Modeling and Hemofiltration Treatment of Acute Inflammation†
AbstractThe 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. View Full-Text
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Parker, R.S.; Hogg, J.S.; Roy, A.; Kellum, J.A.; Rimmelé, T.; Daun-Gruhn, S.; Fedorchak, M.V.; Valenti, I.E.; Federspiel, W.J.; Rubin, J.; Vodovotz, Y.; Lagoa, C.; Clermont, G. Modeling and Hemofiltration Treatment of Acute Inflammation. Processes 2016, 4, 38.
Parker RS, Hogg JS, Roy A, Kellum JA, Rimmelé T, Daun-Gruhn S, Fedorchak MV, Valenti IE, Federspiel WJ, Rubin J, Vodovotz Y, Lagoa C, Clermont G. Modeling and Hemofiltration Treatment of Acute Inflammation. Processes. 2016; 4(4):38.Chicago/Turabian Style
Parker, Robert S.; Hogg, Justin S.; Roy, Anirban; Kellum, John A.; Rimmelé, Thomas; Daun-Gruhn, Silvia; Fedorchak, Morgan V.; Valenti, Isabella E.; Federspiel, William J.; Rubin, Jonathan; Vodovotz, Yoram; Lagoa, Claudio; Clermont, Gilles. 2016. "Modeling and Hemofiltration Treatment of Acute Inflammation." Processes 4, no. 4: 38.