Download PDF Sepsis and Non-infectious Systemic Inflammation From Biology Critical Care by Jean-Marc Cavaillon and Christophe Adire

Sinopsis

The word ‘‘sepsis’’ has its origins in the word ‘‘σ´ηψις’’, which is the original Greek word for decomposition or putrefaction, and has been used in that context since before Hippocrates [1, 2]. However, although the word, sepsis, has been used for more than 2700 years, it is only relatively recently that we have begun to understand the pathophysiology of sepsis in any depth [3]. With this new insight into the mechanisms underlying sepsis has come the potential for new and improved therapeutic interventions, and simultaneously a realization that the available terminology and definitions of sepsis were confusing and inadequate. In this chapter, I will outline progress in the field of sepsis definitions, and discuss possible approaches for the future.

In 1989, Roger Bone [4] proposed the term ‘‘sepsis syndrome’’, defining it as hypothermia (temperature less than 96 ◦F (35.5 ◦C)) or hyperthermia (greater than 101 ◦F (38.3 ◦C)), tachycardia (greater than 90 beat/min), tachypnea (greater than 20 breaths/min), clinical evidence of an infection site, and at least one end-organ demonstrating inadequate perfusion or dysfunction. This terminology was somewhat redundant as sepsis was already a known syndrome, and is no longer used, having being replaced by the term ‘‘severe sepsis’’.

In 1991, a Consensus Conference was held by the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) to create a ‘‘set of definitions that could be applied to patients with sepsis and its sequelae’’ [5]. The goal of the conference was to provide a ‘‘framework’’ to define the systemic inflammatory response to infection, and by so doing to improve the early diagnosis of sepsis, thus allowing earlier therapeutic intervention. It was realized that the lack of a single definition for sepsis created difficulties in identifying patients, particularly for clinical trials, and it was believed that having a single, universally accepted definition would facilitate ongoing research in this field.

It had been recognized that the same systemic response seen in patients with severe infections, could also occur in patients without infection but with other inflammatory processes, e.g. pancreatitis, multiple trauma, ischemia, burns, etc. and the consensus conference believed it was necessary to introduce new terminology to define such patients. The key aspect of the consensus conference definitions was, therefore, the introduction of the term Systemic Inflammatory Response Syndrome or SIRS to define this phenomenon. SIRS was defined as being the presence of more than one of four clinical criteria:

1. Body temperature greater than 38 ◦C or less than 36◦C
2. Heart rate greater than 90 beats/min
3. Respiratory rate greater than 20 breaths/min or hyperventilation with a PaCO2 less than 32 mmHg
4. White blood cell count >12000/mm3, <4000/mm3, or with >10% immature neutrophils.

The combination of SIRS with a confirmed infectious process was then called sepsis. Severe sepsis was defined as sepsis associated with organ dysfunction, hypoperfusion abnormality, or sepsis-induced hypotension, and septic shock was defined as severe sepsis with sepsis-induced hypotension persisting despite adequate fluid resuscitation.

Content

1. Definition of Sepsis and Non-infectious SIRS 
2. Similarities of the Clinical Aspects of Sepsis and Non-infectious SIRS
3. Organ Dysfunctions during Severe Sepsis and Septic-like Syndromes: Epidemiology, Classification, and Mechanisms
4. Pathogens in Sepsis: Gram-negative Bacterial PAMPs and PRRs
5. Pathogens in Sepsis: Gram-positive Bacterial PAMPs, PRRs and Superantigens
6. Pathogens in Sepsis: Fungi, Parasites
7. Physiopathology of Sepsis and SIRS
8. Inflammatory Mediators
9. Apoptosis: A Potential Therapeutic Target in Sepsis and Non-Infectious Systemic Inflammation
10. The Role of Endothelium
11. Coagulation
12. Epithelial Barrier Dysfunction as a Mechanism in the Pathogenesis of Multiple Organ Dysfunction
13. Neural Regulation of Cytokines
14. Genetic Polymorphisms and Other Parameters that Affect Predisposal to Infection and Outcome
15. Altered Immune Status and Leukocytes Reprogramming
16. Experimental Models and Therapies
17. Experimental Models of Sepsis and Non-infectious SIRS
18. The Past, Present and Future of Therapies for Sepsis and Non-infectious Systemic Inflammation

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