title: Management of severe sepsis and septic shock.
abstract: OBJECTIVE
  Severe sepsis and septic shock are common and deadly conditions for which the epidemiology, pathogenesis, and management continue to evolve. Recent publications (2003 and early 2004) have been systematically reviewed for important new original research and scholarly reviews, with an emphasis on clinical advances in adults.
  
  
  RESULTS
  Important new epidemiologic studies establish the increasing frequency (nearly 9% per year) and falling mortality rates associated with sepsis. Sepsis definitions were reviewed by a group of experts, and the principal features of the 1991 consensus conference definitions were supported, with a new framework for evaluation of sepsis proposed. New research and thoughtful reviews continue to elucidate the pathogenesis of sepsis, with emphasis on innate immunity and time-based changes in immune status, varying from hyperreactive immunity and inflammation to immune depression with enhanced risk for nosocomial infections. A comprehensive evidence-based approach to the management of severe sepsis is presented in an important document developed by representatives from many critical care and infectious disease societies. Management includes early targeted resuscitation, broad empiric antibiotic coverage and source control, effective shock evaluation and treatment, adjuvant therapy with recombinant human activated protein C and moderate-dose hydrocortisone in selected patients, and comprehensive supportive care. Recently published multicenter clinical trials for novel agents have been disappointing, particularly for a nitric oxide synthase inhibitor that effectively supported blood pressure but increased mortality.
  
  
  CONCLUSIONS
  The works reviewed reflect the advances in the care of patients with sepsis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University Health System, Richmond, Virginia, USA. Csessler@hsc.vcu.edu
authors.forename: Curtis N
authors.initials: CN
authors.lastname: Sessler
authors.forename: John C
authors.initials: JC
authors.lastname: Perry
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Varney
mesh_terms: D006801:Humans; D012151:Resuscitation; D018805:Sepsis / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D012772:Shock, Septic / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*