Event-based MPC for propofol administration in anesthesia.

BACKGROUND AND OBJECTIVE: The automatic control of anesthesia is a demanding task mostly due to the presence of nonlinearities, intra- and inter-patient variability and specific clinical requirements to be meet. The traditional approach to achieve the desired depth of hypnosis level is based on knowledge and experience of the anesthesiologist. In contrast to a typical automatic control system, their actions are based on events that are related to the effect of the administrated drug. Thus, it is interesting to build a control system that will be able to mimic the behavior of the human way of actuation, simultaneously keeping the advantages of an automatic system. METHODS: In this work, an event-based model predictive control system is proposed and analyzed. The nonlinear patient model is used to form the predictor structure and its linear part is exploited to design the predictive controller, resulting in an individualized approach. In such a scenario, the BIS is the controlled variable and the propofol infusion rate is the control variable. The event generator governs the computation of control action applying a dead-band sampling technique. The proposed control architecture has been tested in simulation considering process noise and unmeasurable disturbances. The evaluation has been made for a set of patients using nonlinear pharmacokinetic/pharmacodynamic models allowing realistic tests scenarios, including inter- and intra-patient variability. Results For the considered patients dataset the number of control signal changes has been reduced of about 55% when compared to the classical control system approach and the drug usage has been reduced of about 2%. At the same time the control performance expressed by the integrated absolute error has been degraded of about 11%. CONCLUSIONS: The event-based MPC control system meets all the clinical requirements. The robustness analysis also demonstrates that the event-based architecture is able to satisfy the specifications in the presence of significant process noise and modelling errors related to inter- and intra-patient variability, providing a balanced solution between complexity and performance.

A modified PID-based control scheme for depth-of-hypnosis control: Design and experimental results.

BACKGROUND AND OBJECTIVE: Many methodologies have been proposed for the control of total intravenous anesthesia in general surgery, as this yields a reduced stress for the anesthesiologist and an increased safety for the patient. The objective of this work is to design a PID-based control system for the regulation of the depth of hypnosis by propofol and remifentanil coadministration that takes into account the clinical practice. METHODS: With respect to a standard PID control system, additional functionalities have been implemented in order to consider specific requirements related to the clinical practice. In particular, suitable boluses are determined and used in the induction phase and a nonzero baseline infusion is used in the maintenance phase when the predicted effect-site concentration drops below a safety threshold. RESULTS: The modified controller has been experimentally assessed on a group of 10 patients receiving general anesthesia for elective plastic surgery. The control system has been able to induce and maintain adequate anesthesia without any manual intervention from the anesthesiologist. CONCLUSIONS: Results confirm the effectiveness of the overall design approach and, in particular, highlight that the new version of the control system, with respect to a standard PID controller, provides significant advantages from a clinical standpoint.

Self-assembly from the gas-phase: design and implementation of small-molecule chromophore precursors with large nonlinear optical responses.

Efficiently organizing molecular nonlinear optical (NLO) chromophores having large first-order hyperpolarizabilities (beta) into acentric microstructures for electro-optic (EO) applications represents a significant materials synthesis and processing challenge, in part due to interchromophore dipolar interactions that promote centrosymmetric organization. Here we report the computational modeling, synthesis, and characterization of a series of eight heteroaromatic organic chromophores, designed to self-organize from the vapor phase via directed hydrogen-bond networks, into acentric thin films. Introduction of alpha,omega-donor-acceptor hydrogen-bonding substituents along the molecular long axes tunes properties such as hyperpolarizability, volatility, thermal stability, film-forming properties, and macroscopic NLO response (chi((2))). DFT-level molecular modeling, INDO/S optical property analysis, and sum-overstates computation indicate that molecular-core fluorination and hydrogen-bond donor incorporation can increase beta(vec) up to 40x versus that of typical fluorine-free chromophores. Furthermore, inclusion of sterically induced biphenyl conjugative decoupling between chromophore pi-donor substituents and the hydrogen-bonding donor sites increases beta by approximately 50%. Experimental thin-film second harmonic generation (SHG) spectroscopy confirms these trends in calculated responses, with chi((2)) increasing 7.5x upon chromophore core fluorination and 15x with hydrogen-bonding donor substitution, thereby achieving macroscopic responses as high as 302 pm/V at omega(o) = 1064 nm. In addition to response trends, cluster calculations also reveal linear additivity in beta(vec) with catenation for all benzoic acid-containing chromophores up to longitudinally aligned trimers. Linear scaling of SHG response with film thickness is observed for benzoic acid-containing chromophores up to 1.0 microm film thickness.