Multi-drug infusion control using model reference adaptive algorithm

Control of physiological states such as mean arterial pressure (MAP) has been successfully achieved using single drug by different control algorithms. Multi-drug delivery demonstrates a significantly challenging task as compared to control with a single-drug. Also the patient’s sensitivity to the drugs varies from patient to patient. Therefore, the implementation of adaptive controller is very essential to improve the patient care in order to reduce the workload of healthcare staff and costs. This paper presents the design and implementation of the model reference adaptive controller (MRAC) to regulate mean arterial pressure and cardiac output by administering vasoactive and inotropic drugs that are sodium nitroprusside (SNP) and dopamine (DPM) respectively. The proposed adaptive control model has been implemented, tested and verified to demonstrate its merits and capabilities as compared to the existing research work

Multi-model adaptive predictive control system for automated regulation of mean blood pressure

After cardiac surgery operation, severe complications may occur in patients due to hypertension. To decrease the chances of complication it is necessary to reduce elevated mean arterial pressure (MAP) as soon as possible. Continuous infusion of vasodilator drugs, such as sodium nitroprusside (Nipride), it is used to reduce MAP quickly in most patients. For maintaining the desired blood pressure, a constant monitoring of arterial blood pressure is required and a frequently adjust on drug infusion rate. The manual control of arterial blood pressure by clinical professionals it is very demanding and time consuming, usually leading to a poor control quality of the hypertension. The objective of the study is to develop an automated control procedure of mean arterial pressure (MAP), during acute hypotension, for any patient, without changing the controller. So, a multi-model adaptive predictive methodology was developed and, for each model, a Predictive Controller can be a priori designed (MMSPGPC). In this paper, a sensitivity analysis was performed and the simulation results showed the importance of weighting factor (phi), which controls the initial drug infusion rate, to prevent hypotension and thus preserve patient's health. Simulation results, for 51 different patients, showed that the MMSPGPC provides a fast control with mean settling time of 04:46 min, undershoots less than 10 mmHg and steady-state error less than +/- 5 % from the MAP setpoint.The authors of this article would like to thank Federal Institute of Rio Grande do Norte for support and University of Minho for structure, which to made possible the development of the research

On adaptive control and particle filtering in the automatic administration of medicinal drugs

Automatic feedback methodologies for the administration of medicinal drugs offer undisputed potential benefits in terms of cost reduction and improved clinical outcomes. However, despite several decades of research, the ultimate safety of many--it would be fair to say most--closed-loop drug delivery approaches remains under question and manual methods based on clinicians' expertise are still dominant in clinical practice. Key challenges to the design of control systems for these applications include uncertainty in pharmacological models, as well as intra- and interpatient variability in the response to drug administration. Pharmacological systems may feature nonlinearities, time delays, time-varying parameters and non-Gaussian stochastic processes. This dissertation investigates a novel multi-controller adaptive control strategy capable of delivering safe control for closed-loop drug delivery applications without impairing clinicians' ability to make an expert assessment of a clinical situation. Our new feedback control approach, which we have named Robust Adaptive Control with Particle Filtering (RAC-PF), estimates a patient's individual response characteristic in real-time through particle filtering and uses the Bayesian inference result to select the most suitable controller for closed-loop operation from a bank of candidate controllers designed using the robust methodology of mu-synthesis. The work is presented as four distinct pieces of research. We first apply the existing approach of Robust Multiple-Model Adaptive Control (RMMAC), which features robust controllers and Kalman filter estimators, to the case-study of administration of the vasodepressor drug sodium nitroprusside and examine benefits and drawbacks. We then consider particle filtering as an alternative to Kalman filter-based methods for the real-time estimation of pharmacological dose-response, and apply this to the nonlinear pharmacokinetic-pharmacodynamic model of the anaesthetic drug propofol. We ultimately combine particle filters and robust controllers to create RAC-PF, and test our novel approach first in a proof-of-concept design and finally in the case of sodium nitroprusside. The results presented in the dissertation are based on computational studies, including extensive Monte-Carlo simulation campaigns. Our findings of improved parameter estimates from noisy observations support the use of particle filtering as a viable tool for real-time Bayesian inference in pharmacological system identification. The potential of the RAC-PF approach as an extension of RMMAC for closed-loop control of a broader class of systems is also clearly highlighted, with the proposed new approach delivering safe control of acute hypertension through sodium nitroprusside infusion when applied to a very general population response model. All approaches presented are generalisable and may be readily adapted to other drug delivery instances

Advanced model-based control studies for the induction and maintenance of intravenous anaesthesia

This paper describes strategies toward model-based automation of intravenous anaesthesia employing advanced control techniques. In particular, based on a detailed compartmental mathematical model featuring pharmacokinetic and pharmacodynamics information, two alternative model predictive control strategies are presented: a model predictive control strategy, based on online optimization, the extended predictive self-adaptive control and a multiparametric control strategy based on offline optimization, the multiparametric model predictive control. The multiparametric features to account for the effect of nonlinearity and the impact of estimation are also described. The control strategies are tested on a set of 12 virtually generated patient models for the regulation of the depth of anaesthesia by means of the bispectral index (BIS) using Propofol as the administrated anaesthetic. The simulations show fast response, suitability of dose, and robustness to induce and maintain the desired BIS setpoint

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

Closed-loop control of anesthesia : survey on actual trends, challenges and perspectives

Automation empowers self-sustainable adaptive processes and personalized services in many industries. The implementation of the integrated healthcare paradigm built on Health 4.0 is expected to transform any area in medicine due to the lightning-speed advances in control, robotics, artificial intelligence, sensors etc. The two objectives of this article, as addressed to different entities, are: i) to raise awareness throughout the anesthesiologists about the usefulness of integrating automation and data exchange in their clinical practice for providing increased attention to alarming situations, ii) to provide the actualized insights of drug-delivery research in order to create an opening horizon towards precision medicine with significantly improved human outcomes. This article presents a concise overview on the recent evolution of closed-loop anesthesia delivery control systems by means of control strategies, depth of anesthesia monitors, patient modelling, safety systems, and validation in clinical trials. For decades, anesthesia control has been in the midst of transformative changes, going from simple controllers to integrative strategies of two or more components, but not achieving yet the breakthrough of an integrated system. However, the scientific advances that happen at high speed need a modern review to identify the current technological gaps, societal implications, and implementation barriers. This article provides a good basis for control research in clinical anesthesia to endorse new challenges for intelligent systems towards individualized patient care. At this connection point of clinical and engineering frameworks through (semi-) automation, the following can be granted: patient safety, economical efficiency, and clinicians' efficacy

Optimal Regulation of Blood Glucose Level in Type I Diabetes using Insulin and Glucagon

The Glucose-Insulin-Glucagon nonlinear model [1-4] accurately describes how the body responds to exogenously supplied insulin and glucagon in patients affected by Type I diabetes. Based on this model, we design infusion rates of either insulin (monotherapy) or insulin and glucagon (dual therapy) that can optimally maintain the blood glucose level within desired limits after consumption of a meal and prevent the onset of both hypoglycemia and hyperglycemia. This problem is formulated as a nonlinear optimal control problem, which we solve using the numerical optimal control package PSOPT. Interestingly, in the case of monotherapy, we find the optimal solution is close to the standard method of insulin based glucose regulation, which is to assume a variable amount of insulin half an hour before each meal. We also find that the optimal dual therapy (that uses both insulin and glucagon) is better able to regulate glucose as compared to using insulin alone. We also propose an ad-hoc rule for both the dosage and the time of delivery of insulin and glucagon.Comment: Accepted for publication in PLOS ON

An Optimized Type-2 Self-Organizing Fuzzy Logic Controller Applied in Anesthesia for Propofol Dosing to Regulate BIS

During general anesthesia, anesthesiologists who provide anesthetic dosage traditionally play a fundamental role to regulate Bispectral Index (BIS). However, in this paper, an optimized type-2 Self-Organizing Fuzzy Logic Controller (SOFLC) is designed for Target Controlled Infusion (TCI) pump related to propofol dosing guided by BIS, to realize automatic control of general anesthesia. The type-2 SOFLC combines a type-2 fuzzy logic controller with a self-organizing (SO) mechanism to facilitate online training while able to contend with operational uncertainties. A novel data driven Surrogate Model (SM) and Genetic Programming (GP) based strategy is introduced for optimizing the type-2 SOFLC parameters offline to handle inter-patient variability. A pharmacological model is built for simulation in which different optimization strategies are tested and compared. Simulation results are presented to demonstrate the applicability of our approach and show that the proposed optimization strategy can achieve better control performance in terms of steady state error and robustness