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- Feedforward adaptive control of the Bispectral Index of the EEG using the intravenous anaesthetic drug propofolPublication . Nunes, Catarina S.; Mendonça, Teresa; Lemos, João M.; Amorim, PedroThe problem of controlling the level of unconsciousness measured by the Bispectral Index (BIS) of the EEG of patients under anaesthesia is considered. The manipulated variable is the infusion rate of the hypnotic drug propofol. In order to tackle the high uncertainties present in the system, the predictive adaptive controller MUSMAR is used. The performance of the controller is illustrated by means of simulations with 50 patient individual adjusted models (nonlinear models), which incorporate the effect of the drugs interaction on BIS. This work presents a feasibility study of the control of the BIS exploring the above ideas. These results show that such a control structure can be adequate to control the BIS signal during total intravenous anaesthesia. The controller was able to adequately achieve and maintain the BIS signal with different patient dynamics, reference values and noise. A major challenge for the automation of anaesthesia consists of replicating the experience of the anaesthetist. Clearly, this calls for the use of feedforward from measurable signals correlated with disturbances (e.g. electromyography—EMG, analgesic drug). The results also show that the analgesic and EMG have different influences on the performance and therefore carry different but relevant information.
- The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anaesthetized patients independently from intubation and surgical stimuliPublication . Ferreira, D. A.; Nunes, Catarina S.; Antunes, L. M.; Santos, I. A.; Lobo, F.; Casal, M.; Ferreira, L.; Amorim, PedroBackground and objective: Remifentanil boluses are used in different clinical situations and the effects on bispectral index monitoring are unclear. We analysed the effect of a remifentanil bolus on the bispectral index of the electroencephalogram (bispectral index) under total intravenous anaesthesia with propofol and remifentanil. Methods: ASA I–III patients were included in this study. All patients received a 2 µg kg 1 remifentanil bolus in a period free from stimuli. Bispectral index and haemodynamic data were collected from an A-2000XP bispectral index monitor (every second) and an AS/3 Datex monitor (every 5 s). Bispectral index data were analysed using the area under the curve. Mean arterial pressure and heart rate were averaged at each 30-s period and analysed using analysis of variance. Results: A total of 240 bispectral index values were obtained per patient. The area under the curve between 90 and 120 s after the bolus was significantly lower than the basal area under the curve (average of all areas before the bolus, P 0.05). Mean arterial pressure and heart rate were significantly reduced from 96.4 19.9 mmHg at the time of the bolus to 74.2 16.6 mmHg 120 s after, and from 70 16.4 bpm at the time of the bolus to 61 13.6 bpm after (P 0.001), respectively. Conclusions: There was a significant reduction in the areas under the curve between 90–120 s following the bolus. Heart rate and blood pressure also showed significant reductions. Thus, remifentanil bolus given under total intravenous anaesthesia with propofol and remifentanil decreases bispectral index, an effect independent of intubation and surgical stimuli.
- EEG entropy monitoring of depth of anaesthesia: pharmacokinetic and dynamic modellingPublication . Castro, Ana; Bressan, Nadja; Antunes, Luís; Nunes, Catarina S.Because of the difficulty in analyzing raw electroencephalographic signal, several electroencephalographic monitors have been developed to aid anaesthetists on their task to maintain adequate anaesthesia. Spectral Entropy is used as a measure of electroencefalographic effects of drugs in human patients, and is a valuable tool to predict depth of anaesthesia. Monitors with implemented entropy algorithms, process the electroencephalogram (EEG) and are in current use at the operating room. In this study we used the EEG collected in rats and applied the Shannon entropy over the signal. The information obtained was used as an indicator of depth of anaesthesia. The main objective was to model the relation between the depth of anaesthesia in rats (entropy) and the propofol infusion rates, with the purpose of obtaining a closed-loop control for propofol infusions. Five adult rats were sedated with isoflurane, cannulated and equipped for the EEG collection. After the preparation, anaesthesia was induced with propofol infusions, using different infusion rates on each rat. The collected EEG (125Hz) was processed using an entropy algorithm developed in MATLAB R 7 that determined the entropy value at each second using the preceding 15s of signal. Pharmacokinetic models were fitted for each rat using bi and tri-compartmental models; the pharmacodynamic phase was also modelled for each rat. The relation between obtained propofol effect-site concentrations and the entropy values was modelled by a Hill Equation. The model obtained for the relation between infusion rates and entropy values was evaluated using the mean absolute deviation (MAD) and the relative mean square error (RMSE) for models comparative analysis.
- Remifentanil bolus dose is a safe procedure to control intense noxious stimuli in hypertensive neurosurgical patientsPublication . Ferreira, David A.; Nunes, Catarina S.; Lobo, Francisco; Antunes, Luís M.; Amorim, PedroPatients with hypertension may be more prone to develop hypotension as a consequence of opioid administration under general anesthesia. The hemodynamic and bispectral index responses to a remifentanil bolus in neurosurgical hypertensive patients under target-controlled infusion with propofol and remifentanil are addressed. Ten healthy patients and 10 patients with diagnosed hypertension under pharmacological treatment were studied. A 2 µg/kg remifentanil bolus was administered to all patients before skin incision under target-controlled infusion with propofol and remifentanil. Mean arterial pressure, heart rate, and the area under the curve for the bispectral index of the electroencephalogram were analyzed within the groups and compared between them every 30 seconds for two minutes following the bolus. Two minutes after the remifentanil bolus, remifentanil predicted effect-site concentrations reached maximum values of 8.46±0.91 ng/ml and 9.74±1.29 ng/ml in the healthy and hypertensive patients, respectively. Both groups showed a significant decrease in mean arterial pressure, heart rate, and in the area under the curve for the bispectral index. Mean arterial pressure decreased by 17.3±10% and 24±9%, heart rate by 11.1±8% and 12±8%, and the bispectral index by 13±9.2% and 8.6±8.4% in the healthy and hypertensive patients, respectively, 120 seconds after the remifentanil bolus. In a clinical situation in which high remifentanil doses may be required, hypertensive patients are expected to have hemodynamic and bispectral index responses similar to those observed in healthy patients.
- A wavelet based method for steady-state detection in anesthesiaPublication . Castro, A.; Almeida, F. G.; Amorim, Pedro; Nunes, Catarina S.With the recent concern on patient’s outcome following general anesthesia, automatic control of drugs has been a field of interest. The Bispectral Index (BIS) is an EEG based hypnosis monitor, in current use at the operating theatre as a guiding tool for the anesthesiologist to titrate drugs, and prevent awareness. When trying to model a certain process, it’s very important to obtain information of the system behavior under steady-state conditions. In this study the hypnotic and analgesic drugs’ effect on the hypnosis index BIS was analyzed, in order to obtain steady-state information of the system response (inputs-output), and in the future model the drugs combined effect. A steady-state index was obtained using a wavelet analysis technique for trend detection. This tool may be used in the future to model the drug’s combined effect on the hypnosis indices, and also to bring some insight on disturbances not related to drug changes.
- Usefulness of brain signals for the detection of loss of consciousness in anesthesia: overview of the problem and results from a Clinical StudyPublication . González, Carmen; Mendes, Marina; Amorim, Pedro; Mendes, Joaquim; Nunes, Catarina S.Loss of consciousness (LOC) detection is essential for better anesthesia guidance. Clinical signs and brain monitoring are currently used in operating rooms to assess the state of consciousness. However, a patientindependent, accurate and reliable indicator of LOC is not currently available. We studied 69 patients undergoing general anesthesia, investigating a possible relationship between loss of consciousness and BIS and EMG signals registered during induction. Neither BIS and EMG values at LOC, nor their abrupt fall proved to be good indicators of loss of consciousness. Further work needs to be done in order to reliably detect loss of consciousness.
- Modelling and multivariable control in anaesthesia using neural-fuzzy paradigmsPublication . Mahfouf, Mahdi; Nunes, Catarina S.; Linkens, Derek A.; Peacock, John E.Objective: Part II of this research study is concerned with the development of a closed-loop simulation linking the patient model as well as the fuzzy relational classifier already introduced in Part I with a control algorithm. The overall architecture is in fact a system advisor, which provides information to the anaesthetist about the adequate infusion-rates of propofol and remifentanil simultaneously. Methods and material: The developed fuzzy multivariable controller includes three rule-bases and takes into account the synergetic interactions between the above drugs and uses such knowledge to achieve rapidly the desired depth of anaesthesia (DOA) level. Results: The result of the study is a closed-loop control scheme, which adjusts efficiently the infusion-rates of two drugs in response to DOA changes. This controller can either be used in an advisory mode or closed-loop feedback mode in the operating theatre during surgery. Conclusion: It is hoped that this control scheme coupled with the patient model presented in Part I of this study will be used routinely in the operating theatre in the very near future.
- Predictive adaptive control of the bispectral index of the EEG (BIS): exploring electromyography as an accessible disturbancePublication . Nunes, Catarina S.; Mendonca, T.; Lemos, J. M.; Amorim, PedroThe problem of controlling the level of unconsciousness measured by the Bispectral Index of the EEG (BIS) of patients under anaesthesia, is considered. It is assumed that the manipulated variable is the infusion rate of the hypnotic drug propofol, while the drug remifentanil is also administered for analgesia. Since electromyography(EMG) interferes with the BIS signal, it is considered as an accessible disturbance. In order to tackle the high uncertain present on the system, the predictive adaptive controller MUS MAR is used. The performance of the controller is illustrated by means of simulation with 45 patient individual adjusted models, which incorporate the effect of the drugs interaction on BIS. This controller structure proved to be robust to the EMG disturbance, changing reference values and noise.
- Radial basis function neural networks versus fuzzy models to predict return of consciousness after general anesthesiaPublication . Nunes, Catarina S.; Mendonca, T. F.; Amorim, Pedro; Ferreira, D. A.; Antunes, L. M.This paper presents two modelling techniques to predict return of consciousness (ROC) after general anaesthesia, considering the effect concentration of the anaesthetic drug at awakening. First, several clinical variables were statistically analysed to determine their correlation with the awakening concentration. The anaesthetic and the analgesic mean dose during surgery, and the age of the patient, proved to have significantly high correlation coefficients. Variables like the mean bispectral index value during surgery, duration of surgery did not present a statistical relation with ROC. Radial basis function (RBF) neural networks were trained relating different sets of clinical values with the anaesthetic drug effect concentration at awakening. Secondly, fuzzy models were built using an Adaptive Network-Based Fuzzy Inference System (ANFIS) also relating different sets of variables. Clinical data was used to train and test the models. The fuzzy models and RBF neural networks proved to have good prediction properties and balanced results.
- Garch models for drug effects on patient heart rate, during general anaesthesiaPublication . Brás, Susana; Nunes, Catarina S.; Amorim, PedroA model that can describe the effect of anaesthetic drugs on patient’s heart rate (HR) is of great importance when considering haemodynamic stability under surgery. A Generalized Autoregressive Conditional Heteroscedasticity (GARCH) model was used to model HR considering the effect concentrations of the anaesthetic propofol and the analgesic remifentanil, using the clinical data of 16 patients. The model was able to capture the HR trend in all 16 patients with very small errors throughout the surgical time. A correlation was found between the GARCH parameters and patient baseline characteristics, leading to the possibility a patient adjusted adaptive model.