Profondità anestesia finale sia 2012 (2)

Monitoring depth of anesthesia(DOA)
Il monitoraggio della profondità
anestetica
Claudio Melloni
Libero professionista
Consulente :
Poliambulatorio S.Lucia ,Bologna,
Day surgery Gynepro,Bologna
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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

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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.
»
it

paziente
Paziente
Chirurgia
chirurgia
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Not always the sea is calm like
this one……
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Navigating in a rough sea….
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Emergence…..
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Monitoring ……….
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depthmeter ……….
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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.”
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Definitions of anaesthesia
Definitions of anaesthesia
Dr ug induced uncosciousness:thepatient does not per ceivenor r ecallnoxiousstimulat ion
Dr ug induced uncosciousness:thepatient does not per ceivenor r ecallnoxiousstimulat ion
Prys -Roberts C. Anaesthes ia: apractical or impracticalcons truct? [ editorial].BrJ Anaesth 1987;59:1341-5.
Prys -Roberts C. Anaesthes ia: apractical or impracticalcons truct? [ editorial].BrJ Anaesth 1987;59:1341-5.
Paralysis uncosciousness& att enuationofthe st ress response
Paralysis uncosciousness& att enuationofthe st ress response
Pins ker MC.Anesthes ia:a pragmaticconstruct.AnesthAnalg1986; 65:819-20.
Pins ker MC.Anesthes ia:a pragmaticconstruct.AnesthAnalg1986; 65:819-20.
Sensoryblock,motor block,blockof reflexes,m
entalblock
Sensoryblock,motor block,blockof reflexes,m
entalblock
Woodbrige
Woodbrige
Allseparate effects usefult opr otect t he patient from thestressofsur ger y
Allseparate effects usefult opr otect t he patient from thestressofsur ger y
Kiss inI ,Gelman S.Components of anaes thes ia. Br JAnaes th1988; 61:237-42.
Kiss inI ,Gelman S.Components of anaes thes ia. Br JAnaes th1988; 61:237-42.
Rever sibleoblivionandim
m
obility
Rever sibleoblivionandim
m
obility
Eger EI II. What is general anesthetic action? [editorial]. AnesthAnalg 1993; 77:408.
Eger EI II. What is general anesthetic action? [editorial]. AnesthAnalg 1993; 77:408.
lREES e GRAY 1950
lWoodbrige 1957
lGray 1960

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Modern balanced anesthesia
Modern balanced anesthesia
Do they fir together?
Do they fir together?
Hypnosis
Hypnosis Amnesia
Amnesia Analgesia
Analgesia Muscle relaxation
Muscle relaxation
Stress protection
Stress protection Reflexes protection
Reflexes protection Absence of movement
Absence of movement

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 non-
responsiveness at defined effect site
concentrations.
• Shafer SL, Stanski DR. Handb Exp Pharmacol.
2008;(182):409-23. Defining depth of anesthesia
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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.
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Depth vs adequacy
• Unresponsiveness to
noxious stimuli.
• Unresponsiveness to
non noxious stimuli .
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Muscle relaxation is not paralysis
Muscle relaxation
• Unresponsiveness without
nmb
• Usually a measure of
hypnosis
• Measure of
anesthetic adequacy
paralysis
• No measure of hypnosis
• No measure of anaesthetic
adequacy
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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……
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Navigating anesthesia
• How much drug
• Which is the concentration at the level of
the effector site
• Measuring effects
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Relationships between drugs and effects:
nonlinear,complex…
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ipnotici analgesici miorilassanti
ipnosi analgesia
Rilasciame
nto
muscolare
Incoscienza
amnesia
Stabilità
autonomica antinocicezione immobilità

INTRODUCTION TO
QUANTITATIVE ANESTHESIA
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The level of stimulation is
continuously changing!
0
2
4
6
8

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assessments in anesthesia
assessments in anesthesia
response to stimulation
response to stimulation
Presurgical
Presurgical
LOC
LOC
MAC awake
MAC awake
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
surgical
surgical
no movement
no movement
MAC
MAC
no cardiovascular changes
no cardiovascular changes
MAC Bar
MAC Bar
no respiration changes
no respiration changes
postsurgical
postsurgical
eye opening
eye opening
obeying to simple commands
obeying to simple commands
date of birth
date of birth
respiration
respiration
spont movements..
spont movements..
walking
walking
dressing
dressing
plasma/effect site concentrations
plasma/effect site concentrations

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MAC
MAC
Mac
awake50-95
Mac
awake50-95
Anesthetic
alveolar
concentration
preventing
awareness in 50%
or 95% of
subjects…(Stoelting
1970);
Anesthetic
alveolar
concentration
preventing
awareness in 50%
or 95% of
subjects…(Stoelting
1970);
MAC
MAC
Minimum alveolar
concentration of
anesthetic
preventing movement
in response to
incision in 50-95% of
subjects..
Minimum alveolar
concentration of
anesthetic
preventing movement
in response to
incision in 50-95% of
subjects..
MAC bar50-95
MAC bar50-95
Minimum alveolar
concentration of
anesthetic preventing
stress response to
surgical stimulation in
50-95% of patients
Minimum alveolar
concentration of
anesthetic preventing
stress response to
surgical stimulation in
50-95% of patients

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MAC Tables
MAC Tables
Mac
awake
Mac
awake
MAC in
O2
MAC in
O2
MAC in
N2O 60%
MAC in
N2O 60%
MAC
bar
MAC
bar
halothane
halothane 0.41
0.41 0.7
0.7 0.3
0.3 1.3Mac
1.3Mac
isoflurane
isoflurane 0.38
0.38 1.14
1.14 0.50
0.50 1.3 Mac
1.3 Mac
sevoflurane
sevoflurane 0.62
0.62 2
2 0.60
0.60 1.5 Mac
1.5 Mac
desflurane
desflurane 2.42
2.42 6
6 2.83
2.83 1.5 Mac
1.5 Mac

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0.5
1.0
1.5
MAC requires
equilibration
between
alveolar
concentration
and blood and
effect site!

I.V.drugs for anaesthesia
EFFECT
CONCENTRATION
Concentration effect curve for a single
drug
Slope  therapeutic
margin
EC50  ED50

Probability
of
no-
response
I.V.drugs for anaesthesia
Concentration effect curve for a single drug
Ce95

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.

Alfentanil di Ausems
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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.
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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
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time
Propofol blood conc
Opioid blood concentration
Three dimensional planes in the
graphs from Vuyk et al.

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.

Strategic choices between opioid / hypnotic interactions

Optimal concentrations(intraabd surgery) for a
rapid recovery

Practical pharmacokinetics as applied to our
daily anesthesia practice . Fiset P.Can J Anesth
1999 / 46 / R122-R126

Controlling the calculated
plasma/effect site concentration
Plasma/effect site
concentration
Propofol
remifentanil
Patient’s
response
Pharmacology
Pharmacokinetics(
Pk)
Pharmacodynamics
(PD)

Using the available technology

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!!!

In conclusion :
•We can measure or
predict drug
concentration not drug
effect

hypnosis
antinociception
Side
effects
EEG,BAEP…..
etO2
etCO2
SaO2
ECG
HR
HRV
BP
responses
MOV
PlPlet
HRV
BP
NMT
FEMG
homeostasis
Physiology
Delta down
Temp centr &
periph
RQ
EE
PRST….
MONITORING
Hypoventilation
Bradycardia
hypotension
arrhythmias
Autonomic
Muscle
Oxygenation
Ccarbon diox
Fluids
Blood
Electrolytes
Energy
temperature
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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…

The PRST Score (Wang & Med
1993)
indexs Condition score
Systolic blood pressure
(mmHg)
<control +15 0
> Control +15 1
> Control +30 2
Heart rate(beat/min) <control +15 0
> Control +15 1
> Control +30 2
Sweating nil 0
Skin moist to touch 1
Visible beads to touch 2
Tears No excess tears in open eyes 0
Excess tears in open eyes 1
Tears overflow from closed eyes 2

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
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Evaluation of the usefulness of a
pEEG
•The scale must vary
according to the anesthestic
depth
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BIS monitoring
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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
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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

Burst suppression
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Burst suppression

PUNJASAWADWONG Y, BOONJEUNGMONKOL N,
PHONGCHIEWBOON A.
BISPECTRAL INDEX FOR
IMPROVING ANAESTHETIC
DELIVERY AND POSTOPERATIVE
RECOVERY.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2007,
ISSUE 4. ART. NO.: CD003843.
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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% CI -0.27 to -0.07).
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• 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

• 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).
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• 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

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
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M-ENTROPY (available with S/5 Anesthesia Monitor using
software L-ANE03(A) or later)
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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.

schematic representation of the power spectra analysis

Entropy and anaesthesia
• EEG signal moves from highly irregular to
more regular when the patient lose
consciousness
EEG entropy decreases

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
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M-ENTROPY
(available with
S/5 Anesthesia
Monitor using
software L-
ANE03(A) or
later)

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 )

Awake:RE
100,SE 85
Indu
ct:R
E=S
E
Intub
RE>SE Mantenim:RE=SE
Risveglio:RE prima di SE
100
60
40
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AEP Monitor:Auditory Evoked
Response
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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
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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
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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.
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The A-line ARX-index (AAI)
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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.

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).
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Screen display
The Narcotrend offers different screen displays which can be chosen
and adjusted according to the user's individual needs.
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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).

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
• complete storage of all data
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SNAP
IITM,Stryker,Kalamazoo
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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.
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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 ….
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EEG frequencies :SNAP vs BIS
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SEDLINE monitor(Hospira-
Masimo):Patient state analyzer(PSI)
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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
• SEDTrace EEG Electrode Set Sia Napoli 2012

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.
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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

4 channel a EEG State index of the patient
EMG
Density Spectral
Array (DSA)

NeuroSENSE
NS-701
bilateral brain monitor
designed with independent
indexes for each brain
hemisphere

• 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
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

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

Paziente adeguatamente anestetizzato
Tps 4 mg/kg
prep
Iniz chir
Max stimul.
Sospens
N2O
risveglio

Paziente non adeguatamente anestetizzato
Tps 4 mg/kg
prep Iniz chir
Max stimul.
Purposefu
l mov
Sospens
N2O
risveg
lio

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

• 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

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

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

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

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) time-
averaged 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

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. (ClinicalTrials.gov
number, NCT00281489.) )
Sia Napoli 2012

Deep anesthesia is too deep?
• Monk TG, Saini V, Weldon C, Sigl JC. Anesthestic management and one-
year 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

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):545-
56
• 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

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

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

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

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.

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!

Technical points
• Alway check electrodes status and position
• Check impedance(skin degrease)
• Automatic checking

Limits of pEEG
• oversimplifications,
• violations of mathematical rules,
• non-linear components
• Misunderstandings
–Use them as a clinical help,but not as
a scientific tool!

OTHER DEPTH OF
ANESTHESIA MONITORS

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.
RBeene@UTmem.edu
Sia Napoli 2012

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

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
and amplitude vary depending upon the patient state.
Sia Napoli 2012

OMT waveform for normal, sedated, and brainstem
dead patients
Sia Napoli 2012

Welcome to EyeTect.net
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

Robertson J,Timmons S..Non-invasive brainstem monitoring:
the ocular microtremor . Neurological Research 2007; 29: 709-
711
• 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

Stress index
and….
Surgical stress response

PULSE PLETHYSMOGRAPHY
SURGICAL
STRESS INDEX

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

PLETHYSMOGRAPHIC
APPLICATIONS …….SPI…..SSI…..

• 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.

construction of the SSI;
surgical stress index
heart beat interval
Vascolarizzaz periferica cuore

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.

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

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.

Measured parameters
• number of skin conductance fluctuations
(NSCF)
• Amplitude of skin conductance fluctuations
(ASCF) (microsiemens)
• Mean SCL (microsiemens)

Anesth induction Stable anesth without stimulation
Stable anesth :+stimulation Emergence

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

METTIAMO D’ACCORDO
TUTTI?
Put it all together…………

FUTURE TRENDS:COMBINATION
OF……

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 intra-
surgery 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

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.

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

Safety vs adequacy
• Monitors for :
• safety:
– ECG,BP,SaO2,etCO2,FiO2,CO,NIRS…
• titration(adequacy);
– pEEG,AEP,SSI,Sweat…

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

While some must watch while some
must sleep.Shakespeare Hamlet,Prince od Danmark,atto
III,scena II
Act III. Scene II

THE END
Eternal vigilance is the price
of freedom

• 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 open-
eye 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
monitor.
Sia Napoli 2012

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

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).
(5) skin incision and start of surgery, 8) strong surgical stimulus to the uterus region,
1,7,10 )Propofol
concentration increase

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

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

Esempi di registrazione dello NFSC dei Casi
clinici dello studio diA 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

BETTER P EEG MONITORS
?OR ANESTHESIOLOGISTS?

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 !!!

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).

• 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

• 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 non-
parametric ROC area. Stat Med
1996;15:1199–215

Plasma alfentanil vs blood propofol concentrations
associated with a 95% probability of no response to
surgical stimuli
Sia Napoli 2012

Interaction between remifentanil and isoflurane
Isoflurane concentration reduction by increasing remifentanil whole
blood concentration.Anesthesiology 85:721-8, 1996
Sia Napoli 2012

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.

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
response are shown.
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. 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
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.

Fig. 4. Pharmacodynamic curves
from the models showing the
effect of different combinations of
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

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