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- Title
Modeling and Hemofiltration Treatment of Acute Inflammation.
- Authors
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
- 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.
- Subjects
INFLAMMATION treatment; BLOOD filtration; ENDOTOXINS; MEDICAL decision making; GRAM-negative bacteria; TUMOR necrosis factors
- Publication
Processes, 2016, Vol 4, Issue 4, p38
- ISSN
2227-9717
- Publication type
Article
- DOI
10.3390/pr4040038