Parker, Robert S., Hogg, Justin S., Roy, Anirban, Kellum, John A., Rimmele, Thomas, Daun-Gruhn, Silvia, Fedorchak, Morgan V., Valenti, Isabella E., Federspiel, William J., Rubin, Jonathan, Vodovotz, Yoram, Lagoa, Claudio and Clermont, Gilles (2016). Modeling and Hemofiltration Treatment of Acute Inflammation. Processes, 4 (4). BASEL: MDPI. ISSN 2227-9717

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Parker, Robert S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogg, Justin S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roy, AnirbanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kellum, John A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rimmele, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daun-Gruhn, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fedorchak, Morgan V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valenti, Isabella E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Federspiel, William J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubin, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vodovotz, YoramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lagoa, ClaudioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clermont, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-255057
DOI: 10.3390/pr4040038
Journal or Publication Title: Processes
Volume: 4
Number: 4
Date: 2016
Publisher: MDPI
Place of Publication: BASEL
ISSN: 2227-9717
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REDUCED MATHEMATICAL-MODEL; SURVIVING SEPSIS CAMPAIGN; ACUTE-RENAL-FAILURE; SHORT-TERM SURVIVAL; ACUTE LUNG INJURY; SEPTIC SHOCK; GLOBAL IDENTIFIABILITY; ANTIINFLAMMATORY CYTOKINE; INTERNATIONAL GUIDELINES; BLOOD PURIFICATIONMultiple languages
Engineering, ChemicalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25505

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