Modelling, Optimisation and Explicit Model Predictive Control of Anaesthesia Drug Delivery Systems

173 Pages·2014·2.3 MB·English

Imperial College London
Department of Chemical Engineering
Modelling, Optimisation and
Explicit Model Predictive Control
of Anaesthesia Drug Delivery
Systems
Alexandra Krieger
December 2013
Supervised by Professor Stratos Pistikopoulos
Submitted in part fulfilment of the requirements for the degree of
Doctor of Philosophy in Chemical Engineering of Imperial College London
and the Diploma of Imperial College London

Declaration
I herewith certify that all material in this dissertation which is not my own
work has been properly acknowledged.
Alexandra Krieger
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© The copyright of this thesis rests with the author and is made available
under a Creative Commons Attribution Non-Commercial No Derivatives
licence. Researchers are free to copy, distribute or transmit the thesis on
the condition that they attribute it, that they do not use it for commercial
purposes and that they do not alter, transform or build upon it. For any
reuse or redistribution, researchers must make clear to others the licence
terms of this work.
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Abstract
The contributions of this thesis are organised in two parts. Part I presents a
mathematical model for drug distribution and drug effect of volatile anaesthe-
sia. Part II presents model predictive control strategies for depth of anaesthe-
sia control based on the derived model.
Closed-loop model predictive control strategies for anaesthesia are aiming
to improve patient’s safety and to fine-tune drug delivery, routinely performed
by the anaesthetist.
The framework presented in this thesis highlights the advantages of ex-
tensive modelling and model analysis, which are contributing to a detailed
understanding of the system, when aiming for the optimal control of such sys-
tem. As part of the presented framework, the model uncertainty originated
from patient-variability is analysed and the designed control strategy is tested
against the identified uncertainty.
An individualised physiologically based model of drug distribution and up-
take, pharmacokinetics, anddrugeffect, pharmacodynamics, ofvolatileanaes-
thesiaispresented,wherethepharmacokineticmodelisadjustedtotheweight,
height, gender and age of the patient. The pharmacodynamic model links the
hypnotic depth measured by the Bispectral index (BIS), to the arterial con-
centration by an artificial effect site compartment and the Hill equation. The
individualised pharmacokinetic and pharmacodynamic variables and parame-
tersareanalysedwithrespecttotheirinfluenceonthemeasurableoutputs,the
end-tidal concentration and the BIS. The validation of the model, performed
with clinical data for isoflurane and desflurane based anaesthesia, shows a
good prediction of the drug uptake, while the pharmacodynamic parameters
are individually estimated for each patient.
The derived control design consists of a linear multi-parametric model pre-
dictive controller and a state estimator. The non-measurable tissue and blood
concentrationsareestimatedbasedontheend-tidalconcentrationofthevolatile
anaesthetic. The designed controller adapts to the individual patient’s dy-
namics based on measured data. In an alternative approach, the individual
patient’s sensitivity is estimated on-line by solving a least squares parameter
estimation problem.
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Acknowledgements
This thesis was funded by the European Research Council (MOBILE, ERC
Advanced Grant, No: 226462). Further I would like to acknowledge the finan-
cial support by the CPSE Industrial Consortium. I would like to thank Dr.
med. Rainer R¨ohrig and the Department of Medical Informatics in Anesthe-
siology and Intensive Care Medicine of the University of Gießen in Germany
for providing the anonymised patient data used in this study. I would like to
thankmysupervisorStratosPistikopoulosforhisguidanceandencouragement
during the time in his group at Imperial College London. Further, I would
also like to thank my examiners, Prof. Robin de Keyser and Prof. Claire
Adjiman, who provided detailed comments and constructive feedback on my
thesis. A great thank you to all my colleagues for their good friendship, fruit-
ful discussions and occasional weekend activities. My time in London would
not have been the same without participating actively in the volleyball com-
munity. Thanks to all of you. You truly kept me fit and busy. I met so many
amazing personalities from all over the world during my PhD. You all made
my time worthwhile. Most of all I would like to thank my flatmates. You
were my family abroad and always there for me. We are truly “the best flat
ever”. I also would like to thank my friends back home in Germany, who kept
in touch and dropped me occasional visits. You gave me the feeling nothing
changed although I was away. Finally I would like to thank my sister and my
parents for their support. You were always there for me. Danke.
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