title: Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.
abstract: Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine, Loma Linda University, Loma Linda, CA, USA.|Department of Emergency Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: H Bryant
authors.initials: HB
authors.lastname: Nguyen
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.|Department of Quality Assurance, Aspirus Hospital, Iron River, MI, USA.
authors.forename: Anja Kathrin
authors.initials: AK
authors.lastname: Jaehne
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, MN, USA.
authors.forename: Namita
authors.initials: N
authors.lastname: Jayaprakash
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Semler
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Hegab
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, KY, USA.
authors.forename: Angel Coz
authors.initials: AC
authors.lastname: Yataco
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Geneva
authors.initials: G
authors.lastname: Tatem
authors.affiliation: Department of Internal Medicine, Mercy Hospital Medical Center, Chicago, IL, USA.
authors.forename: Dhafer
authors.initials: D
authors.lastname: Salem
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Moore
authors.affiliation: Department of Internal Medicine, Division of Critical Care Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Kamran
authors.initials: K
authors.lastname: Boka
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Jasreen Kaur
authors.initials: JK
authors.lastname: Gill
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.|Department of Medicine, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Jayna
authors.initials: J
authors.lastname: Gardner-Gray
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.|Department of Medicine, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Pflaum
authors.affiliation: Department of Internal Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.|CONEVID, Conocimiento y Evidencia Research Unit, Universidad Peruana Cayetano Heredia, Lima, PERU.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Domecq
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.|Department of Medicine, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Hurst
authors.affiliation: Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Justin B
authors.initials: JB
authors.lastname: Belsky
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Fowkes
authors.affiliation: Pulmonary and Critical Care Medicine, California Pacific Medical Center, San Francisco, CA, USA.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Elkin
authors.affiliation: Pulmonary and Critical Care Medicine, University of Kansas, Kansas City, Kansas, USA.
authors.forename: Steven Q
authors.initials: SQ
authors.lastname: Simpson
authors.affiliation: Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, Florida, USA.|University of Central Florida College of Medicine, Orlando, Florida, USA.|University of Florida College of Medicine, Orlando, Florida, USA.|University of South Florida College of Medicine, Orlando, Florida, USA.|Florida State University College of Medicine, Orlando, Florida, USA.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Falk
authors.affiliation: Department of Surgery, Division of Surgical Critical Care, Icahn School of Medicine, Mount Sinai Hospital,, New York, NY, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Singer
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA. erivers1@hfhs.org.|Department of Surgery, Henry Ford Hospital, Wayne State University, Detroit, MI, USA. erivers1@hfhs.org.
authors.forename: Emanuel P
authors.initials: EP
authors.lastname: Rivers
mesh_terms: D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D010347:Patient Care Planning; D012151:Resuscitation / Q000379:methods; D018805:Sepsis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D012772:Shock, Septic / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*