Review: Intelligent Modeling and Control in Anesthesia

This paper provides a detailed review of the clinical aspect and engineering view of how to measure, interpret, model, and control general anesthesia. The mechanisms of anesthesia in terms of unconsciousness, amnesia, analgesia, and akinesia in modern balanced anesthesia are reviewed. The assessment and interpretation of anesthesia according to clinical signs (i.e., lacrimation, sweating, papillary dilatation), physiological monitors (i.e., electromyography, electrocardiography, blood pressure, electroencephalography, oxyhemoglobin saturation), and evaluation indices (i.e., bispectral index scale, entropy, auditory evoked potentials, and surgical stress index) are reviewed in order to define the objectives of general anesthesia. Finally, the intelligent modeling and control of anesthesia are thoroughly reviewed. Modern general anesthesia is moving towards the monitoring, interpretation, modeling, and control of multi-inputs from quantitative and qualitative nonlinear physiological signals and multi-outputs for drug control of unconsciousness, amnesia, analgesia, and akinesia. A multistage hierarchical system should thus be developed for the modeling and control of general anesthesia in the future.

[1]  Madalena Costa,et al.  Multiscale entropy analysis of biological signals. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  L. Barvais,et al.  The Influence of a Muscle Relaxant Bolus on Bispectral and Datex-Ohmeda Entropy Values During Propofol-Remifentanil Induced Loss of Consciousness , 2005, Anesthesia and analgesia.

[3]  J. Jakobsson,et al.  Nitrous oxide does not alter bispectral index: study with nitrous oxide as sole agent and as an adjunct to i.v. anaesthesia. , 1999, British journal of anaesthesia.

[4]  P. Coriat,et al.  Overestimation of Bispectral Index in Sedated Intensive Care Unit Patients Revealed by Administration of Muscle Relaxant , 2003, Anesthesiology.

[5]  P Hans,et al.  Comparative effects of ketamine on Bispectral Index and spectral entropy of the electroencephalogram under sevoflurane anaesthesia. , 2005, British journal of anaesthesia.

[6]  Teresa Mendonça,et al.  Hipocrates: a Robust System for the Control of Neuromuscular Blockade , 2005, Journal of Clinical Monitoring and Computing.

[7]  Maysam F. Abbod,et al.  Survey of utilisation of fuzzy technology in Medicine and Healthcare , 2001, Fuzzy Sets Syst..

[8]  A M Zbinden,et al.  Prediction of the haemodynamic response to tracheal intubation: comparison of laser-Doppler skin vasomotor reflex and pulse wave reflex. , 2002, British journal of anaesthesia.

[9]  Yaochu Jin,et al.  Fuzzy Systems in Bioinformatics and Computational Biology , 2009, Fuzzy Systems in Bioinformatics and Computational Biology.

[10]  Efstratios N. Pistikopoulos,et al.  Modelling and multi-parametric control for delivery of anaesthetic agents , 2010, Medical & Biological Engineering & Computing.

[11]  A. Yli-Hankala,et al.  Assessment of surgical stress during general anaesthesia. , 2007, British journal of anaesthesia.

[12]  C P Heneghan,et al.  Effect of surgical stimulation on the auditory evoked response. , 1988, British journal of anaesthesia.

[13]  S. Petersen-Felix,et al.  Fuzzy logic control of mechanical ventilation during anaesthesia. , 1996, British journal of anaesthesia.

[14]  K. Olkkola,et al.  Pharmacodynamics of mivacurium in children, using a computer-controlled infusion. , 1993, British journal of anaesthesia.

[15]  D.A. Linkens,et al.  Adaptive and intelligent control in anesthesia , 1992, IEEE Control Systems.

[16]  M. Mccaffery,et al.  Pain ratings: the fifth vital sign. , 1997, The American journal of nursing.

[17]  J. Antognini,et al.  Propofol Produces Immobility via Action in the Ventral Horn of the Spinal Cord by a GABAergic Mechanism , 2009, Anesthesia and analgesia.

[18]  I Korhonen,et al.  Photoplethysmography and nociception , 2009, Acta anaesthesiologica Scandinavica.

[19]  S J GALLA,et al.  EVALUATION OF THE TRADITIONAL SIGNS AND STAGES OF ANESTHESIA: AN ELECTROENCEPHALOGRAPHS AND CLINICAL STUDY , 1958, Anesthesiology.

[20]  Steven Edward Kern,et al.  Pharmacokinetic-Based Minibolus Delivery as an Alternative to Continuous Infusion for Drugs That Exhibit a Biophase Lag , 1997, Journal of Pharmacokinetics and Biopharmaceutics.

[21]  S. Barker,et al.  The Bispectral Index Declines During Neuromuscular Block in Fully Awake Persons , 2003, Anesthesia and analgesia.

[22]  Derek A. Linkens,et al.  A hierarchical system of on-line advisory for monitoring and controlling the depth of anaesthesia using self-organizing fuzzy logic , 2005, Eng. Appl. Artif. Intell..

[23]  C. Doré,et al.  The auditory evoked response as an indicator of awareness. , 1989, British journal of anaesthesia.

[24]  S. Roberts,et al.  EEG signal processing in anaesthesia. Use of a neural network technique for monitoring depth of anaesthesia. , 2002, British journal of anaesthesia.

[25]  J. Feldman,et al.  Looking for inspiration: new perspectives on respiratory rhythm , 2006, Nature Reviews Neuroscience.

[26]  M. Lema,et al.  Postoperative Epidural Opioid Analgesia: What Are the Choices? , 1996, Anesthesia and analgesia.

[27]  Constantin V. Negoita,et al.  On Fuzzy Systems , 1978 .

[28]  D. Spahn,et al.  Antagonism of neuromuscular blockade but not muscle relaxation affects depth of anaesthesia. , 2005, British journal of anaesthesia.

[29]  Crofts Sl,et al.  Clinical monitoring of neuromuscular function. , 1992 .

[30]  B. Antkowiak,et al.  Molecular and neuronal substrates for general anaesthetics , 2004, Nature Reviews Neuroscience.

[31]  A. Bjorksten,et al.  Alfentanil Blocks Reflex Pupillary Dilation in Response to Noxious Stimulation But Does Not Diminish the Light Reflex , 1997, Anesthesiology.

[32]  T. Kudo,et al.  [Effects of sevoflurane anesthesia and surgery on anterior pituitary and adrenocortical function in man]. , 1987, Masui. The Japanese journal of anesthesiology.

[33]  E Pöppel,et al.  Effects of increasing doses of alfentanil, fentanyl and morphine on mid-latency auditory evoked potentials. , 1993, British journal of anaesthesia.

[34]  Steven L Shafer,et al.  Is Synergy the Rule? A Review of Anesthetic Interactions Producing Hypnosis and Immobility , 2008, Anesthesia and analgesia.

[35]  Jiann-Shing Shieh,et al.  AN ENHANCED PATIENT CONTROLLED ANALGESIA (EPCA) FOR THE EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY (ESWL) , 2007 .

[36]  Patrick van der Smagt,et al.  Introduction to neural networks , 1995, The Lancet.

[37]  Yeong-Ray Wen,et al.  A Novel Fuzzy Pain Demand Index Derived From Patient-Controlled Analgesia for Postoperative Pain , 2007, IEEE Transactions on Biomedical Engineering.

[38]  I Korhonen,et al.  Novel multiparameter approach for measurement of nociception at skin incision during general anaesthesia. , 2006, British journal of anaesthesia.

[39]  Andrzej Cichocki,et al.  Neural networks for optimization and signal processing , 1993 .

[40]  J. Shieh,et al.  Pain model and fuzzy logic patient-controlled analgesia in shock-wave lithotripsy , 2006, Medical and Biological Engineering and Computing.

[41]  H. Doğan,et al.  Assessing Propofol Induction of Anesthesia Dose Using Bispectral Index Analysis , 2004, Anesthesia and analgesia.

[42]  Dwayne R. Westenskow,et al.  A Model-Based Self-Adjusting Two-Phase Controller for Vecuronium-Induced Muscle Relaxation Durng Anesthesia , 1987, IEEE Transactions on Biomedical Engineering.

[43]  Thomas Standl,et al.  ARX-Derived Auditory Evoked Potential Index and Bispectral Index During the Induction of Anesthesia with Propofol and Remifentanil , 2003, Anesthesia and analgesia.

[44]  H Schwilden,et al.  Model‐based adaptive closed‐loop feedback control of atracurium‐induced neuromuscular blockade , 1991, Acta anaesthesiologica Scandinavica.

[45]  Entropy and Bispectral Index during Anaesthesia in Children , 2004, Anaesthesia and intensive care.

[46]  H. Storm,et al.  Skin conductance correlates with perioperative stress , 2002, Acta anaesthesiologica Scandinavica.

[47]  L. Kearse,et al.  Bispectral Analysis of the Electroencephalogram Predicts Conscious Processing of Information during Propofol Sedation and Hypnosis , 1998, Anesthesiology.

[48]  S. Barnason,et al.  Managing pain: the fifth vital sign. , 2000, The Nursing clinics of North America.

[49]  M. Ozaki,et al.  Entropy indices vs the bispectral index for estimating nociception during sevoflurane anaesthesia. , 2006, British journal of anaesthesia.

[50]  J. Jakobsson,et al.  The AAITM index, the BIS index and end‐tidal concentration during wash in and wash out of sevoflurane , 2003, Anaesthesia.

[51]  Steven M. Pincus,et al.  A regularity statistic for medical data analysis , 1991, Journal of Clinical Monitoring.

[52]  Carolyn L. Beck,et al.  On the use of hybrid multivariable models for predicting human response to anesthesia , 2002, Proceedings of the 41st IEEE Conference on Decision and Control, 2002..

[53]  Tatiana Witjas,et al.  Differential Dynamic of Action on Cortical and Subcortical Structures of Anesthetic Agents during Induction of Anesthesia , 2007, Anesthesiology.

[54]  K. Leslie,et al.  For Personal Use. Only Reproduce with Permission from the Lancet , 2022 .

[55]  J. Johansen,et al.  Update on bispectral index monitoring. , 2006, Best practice & research. Clinical anaesthesiology.

[56]  I. Rezek,et al.  Stochastic complexity measures for physiological signal analysis , 1998, IEEE Transactions on Biomedical Engineering.

[57]  Rainer Lenhardt,et al.  The effect of anesthesia on body temperature control. , 2010, Frontiers in bioscience.

[58]  Chung-Kang Peng,et al.  Heritability of abnormalities in cardiopulmonary coupling in sleep apnea: use of an electrocardiogram-based technique. , 2010, Sleep.

[59]  Jiann-Shing Shieh,et al.  Genetic fuzzy modelling and control of bispectral index (BIS) for general intravenous anaesthesia. , 2006, Medical engineering & physics.

[60]  N R Webster,et al.  Auditory evoked response and awareness: a study in volunteers at sub-MAC concentrations of isoflurane. , 1992, British journal of anaesthesia.

[61]  M. Devor,et al.  Reversible analgesia, atonia, and loss of consciousness on bilateral intracerebral microinjection of pentobarbital , 2001, Pain.

[62]  Peter S. Sebel,et al.  Development and Clinical Application of Electroencephalographic Bispectrum Monitoring , 2000, Anesthesiology.

[63]  A. Yli-Hankala,et al.  Description of the Entropy™ algorithm as applied in the Datex‐Ohmeda S/5™ Entropy Module , 2004, Acta anaesthesiologica Scandinavica.

[64]  B H Brown,et al.  Closed-loop control of muscle relaxation during surgery , 1980 .

[65]  D. Linkens,et al.  Self-learning fuzzy logic control of neuromuscular block. , 1997, British journal of anaesthesia.

[66]  I. Rampil A Primer for EEG Signal Processing in Anesthesia , 1998, Anesthesiology.

[67]  K. Uutela,et al.  Surgical stress index reflects surgical stress in gynaecological laparoscopic day-case surgery. , 2007, British journal of anaesthesia.

[68]  G N Kenny,et al.  Auditory Evoked Potential Index Predicts the Depth of Sedation and Movement in Response to Skin Incision during Sevoflurane Anesthesia , 2001, Anesthesiology.

[69]  J. Pérez-Cajaraville,et al.  [Neuromuscular blockade monitoring. Part 1]. , 2010, Revista espanola de anestesiologia y reanimacion.

[70]  Jin Liu,et al.  Electroencephalographic Bispectral Index Correlates with Intraoperative Recall and Depth of Propofol-Induced Sedation , 1997, Anesthesia and analgesia.

[71]  Sang Joon Kim,et al.  A Mathematical Theory of Communication , 2006 .

[72]  Mouloud Denai,et al.  Self-Tuning PID Control of Atracurium Induced Muscle Relaxation in Surgical Patients , 1990 .

[73]  Nassib G. Chamoun,et al.  An introduction to bispectral analysis for the electroencephalogram , 1994, Journal of Clinical Monitoring.

[74]  Peng Wen,et al.  Robust internal model control for depth of anaesthesia , 2011, Int. J. Mechatronics Autom..

[75]  A. Yli-Hankala,et al.  Description of the EntropyTM algorithm as applied in the Datex-Ohmeda S / 5 TM Entropy Module , 2004 .

[76]  D. Chernik,et al.  Validity and Reliability of the Observer's: Assessment of Alertness/Sedation Scale Study with Intravenous Midazolam , 1990, Journal of clinical psychopharmacology.

[77]  Maysam F. Abbod,et al.  Multivariable Fuzzy Logic/Self-organizing for Anesthesia Control , 2010 .

[78]  Derek A. Linkens,et al.  Fuzzy logic for auditory evoked response monitoring and control of depth of anaesthesia , 1998, Fuzzy Sets Syst..

[79]  Maysam F Abbod,et al.  Neuro-fuzzy modeling: an accurate and interpretable method for predicting bladder cancer progression. , 2006, The Journal of urology.

[80]  P. Gambús,et al.  Can Bispectral Index Monitoring Predict Recovery of Consciousness in Patients with Severe Brain Injury? , 2004, Anesthesiology.

[81]  S L Shafer,et al.  Electromyographic activity falsely elevates the bispectral index. , 2000, Anesthesiology.

[82]  C E Blogg,et al.  Feedback control of neuromuscular blockade , 1987, Anaesthesia.

[83]  Hani Hagras,et al.  Toward General Type-2 Fuzzy Logic Systems Based on zSlices , 2010, IEEE Transactions on Fuzzy Systems.

[84]  J. Pérez-Cajaraville,et al.  Monitorización del bloqueo neuromuscular. 1ª parte , 2010 .

[85]  Helmut Schwilden,et al.  Concepts of EEG processing: from power spectrum to bispectrum, fractals, entropies and all that. , 2006, Best practice & research. Clinical anaesthesiology.

[86]  Derek A. Linkens,et al.  Hierarchical rule-based and self-organizing fuzzy logic control for depth of anaesthesia , 1999, IEEE Trans. Syst. Man Cybern. Part C.

[87]  Jiann-Shing Shieh,et al.  Rule extraction by fuzzy modeling algorithm for fuzzy logic control of cisatracurium as a neuromuscular block , 2009, Eng. Appl. Artif. Intell..

[88]  Paul F White,et al.  A Comparison of State and Response Entropy Versus Bispectral Index Values During the Perioperative Period , 2006, Anesthesia and analgesia.

[89]  E. Eger,et al.  Pancuronium Reduces Halothane Requirement in Man , 1979, Anesthesia and analgesia.

[90]  B. Orser,et al.  Emerging molecular mechanisms of general anesthetic action. , 2005, Trends in pharmacological sciences.

[91]  T. Sakai,et al.  The effect of ketamine on clinical endpoints of hypnosis and EEG variables during propofol infusion , 1999, Acta anaesthesiologica Scandinavica.

[92]  F J Overdyk,et al.  Closed-loop infusion of atracurium with four different anesthetic techniques. , 1991, Anesthesiology.

[93]  C. Bolger,et al.  Comparison of ocular microtremor and bispectral index during sevoflurane anaesthesia. , 2002, British journal of anaesthesia.

[94]  H Terasaki,et al.  Skin Vasomotor Reflex Predicts Circulatory Responses to Laryngoscopy and Intubation , 1998, Anesthesiology.

[95]  Patrick Karasinski,et al.  Monitoring anesthesia using neural networks: A survey , 2002, Journal of Clinical Monitoring and Computing.

[96]  Giorgio Bonmassar,et al.  Simultaneous Electroencephalography and Functional Magnetic Resonance Imaging of General Anesthesia , 2009, Annals of the New York Academy of Sciences.

[97]  P. Crago,et al.  Feedback control methods for task regulation by electrical stimulation of muscles , 1991, IEEE Transactions on Biomedical Engineering.

[98]  Hugo Vereecke,et al.  Ability of the Bispectral Index, Autoregressive Modelling with Exogenous Input-derived Auditory Evoked Potentials, and Predicted Propofol Concentrations to Measure Patient Responsiveness during Anesthesia with Propofol and Remifentanil , 2003, Anesthesiology.

[99]  D. A. Linkens,et al.  Self-learning fuzzy control of atracurium-induced neuromuscular block during surgery , 1997, Medical and Biological Engineering and Computing.

[100]  Olaf Simanski,et al.  Progress of automatic drug delivery in anaesthesia—The ‘Rostock assistant system for anaesthesia control (RAN)’ , 2008 .

[101]  B. Lampe,et al.  A fuzzy system for regulation of the analgesic remifentanil during general anaesthesia , 2008, 2008 16th Mediterranean Conference on Control and Automation.

[102]  D. Linkens,et al.  Identification and control of muscle-relaxant anaesthesia , 1982 .

[103]  Friedrich Steimann,et al.  Fuzzy set theory in medicine , 1997, Artif. Intell. Medicine.

[104]  Yeong-Ray Wen,et al.  A Novel Continuous Visual Analog Scale Model Derived from Pain-relief Demand Index via Hilbert Huang Transform for Postoperative Pain , 2011 .

[105]  Bruno Guignard,et al.  Monitoring analgesia. , 2006, Best practice & research. Clinical anaesthesiology.

[106]  N. Schiff Central Thalamic Contributions to Arousal Regulation and Neurological Disorders of Consciousness , 2008, Annals of the New York Academy of Sciences.

[107]  J. Bruhn,et al.  Shannon Entropy Applied to the Measurement of the Electroencephalographic Effects of Desflurane , 2001, Anesthesiology.

[108]  S. Hert,et al.  Volatile Anesthetics and Cardiac Function , 2006 .

[109]  T. Kudo,et al.  [Effects of sevoflurane anesthesia and surgery on plasma catecholamine levels]. , 1989, Masui. The Japanese journal of anesthesiology.

[110]  E. Plunkett,et al.  Physics, Pharmacology and Physiology for Anaesthetists: Neuromuscular blockade monitoring , 2008 .

[111]  J. Shieh,et al.  Detrended fluctuation analysis of short-term heart rate variability in late pregnant women , 2009, Autonomic Neuroscience.

[112]  Paul F. White,et al.  Electroencephalogram bispectral analysis predicts the depth of midazolam-induced sedation. , 1996 .

[113]  J. Bruhn,et al.  Correlation of Approximate Entropy, Bispectral Index, and Spectral Edge Frequency 95 (SEF95) with Clinical Signs of “Anesthetic Depth” during Coadministration of Propofol and Remifentanil , 2003, Anesthesiology.

[114]  Maysam F. Abbod,et al.  Visual Analog Scale of Pain Intensity Prediction Based on Ensembled Artificial Neural Networks via i-Pain System , 2010, ICDM.

[115]  H. Schwilden,et al.  Use of a pharmacokinetic-dynamic model for the automatic feedback control of atracurium , 2004, European Journal of Clinical Pharmacology.

[116]  Hani Hagras,et al.  An Incremental Adaptive Life Long Learning Approach for Type-2 Fuzzy Embedded Agents in Ambient Intelligent Environments , 2007, IEEE Transactions on Fuzzy Systems.

[117]  Jinbao Li,et al.  Anesthesia awareness and the bispectral index. , 2008, The New England journal of medicine.

[118]  K. Miller,et al.  Mechanisms of actions of inhaled anesthetics. , 2003, The New England journal of medicine.

[119]  A. Zbinden,et al.  Anesthetic Depth Defined Using Multiple Noxious Stimuli during Isoflurane/Oxygen Anesthesia: II. Hemodynamic Responses , 1994, Anesthesiology.

[120]  S. Brull,et al.  Monitoring of neuromuscular function in the clinical setting. , 1993, The Yale journal of biology and medicine.

[121]  A. Zbinden,et al.  Anesthetic Depth Defined Using Multiple Noxious Stimuli during Isoflurane/Oxygen Anesthesia I. Motor Reactions , 1994, Anesthesiology.

[122]  D R Westenskow Fundamentals of feedback control: PID, fuzzy logic, and neural networks. , 1997, Journal of clinical anesthesia.

[123]  H. Edmonds,et al.  Effect of Ketamine on Bispectral Index and Levels of Sedation , 1998, Journal of Clinical Monitoring and Computing.

[124]  Y. P. Liu,et al.  Modeling and estimation for patient controlled analgesia of chronic pain , 1995, IEEE Trans. Biomed. Eng..

[125]  J. Klockars,et al.  Spectral Entropy as a Measure of Hypnosis in Children , 2006, Anesthesiology.

[126]  Madalena Costa,et al.  Multiscale entropy analysis of complex physiologic time series. , 2002, Physical review letters.

[127]  L. Johnson,et al.  Bispectrum Analysis of Electroencephalogram Signals during Waking and Sleeping , 1971, Science.

[128]  I F Russell,et al.  The Narcotrend 'depth of anaesthesia' monitor cannot reliably detect consciousness during general anaesthesia: an investigation using the isolated forearm technique. , 2006, British journal of anaesthesia.

[129]  José Valente de Oliveira,et al.  A survey of fuzzy control strategies for neuromuscular blockade using continuous infusion of atracurium , 2002, 2002 IEEE World Congress on Computational Intelligence. 2002 IEEE International Conference on Fuzzy Systems. FUZZ-IEEE'02. Proceedings (Cat. No.02CH37291).

[130]  D. Linkens,et al.  Neurofuzzy Modeling to Determine Recurrence Risk Following Radical Cystectomy for Nonmetastatic Urothelial Carcinoma of the Bladder , 2009, Clinical Cancer Research.

[131]  P C Uys,et al.  Self-tuning, microprocessor-based closed-loop control of atracurium-induced neuromuscular blockade. , 1988, British journal of anaesthesia.

[132]  Maysam F. Abbod,et al.  Monitoring and control of unconsciousness during clinical surgery: Auditory evoked potentials (AEP) versus the clinical gold standard (CGS) , 2008 .

[133]  R. Rodríguez-Roisín,et al.  Contribution of multiple inert gas elimination technique to pulmonary medicine , 1994 .

[134]  Rolf Unbehauen,et al.  Nonlinear Model-Based Predictive Control of Non-Depolarizing Muscle Relaxants using Neural Networks , 1999, Journal of Clinical Monitoring and Computing.

[135]  J. Pérez-Cajaraville,et al.  [Neuromuscular blockade monitoring. Part 2]. , 2010, Revista espanola de anestesiologia y reanimacion.

[136]  U. Hofmann,et al.  Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK-PD modelling analysis. , 2001, British journal of clinical pharmacology.

[137]  A. C. Morales Martín,et al.  Extremely prolonged neuromuscular blockade after rocuronium: a case report , 2009, Acta anaesthesiologica Scandinavica.

[138]  E. Brown,et al.  General anesthesia, sleep, and coma. , 2010, The New England journal of medicine.

[139]  Arvi Yli-Hankala,et al.  Spectral Entropy Monitoring Is Associated with Reduced Propofol Use and Faster Emergence in Propofol–Nitrous Oxide–Alfentanil Anesthesia , 2005, Anesthesiology.

[140]  M. Struys,et al.  Changes in a surgical stress index in response to standardized pain stimuli during propofol-remifentanil infusion. , 2007, British journal of anaesthesia.

[141]  Jiann-Shing Shieh,et al.  The Intelligent Model of a Patient Using Artificial Neural Networks for Inhalational Anaesthesia , 2002 .

[142]  O. Chi,et al.  Power spectral analysis of EEG during sufentanil infusion in humans , 1991, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[143]  N. P. Franks,et al.  Inhibitory synapses: Anaesthetics set their sites on ion channels , 1997, Nature.

[144]  N. T. Smith,et al.  Performance of the ARX-derived Auditory Evoked Potential Index as an Indicator of Anesthetic Depth: A Comparison with Bispectral Index and Hemodynamic Measures during Propofol Administration , 2002, Anesthesiology.

[145]  C. Lennmarken,et al.  Reduction in the incidence of awareness using BIS monitoring , 2004, Acta anaesthesiologica Scandinavica.

[146]  J. Shieh,et al.  Parameter Investigation of Detrended Fluctuation Analysis for Short-term Human Heart Rate Variability , 2010 .

[147]  Günther Rau,et al.  Design and validation of an intelligent patient monitoring and alarm system based on a fuzzy logic process model , 1997, Artif. Intell. Medicine.

[148]  S. Crofts,et al.  Clinical monitoring of neuromuscular function. , 1992, British journal of hospital medicine.

[149]  Maysam F. Abbod,et al.  Monitoring and Control of Anesthesia Using Multivariable Self-Organizing Fuzzy Logic Structure , 2009, Fuzzy Systems in Bioinformatics and Computational Biology.

[150]  A. Yli-Hankala,et al.  EEG spectral entropy, heart rate, photoplethysmography and motor responses to skin incision during sevoflurane anaesthesia , 2005, Acta anaesthesiologica Scandinavica.

[151]  P. Glass,et al.  Changes in the Auditory Evoked Potentials and the Bispectral Index following Propofol or Propofol and Alfentanil , 2000, Anesthesiology.

[152]  G N Kenny,et al.  Auditory evoked potential index: a quantitative measure of changes in auditory evoked potentials during general anaesthesia , 1997, Anaesthesia.

[153]  B. Palanca,et al.  Mechanisms of anesthesia and consciousness , 2013 .

[154]  S. Henneberg,et al.  On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats. , 1999, Medical engineering & physics.

[155]  D. A. Linkens,et al.  Self-organising fuzzy logic control and application to muscle relaxant anaesthesia , 1990 .

[156]  Jose Alvarez-Ramirez,et al.  Detrended fluctuation analysis of heart intrabeat dynamics , 2007 .

[157]  R. Thomas,et al.  ECG-derived cardiopulmonary analysis of pediatric sleep-disordered breathing. , 2011, Sleep medicine.

[158]  Derek A. Linkens,et al.  Modelling and multivariable control in anaesthesia using neural-fuzzy paradigms: Part I. Classification of depth of anaesthesia and development of a patient model , 2005, Artif. Intell. Medicine.

[159]  Derek A. Linkens,et al.  Intelligent signal processing of evoked potentials for anaesthesia monitoring and control , 1997 .

[160]  K. Leslie,et al.  Monitoring the Depth of Anesthesia , 2010 .

[161]  G. Tononi,et al.  Consciousness and Anesthesia , 2008, Science.

[162]  C. Ménigaux,et al.  Nitrous Oxide Prevents Movement During Orotracheal Intubation Without Affecting BIS Value , 2000, Anesthesia and analgesia.

[163]  Peter Kienbaum,et al.  Sympathetic Nervous System: Evaluation and Importance for Clinical General Anesthesia , 2008, Anesthesiology.

[164]  D.A. Linkens,et al.  Automated delivery of muscle relaxants using fuzzy logic control , 1994, IEEE Engineering in Medicine and Biology Magazine.

[165]  G Dumermuth,et al.  Analysis of the interrelations between frequency bands of the EEG by means of the bispectrum. A preliminary study. , 1971, Electroencephalography and clinical neurophysiology.

[166]  Babita Pandey,et al.  Knowledge and intelligent computing system in medicine , 2009, Comput. Biol. Medicine.

[167]  D. Bogen,et al.  The Use of Computers for Controlling the Delivery of Anesthesia , 1992, Anesthesiology.

[168]  Peter S. Sebel,et al.  Bispectral Index Monitoring Allows Faster Emergence and Improved Recovery from Propofol, Alfentanil, and Nitrous Oxide Anesthesia , 1997 .

[169]  B. Shapiro Bispectral Index: better information for sedation in the intensive care unit? , 1999, Critical care medicine.

[170]  Robert Allen,et al.  Neuro-fuzzy closed-loop control of depth of anaesthesia , 2001, Artif. Intell. Medicine.

[171]  Shigehito Sato,et al.  Influence of Age on Hypnotic Requirement, Bispectral Index, and 95% Spectral Edge Frequency Associated with Sedation Induced by Sevoflurane , 2000, Anesthesiology.

[172]  J. Y. Kao,et al.  Cerebral Metabolism during Propofol Anesthesia in Humans Studied with Positron Emission Tomography , 1995, Anesthesiology.

[173]  W. N. Ngan Kee,et al.  Postoperative epidural opioid analgesia: what are the choices? , 1997, Anesthesia and analgesia.

[174]  Le Yi Wang,et al.  Decision-Oriented Multi-Outcome Modeling for Anesthesia Patients , 2010, The open biomedical engineering journal.

[175]  Tzu-Chien Hsiao,et al.  USING NEUROFUZZY NETWORKS TO MIMIC ANESTHESIOLOGIST KNOWLEDGE IN DECISION MAKING ON PROPOFOL ADMINISTRATION , 2010 .

[176]  R. Melzack,et al.  Pain – an overview , 1999, Lancet.

[177]  T. Kazama,et al.  Reduction by Fentanyl of the Cp50 Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli , 1997, Anesthesiology.

[178]  K. Ikeda,et al.  Electroencephalographic Derivatives as a Tool for Predicting the Depth of Sedation and Anesthesia Induced by Sevoflurane , 1998, Anesthesiology.

[179]  P. Coriat,et al.  Detection of brain death onset using the bispectral index in severely comatose patients , 2002, Intensive Care Medicine.

[180]  Derek A. Linkens,et al.  Hierarchical fuzzy modelling for monitoring depth of anaesthesia , 1996, Fuzzy Sets Syst..

[181]  P Fiset,et al.  Auditory Steady-State Response and Bispectral Index for Assessing Level of Consciousness During Propofol Sedation and Hypnosis , 2000, Anesthesia and analgesia.