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Critical Care Medicine

Journal Watch Publishes Perspective on Meta-analysis of Randomized Controlled Trials Involving Sepsis

Chad M. Cannon, MD, FACEP
Department of Emergency Medicine, University of Kansas Hospital
Kansas City, Kansas

It was George Washington Carver who said "excellence is performing common things in uncommon places."  What was known to be best practice for stroke, acute myocardial infarction and trauma was applied to septic emergency department patients resulting in the 2001 New England Journal of Medicine publication "Early Goal-Directed Therapy in Severe Sepsis and Septic Shock (EGDT)".[1]  After seven years and multiple replications of its results in peer reviewed medical literature, a non-peer review business article brought EGDT into question and characterized it as a "new therapy".

A quick review of the literature finds ample data demonstrating the contrary. A recent review found 11 peer-reviewed publications totaling 1569 patients, and 28 abstracts totaling 4,429 patients, demonstrating a mean absolute risk reduction of 20% which exceeds the original study.[2]  The concepts of EGDT have been recommended by expert opinion as far back as 32 years ago.[3, 4]  Dr. Rivers and many others have been applying this concept to several other shock states for years prior to the EGDT study quietly and without fanfare.[5-9]  Simply, instead of waiting until a patient was admitted to the intensive care unit (ICU) which may take many hours to a full day, definitive treatment was initiated in the ED.[10] 

Of available sepsis treatments, EGDT has had the greatest impact on mortality reduction in the last 20 years.  Although unclear why such an abundance of data was not reported in this non-peer review business article, it is a serious warning nevertheless to those who may interface with the media and rely on it as an information source.  Additionally, it is perfect timing for the meta-analysis by Alan Jones et al followed by this summary and commentary by Dr. Tiffany Osborn.  In Emergency Medicine, our practice is based on best evidence and peer-review.  In the case of EGDT, the evidence is clear and the peer review unquestionable.

Early Goal Directed Therapy for Sepsis: Show Me the Data!
Meta-analysis of randomized sepsis trials showed mortality benefit with early goal-directed, therapy.


  1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early goal-directed therapy in the treatment of severe sepsis and septic shock. The New England journal of medicine 2001, 345(19):1368-1377.
  2. Rivers EP, Coba V, Whitmill M: Early goal-directed therapy in severe sepsis and septic shock: a contemporary review of the literature. Current opinion in anaesthesiology 2008, 21(2):128-140.
  3. 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. Critical care medicine 1999, 27(3):639-660.
  4. Wilson RF, Wilson JA, Gibson D, Sibbald WJ: Shock in the emergency department. Jacep 1976, 5(9):678-690.
  5. Rivers EP, Rady MY, Martin GB, Fenn NM, Smithline HA, Alexander ME, Nowak RM: Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization. Chest 1992, 102(6):1787-1793.
  6. Rivers EP, Wortsman J, Rady MY, Blake HC, McGeorge FT, Buderer NM: The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest 1994, 106(5):1499-1507.
  7. Rady MY, Rivers EP, Nowak RM: Resuscitation of the critically ill in the ED: responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate. The American journal of emergency medicine 1996, 14(2):218-225.
  8. Ander DS, Jaggi M, Rivers E, Rady MY, Levine TB, Levine AB, Masura J, Gryzbowski M: Undetected cardiogenic shock in patients with congestive heart failure presenting to the emergency department. Am J Cardiol 1998, 82(7):888-891.
  9. Rivers EP, Martin GB, Smithline H, Rady MY, Schultz CH, Goetting MG, Appleton TJ, Nowak RM: The clinical implications of continuous central venous oxygen saturation during human CPR. Annals of emergency medicine 1992, 21(9):1094-1101.
  10. Trzeciak S, Rivers EP: Emergency department overcrowding in the United States: an emerging threat to patient safety and public health. Emerg Med J 2003, 20(5):402-405.

About the Author:
Dr. Cannon practices emergency medicine, and is the assistant medical director of the emergency department at the University of Kansas Hospital in Kansas City, Kansas.  He is the vice president of the Kansas Chapter of ACEP.  Dr. Cannon resides in Overland Park, Kansas.

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