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Proceedings of the 29th Annual International

Conference of the IEEE EMBS
Cité Internationale, Lyon, France
August 23-26, 2007.

FrP2A1.18

Automated Estimation of Sedation depth from the EEG
B.R. Greene, P. Mahon, B. McNamara, G.B. Boylan, G. Shorten,

Abstract— A method is presented for the automatic
determination of a patient’s level of sedation from the EEG. Six
bipolar channels of EEG recorded from 12 adult patients
sedated with low-dose propofol (2, 6-disopropylphenol) were
used to develop a linear discriminant based system for depth of
sedation monitoring using a number of quantitative EEG
measures. A cross fold validation estimate of the performance
of the algorithm as a patient independent system yielded a
sensitivity of 74.70% and a specificity of 81.67%. It is hoped
that the methodology reported here could lead to fully
automated systems for depth of sedation monitoring.

C

I. INTRODUCTION

ONCIOUS sedation allows patients to tolerate
unpleasant procedures by alleviating anxiety and
discomfort. Sedation may also expedite the conduct of
procedures particularly those that require the patient does not
move [1]. With sedation comes risk, in particular those of
cardiovascular and respiratory compromise that accompany
excess hypnotic drug use [2]. Currently many practitioners
rely on intuition and experience to judge depth of sedation.
In the research setting sedation scales [such as the Modified
Observer’s Assessment of Alertness/Sedation Score
(MOAA/S)] [3] are used to quantify depth of sedation. The
disadvantage of this method when applied to clinical practice
is that it requires continuous stimulation (verbal or tactile) of
the patient. Paradoxically this may increase the amount of
hypnotic drug used. Thus the need exists for a reliable,
passive depth-of-sedation monitor.
The electroencephalographic (EEG) is the obvious starting
point. The changes that occur in the EEG during
pharmacologic or physiologic drowsiness, when viewed by
an experienced clinician are unequivocal and objective [4,
5]. These changes include alpha wave drop out in the
posterior brain regions and increased frontal beta activity
during propofol sedation (Table 1) [6, 7]. A number of
commercially available devices including BIS™, Entropy™,
Manuscript received April 2nd 2007. This work was supported in part by
Science Foundation Ireland (SFI/05/PICA/1836).
B.R. Greene is with the Department of Electrical & Electronic
Engineering, University College Cork, Ireland (phone +353-21-490-3793; email: barryg@rennes.ucc.ie).
P. Mahon is with the department of Anaesthesia and Intensive Care
Medicine, Cork University Hospital, Cork, Ireland. (e-mail:
rsimahon@hotmail.com).
B. McNamara is with the department of Clinical Neurophysiology, Cork
University Hospital, Cork, Ireland.
G.B. Boylan is with the School of Medicine, University College Cork,
Ireland (e-mail: g.boylan@ucc.ie).
G. Shorten is with the department of Anaesthesia and Intensive Care
Medicine, Cork University Hospital, Cork, Ireland. (e-mail:
George.Shorten@mailp.hse.ie).

1-4244-0788-5/07/$20.00 ©2007 IEEE

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and Narcotrend™ are used in the context of depth-ofanesthesia monitoring. Each of these monitors is based on
the calculation of one or more quantitative EEG measures [8,
9], that are thought to contain anesthesia/sedation-specific
information. General anesthesia is very deep sedation with
the absence of a cortical response to pain. Some of these
devices [particularly the Bispectral or BIS™ monitor
(Aspect Medical)] have been studied in the context of light
sedation and are unable to reliably distinguish between light
and deep sedation [1]. We set out to determine if the
combination of a number of quantitative EEG measures or
‘features’ could be used to automatically determine a
patient’s level of sedation.
Grade
0
1

Criterion
Awake alpha rhythm
Decrease in α amplitude and α drop out
/ β activity ± theta activity
2
Theta wave activity, sleep spindles / K
complexes
3
Generalised delta activity 20-50%
epoch duration
Table 1: EEG criteria for assignment of sedation grade

II. METHOD
A. Data set
We used an independently validated dataset of EEG
recordings from 12 healthy patients aged 37+/-9yrs
(M:F::4:8), who underwent sedation prior to anesthesia using
propofol (2,6-disopropylphenol). The study protocol was
approved by the Clinical Research Ethics Committee of the
Cork Teaching Hospitals. All patients gave prior written
informed consent.
B. Clinical Protocol
A target-effect site propofol infusion was commenced to
provide a target-effect site concentration of 0.5 µgml-1. The
target-effect site was brain. The target effect concentration
was increased in 0.5 µgml-1 increments every four minutes to
a maximum of 2 µgml-1. A period of 4 minutes was allowed
at each concentration level to allow adequate equilibrium to
be achieved across the blood-brain-barrier. For each patient
the data acquisition period was thus 16 minutes.
C. EEG Acquisition
Nineteen channels of EEG were recorded for each patient
using a NicVue™ digital EEG machine. For the purposes of
analysis and comparison we calculated each quantitative
EEG measure or ‘feature’ in the following bipolar channels:

which normalizes HS to the range 0-1 [9]. The Alpha sub-band is defined as the spectral power in the range 8-13Hz. • Spectral Entropy (HS) • Spectral Edge frequency (SEF) • Relative Alpha band power (Pα) • Relative Beta band power (Pβ) • Relative Delta band power (Pδ) • Relative Theta band power (Pθ) Many of these measures have been used in previously reported studies [7.4Hz and 4-7Hz respectively [16]. Sedation Measurement The EEG recordings were retrospectively assessed by a clinical neurophysiologist blinded to the clinical sedation score.3 16. 116 minutes of EEG were assigned the labeled ‘sedated’ while 76 minutes of EEG were assigned the label ‘non-sedated’. similarly the Beta subband is defined in the range 14-40Hz. A sedation grade was assigned to each time period of four minutes corresponding to a set propofol concentration.9 Mean: 19.8 22. The spectral power in a number of EEG sub-bands was then calculated as the total spectral power in a given frequency range from the power spectral density estimate for each epoch. To identify the artifact sections of each EEG channel a .6 16.• 'P4-O2' • 'P3-O1' • 'Fp1-Fp2' • 'F3-C3' • 'F4-C4' • 'F3-F4' Even numbers by convention refer to electrodes placed on the right side of the scalp. The dataset contained a total of 192 minutes of 19 channel EEG. 11]. 10] and are currently in use in commercially available depth of anesthesia monitors [9. The PSD is calculated in the range 0. There were 48 four minute intervals in twelve patients. F.5. The total EEG power in the range 0.2 16. HS ( X ) = − 1 log N f ∑ P ( X ) log f e Pf ( X ) (1) f Pf(X) is an estimate of the probability density function (PDF) and is calculated by normalizing the power spectral density (PSD) estimate with respect to the total spectral power. Six features for each of the six channels were then combined into a feature vector (of length 36) which was then applied to the classifier. Spectral Edge frequency (SEF) was calculated according to the methodology discussed by a number of authors [1214].0 19. A number of authors have investigated the variation of EEG power bands with sedation and anesthesia [7.5-32Hz for each epoch using a 500-point fast fourier transform (FFT). Nf is the number of frequency components in the PSD estimate.6 17.1. and ‘zero-signal’ artifact caused by the amplifier being ‘powered-off’ in the course of a recording. The EEG spectral entropy (HS) was calculated for 2 second epoch using Eqn. Table 2 summarizes the characteristics of each of the recordings. Twenty nine had evidence of sedation with 19 ‘non-sedated’.6 16.8 Table 2: Record information Sedated Time (mins) 16 4 4 8 12 8 16 12 0 12 12 12 Total: 116 Nonsedated time (mins) 0 12 12 8 4 8 0 4 16 4 4 4 Total: 76 E.6 22. EEG Artifact Rejection The EEG signal often contains variety of biological and non-biological artifacts [17]. Records had a mean duration of 19. Patient # 1 2 3 4 5 6 7 8 9 10 11 12 Record Length (mins) 16. 15]. In this paper we have attempted to reject two kinds of artifact from subsequent analysis.5-32 Hz band. The Delta and Theta sub-bands are defined in the ranges 0. D. Activity in the three other channels is representative of frontal and central lobe activity. The relative power feature for each band was then the ratio of the power in a given sub-band to the total power in the 0. The SEF was then calculated as that frequency (in Hertz) below which 90% of the total spectral power resides.3 17. The EEG for each channel was then considered in epochs of 2 seconds duration. The sedation grade was assigned according to preset criteria set out in table 1.7 34.6 21.8 minutes. namely: ‘movement’ artifacts which are large signal spikes caused by movement of the electrodes.5-32Hz was calculated for each 2 second EEG epoch. Fp1 – Fp2 represents a prefrontal location likely to be contaminated by EMG artifact from the frontalis muscle. The occipito-parietal leads were chosen as alpha rhythm which originates in the posterior cortex is best seen in these leads. Feature Extraction The EEG for each channel was low-pass filtered using a type II Chebyshev IIR filter with a corner frequency of 34Hz to remove power line noise along with out-of-band noise. For the purposes of this analysis any four minute period in which the sedation score was greater then zero was deemed to be ‘sedated’. Each record contained 19 EEG channels and was sampled at 250Hz. The following features were extracted 3189 for each 2 s EEG epoch for each channel. The SEF features for each channel and for each patient were then normalized to have zero mean and unity standard deviation.

21 69. The area under the Combined SEF H Pα Pβ Pδ Pθ Acc (%) 77. The sensitivity (Sens) is defined as the percentage of ‘sedated’ epochs (as labeled by a Clinical Neurophysiologist) correctly identified as ‘sedated’ epochs by the system.07 65.49 70.5 under the curve while perfect discrimination between the two classes will give unity area under the ROC curve. An LD model assumes normal class distributions and the same variance across classes.70 62. . This involved training the classifier model on 11 of the 12 records and using the 12th record to test the classifier performance and then rotating through the 12 possible combinations of training and test sets. A linear discriminant classifier model.89 70. G.55 72.71 0. is used as an index of sedated/non-sedated class discrimination for the patient independent classifier.98 65. A receiver operating characteristic (ROC) curve is a graphical representation of class sensitivity against specificity as a threshold parameter is varied. Weighting of the class conditional mean vectors and common covariance matrix by the duration of each record was implemented as discussed by Greene et al. The performance of the patient-independent system was estimated using cross validation across all records.10 67.28 69. The area under the ROC curve (ROC Area).86. 74.45 61. The mean of the results for all iterations is taken as a patient-independent classifier performance estimate.71 0. H.92 53.77 0.1 shows an ROC plot for the output discriminant value of the patient independent classifier.zero mean EEG signal was first calculated by subtracting the mean of the EEG from each sample and then processing this signal as follows: • The standard deviation of the absolute value of signal was calculated and any signal samples greater than six times the standard deviation were flagged as ‘movement’ artifact. III.70%) while 81.70% of sedated epochs were correctly classified as sedated (sensitivity of 74. Classifier Model A linear discriminant (LD) based classifier model was employed in this study. the epoch was considered to contain artifact.81 ROC Area 0.86 0.63 0.67%). Classifier Performance Estimation The automated depth of sedation monitoring system was considered as a patient-independent or ‘generalized’ classifier.67 59. [18].63 Measure Table 3: Overall performance results for each feature taken individually as well as all features combined together and classified using a linear discriminant classifier model. On a patient independent basis using the combined features. Algorithm Performance Measures The classification accuracy (Acc) is defined as the percentage of 2 s epochs correctly classified by the system. • Any 10 sample epoch whose mean was 100 times smaller than the 5% trimmed mean of the signal was flagged ‘zero-signal artifact’ Any 10 sample epoch on a given channel containing artifact was assigned the value 1.28 67.70 56. All epochs for each channel that did not contain artifact was assigned the value 0. in classifying epochs of EEG as ‘sedated’ or ‘non-sedated’. A random discrimination will give an area of 0.52 Spec (%) 81. (based on the Mahalanobis distance). This ensures that records of differing lengths contribute equally to the training of the classifier. RESULTS Table 3 gives the classification performance for each feature taken individually as well as all features combined. If the mean artifact value across all channels exceeded an empirically derived threshold.32 66. Feature I.38 60. the specificity (Spec) is defined as the percentage of epochs labeled ‘non-sedated’ correctly classified as ‘non-sedated’ by the system.27 66.67% of non-sedated epochs were correctly classified as non-sedated (specificity of 81.32 75. Fig.90 Sens (%) 74. The class conditional mean vectors and a common covariance matrix were estimated entirely from the training data. 3190 ROC curve was 0.77 0. This test provides a measure of the systems’ ability to generalize from the training set and classify ‘unseen’ records as ‘sedated’ or ‘non-sedated’. Similarly. is defined completely by a mean vector for each class and a common covariance matrix.

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