Modeling and Hemofiltration Treatment of Acute Inflammation †
Abstract
:1. Introduction
1.1. Inflammation
1.2. Sepsis
1.3. Mathematical Models of Inflammation
1.4. Endotoxemia: A Model of Sepsis
1.5. Hemoadsorption: A Potential Treatment for Sepsis
1.6. Model-Based Treatment
1.6.1. Model Predictive Control
1.6.2. State Estimation: Mapping Diagnostics into Model Representations
1.7. Manuscript Overview
2. Materials and Methods
2.1. Experimental Data
2.2. Mathematical Model of Acute Inflammation
2.3. Parametric Sensitivity by Finite Difference Method
2.4. In Silico Treatment
2.5. Stochastic Endotoxemia Model
2.6. Observation Model
2.7. Hemoadsorption Model
2.8. WBC Capture Model
2.9. HA Device Configurations
2.10. Model Predictive Control
2.11. HA Performance Metric
2.12. Particle Filter State Estimation
2.13. State Estimation Performance Metric
3. Results
3.1. Parameter Sensitivity Analysis
3.2. Controlling the Inflammatory Response
3.2.1. MPC Using HA
3.2.2. HA Efficacy: Cytokine Versus WBC Capture
3.2.3. Differential Capture of Inflammatory Mediators
3.2.4. Particle Filter State Estimation
3.2.5. Hemoadsorption Control with State Estimation
4. Discussion
4.1. Trading Off Biological Fidelity and Model Structure
4.2. Biological Fidelity Challenges Parameter Estimation
4.3. Cell Capture Is Predicted Key to HA Efficacy
4.4. HA Devices with Differential Cytokine and WBC Capture May Have Little Benefit
4.5. MPC Reference Trajectory
4.6. State Estimation
4.7. Real-Time Control of HA
4.8. Limitations
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Appendix A. Model Structure Justification
Appendix A.1. Model Selection Technique
Appendix A.2. Model Selection Comparisons
Model (Equation) | AIC | BIC |
---|---|---|
IL-6 (Equation (14)) | 274.1 | 299.7 |
AV-1 (Equation (A4)) | 303.3 | 328.2 |
AV-2 (Equation (A5)) | 280.0 | 305.6 |
TNF (Equation (18)) | 274.1 | 299.7 |
AV-3 (Equation (A6)) | 282.2 | 307.8 |
AV-4 (Equation (A7)) | 277.0 | 303.2 |
IL-10 (Equation (22)) | 274.1 | 299.7 |
AV-5 (Equation (A8)) | 290.2 | 315.1 |
AV-6 (Equation (A9)) | 287.4 | 312.4 |
Effect of D on IL-10 (Equation (12)) | 274.1 | 299.7 |
AV-7 | 279.4 | 305.0 |
AV-8 | 281.1 | 306.7 |
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IL-6 | TNF | IL-10 | N | |
---|---|---|---|---|
0.62 | 0.188 | 0.682 | 0.177 | |
0.013 | 0.015 | 0.072 | 0.010 | |
0.006 | 0.007 | 0.022 | 0 |
HA | Specificity | ||
---|---|---|---|
Configuration | Column 1 | Column 2 | Column 3 |
A | TNF, IL-6, IL-10 | - | - |
B | N, TNF, IL-6, IL-10 | - | - |
C | N | TNF, IL-6, IL-10 | - |
D | N | TNF, IL-6 | IL-10 |
No. | Parameter | No. | Parameter | No. | Parameter | No. | Parameter |
---|---|---|---|---|---|---|---|
1 | 11 | 21 | 31 | ||||
2 | 12 | 22 | 32 | ||||
3 | 13 | 23 | 33 | ||||
4 | 14 | 24 | 34 | ||||
5 | 15 | 25 | 35 | ||||
6 | 16 | 26 | 36 | ||||
7 | 17 | 27 | 37 | ||||
8 | 18 | 28 | 38 | ||||
9 | 19 | 29 | 39 | ||||
10 | 20 | 30 | 40 |
Parameter Groups | Parameters |
---|---|
, , , , , , , , , , | |
, , | |
, , | |
, , , , , , , | |
, , , | |
, , , , , , | |
, , |
States | Relative Sensitivity (%) | |||||||
---|---|---|---|---|---|---|---|---|
100 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
13.8 | 64 | 0.2 | 1.9 | 2.8 | 5.7 | 11 | 0.5 | |
11.8 | 41.0 | 28.7 | 1.6 | 2.4 | 4.9 | 9.4 | 0.3 | |
13.0 | 45.8 | 0.1 | 23.3 | 2.3 | 5.1 | 10.0 | 0.2 | |
5.4 | 17.0 | 7.0 | 1.4 | 36.3 | 5.1 | 23.3 | 4.6 | |
9.8 | 23.9 | 0.3 | 21.2 | 3.9 | 33.3 | 7.3 | 0.2 | |
8.5 | 31.0 | 30.8 | 1.1 | 3.5 | 3.9 | 8.0 | 12.9 | |
8.7 | 29.6 | 33.2 | 1.1 | 1.6 | 3.6 | 6.9 | 15.3 |
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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.; et al. Modeling and Hemofiltration Treatment of Acute Inflammation. Processes 2016, 4, 38. https://doi.org/10.3390/pr4040038
Parker RS, Hogg JS, Roy A, Kellum JA, Rimmelé T, Daun-Gruhn S, Fedorchak MV, Valenti IE, Federspiel WJ, Rubin J, et al. Modeling and Hemofiltration Treatment of Acute Inflammation. Processes. 2016; 4(4):38. https://doi.org/10.3390/pr4040038
Chicago/Turabian StyleParker, Robert S., Justin S. Hogg, Anirban Roy, John A. Kellum, Thomas Rimmelé, Silvia Daun-Gruhn, Morgan V. Fedorchak, Isabella E. Valenti, William J. Federspiel, Jonathan Rubin, and et al. 2016. "Modeling and Hemofiltration Treatment of Acute Inflammation" Processes 4, no. 4: 38. https://doi.org/10.3390/pr4040038
APA StyleParker, 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. (2016). Modeling and Hemofiltration Treatment of Acute Inflammation. Processes, 4(4), 38. https://doi.org/10.3390/pr4040038