Epidemiology 1979–2000

Before 2000, solid epidemiology data on sepsis were lacking. No formalized, generally accepted definition existed, even for septicemia, which was more commonly used. Additionally, prior to 2002, diagnostic codes for sepsis, severe sepsis, and septic shock were nonexistent.

Martin et al estimated that there were more than 10 million septic patients during a 22-year span, increasing 9 percent annually from 164,000 cases to 660,000.² Angus et al estimated 750,000 cases, representing more than cases of breast cancer, colon cancer, and AIDS combined. With a reported 500 deaths per day, mortality for sepsis paralleled that of out-of-hospital myocardial infarction, costing $16.7 billion nationally.³ Mortality estimates for the period ranged from 18 to 75 percent, depending on illness severity and population.^2–5 A meta-analysis reported mortality as 47 percent from 1991 to 1995 and 29 percent from 2006 to 2009, representing a 3 percent annual reduction across studies.

Most sepsis occurred external to the ICU. Approximately 60 percent of the Angus et al cases were identified outside of the ICU. In a global study, 88 percent of septic patients were identified outside of the ICU (56 percent in the emergency department, 32 percent on the ward, and 12 percent in the ICU).⁶

2001–2004

Wang et al estimated that there were 571,000 suspected community-acquired severe sepsis cases presenting annually to emergency departments. Mean ED length of stay was almost five hours, with more than 20 percent of the visits lasting in excess of six hours.⁷

2009–2011

Revised estimates total 850,000 ED sepsis visits per year. This constitutes one out of every 120 ED patients. More than 70 percent of septic ED patients were admitted, with 34 percent requiring ICU admission. However, almost half had an ED length of stay of more than four hours, and more than 10 percent stayed more than eight hours.⁷

Gaieski et al demonstrated how sepsis prevalence and mortality rates change depending on the definition applied. However, what is clear is that the majority of sepsis cases are identified and initial resuscitation for them is completed outside of the ICU.⁸

“And yet, at the present time, the subject is by no means fully elucidated, and it is not even possible to give a general definition of the term septicemia, which could currently represent all the different conceptions of its nature … at the present time.” —W.W. Van Arsdale

Sepsis Definitions 1990s

Sepsis definitions have evolved over time (see Table 1). The 1991 American College of Chest Physicians/Society of Critical Care Medicine conference definitions were based on a definition Bone et al decided upon when the investigators realized they needed to identify severe sepsis patients early in their course, prior to traditional culture availability, for a trial of high-dose methylprednisolone.^10,11 They defined the pragmatic, inflammatory criteria with organ dysfunction as “sepsis syndrome.”¹² Despite apparent face validity, problems with applicability resulted in dissatisfaction and prompted the 1992 consensus conference.¹⁰ Conference participants considered infection to be associated with microbial penetration and sepsis to be associated with the clinical, inflammatory response. Within this framework, the terminology of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock was developed. However, SIRS was criticized for lack of specificity and imperfect sensitivity.¹² Additionally, the process was criticized for predominantly involving North American representation.^13,14