Severe Sepsis and Septic Shock.pdf

review article T h e n e w e ngl a nd j o u r na l o f m e dic i n e n engl j med 369;9 august 29, 2013840 Critical Care Medicine Simon R. Finfer, M.D., and Jean-Louis Vincent, M.D., Ph.D., Editors Severe Sepsis and Septic Shock Derek C. Angus, M.D., M.P.H., and Tom van der Poll, M.D., Ph.D. From the CRISMA (Clinical Research, Inves- tigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh (D.C.A.); and the Center for Experimental and Mo- lecular Medicine, Division of Infectious Diseases, and Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Am- sterdam (T.P.). Address reprint requests to Dr. Angus at the Department of Criti- cal Care Medicine, University of Pitts- burgh, 614 Scaife Hall, 3550 Terrace St., Pittsburgh, PA 15261, or at angusdc@ ; or to Dr. van der Poll at the Division of Infectious Diseases, Academ- ic Medical Center, Meibergdreef 9, Rm. G2-130, 1105 AZ Amsterdam, the Nether- lands, or at t.vanderpoll@amc.uva.nl. This article was updated on November 21, 2013, at NEJM.org. N Engl J Med 2013;369:840-51. DOI: 10.1056/NEJMra1208623 Copyright ? 2013 Massachusetts Medical Society. Sepsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis (????????) was the process by which flesh rots, swamps generate foul airs, and wounds fester.1 Galen later considered sepsis a laudable event, necessary for wound healing.2 With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was recast as a systemic infec- tion, often described as ??blood poisoning,?? and assumed to be the result of the host??s invasion by pathogenic organisms that then spread in the bloodstream. However, with the advent of modern antibiotics, germ theory did not fully explain the pathogenesis of sepsis: many patients with sepsis died despite successful erad- ication of the incit