Clinical Electroencephalography for Anesthesiologists: Part I Background and Basic Signatures

The widely used electroencephalogram-based indices for depth-of-anesthesia monitoring assume that the same index value defines the same level of unconsciousness for all anesthetics. In contrast, we show that different anesthetics act at different molecular targets and neural circuits to produce distinct brain states that are readily visible in the electroencephalogram. We present a two-part review to educate anesthesiologists on use of the unprocessed electroencephalogram and its spectrogram to track the brain states of patients receiving anesthesia care. Here in part I, we review the biophysics of the electroencephalogram and the neurophysiology of the electroencephalogram signatures of three intravenous anesthetics: propofol, dexmedetomidine, and ketamine, and four inhaled anesthetics: sevoflurane, isoflurane, desflurane, and nitrous oxide. Later in part II, we discuss patient management using these electroencephalogram signatures. Use of these electroencephalogram signatures suggests a neurophysiologically based paradigm for brain state monitoring of patients receiving anesthesia care.

[1]  E. Andrews The Oxygen Mixture, a New Anæsthetic Combination , 1869, The American journal of dental science.

[2]  F. Gibbs,et al.  EFFECT ON THE ELECTRO-ENCEPHALOGRAM OF CERTAIN DRUGS WHICH INFLUENCE NERVOUS ACTIVITY , 1937 .

[3]  Electroencephalographic Changes after Eye Opening and Visual Stimulation * , 1946, The Yale journal of biology and medicine.

[4]  R. Bickford,et al.  THE INFLUENCE OF PARTIAL PRESSURE OF NITROUS OXIDE ON THE DEPTH OF ANESTHESIA AND THE ELECTRO‐ENCEPHALOGRAM IN MAN , 1949, Anesthesiology.

[5]  R. Bickford,et al.  Electro-encephalographic patterns produced by thiopental sodium during surgical operations; description and classification. , 1951, British journal of anaesthesia.

[6]  A FAULCONER,et al.  CORRELATION OF CONCENTRATIONS OF ETHER IN ARTERIAL BLOOD WITH ELECTRO–ENCEPHALOGRAPHIC PATTERNS OCCURRING DURING ETHER–OXYGEN AND DURING NITROUS OXIDE, OXYGEN AND ETHER ANESTHESIA OF HUMAN SURGICAL PATIENTS , 1952, Anesthesiology.

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

[8]  J. T. Martin,et al.  ELECTROENCEPHALOGRAPHY IN ANESTHESIOLOGY , 1959, Anesthesiology.

[9]  K. Huse,et al.  Power Spectral Density of the Electroencephalogram During Halothane and Cyclopropane Anesthesia in Man , 1969, Anesthesia and analgesia.

[10]  E. Kandel Nerve cells and behavior. , 1970, Scientific American.

[11]  A. J. Bart,et al.  Changes in Power Spectra of Electroencephalograms During Anesthesia With Fluroxene, Methoxyflurane and Ethrane , 1971, Anesthesia and analgesia.

[12]  R. Bickford,et al.  Compression of EEG data. , 1971, Transactions of the American Neurological Association.

[13]  J. Dundee,et al.  Ketamine , 1971, Reactions Weekly.

[14]  R G Bickford,et al.  The use of on-line telephonic computer analysis of the E.E.G. in anaesthesia. , 1973, British journal of anaesthesia.

[15]  F W Sharbrough,et al.  Anterior shift of the dominant EEG rhytham during anesthesia in the Java monkey: correlation with anesthetic potency. , 1977, Anesthesiology.

[16]  N. T. Smith,et al.  An inexpensive device for analyzing and monitoring the electroencephalogram. , 1979, Anesthesiology.

[17]  H. Shapiro,et al.  Automated EEG processing for intraoperative monitoring: a comparison of techniques. , 1980, Anesthesiology.

[18]  T. Yamamura,et al.  Fast Oscillatory EEG Activity Induced by Analgesic Concentrations of Nitrous Oxide in Man , 1981, Anesthesia and analgesia.

[19]  S. Dimolitsas The compression of eeg data , 1982 .

[20]  N. P. Franks,et al.  Do general anaesthetics act by competitive binding to specific receptors? , 1984, Nature.

[21]  W. Levy Intraoperative EEG Patterns: Implications for EEG Monitoring , 1984, Anesthesiology.

[22]  H Schwilden,et al.  Closed‐loop Feedback Control of Methohexital Anesthesia by Quantitative EEG Analysis in Humans , 1987, Anesthesiology.

[23]  E. Oka,et al.  The early-infantile epileptic encephalopathy with suppression-burst: Developmental aspects , 1987, Brain and Development.

[24]  C. Porro,et al.  Ketamine Effects on Local Cerebral Blood Flow and Metabolism in the Rat , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  Ira J. Rampil,et al.  1653 and Isoflurane Produce Similar Dose‐related Changes in the Electroencephalogram of Pigs , 1988, Anesthesiology.

[26]  K. Shingu,et al.  Progressive Changes in Electroencephalographic Responses to Nitrous Oxide in Humans: A Possible Acute Drug Tolerance , 1990, Anesthesia and analgesia.

[27]  J. Drummond,et al.  A comparison of median frequency, spectral edge frequency, a frequency band power ratio, total power, and dominance shift in the determination of depth of anesthesia , 1991, Acta anaesthesiologica Scandinavica.

[28]  R. Weiskopf,et al.  The electroencephalographic effects of desflurane in humans. , 1991, Anesthesiology.

[29]  Thomas P. Bronez,et al.  On the performance advantage of multitaper spectral analysis , 1992, IEEE Trans. Signal Process..

[30]  J. Antognini,et al.  Exaggerated Anesthetic Requirements in the Preferentially Anesthetized Brain , 1993, Anesthesiology.

[31]  R. Ilmoniemi,et al.  Magnetoencephalography-theory, instrumentation, and applications to noninvasive studies of the working human brain , 1993 .

[32]  J. Stamford,et al.  Actions of the hypnotic anaesthetic, dexmedetomidine, on noradrenaline release and cell firing in rat locus coeruleus slices. , 1993, British journal of anaesthesia.

[33]  L. Kearse,et al.  Bispectral Analysis of the Electroencephalogram Correlates with Patient Movement to Skin Incision during Propofol/Nitrous Oxide Anesthesia , 1994, Anesthesiology.

[34]  M. Maze,et al.  Perturbation of Ion Channel Conductance Alters the Hypnotic Response to the α2-Adrenergic Agonist Dexmedetomidine in the Locus Coeruleus of the Rat , 1994, Anesthesiology.

[35]  S. Strebel,et al.  Effects of ketamine on cerebral blood flow velocity in humans Influence of pretreatment with midazolam or esmolol , 1995, Anaesthesia.

[36]  J. Olney,et al.  Glutamate receptor dysfunction and schizophrenia. , 1995, Archives of general psychiatry.

[37]  K. L. Leenders,et al.  Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET) , 1997, European Neuropsychopharmacology.

[38]  M Danhof,et al.  Pharmacokinetic-pharmacodynamic characterization of the cardiovascular, hypnotic, EEG and ventilatory responses to dexmedetomidine in the rat. , 1997, The Journal of pharmacology and experimental therapeutics.

[39]  P Manberg,et al.  Bispectral Analysis Measures Sedation and Memory Effects of Propofol, Midazolam, Isoflurane, and Alfentanil in Healthy Volunteers , 1997, Anesthesiology.

[40]  Bita Moghaddam,et al.  Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex , 1997, The Journal of Neuroscience.

[41]  D. Contreras,et al.  Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells. , 1998, Journal of neurophysiology.

[42]  C. Saper,et al.  Innervation of Histaminergic Tuberomammillary Neurons by GABAergic and Galaninergic Neurons in the Ventrolateral Preoptic Nucleus of the Rat , 1998, The Journal of Neuroscience.

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

[44]  J. Olney,et al.  Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin , 1998, Nature Medicine.

[45]  T. Sloan,et al.  Anesthetic effects on electrophysiologic recordings. , 1998, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[46]  B. Matta,et al.  Burst suppression or isoelectric encephalogram for cerebral protection: evidence from metabolic suppression studies. , 1999, British journal of anaesthesia.

[47]  B. Orser,et al.  The General Anesthetic Propofol Slows Deactivation and Desensitization of GABAA Receptors , 1999, The Journal of Neuroscience.

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

[49]  E R John,et al.  Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane. , 2001, British journal of anaesthesia.

[50]  E. John,et al.  Invariant Reversible QEEG Effects of Anesthetics , 2001, Consciousness and Cognition.

[51]  J. Bavaria,et al.  Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials. , 2001, The Annals of thoracic surgery.

[52]  T. Guo,et al.  The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway , 2002, Nature Neuroscience.

[53]  S. Ohtahara,et al.  Early-infantile epileptic encephalopathy with suppression-bursts, Ohtahara syndrome; its overview referring to our 16 cases , 2002, Brain and Development.

[54]  U. Grouven,et al.  [The Narcotrend monitor. Development and interpretation algorithms]. , 2003, Der Anaesthesist.

[55]  E. Kochs,et al.  Detection of awareness in surgical patients with EEG-based indices--bispectral index and patient state index. , 2003, British journal of anaesthesia.

[56]  I. Rampil Consciousness, awareness, and the clinician , 2003 .

[57]  Jun Lu,et al.  The &agr;2-Adrenoceptor Agonist Dexmedetomidine Converges on an Endogenous Sleep-promoting Pathway to Exert Its Sedative Effects , 2003, Anesthesiology.

[58]  A. Schultz,et al.  Der Narcotrend®-Monitor , 2003, Der Anaesthesist.

[59]  Thomas W. Bouillon,et al.  Bispectral Index (BIS) and Burst Suppression: Revealing a Part of the BIS Algorithm , 2004, Journal of Clinical Monitoring and Computing.

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

[61]  V. Jäntti,et al.  Spectral entropy--what has it to do with anaesthesia, and the EEG? , 2004, British journal of anaesthesia.

[62]  Michael D Sharpe,et al.  Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. , 2004, Archives of neurology.

[63]  E R John,et al.  The Patient State Index as an indicator of the level of hypnosis under general anaesthesia. , 2004, British journal of anaesthesia.

[64]  Stephen R. Morairty,et al.  Disinhibition of ventrolateral preoptic area sleep-active neurons by adenosine: a new mechanism for sleep promotion , 2004, Neuroscience.

[65]  Julien Bogousslavsky,et al.  Propofol Treatment of Refractory Status Epilepticus: A Study of 31 Episodes , 2004, Epilepsia.

[66]  V. Feshchenko,et al.  Propofol-Induced Alpha Rhythm , 2004, Neuropsychobiology.

[67]  C. Saper,et al.  Hypothalamic regulation of sleep and circadian rhythms , 2005, Nature.

[68]  S. Hughes,et al.  Thalamic Mechanisms of EEG Alpha Rhythms and Their Pathological Implications , 2005, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[69]  Anthony G. Hudetz,et al.  Volatile anesthetics disrupt frontal-posterior recurrent information transfer at gamma frequencies in rat , 2005, Neuroscience Letters.

[70]  J. Feiner,et al.  Progressive Suppression of Motor Evoked Potentials During General Anesthesia: The Phenomenon of "Anesthetic Fade" , 2005, Journal of neurosurgical anesthesiology.

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

[72]  Synchronization by Oscillation , 2006 .

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

[74]  R. Chabot,et al.  Patient state index. , 2002, Best practice & research. Clinical anaesthesiology.

[75]  S. Kreuer,et al.  The Narcotrend monitor. , 2006, Best practice & research. Clinical anaesthesiology.

[76]  Peter W Kaplan,et al.  Clinical neurophysiologic monitoring and brain injury from cardiac arrest. , 2006, Neurologic clinics.

[77]  C. Berridge,et al.  Organization of noradrenergic efferents to arousal‐related basal forebrain structures , 2006, The Journal of comparative neurology.

[78]  A. Samarkandi The bispectral index system in pediatrics--is it related to the end-tidal concentration of inhalation anesthetics? , 2006, Middle East journal of anaesthesiology.

[79]  Florin Amzica,et al.  Hypersensitivity of the Anesthesia-Induced Comatose Brain , 2007, The Journal of Neuroscience.

[80]  J. Barnard,et al.  Can anaesthetists be taught to interpret the effects of general anaesthesia on the electroencephalogram? Comparison of performance with the BIS and spectral entropy. , 2007, British journal of anaesthesia.

[81]  Robert W McCarley,et al.  Neurobiology of REM and NREM sleep. , 2007, Sleep medicine.

[82]  Partha P. Mitra,et al.  Observed Brain Dynamics , 2007 .

[83]  T Sawa,et al.  Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol. , 2007, British journal of anaesthesia.

[84]  J. Sleigh,et al.  Monitoring consciousness: the current status of EEG-based depth of anaesthesia monitors. , 2007, Best practice & research. Clinical anaesthesiology.

[85]  S. Hagihira,et al.  Ketamine, an NMDA‐antagonist, increases the oscillatory frequencies of α‐peaks on the electroencephalographic power spectrum , 2007, Acta anaesthesiologica Scandinavica.

[86]  L. Senhadji,et al.  Variation of bispectral index under TIVA with propofol in a paediatric population. , 2008, British journal of anaesthesia.

[87]  J. Sigl,et al.  Anesthesia awareness and the bispectral index. , 2008, The New England journal of medicine.

[88]  M. Scheinin,et al.  Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep , 2008, Acta anaesthesiologica Scandinavica.

[89]  Emery N Brown,et al.  Potential Network Mechanisms Mediating Electroencephalographic Beta Rhythm Changes during Propofol-Induced Paradoxical Excitation , 2008, The Journal of Neuroscience.

[90]  J. Seamans,et al.  Losing inhibition with ketamine. , 2008, Nature chemical biology.

[91]  George A Mashour,et al.  Processed electroencephalogram in depth of anesthesia monitoring , 2009, Current opinion in anaesthesiology.

[92]  Florin Amzica,et al.  Basic physiology of burst‐suppression , 2009, Epilepsia.

[93]  J. Sleigh,et al.  Practical Use of the Raw Electroencephalogram Waveform During General Anesthesia: The Art and Science , 2009, Anesthesia and analgesia.

[94]  E. Brown,et al.  Thalamocortical model for a propofol-induced α-rhythm associated with loss of consciousness , 2010, Proceedings of the National Academy of Sciences.

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

[96]  Maxim Volgushev,et al.  Properties of Slow Oscillation during Slow-Wave Sleep and Anesthesia in Cats , 2011, The Journal of Neuroscience.

[97]  Emery N. Brown,et al.  Tracking brain states under general anesthesia by using global coherence analysis , 2011, Proceedings of the National Academy of Sciences.

[98]  Brett L Foster,et al.  Nitrous Oxide Paradoxically Modulates Slow Electroencephalogram Oscillations: Implications for Anesthesia Monitoring , 2011, Anesthesia and analgesia.

[99]  E. Samain,et al.  Occurrence of and risk factors for electroencephalogram burst suppression during propofol-remifentanil anaesthesia. , 2011, British journal of anaesthesia.

[100]  A. Engel,et al.  Cortical Hypersynchrony Predicts Breakdown of Sensory Processing during Loss of Consciousness , 2011, Current Biology.

[101]  G. Mashour,et al.  Prevention of intraoperative awareness in a high-risk surgical population. , 2011, The New England journal of medicine.

[102]  A. Macario,et al.  Titration of sevoflurane in elderly patients: blinded, randomized clinical trial, in non-cardiac surgery after beta-adrenergic blockade , 2011, Journal of Clinical Monitoring and Computing.

[103]  E. Brown,et al.  General anesthesia and altered states of arousal: a systems neuroscience analysis. , 2011, Annual review of neuroscience.

[104]  I. Fried,et al.  Regional Slow Waves and Spindles in Human Sleep , 2011, Neuron.

[105]  Emery N Brown,et al.  A neurophysiological–metabolic model for burst suppression , 2012, Proceedings of the National Academy of Sciences.

[106]  M. Takashina,et al.  The Impact of Nitrous Oxide on Electroencephalographic Bicoherence During Isoflurane Anesthesia , 2012, Anesthesia and analgesia.

[107]  Laura D. Lewis,et al.  Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness , 2012, Proceedings of the National Academy of Sciences.

[108]  G. B. Young,et al.  Status Epilepticus: A Review, With Emphasis on Refractory Cases , 2012, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[109]  M. Kertai,et al.  Brain Monitoring with Electroencephalography and the Electroencephalogram-Derived Bispectral Index During Cardiac Surgery , 2012, Anesthesia and analgesia.

[110]  C. Koch,et al.  The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes , 2012, Nature Reviews Neuroscience.

[111]  Emery N. Brown,et al.  Local cortical dynamics of burst suppression in the anaesthetized brain , 2013, Brain : a journal of neurology.

[112]  Emery N. Brown,et al.  A Brain-Machine Interface for Control of Medically-Induced Coma , 2013, PLoS Comput. Biol..

[113]  UnCheol Lee,et al.  Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane , 2013, Anesthesiology.

[114]  Emery N. Brown,et al.  Electroencephalogram signatures of loss and recovery of consciousness from propofol , 2013, Proceedings of the National Academy of Sciences.

[115]  Bernhard Hemmer,et al.  Simultaneous Electroencephalographic and Functional Magnetic Resonance Imaging Indicate Impaired Cortical Top–Down Processing in Association with Anesthetic-induced Unconsciousness , 2013, Anesthesiology.

[116]  Duan Li,et al.  Effects of Volatile Anesthetic Agents on Cerebral Cortical Synchronization in Sheep , 2013, Anesthesiology.

[117]  D. Liley,et al.  Effects of nitrous oxide sedation on resting electroencephalogram topography , 2013, Clinical Neurophysiology.

[118]  Mary M. Conte,et al.  Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury , 2013, eLife.

[119]  Emery N. Brown,et al.  A brain-machine interface for control of burst suppression in medical coma , 2013, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[120]  ShiNung Ching,et al.  Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression , 2013, Journal of neural engineering.

[121]  Emery N. Brown,et al.  A Review of Multitaper Spectral Analysis , 2014, IEEE Transactions on Biomedical Engineering.

[122]  Ciprian Catana,et al.  Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness , 2014, eLife.

[123]  E. Brown,et al.  Effects of Sevoflurane and Propofol on Frontal Electroencephalogram Power and Coherence , 2014, Anesthesiology.

[124]  Gabriel Obregon-Henao,et al.  Tracking the Sleep Onset Process: An Empirical Model of Behavioral and Physiological Dynamics , 2014, PLoS Comput. Biol..

[125]  S. Cash,et al.  Dietary protein and stroke prevention , 2014, Neurology.

[126]  Marcus T. Wilson,et al.  EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory , 2014, Front. Syst. Neurosci..

[127]  K. M. Ropella,et al.  Graded defragmentation of cortical neuronal firing during recovery of consciousness in rats , 2014, Neuroscience.

[128]  Michael J. Prerau,et al.  A Comparison of Propofol- and Dexmedetomidine-induced Electroencephalogram Dynamics Using Spectral and Coherence Analysis , 2014, Anesthesiology.

[129]  E. Brown,et al.  Nitrous oxide-induced slow and delta oscillations , 2015, Clinical Neurophysiology.

[130]  K. Misulis,et al.  Atlas of EEG & seizure semiology , 2016 .