Modeling and Hemofiltration Treatment of Acute Inflammation

• Main Authors: Robert S. Parker, Justin S. Hogg, Anirban Roy, John A. Kellum, Thomas Rimmelé, Silvia Daun-Gruhn, Morgan V. Fedorchak, Isabella E. Valenti, William J. Federspiel, Jonathan Rubin, Yoram Vodovotz, Claudio Lagoa, Gilles Clermont
• Format: Article
• Language: English
• Published: MDPI AG 2016-10-01
• Series: Processes
• Subjects: mathematical model; inflammation; cytokines; sepsis; endotoxemia; hemoadsorption; nonlinear MPC; particle filter; state estimation
• Online Access: http://www.mdpi.com/2227-9717/4/4/38

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.