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1. Systemic inflammation is characterized by exaggerated immune responses to either a sterile or infectious process. The cause of inflammatory activation needs to be addressed to resolve the dysregulated immune state.

2. An understanding of the signaling mechanisms and pathways underlying systemic inflammation can help guide therapeutic interventions in injured and/or septic patients.

3. Management of such patients is optimized with the use of evidence-based and algorithm-driven therapy.

4. Nutritional assessments, whether clinical or laboratory guided, and intervention should be considered at an early juncture in all surgical and critically ill patients.

5. Excessive feeding should be avoided in an effort to limit complications, including ventilator dependency, aspiration events, and infections.

The immune system has developed to respond to and neutralize pathogenic micro-organisms as well as coordinate tissue repair. The inflammatory response to injury or infection involves cell signaling, cell migration, and mediator release. Minor host insults instigate a local inflammatory response that is transient and in most cases beneficial. Major host insults may propagate reactions that can become amplified, resulting in systemic inflammation and potentially detrimental responses. This topic is highly relevant because systemic inflammation is a central feature1 of both sepsis and severe trauma. Understanding the complex pathways that regulate local and systemic inflammation is necessary to develop therapies to intervene during overwhelming sepsis or after severe injury. Sepsis, defined by a systemic inflammatory response to infection, is a disease process with an increasing incidence of over 900,000 cases per year. Trauma is the leading cause of mortality and morbidity for individuals under 50 years of age.

This chapter reviews the autonomic, cellular, and hormonal responses to injury. These facets of the inflammatory response to injury and infection are discussed in reference to the specific response being considered.

The systemic inflammatory response syndrome (SIRS) is characterized by a sequence of host phenotypic and metabolic responses to systemic inflammation that includes changes in heart rate, respiratory rate, blood pressure, temperature regulation, and immune cell activation (Table 2-1). The systemic inflammatory response includes two general phases: (1) an acute proinflammatory state resulting from innate immune system recognition of ligands, and (2) an anti-inflammatory phase that may serve to modulate the proinflammatory phase. Under normal circumstances, these coordinated responses direct a return to homeostasis2 (Fig. 2-1).

Table 2-1 Clinical Spectrum of Infection and Systemic Inflammatory Response Syndrome (SIRS)

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