Robust internal model control for depth of anaesthesia

This paper investigates the depth of anaesthesia control problem during a surgery, where paralytic, analgesic and hypnotic are regulated by means of monitored administration of specific drugs. A robust internal model controller (RIMC) based on the Bispectral Index (BIS) is proposed. The controller compares the measured BIS with its input reference to provide the expected propofol concentration, and then the controller manipulates the anaesthetic propofol concentration entering the anaesthetic system to achieve the desired BIS value. This study develops patient dose-response models and provides an adequate drug administration regimen to avoid under or over dosing of patients. Numerical simulations illustrate that the RIMC performed better than the traditional PID controller. The robust performance of the two controllers is evaluated for a wide range of patient models by varying in patient parameters. The other relative performance is also compared for different BIS step settings

Depth of anesthesia control using internal model control techniques

The major difficulty in the design of closed-loop control during anaesthesia is the inherent patient variability due to differences in demographic and drug tolerance. These discrepancies are translated into the pharmacokinetics (PK), and pharmacodynamics (PD). These uncertainties may affect the stability of the closed loop control system. This paper aims at developing predictive controllers using Internal Model Control technique. This study develops patient dose-response models and to provide an adequate drug administration regimen for the anaesthesia to avoid under or over dosing of the patients. The controllers are designed to compensate for patients inherent drug response variability, to achieve the best output disturbance rejection, and to maintain optimal set point response. The results are evaluated compared with traditional PID controller and the performance is confirmed in our simulation

Neuronal entropy depends on the level of alertness in the parkinsonian globus pallidus in vivo

A new working hypothesis of Parkinson's disease (PD) proposes to focus on the central role of entropy increase in the basal ganglia (BG) in movement disorders. The conditions necessary for entropy increase in vivo are, however, still not fully described. We recorded the activity of single globus pallidus pars interna neurons during the transition from deep anesthesia to full alertness in relaxed, head-restrained, control, and parkinsonian (6-hydroxydopamine-lesioned group-lesioned) rats. We found that during awakening from anesthesia, the variation of neuronal entropy was significantly higher in the parkinsonian than in the control group. This implies in our view that in PD the entropy of the output neurons of the BG varies dynamically with the input to the network, which is determined by the level of alertness. Therefore, entropy needs to be interpreted as a dynamic, emergent property that characterizes the global state of the BG neuronal network, rather than a static property of parkinsonian neurons themselves. Within the framework of the "entropy hypothesis," this implies the presence of a pathological feedback loop in the parkinsonian BG, where increasing the network input results in a further increase of neuronal entropy and a worsening of akinesia.Fil: Andres, Daniela Sabrina. Universitat Zurich; Suiza. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cerquetti, Daniel. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas ; ArgentinaFil: Merello, Marcelo Jorge. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stoop, Ruedi. Universitat Zurich; Suiz

Ultrasonic locating devices for central venous cannulation: meta-analysis

OBJECTIVES: To assess the evidence for the clinical effectiveness of ultrasound guided central venous cannulation. DATA SOURCES: 15 electronic bibliographic databases, covering biomedical, science, social science, health economics, and grey literature. DESIGN: Systematic review and meta-analysis of randomised controlled trials. POPULATIONS: Patients scheduled for central venous access. INTERVENTION REVIEWED: Guidance using real time two dimensional ultrasonography or Doppler needles and probes compared with the anatomical landmark method of cannulation. DATA EXTRACTION: Risk of failed catheter placement (primary outcome), risk of complications from placement, risk of failure on first attempt at placement, number of attempts to successful catheterisation, and time (seconds) to successful catheterisation. DATA SYNTHESIS: 18 trials (1646 participants) were identified. Compared with the landmark method, real time two dimensional ultrasound guidance for cannulating the internal jugular vein in adults was associated with a significantly lower failure rate both overall (relative risk 0.14, 95% confidence interval 0.06 to 0.33) and on the first attempt (0.59, 0.39 to 0.88). Limited evidence favoured two dimensional ultrasound guidance for subclavian vein and femoral vein procedures in adults (0.14, 0.04 to 0.57 and 0.29, 0.07 to 1.21, respectively). Three studies in infants confirmed a higher success rate with two dimensional ultrasonography for internal jugular procedures (0.15, 0.03 to 0.64). Doppler guided cannulation of the internal jugular vein in adults was more successful than the landmark method (0.39, 0.17 to 0.92), but the landmark method was more successful for subclavian vein procedures (1.48, 1.03 to 2.14). No significant difference was found between these techniques for cannulation of the internal jugular vein in infants. An indirect comparison of relative risks suggested that two dimensional ultrasonography would be more successful than Doppler guidance for subclavian vein procedures in adults (0.09, 0.02 to 0.38). CONCLUSIONS: Evidence supports the use of two dimensional ultrasonography for central venous cannulation

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

The contributions of this thesis are organised in two parts. Part I presents a mathematical model for drug distribution and drug effect of volatile anaesthesia. Part II presents model predictive control strategies for depth of anaesthesia 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 extensive modelling and model analysis, which are contributing to a detailed understanding of the system, when aiming for the optimal control of such system. 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 uptake, pharmacokinetics, and drug effect, pharmacodynamics, of volatile anaesthesia is presented, where the pharmacokinetic model is adjusted to the weight, height, gender and age of the patient. The pharmacodynamic model links the hypnotic depth measured by the Bispectral index (BIS), to the arterial concentration by an artificial effect site compartment and the Hill equation. The individualised pharmacokinetic and pharmacodynamic variables and parameters are analysed with respect to their influence on the measurable outputs, 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 predictive controller and a state estimator. The non-measurable tissue and blood concentrations are estimated based on the end-tidal concentration of the volatile anaesthetic. The designed controller adapts to the individual patient's dynamics 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.Open Acces

Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible.Peer reviewe

Advanced multiparametric optimization and control studies for anaesthesia

Anaesthesia is a reversible pharmacological state of the patient where hypnosis, analgesia and muscle relaxation are guaranteed and maintained throughout the surgery. Analgesics block the sensation of pain; hypnotics produce unconsciousness, while muscle relaxants prevent unwanted movement of muscle tone. Controlling the depth of anaesthesia is a very challenging task, as one has to deal with nonlinearity, inter- and intra-patient variability, multivariable characteristics, variable time delays, dynamics dependent on the hypnotic agent, model analysis variability, agent and stability issues. The modelling and automatic control of anaesthesia is believed to (i) benefit the safety of the patient undergoing surgery as side-effects may be reduced by optimizing the drug infusion rates, and (ii) support anaesthetists during critical situations by automating the drug delivery systems. In this work we have developed several advanced explicit/multi-parametric model predictive (mp-MPC) control strategies for the control of depth of anaesthesia. State estimation techniques are developed and used simultaneously with mp-MPC strategies to estimate the state of each individual patient, in an attempt to overcome the challenges of inter- and intra- patient variability, and deal with possible unmeasurable noisy outputs. Strategies to deal with the nonlinearity have been also developed including local linearization, exact linearization as well as a piece-wise linearization of the Hill curve leading to a hybrid formulation of the patient model and thereby the development of multiparametric hybrid model predictive control methodology. To deal with the inter- and intra- patient variability, as well as the noise on the process output, several robust techniques and a multiparametric moving horizon estimation technique have been design and implemented. All the studies described in the thesis are performed on clinical data for a set of 12 patients who underwent general anaesthesia.Open Acces

Measurement of outflow facility using iPerfusion

Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion™, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems