Bacterial Sepsis

Bacterial sepsis is a life-threatening condition that arises when the body’s response to an infection injures its tissues and organs. Sepsis has recently been re-defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis, as a medical condition, was first introduced by Hippocrates (460 through 470 BC), and is derived from the Greek word sipsi , i.e., “to make rotten.” This disease entity has had many iterations since that time, with the foundations for the modern understanding of sepsis coming about through breakthroughs in the late 19 century.  The development of antiseptic measures, the germ theory of disease, and bacteriology lead to the widely held belief that sepsis was a systemic infection resulting from a pathogenic organism invading the host that spreads via the bloodstream (i.e., septicemia). It was not until the further widespread use of antibiotics and the discovery of endotoxin that suggested the pathophysiology of sepsis was far more complex. Despite the increased understanding of this complex disease process, mortality from sepsis remains the most common cause of death in the non-coronary intensive care unit. In the hopes of allowing earlier therapeutic intervention, an international consensus meeting in 1991, created and defined terms, such as systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock (known now as Sepsis-1). SIRS describes the inflammatory process, independent of cause based on a combination of vital signs and blood work. SIRS SIRS includes 2 or more of the following: Temperature greater than 38 C or less than 36 C. Heart rate greater than 90 beats per minute. Tachypnea greater than 20 breaths per minute or PaCO2 less than 32 mm Hg. White blood cell (WBC) count greater than 12,000 per cubic millimeter or fewer than 4000 per cubic millimeter, or greater than 10% immature (band) forms. Sepsis: SIRS as the result of an infection. Severe Sepsis: Sepsis associated with organ dysfunction (1 or more), hypo-perfusion abnormality, or sepsis-induced hypotension. Hypo-perfusion abnormalities may include but are not limited to lactic acidosis, oliguria, or acute change in mental status. Septic Shock: Sepsis-induced hypotension despite adequate fluid resuscitation. Multi-Organ Dysfunction Syndrome  Multi-organ dysfunction syndrome (MODS) is the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention. Sepsis-3 redefined sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is importantly noted that not all patients that present with SIRS have an infection, as well, not all patients who have an infection are septic. Sepsis is differentiated from infection by a dysregulated host response and the presence of end-organ dysfunction. Sepsis and its sequelae represent a continuum of clinical and pathophysiologic severity, resulting in progressive physiologic failure of several inter-dependent organ systems. The Surviving Sepsis Campaign (SSC) and its accompanying treatment bundle were developed with the intention of rapid identification and treatment of septic patients. In 2001, Rivers et al. showed the benefits of a specific protocol termed early goal-directed therapy (EGDT) versus standard therapy, with a resulting significant decrease in mortality. EGDT was subsequently incorporated into the first iteration of the 6hr resuscitation bundle of the Surviving Sepsis Campaign guidelines. These guidelines have changed since their first publication with revisions in 2008, 2012, and finally 2016. Heightened scrutiny of these guidelines and recommendations was the result of the Centers for Medicare and Medicaid Services(CMS) using the bundled care as a hospital quality measure. These were initially adopted by the National Quality Forum 0-500 and subsequently became the Sepsis CMS Core measures known as SEP-1 . These measures have come under criticism primarily for the assumption that bundled and structured care is superior to individualized treatment guided by the bedside clinician. In addition to the numerous criticisms of the measures or the evidence supporting them, their mortality benefit remains a point of controversy for many clinicians.
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