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

• Published in: Journal of critical care Vol. 27; no. 3; pp. 314.e1 - 314.e11
• Main Authors: Namas, Rami, MD, Zamora, Ruben, PhD, Namas, Rajaie, MD, An, Gary, MD, Doyle, John, PhD, Dick, Thomas E., PhD, Jacono, Frank J., MD, Androulakis, Ioannis P., PhD, Nieman, Gary F., PhD, Chang, Steve, MS, Billiar, Timothy R., MD, Kellum, John A., MD, Angus, Derek C., MD, MPH, FRCP, Vodovotz, Yoram, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2012; Elsevier Limited
• Subjects: Critical Care; Cytokines; Design; Humans; Inflammation - physiopathology; Inflammatory response; Intensive care; Mathematical model; Mathematical models; Models, Biological; Mortality; Nonlinear Dynamics; Physiologic variability; Principal components analysis; Sepsis; Sepsis - physiopathology; Studies; Systems Biology; Tissue engineering; United States > US; Sepsis; Inflammatory response; Mathematical model; Physiologic variability
• ISSN: 0883-9441; 1557-8615
• DOI: 10.1016/j.jcrc.2011.05.025

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.