Chapter 32 Sepsis, Severe Sepsis, and Septic Shock
1 What is sepsis?
Sepsis is an overwhelming inflammatory and coagulopathic response to a source of infection, usually from the lung or abdomen. If not recognized early, or not treated properly and aggressively, it is often a lethal syndrome. Please note that it is different from bacteremia, which only refers to the presence of bacteria in the bloodstream.
2 Explain the nomenclature for disorders related to sepsis
In 1991, the American College of Chest Physicians and the Society of Critical Care Medicine determined the nomenclature for disorders related to sepsis. The following terms describe the progression of signs and symptoms regarding this somewhat confusing terminology:
Systemic inflammatory response syndrome (SIRS): characterized by
Sepsis: a suspected or documented source of infection plus two or more SIRS criteria.
Severe sepsis: sepsis with acute sepsis-induced organ dysfunction of one or more organ systems.
Septic shock: a subset of severe sepsis syndrome in which the organ dysfunction is cardiovascular, that is, a subset of severe sepsis in which there is cardiovascular dysfunction. Specifically, sepsis-induced hypotension (mean arterial pressure [MAP] < 65 mm Hg) that persists despite adequate and aggressive volume resuscitation. Patients will often require vasopressors to keep MAP ≥ 65 mm Hg.
Multiple organ dysfunction syndrome (MODS): Failure in more than one organ system that requires acute intervention. Once the patient reaches this degree of illness, the chances of making a meaningful recovery can often be quite low.
In 2001, the International Sepsis Definitions Conference convened to once again address the difficulties in defining sepsis. During this meeting, conference members expressed the need for a better, more sophisticated way to stage the severity of sepsis. At this time PIRO was introduced. Over the past several years, several studies have been published correlating a total PIRO score with mortality. However, the studies are not identical, and they still need to be corroborated by other investigators. In brief, PIRO represents the following:
3 What is the incidence of sepsis?
Septic shock and MODS are relatively common and associated with substantial mortality and consumption of health care resources. In 2007, an estimated 700,000 cases of severe sepsis or MODS occurred in the United States alone. This was a substantial increase over 2003. The numbers continue to rise every year. The incidence of sepsis is substantially higher in elderly than in younger people. The projected growth of the elderly population in the United States will contribute to an increase in incidence of 1.5% per year, yielding an estimated 934,000 and 1,110,000 cases by the years 2010 and 2020, respectively. The present annual cost of severe sepsis and septic shock in the United States is estimated at $25 billion.
4 How does the nomenclature relate to outcome?
Previous studies have shown that as the disorder progresses from SIRS to septic shock, the mortality rate increases. Of interest, some data support the concept that, although the degree of illness at presentation may have some correlation with outcomes, it is the change in clinical status from baseline that may have the closest correlation with outcomes. Regardless, sepsis progresses to MODS with tragic consequences. The mortality rate for patients with acute renal failure in the setting of sepsis ranges from 50% to 80%. For most patients with sepsis syndrome, the failure of three or more organ systems results in a mortality rate > 90%. The organ systems most often affected early in the process are pulmonary, hematologic, renal, and cardiovascular. Despite the growing number of patients with septic shock and increase in likelihood of death with multiple organ failure, overall mortality appears to be declining in recent years. This could be related to an improvement in therapy and improvement in supportive measures but is more likely related to medical coding issues and the heterogeneity of the disease and the available data.
5 Discuss current understanding of the pathogenesis of sepsis and septic shock
Sepsis syndrome begins with the invasion and growth of microorganisms (gram positive, gram negative, fungal, or viral) in a normally sterile tissue space. The endothelium is damaged by infection, trauma, or other insult, and activation of the host immune response begins. Tumor necrosis factor α, interleukin (IL)-6, and IL-8 are associated with the activation of an inflammatory cascade and chemotaxis of leukocytes, monocytes, and macrophages. Antiinflammatory substances such as IL-4, IL-10, prostaglandins, and other components of the immune system work to maintain homeostasis in the face of an infectious insult. Sepsis syndrome develops when the balance between the proinflammatory and antiinflammatory substances is lost.
The coagulation pathway plays a critical role in sepsis. The complement system, vasoregulatory system (nitric oxide, bradykinin, prostaglandins), the coagulation cascade (tissue factor, protein C, thrombin, antithrombin III), and fibrinolysis (fibrin, plasmin, and plasminogen-activating factor) play roles as well. The result is the development of a vicious circle that promotes, both locally and systemically, further inflammation, release of oxygen free radicals, and deposition of microvascular thrombi, resulting in a cycle of ischemia, reperfusion injury, and tissue hypoxia. Global tissue hypoxia independently contributes to endothelial activation and further disruption of the homeostatic balance among coagulation, vascular permeability, and vascular tone. These are key mechanisms leading to microcirculatory failure, refractory tissue hypoxia, and organ dysfunction.
It is becoming clear that the processes of coagulation and inflammation are tightly linked. Recent studies have shown that patients with severe sepsis have depleted levels of protein C, protein S, and antithrombin III.
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