SedLine EEG-Guided Depth of Anesthesia: Effect of Anesthetic Dosage
Phase: NA
Conditions: Anesthesia, Surgery
Sponsor: Indiana University

 
 
 
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SedLine EEG-Guided Depth of Anesthesia: Effect of Anesthetic Dosage 
 
 
 
 
 
 
 
Dr. Timothy Webb 
Asst. Prof., Dept. of Anesthesiology,  
Indiana University School of Medicine 
Fesler Hall Room 204 
Indianapolis, Indiana 46202 
 
 
 
Dr. John Wolfe 
Asst. Prof., Dept. of Anesthesiology,  
Indiana University School of Medicine 
Fesler Hall Room 204 
Indianapolis, Indiana 46202 
 
V1.1-28.2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Table of Contents: 
 
Study Schema 
1.0 
Background & Rationale 
2.0 
Objective(s) 
2.1 
Primary Objective 
2.2 
Secondary Objective 
2.3 
Tertiary/Exploratory/Correlative Objectives 
3.0 
Outcome Measures 
3.1 
Primary Outcome Measures 
3.2 
Secondary Outcome Measures 
3.3 
Tertiary/ Exploratory/ Correlative Outcome Measures 
4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
4.2 
Exclusion Criteria 
5.0 
Study Design 
6.0 
Enrollment/Randomization 
7.0 
Study Procedures 
8.0 
Study Calendar 
9.0 
Reportable Events 
10.0 Data Safety Monitoring 
11.0 Study Withdrawal/Discontinuation 
12.0 Statistical Considerations 
13.0 Data Management 
14.0 Privacy/Confidentiality Issues 
15.0 Follow-up and Record Retention 
16.0 References 
17.0 Appendix 
 
 
 

 
 
 
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1.0 
Background & Rationale 
 
 
Electroencephalogy (EEG) was first described in 1875 in dogs and apes.1 The 
technology was shortly after applied to humans and within 10 years the changes 
to the EEG tracing was studied when certain sedatives drugs were administered.1   
Over the last several decades EEG based monitors have been developed with the 
hopes of aiding anesthesiologists at evaluating the “depth” of a patient’s 
anesthetic while under general anesthesia.  Currently, typical anesthesia practice 
is to measure and adjust depth of a general anesthetic based on the medications 
administered and hemodynamic parameters of the patient, potentially exposing 
high risk patients to un-needed excessive depths of anesthesia which can 
potentially result in adverse post-operative outcomes.2,3  
 
The use of intraoperative EEG monitoring to guide the depth of an anesthetic 
seems to have the potential to reduce the total dose of anesthetic required.  Use 
of the EEG based monitor called the Bispectral Index Monitor (BIS Monitor) in an 
older study was shown to reduce sedative use and total cost in ICU patients who 
were receiving intravenous infusions of sedatives and neuromuscular blockers.4  
And recently, the BIS monitor was used in a large randomized control study in 
order to investigate whether providing an anesthetic guided by an EEG based 
monitoring device in individuals at high risk for postoperative delirium would 
significantly reduce postoperative delirium.  While the primary results reported a 
negative results, the study did have other interesting findings – most notably a 
significant reduction in the dosage of volatile anesthetic (the primary anesthetic 
agent used in general anesthetic procedures).  Furthermore, the study showed 
using a protocolized adjustment in anesthetic depth using an EEG based 
monitoring system for guidance in human subjects resulted in no significant 
change in adverse outcomes in a large trial of patients in this population5 
 
The Masimo Sedline Brain Function Monitor (SedLine), is an EEG based 
monitoring device that is approved by the Food and Drug Administration for 
monitoring of brain function under anesthesia.  This new generation device 
provides processed EEG information (as the BIS monitor does) as well as raw EEG 
waveforms and a Density Spectral Array (DSA) display – providing information of 
the power of the EEG signal over a spectrum of frequencies.  This additional 

 
 
 
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information allows the anesthesiologist to evaluate the depth and 
appropriateness of the anesthetic in detail.6  
 
We hypothesize that the use of a Sedline processed EEG monitor (using a 
protocolized adjustment in anesthetic depth using this EEG monitoring device) 
will allow anesthesiologists to reduce the doses of anesthetic drugs during general 
anesthesia in patients 65 or older (resulting in less exposure of anesthetic 
medications to a high-risk patient population as well as a potential reduction in 
cost).  In addition, an added benefit of safely reducing the amount of volatile 
anesthetic used in everyday anesthesia practice may prove to also be helpful to 
environment and cut down on their contribution to ozone layer depletion.7   
 
We plan to investigate this hypothesis in a study in which we will randomize 
patients to either anesthetic drug doses guided by Sedline processed EEG 
characteristics or standard anesthesia care.  We plan to evaluate the hypothesis 
that SedLine monitoring reduces anesthetic drug doses.   
 
Of note, we have recently completed a pilot study with a similar study design and 
have confirmed we have the capabilities and resources to conduct this study. 
 
 
2.0 
Objective(s) 
2.1 
Primary Objective 
The primary objective of this study will be to determine whether an 
anesthetic guided by the Sedline EEG based monitor will reduce the total 
dosage of anesthetic under general anesthetics in this population (patients 
65 or older).   
 
 
3.0 
Outcome Measures/Endpoints 
3.1 
Primary Outcome Measures 
The primary outcome measured will be the total average percent of volatile 
anesthetic (sevoflurane) utilized while subjects are under anesthesia 
(maintenance phase).  The time considered “maintenance phase” under 
general anesthesia will be measured starting 5 minutes after the induction 
agents are administered and measurements will stop following 

 
 
 
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administration of neuromuscular blocker reversal drugs.  Data will be 
collected from computerized anesthetic records.   
 
 
3.2 
Secondary Outcome Measures 
The secondary outcomes measured will be the total dosage of hypnotic 
agents administered while in the maintenance phase of anesthesia.  These 
agents include: midazolam, lorazepam, diazepam, fentanyl, sufentanil, 
ketamine, propofol, morphine, and hydromorphone. Additional secondary 
outcomes measured will include episodes of hypotension (this will be 
defined as an episode of mean arterial pressure of <65 mmHg), total 
dosage of vasopressors (such as phenylephrine, ephedrine, vasopressin, or 
norepinephrine), and the occurrence of EEG isoelctricity, or burst 
suppression.  SedLine images will be recorded for both groups in order to 
compare rates and duration of burst suppression events.  Of note, if the 
patient has a functioning arterial line in place, we will use measurements 
from this in preference to a non-invasive blood pressure cuff). 
 
4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
• 
Patients undergoing a scheduled surgery (laparotomy, 
hepatobiliary surgery, gynecologic surgery, and/or urologic surgery 
procedures) at Indiana University Health University Hospital that is 
expected to have at least a 3 day post-operative hospital stay. 
• 
ASA class 1, 2, 3, or 4. 
• 
Age 65 years or older. 
• 
Male or Female 
• 
Surgical procedure requiring general anesthesia. 
 
4.2 
Exclusion Criteria 
• 
Any previous diagnosis of dementia or other cognitive 
impairment. 
• 
Any patient undergoing emergency surgery. 
• 
Any patient undergoing surgery who is currently an inpatient. 
• 
Patient refusal to participate in study. 

 
 
 
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• 
Any patient undergoing surgery that would prevent placement of 
the Sedline monitor leads (for example – surgery on the patient’s 
forehead/scalp). 
• 
Any physical, mental, or medical conditions which, in the opinion 
of the investigators, may confound the ability to assess the patient for 
delirium in the post-operative period. 
 
 
5.0 
Study Design 
 
- Prior to study commencement, select anesthesiologists from the Indiana 
University Health University Hospital Anesthesia Group will be trained on 
usage and interpretation of the Sedline.  Training for this group of providers 
will include a PowerPoint presentation recording presented by Dr. Wolfe to 
aid in interpretation of the Sedline data.  Representatives from the study 
will also be available as needed to answer questions as they arise.  They will 
also be given certain guidelines for anesthetic administration based on the 
processed EEG findings.  These will include the following:   
o Usage of sevoflurane as the primary anesthetic agent 
o Reducing sevoflurane dosage if the EEG indicates signs of burst 
suppression (excessive anesthetic depth), if the PSI on the Sedline 
reads less than 25, or if hypotension is occurring and the anesthesia 
provider believes that depth of anesthesia may be a contributing 
factor. 
o Increasing sevoflurane dosage if the EEG pattern is not consistent 
with general anesthesia (not enough depth of anesthetic).   
- We anticipate 5-10 anesthesiologists being included in this group.  Given 
that this group of anesthesiologists will be assigned to both groups (study 
and control), the size of the groups, and the instructions regarding the 
maintenance phase of anesthesia, diazepam, and dexmedetomidine we 
anticipate the difference in practice patterns between providers will not 
affect the data.  We will discourage the use of nitrous oxide as well as IV 
anesthetics including midazolam.   In the control group, the 
anesthesiologist will be asked to provide the anesthetic as he or she would 
under normal care with the exception of avoidance of nitrous oxide and IV 
anesthetics during the maintenance phase of anesthesia.   We anticipate 

 
 
 
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that the surgical procedures included in this study will be similar enough 
that the type of surgical procedure will not affect anesthetic dosing. 
 
We will identify subjects who meet inclusion/exclusion criteria on the day 
of surgery.  Following explanation of the study and completion of informed 
consent, the patient will be randomized into 1 of 2 groups – study group or 
control group.  We plan to use block randomization to keep the groups 
relatively balanced throughout enrollment. The patient will then be taken 
to the operating room in normal fashion.  Prior to the induction of 
anesthesia, the Sedline monitor will be placed on the patient’s head to 
ensure the monitor is working properly.  For those in the study group, the 
monitor will be in full view of the anesthesiologist administering the 
anesthetic.  For those in the control group, an apparatus will be placed over 
the monitor will not be in view of the anesthesiologist. The monitor will still 
be processing and recording EEGs for both groups. The patient will then be 
placed under anesthesia and surgery will commence.  While under 
anesthesia, images of the display screen of the Sedline will be collected for 
later evaluation.  Once the surgery is complete, the patient will have the 
monitor removed and image capture of the display will be stopped prior to 
exiting the operating room. 
 
Following finalization of the anesthetic record by the staff anesthesiologist, 
the primary and secondary outcomes will be collected by investigators.  The 
images of the Sedline EEG monitor will also be reviewed by investigators to 
ensure that appropriate depth of anesthetic was utilized throughout the 
maintenance phase of anesthesia in the study group.  Blinding of the study 
investigators will not be possible due to the manner in which images of the 
Sedline readings are collected (it will be readily apparent on the images 
whether the SedLine data was readily available or concealed from the 
anesthesia team).  
 
 
 

 
 
 
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Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
6.0 
Enrollment/Randomization 
The surgical schedule will be assessed daily to identify patients scheduled for 
surgery who may be eligible to participate in this study.  A member of the 
research team, either principal investigator, co-investigator, or study coordinator 
will approach the potential subject the day of their scheduled procedure.  They 
will conduct the visit in a private area such as a patient’s room, secluded hospital 
room, or an area free from the general public.  All study procedures will be 
reviewed, questions answered, and the subject will be given ample time to 
discuss and determine if they will sign the consent to participate in the study.   
 
We plan to enroll 110 subjects in this study.  Patients will be randomized to either 
the control or the study group. 
 
 
7.0 
Study Procedures 
As noted above, following enrollment on the day of surgery, the Sedline device 
will be placed on the patient just prior to the induction of anesthesia.  Anesthesia 
Data Analysis, Statistical Analysis 
Total N: 110  Obtain informed consent. Screen potential participants by inclusion 
and exclusion criteria.  Obtain history.  Document. 
Study Group 
N = 55 
Control Group 
N = 55  
Randomize 
1:1 
Sedline placement in the operating room 
Data Collection from Anesthesia Records 
 
Review of Sedline Readings  

 
 
 
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will then be induced, and surgery will proceed as usual.  Images will be captured 
of the display of the Sedline monitor while under anesthesia during the surgical 
procedure using a recording device.  The study group will have the Sedline 
readings visible to the anesthesiologist in the room and will use the Sedline to 
guide anesthetic depth. The control group will have the monitor out of view and 
not visible to the anesthesiologist, but the images of the Sedline monitor will be 
recorded.     
 
Once the procedure is complete, the Sedline monitor will be removed from the 
patient and the collection of images will be stopped prior to the patient exiting 
the operating room. 
 
Following the finalization of the anesthetic records, the desired data will be 
collected from the anesthetic record.  The images of the Sedline readings will also 
be reviewed by investigators to confirm an appropriate depth of anesthetic was 
achieved in the study group. 
 
8.0 
Study Calendar 
We will begin to enroll patients once we receive approval for study 
commencement from the IRB and following selection/training of the 
anesthesiology study team.  We plan to enroll 110 patients total.  Following data 
collection of the last patient the study will be closed. 
 
9.0 
Reportable Events 
Patients will be monitored by the primary team during the postoperative period, 
and any adverse events or unanticipated problem will be reported to the 
anesthesia service and research team. All unanticipated problems will be reported 
to the IRB committee using the prompt reporting form. 
 
10.0 Data Safety Monitoring 
In order to protect the privacy of our patients, any data which has identifiable 
patient data attached to it will be stored in the REDcap system.  Of note, the 
images obtained from the Sedline monitor display will not contain ANY 
identifiable patient data (these images will be stored on a research computer). 
 
 
 

 
 
 
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11.0 Study Withdrawal/Discontinuation 
The patient can withdraw from the study at any time by contacting the research 
team or the anesthesia service.  
 
 
12.0 Statistical Considerations 
 
Primary outcome: total average percent of volatile anesthetic (sevoflurane) 
utilized while subjects are under anesthesia. 
 
Secondary outcomes: total dosage of hypnotic and opioid agents administered 
while in the maintenance phase of anesthesia.  These agents include midazolam, 
lorazepam, diazepam, fentanyl, sufentanil, ketamine, propofol, morphine, and 
hydromorphone during the maintenance phase of anesthesia. Additional 
secondary outcomes measured will include episodes of hypotension, episodes of 
burst suppression, and total dosage of vasopressors and hypnotic agents. 
 
Statistical analysis will be performed using a standard statistical program (SAS or 
Stata). All data will be summarized (either means and standard deviations or 
medians and quartiles for continuous variables; frequencies and percentages for 
categorical variables) by treatment group. Demographic data will be compared 
between the two groups using t-test or Wilcoxon rank sum test as appropriate for 
continuous variables, and chi-square tests or Fisher's exact test for categorical 
variables as appropriate. The primary outcome, total average percent of volatile 
anesthetic (sevoflurane) utilized along with secondary outcomes of total dosage 
of hypnotic agents administered, will be compared between the two groups using 
t-test or Wilcoxon rank sum test as appropriate. To account for the possible 
effects of covariates age, sex, and BMI and anesthesiologist, a mixed model with a 
random effect for anesthesiologists will be employed. Here we could treat surgery 
type and duration as fixed effects if needed. The secondary outcome of episodes 
of hypotension which will be compared using chi-square tests or Fisher's exact 
test for the occurrence of hypotension. Distributions of the continuous variables 
will be examined, and a transformation of the data (e.g. natural logarithm) or 
nonparametric tests will be used as necessary. A 5% significance level will be used 
for all comparisons. 
 

 
 
 
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From a similar study using an outcome (minimum alveolar concentration or MAC) 
comparable to ours we were able to estimate a coefficient of variation for total 
average percent of volatile anesthetic to be 0.15.4  Working with a feasible sample 
size of 44 per group and using a power of 90%, 5% significance level, and 
employing a two-sided test, the study will be able to detect a reduction of 10% in 
for total average percent of volatile anesthetic between the two groups.  
Assuming a dropout rate of up to 20%, we will enroll up to 55 patients per group 
for this study. Here we used a “Tests for the Ratio of Two Means” using sample 
size software PASS 2019. 
 
 
13.0 Statistical Data Management 
 
 
Primary data will be collected via review of electronic medical records, anesthesia 
records, and screenshot images of the SedLine EEG monitor and will be stored 
electronically in REDCap.  The storage location will be backed up 
automatically.  Quality assurance steps will include, built-in range checks and 
testing of the database by the study team prior to moving to production 
mode.  The following quality control methods will be used:  1) single data entry 
with random checks of accuracy; and 2) extraction and cleaning of data that will 
be used for analysis every 6 months. 
 
14.0 Privacy/Confidentiality Issues 
Any private data or potentially identifiable patient data will be stored in the 
REDcap system.   
 
 
15.0 Follow-up and Record Retention 
The study will start upon approval of the IRB and following selection/training of 
the anesthesiology study team and the study will stop following completion of 
data collection from the 110th subject.  We anticipate that this should not take 
longer than 24 months. 
 
 
 
 

 
 
 
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16.0 References 
1. Hajat Z, Ahmad N, Andrzejowski J.  The role and limitations of EEG-based 
depth of anaesthesia monitoring in theatres and intensive care.  
Anaesthesia 2017; 72 (Suppl. 1):  38-47. 
 
2. MacKenzie KK, Britt-Spells AM, Sands LP, Leung JM.  Processed 
Electroencephalogram Monitoring and Postoperative Delirium:  A Systemt 
Review and Meta-Analysis.  nesthesiology, 129(3), 417–427. 
 
3. Purdon PL, Sampson A, Pavone KJ, Brown EN.  Clinical 
Electroencephalography for Anesthesiologists.  Anesthesiology.  2015; 
123(4):  937-960. 
 
 
4. Kaplan LJ, Bailey H.  Bispectral index (BIS) monitoring of ICU patients on 
continuous infusion of sedatives and paralytics reduces sedative drug 
utilization and cost. 
 
5. Wildes TS, Mickel AM et al.  Effect of Electroencephalography-Guided 
Anesthetic Administration on Postoperative Delirium Among Older Adults 
Undergoing Major Surgery:  The ENGAES Randomized Clinical Trial.  JAMA.  
2019 5;321(5):  473-483.   
 
 
6. Masimo.  Sedline Sedation Monitor.  Operator’s Manual.      
 
7. Ishizawa Y.  General Anesthetic Gases and the Global Environment.  
Anesthesia & Analgesia.  2011;  112(1) 213-217).