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.

Improved Individualized Patient-Oriented Depth-of-Hypnosis Measurement Based on Bispectral Index.

Total intravenous anesthesia is an anesthesiologic technique where all substances are injected intravenously. The main task of the anesthesiologist is to assess the depth of anesthesia, or, more specifically, the depth of hypnosis (DoH), and accordingly adjust the dose of intravenous anesthetic agents. However, it is not possible to directly measure the anesthetic agent concentrations or the DoH, so the anesthesiologist must rely on various vital signs and EEG-based measurements, such as the bispectral (BIS) index. The ability to better measure DoH is directly applicable in clinical practice-it improves the anesthesiologist's assessment of the patient state regarding anesthetic agent concentrations and, consequently, the effects, as well as provides the basis for closed-loop control algorithms. This article introduces a novel structure for modeling DoH, which employs a residual dynamic model. The improved model can take into account the patient's individual sensitivity to the anesthetic agent, which is not the case when using the available population-data-based models. The improved model was tested using real clinical data. The results show that the predictions of the BIS-index trajectory were improved considerably. The proposed model thus seems to provide a good basis for a more patient-oriented individualized assessment of DoH, which should lead to better administration methods that will relieve the anesthesiologist's workload and will benefit the patient by providing improved safety, individualized treatment, and, thus, alleviation of possible adverse effects during and after surgery.

The effect of ketamine on depth of hypnosis indices during total intravenous anesthesia-a comparative study using a novel electroencephalography case replay system.

Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg-1 bolus followed by a 10 mcg kg-1 min-1 infusion], Group 0.25 [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion], and Control [no ketamine]. EEG data were replayed to three monitors: NeuroSENSE (WAV), Bispectral Index (BIS), and Entropy (SE). Differences in depth-of-hypnosis indices during the initial 15 min after induction of anesthesia were compared between monitors, and between groups. Monitor agreement was evaluated using Bland-Altman analysis. Available data included 45.6 h of EEG recordings from 27 cases. Ketamine was associated with higher depth-of-hypnosis index values measured at 10 min (BIS, χ2 = 8.01, p = 0.018; SE, χ2 = 11.44, p = 0.003; WAV, χ2 = 9.19, p = 0.010), and a higher proportion of index values > 60 for both ketamine groups compared to the control group. Significant differences between monitors were not observed, except between BIS and SE in the control group. Ketamine did not change agreement between monitors. The ketamine-induced increase in depth-of-hypnosis indices was observed consistently across the three EEG monitoring algorithms evaluated. The observed increase was likely caused by a power increase in the beta and gamma bands. However, there were no lasting differences in depth-of-hypnosis reported between the three compared indices.

Robust PID control of propofol anaesthesia: Uncertainty limits performance, not PID structure.

BACKGROUND AND OBJECTIVE: New proposals to improve the regulation of hypnosis in anaesthesia based on the development of advanced control structures emerge continuously. However, a fair study to analyse the real benefits of these structures compared to simpler clinically validated PID-based solutions has not been presented so far. The main objective of this work is to analyse the performance limitations associated with using a filtered PID controller, as compared to a high-order controller, represented through a Youla parameter. METHODS: The comparison consists of a two-steps methodology. First, two robust optimal filtered PID controllers, considering the effect of the inter-patient variability, are synthesised. A set of 47 validated paediatric pharmacological models, identified from clinical data, is used to this end. This model set provides representative inter-patient variability Second, individualised filtered PID and Youla controllers are synthesised for each model in the set. For fairness of comparison, the same performance objective is optimised for all designs, and the same robustness constraints are considered. Controller synthesis is performed utilising convex optimisation and gradient-based methods relying on algebraic differentiation. The worst-case performance over the patient model set is used for the comparison. RESULTS: Two robust filtered PID controllers for the entire model set, as well as individual-specific PID and Youla controllers, were optimised. All considered designs resulted in similar frequency response characteristics. The performance improvement associated with the Youla controllers was not significant compared to the individually tuned filtered PID controllers. The difference in performance between controllers synthesized for the model set and for individual models was significantly larger than the performance difference between the individual-specific PID and Youla controllers. The different controllers were evaluated in simulation. Although all of them showed clinically acceptable results, the robust solutions provided slower responses. CONCLUSION: Taking the same clinical and technical considerations into account for the optimisation of the different controllers, the design of individual-specific solutions resulted in only marginal differences in performance when comparing an optimal Youla parameter and its optimal filtered PID counterpart. The inter-patient variability is much more detrimental to performance than the limitations imposed by the simple structure of the filtered PID controller.

Feasibility of continuous sedation monitoring in critically ill intensive care unit patients using the NeuroSENSE WAVCNS index.

Sedation in the intensive care unit (ICU) is challenging, as both over- and under-sedation are detrimental. Current methods of assessment, such as the Richmond Agitation Sedation Scale (RASS), are measured intermittently and rely on patients' behavioral response to stimulation, which may interrupt sleep/rest. A non-stimulating method for continuous sedation monitoring may be beneficial and allow more frequent assessment. Processed electroencephalography (EEG) monitors have not been routinely adopted in the ICU. The aim of this observational study was to assess the feasibility of using the NeuroSENSE™ monitor for EEG-based continuous sedation assessment. With ethical approval, ICU patients on continuous propofol sedation were recruited. Depth-of-hypnosis index (WAVCNS) values were obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE, performed regular RASS assessments and maintained the sedation regimen as per standard of care. Participants were monitored throughout the duration of their propofol infusion, up to 24 h. Fifteen patients, with median [interquartile range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7-20.1] h. Valid WAVCNS values were obtained for 89% [66-99] of monitoring time and were widely distributed within and between individuals, with 6% [1-31] spent < 40 (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89 (40%) assessments. The WAVCNS variability, and incidence of EEG suppression, highlight the limitations of using RASS as a standalone sedation measure, and suggests potential benefit of adjunct continuous brain monitoring.

Event-Based control of depth of hypnosis in anesthesia.

BACKGROUND AND OBJECTIVE: In this paper, we propose the use of an event-based control strategy for the closed-loop control of the depth of hypnosis in anesthesia by using propofol administration and the bispectral index as a controlled variable. METHODS: A new event generator with high noise-filtering properties is employed in addition to a PIDPlus controller. The tuning of the parameters is performed off-line by using genetic algorithms by considering a given data set of patients. RESULTS: The effectiveness and robustness of the method is verified in simulation by implementing a Monte Carlo method to address the intra-patient and inter-patient variability. A comparison with a standard PID control structure shows that the event-based control system achieves a reduction of the total variation of the manipulated variable of 93% in the induction phase and of 95% in the maintenance phase. CONCLUSIONS: The use of event based automatic control in anesthesia yields a fast induction phase with bounded overshoot and an acceptable disturbance rejection. A comparison with a standard PID control structure shows that the technique effectively mimics the behavior of the anesthesiologist by providing a significant decrement of the total variation of the manipulated variable.

Optimized PID control of depth of hypnosis in anesthesia.

BACKGROUND AND OBJECTIVE: This paper addresses the use of proportional-integral-derivative controllers for regulating the depth of hypnosis in anesthesia by using propofol administration and the bispectral index as a controlled variable. In fact, introducing an automatic control system might provide significant benefits for the patient in reducing the risk for under- and over-dosing. METHODS: In this study, the controller parameters are obtained through genetic algorithms by solving a min-max optimization problem. A set of 12 patient models representative of a large population variance is used to test controller robustness. The worst-case performance in the considered population is minimized considering two different scenarios: the induction case and the maintenance case. RESULTS: Our results indicate that including a gain scheduling strategy enables optimal performance for induction and maintenance phases, separately. Using a single tuning to address both tasks may results in a loss of performance up to 102% in the induction phase and up to 31% in the maintenance phase. Further on, it is shown that a suitably designed low-pass filter on the controller output can handle the trade-off between the performance and the noise effect in the control variable. CONCLUSIONS: Optimally tuned PID controllers provide a fast induction time with an acceptable overshoot and a satisfactory disturbance rejection performance during maintenance. These features make them a very good tool for comparison when other control algorithms are developed.

Characteristics of electroencephalogram signatures in sedated patients induced by various anesthetic agents.

Devices that monitor the depth of hypnosis based on the electroencephalogram (EEG) have long been commercialized, and clinicians use these to titrate the dosage of hypnotic agents. However, these have not yet been accepted as standard monitoring devices for anesthesiology. The primary reason is that the use of these monitoring devices does not completely prevent awareness during surgery, and the development of these devices has not taken into account the neurophysiological mechanisms of hypnotic agents, thus making it possible to show different levels of unconsciousness in the same brain status. An alternative is to monitor EEGs that are not signal processed with numerical values presented by these monitoring devices. Several studies have reported that power spectral analysis alone can distinguish the effects of different hypnotic agents on consciousness changes. This paper introduces the basic concept of power spectral analysis and introduces the EEG characteristics of various hypnotic agents that are used in sedation.

Characteristics of electroencephalogram signatures in sedated patients induced by various anesthetic agents

Devices that monitor the depth of hypnosis based on the electroencephalogram (EEG) have long been commercialized, and clinicians use these to titrate the dosage of hypnotic agents. However, these have not yet been accepted as standard monitoring devices for anesthesiology. The primary reason is that the use of these monitoring devices does not completely prevent awareness during surgery, and the development of these devices has not taken into account the neurophysiological mechanisms of hypnotic agents, thus making it possible to show different levels of unconsciousness in the same brain status. An alternative is to monitor EEGs that are not signal processed with numerical values presented by these monitoring devices. Several studies have reported that power spectral analysis alone can distinguish the effects of different hypnotic agents on consciousness changes. This paper introduces the basic concept of power spectral analysis and introduces the EEG characteristics of various hypnotic agents that are used in sedation.

Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used.