The influence of age on EEG signals and consciousness during anesthesia (TIARA)

Brain function monitoring with Bispectral Index* (BIS*) technology during
surgical procedures gives anesthesia providers the ability to directly monitor
the anesthetic effect on the patient*s brain and optimize the anesthetic dosing
for the individual.
The BIS technology converts raw EEG data acquired from the frontal cortex into
a single number between 0 (isoelectric EEG) and 100 (fully awake). Given the
numerous changes that occur in brain anatomy and physiology with typical aging,
it is reasonable to assume that the EEG patterns of elderly patients and young
patients under general anesthesia differ.
In general, elderly patients are more sensitive to anesthetic agents. Less
medication is usually required to achieve a desired clinical effect, and drug
effect is often prolonged[1]. We might thus hypothesize that the BIS*
technology should be age adjusted under the assumption that the anesthetic
state is also dependent on the patient's physical, mental, and cognitive state.

To evaluate the relationships between BIS* parameters, age, and depth of
anesthesia in patients undergoing surgery under general anesthesia.

this is a multicenter, non-invasive, interventional data collection study to
improve the current BIS* algorithm. Subjects undergoing a standard of care,
elective non-ambulatory surgery under general anesthesia will be recruited.
Eligible patients 18 years and older, will be informed of the study and invited
to participate. Each eligible and consented subject will undergo the study
assessments and procedures. The BIS* sensors will be applied to the patient*s
forehead before anesthesia is administered. The BIS* data will be collected
throughout the surgery. The data recorded during the surgery will be provided
to Medtronic.
It is planned to enroll up to 100 subjects from 2 centers. It is anticipated
that approximately 35% of enrolled patients will be between ages 18-64 years
old, and approximately 65% of patients will be above the age of 65 years. In
addition to basic demographic data collection, three assessments, the Mini
Mental State Examination (MMSE), the Mini Nutritional Assessment (MNA®-SF), and
the Edmonton Frail Scale (EFS) will be administered to each subject prior to
surgery.

Subjects will be considered enrolled at the time they sign the informed
consent. Basic demographic and Medical History data will be collected at the
baseline visit, and subjects will be given three assessments:
* Mini Mental State Examination (MMSE)
* Mini Nutritional Assessment (MNA®-SF)
* The Edmonton Frail Scale (EFS)
During the surgical procedure, the BIS* sensors will be placed on the subject*s
forehead before any anesthetics are given, and data will be collected
throughout the duration of the surgery. The subject will also be fitted with
Nellcor* pulse oximetry sensors.
Prior to induction subjects will be assessed using the Modified Observer*s
Assessment of Alertness/Sedation Scale (MOAA/S).
A slower induction of anesthesia will be achieved by setting a lower initial
target propofol dose and making an incremental increase in the targeted dose.
This is a conservative approach which maintains consistency across all study
subjects, and will ensure safety of the elderly patients included in the study,
which should also closely align with standard institutional practices. The
propofol will be administered using target-controlled infusion (TCI) pump, and
the initial targeted effective site concentration (Ce) will be half of the
effective site propofol concentration based on drug Instructions for Use (IFU)
and on the subject*s body mass used for induction. The TCI will calculate the
initial bolus and infusion rate required to rapidly achieve and maintain this
drug level based on propofol's population pharmacokinetics using the Schnider
Model. At this step, the depth of anesthesia will be assessed using MOAA/S
after an equilibrium time of approximately 5 minutes (from the start of
propofol infusion.) After this initial step, the target effect site
concentration is subsequently adjusted in an attempt to maintain the desired
level of sedation and three-quarters of the Ce will be administered. This
second step will also require depth of anesthesia assessment using MOAA/S after
an equilibrium time of approximately 5 minutes. Lastly, the final/full Ce of
the propofol will be administered, and the MOAA/S will be assessed after
another equilibrium time of 5 minutes is reached. The specified induction
period will last approximately 15 minutes in order to record and monitor the
BIS values, EEG readings, and MOAA/S scores across the anesthetic agent
introduction into the subject. After these steps, anesthesia will be delivered
and maintained per institutional guidance.
During the anesthesia maintenance phase, anesthesia medications will continue
according to standard practice without any other intervention.

At the beginning of induction, the depth of anesthesia will be assessed to
ensure a MOAA/S of 0 has been obtained.

The administration of anesthetic drugs, neuro-muscular blocking agents (NMBA),
NMBA reversal drugs, anti-nausea drugs, and drugs that reduce pain will be
recorded on the eCRF (administration time and dosage).
BIS values and EEG data will be recorded with a USB storage device connected to
the BIS complete monitor. Blood pressure, EtCO2, SpO2, pulse rate, respiration
rate, end-tidal anesthetic gas, FiO2%, EtO2%, and temperature will be gathered
from the hospital computerized database and the Nellcor system, digital
records, labeled with patient ID, will be provided to Medtronic. The BIS data
file labeled with patient ID will be provided to Medtronic.
Only adverse events related to the BIS* and Nellcor* systems will be reported.

Medtronic has determined that this is a study of a *non-significant risk
device* due to the nature of the devices being tested. Utilizing the FDA
criteria1,2 listed below to distinguish between significant and non-significant
risk devices, Medtronic has determined that:

* The investigational device is not intended as an implant and does not present
a potential for serious risk to the health, safety, or welfare of a subject;
* The investigational device is not purported or represented to be for use
supporting or sustaining human life and does not present a potential for
serious risk to the health, safety, or welfare of a subject;
* The investigational device is not for a use of substantial importance in
diagnosing, curing, mitigating, or treating disease, or otherwise preventing
impairment of human health, and does not present a potential for serious risk
to the health, safety, or welfare of a subject; and
* The investigational device does not otherwise present a potential for serious
risk to the health, safety, or welfare of a subject.

The potential risks of these devices have been assessed and are not greater
than those of currently approved and marketed devices of the same type (e.g.,
pulse and tissue oximeters, EtCO2 monitors, non-invasive blood pressure
monitors, ECG or respiration monitors). Society may benefit from more accurate
anesthesia monitors.