Taking Brain Monitoring to the Next Level (HDBRAIN)

This one arm clinical study will assess the impact of a goal directed therapy intervention, aiming at optimizing depth of anesthesia and intraoperative blood pressure on the incidence of postoperative cognitive dysfunction and delirium relative to a standardized anesthetic plan. We will enroll 60 patients and will measure the neurocognitive status (MoCA test) of patients before and after surgery (at discharge, within 2 weeks after surgery and 6 months after surgery) to determine the relative impact of anesthetic care on the development of postoperative delirium and cognitive decline. All patients will have a brain scan (fMRI) before and after surgical intervention. Patients will also be asked to participate in an optional blood draw which will take place during their brain imaging visit and post operatively (within 2 days after surgery).

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea; Postoperative Delirium; Postoperative Cognitive Dysfunction
• Intervention / Treatment: Other: Goal directed therapy (GDT)

Detailed Description

This study will test the hypothesis that a goal directed therapy intervention, which optimizes depth of anesthesia and intraoperative blood pressure can decrease the incidence of postoperative neurocognitive dysfunction

Subjects will be recruited for the study and the protocol explained. In addition to standard American Society of Anesthesiologists (ASA) monitoring, we will monitor continuous non-invasive blood pressure and 4 lead electroencephalogram (EEG) channels. Patients will receive standardized anesthesia care in addition to a goal directed therapy hemodynamic management (MAP > 60 mmHg) and processed EEG-guided anesthesia (PSI targeted between 30-50).

Neurocognitive testing: In order to assess general cognitive function, the Montreal Cognitive Assessment test will be used. Cognitive function will be measured preoperatively and postoperatively at discharge, 1 month and 6 months after surgery. For delirium measurement, we will administer daily the Confusion Assessment Method (CAM-ICU) for up to 3 days.

The Montreal Cognitive Assessment (MoCA) is a screening tool to assess mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructionals skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal.

The Wide Range Assessment of Memory and Learning (WRAML2) is a broad-based memory battery that provides a flexible measure of memory functioning and learning and takes approximately 45-60 minutes to administer. This assessment will be conducted at the first MRI visit and at the 6 month follow up.

The Confusion Assessment Method for the ICU (CAM-ICU) screens for the development of delirium and assesses four features: 1) acute change or fluctuation in mental status from baseline, 2) inattention, 3) altered level of consciousness, and 4) disorganized thinking. The CAM-ICU is positive, and the patient is considered to have delirium, if features 1 and 2 and either feature 3 or 4 are present.

Brain imaging: The timing of pre-operative brain imaging will be as allowed by patient factors and scanner availability, typically less than 15 days before surgery, when the patient comes for the preoperative evaluation, and postoperatively within 2 weeks after surgery.

Optional Blood Draws: Patients will be asked to provide 2 optional blood samples, drawn the day of their brain imaging visit and post-operatively (within 2 days). These samples will be used to asses blood inflammatory biomarkers in obstructive sleep apnea (OSA) subjects and non-OSA subjects between baseline and post-surgery.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 45-75 years old,
• undergoing abdominal, orthopedic, gynecological, or urological surgery
• expected to stay in hospital for at least 24hours

Exclusion Criteria:

• Substantial hearing impairment or inability to understand English, since there needs to be neurocognitive testing done
• status post craniotomy
• severe dementia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Patients monitored and receiving a standard anesthesia plan in addition of a goal directed therapy (GDT) hemodynamic management (MAP > 60 mmHg) and processed EEG-guided anesthesia (PSI targeted between 30-50).	Other: Goal directed therapy (GDT); Goal directed therapy (GDT) hemodynamic management (MAP > 60 mmHg) and processed EEG-guided anesthesia (PSI targeted between 30-50).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative cognitive dysfunction	Montreal Cognitive Assessment (MoCA) test	Preoperatively (within 15 days of surgery)
Postoperative cognitive dysfunction	Montreal Cognitive Assessment (MoCA) test	postoperatively at discharge (within 2 weeks of surgery).
Postoperative cognitive dysfunction	Montreal Cognitive Assessment (MoCA) test	6 months after surgery.
Postoperative Delirium	Confusion Assessment Method (CAM-ICU)	Daily for up to 3 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examining brain changes	Using non-invasive magnetic resonance imaging based diffusion tensor imaging	Typically less than 15 days before surgery, when the patient comes for the preoperative evaluation, postoperatively at up to 48 hours after surgery, and 6 months post surgery
Examining brain changes II	Using non-invasive magnetic resonance imaging based diffusion tensor imaging	postoperatively within 2 weeks of surgery
Examining brain changes III	Using non-invasive magnetic resonance imaging based diffusion tensor imaging	6 months post surgery
Blood anti-inflammatory biomarkers	Assess blood inflammatory biomarkers (Il6, Il10, TNFa, IL1b, HMGB1) in OSA subjects and non-OSA subjects	pre-operatively (within 15 days before surgery)
Blood anti-inflammatory biomarkers	Assess blood inflammatory biomarkers (Il6, Il10, TNFa, IL1b, HMGB1) in OSA subjects and non-OSA subjects	post-operatively (within 2 days of surgery)

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Susana Vacas, M.D., Ph.D., Massachusetts General Hospital

Publications and helpful links

General Publications

• Joosten A, Rinehart J, Bardaji A, Van der Linden P, Jame V, Van Obbergh L, Alexander B, Cannesson M, Vacas S, Liu N, Slama H, Barvais L. Anesthetic Management Using Multiple Closed-loop Systems and Delayed Neurocognitive Recovery: A Randomized Controlled Trial. Anesthesiology. 2020 Feb;132(2):253-266. doi: 10.1097/ALN.0000000000003014.
• Vacas S, Cannesson M. Noninvasive Monitoring and Potential for Patient Outcome. J Cardiothorac Vasc Anesth. 2019 Aug;33 Suppl 1(Suppl 1):S76-S83. doi: 10.1053/j.jvca.2019.03.045. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2020
• Primary Completion (Actual): August 13, 2022
• Study Completion (Actual): August 13, 2022

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Estimate): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: magnetic resonance imaging (MRI); goal directed therapy (GDT); neurocognitive testing
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Postoperative Complications; Neurocognitive Disorders; Sleep Apnea Syndromes; Cognition Disorders; Sleep Apnea, Obstructive; Cognitive Dysfunction; Postoperative Cognitive Complications
• Other Study ID Numbers: HDBRAIN 16-001040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes