Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Parker, Robert S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hogg, Justin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Roy, Anirban UNSPECIFIED UNSPECIFIED UNSPECIFIED Kellum, John A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rimmele, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Daun-Gruhn, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Fedorchak, Morgan V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Valenti, Isabella E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Federspiel, William J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubin, Jonathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Vodovotz, Yoram UNSPECIFIED UNSPECIFIED UNSPECIFIED Lagoa, Claudio UNSPECIFIED UNSPECIFIED UNSPECIFIED Clermont, Gilles UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language REDUCED MATHEMATICAL-MODEL; SURVIVING SEPSIS CAMPAIGN; ACUTE-RENAL-FAILURE; SHORT-TERM SURVIVAL; ACUTE LUNG INJURY; SEPTIC SHOCK; GLOBAL IDENTIFIABILITY; ANTIINFLAMMATORY CYTOKINE; INTERNATIONAL GUIDELINES; BLOOD PURIFICATION Multiple languages Engineering, Chemical Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25505