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Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för systemteknik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Reglerteknik.
Vise andre og tillknytning
2014 (engelsk)Inngår i: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 113, nr 1, s. 23-36Artikkel i tidsskrift (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
2014. Vol. 113, nr 1, s. 23-36
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-207830DOI: 10.1016/j.cmpb.2013.07.020ISI: 000327180900003OAI: oai:DiVA.org:uu-207830DiVA, id: diva2:649897
Tilgjengelig fra: 2013-08-28 Laget: 2013-09-19 Sist oppdatert: 2018-08-17bibliografisk kontrollert
Inngår i avhandling
1. Nonlinear Modeling and Feedback Control of Drug Delivery in Anesthesia
Åpne denne publikasjonen i ny fane eller vindu >>Nonlinear Modeling and Feedback Control of Drug Delivery in Anesthesia
2014 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

General anesthesia is a drug-induced reversible state where neuromuscular blockade (NMB), hypnosis, and analgesia (jointly denoted by depth of anesthesia - DoA) are guaranteed. This thesis concerns mathematical modeling and feedback control of the effect of the muscle relaxants atracurium and rocuronium, the hypnotic propofol, and the analgesic remifentanil. It is motivated by the need to reduce incidences of awareness and overdose-related post-operative complications that occur in standard clinical practice. A major challenge for identification in closed-loop is the poor excitation provided by the feedback signal. This applies to the case of drugs administered in closed-loop. As a result, the standard models for the effect of anesthetics appear to be over-parameterized. This deteriorates the result of system identification and prevents individualized control.

In the first part of the thesis, minimally parameterized models for the single-input single-output NMB and the multiple-input single-output DoA are developed, using real data. The models have a nonlinear Wiener structure: linear time-invariant dynamics cascaded with a static nonlinearity. The proposed models are shown to improve identifiability as compared to the standard ones.

The second part of the thesis presents system identification methods for Wiener systems: a batch prediction error method, and two recursive techniques, one based on the extended Kalman filter, and another based on the particle filter. Algorithms are given for both the NMB and the DoA using the minimally parameterized models.

Nonlinear adaptive controllers are proposed in the third part of the thesis. Using the model parameter estimates from the extended Kalman filter, the controller performs an online inversion of the Wiener nonlinearity. A pole-placement controller or a linear quadratic Gaussian controller is used for the linearized system. Results show good reference tracking performance both in simulation and in real trials.

Relating to patient safety, the existence of undesirable sustained oscillations as consequence of Andronov-Hopf bifurcations for a NMB PID-controlled system is analyzed. Essentially the same bifurcations are observed in the standard and the minimally parameterized models, confirming the ability of the latter to predict the nonlinear behavior of the closed-loop system. Methods to design oscillation-free controllers are outlined.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2014. s. 75
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1187
Emneord
anesthesia, drug delivery, feedback control, nonlinear modeling, pharmacokinetics/pharmacodynamics, PID control, system identification, Wiener model
HSV kategori
Forskningsprogram
Elektroteknik med inriktning mot reglerteknik
Identifikatorer
urn:nbn:se:uu:diva-233290 (URN)978-91-554-9054-6 (ISBN)
Disputas
2014-11-21, Room 2347, Polacksbacken, Lägerhyddsvägen 2, Uppsala, 09:15 (engelsk)
Opponent
Veileder
Forskningsfinansiär
EU, European Research Council, 247035
Tilgjengelig fra: 2014-10-30 Laget: 2014-10-01 Sist oppdatert: 2018-08-17

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