CEReBral AutorEgulation in Non-cardiac SuRgery and Relationship to Postoperative DeliriUm State

The goal of this observational study is to learn the how to determine the mean arterial pressure(MAP) or blood pressure level to be maintained during non-cardiac surgery for optimal brain health in patients above the age of 60 undergoing major non-cardiac surgery. The main question\[s\] it aims to answer are:

* Is there a way to tailor the blood pressure to be maintained in such patients during surgery for optimal brain health using non-invasive monitors that check the brains electrical activity, the electroencephalogram(EEG) monitor, and the brain's blood oxygen levels, the cerebral oximetry(CO) monitor?
* How much does this optimal blood pressure level vary between patients?

Participants will be asked to:

* Complete a questionnaire at the time they enroll into the study, as well as a daily questionnaire to help determine their level of thinking and brain health. This questionnaire will be administered by a member of the study team.
* They will also have an EEG and CO monitoring sticker placed on their foreheads. This will be connected to a monitor that will collect this data just before, during, and after their surgery. The data collected through these monitors will help us with our study goals.

Study Procedures:

Pre-operative:

1. Assessment by an anesthesiologist, and brief patient education about cerebral autoregulation and post-operative delirium.
2. MOCA baseline cognitive assessment by study team member.

Intra-operative:

1. Perioperative EEG Monitoring: EEG stickers will be applied to patient's forehead in pre-op holding area and attached to SedLine Root Monitor (described below in perioperative EEG and Cerebral Oximetry10 (CO) monitoring) at least 5 minutes prior to start of induction.
2. Perioperative CO monitoring: NIRS stickers will be applied to patient's forehead in pre-op holding area and attached to SedLine Root Monitor (described below in perioperative EEG and Cerebral Oximetry (CO) monitoring) at least 5 minutes prior to start of induction.
3. Live collection and processing of data: During surgery, the SedLine Root Monitor (which collects EEG \& CO data) and the Operating Room's en-suite Phillips Intellivue monitor (which collects MAP data during surgery) will both be connected to a BIDMC-issued, IS-approved laptop or tablet running the ICM+ software suite. The SedLine Root Monitor and Philips Intellivue Monitor will output their data locally via cables to the system running the ICM+ software suite, which will process and integrate this data in real-time. This processed information will only be collected passively during the surgery, and will not inform or affect clinical care in any way.

   * Perioperative EEG and CO monitoring All patients will undergo EEG and CO monitoring during intraoperative, and possibly the postoperative period (up through 24 hours/until extubation, whichever occurs earlier). The EEG and CO leads will be removed from the patient and monitoring stopped at one of three end-points: a) 24 hours after the end of the surgical procedure b) at time of extubation c) when patient is shifted out of the PACU; whichever comes first. This is to ensure that comprehensive data on cerebral autoregulation during the critical perioperative period is available for any given patient for analysis. Electroencephalograms and CO will be recorded using the SedLine monitor (Masimo Corporation, Irvine California). SedLine is a FDA approved, patient-connected, 4-channel processed electroencephalograph EEG and Cerebral oximetry monitor designed specifically for intraoperative or intensive care use. It displays electrode status, EEG waveforms, Density Spectral Array (DSA) and bilateral regional cerebral oxygen saturation.

The SedLine EEG electrode array records approximately at positions Fp1, Fp2, F7, and F8, with reference approximately 1 cm above Fpz and ground at Fpz. The spectrograms will be computed using the Multitaper method from the unprocessed EEG signals recorded at a sampling frequency of 250 Hz. Individual spectra will be computed in 3-sec windows with 0.5 sec overlap between adjacent windows. Multitaper spectral estimates have near optimal statistical properties that substantially improve the clarity of spectral features.

The CO sensors are applied on the forehead.

* EEG Display The EEG waveforms reflect electrical activity mostly from the front of the brain. The display is configured to contain 4 data input sources, acquired from the 4 sensor electrodes: L1, R1, L2, and R2.

Patient State Index (PSi)31,32 The PSi is a processed EEG parameter that is related to the effect of anesthetic agents, and takes into consideration, among other factors:

1. changes in power in various EEG frequency bands
2. changes in symmetry and synchronization between critical brain regions
3. the inhibition of regions of the frontal cortex.

Density Spectral Array (DSA)31,32 The DSA contains left and right spectrograms representing the power of the EEG on both sides of the brain.

Multitaper DSA32 When using a Multitaper DSA, EEG data are transformed into the frequency domain, which may provide a better display of EEG features.

* Post-operative:

Postoperative pain assessment

Postoperative pain will be assessed with a standard 11-point scale and by pain medication intake. Pain scores will be obtained by asking the subject and also collected from the medical record when documented clinically. Pain medication intake will be extracted from the medical record.

Delirium and cognition assessment Once consent is obtained, a trained research team member will proceed with baseline preoperative and postoperative cognitive, delirium, and depression assessments.

Baseline assessment

This will be conducted by study staff at the time of consent. If the patient cannot complete baseline assessment at time of consent, it may be conducted at a later time before surgery as per the patient's convenience on hospital premises. This will include the assessment of cognitive function using the:

1. Montreal Cognitive Assessment (MoCA)11, supplemented with
2. Days of the week (DOW) \& Months of the year (MOY) for additional attention testing
3. Delirium Symptom Interview (DSI) to capture symptoms of delirium
4. Confusion Assessment Method (CAM)12,13: Using data from the cognitive testing and DSI, the researcher will complete the long CAM which includes the diagnosis of delirium using the CAM diagnostic algorithm.

These detailed assessments will take no more than 45 minutes. If this baseline assessment shows a MoCA score \<10, the subject will be excluded from the study.

Postoperative assessment On each postoperative day during the hospital stay a research team member will administer a

1. Standard cognitive assessment, including DOW, MOY, CAM, and DSI. These daily assessments will take approximately 10-15 minutes.
2. If a subject is intubated postoperatively, a CAM-ICU will be performed instead of a CAM assessment.
3. If a participant declines to complete a daily standard cognitive assessment, trial staff will offer the 3D-CAM as a shorter alternative. If the participant refuses both the daily standard cognitive assessments and the 3D-CAM, trial staff will use the CAM Only, a conversation-based method to score the CAM.
4. If daily assessments have plateaued for 3 consecutive days (CAM negative each day), they will then only need to be completed every other day, as long as the subject remains CAM negative, until the date of discharge.
5. In addition, medical charts will be reviewed every day until discharge or day 30 (whichever occurs first) to identify delirium. Any events related to delirium during the hospital stay and at the follow-up time points (1 month and 6 months) will be recorded on REDCap eCRF. Events such as trying to get out of bed, verbal abuse, falls, pulling tubes, inappropriate behavior during the hospital stay as noted in the medical charts will be recorded. At phone follow-up: prolonged rehabilitation, cognitive decline will be recorded.

Remote assessments After the patient consents to participate in the study and opts in for phone call assessments, the study team may use the t-MoCA as a substitute to the MoCA for remote assessment of baseline cognition. Additionally, for in-hospital assessments, study investigators may use the a-MoCA as a substitute to the MoCA if an inability for in-person visits arises. Sites may conduct substitution assessments via phone or site-specific HIPAA approved telemedicine video conferencing platform. The a-MoCA and the t-MoCA are identical assessments but differ in naming, where the term "a-MoCA" is used for in-person assessments, and the term "t-MoCA" is used for assessments conducted via phone. Both assessments exclude the visuoconstructional tests of alternating trails, drawing of cube and clock, and animal naming.

Discharge assessment On the day of discharge, the MoCA, with DOW and MOY, the CAM, and the DSI will be completed. (If the discharge assessment was performed in anticipation of discharge on a specific day but the discharge was delayed (i.e., logistical reasons, clinical reasons), this will not be considered a protocol deviation.) If the patient is discharged before a discharge assessment can be done, study staff may contact patient to administer t-MoCA along with DOW and MOY, CAM and DSI.

Follow-up assessment Follow-up assessments will be administered at 1 month (+14 days /- 7 days) and 6 months (+/- 30 days) after the date of surgery. These will be completed by a research team member via telephone and will include a telephone version of the MoCA (t-MoCA), with DOW and MOY, the CAM, SF-12, FRAIL scale, functional activity scale, and long term pain scale and the DSI. These assessments will be done at the patient's convenience and ability to finish the evaluations.

* Delirium treatment The delirium research assessments will not be provided to the treating clinicians. Treating clinicians will assess and treat delirium per the standard of care.
* Data Collection

Patient related information such as baseline characteristics including, comorbid conditions, medications, surgical and anesthetic data will be obtained from Society of Thoracic Surgery database, Anesthesia Information Management Systems and patient's medical record. EEG changes, waveforms and other related data will be recorded from the monitor. Additionally, to track other important factors related to outcome and protocol adherence, study investigators may extract clinical data from the medical record including, but not limited to:

1. Anthropometric data (e.g. age, height, weight, race/ethnicity)
2. Admission type
3. Medications
4. Pain scores
5. Respiratory physiological data
6. Hemodynamic data (e.g. heart rate, blood pressure)
7. Laboratory data
8. Complications data
9. Hospitalization-related time data (e.g. admitting diagnosis, hospital and ICU length of stay)
10. Vital status These data will be merged with subject cognitive assessment data. All data will be stored on password-protected computers, in locked file cabinets and/or offices, or REDCap.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 60 years
* Undergoing any non-cardiac surgeries including but not limited to vascular, hepatobiliary, or complex spine surgeries requiring general anesthesia with arterial catheterization for monitoring

Exclusion Criteria:

1. Non-English speaking (Justification: cognitive assessment instruments are not validated in a sufficient range of languages, and the research team lacks polylingual capabilities or the financial resources to hire interpreters for the duration of all proposed assessments.)
2. Cognitive impairment as defined by total MoCA score \< 10 (justification: baseline cognitive dysfunction will confound primary outcome measure)
3. Significant visual impairment (justification: will be difficult for patients to draw individual components in MOCA score)
4. Emergent surgery (justification: insufficient time to initiate intervention)
5. History of stroke within the last 3 months (justification: cognitive dysfunction secondary to stroke can confound outcome measures