Modeling and Hemofiltration Treatment of Acute Inflammation

Parker, Robert; Rubin, Jonathan; Valenti, Isabella; Hogg, Justin; Lagoa, Claudio; Clermont, Gilles; Federspiel, William; Vodovotz, Yoram; Rimmelé, Thomas; Kellum, John; Roy, Anirban; Fedorchak, Morgan; Daun-Gruhn, Silvia

doi:10.3390/pr4040038

Journal Article

FZJ-2017-00246

Modeling and Hemofiltration Treatment of Acute Inflammation

Parker, R. (Corresponding author) ; Hogg, J. ; Roy, A. ; Kellum, J. ; Rimmelé, T. ; Daun-Gruhn, S.FZJ* ; Fedorchak, M. ; Valenti, I. ; Federspiel, W. ; Rubin, J. ; Vodovotz, Y. ; Lagoa, C. ; Clermont, G.

2016
MDPI Basel

Processes 4(4), 38 - (2016) [10.3390/pr4040038]

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Please use a persistent id in citations: http://hdl.handle.net/2128/13421 doi:10.3390/pr4040038

Abstract: The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin) and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D) differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL)-6, tumor necrosis factor (TNF), and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC) algorithm was synthesized to control a hemoadsorption (HA) device, a blood purification treatment for acute inflammation. A particle filter (PF) algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i) the apparent primary mechanism of HA efficacy is white blood cell (WBC) capture, with cytokine capture a secondary benefit; and (ii) differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

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