Pediatric Anesthesia ISSN 1155-5645

REVIEW ARTICLE

The EEG signal: a window on the cortical brain activity

Isabelle Constant & Nada Sabourdin
Department of Anesthesiology, Armand Trousseau Hospital, AP-HP, UPMC, Paris, France

Keywords
EEG < audit; depth of anesthesia < audit;
monitors < equipment; general anesthesia;
neurodevelopment
Correspondence
Isabelle Constant, Service dAnesthesie-
Reanimation chirurgicale, Hopital denfants
Armand Trousseau, AP-HP, UPMC, 26 av.
du Dr Arnold Netter, 75571 Paris Cedex 12,
France
Email: isabelle.constant@trs.aphp.fr
Section Editor: Neil Morton
Accepted 13 April 2012
doi:10.1111/j.1460-9592.2012.03883.x
Summary
The accurate assessment of the depth of anesthesia, allowing a more accu-
rate adaptation of the doses of hypnotics, is an important end point for
the anesthesiologist. It is a particularly crucial issue in pediatric anesthesia,
in the context of the recent controversies about the potential neurological
consequences of the main anesthetic drugs on the developing brain. The
electroencephalogram signal reects the electrical activity of the neurons in
the cerebral cortex. It is thus the key to assessment of the level of hypnosis.
Beyond visual analysis, several monitoring devices allow an automated
treatment of the electroencephalographic (EEG) signal, combining time
and frequency domain analysis. Each of these monitors focuses on a spe-
cic combination of characteristics of the signal and provides the clinician
with useful information that remains, however, partial. For a comprehen-
sive approach of the EEG-derived indices, the main features of the normal
EEG, in adults and children, will be presented in the awake state and dur-
ing sleep. Age-related modications accompanying cerebral maturation
during infancy and childhood will be detailed. Then, this review will pro-
vide an update on how anesthetic drugs, particularly hypnotics, inuence
the EEG signal, and how the main available monitors analyze these drug-
induced modications. The relationships between pain, memory, and the
EEG will be discussed. Finally, this review will focus on some specic EEG
features such as the electrical epileptoid activity observed under sevourane
anesthesia. The EEG signal is the best window we have on cortical brain
activity and provides a fair pharmacodynamic feedback of the effects of
hypnotics. However, the cortex is only one of several targets of anesthesia.
Hypnotics and opiates, have also subcortical primary targets, and the EEG
performances in the evaluation or prediction of nociception are poor. Mon-
itoring subcortical structures in combination with the EEG might in the
future allow a better evaluation and a more precise adaptation of balanced
anesthesia.

activity (mainly cortical) over time. The tracing is a

Basics
The EEG is today the main element allowing us to
measure the depth of anesthesia or, more precisely, the
level of hypnosis. This central role is explained by the
easy and noninvasive nature of the monitor, and
because the main hypnotic agents cause characteristic
and dose-dependant changes in the signal it measures.
The EEG is a representation of cerebral electrical
sum of excitatory and inhibitory postsynaptic activi-
ties. Axonal transmission contributes little to the sig-
nal. The recorded differences of potential come mainly
from pyramidal cells, which have long dendrites
oriented perpendicular to the cortical surface. This
geometry allows the summing of millions of those dif-
ferences of potential. When the cortex is quiet, the
pyramidal cells are synchronized, and the EEG shows

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EEG in pediatric anesthesia
wide and slow complexes. Inversely, during cortical
stimulation, these cells are desynchronized, and the
tracing shows rapid oscillations and low-amplitude sig-
nal.
EEG activity, as a biorhythm, is inuenced by age
and environment, and shows circadian variations.
The amplitude of the EEG signal is 10100 lV, thus
100 times weaker than that of an electrocardiogram.
Analysis of the EEG trace
Each of our states of awareness, awake, slow sleep,
and deep sleep has its characteristic rhythm of EEG
oscillation. The rhythmicity is a result of interactions
between the thalamus and the cortex (1).
Visual analysis of EEG
The EEG tracing can be analyzed visually, without
mathematical tools. It is a complex mixture of oscilla-
tions of different frequencies (calculated by the wave
length, expressed in Hz (hertz), the number of waves
per second). Historically, the rst analysis of EEG
consisted in a description of the main oscillations in
terms of amplitude, form, and duration. Classically,
this produces four types of waves in the frequency
interval of 030 Hz (Figure 1).
l Beta rhythm (b), characterized by rapid oscillations
of 1330 Hz and around 30 lV amplitude, is the
characteristic tracing of the awake alert subject
who is actively thinking. This rhythm would result
from cortico-cortical activity.
l Alpha rhythm (a), the rst described historically, cor-
responds to that of a subject who is awake with eyes
closed, relaxed, or meditating, with a frequency of 8
13 Hz and an amplitude of 3050 lV. This tracing
may be the result of the interaction of cortical and
thalamic pacemakers (cortico-thalamic network).
Beta () 1330 Hz
Alpha () 813 Hz
Theta () 48 Hz
200
V [V]
Delta () 0.54 Hz 100
0 neuroelectrophysiological denition (d, h, a, b).
0 1 2 3 Time [s] 4
Figure 1 Main constitutive waves of the EEG.
540
I. Constant and N. Sabourdin
l Theta rhythm (h) is the rather slow frequency
between 4 and 7 Hz, with an amplitude of
50100 lV. This rhythm is observed in light sleep
(stage 2) and may represent the inhibitory action of
GABAergic interneurons affecting the cortico-tha-
lamic network. It could be associated with limbic
activity (memory and emotions).
l Delta rhythm (d) has a slow frequency between 0.5
and 34 Hz, and a large amplitude (100200 lV).
This rhythm is observed in deep sleep and coma. It
is generated by the cortex with no sensory input
(cortico-thalamic dissociation).
l Gamma rhythm (c), described recently, consists of
very rapid oscillations above 30 Hz. This rhythm
may be associated with consciousness; that is, the
association of input from different cerebral areas to
form a coherent concept. Reecting the intercon-
nection of cortico-cortical and cortico-thalamo-cor-
tical networks (loop activity), this rhythm may be
involved in the processes of perception.
Automated analysis of EEG
With the technology allowing the digitizing and analy-
sis of these analog signals has come a more sophisti-
cated analysis, both in time and in frequency domains
(2).
Time domain analysis
The time domain analysis allows a measure of mean
signal amplitude, frequency, and the burst suppression
ratio (BSR), which represents the proportion of time
the EEG trace is at.
Frequency domain analysis
l Spectral analysis (Figure 2) is derived from the
decomposition of light via a prism. It is based on
a mathematical process called the fast Fourier
transform (FFT), which separates a complex sinu-
soidal wave into a sum of simple wave forms of
specic frequency and voltage. The result is a
spectrum with, for the abscissa, a frequency scale
in Hz, from which are plotted the spectral powers
of each constituent oscillation. Various numerical
parameters can be deduced from the spectral
analysis of the EEG: the total spectral power, in
microvolts2, which is a measure of the overall sig-
nal variability; the spectral power of four constitu-
ent frequency bands according to the
The spectral power of the different bands is
commonly expressed as a percentage of total
power, which allows evaluation of the relative
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Pediatric Anesthesia 22 (2012) 539552
I. Constant and N. Sabourdin
Figure 2 EEG traces recording at baseline,
and under general anesthesia and the
corresponding spectra. The F95 (the
frequency under which occurs 95% of total
spectral power) and the F50 or median
frequency (the frequency under which
occurs 50% of total spectral power) are
represented. General anesthesia is
associated with an increase of slow
oscillations (delta and theta), which results
on the spectra, in a shift to the left of the
F50 and the F95.
contribution of each band to the global variabil-
ity of the signal. One can also determine the F95
(the frequency under which occurs 95% of total
spectral power) and the F50 or median frequency
under which occurs 50% of total spectral power.
These calculations allow statistical comparisons
between different EEG traces.
l The bispectral analysis is a second level of analy-
sis in the frequency domain. Preceded by an
FFT, this process compares two by two the
waveforms to nd a third sinusoid (harmonic)
that measures the degree of synchronization
between the two waveforms, in terms of phase
shift (lag). Having examined the pairs of wave-
forms, the degree of synchrony is calculated
between the number of harmonics and the num-
ber of waveforms of the spectrum. Synchroniza-
tion is near 0 when the subject is awake, that is,
there is little synchrony between waveforms. The
number rises with the increasing depth of anes-
thesia, similar to the way the EEG becomes more
synchronous during coma.
l Measure of entropy (approximate or spectral) or
complexity. The principle is the following: if you
compare successive segments of EEG, the varia-
tion from one to the next may be described by a
mathematical model. The last segment in the ser-
ies may obey or diverge from the model, more or
less. If it follows the model, the regularity of the
signal is high and the predictability is good: one
can say the entropy and complexity are low. As
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Pediatric Anesthesia 22 (2012) 539552
EEG in pediatric anesthesia
individual segments vary from the general form
of the series, complexity grows and regularity
and predictability diminish. If the various EEG
segments bear no relationship to one another,
and analysis of a particular EEG segment does
not allow prediction of the subsequent trace,
entropy and complexity are maximal. It has been
written that the entropy and desynchronization
of the EEG increase during awareness or con-
scious thinking during anesthesia. Thus, these
parameters are high during the awake state and
diminish with deepening anesthesia.
EEG-based monitoring devices
The EEG varies in a dose-dependent fashion with the
hypnotic agent. However, in some particular conditions,
the raw EEG can be a misleading source when conduct-
ing anesthesia and evaluating anesthetic depth. This
weakness is due in part to differing effects depending on
the agent used (halogenated vs IV hypnotics, for exam-
ple) and also to the difculty in monitoring an analyzing
the raw EEG while conducting the anesthesia. These
problems lead to the development of more sophisticated
EEG-based monitors, with performance enhanced by
the use of algorithms which integrate parameters derived
from spectral analysis of the raw signal. Among these
monitors, the bispectral index (BIS; Covidien, Boulder,
CO, USA), the spectral entropy (Entropy, GE Health-
care, UK), and the Narcotrend (Schiller, Switzerland)
have been evaluated in children.
541
EEG in pediatric anesthesia
100
Bispectral index
80 Beta ratio
60
Bispectral analysis
Analysis
40
20 Burst suppression ratio
Hypnotic dose
Figure 3 Bispectral index calculation, based on frontal EEG trace
using a secret algorithm including beta ratio, bispectral analysis,
and burst suppression ratio.
The bispectral index (BIS) (Figure 3)
The BIS is calculated from three sources: the spectral
analysis (which permits calculation of the beta ratio),
the bispectral analysis (which basically makes an esti-
mation of the synchronization between pairs of traces),
and the temporal analysis including the periods of at
EEG or nearly at EEG. So, the three parameters in
the BIS algorithm are as follows:
l the synchfastslow, or degree of synchronization,
a parameter derived from the bispectral analysis
of the EEG this increases with depth of anes-
thesia.
l The beta ratio, the percentage of rapid beta fre-
quencies measured by spectral analysis of the
EEG, predominating during light sedation.
l The BSR, or proportion of at or almost at
EEG during deep sleep.
These three factors are weighted according to the level
of the BIS value. Thus, for a BIS above 60 (sedation),
the beta ratio is favoured, whereas during surgical anes-
thesia (6040) the BIS predominates and under deep
anesthesia (BIS < 40) the BIS varies linearly with the
BSR. In addition, the XP version of the BIS measures
and subtracts the electromyograph (EMG) contribution
to those parts of the EEG which are included in the cal-
culation.
The Entropy
The measure of spectral entropy is made from an ana-
lysis of the frontal EEG. The calculation is based on a
public algorithm that estimates predictability and regu-
larity of the signal. The entropy monitor produces two
numerical measurements, which differ by the frequency
interval at which they are calculated (3,4):
l The value of state entropy or SE varies from 0
(at EEG) to 91 (awake) and is calculated on a
frequency interval of 032 Hz reecting the clas-
sical EEG oscillations.
l Response entropy or RE is calculated on the
interval of 047 Hz, thus going beyond the EEG
542
I. Constant and N. Sabourdin
frequency to include, in theory, the range of the
EMG oscillations and the subclinical muscular
contractions, which may indicate insufcient
depth of anesthesia or insufcient analgesia (mus-
cular activity in response to noxious stimulus).
l In addition, the entropy calculation includes a
temporal factor of percentage of time with at or
nearly at EEG in deep anesthesia.
The Narcotrend
Commercialized in 1981, this monitor is based on spec-
tral analysis of the frontal EEG and produces a classi-
cation A to F with three subclasses. They are derived
directly from a calculation of the spectral power of
each band, delta, theta, alpha, and beta (5).
Class A and B correspond to awake state; D to E
represent surgical anesthesia; and F corresponds to
burst suppression. In parallel, to permit comparison
with other monitors, the Narcotrend produces a value
on a scale of 100 to 0 of increasing anesthetic depth.
Of these three monitors, the BIS, because of its
longer time on the market, has been the most exten-
sively studied one in children. All three include a scale
from 100 (awake) to 0 (deeply anesthetized). The scale
is constructed to decrease in value as the EEG regular-
izes and slows. The three monitors are insensitive to
products that do not induce these typical EEG
changes. The BIS does have one added tool, the beta
ratio, which provides a more accurate evaluation of
the signal with higher frequencies. This may explain its
sensitivity to periodic epileptoid features.
Regarding the Entropy monitor, the State Entropy
values tend to evolve like the BIS, with however a tar-
get interval, which probably needs to be adjusted (6).
It should be noted that the Entropy does include the
EMG factor, as additional information, but for the
moment its utility is not demonstrated.
The Narcotrend has been used mainly in Germany.
Because of the difculty in calibration, its use is less
appealing. However, it is the only one with a pediatric
algorithm. Its changes seem parallel to those of the
BIS.
Main characteristics of the normal EEG
EEG in adults
In the awake subject, the main frequency is the beta
rhythm (>13 Hz) with low amplitude (1020 lV).
With eye closing, there is an immediate enrichment
with alpha (813 Hz) waves of slightly higher ampli-
tude (2040 lV). When the subject becomes tired and
tends to fall asleep, the alpha rhythm disappears and is
replaced by slower and more ample oscillations called
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I. Constant and N. Sabourdin
theta (47 Hz, 4080 lV). During deep sleep, the EEG
waves are slower (<3 Hz and 100120 lV).
In the awake subject, some pathological factors such
as hypocapnia, hyponatremia, hypocalcemia, hypothy-
roidism, hypothermia, hypoxia, and hypoglycemia may
cause a slowing of the EEG.
Specific features of the pediatric EEG
The age-dependant EEG changes reect the process of
cerebral maturation, in particular the neuronal myeli-
nation (7). (Figure 4)
In the awake state, some EEG parameters evolve
from birth to adolescence. Basically, the newborns
EEG is rich in slow oscillations; the dominant fre-
quency of the EEG increases progressively with age, as
the amplitude of oscillations diminishes. This matura-
tion is quite rapid in the rst year of life and pro-
gresses more slowly thereafter.
Developmental stages in detail:
l From birth to 2 months: Sleep spindles appear.
l From 3 to 5 months: Parieto-occipital sinusoidal
activity appears, announcing alpha rhythm, with
increasing frequency: from 46 Hz initially to 8
9 Hz by the age of 3.
l In the normal child aged 3 years and older: The
alpha parieto-occipital rhythm, initially discreet and
slow (8 Hz), with high voltage and asymmetry.
Theta rhythm is abundant, diffuse, and mixed with
alpha in the posterior leads and predominates. Slow
waves appear, grouped in bursts, and become
rhythmic at 23 Hz.
l From 3 to 10 years: Alpha rhythm becomes more
important and abundant, with voltage up to 60 lV,
1 sec
1 month
1 year
3 years
6 years
12 years
Adult
Figure 4 EEG changes with age. In the newborn, the awake trace
shows slow waves of high amplitude. The latter diminishes with
age, and the dominant frequency of the constituent waves increase
until adolescence when it achieves the adult pattern.
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Pediatric Anesthesia 22 (2012) 539552
EEG in pediatric anesthesia
with an increasing reactivity; theta waves become
rare in the occipital leads and are seen more clearly
in parietal and posterior-frontal areas. Slow waves
disappear, although they are seen occasionally in
certain individuals in posterior leads.
At this age, hyperpnea (hyperventilation) induces
the appearance of slow and generalized hypersynchro-
ny, from posterior to anterior. This phenomenon is
practically universal at 35 years of age, but becomes
less pronounced with maturation.
l From 10 to 14 years: Certain patterns become more
clear: ample alpha rhythm, limited abundant theta,
and slow patterns becoming less evident or more
organized as posterior slow waves.
l From 14 to 19 years: Alpha rhythm predominates
with reduced voltage to adult levels (50 lV), theta
becomes more discreet, and posterior slow waves
disappear. Asymmetry diminishes from its prior
prominence in the very young.
l After 19 years: The tracing is that of the adult,
although there may remain some theta activity.
Posterior slow waves have generally disappeared.
EEG and Anesthesia
Effects of hypnotics
The GABAergic anesthetics have EEG effects similar
to that of physiologic sleep, with the exception of
those seen in deep anesthesia (burst suppression or at
EEG).
In general, the effects of these agents can be summa-
rized as follows: the effects are proportional to the
potency of the GABA stimulation, which is responsible
for cortical inhibition. Classically, the effect is
described as biphasic, with initial stimulation followed
by inhibition (8) (Figure 5).
l At subanesthetic doses (early sedation), the IV and
inhaled hypnotics induce rapid oscillations (mainly
beta).
l At anesthetic dose, there is an increasing amplitude
of the signal with a decreasing frequency. Rapid
alpha and beta waves diminish as slow theta and
delta waves supervene. This is measured as an
increase in total spectral power, dependent mainly
on oscillation amplitude, and associated with a shift
to the left (slower frequencies on the spectrum) of
F50 and F95.
l At supra-anesthetic doses or more precisely, under
very deep anesthesia, most of the hypnotics induce
a subtotal inhibition of EEG electrical activity. The
tracing is nearly isoelectric with short salves of slow
activity (burst suppression), which disappear with
further deepening of anesthesia (at EEG).
543
EEG in pediatric anesthesia
Awake : Fast oscillations of small amplitude
Sedation : Fast and ample oscillations
Anesthesia : Slow and ample oscillations
50 Burst suppression
mvolt
0 0
50
Benzodiazepines, used as sedative agents, show only
the rst part of the previously described EEG changes
(sedation). Benzodiazepines decrease alpha activity and
increase beta, with EEG effect reecting blood levels
of the drug. Quantitative EEG parameters have been
shown to provide continuous, objective reproducible,
and sensitive measures of the central nervous system
effects of benzodiazepines as anticonvulsant activity
(9). Changes in amplitude in 11.530 Hz frequency
band of the EEG (beta) is a relevant measure of the
afnity and the intrinsic efcacy of midazolam at the
central GABAbenzodiazepine receptor complex (10).
Ketamine and nitrous oxide are NMDA receptor
antagonists that have modest EEG effects far different
from those of the GABA agonists. They are known to
activate the electroencephalogram, despite their seda-
tive effects (11). They increase rapid beta waves, and
under certain conditions increase the BIS value; how-
ever, most of the time the addition of nitrous oxide or
ketamine under general anesthesia does not change the
value of the EEG-derived parameters (12).
Compared to the racemic ketamine, the S + keta-
mine seems to have a more potent effect, associated
with an increase in slow EEG waves when used at high
doses (13).
Xenon is associated with an increase in fast oscilla-
tions at low doses (fe:30%) (14), while increase in slow
waves may appear at high concentrations (Fe 70%) (15).
Interaction of EEG and muscle relaxants
Muscle relaxants have no direct action on the EEG;
however, the suppression of waveforms coming from
544
I. Constant and N. Sabourdin
50
mvolt
0
50
50
mvolt
0
50
50
mvolt
50
Figure 5 EEG changes and anesthesia.
possible contraction of cranial muscles under the EEG
electrodes might interfere with the measurement. These
are rapid oscillations 2080 Hz and can inuence the
calculations in a portion of automated EEG analysis,
with their upper limit of 3040 Hz. Supporting this is
the observation that in the adult under light propofol
anesthesia, the BIS value diminishes with use of muscle
relaxants (16). In children under light levels of propo-
fol anesthesia, this effect may be seen, but not under
sevourane anesthesia (Figure 6) (17).
In the adult under light sevourane anesthesia
(1.2%), administration of muscle relaxant (95%
depression of T1) does not change the BIS reading,
but may inhibit the increase in BIS seen during tetanic
stimulation. The explanation of this is not clear, per-
haps deafferenting sensitive muscle or suppression of
EMG effect on EEG is the cause (18).
Effects of narcotics
High doses of narcotic agents may cause a slowing
with large amplitude waveforms and without burst
suppression. These effects are only seen with high con-
centrations, well above those used for routine balanced
anesthesia. In their ordinary dose, these agents do not
inuence the EEG to a noticeable degree (Figure 7).
The weakness of this effect is also tied to the intensity
of the painful stimulus (balance of activation related
to pain and inhibition related to narcotic).
In terms of reaction to pain, the narcotic agents
reduce the EEG changes during painful stimulus,
which testies indirectly of their efcacity. Because of
this relatively minor effect on the EEG, all EEG-based
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Pediatric Anesthesia 22 (2012) 539552
I. Constant and N. Sabourdin EEG in pediatric anesthesia

*p<0.05, **p<0.01, c+ versus c-

Propofol concentration (gml1) Fe sevoflurane (%)

Figure 6 Effects of myorelaxants on the bi-
Curarisation decreases the BIS only under low concentrations of propofol (Cp =
spectral index in children, anesthetized with
2 et 3 gml1)
propofol (left) and sevoflurane (right). From
(17) and personal data. Under sevoflurane anesthesia, curarisation does not influence the BIS

Effects of Opiods (alfentanil 20 mcgkg 1) on HR, BIS, SE and RE the decision algorithms that generate a higher BIS
140 score and indicate a lack of analgesia.
120 *** The value of the EEG or an EEG-derived parame-
ter in predicting movement attributed to a painful
HR, BIS, SE or RE

100
stimulus under anesthesia depends on the prole of
80 the relationship between the anesthetic agent and the
60
EEG parameter: thus, if the concentration being
examined lies in the horizontal portion of the dose
40
response curve, the relationship will be weak, but if it
20 lies in the steep part, the predictive value will be bet-
0 ter. This explains why the BIS is more predictive dur-
Heart BIS SE RE ing propofol infusion than under sevourane
Rate anesthesia. The motor response to each hypnotic
Before alfentanil agent, which is mediated by cortical and spinal mech-
After alfentanil
anisms, is in proportion to the agents specic corti-
Figure 7 Effect of alfentanil (20 l/kg) on heart rate (HR), bispectral cal, subcortical, and spinal actions (spinal effects of
index, state entropy (SE), and response entropy (RE) in children sevourane are more marked than for propofol) (20).
anesthetized with sevoflurane. From (57) and personal data. These (dissociated) effects have been demonstrated
in an elegant study by Velly based on simultaneous
recording of cortical and subcortical (thalamic) EEG
monitors of depth of anesthesia are poorly sensitive to in anesthetized subjects under sevourane and propo-
narcotics. fol. They found that the cortical inhibition preceded
the subcortical and that the features of the cortical
EEG allowed prediction of loss of consciousness, but
EEG and pain
inversely, the subcortical recording predicted the reac-
In a schematic sense, pain causes EEG activation in tion to laryngoscopy (21).
the deeply asleep patient, similar to a startle, with Under balanced anesthesia, in the child as in the
decrease in slow delta and augmentation of fast alpha adult, the BIS does not predict response to painful
and beta. This depends on the type of stimulus and on stimulus with accuracy, because the narcotics used in
the degree of pain (articular > muscular > cutaneous) balanced anesthesia have little EEG effect. Further-
(19). In the anesthetized patient (with hypnotics), the more, if the BIS reaction to nociceptive stimulus indi-
same response is observed, similar to a startle, and is cates insufcient analgesic or hypnotic anesthesia
diminished by the increasing depth of anesthesia or by levels, the opposite is not true. In fact, in children
increasing the dose of analgesic agent. This activation under sevourane (Fe 2.5% in O2-N2O, 50-50) in
of rapid frequencies in response to pain is the basis of steady state, a skin incision induces a pupillary reex

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Pediatric Anesthesia 22 (2012) 539552
EEG in pediatric anesthesia
(dilatation, via subcortical pathways) in all patients,
while the BIS remains unchanged (22).
EEG and recall
Episodes of intraoperative recall occur in children and
perhaps more frequently than in adults (about 1%)
(23,24). In addition, 1020% of children describe
dreams during anesthesia (25). Such dreaming in adults
is thought to be associated with a higher risk of recall,
and their occurrence reminds us that the anesthetized
brain is not inactive.
There is no study in children on the use of EEG or
its derived parameters to diminish the frequency of
recall. The explicit character of recall requires cortical
activity, which is theoretically inhibited by low doses
of hypnotics. Such an effect is measurable by BIS, and
in adults, a value of 4060 is thought to be a good tar-
get range for suppressing recall; however, the useful-
ness of the BIS monitor for preventing awareness is
still debated (26,27).
Implicit recall is more complex, and the factors that
inuence it are being studied in adults. Some studies
show ability to learn and remember words by subcorti-
cal pathways, even under sedation and general anesthe-
sia deemed adequate by BIS. The signicance of such
episodes including their cause and deleterious effects is
unknown. The cortical EEG is not of interest in these
studies, because the processes are mainly subcortical
and are inhibited only by deeper levels of anesthesia
than that required to inhibit explicit recall. The cortical
Baseline
0.0000 5.0000 10.000 15.000 20.000 25.000 30.000
Propofol infusion (1 mgkg1min1) during 5 min
F50
0.0000 5.0000 10.000 15.000 20.000 25.000 30.000
Propofol infusion (1 mgkg1min1) during 6 min
Burst suppression
End of propofol infusion
F50
0.
Eye opening
100
volts
0
100
0.
0 5 sec
546
I. Constant and N. Sabourdin
vs subcortical relationship of each agent would dictate
the utility of cortical monitoring, and the possible
effects of narcotics on subcortical learning, particularly
under stressful conditions, further complicates the
picture.
EEG and anesthesia for the child
Studies of the pediatric EEG under anesthesia are few
and focus mainly on paroxysmal epileptoid phenom-
ena. In spite of this short bibliography, one may pos-
tulate that the action of anesthetic agents on the EEG
above the age of 1 year are comparable to those in
older patients, although the concentration to attain a
specic effect may be correlated with age. In this idea,
the evolution of the EEG tracing under propofol infu-
sion in the child from age 310 illustrates the different
proles previously described in the adult (28) (Fig-
ure 8). In this context, the main spectral parameters
(F50, F95, and delta ratio) are correlated with plasma
concentration during continuous infusion. In addition,
in the child anesthetized with halothane or sevourane,
one sees the various proles described in the adult
(29). It is interesting to note that in the child aged 4
12 years, the resting awake spectral power is higher
than in the awake adult (because of greater amplitude
of the waveforms), with a similar distribution of the
various waves (Figure 9). These observations are
also seen under anesthesia; the spectral parameters
(F50, F95, delta ratio, and total spectral power) are
correlated with endtidal sevourane concentrations.
F50 SEF
Hz
SEF
Hz
Figure 8 EEG changes during propofol ane-
sthesia in children. (Personal data). In
children receiving IV propofol (bolus of
SEF 6 mg/kg during 6 min), the EEG trace
shows slow oscillations up to the
occurrence of burst suppression periods.
5. 10. 15. 20. 25. 30 The corresponding spectrum shows a shift
of the F50 and SEF to the left (slow
F50 SEF frequencies). During recovery, when the
child opens his eyes, the EEG trace and the
corresponding spectrum are close to those
5. 10. 15. 20. 25. 30
recorded at baseline.
2012 Blackwell Publishing Ltd
Pediatric Anesthesia 22 (2012) 539552
I. Constant and N. Sabourdin
()
Delta waves ()
v2 or % (slow oscillations)
60
50
40
30
20 * 15
* 10
10
* 5
**
0 0
0 1% 2% 4%
Exp ire d sev ofluran e
CHILDREN (9 4 yrs)
ADULTS (19 6 yrs)
Figure 9 Spectral component of EEG in prepubertal children (blue)
and young adults (red) under sevoflurane anesthesia. From (28). The
spectral power of the main slow (delta on the left) and fast (beta on
the right) oscillations. In children as in adults, the spectral power of
delta oscillations increases and the spectral power of beta oscilla-
tions decreases with the depth of anesthesia. At all studied points,
the spectral power which is on the y axis, reflecting the amplitude of
Davidson (30) found in the child aged 212 years a
decrease in spectral power and an increase in F90 (not
F95) during awakening from anesthesia; however these
variations were not found in the young infant
(<6 months). In the child over the age of one, expired
sevourane concentration associated with a specic
BIS value (=50) (FeBIS50) decreases as age increases
(31,32). This inverse relationship of FeBIS50 to age is
dissociated from the relationship of minimal alveolar
concentration required to inhibit movement response
to skin incision (MAC) to age, which theoretically
does not change from 6 months to 12 years (33). This
dissociation is related to the nature of MAC (move-
ment in response to noxious stimulus) and reects the
level of subcortical (brainstem and spinal cord) inhibi-
tion that is not measured by the BIS. In the same vein,
the BIS value at one MAC sevourane rises as the age
of the child falls (34), suggesting again that MAC is
not a good predictor of hypnotic power of a haloge-
nated agent. A bias because of the BIS algorithm, cal-
culated on adult traces, is unlikely because pediatric
EEGs specicities should lead to opposite results
(EEG slower and BIS lower as the child is young).
A similar effect of age is found for propofol infu-
sion: for a given BIS level (BIS 50 for example), a
higher concentration is needed in the child compared
to the adult (35) in whom this target concentration
actually decreases with greater age.
2012 Blackwell Publishing Ltd
Pediatric Anesthesia 22 (2012) 539552
EEG in pediatric anesthesia
v2or % Beta waves ()
(fast oscillations)
45
40
35
30
25
20
**
** *
*
0 1% 2% 4%
Ex pire d s ev oflu ra ne
v2 % of TSP
v2 % of TSP
oscillations, was higher in prepubertal children compared to young
adults despite these two populations being very close in age. How-
ever, despite these significant and relatively expected differences in
amplitude of oscillations between adults and children, the relative
parts of contribution of oscillations expressed in percentage of total
power do not differ.
Comparative EEG effects of propofol and sevoflurane
These are the two main agents used for anesthesia
in children and adults. They both produce clinical
effects of rapid induction and emergence from anes-
thesia, with excellent cardiovascular tolerance. With
this similarity of clinical effect, quite different EEG
proles are seen. During induction, while similar
dynamic clinical events are occurring, the EEG pro-
les of the two agents differ markedly. With propo-
fol, the EEG demonstrates progressive slowing
associated with falling BIS values, until intubation,
while during the same events the EEG with sevou-
rane shows a paradoxical and biphasic progression
(see further) (36). In steady-state measurements, fur-
ther deepening of anesthesia with propofol inhibits
the cortex more and more, until burst suppression
(progressive lowering of BIS). One sees this same
slowing with sevourane until just over 3% Fe (1.2
MAC) after which there is acceleration of the EEG
frequencies with appearance of epileptoid signs, rst
isolated and then periodic (2 MAC) (37).
Electrical epileptoid effects of sevoflurane
EEG changes specific to sevoflurane anesthesia
Sevourane induction and deepening of anesthesia fol-
low a similar pattern to that described above, with one
547
EEG in pediatric anesthesia
exception: during rapid induction with 78% sevou- a background of slow (delta) activity or burst suppres-
rane in O2-N2O (50:50), the EEG shows a brief increase
in beta activity occurring around the loss of eyelash
reex (3060 s after beginning induction), which is rap-
idly followed by sudden slowing down to <2 Hz delta
activity maximal at the end of the second minute of
induction, and then acceleration to delta predominance
(24 Hz) until pupils are constricted and central. The
bispectral index monitor (BIS) also shows a higher
index number at central pupils than during the middle
of induction, where slowing down is maximal (36).
Some subjects show episodes of burst suppression with
deeper anesthesia (higher endtidal sevourane and
longer duration of anesthesia). Basically, EEG oscilla-
tions at 2 MAC sevourane are faster than at 1.5 MAC
(38), and they seem to be faster under sevourane than
under propofol at equipotent doses.
Epileptiform activity under sevoflurane
Describing electrical epileptiform activity is complex
and differs among authors. An example of this activity
is presented in relation to deepening anesthesia during
sevourane induction in Figure 10.
Spikes are the earliest elements to appear, usually
during delta oscillations (spike-wave). They may be
simple or complex (spike with >2 positive or negative
deexions, multiple spike-waves, or multiple spikes) or
in periodic discharge (rhythmic polyspikes) leading to
periods of epileptiform discharges or frank electroen-
cephalographic seizure. These elements may appear in
BASELINE
SEVO 1%
SEVO 2%
SEVO 3%
SEVO 4%
SEVO 5%
548
I. Constant and N. Sabourdin
sion. Generally, major seizure manifestations (periodic
discharge or frank seizure activity) are observed under
deep anesthesia around the occurrence of burst sup-
pression, sometimes accompanied by tonicclonic
movements, but most often without clinical signs.
Abnormal uctuation in BIS or entropy parameters
caused by EEG epileptoid changes may be observed
(Figure 10).
In adults, during induction with sevourane, risk
factors for the occurrence of epileptiform EEG activity
were hyperventilation (39), female sex, short delay of
onset of anesthesia, and high alveolar sevourane con-
centrations (40). In children during sevourane induc-
tion (8% in O2-N2O, 50-50), Vakkuri (41) described
epileptiform discharges in 88% of children under con-
trolled ventilation. The speed of induction seems to
play a major role: incremental induction (246% of
sevourane) is associated with lower incidence of epi-
leptiform discharges when compared to rapid induc-
tion (6% of sevourane) (42). Under steady-state
conditions in adults, Jaaskelainen and Sato found sei-
zure-like activity in all patients at >1.5 MAC sevou-
rane in 100% O2 (38,43). Under steady-state
conditions, the relationship between expired sevoura-
ne concentrations and EEG-derived parameters such
as the BIS follows a typical prole with a dose-depen-
dant decrease from 0% to 3% and then a rise of the
EEG-derived parameter from 4% to 5% of expired
concentration of sevourane. This paradoxical increase
in the BIS may be explained by a look at the raw
98 89 97
63 81 85
49 51 57
35 21 27
Figure 10 EEG and EEG-based indices
42 27 37 (bispectral index and response entropy and
SE) changes recorded during steady state
periods at different sevoflurane concentra-
tions in children. Some major epileptoid
signs occurred at 4% and 5% of expired
60 35 45 concentrations of sevoflurane, associated
with an increase of the EEG-based indices.
Personal data.
2012 Blackwell Publishing Ltd
Pediatric Anesthesia 22 (2012) 539552
I. Constant and N. Sabourdin
EEG showing polyspikes at 4% and 5%. In children
studied in steady-state conditions, the minimal alveolar
concentration of sevourane associated with major epi-
leptoid signs in 50% of patients was calculated using
the Dixon method, at 4.3% (1.7 MAC), in 100% of
O2. The adjunction of 50% N2O or a bolus of alfenta-
nil seems to have a protective effect (44).
EEG and anesthesia of the infant: some
questions
Although the EEG effects of anesthetic agents on
patients older than 2 years are similar to those
observed in adults, there are unsolved questions for
the infant. In fact, most studies of the automated EEG
in the infant under anesthesia show results quite differ-
ent from those in an older child. In the infant, the Fe
sevourane necessary to reach a steady-state BIS 50 is
higher than in a child over 2 years: 1.55% vs 1.25%,
and the evolution of the BIS during awakening shows
an on-off pattern instead of the progressive change
seen in older patients (32). Caudal anesthesia causes a
diminution of BIS in the child over 2 years at 1.5%
sevourane, but this effect is not seen in the infant
(45). In addition, the differences in BIS seen using hal-
othane vs sevourane, at equivalent MAC over the age
of 2, are not seen in the infant (46). The EEG of the
infant shows episodes of burst suppression (bursts of
activity alternating with electrical silence) more fre-
quently than older children (30). These episodes persist
up to the clinical wakeup and differ from the older
patient who, under deep anesthesia, has prolonged
periods of at EEG. In a similar vein, during sevou-
rane anesthesia, cortical neuronal inhibition, evaluated
either at a BIS = 50 or with a BSR > 50%, occurs at
lower concentrations in the younger infant than in the
child. (30,47). These results emphasize a pharmacody-
namic cerebro-cortical difference in the infant, suggest-
ing the earlier appearance of neuronal inhibition, in
contrast to a later appearance of a subcortical inhibi-
tion, as measured by MAC. Presently, the regular and
blind use of an automated EEG monitor in the infant
under the age of 1 requires more clinical and EEG
investigation, to dene its usefulness in this popula-
tion. These studies are all the more important given
the possible greater susceptibility of this age group to
the toxic effects of general anesthetics, extrapolated
from animal studies (4850). As an opening thought in
this consideration, one may consider the occurence of
burst suppression in more than 50% of pediatric
patients under 2 years of age during routine anesthesia
practice, and the fact is that in newborns, these epi-
sodes are particularly frequent and prolonged (51).
2012 Blackwell Publishing Ltd
Pediatric Anesthesia 22 (2012) 539552
EEG in pediatric anesthesia
The limits of the EEG, in monitoring depth of
anesthesia
As previously described, the EEG provides informa-
tion mainly limited to cortical brain activity.
Using cortical and subcortical recordings of EEG in
patients undergoing neurosurgery, Velly et al. have
demonstrated that quantitative parameters derived
from cortical EEG but not from the subcortical EEG
were able to predict consciousness vs unconsciousness.
Conversely, quantitative parameters derived from the
subcortical EEG but not from the cortical EEG were
able to predict movement in response to laryngoscopy
(21). They conclude that in humans, unconsciousness
mainly involves the cortical brain, but that suppres-
sion of movement in response to noxious stimuli is
mediated through the effect of anesthetic agents on
subcortical structures. This has important implications
for predicting movements with EEG-derived parame-
ters. It is likely that renements in algorithms for ana-
lyzing the EEG will improve our ability to detect
consciousness or unconsciousness. But the risk of
movement in response to noxious stimulation will
probably be much more difcult to assess because it is
under the control of brain structures not monitored
by the EEG.
On the other hand, Mourisse et al. (20,52) demon-
strated that the blink reex (brainstem function) is
more sensitive to sevourane than BIS (forebrain func-
tion), while tetanic stimulus-induced withdrawal reex
(spinal cord) is less sensitive than BIS. These authors
concluded that anesthetics may act differently accord-
ing to the effect site. Up to now, there are very few
pediatric data investigating the relative effect of anes-
thetics on cortical and subcortical sites. A simple way
to consider this issue could be to compare the ratio
between surgical MAC and a given target of cortical
EEG, that is, a BIS value of 50; this was done by
Davidson et al. (31), who have demonstrated an age-
related discrepancy between MAC and EEG suppres-
sion with a less active EEG relative to MAC gradually
as the child grows from one to 12 years; these authors
concluded that the relationship between the two differs
with brain maturation. Recently, using noninvasive
devices, we assessed cortical (BIS derived from EEG)
and subcortical (pupillary reex) response to noxious
stimulus in prepubertal children vs young adults. Our
data suggested that sensitivity to sevourane of some
subcortical structures (i.e. mesencephalic control of
pupillary reex dilatation) is lower in children than in
older subjects. Interestingly, we found some children
with a BIS under 10, and still showing a signicant
pupillary response to noxious stimulation. These nd-
549
EEG in pediatric anesthesia I. Constant and N. Sabourdin

ings suggested that prepubertal children anesthetized
with sevourane may keep subcortical reactivity to
noxious stimulus despite the major cortical inhibition
attested by EEG.
Taken together, all these data support Kissins view
that the search for a reliable index of anesthetic depth
should be transformed into a search for separate
indices of different components of anesthesia (53). So
we need an index allowing assessment of subcortical
activity, and this activity may be considered at multi-
ple levels, for instance diencephalic, mesencephalic,
brain stem. In fact, most of them are based on the
investigation of autonomic responses to nociceptive
stimulation. Among the emerging clinical devices, we
can mention those that assess vascular sympathetic
response (skin conductance) (54), cardiac and vascular
sympathetic response (Surgical Stress Index) (55),
parasympathetic cardiac response (antinociception
index) (56), and nally the pupillometry, which is
based on the assessment of the pupillary reex dilata-
tion induced by nociceptive stimulation and seems a
more sensitive index than hemodynamic parameters
(22).
Conclusions
The EEG is a measurable biorhythm inuenced by the
internal and external environments of the subject, dem-
onstrating circadian variation and changing with age.
The sensitivity of this signal to physiologic and phar-
macologic changes, and its oscillatory nature, make it
a good subject of mathematical analysis of various
types in measuring changes of state of consciousness.
Thus the EEG signal, as a pharmacodynamic window
on the cerebral cortex, is presently the basic element in
evaluation of anesthetic depth, even if the automated
mathematical algorithm only quanties the degree of
cortical inhibition (slowing and synchronization)
induced by anesthetic agents.
Cerebral maturation is measured as a progressive
acceleration of the EEG pattern. In general terms, the
pediatric EEG has specic characteristics according to
age, but after 2 years, the changes induced by anesthe-
sia are quite similar to those in the adult. Nonetheless,
there is a dose dependency related to age.
The two main hypnotic agents used in children,
sevourane and propofol, show different EEG effects,
particularly under deep anesthesia. At higher concen-
trations, sevourane induces signicant epileptoid
activity, the possible deleterious effect of which
remains to be determined.
Over the age of 2, the changes in the EEG in the
maturing pediatric population have little inuence on
the BIS prole compared to that of the adult. How-
ever, for a given level of cortical inhibition, children
require a higher concentration of anesthetic agent than
adults. The pharmacologic implication that the child is
less sensitive to anesthetic agents emphasizes the inter-
est in an effective monitoring of central effects of anes-
thetics in this population.
During infancy, the EEG prole under anesthesia
differs markedly from that of the older child. These
differences are the subject of numerous current studies,
evaluating the effects of anesthetic drugs, in view of
concerns raised by animal studies demonstrating a
toxic effect of these same agents on the developing
brain.
The EEG gives us a useful pharmacodynamic win-
dow on the cortical effects of the anesthetics. However,
it provides information mainly limited to cortical brain
activity. As anesthetics act on both cortical (conscious
processes) and subcortical (nonconscious processes)
structures, we need indices that investigate subcortical
processes, for instance by assessment of autonomic
responses to nociception.
Funding
This research was carried out without funding.
Conflict of interest
No conicts of interest declared.

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