Comparing EEG Patterns in Different Age Groups During General Anesthesia With Sevoflurane
Conditions: Anesthesia
Sponsor: Second Affiliated Hospital of Wenzhou Medical University

 
Comparing EEG patterns in different 
age groups during general anesthesia 
with sevoflurane. 
 
 
 
 
 
 
NTC number: NCT03559504 
Date: 28/7/2018

Comparing EEG patterns in different age groups during general anesthesia with 
sevoflurane. 
 
Background 
Analyzing the raw electroencephalography (EEG) waves during anesthesia is still 
challenging and has not been fully demonstrated. Alterations of consciousness are due to 
effects of anesthetic agents that act on the central nervous system, more precisely, on the 
brain. These alterations are major clinical endpoints of general anesthesia and can be 
analyzed and monitored throughout recordings of surface brain electrical activity, called 
electroencephalography (EEG). EEG is a powerful tool that refers to the recording of the 
brain's spontaneous electrical activity along the scalp and it can be used to measure 
voltage fluctuations which result from ionic current flows within neurons found in the 
brain. The electroencephalogram is increasingly used to measure anesthetic drug effect 
on 
the 
central 
nervous 
system. 
Since, 
analyzing 
the 
real-time 
raw 
electroencephalographic 
signal 
during 
anesthesia 
is 
difficult, 
several 
electroencephalographic monitors have been developed to extract and process 
information and to present the content in a continuous index from 0 to 100. Zero 
represents the deepest level of anesthesia (isoelectric encephalographic line), and 100 
represents the awake state of a patient. The use of electroencephalographic monitors has 
been proven to decrease drug consumption during anesthesia and to lead to a faster 
recovery from anesthesia. Recently, the use of the Bispectral Index® (BIS®) monitor 
(Aspect Medical Systems, Newton, MA) has been shown to decrease the incidence of 
intraoperative awareness. 
Depth 
of anesthesia is 
frequently assessed using 
electroencephalogram processing systems, such as BIS and M-Entropy® (Datex-Ohmeda, 
Helsinki, Finland). The use of these monitors has been claimed to allow more accurate 
drug administration which has the theoretical benefit of avoiding phases of too light or 
too profound anesthesia and the associated risks of hemodynamic instability. Inadequate 
general anesthesia caused by under dosage causes intraoperative awareness whereas 
prolonged anesthesia increases the risk of postoperative complications because of over 
dosage. The most important factor that contributes to the inadequate general anesthesia is 
the current limited ability to determine the level of awareness. In this study, we want to 

analyze the raw EEG waves under general anesthesia using sevoflurane of MAC 1.0 for 
different age groups from 0 to 80 years old.  
Like other organ systems, the nervous system is functionally immature at birth, 
myelination is rapid during the first 2 years and completed by 7 years of age.i Therefore, 
the BIS algorithm cannot automatically be extrapolated to young children. Some 
investigations suggest that BIS may be valid in children older than 2 years of age.ii Only 
one study, as far as we know, evaluated prospectively the correlation of BIS with end-
tidal sevoflurane concentration in children. Regarding the effect of age on BIS values, 
there have been reports comparing the BIS between infants and children or between 
children and adultsiii but there have been no reports comparing the raw EEG waves in all 
age groups (0-80 years old) under sevoflurane of 1.0 MAC. Minimal alveolar 
concentration (MAC) was introduced to compare the potencies of inhalation anesthetic 
agents. Sevoflurane is a commonly used inhalation anesthesia agent today. However, the 
relation between concentration of 1.0 MAC sevoflurane and raw EEG states in different 
age groups is relatively unstudied. In this prospective randomized study we want to know 
if there is any correlation of brain waves under general anesthesia in different age groups. 
It is therefore of neuroscientific interest to assess whether the electroencephalographic 
correlates of sevoflurane-induced unconsciousness have different or similar frequency 
range among the age groups. 
General anesthetic and sedative agents induce highly structured oscillations in the EEG.iv 
There is growing evidence that these oscillations relate directly to the systems-level 
mechanisms by which anesthetics produce altered states of consciousness. During normal 
brain function, oscillations regulate the timing and coordination of brain activity within 
and between functional systems and circuits. Anesthesia induced oscillations are thought 
to disrupt this coordinated activity, producing different states of altered arousal depending 
upon the receptors and circuits upon which the drugs act. v General anesthesia with 
sevoflurane is characterized in the EEG by frontally coherent alpha (8–12 Hz), delta (1–4 
Hz), and high amplitude slow (0.1–1Hz) oscillations.vi This pattern, observed when adult 
patients are sufficiently anaesthetized to conduct surgery, is similar to that observed under 
propofol-induced general anesthesia and suggests a common systems-level mechanism of 
action.vii Given that the brain rapidly develops and undergoes significant changes from 

childbirth into adulthood, anesthesia induced EEG oscillations in children might differ 
from those of adults, and could vary significantly with age. Characterizing the structure 
of the EEG in relation to age would help establish the foundations for age-appropriate 
monitoring of brain states during general anesthesia and sedation in children. We aimed 
to examine the effects of age on the EEG during general anesthesia, with sevoflurane as 
the sole hypnotic agent. The EEG is typically described in terms of rhythmic activity and 
transients. The rhythmic activity is divided into bands by frequency (figure 1 and figure 
3). 
 
Objective 
Aim: 
This study is designed to evaluate the correlation of raw EEG patterns and age under 1.0 
MAC sevoflurane.  
 
Study design and purpose 
This study is being conducted to evaluate and assess the electroencephalography wave 
patterns in different age patients undergoing surgery under general anesthesia. The aim of 
our study is to compare the raw EEG waves in different age patients and analyze any 
changes in these patterns among various age groups and which of these groups will have 
the EEG signal of high-frequency waves or low frequency waves. Previous studies have 
shown that light sedation is often accompanied by decreasing posterior alpha waves and 
increasing the intensity of frontal/central beta waves.  
 
Sample size: 120 
Based on 6 different age groups from infants to elderly (0-80 years old), we are recruiting 
120 patients with an American Society of Anesthesiology score (ASA) I or II, scheduled 
for elective surgery under general anesthesia lasting less than 2 hours. Each group will 
have 20 cases. 
 
 
 

Methods: 
A sample of 120 healthy patients from the Second Affiliated Hospital of Wenzhou 
Medical University with American Society of Anesthesiologists (ASA) physical status I 
or II will be randomly selected and included in this study. After obtaining ethical 
approval and written informed consent, we will enroll 120 patients (ASA I and II), aged 
0-80 years of either gender undergoing minor elective surgery. The selected patients will 
be divided into 6 different groups according to their age (figure 2). The surgeries will last 
less than two hours each and will be performed under general anesthesia which is an 
indispensable part of surgery. Depth of anesthesia and electrical brain activity will be 
monitored using Bispectral index monitoring system. However, these are based on the 
underlying changes in the features of an EEG signal as the signals vary with the level of 
anesthesia. We will compare the different EEG waves (alpha, delta, theta and gamma) for 
all age patients while maintaining 1.0 MAC sevoflurane. Data related to non-invasive 
blood pressure, heart rate, respiration rate, oxygen saturation, EEG waves frequencies, 
end tidal volume of sevoflurane and BIS values will be recorded. These data will be 
analyzed every 1 min for the first 10mins during maintenance of anesthesia with 1.0 
MAC sevoflurane. Data collection will be first recorded after tracheal intubation. The raw 
EEG wave will be recorded by means of a Universal Serial Bus (USB) which will later be 
analyzed and processed offline. 
120 patients undergoing minor elective surgeries will be allocated in 6 age groups: 
1month-1 year old (infant period), 1-3 years old (toddler period), 3-6 years old (preschool 
age period), 7-18 years old (school age period), 18-65 years old (adults) and 65-80 years 
old (elderly). After arrival in the operating room, an intravenous line will be inserted into 
a large forearm vein, and standard monitors will be applied. Each patient will be 
continuously monitored by a 3-lead electrocardiogram, noninvasive arterial pressure, 
pulse oximetry, and end-tidal carbon dioxide concentration. In addition to the standard 
conventional monitors, BIS electrodes will be placed before induction on each patient. 
The electroencephalogram will be recorded continuously over a period of 10 minutes 
using the Aspect A-2000 BIS®monitor (version XP).  All the 120 patients enrolled in this 
study will be studied for 10 minutes after induction and tracheal intubation without any 
surgical stimulus.  After the skin of the forehead had been prepared and cleaned with 

alcohol, the BIS® (BIS-XP sensor) and BIS electrodes will be positioned as 
recommended by the manufacturers. Anesthesia will be induced by sevoflurane 
inhalation only with a tight-fitting facemask and a 4-l airflow of 100% oxygen. As 
spontaneous breathing diminishes, patients will be manually assisted and with cessation 
of spontaneous breathing, will be mechanically ventilated via the facemask to an end-
tidal carbon dioxide of 35 mmHg. The induction of anesthesia will be the same in all age 
groups and will consist of sufentanil 0.2-0.3mcg/kg or fentanyl 1-2 mcg/kg before 
intubation and 0.2 mg/kg cisatracurium to facilitate intubation. Sevoflurane inhalation 
will be adjusted in all age groups to maintain 1.0 MAC concentration. After tracheal 
intubation, patients will be ventilated with a tidal volume of 6-8 ml/kg and the respiratory 
rate will be adapted to obtain an end-tidal carbon dioxide concentration of 30–35 mmHg. 
After intubation, sevoflurane will be titrated to generate an end-tidal concentration 
(ETsevo) of 2.0, 3.0, and 4.0% in a stepwise increase or decrease pattern in each age 
group to maintain 1.0 MAC concentration. 
All patients will be ventilated using an Ohmeda-Datex anesthetic machine with soda lime 
(CO2 absorber). Hypotension, defined as a decrease in blood pressure by 25% from 
baseline, will be treated with intravenous fluid or phenyl ephedrine (20 microgram bolus). 
Raw EEG data, BIS values and end target expiratory concentration of sevoflurane will be 
recorded every one minute for a period of 10 mins after induction and intubation. Raw 
EEG data (figure4-patient of 80 years old), will be analyzed and processed using the pdf 
screenshot from the BIS vista monitor. The pdf screenshots of the raw EEG will be 
recorded by means of a Universal Serial Bus (USB). The pdf screenshots will be taken 
twice during the 10 minutes of recording to minimize any loss of data. 
 
Inclusion Criteria:  
Patients age between 0 to 80 years old, ASA I or II scheduled for minor surgeries under 
general anesthesia lasting less than 2 hours each.  
 
Exclusion Criteria: 
Potential subjects with any neurologic or psychiatric disease, relative or absolute 
contraindication to sevoflurane including pregnancy by patient self-report, and any recent 

prescription or illicit medication use will be excluded. Patients with a history of any 
disabling central nervous or cerebrovascular disease and patients who had received 
central nervous system–active drugs will be excluded from the study. We will exclude 
patients with poor quality data, most likely because of poor electrode contact. 
 
Potential benefits 
The advantages of this study are to help the anesthesiologist have a better understanding 
of the brain waves under general anesthesia. EEG monitoring provides assessment of 
brain perfusion during state of general anesthesia. Brain death during anesthesia can be 
assessed and prevented with the use of raw EEG patterns. 
EEG waves monitoring is a key aspect in preventing brain damage and ensuring the level 
of anesthesia is within the required range.  
Maintaining the required range of deep anesthesia (BIS value of 40 to 60) helps avoid the 
incidence of awareness with recall in adults during general anesthesia and sedation. 
 
Potential risks 
There are no risks and complications associated with this study. However, mild redness 
may appear on the forehead in some patients from the BIS electrodes.  
 
Statistics: 
Statistical analyses will be performed with a statistical package (SPSS version 21.0; 
SPSS, Chicago, IL) and Microsoft excel. All data will be presented as mean±sd. 
Demographic data will be compared by using standard t-tests; comparison of incidence 
data between groups performed by using Fisher’s exact tests. A P value < 0.05 will be 
considered significant. 
 
Study duration:  
We are estimating that the entire study will require one year, including patient recruitment, 
data collection, data analysis and report writing. 
 
 

Co-Investigators: 
Name 
Department 
Role 
Beekoo Deepti 
Anesthesiology, The second affiliated 
hospital of Wenzhou Medical 
University. 
Principal 
Investigator 
Shangguan Wangning 
Anesthesiology, The second affiliated 
hospital of Wenzhou Medical 
University. 
Co-Clinical 
Investigator 
 
Payment: 
There is no financial benefit or any reimbursement for participation in this study. 
 
 
Figure 1: 
 
 
Figure 2: 
Groups 
Age 
1- Infant period 
1month-1 year old 
2- Toddler period 
1-3 years old 
3- Preschool age period 
3-6 years old 
4- School age period 
7-18 years old 
5- Adults 
18-65 years old 
6- Elderly 
65-80 years old 
 
Figure 3: 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure 4: 
 
 
 

 
References: 
                                                          
i Prashant J. General growth and tissue development throughout childhood. In: Bruno B, 
Bernard JD, eds. Pediatric Anesthesia: Principles and Practice. New York: McGraw-Hill, 
2002; 32–3 
 
ii McCann ME, Bacsik J, Davidson A, Auble S, Sullivan L, Laussen P.The correlation of 
bispectral index with endtidal sevoflurane concentration and haemodynamic parameters 
in preschoolers.Paediatr Anaesth 2002; 12: 519–25 
 
iii Davidson AJ, McCann ME, Devavaram P, et al. The differences in the bispectral index 
between infants and children during emergence from anesthesia after circumcision 
surgery. Anesth Analg 2001; 93: 326–30 
iv Gibbs FA, Gibbs LE, Lennox WG. Effects on the electroencephalogramof certain drugs 
which influence nervous activity.Arch Intern Med 1937; 60: 154–66 
 
v Lewis LD,Weiner VS, Mukamel EA, et al. Rapid fragmentation of neuronal networks at 
the onset of propofol-induced unconsciousness. Proc Natl Acad Sci USA 2012; 109: 
E3377–8 
 
vi Brown EN, Solt K, Purdon PL, Akeju O. Monitoring Brain State During General 
Anesthesia and Sedation. Miller’s Anesthesia:Philadelphia: Elsevier, 2014 (Chapter 50) 
 
vii Brown EN, Lydic R, Schiff ND. General anesthesia, sleep,and coma. The New 
England Journal of Medicine 2010; 363:2638–50