Sepsis: Something old, something new, and a systems view

Rami Namas, Ruben Zamora, Rajaie Namas, Gary An, John Doyle, Thomas E. Dick, Frank J. Jacono, Ioannis P. Androulakis, Gary F. Nieman, Steve Chang, Timothy R. Billiar, John A. Kellum, Derek C. Angus, Yoram Vodovotz

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Sepsis is a clinical syndrome characterized by a multisystem response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation that, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, proinflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis and focus specifically on the biologic cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multidimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology.

Original languageEnglish (US)
Pages (from-to)314.e1-314.e11
JournalJournal of Critical Care
Volume27
Issue number3
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Keywords

  • Inflammatory response
  • Mathematical model
  • Physiologic variability
  • Sepsis

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