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This chapter is dedicated to Dr. Stephen Lowry, my mentor and friend.

KEY POINTS

Key Points

  1. Endogenous damage-associated molecular patterns (DAMPs) are produced following tissue and cellular injury. These molecules interact with immune and nonimmune cell receptors to initiate a “sterile” systemic inflammatory response following severe traumatic injury.

  2. In many cases, DAMP molecules are sensed by pattern recognition receptors (PRRs), which are the same receptors that cells use to sense invading pathogens. This explains in part, the similar clinical picture of systemic inflammation observed in injured and/or septic patients.

  3. The central nervous system receives information with regard to injury-induced inflammation via soluble mediators as well as direct neural projections that transmit information to regulatory areas in the brain. The resulting neuroendocrine reflex plays an important modulatory role in the immune response.

  4. Inflammatory signals activate key cellular stress responses (the oxidative stress response; the heat shock protein response; the unfolded protein response; autophagy; pyroptosis), which serve to mobilize cellular defenses and resources in an attempt to restore homeostasis.

  5. The cells, mediators, signaling mechanisms, and pathways that comprise and regulate the systemic inflammatory response are closely networked and tightly regulated by transcriptional events as well as by epigenetic mechanisms, posttranslational modification, and microRNA synthesis.

  6. Management of critically ill and injured patients is optimized with the use of evidence-based and algorithm-driven therapy.

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

OVERVIEW: INJURY-ASSOCIATED SYSTEMIC INFLAMMATORY RESPONSE

The inflammatory response to injury occurs as a consequence of the local or systemic release of “damage-associated” molecules to mobilize the necessary resources required for the restoration of homeostasis. Minor host insults result in a localized inflammatory response that is transient and, in most cases, beneficial. Major host insults follow a different trajectory. A subset of these patients will die within 24 hours of hospital admission, succumbing to overwhelming tissue injury and immediate organ damage. With advances in prehospital care and improved trauma management, these numbers have diminished. A second subgroup of patients who suffer a major host insult succumb to secondary organ damage remote from the injury site and die later (weeks) in their hospital course. They form an increasing percentage of the in hospital trauma-related deaths. A dysregulated, overwhelming systemic inflammatory response to the injury/hemorrhage and associated ischemia/reperfusion events has been implicated as the cause of multiple organ failure in these patients. Moreover, it has been linked to immune suppression that increases the risk of infectious complications and poor outcome. Finally, a third subgroup, characterized by extended length of stay in the ICU, complicated postdischarge courses, and failure to regain/recover to their preinjury status, has been described and also linked to persistent inflammation and suppressed host protective immunity. The term persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been applied to this group.1 Recent data suggest that severely injured patients who are destined ...

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