Mathematical Biosciences and Engineering (MBE)

Using nonlinear model predictive control to find optimal therapeutic strategies to modulate inflammation

Pages: 739 - 763, Volume 7, Issue 4, October 2010      doi:10.3934/mbe.2010.7.739

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Judy Day - Mathematical Biosciences Institute, The Ohio State University, 1735 Neil Ave, 377 Jennings Hall, Columbus, OH 43210, United States (email)
Jonathan Rubin - Department of Mathematics, University of Pittsburgh, 301 Thackeray Hall, Pittsburgh, PA 15260, United States (email)
Gilles Clermont - Department of Critical Care Medicine, University of Pittsburgh Medical Center, 3550 Terrace St, Pittsburgh, PA 15261, United States (email)

Abstract: Modulation of the inflammatory response has become a key focal point in the treatment of critically ill patients. Much of the computational work in this emerging field has been carried out with the goal of unraveling the primary drivers, interconnections, and dynamics of systemic inflammation. To translate these theoretical efforts into clinical approaches, the proper biological targets and specific manipulations must be identified. In this work, we pursue this goal by implementing a nonlinear model predictive control (NMPC) algorithm in the context of a reduced computational model of the acute inflammatory response to severe infection. In our simulations, NMPC successfully identifies patient-specific therapeutic strategies, based on simulated observations of clinically accessible inflammatory mediators, which outperform standardized therapies, even when the latter are derived using a general optimization routine. These results imply that a combination of computational modeling and NMPC may be of practical use in suggesting novel immuno-modulatory strategies for the treatment of intensive care patients.

Keywords:  Inflammation, nonlinear model predictive control, immuno-modulation, dosing control.
Mathematics Subject Classification:  Primary: 92C50, 93C15; Secondary: 93C83.

Received: March 2010;      Accepted: May 2010;      Available Online: October 2010.