Sepsis and Organ(s) Dysfunction — Key Points, Reflections, and Perspectives

Abstract

Sepsis is one of the main problems in medicine due to its complexity from pathophysiology, clinical, and therapeutic standpoints. Although several definitions have been proposed for this syndrome, it can in general be assumed that it represents the clinical manifestation of a system response of the body to infection or to an inflammatory-associated acute disease [1,2]. Despite advances in medical practice, sepsis, severe sepsis, and septic shock, associated with different grading of organ(s) dysfunction/failure, are conditions that significantly limit quality of life and the ultimate survival of intensive care unit (ICU)patients. In any case, the health cost implications remain exorbitant [3]. Mortality rates as a result of sepsis are associated with a pattern characterized by progressive dysfunction/failure of non-pulmonary organ systems and, in particular, worsening neurologic, coagulation, and renal dysfunction over the first three days. Although initial pulmonary dysfunction is common in patients with sepsis syndrome, it is not associated with an increased mortality rate [4]. In five recent clinical trials that enrolled a total of 5661 patients with severe sepsis — the criteria being evidence of infection, systemic inflammatory response syndrome (SIRS), and at least one organ dysfunction/hypoperfusion — the incidences of septic shock ranged from 52 to 71% in the group of patients with severe sepsis. The mean was 58% [5, 6, 7, 8, 9]. A recent study used the International Classification of Diseases (ICD) nine hospital diagnostic codes for infection and acute organ dysfunction — to estimate 751 000 cases of severe sepsis per annum in the United States [3]. According to this data, septic shock would, therefore, be predicted to occur annually in 435 580 patients in the US. Mortality rate is a consequence of one or more factors such as:age, immunodepression, presence of diseases and/or chronic failure of one or multiple organ system dysfunctions and/or failure [10, 11]. Pathophysiologic mechanisms are basically related to Gram-negative bacteria endotoxin [12], but also Gram-positive micro-organisms, viruses, and mycetes, which are supposedly responsible for the local and systemic release of several mediators that, in turn, might be responsible for the organic response to infection, characterised by cardiovascular instability, hyperthermia, hypothermia, leukocytes, and coagulation alterations as well as by involvement of one or multiple organs [13]. The term sepsis is related to the concept of multiple organ dysfunction syndrome (MODS), which is frequently identified with the end result of infection, although it has been shown that septic syndrome is not specific to infection and can also originate as a result of a variety of non-infectious stimuli such as pancreatitis, burns, and trauma [14]. The American College of Chest Physicians proposed new definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis [15]. Indeed, although remarkable progress has been achieved in defining the pathophysiology of sepsis, the terminology associated with research in this field has remained confusing.