In spite of multiple publications supporting its findings, questions continue about its therapeutic endpoints, general applicability in “real world’ scenarios, and whether continued research comparing EGDT to a control group is unethical, among others.

Sepsis is common, lethal, and expensive. It is responsible for over 225,000 deaths per year and is the most expensive disease requiring hospitalization since 1997, accounting for over $50 billion per year in health care costs. This disease is highly relevant to emergency medicine as over 50% of these patients are admitted through the emergency department (ED). To answer the question of “Does EGDT work?” one needs to only look at the data to find socioeconomic benefits.


The original EGDT trial found a mortality reduction from 46.5% in the control group to 30.0% in the EGDT group. In 2006, analysis of available randomized and observational data from 12 other academic and community centers, totaling 1,298 patients, yielded similar results. Mortality was reduced from 44.8% in the control group to 24.5% in the EGDT group. Put another way, for every 5 patients treated with EGDT, one life was saved! This is a better number than aspirin + streptokinase for acute myocardial infarction 5-week mortality (NNT=19) or tPA for acute ischemic stroke within 4.5 hours (NNT=15). To date, there are at least 24 peer reviewed publications, totaling over 2,000 patients citing outcome benefit with EGDT, with mortality reductions ranging from 9% to 40%. Furthermore, there are at least 28 published abstracts, increasing the total to over 10,000 patients, with similar results.

Not only does EGDT provide mortality benefit it also decreases health care resource consumption. Examples include decrease in vasopressor use, hospital and intensive care unit length of stay, and mechanical ventilation days. In summary, data from over 10,000 patients shows that an early, upstream intervention (EGDT) provided in the ED has significant positive downstream benefits. With an average ED wait time of over 5 hours for an ICU bed, there are few options other than making this an ED intervention. This benefit has been shown not only in the academic setting, but in the community as well. In fact, this data includes over 1,100 patients in the community setting and it shows an average absolute mortality reduction of 20.9%.

In an era of increasing scrutiny with respect to health care dollars, a program such as EGDT should demonstrate fiscal justification. It has been shown in academic centers that EGDT provides a 23.4% reduction in hospital costs, a cost per life saved of $32,336, and a median reduction in hospital facility charges of 39.2%. Implementation of a sepsis protocol has been shown to decrease total costs ($16,103 vs. $21,985), showing that implementation of a sepsis protocol can save lives and “result in substantial savings in an otherwise very expensive condition”. In a before and after implementation study, EGDT decreased cost on average by $9,346.60 per patient, resulting in an average cost savings of $4 million every six months. Whether EGDT is provided by an ED based, mobile intensive care unit team, or ICU based approach, all have similar cost effectiveness ratios.

The concept of EGDT was provided in 1976 in the first emergency medicine journal. Building on these concepts, the original EGDT trial proved benefit of an aggressive and early goal-oriented approach to shock reversal. Unfortunately, EGDT remains controversial. Despite the data, current detractors to EGDT continue to question which parts of the protocol drive benefit. Why should we really care? In the early stages of shock, whether you resuscitate your patient to a preset oxygen delivery, central venous pressure, or central venous mixed oxygen saturation, it may not matter. It is likely that EGDT is greater as a whole than the sum of its parts and searching for the most effective component is missing the point: EGDT has been shown for almost a decade and in thousands of patients that it is beneficial. Detractors also state that the benefit of EGDT is that we are simply monitoring our patients better when instituting the protocol. No monitoring device in the history of medicine, unless linked with a therapy that improves outcome, has ever been shown to improve outcome. That is true for pulse oximetry all the way to pulmonary artery catheterization. Understanding these historical precedents, one can understand that it is not the monitoring, but EGDT,  that is improving outcome.


The overwhelming majority of the data shows that EGDT works and shows how important a specialty response is to saving lives. Despite this, we may be losing the vision of responding to challenge as well as change. We follow stroke protocols, acute coronary syndrome protocols and trauma protocols routinely. And yet, a study originating from our own specialty with robust supportive evidence continues to be questioned. These questions are not supported by evidence. So if you want to save lives, save your institution money, and improve your department’s standing in the house of medicine, employing EGDT in the treatment of severe sepsis and septic shock will accomplish all of your goals!

Brian Fuller, MD, is an assistant professor of anesthesiology and emergency medicine at Washington University School of Medicine in St. Louis.

Emanuel Rivers, MD, MPH, IOM, is the vice chairman and research director at Henry Ford Hospital, and is a clinical professor at Wayne State University.

Continue next to read the Con side by Kevin Klauer, DO
Too Many Assumptions


  1. Brian Donoghue, M.D. on

    While I think careful scrutiny of any research is essential, Kevin’s conclusions seem to ignore even the original 2001 NJEM article’s facts. In his conclusion, Kevin writes:

    “Early recognition of sepsis, aggressive volume resuscitation to maintain perfusion and early broad-spectrum antibiotics are clearly interventions that positively influence mortality.”

    The control group in this study received the same aggressive early recognition of sepsis as the study group and received an average of 3500mL of fluids. Antibiotics weren’t as closely studied in the original study. Bottom line, the control group received therapy that many EPs would still consider relatively aggresive: and that’s the point, they did worse than the EGDT patients.

    It may be helpful to parse out which components of EGDT therapy are most effective in order to optimize therapy, but the bottom line is that these various “slices of pie” beyond the basics ARE important.

  2. Scott Wilber on

    With all respect to Dr. Klauer, I think he is confusing EGDT with the Sepsis Resuscitation Bundle and the Sepsis Management Bundle promoted by the now concluded Surviving Sepsis campaign (

    The Sepsis Resuscitation Bundle closely mirrors Dr. River’s description of EGDT from his 2001 NEJM article, Figure 2 (available at Many of the treatments mentioned by Dr. Klauer, including Xigris, steroids, and glycemic control, are part of the Sepsis Management Bundle. As readers may remember from a recent LLSA article, there has been criticism of some of the recommendations of the Surviving Sepsis Campaign, especially the Sepsis Management Bundle. However, it should be remembered in this debate that EGDT and the Sepsis Management Bundle are 2 different things.

    Furthermore, the inclusion criteria for EGDT are not simply the presence of 2 or more SIRS criteria. To be eligible for EGDT, patients require 2 or more SIRS criteria “…and a systolic blood pressure no higher than 90 mm Hg (after a crystalloid-fluid challenge of 20 to 30 ml per kilogram of body weight over a 30-minute period) or a blood lactate concentration of 4 mmol per liter or more”. So they must have signs of infection and either refractory hypotension or evidence of hypoperfusion.

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