Chest
Volume 130, Issue 5, November 2006, Pages 1579-1595
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Postgraduate Education Corner
Early Goal-Directed Therapy in Severe Sepsis and Septic Shock Revisited: Concepts, Controversies, and Contemporary Findings

https://doi.org/10.1378/chest.130.5.1579Get rights and content

Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.

Section snippets

Early and Late Sepsis: A Hemodynamic Comparison

Sepsis represents a continuum from an inciting infectious event and host-pathogen interaction to the hemodynamic consequences caused by the relationship among proinflammatory, antiinflammatory, and apoptotic mediators.4 The early stages of sepsis can be accompanied by circulatory insufficiency resulting from hypovolemia, myocardial depression, increased metabolic rate, and vasoregulatory perfusion abnormalities. As a consequence, a variety of hemodynamic combinations create a systemic imbalance

The Therapeutic Components of EGDT

Since the publication of the EGDT study, numerous questions have been raised regarding specific components of treatment. While the trial began patient enrollment in 1997, the protocol goals were consistent with the practice parameters for hemodynamic support of sepsis recommended by the American College of Critical Care Medicine in 1999 (Table 2).35 More recently, these recommendations have been updated,36 but the therapeutic tenets remain the same.

Scvo2 vs S Vo2: Does it Matter?

An S Vo2 gives an estimate of the

Myocardial Dysfunction and Brain Natriuretic Peptide

At the hemodynamic juncture at which the goals of central venous pressure (CVP), MAP, and hematocrit are met, a low Scvo2 implies decreased myocardial compliance or dysfunction. Previous work by Parillo et al81 has shown that 10 to 15% of patients with near-normal BP and preload optimization will continue to have significant myocardial depression, necessitating inotropic support. Similar findings were detected in the EGDT study with 13.7% of patients receiving inotropic therapy, which is not

Conclusion

EGDT results in significant reductions in morbidity, mortality, vasopressor use, and health-care resource consumption. Five years after its publication, this study has generated much discussion with regard to the concepts of early sepsis, and has fueled debate regarding diagnostic and therapeutic interventions. Further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some components of inflammation, which are reflected by

ACKNOWLEDGMENT

The authors acknowledge the assistance of our research assistants, Quannience Rivers, Beth Fasbinder, Arturo Suarez, and Alexandria Podczervinski, and our biostatisticians, Suzanne Havstad and Gordon Jacobsen, for their assistance and support in preparing the data presented.

References (118)

  • CerraFB et al.

    Vasodilator therapy in clinical sepsis with low output syndrome

    J Surg Res

    (1978)
  • SpronkPE et al.

    Nitroglycerin in septic shock after intravascular volume resuscitation

    Lancet

    (2002)
  • NasrawaySA et al.

    Inotropic response to digoxin and dopamine in patients with severe sepsis, cardiac failure, and systemic hypoperfusion

    Chest

    (1989)
  • WorthleyLI et al.

    Digoxin in the critically ill patient

    Crit Care Resusc

    (1999)
  • KollefMH et al.

    Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients

    Chest

    (1999)
  • TrzeciakS et al.

    Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department

    Chest

    (2006)
  • RackowEC et al.

    Mechanisms and management of septic shock

    Crit Care Clin

    (1993)
  • RadyMY et al.

    A comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department

    Ann Emerg Med

    (1994)
  • DonninoMW et al.

    Cryptic septic shock: a sub-analysis of early, goal-directed therapy [abstract]

    Chest

    (2003)
  • OpalSM et al.

    Clinical trials for severe sepsis: past failures, and future hopes

    Infect Dis Clin North Am

    (1999)
  • MullinsR et al.

    Population based research assessing the effectiveness of trauma systems

    J Trauma

    (1999)
  • YangQ et al.

    Improvement in stroke mortality in Canada and the United States, 1999 to 2002

    Circulation

    (2006)
  • RackowEC et al.

    Pathophysiology and treatment of septic shock

    JAMA

    (1991)
  • AstizME et al.

    Oxygen delivery and utilization during rapidly fatal septic shock in rats

    Circ Shock

    (1986)
  • Brun-BuissonC et al.

    Incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter prospective study in intensive care units; French ICU Group for Severe Sepsis

    JAMA

    (1995)
  • VincentJL et al.

    Oxygen uptake/oxygen supply dependency: fact or fiction?

    Acta Anaesthesiol Scand Suppl

    (1995)
  • ParrilloJE et al.

    Septic shock in humans: advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy

    Ann Intern Med

    (1990)
  • AstizME et al.

    Relationship of oxygen delivery and mixed venous oxygenation to lactic acidosis in patients with sepsis and acute myocardial infarction

    Crit Care Med

    (1988)
  • SilancePG et al.

    Oxygen extraction in patients with sepsis and heart failure: another look at clinical studies

    Clin Intensive Care

    (1994)
  • RiversE et al.

    Early goal-directed therapy in the treatment of severe sepsis and septic shock

    N Engl J Med

    (2001)
  • AduenJ et al.

    The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations

    JAMA

    (1994)
  • BroderG et al.

    Excess lactate: an index of reversibility of shock in human patients

    Science

    (1964)
  • CadyLD et al.

    Quantitation of severity of critical illness with special reference to blood lactate

    Crit Care Med

    (1973)
  • MiddletonP et al.

    Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate

    Emerg Med J

    (2006)
  • YoungerJG et al.

    Relationship between arterial and peripheral venous lactate levels

    Acad Emerg Med

    (1996)
  • GarciaAJ et al.

    Point-of-care lactate testing as a predictor of mortality in a heterogeneous emergency department population [abstract]

    Acad Emerg Med

    (2006)
  • TrzeciakS et al.

    Operationalizing the use of serum lactate measurement for identifying high risk of death in a clinical practice algorithm for suspected severe sepsis [abstract]

    Acad Emerg Med

    (2006)
  • WiraC et al.

    Surrogate markers for lactic acidosis in patients with severe sepsis and septic shock [abstract]

    Crit Care Med

    (2004)
  • NguyenHB et al.

    Early lactate clearance is associated with improved outcome in severe sepsis and septic shock

    Crit Care Med

    (2004)
  • De BackerD

    Lactic acidosis

    Minerva Anestesiol

    (2003)
  • HayesMA et al.

    Elevation of systemic oxygen delivery in the treatment of critically ill patients

    N Engl J Med

    (1994)
  • GattinoniL et al.

    A trial of goal-oriented hemodynamic therapy in critically ill patients: s Vo2Collaborative Group

    N Engl J Med

    (1995)
  • KernJW et al.

    Meta-analysis of hemodynamic optimization in high-risk patients

    Crit Care Med

    (2002)
  • EngorenM

    The effect of prompt physician visits on intensive care unit mortality and cost

    Crit Care Med

    (2005)
  • KumarA et al.

    Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock

    Crit Care Med

    (2006)
  • LundbergJS et al.

    Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units

    Crit Care Med

    (1998)
  • VarpulaM et al.

    Hemodynamic variables related to outcome in septic shock

    Intensive Care Med

    (2005)
  • GrzybowskiM

    Systemic inflammatory response syndrome criteria and lactic acidosis in the detection of critical illness among patients presenting to the emergency department [abstract]

    Chest

    (1996)
  • AnderD et al.

    A comparison of standard versus goal directed therapy in resuscitation of critically ill emergency department patients

    Acad Emerg Med

    (1997)
  • American College of Critical Care Medicine, Society of Critical Care Medicine. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine

    Crit Care Med

    (1999)
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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    Dr. Otero receives research grant support from Biosite, Hutchinson Technologies, Spectral Diagnostics, and the National Institute of Allergy and Infectious Diseases. Dr. Rivers has received advisory board fees from the Lilly Corporation, Hutchinson Technologies, and Chiron; lecture fees from the Lilly Corporation and Edwards Lifesciences; and research support from the National Institute of Allergy and Infectious Diseases, Hutchinson Technologies, and Biosite Inc.

    The writing of this manuscript was partially supported (Drs. Otero and Rivers) by grant No. U01AI066569–01 from the National Institutes of Health, National Institute of Allergy and Infectious Disease (NIAID).

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