## INTRODUCTION

Since the days of Hippocrates, infection has been a leading cause of death. Major scientific discoveries and the findings of medical research have shaped the way we think about and manage infections. Severe sepsis and septic shock remain a major healthcare challenge worldwide, affecting an estimated 56 to 91 out of every 100,000 individuals. Of the 120 million patients presenting to United States (US) emergency departments (EDs) each year, 2.9% or over 600,000 are diagnosed with severe sepsis or septic shock. Sepsis is responsible for 9% of all deaths in the United States each year—a total of approximately 210,000 fatalities. By comparison, only 180,000 people die of acute myocardial infarction (MI) and only 200,000 of lung or breast cancer annually. With healthcare costs in the United States totaling $387 billion in 2011, septicemia was the most expensive admission diagnosis, at a cost of over$20.3 billion, or 5.2% of the total aggregate cost of all hospitalizations. Historically, hospital mortality for sepsis, severe sepsis, and septic shock has been 15%, 20%, and 47%, respectively.14 Since the advent of the Surviving Sepsis Campaign (SSC), sepsis mortality decreased from 35% to 15.4% in Australia and New Zealand, and from over 45% to 25% in the United Kingdom.510 Increased compliance with quality improvement measures and sepsis initiatives have resulted in similar mortality risk reductions in the United States. During a 7.5-year study period, a 25% reduction was observed.11 In countries without sepsis quality initiatives, mortality for severe sepsis and septic shock is reported between 22% and 76%.12,13

The ED is the portal of entry for over 50% of septic patients admitted to US hospitals.14,15 Detection of sepsis in the early phase has been shown to be crucial to preventing disease progression and improving outcomes.

Risk factors and comorbidities associated with the increased incidence and mortality in severe sepsis and septic shock include age, gender, race, multidrug-resistant organisms, and severity of chronic illnesses.16 Elderly patients are most severely affected by this disease. The estimated incidence of sepsis in patients over 85 years of age is 26.2/1,000 versus 0.2/1,000 in children.17 Patients with suspected sepsis had a mean ED length of stay (LOS) of 4.7 hours, with approximately 20.4% of patients staying longer than 6 hours.3 For these reasons, the emphasis on improving ED management of sepsis has been a revolutionary approach to decreasing morbidity and mortality from this disease.

## THE DEFINITION OF SEPSIS

A 1992 Consensus Conference provided a definition of sepsis as “suspected or known infection with two or more systemic inflammatory response criteria,” and defined a systemic inflammatory response syndrome (SIRS) as “a physiological response to an inflammatory process arising from nonspecific insult as seen in a variety of infectious or noninfectious processes such as infection, pancreatitis, trauma, burn and other diseases.” The conference ...

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