Controlling the depth of anesthesia by a novel positive control strategy

In this paper a positive control law is designed for multi-input positive systems that ensures asymptotic tracking of a desired output reference value. This control law can be viewed as a generalization of another one proposed in the literature for the control of the total mass in SISO compartmental systems, but is suitable for a wider class of positive systems. The controller proposed here is applied to the control of the depth of anesthesia (DoA), by means of the administration of propofol and remifentanil, when using a parameter parsimonious Wiener model recently introduced in the literature. Its performance is illustrated by realistic simulations

Robust fractional order PI control for cardiac output stabilisation

Drug regulatory paradigms are dependent on the hemodynamic system as it serves to distribute and clear the drug in/from the body. While focusing on the objective of the drug paradigm at hand, it is important to maintain stable hemodynamic variables. In this work, a biomedical application requiring robust control properties has been used to illustrate the potential of an autotuning method, referred to as the fractional order robust autotuner. The method is an extension of a previously presented autotuning principle and produces controllers which are robust to system gain variations. The feature of automatic tuning of controller parameters can be of great use for data-driven adaptation during intra-patient variability conditions. Fractional order PI/PD controllers are generalizations of the well-known PI/PD controllers that exhibit an extra parameter usually used to enhance the robustness of the closed loop system. (C) 2019, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved

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

Passive exercise of the hind limbs after complete thoracic transection of the spinal cord promotes cortical reorganization.

Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain

Type-2 fuzzy sets applied to multivariable self-organizing fuzzy logic controllers for regulating anesthesia

In this paper, novel interval and general type-2 self-organizing fuzzy logic controllers (SOFLCs) are proposed for the automatic control of anesthesia during surgical procedures. The type-2 SOFLC is a hierarchical adaptive fuzzy controller able to generate and modify its rule-base in response to the controller's performance. The type-2 SOFLC uses type-2 fuzzy sets derived from real surgical data capturing patient variability in monitored physiological parameters during anesthetic sedation, which are used to define the footprint of uncertainty (FOU) of the type-2 fuzzy sets. Experimental simulations were carried out to evaluate the performance of the type-2 SOFLCs in their ability to control anesthetic delivery rates for maintaining desired physiological set points for anesthesia (muscle relaxation and blood pressure) under signal and patient noise. Results show that the type-2 SOFLCs can perform well and outperform previous type-1 SOFLC and comparative approaches for anesthesia control producing lower performance errors while using better defined rules in regulating anesthesia set points while handling the control uncertainties. The results are further supported by statistical analysis which also show that zSlices general type-2 SOFLCs are able to outperform interval type-2 SOFLC in terms of their steady state performance

On Automation in Anesthesia

The thesis discusses closed-loop control of the hypnotic and the analgesic components of anesthesia. The objective of the work has been to develop a system which independently controls the intravenous infusion rates of the hypnotic drug propofol and analgesic drug remifentanil. The system is designed to track a reference hypnotic depth level, while maintaining adequate analgesia. This is complicated by inter-patient variability in drug sensitivity, disturbances caused foremost by surgical stimulation, and measurement noise. A commercially available monitor is used to measure the hypnotic depth of the patient, while a simple soft sensor estimates the analgesic depth. Both induction and maintenance of anesthesia are closed-loop controlled, using a PID controller for propofol and a P controller for remifentanil. In order to tune the controllers, patient models have been identified from clinical data, with body mass as only biometric parameter. Care has been taken to characterize identifiability and produce models which are safe for the intended application. A scheme for individualizing the controller tuning upon completion of the induction phase of anesthesia is proposed. Practical aspects such as integrator anti-windup and loss of the measurement signal are explicitly addressed. The validity of the performance measures, most commonly reported in closed-loop anesthesia studies, is debated and a new set of measures is proposed. It is shown, both in simulation and clinically, that PID control provides a viable approach. Both results from simulations and clinical trials are presented. These results suggest that closed-loop controlled anesthesia can be provided in a safe and efficient manner, relieving the regulatory and server controller role of the anesthesiologist. However, outlier patient dynamics, unmeasurable disturbances and scenarios which are not considered in the controller synthesis, urge the presence of an anesthesiologist. Closed-loop controlled anesthesia should therefore not be viewed as a replacement of human expertise, but rather as a tool, similar to the cruise controller of a car

Automatic control of the depth of anesthesia-clinical results

This paper presents clinical results of the implementation of an automatic controller previously designed by the authors for the BIS level of patients subject to general anesthesia. Since the controller has a state feedback component, an observer is introduced in order to estimate state

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

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