Critical Care Medicine Severe Sepsis and Septic Shock

S epsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis (σήψις) 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 infection, 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 eradication of the inciting pathogen. Thus, researchers suggested that it was the host, not the germ, that drove the pathogenesis of sepsis. Incidence a nd C ause s The incidence of severe sepsis depends on how acute organ dysfunction is defined and on whether that dysfunction is attributed to an underlying infection. Organ dysfunction is often defined by the provision of supportive therapy (e.g., mechanical ventilation), and epidemiologic studies thus count the "treated incidence" rather than the actual incidence. In the United States, severe sepsis is recorded in 2% of patients admitted to the hospital. Of these patients, half are treated in the intensive care unit (ICU), representing 10% of all ICU admissions. 6,7 The number of cases in the United States exceeds 750,000 per year 7 and was recently reported to be rising. 8 However, several factors -new International Classification of Diseases, 9th Revision (ICD-9) coding rules, confusion over the distinction between septicemia and severe sepsis, the increasing capacity to provide intensive care, and increased awareness and surveillance -confound the interpretation of temporal trends. Studies from other high-income countries show similar rates of sepsis in the ICU. The New England Journal of Medicine Downloaded from nejm.org at GIOVANNI DIO on May 29, 2014. For personal use only. No other uses without permission

Critical Care Medicine Severe Sepsis and Septic Shock

S epsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis (σήψις) 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 infection, 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 eradication of the inciting pathogen. Thus, researchers suggested that it was the host, not the germ, that drove the pathogenesis of sepsis. Incidence a nd C ause s The incidence of severe sepsis depends on how acute organ dysfunction is defined and on whether that dysfunction is attributed to an underlying infection. Organ dysfunction is often defined by the provision of supportive therapy (e.g., mechanical ventilation), and epidemiologic studies thus count the "treated incidence" rather than the actual incidence. In the United States, severe sepsis is recorded in 2% of patients admitted to the hospital. Of these patients, half are treated in the intensive care unit (ICU), representing 10% of all ICU admissions. 6,7 The number of cases in the United States exceeds 750,000 per year 7 and was recently reported to be rising. 8 However, several factors -new International Classification of Diseases, 9th Revision (ICD-9) coding rules, confusion over the distinction between septicemia and severe sepsis, the increasing capacity to provide intensive care, and increased awareness and surveillance -confound the interpretation of temporal trends. Studies from other high-income countries show similar rates of sepsis in the ICU. The New England Journal of Medicine Downloaded from nejm.org on October 5, 2014. For personal use only. No other uses without permission

Critical Care Medicine Severe Sepsis and Septic Shock

S epsis is one of the oldest and most elusive syndromes in medicine. Hippocrates claimed that sepsis (σήψις) 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 infection, 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 eradication of the inciting pathogen. Thus, researchers suggested that it was the host, not the germ, that drove the pathogenesis of sepsis. Incidence a nd C ause s The incidence of severe sepsis depends on how acute organ dysfunction is defined and on whether that dysfunction is attributed to an underlying infection. Organ dysfunction is often defined by the provision of supportive therapy (e.g., mechanical ventilation), and epidemiologic studies thus count the "treated incidence" rather than the actual incidence. In the United States, severe sepsis is recorded in 2% of patients admitted to the hospital. Of these patients, half are treated in the intensive care unit (ICU), representing 10% of all ICU admissions. 6,7 The number of cases in the United States exceeds 750,000 per year 7 and was recently reported to be rising. 8 However, several factors -new International Classification of Diseases, 9th Revision (ICD-9) coding rules, confusion over the distinction between septicemia and severe sepsis, the increasing capacity to provide intensive care, and increased awareness and surveillance -confound the interpretation of temporal trends. Studies from other high-income countries show similar rates of sepsis in the ICU. The New England Journal of Medicine Downloaded from nejm.org at RADBOUD UNIVERSITEIT NIJMEGEN on February 11, 2014. For personal use only. No other uses without permission