Profondità anestesia finale sia 2012 (2)


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Profondità anestesia finale sia 2012 (2)

  1. 1. Monitoring depth of anesthesia(DOA) Il monitoraggio della profondità anestetica Claudio Melloni Libero professionista Consulente : Poliambulatorio S.Lucia ,Bologna, Day surgery Gynepro,Bologna Sia Napoli 2012
  2. 2. Sia Napoli 2012
  3. 3. GOING under…………. • Health News. 2004 Feb;10(2):4-5. • Anesthesia: what you should know. People often fret about "going under", but recent improvements in anesthesia methods and materials should calm their concerns. • • Brull SJ. University of Florida in Gainesville, USA • • • • Anaesthesia. 1994 Jul;49(7):645-6. Patients' desire for information about anaesthesia: Australian attitudes. Hutchison GL, Lonsdale M. Comment on:Patients' desire for information about anaesthesia: Australian attitudes. [Anaesthesia. 1994 • FDA Consum. 1989 Dec-1990 Jan;23(10):13-7. • Modern anesthesia. Going under safely. • Modeland V Sia Napoli 2012
  4. 4. it Before You Go Under: A Step by Step Guide to Ease Your Mind Before Going Under Anesthesia Benjamin Taimoorazy 08/feb/2008 - 199 pagg. To alleviate the worries and to provide the general public all the necessary information related to the anesthetic experience, Benjamin Taimoorazy, M.D has written Before You Go Under. The inspiration for this book came from hundreds of questions Taimoorazy received from patients over his 14 year career as a Board Certified Anesthesiologist. In a clear and direct manner, Taimoorazy guides the reader through the step-by-step process of anesthesia, alleviating fears and addressing myths while also providing information unknown to most patients. » Sia Napoli 2012
  5. 5. Chirurgia paziente Paziente chirurgia Sia Napoli 2012
  6. 6. Not always the sea is calm like this one…… Sia Napoli 2012
  7. 7. Sia Napoli 2012
  8. 8. Navigating in a rough sea…. Sia Napoli 2012
  9. 9. Emergence….. Sia Napoli 2012
  10. 10. Sia Napoli 2012
  11. 11. Sia Napoli 2012
  12. 12. Monitoring ………. Sia Napoli 2012
  13. 13. depthmeter ………. Sia Napoli 2012
  14. 14. On October 16, 1846, in the amphitheater of the hospital’s main building (designed by Charles Bulfinch, and still standing), Dr. Warren operated on Gilbert Abbott for removal of a tumor on the jaw while Dr. Morton administered the ether with a device he had designed. Afterward Abbott declared, “I have felt no pain,” and Dr. Warren endorsed the procedure with the remark, “Gentlemen, this is no humbug.” Within a year of that successful operation, ether was being used worldwide to relieve the pain of surgery. The Massachusetts General amphitheater quickly became known as “the Ether Dome.” Sia Napoli 2012
  15. 15. Definitions of anaesthesia Definitions of anaesthesia lREES e GRAY 1950 lWoodbrige lGray 1957 1960 D rruginduceduncosciousne he patient doesnot per ceivenor recall noxiousstim ulation d ciousness:t he at ient oes not per ceie nor recall no ss:t v xious stim ulation D g induce uncos u p d Prys-R oberts C .. A naesthesi a: a practi cal or iim practi cal construct? [edi tori al ]. B rr J Anaesth 1987; 59: 1341-5. Prys-R oberts C A naesthesi a: a practi cal or m practi cal construct? [edi tori al ]. B J Anaesth 1987; 59: 1341-5. P aralysis uncosciou sness &at en ion f he str ess sponse uat P aralysis ncosciousness&at ttenuation oftthe str ess rresponse u o e Pi nsker MC .. Anesthesi a: a pragmati c construct. A nesth A nal g 1986; 65: 819-20. Pi nsker MC Anesthesi a: a pragmati c construct. A nesth A nal g 1986; 65: 819-20. S ensory block,motor block,blockofrreflexes,mental block sor ck,m otor block ,block f eflexe s,m ental block S en y blo o W oodbrige W oodbrige A ll separate effect susefultto pr otect tthepat ient fr om the st rressof surger y A ll epar ate effect suseful o pr otect hepat ient fr om the st ss of surger y s e K iissi n I, G elm an S. C om ponents of anaesthesi a. B rr J A naesth 1988; 61: 237-42. K ssi n I, G elm an S. C om ponents of anaesthesi a. B J A naesth 1988; 61: 237-42. R eversibleoblivionand im mobilit y er R ev sibleoblivionand im mobilit y Eger EI II. W hat iis general anestheti c acti on? [edi torial ]. Anesth A nal g 1993; 77: 408. Eger EI II. W hat s general anestheti c acti on? [edi torial ]. Anesth A nal g 1993; 77: 408. Sia Napoli 2012
  16. 16. Modern balanced anesthesia Modern balanced anesthesia Do they fir together? Hypnosis Hypnosis Amnesia Amnesia Analgesia Analgesia Stress protection Stress protection Reflexes protection Reflexes protection Absence of movement Absence of movement Sia Napoli 2012 Muscle relaxation Muscle relaxation
  17. 17. Anesthetic depth • probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of nonresponsiveness at defined effect site concentrations. • Shafer SL, Stanski DR. Handb Exp Pharmacol. 2008;(182):409-23. Defining depth of anesthesia Sia Napoli 2012
  18. 18. Shafer & Stanski • This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. The "clinical art" of anesthesia requires calibration of these observations of stimuli and responses (verbal responses, movement, tachycardia) against the dose and concentration of anesthetic drugs used to reduce the probability of response, constantly adjusting the administered dose to achieve the desired anesthetic depth. In our definition of "depth of anesthesia" we define the need for two components to create the anesthetic state: hypnosis created with drugs such as propofol or the inhalational anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness. Sia Napoli 2012
  19. 19. Depth vs adequacy • Unresponsiveness to noxious stimuli. • Unresponsiveness to non noxious stimuli . Sia Napoli 2012
  20. 20. Muscle relaxation is not paralysis Muscle relaxation • Unresponsiveness without nmb • Usually a measure of hypnosis paralysis • No measure of hypnosis • No measure of anaesthetic adequacy • Measure of anesthetic adequacy Sia Napoli 2012
  21. 21. essential features of a successful GA • • • • • reversible loss of consciousness lack of movement lack of awareness unresponsiveness to painful stimuli lack of recall of the surgical intervention • Fast recovery????pain free recovery????minimal haemodynamic changes…… Sia Napoli 2012
  22. 22. Navigating anesthesia • How much drug • Which is the concentration at the level of the effector site • Measuring effects Sia Napoli 2012
  23. 23. Relationships between drugs and effects: nonlinear,complex… ipnotici ipnosi Incoscienza amnesia analgesici miorilassanti analgesia Stabilità Sia Napoli 2012 antinocicezione autonomica Rilasciame nto muscolare immobilità
  25. 25. The level of stimulation is continuously changing! 8 6 4 2 0
  26. 26. Grading of stimulation
  27. 27. assessments in anesthesia assessments in anesthesia response to stimulation Presurgical Presurgical LOC LOC MAC awake MAC awake surgical surgical no movement no movement eye opening eye opening MAC MAC obeying to simple commands obeying to simple commands no cardiovascular changes no cardiovascular changes loss of response to voice loss of response to voice loss of eyelash reflex loss of eyelash reflex decrease in motor tone decrease in motor tone postsurgical postsurgical MAC Bar MAC Bar date of birth date of birth respiration respiration no respiration changes no respiration changes spont movements.. spont movements.. walking walking dressing dressing Sia Napoli 2012 plasma/effect site concentrations plasma/effect site concentrations
  28. 28. MAC MAC Mac Mac awake50-95 awake50-95 MAC MAC MAC bar50-95 MAC bar50-95 Anesthetic Anesthetic alveolar alveolar Minimum alveolar Minimum alveolar concentration of concentration of Minimum alveolar Minimum alveolar concentration of concentration of concentration concentration preventing preventing anesthetic anesthetic preventing movement preventing movement anesthetic preventing anesthetic preventing stress response to stress response to awareness in 50% awareness in 50% or 95% of or 95% of in response to in response to incision in 50-95% of incision in 50-95% of surgical stimulation in surgical stimulation in 50-95% of patients 50-95% of patients subjects…(Stoelting subjects…(Stoelting 1970); 1970); subjects.. subjects.. Sia Napoli 2012
  29. 29. MAC Tables MAC Tables Mac aw ake MAC in O2 MAC in N2O 60% MAC bar halothane 0.41 0.7 0.3 1.3Mac isoflurane 0.38 1.14 0.50 1.3 Mac sevoflurane 0.62 2 0.60 1.5 Mac desflurane 2.42 6 2.83 1.5 Mac Sia Napoli 2012
  30. 30. MAC requires equilibration between alveolar concentration and blood and effect site! 1.5 1.0 0.5 Sia Napoli 2012 fraction of MAC
  31. 31. I.V.drugs for anaesthesia EFFECT Concentration effect curve for a single drug Slope  therapeutic margin EC50  ED50 CONCENTRATION
  32. 32. I.V.drugs for anaesthesia Ce95 Probability of no- response Concentration effect curve for a single drug
  33. 33. Andrews, D T, Leslie K; Sessler DI, Bjorksten AR. The Arterial Blood Propofol Concentration Preventing Movement in 50% of Healthy Women After Skin Incision .Anesth Analg 1997; 85:414–9.
  34. 34. Alfentanil di Ausems Sia Napoli 2012
  35. 35. Sevoflurane Mac awake reduction by fentanyl Katoh T,Iked K. The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision ANESTHESIOLOGY 1998; 88:5—6. Sia Napoli 2012
  36. 36. Wong CM, Critchley LA, Lee A,Khaw KS,. Ngan Kee WD Fentanyl dose– response curves when inserting the LMA ClassicTM laryngeal mask airway.Anesthesia 2007;62:654-660 Sia Napoli 2012
  37. 37. Three dimensional planes in the graphs from Vuyk et al. time Opioid blood concentration Propofol blood conc
  38. 38. Mertens MJ, Olofsen E, Burm AG, Bovill JG. Propofol anesthesia and rational opioid selection: determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology. 1997 ;87:1549-62.
  39. 39. Strategic choices between opioid / hypnotic interactions
  40. 40. CSHT and decrement time
  41. 41. Optimal concentrations(intraabd surgery) for a rapid recovery
  42. 42. Practical pharmacokinetics as applied to our daily anesthesia practice . Fiset P.Can J Anesth 1999 / 46 / R122-R126
  43. 43. Controlling the calculated plasma/effect site concentration Pharmacology Propofol remifentanil Pharmacokinetics( Pk) Plasma/effect site concentration Patient’s response Pharmacodynamics (PD)
  44. 44. Using the available technology
  45. 45. Ist conclusion from quantitative anesthesia • Hypnotic/opioid interactions deeply modify the EC needed to suppress the different stimuli arising from anesthesia and surgery • Other factors influence drug requirements • To take them into account we shall monitor!!!
  46. 46. In conclusion : • We can measure or predict drug concentration not drug effect
  47. 47. MONITORING EEG,BAEP….. hypnosis etO2 etCO2 SaO2 ECG HR HRV BP Physiology Delta down Temp centr & periph RQ EE Sia Napoli 2012 Oxygenation Ccarbon diox Fluids Blood Electrolytes Energy temperature responses Side effects Hypoventilation Bradycardia hypotension arrhythmias PRST…. homeostasis antinociception MOV PlPlet HRV BP NMT FEMG Autonomic Muscle
  48. 48. Methods of assessing depth of anesthesia • Subjective: – – – – Autonomic response Isolated forearm technique(IFR) Patient response to surgical stimuli Sedation scales:OAASS,Ransay,etc • objective • . • • Spontaneous surface electromyogram (SEMG);FEMG Lower oesophageal contractility (LOC);Spont AND PROVOKED(SLOC;PLOC) Heart rate variability (HRV) . Electroencephalogram and derived indices – – – – – – – • Compressed spectral array/ Spectral edge frequency/ Median frequency • Bispectral index • Entropy • Narcotrend index • Patient state index • Snap index • Cerebral state index – Evoked potentials:• Somatosensory evoked potentials,• Visual evoked potentials,Auditory evoked potentials,• Auditory evoked potential index,• A-Line autoregressive index…
  49. 49. The PRST Score (Wang & Med indexs Condition score 1993) Systolic blood pressure <control +15 0 (mmHg) > Control +15 > Control +30 0 1 2 nil 0 Skin moist to touch 1 Visible beads to touch Tears <control +15 > Control +30 Sweating 2 > Control +15 Heart rate(beat/min) 1 2 No excess tears in open eyes 0 Excess tears in open eyes 1 Tears overflow from closed eyes 2
  50. 50. I «PEEG» Sia Napoli 2012
  51. 51. Window on the brain
  52. 52. Principles of EEG analysis EEG directly measured by an algorythm • Entropy GE • AEPx • Advantages: • Robust • Real time EEG from historical database or knowledge based systems • • • • Narcotrend BIS CSI Danmeter PSI(patient state analyzer) • SNAPI Sia Napoli 2012
  53. 53. Sia Napoli 2012
  54. 54. Evaluation of the usefulness of a pEEG • The scale must vary according to the anesthestic depth Sia Napoli 2012
  55. 55. BIS monitoring Sia Napoli 2012
  56. 56. Sia Napoli 2012
  57. 57. BIS VISTA
  58. 58. Bis modules • Licensed for integration into the patient monitoring systems of leading manufacturers: • • • • • • • • • Datascope Datex Ohmeda Dixtal Medical GE Healthcare Mennen Medical Mindray Nihon Kohden Philips Spacelabs Healthcare Sia Napoli 2012
  59. 59. Sia Napoli 2012
  60. 60. Monitoring Level of Consciousness during anesthesia & sedation :A Clinician’s Guide to the Bispectral Index Book details: Author:Scott D. Kelley, M.D., Publisher:Aspect Medical Systems, Inc. Pages:141 Size: 4,629 MB Format: pdf Download password:DrWael
  61. 61. Burst suppression BurstSia Napoli 2012 suppression
  63. 63. Cochrane review results • BIS-guided anaesthesia: • reduced the requirement for propofol by 1.30 mg/kg/hr (578 participants; 95% confidence interval (CI) -1.97 to -0.62) • Reduced requirements for volatile anaesthetics (desflurane, sevoflurane, isoflurane) by 0.17 minimal alveolar concentration equivalents (MAC) (689 participants; 95%Sia Napoli 2012 to -0.07). CI -0.27
  64. 64. Cochrane review results • Irrespective of the anaesthetic, BIS reduced the recovery times • time for eye opening by 2.43 min (996 participants; 95% CI -3.60 to -1.27) • response to verbal command by 2.28 min (717 participants; 95% CI -3.47 to -1.09), • time to extubation by 3.05 min (1057 participants; 95% CI -3.98 to -2.11) • orientation by 2.46 min (316 participants; 95% CI -3.21 to -1.71). Sia Napoli 2012
  65. 65. Cochrane review results • BIS shortened the duration of postanaesthesia care unit stay by 6.83 min (584 participants; 95% CI -12.08 to -1.58) • but did not reduce time to home readiness (329 participants; 95% CI -30.11 to 16.09). • The BIS-guided anaesthesia significantly reduced the incidence of intraoperative recall awareness in surgical patients with high risk of awareness (OR 0.20, 95% CI 0.05 to 0.79). Sia Napoli 2012
  66. 66. Cochrane review results • This review of 20 trials found that anaesthesia guided by BIS, to keep it within the recommended range (40 to 60), could decrease the consumption of anaesthetic drugs and enhance recovery from relatively deep anaesthesia. Moreover, BIS could reduce the incidence of perioperative recall in surgical patients with high risk of awareness. Sia Napoli 2012
  67. 67. CSM(Danmeter) Sia Napoli 2012
  68. 68. Sia Napoli 2012
  69. 69. Sia Napoli 2012
  70. 70. Sia Napoli 2012
  71. 71. Sia Napoli 2012
  72. 72. Sia Napoli 2012
  73. 73. Sia Napoli 2012
  74. 74. Sia Napoli 2012
  75. 75. 19 09 08 140420 GS,47,70,168,asa 2(epatite C),chiusura fistola alveolare con osso iliaco. Tiva prop/remi,poi sevor 0.6/0.8 dalle 15.20 alle 16.20 ;ipertensione intraop Sia Napoli 2012
  76. 76. M-ENTROPY (available with S/5 Anesthesia Monitor using software L-ANE03(A) or later) Sia Napoli 2012
  77. 77. What is entropy ? • Measure of the signal irregularity : – High when there are many irrefularities,i.e wide spectrum of frequencies • Low when irregularity scarce 4.3 2.5 3.5 4.5 A sinusoidal wave has a 0 entropy.
  78. 78. schematic representation of the power spectra analysis
  79. 79. Entropy and anaesthesia • EEG signal moves from highly irregular to more regular when the patient lose consciousness EEG entropy decreases
  80. 80. State Entropy (SE) & Response entropy(RE) • Entropy parameters are calculated from two different frequency ranges. State Entropy (SE) is computed from 0.8 to 32 Hz,(value 0-91) which consists mostly of EEG. Response Entropy (RE)(value 0-100) includes additional higher frequencies up to 47 Hz, thus reflecting both EEG and FEMG. • The high frequency components between 32 Hz and 47 Hz are evaluated from a time window of 1.92 seconds resulting in a fast response of RE. The frequency components of SE are mostly derived from the previous 15 seconds of EEG data. Entropy parameters range from 0 (suppression state of EEG) to 100 (awake) for RE, and from 0 to 91 for SE. The difference between SE and RE corresponds to a contribution of the FEMG. During periods of EEG suppression, signal is treated as a totally regular signal with zero entropy Sia Napoli 2012
  81. 81. Frequencies superimposition
  82. 82. M-ENTROPY (available with S/5 Anesthesia Monitor using software LANE03(A) or later)
  83. 83. Sensors… • Integrated multisensor electrodes facilitate application and impede reuse ……..but constitute a flow of revenue for the producer and a continuous cost for customers – Not quite so with some other pEEG(Narcotrend,CSI Danmeter )
  84. 84. 100 60 40 Awake:RE Indu 100,SE 85 ct:R E=S E Intub RE>SE Mantenim:RE=SE Sia Napoli 2012 Risveglio:RE prima di SE
  85. 85. AEP Monitor:Auditory Evoked Response Sia Napoli 2012
  86. 86. • • • • AEP Principles - how it works Acoustic stimulation is provided to the patient’ 9 times a second EEG is measured by 3 cost-effective disposable electrodes The AEP, embedded in the EEG, is extracted using ARX modeling The AAI™ index in the range 100 – 0 is calculated Sia Napoli 2012
  87. 87. What is AEP? • Auditory Evoked Response is a response to an acoustic stimulus. The response, seen as waveforms, is often referred to in three sections: • Brainstem response • Middle latency (early cortical) response • Late cortical response • The Brainstem response waves occur within the first 10 ms after the click stimulus. These responses are relative insensitive to general anaesthetics • The Middle latency waves occur 10 to 80 ms after the click stimulus – the AAI Monitor extracts the MLAP in the 20 – 80 ms window. They show graded changes with general anaesthetics over the clinical concentration range. • The late cortical changes occur 80 ms after the click stimulus and later. These potentials disappear at sedative concentrations of general anaesthetics Sia Napoli 2012
  88. 88. Sia Napoli 2012
  89. 89. AEP waves Sia Napoli 2012
  90. 90. AAI index • EEG information processing + AEP signal processing, • more complete evaluation of the level of consciousness in the AAI index. • The composite AAI index retains its character, while adding information from spontaneous EEG signal processing. Sia Napoli 2012
  91. 91. The A-line ARX-index (AAI) Sia Napoli 2012
  92. 92. Ioc view • The core technology of the IoC-view is the symbolic dynamics method. The combination of spectral ratios, symbolic dynamics EEG and Suppression Rate (ESR) for analyzing the EEG gives a superior suppression of facial EMG which otherwise could influence the index.
  93. 93. Narcotrend Sia Napoli 2012
  94. 94. NARCOTREND (MONITORTECHNIK, BAD BRAMSTEDT, GERMANY:Schiller,Switzerland) • The Narcotrend monitor is developed from visual classification system of different EEG waveforms typically related to different stages of sleep. • The system classifies EEG to A (awake), B (sedated), C (light anaesthesia),D (general anaesthesia), E (general anaesthesia with deep hypnosis), and F (general anaesthesia with burst suppression). • Further classification is done into 14 different sub-stages, which has been further developed into a numerical index from 100 (awake) to 0 (deep anaesthesia). Sia Napoli 2012
  95. 95. Screen display The Narcotrend offers different screen displays which can be chosen and adjusted according to the user's individual needs. Sia Napoli 2012
  96. 96. Narcotrend measurements • a multivariate statistical algorithm transforms the raw EEG data in a 6-letter classification of the depth of anaesthesia: A(awake), B(sedated), C(light anaesthesia), D(general anaesthesia), E(general anaesthesia with deep hypnosis), F(general anaesthesia with increasing burst suppression). The system included a • series of sub-classifications resulting in a total of 14 possible sub-stages:A, B0–2, C0–2, D0–2, E0–1, and F0–13167. • In the most recent version (4.0) of the Narcotrend® software, the alphabet-based scale has been “translated” into a numerical scaling index system which called as the Narcotrend® index. This is scaled quantitatively similar to BIS scale viz. 0 (deeply anaesthetized) to 100 (awake).
  97. 97. Advantages of Narcotrend • • Clearly arranged screen display cerebrogram (trend display of the automatic EEG classifications) raw-EEG signal • power spectrum • two quantiles of the power spectrum (median and spectral edge frequency) • power and cumulative representation of relative power in the standard frequency bands • • • • • • • • • • comparison of signals from both hemispheres 1 or 2 channels Additional trend display cerebrogram power and two quantiles of the power spectrum relative power in the standard frequency bands comparison of signals from both hemispheres trend displays on screen up to 24 hours Comfortable program handling easy, menu-driven operation individually adjustable scaling of diagrams 2012 Sia Napoli complete storage of all data
  98. 98. SNAP IITM,Stryker,Kalamazoo Sia Napoli 2012
  99. 99. Sia Napoli 2012
  100. 100. • • • • • SNAP II In contrast to other monitors,the SNAP II™ algorithm ignores contaminated frequencies from 40 to 80 Hz. The SNAP II™ algorithm, instead, incorporates ultra-fast, high frequency(80 – 420 Hz) EEG signals, a range thought to provide useful information regarding the state of consciousness and cognitive function (Wong et al., 2006; Sing et al., 2005).Given the infl uence of anesthesia on this frequency range, analysis of high-frequency EEG signals may be particularly useful in evaluating transition phases between the awake and anesthetized states (Draguhn et al., 1998, as reviewed by Wong et al., 2005). Monitoring both high- and low-frequency EEG signals is a novel technique Compares them to the signals of other patients that have undergone surgery. The device uses the information provided by the algorithm and historical database to determine a probability projection of a given patient’s LOC , The SNAP Index, reflected in the large readout in the upper left-hand corner of the device is derived from the database and uses a scale from 0 – 99. The index is not a definite determination of a patient’s state of consciousness, but a probability projection. Sia Napoli 2012
  101. 101. SNAP II advantages • • • • • Ultraportable,hand held Crystal clear,high resolution color screen Visual ad audible alarms set by user Memory expandable Disadvantages – 4 hr on batteries – 18 hr of recording max(but …. Sia Napoli 2012
  102. 102. EEG frequencies :SNAP vs BIS Sia Napoli 2012
  103. 103. SEDLINE monitor(HospiraMasimo):Patient state analyzer(PSI) Sia Napoli 2012
  104. 104. PSA 4000
  105. 105. Sia Napoli 2012
  106. 106. SEDLine System • Hospira's next generation brain monitor. It is a patient-connected, 4-channel processed electroencephalograph (EEG) monitor designed specifically for intraoperative or intensive care use. It displays: • Electrode Status • EEG Waveforms • Density Spectral Array (DSA) • SEDLine PSI trend Plots • PSI is a proprietary computed EEG variable that is related to the effect of anesthetic agents. The operator controls the unit using both a menu and dedicated buttons and keys to select various display options. • The system consists of four major components: • SEDLine Monitor • SEDLine Patient Module • SEDLine Patient Cable Sia Napoli 2012 • SEDTrace EEG Electrode Set
  107. 107. Sedline algorithm • The algorithm relies on EEG power, frequency and phase information from anterior–posterior relationships of the brain as well as coherence between bilateral brain regions. The EEG monitor, initially called the PSA4000®, is also the SEDLine® monitor, the newest generation of the device. The SEDLine® system provides the clinician the option of storing and downloading patient data for future use as well as monitoring bilateral brain function and symmetry with a density spectral array (DSA) display. Sia Napoli 2012
  108. 108. PSA_PSI • PSI values between 25-50 shows a green trend which represents the patient is in sufficient hypnotic state and has a low probability of surgical recall. • · Below 25 is shown in yellow, representing a very deep sleep that may result in long recovery from anesthesia. • >50, also in yellow, represents a lightening hypnosis. • +HR and BP
  109. 109. 4 channel a EEG State index of the patient EMG Density Spectral Array (DSA)
  110. 110. NeuroSENSE NS-701 bilateral brain monitor designed with independent indexes for each brain hemisphere
  111. 111. NeuroSENSE NS-701(NeuroWave Systems Inc). 2490 Lee Boulevard, Suite 300,Cleveland Heights, OH 44118 Toll-Free: 1.866.99N.WAVE,Phone: 1.216.361.1591 . Fax: 1.216.361.1554,info@neurowavesystems com • WAVCNS1 bilateral indices ◦WAVCNS (Wavelet Anesthetic Value for Central Nervous System) • ◦Automatic trending • bilateral monitoring with great inter-hemispheric reproducibility and redundancy • •◦High-resolution clinical EEG tracings • review capability for both EEG tracings and processed data trends • touch-screen interface for case browsing • case archive ◦Includes raw EEG signals, processed EEG parameters, automated annotations, markers and signal quality indicators • ◦All data transferrable to USB drive in EDF+ format • •Published and biologically understandable WAVCNS algorithm1◦WAVCNS is based on the gamma-band of the normalized EEG signal, linked to conscious processing and awareness
  112. 112. EMG
  113. 113. Frontal electromyographic (FEMG) activity • Frontal electromyographic (FEMG) activity is present during light levels of anaesthesia. The facial muscles are less sensitive to the effects of NMBAs than are the hand muscles [7]. Although NMBAs suppress spontaneous FEMG activity, they seldom completely abolish the ability of facial muscles to react to noxious stimuli,if not used in excessive amounts. • Inadequate anaesthesia during high intensity nociceptive stimuli is reflected by an increase in FEMG. Arousal at the end of anaesthesia is associated with an abrupt increase in FEMG activity, often preceded by a more gradual, predictive rise [7]. This feature of FEMG is utilized in the Entropy algorithm. Sia Napoli 2012
  114. 114. Paziente adeguatamente anestetizzato Tps 4 mg/kg Sospens N2O Max stimul. prep Iniz chir risveglio
  115. 115. Paziente non adeguatamente anestetizzato Tps 4 mg/kg prep Max stimul. Iniz chir Purposefu l mov Sospens N2O risveg lio
  116. 116. TO monitor EEG or NOT???
  117. 117. FOR WHOM? When should we use these monitors? • Awareness can occur without tachycardia or hypertension • In the absence of muscle relaxation, reflex movements indicate inadequate anaesthesia and most likely inadequate analgesia. A rationally reacting anaesthetist will increase either analgesic or hypnotic medication or both. • However, if the anaesthetic relies heavily on the NMBAs, a high risk situation for intraoperative awareness is created. Sia Napoli 2012
  118. 118. • EEG monitoring reduces the risk of intraoperative awareness both in high risk groups as well as in general patient population. To reduce explicit recall, at least high risk groups should be monitored. Sia Napoli 2012
  119. 119. What is a high risk case? • • • • • • • Trauma Caesarean section Cardiac surgery rigid bronchoscopy emergency surgery TIVA patients Patients who tolerate hypnotic medication poorly, such as those with compromised cardiovascular capacity, • Patients who have experienced awareness during general anaesthesia previously • those who might have an increased tolerance to sedative drugs due to prior medication or substance abuse. • If the surgery must be performed under heavy neuromuscular blockade Sia Napoli 2012
  120. 120. Advantages of EEG monitoring • more precise titration of anaesthetic agents to individual patients • resulting in lower consumption • enhanced recovery • speed up day case surgery • improve operating room efficiency in any type of surgery Sia Napoli 2012
  121. 121. Disadvantages(for all EEG monitors) • Proprietary disposable electrodes---costs • Monitor:cost of purchase • Cost of eeg monitoring and consumables against other monitors or equipment………. – Except:Narcotrend and CSI use normal ECG electrodes Sia Napoli 2012
  122. 122. Avidan MS, Zhang L, Burnside BA, Finkel KJ, Searleman AC, Selvidge JA, Saager L, Turner MS, Rao S, Bottros M, Hantler C. Jacobsohn E,Evers AS. Anesthesia Awareness and the Bispectral Index., N Engl J Med • • • • • 2008;358:1097-108. In this trial, we sought to determine whether a BIS-based protocol is better than a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for decreasing anesthesia awareness in patients at high risk for this complication. Methods We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum alveolar concentration [MAC]). Postoperatively, patients were assessed for anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30 days after extubation). Results We assessed 967 and 974 patients from the BIS and ETAG groups, respectively. Two cases of definite anesthesia awareness occurred in each group (absolute difference, 0%; 95% confidence interval [CI], −0.56 to 0.57%). The BIS value was greater than 60 in one case of definite anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three cases. For all patients, the mean (±SD) timeaveraged ETAG concentration was 0.81±0.25 MAC in the BIS group and 0.82±0.23 MAC in the ETAG group (P = 0.10; 95% CI for the difference between the BIS and ETAG groups, −0.04 to 0.01 MAC). Sia Napoli 2012
  123. 123. Avidan et al. Anesthesia Awareness and the Bispectral Index., N Engl J Med 2008;358:1097-108. • Conclusions • We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. ( number, NCT00281489.) ) Sia Napoli 2012
  124. 124. Deep anesthesia is too deep? • Monk TG, Saini V, Weldon C, Sigl JC. Anesthestic management and oneyear mortality after noncardiac surgery. Anesth Analg 2005;100:4–10. • Outcome after 1 year following major noncardiac surgery linked to – Hypotension duration – Comorbidities – cumulative deep hypnotic time (BIS<45) Sia Napoli 2012
  125. 125. Kertai MD, Palanca BJ, Pal N, Burnside BA, Zhang L, Sadiq F, Finkel KJ, Avidan MS; B-Unaware Study Group.Bispectral index monitoring, duration of bispectral index below 45, patient risk factors, and intermediate-term mortality after noncardiac surgery in the B-Unaware Trial. Anesthesiology. 2011 Mar;114(3):54556 • • • • • Postoperative mortality has been associated with cumulative anesthetic duration below an arbitrary processed electroencephalographic threshold (bispectral index [BIS] <45). This substudy of the B-Unaware Trial tested whether cumulative duration of BIS values lower than 45, cumulative anesthetic dose, comorbidities, or intraoperative events were independently associated with postoperative mortality. METHODS: The authors studied 1,473 patients (mean ± SD age, 57.9 ± 14.4 yr; 749 men) who underwent noncardiac surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Multivariable Cox regression analysis was used to determine whether perioperative factors were independently associated with all-cause mortality. RESULTS: A total of 358 patients (24.3%) died during a follow-up of 3.2 ± 1.1 yr. There were statistically significant associations among various perioperative risk factors, including malignancy and intermediate-term mortality. BIS-monitored patients did not have lower mortality than unmonitored patients (24.9 vs. 23.7%; difference = 1.2%, 95% CI, -3.3 to 5.6%). Cumulative duration of BIS values less than 45 was not associated with mortality (multivariable hazard ratio, 1.03; 95% CI, 0.93-1.14). Increasing mean and cumulative end-tidal anesthetic concentrations were not associated with mortality. The multivariable
  126. 126. Bispectral index monitoring, duration of bispectral index below 45, patient risk factors, and intermediate-term mortality after noncardiac surgery in the B-Unaware trial • CONCLUSIONS: • This study found no evidence that either cumulative BIS values below a threshold of 40 or 45 or cumulative inhalational anesthetic dose is injurious to patients. These results do not support the hypothesis that limiting depth of anesthesia either by titration to a specific BIS threshold or by limiting end-tidal volatile agent concentrations will decrease postoperative mortality
  127. 127. What? Me Worry • ? • ―The brain is the least important organ in the body. You can’t live without a liver or kidney but plenty of people seem to get along without a brain.‖ • --John McGillicuddy, MD Sia Napoli 2012
  128. 128. Combination • Combination of information from different sources may be required for monitoring the adequacy of analgesia during anaesthesia. • EEG spectral entropy, heart rate, photoplethysmography and motor responses to skin incision Sia Napoli 2012
  129. 129. Anaesthesia maintained by Entropy closed loop • Anesthesiology. 2012 Feb;116(2):286-95. Feasibility of closed-loop titration of propofol and remifentanil guided by the spectral M-Entropy monitor.Liu N, Le Guen M, Benabbes-Lambert F, Chazot T, Trillat B, Sessler DI, Fischler M. • TIVA TCI guided by Entropy module vs manual tiva administration ( 40- 60 SE e RE) • Entropy values better maintained with the automatic control ;slight decrease of propofol and remifentanil consumption • The automatic system made a median of 28 remifentanil and 21 propofol dose adjustments per hour during the maintenance phase, compared with 10 and eight adjustments, respectively, by the anesthesiologists. The primary outcome was a global score of SE, which included maintenance of SE between 40 and 60. The average score was significantly lower in the M-Entropy group than in the manual control group, at 25 • versus 44, indicating tighter control of anesthesia by the automatic system. • Automatic control maintained SE within the 40–60 range 80% of the time versus 60% of the time with manual control.
  130. 130. Interpretation ( pEEG) and recommendation Cambell Bennett,Logan J. Voss,John P. M. Barnard.James W. Sleigh .Interpretation ( pEEG) and recommendation.Practical Use of the Raw Electroencephalogram Waveform During General Anesthesia: The Art and Science.Anesth Analg 2009;109:539–45. • The « number « must be interpreted within its clinical context – As all other monitors………… – The anesthesiologist must ascertain that the pEEG number is: – consistent with the apparent state of the patient, the doses of various anesthetic drugs,the degree of surgical stimulation – consistent with the appearance of the raw EEG signal • Any discrepancy should function as a stimulus to critically reevaluate the patient ,collecting all the available informations(surgical field,surgeons ,monitors….)instead of «treating the number» • Observe the patient!
  131. 131. Technical points • Alway check electrodes status and position • Check impedance(skin degrease) • Automatic checking
  132. 132. Limits of pEEG • • • • oversimplifications, violations of mathematical rules, non-linear components Misunderstandings – Use them as a clinical help,but not as a scientific tool!
  134. 134. Ocular microtremor • Robertson J,Timmons S..Non-invasive brainstem monitoring: the ocular microtremor . Neurological Research 2007; 29: 709-711. – Department of Neurosurgery, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. Sia Napoli 2012
  135. 135. EyeTect® Tremor Monitor Unit (the “TMU”) • The EyeTect® Tremor Monitor Unit (the “TMU”) is currently in the prototype stage but has already received FDA clearance (see Appendix A) as a Class II medical device that directly monitors brainstem activity by measuring Ocular Microtremor (“OMT”). Sia Napoli 2012
  136. 136. What is OMT? • OMT is a high frequency, low amplitude tremor of the eyes triggered by impulses originating in the oculomotor area of the brainstem. • • • The oculomotor neurons are embedded in the reticular activating system, which is a group of nerve pathways concerned with the level of consciousness from the states of sleep, drowsiness, and relaxation to full alertness and attention. These reticular groups of small and large neurons have crossing, ascending and descending fibers that connect with pathways in the brainstem and spinal cord. Signals projecting upward through these pathways cause a tonic vibration of the muscles attached to the eye, thus creating micro-motion that is unnoticeable, yet present in all individuals, even when the eyes are at rest. OMT is the highest in frequency and lowest in amplitude of all physiological tremors. Studies have concluded that the mean frequency of OMT in normal healthy humans is 84 Hz (+/- 6 Hz) with a mean amplitude of six seconds of arc. Normal OMT consists of an irregular baseline with superimposed regular sinusoidal episodes of activity called bursts. It has been demonstrated that OMT’s frequency Sia Napoli 2012 and amplitude vary depending upon the patient state.
  137. 137. OMT waveform for normal, sedated, and brainstem dead patients Sia Napoli 2012
  138. 138. Welcome to Our Mission To improve people’s lives by helping healthcare professionals deliver the best care using innovative monitoring of the brainstem. The Company has developed the work of Ciaran Bolger, MD and is 18 months from launching its initial application of a new technology for physicians. The company has received its first patent, and FDA 510k marketing clearance on the first ever non-invasive continuous brainstem function monitor that will improve outcomes for neurologically disabled patients while reducing hospital costs for treatment and diagnosis by over $6 billion annually. The EyeTect® Tremor Monitor Unit (TMU) measures ocular micro-tremor (OMT), which has been shown in published clinical trials to have four market applications Sia Napoli 2012
  139. 139. Robertson J,Timmons S..Non-invasive brainstem monitoring: the ocular microtremor . Neurological Research 2007; 29: 709711 • Abstract: • The ocular microtremor (OMT) is mediated by the oculomotor area of the brainstem and is altered in several pathologic states, including traumatic brain injury, general anesthesia, brain death, coma, Parkinsonism and multiple sclerosis. The EYETECT tremor monitor is a non-invasive means of measuring the frequency and amplitude of this microscopic tremor. It has been clinically tested in these clinical scenarios and has been found to be a reliable means of detecting the depth of anesthesia, and has been useful in predicting outcome in coma and traumatic brain injury patients and in confirming brain death. This paper reviews the scientific literature on the EYETECT OMT monitor, describes the underlying physiology and discusses the potential for future works and clinical use of this innovative technology. Sia Napoli 2012
  140. 140. Stress index and…. Surgical stress response
  142. 142. Response of the pulse oximeter waveform (Pleth) to surgical stimulation. In this case, a patient undergoing general anesthesia experiences the first surgical incision of an operative procedure. The pulse oximeter waveform is noteworthy for the sudden reduction in amplitude. This is felt to be indicative of a sudden increase in sympathetic tone causing peripheral vasoconstriction. A concomitant increase in the arterial blood pressure (BP) supports this explanation. This is felt to be indicative of a sudden increase in sympatheticant increase in the arterial blood pressure (BP) supports this explanation
  144. 144. • Changes in PPGA mostly reflect changes in the peripheral vascular bed,controlled by the sympathetic nervous system,and hence PPGA is a sensitive marker for sympathetic reactions caused, e.g. by nociception during general anaesthesia.
  145. 145. ; construction of the SSI surgical stress index Vascolarizzaz periferica heart beat interval cuore
  146. 146. Sviluppi tecnologici; SPI(Surgical Pleth Index) • • • • • • • • • a digit that may be used to monitor the patient’s hemodynamic responses to surgical stimuli and analgesic medications during general anesthesia. SPI reflects the patient’s responses, which result from increased sympathetic activity as a reaction to painful (nociceptive) stimuli. SPI monitoring is based on the acquisition of the readily available plethysmographic pulse wave, which is processed with a unique algorithm. The calculation analyzes the photoplethysmographic amplitude and the photoplethysmographic pulse interval, and then combines these two parameters to create a single digit, the Surgical Pleth Index.(assomiglia insomma alla semplificazione eeg del BIS o CSM) Clinical use of the SPI SPI can be used to help assess both acute nociceptive events, as well as long-term state reactions during general anesthesia. In general, when the SPI goes up, the patient is responding to the events. When the index goes down, the level of surgical rsponsiveness has decreased. At the beginning of measurement, and as needed, the SPI’s algorithm starts learning and processing the signals. The digit will be grey in color, and a “learning”message is shown. Learning is marked in the trends as a dashed, vertical line. When the measurement is started, it will take about three minutes for the learning process to take place. to function.
  148. 148. Physiological reactions during changes in skin conductance: skin sympathetic nerves release acetylcholine, which acts on muscarine receptors with subsequent release of sweat that increases the skin conductance when the sweat reaches the skin
  149. 149. Placement of electrodes. The C-electrode was placed on the hypothenar eminence, the M-electrode on the hypothenar eminence, and the Relectrode on the dorsal side of the hand.
  150. 150. Measured parameters • number of skin conductance fluctuations (NSCF) • Amplitude of skin conductance fluctuations (ASCF) (microsiemens) • Mean SCL (microsiemens)
  151. 151. Anesth induction Stable anesth :+stimulation Stable anesth without stimulation Emergence
  152. 152. NFSC Durante intubazione C GJERSTAD, H STORM, R HAGEN, M HUIKU, E QVIGSTAD,J RÆDER.Comparison of skin conductance with entropy during intubation, tetanic stimulation and emergence from general anaesthesia. Acta Anaesthesiol Scand 2007; 51: 8–15
  153. 153. Put it all together………… METTIAMO D’ACCORDO TUTTI?
  155. 155. Sarén-Koivuniemi TJ, Yli-Hankala AM, van Gils MJ..Increased variation of the response index of nociception during noxious stimulation in patients during general anaesthesia. Comput Methods Programs Biomed. 2010 Oct 29. [Epub ahead of print] • Response Index of Nociception (RN) is a multiparameter approach which combines photoplethysmographic waveform (PPG), State Entropy (SE), Response Entropy (RE), and heart rate variability (HRV). • • • • • • • 60 women undergoing gynaecological or breast surgery anaesthesia was maintained with propofol-remifentanil target controlled infusion. Neuromuscular blocking agent rocuronium was used at the beginning of the surgery. The RN index, reflecting amplitude and frequency of occurrence of abrupt increases ("peaks") in the RN was evaluated during surgery in general and around occurrences of predefined noxious stimuli in particular. Patient movement was associated with increased index values, both before and after the event. Post-event values of the index for intubation and skin incision were higher than its intrasurgery baseline, while pre-event values remained unchanged. CONCLUSION: Changes in RN can be used to detect noxious stimuli during surgery. RN also predicted movement in our patients under propofol-remifentanil anaesthesia
  156. 156. Ledowski T, Ang B, Schmarbeck T, Rhodes J.Monitoring of sympathetic tone to assess postoperative pain: skin conductance vs surgical stress index. Anaesthesia. 2009 Jul;64(7):727-31. • number of fluctuations in skin conductance per second (NFSC) vs surgical stress index(SSI) to assess postoperative pain, in 100 postoperative patients who were also asked to quantify their level of pain at different time points in the recovery room.(VAS Numerical scale 0-10) • The number of fluctuations per second and surgical stress index were significantly different between pain scoring <or= 5/10 and > 5/10 on a numeric rating scale (mean (SE) number of fluctuations per second 0.12 (0.02) vs 0.21 (0.03), respectively; p = 0.017, and surgical stress index 57 (1.4) vs 64 (1.9) points, respectively; p = 0.001). • Both number of fluctuations in skin conductance per second and surgical stress index identified timepoints with moderate to severe pain with only moderate sensitivity and specificity • Osservaz sul metodo:Ma NFSC ha un intervallo di tempo troppo breve( 5 sec);forse sarebbe meglio aumentarlo a 20 sec;poi l’algoritmo dell’SSI è stato creato su pazienti in anestesia generale e dunque potrebbe non adattarsi a paz coscienti.
  157. 157. Which are the requirements for a useful depth of anesthesia monitor? • validation of the index for detecting clinical signs of anaesthesia during anaesthesia induction and recovery, • pharmacokinetic-dynamic validation, • validation of performance under clinical conditions, • demonstrating improvement of outcome • demonstrating cost-benefit effectiveness. – Heyse, B.; Van Ooteghem, B.; Wyler, B.; Struys, M.M.; Herregods, L.; Vereecke, H. Comparison of contemporary EEG derived depth of anesthesia monitors with a 5 step validation process. Acta Anaesthesiol. Belg. 2009, 60, 19-33. Sia Napoli 2012
  158. 158. Safety vs adequacy • Monitors for : • safety: – ECG,BP,SaO2,etCO2,FiO2,CO,NIRS… • titration(adequacy); – pEEG,AEP,SSI,Sweat…
  159. 159. Navigator view(GE)
  160. 160. Smart Pilot view (Draeger)
  161. 161. Clive Ballard, Emma Jones, Nathan Gauge, Dag Aarsland, Odd Bjarte Nilsen, Brian K. Saxby, David Lowery, Anne Corbett, Keith Wesnes, Eirini Katsaiti, James Arden, Derek Amaoko,Nicholas Prophet, Balaji Purushothaman, David June Green.Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial. PLOS ONE 2012 | Volume 7 | Issue 6 | e37410 • BIS maintained at 40-60 +-5 and Non invasive Cerebral oxygen monitoring decreased the incidence of POCD even at 53 weeks postop major noncardiac surgery
  162. 162. While some must watch while some must sleep.Shakespeare Hamlet,Prince od Danmark,atto III,scena II Act I II. Scene II
  163. 163. THE END Eternal vigilance is the price of freedom
  164. 164. • • • • OMT’s behavior has been studied for over seventy years. Researchers, including the world’s foremost expert, Ciaran Bolger, Ph.D., FRCS, FRCSI, have demonstrated its clinical relevance in monitoring anesthesia, coma, brainstem death, Parkinson’s disease, Multiple Sclerosis, and sleep disorders. The initial studies were performed using an openeye sensor for very short periods of time and utilizing post experiment signal analysis, neither of which is practical from a clinical perspective. In 2000, Dr. Bolger and a group of neurosurgeons, engineers, and business leaders formed EyeTect, LLC to develop a real-time, closed-eye OMT monitoring system – the TMU – that is more clinically useful and user-friendly than the open-eye device. EyeTect’s TMU has been proven effective in clinical studies, and has received 510(k) clearance from the USFDA for use in the OR and ICU (See Appendix A), as well as patent protection from the USPTO. The EyeTect® TMU system provides an easy-to-use method of measuring OMT through a closed eyelid and displaying the measurements in real time on a standard patient monitor or a freestanding monitor. A small sensor is placed on the patient’s closed eyelid that picks up the micro-movement through the eyelid. The OMT frequency, amplitude, waveform, and trend over time are then instantaneously displayed on the TMU or bedside Sia Napoli 2012 monitor.
  165. 165. ocular microtremor:Eyetect monitor • The ocular microtremor (OMT) is mediated by the oculomotor area of the brainstem and is altered in several pathologic states, including traumatic brain injury, general anesthesia, brain death, coma, Parkinsonism and multiple sclerosis. The EYETECT tremor monitor is a non-invasive means of measuring the frequency and amplitude of this microscopic tremor. It has been clinically tested in these clinical scenarios and has been found to be a reliable means of detecting the depth of anesthesia, and has been useful in predicting outcome in coma and traumatic brain injury patients and in confirming brain death. This paper reviews the scientific literature on the EYETECT OMT monitor, describes the underlying physiology and discusses the potential for future works and clinical use of this innovative technology. Sia Napoli 2012
  166. 166. 1,7,10 )Propofol concentration increase (5) skin incision and start of surgery, 8) strong surgical stimulus to the uterus region, An example case (female 55 years, ASA I, laparotomy) of the typical changes and reactions of PPGA during general anaesthesia and surgery. Some significant events are marked: (1) start of anaesthesia with propofol 5mg/ml and remifentanil 1 ng/ml (TCI), (2) intubation, (3) propofol change to 4mg/ml and (4) to 3.5 mg/ml, (5) skin incision and start of surgery, (6) remifentanil change to 3 ng/ml, (7) propofol change to 6 mg/ml, (8) strong surgical stimulus to the uterus region, (9) propofol change to 3 mg/ml, and (10) 6 mg/ml. Note the effects of changing propofol levels due to vasodilatation it is known to cause (events with increasing levels: 1, 7 and 10, and decreasing levels: 3, 4 and 9).
  167. 167. 3 instants are extracted for special attention: (A)intubation shortly after induction of anaesthesia as a noxious stimulus causes an increase in HR at 11 : 55 : 50 and a slight decline in PPGA, which is partially masked by vasodilatation caused by propofol. Also, the RE–SE difference increases. (B) Incision causes a dramatic decline in PPGA, accompanied by increasing HR and NIBP. Together, these changes may be considered as a typical fingerprint of sympathetic activation related to nociception. (C) Strong surgical stimulation of the uterus area causes a similar decline as an incision on PPGA but this time this is accompanied by decreased HR and NIBP due to a direct vagal stimulus caused by uterus area manipulation. These parallel changes are concurrent with parallel activation of both sympathetic (due to nociception) and parasympathetic (due to direct autonomic nervous system stimulation) nervous systems
  168. 168. Readings from a patient with per-operative awakening. one of the patients awakened before the surgery had been terminated, and all the skin conductance variables increased simultaneously, before the BIS increased
  169. 169. Esempi di registrazione dello NFSC dei Casi clinici dello studio di A C GJERSTAD, H STORM, R HAGEN, M HUIKU, E QVIGSTAD,J RÆDER.Comparison of skin conductance with entropy during intubation, tetanic stimulation and emergence from general anaesthesia. Acta Anaesthesiol Scand 2007; 51: 8–15
  171. 171. Br J Anaesth. 2007 Oct;99(4):532-7.Can anaesthetists be taught to interpret the effects of general anaesthesia on the electroencephalogram? Comparison of performance with the BIS and spectral entropy.Barnard JP, Bennett C, Voss LJ, Sleigh JW. • Training session then short EEG tracings evaluation – Human errors i 41%,pEEG 30%, • But monitors did not make major errors ,i.e interpreting as anesthetized EEG values of awake patients vs 10% of MD’s anesthesiologists !!!
  172. 172. difference between man and machine • • • • • rate of major errors; that is, judging that anaesthesia was adequate when the patient was conscious, or the converse,judging that the patient was conscious when they were anaesthetized No major errors were made by either of the pEEG machines,anaesthetists made these errors on 80 (10)% occasions. One or more of these errors was made by 32 (78)% anaesthetists.The major error rate [1.98 (SD 1.92)] varied much more markedly between anaesthetists than the minor errorrate [10.3 (2.9)] ( The BIS and entropy monitors each made nine minor errors (Table 1, italic values). The BIS errors were evenly spread among the four minor error options, whereas the entropy wrongly classified 8 (80)% of the sedated/transition EEGs as anaesthetized. The rate of major errors was unevenly distributed across the EEG tracings. Two of the tracings from awake patients accounted for 30 (59)% of the major errors when the patient was awake (Fig. 4). Similarly, two tracings from anaesthetized patients accounted for 15 (54)% of the major errors when patients were anaesthetized (Fig. 5).
  173. 173. • the prediction probability (PK) can be used as a nonparametric measure of the goodness of the correlation between drug concentration and effect, we hypothesized that maximizing the prediction probability could be a promising new semiparametric method for estimating ke0. The prediction probability14 has become a standard measure for the performance of anesthetic depth monitors.4,6,15–17 Given 2 randomly
  174. 174. • Smith WD, Dutton RC, Smith NT. Measuring the performance of anesthetic depth indicators. Anesthesiology 1996;84:38–51. • Smith WD, Dutton RC, Smith NT. A measure of association for assessing prediction accuracy that is a generalization of nonparametric ROC area. Stat Med 1996;15:1199–215
  175. 175. Plasma alfentanil vs blood propofol concentrations associated with a 95% probability of no response to surgical stimuli Sia Napoli 2012
  176. 176. Interaction between remifentanil and isoflurane Isoflurane concentration reduction by increasing remifentanil whole blood concentration.Anesthesiology 85:721-8, 1996 Sia Napoli 2012
  177. 177. Johnson, KB,,Noah D. Syroid,,Dhanesh K. Gupta,,Sandeep C. Manyam,,Talmage D. Egan, Jeremy Huntington, Julia L. White, Diane Tyler,wayne R. Westenskow,.An Evaluation of Remifentanil Propofol Response Surfaces for Loss of Responsiveness, Loss of Response to Surrogates of Painful Stimuli and Laryngoscopy in Patients Undergoing Elective Surgery..Anesth Analg 2008;106:471–9.
  178. 178. Mertens et al Anesthesiology 2003; 99:347–59 .Propofol Reduces Perioperative Remifentanil Requirements in a Synergistic Manner Response Surface Modeling of Perioperative Remifentanil–Propofol Interactions Fig. 1. Concentration–effect relation of the combination of propofol and remifentanil for suppression of responses to laryngoscopy. The curve (top) was obtained by response surface modeling, of the response (open squares)–no response (closed squares) data versus the corresponding measured blood propofol concentrations and blood remifentanil concentrations. The displayed curve represents remifentanil and propofol concentrations associated with a 50% probability of no response,. In the concentration– response surface (bottom) for the combination of propofol and remifentanil, the isoboles for 25, 50, and 75% probability of no
  179. 179. Fig. 2. Concentration–effect relation of the combination of propofol and remifentanil for suppression of responses to intubation. The curve (top) was obtained by response surface modeling, of the response (open squares)–no response (closed squares) data versus the corresponding measured blood propofol concentrations and blood remifentanil concentrations. The displayed curve represents remifentanil and propofol concentrations associated with a 50% probability of no response, In the concentration– response surface (bottom) for the combination of propofol and remifentanil, the isoboles for 25, 50, and 75% probability of no response are shown.
  180. 180. Fig. 4. Pharmacodynamic curves from the models showing the effect of different combinations of remifentanil and propofol on blunting response to two different surrogate stimuli, laryngoscopy (top) and algometry (bottom). Each curve represents the concentration–response curve for remifentanil in combination with a fixed concentration of propofol. These curves represent the significant synergism, indicated by the leftward shift of the concentration–response curves, when the two agents are combined. Kern SE et al .Anesthesiology 2004; 100:1373–81 Opioid–Hypnotic Synergy A Response Surface Analysis of Propofol–Remifentanil Pharmacodynamic Interaction in Volunteers
  181. 181. • Minto CF, Schnider TW, Short TG, Gregg KM, Gentilini A, Shafer SL.Response surface model for anesthetic drug interactions.Anesthesiology 2000; 92: 1603–16. • Drews FA, Syroid N, Agutter J, Strayer DL, Westenskow DR. Drug delivery as control task: improving performance in a common anesthetic task. Hum Fact 2006; 48: 85–94 • Syroid ND, Agutter J, Drews FA, et al. Development and evaluation of a graphical anesthesia drug display. Anesthesiology 2002; 96:565–75 •
  182. 182. • Schumacher PM, Bouillon TW, Leibundgut D, Sartori V,Zbinden AM. Anesthesia advisory display (AAD): real time guidance through the pharmacokinetic and interaction harmacodynamic relationship during simultaneous administration of multiple drugs. Anesthesiology 2004; 101: A504 • Albert RW, Agutter JA, Syroid ND, Johnson KB, Loeb RG,Westenskow DR. A simulation-based evaluation of a graphic cardiovascular display. Anesth Analg 2007; 105: 1303–11. • Absalom A, Struys MMRF. An Overview of TCI & TIVA, 2nd Edn.Ghent: Academia Press, 2007