An MRI Study of Post-operative Delirium in Patients Undergoing Major Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02126215
Recruitment Status : Recruiting
First Posted : April 29, 2014
Last Update Posted : December 2, 2017
Information provided by (Responsible Party):
University of Manitoba

Brief Summary:

Hypothesis: Patients with blue cerebrovascular reactivity (CVR) regional maps during a hypercapnic CO2 challenge will be at greater risk of developing post-operative delirium (POD) and stroke following major surgery. The blue CVR map will be shown to be predictive of POD and stroke and ultimately represent a diagnostic test for patients at risk. These blue CVR maps will enable neurologic risk stratification for patients undergoing major surgery. A secondary hypothesis is that location and extent of the blue CVR maps will strongly indicate risk of neurologic sequelae after operative procedures. Background: Major surgery is associated with a significant risk of postoperative morbidity and mortality. POD is a dreaded complication with such anesthesia and surgery. The prevalence of delirium after cardiac surgery has been reported to occur in up to 50% of patients. Using a definitive diagnostic tool such as the Confusion Assessment Method - Intensive Care Unit (CAM-ICU) results in the higher proportion reported. Delirium is a serious complication that results in prolonged length of stay, increased health care costs, and higher mortality. As much as $6.9 billion of Medicare hospital expenditures can be attributed to delirium. At such a cost, better diagnosis and treatment is urgently needed. Pre-emptive diagnosis leading to better management of delirium post-operatively is clearly one of the fundamental problems confronting modern anesthesia and peri-operative medicine.

Specific Objectives: The investigators seek to address (a) the identity of patients who have the greatest vulnerability to the surgery and (b) investigate the risks and test appropriate risk mitigations. Understanding POD is of immense import to help control a hospital's surgical and critical care costs. Patients with neurological consequences including POD often represent a choke point for optimized critical care utilization. At the very least, improved understanding and a diagnostic test to highlight patients at risk of POD would be most welcome. Such an advance would permit rational strategies to limit the problem and allow better designed therapeutic arcs for patients now known to be at risk. This is especially important for patients undergoing complicated major surgery and is the focus of this pilot project.

Condition or disease Intervention/treatment
Postoperative Delirium Procedure: MRI CO2 stress testing

Detailed Description:

Methods: Informed witnessed consent will be obtained from all participants. Patients will have a Mini Mental State Exam (MMSE) prior to their MRI studies. This will take 10 - 15 minutes. Patients will have CVR maps with blood oxygen level dependent (BOLD-MRI) pulse sequences done with standard RespirAct (a computer-controlled gas blender) protocols in association with anatomic imaging in a 3.0 Tesla magnet. The clinical care team and patient will be blinded as to the CVR results. Patients will have standardized anesthesia and per usual approaches for their major surgery and have standard POD assessment tools (CAM-ICU). Storage of anesthesia hemodynamics will be to digital data acquisition systems for later collation. End-tidal CO2 will be targeted at 40 mmHg during the surgical procedure and if ventilated for any period post-operatively. Standard fast-track protocols and admission to the surgical special care unit (SSCU) will be undertaken to facilitate patient management. Any patient with obvious POD, post-op delirium or stroke will be managed per usual protocols. Prior to discharge a second 3.0T CVR imaging sequence will be done - and additional diffusion weighted imaging (DWI) pulse sequencing (a sensitive approach to identify low level ischemia). Multiple CVR maps (650 studies) have been done at University Health Network in Toronto. As well over 75 studies have been conducted at the Health Sciences Centre at the University of Manitoba in the past 2 years.

Significance/Importance: This study has the potential to make an important contribution in the understanding of POD for all surgical procedures and specifically a window into the problem with major surgery. A positive study based on our hypothesis can fundamentally change our understanding of cognitive dysfunction after surgery. Large follow-up multicentre trials can be constructed based on initial findings from this pilot study if the study bears fruit. At the least, further elucidation into POD for major surgery is expected with this study.

Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: "Blue" Cerebrovascular Reactivity (CVR) Maps as a Marker for Post-operative Delirium (POD) in Patients Undergoing Abdominal Aortic Aneurysm (AAA) Surgery: A Pilot Study: Addition of Other Patients Being Admitted to SSCU After Major Surgery
Study Start Date : July 2014
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium
U.S. FDA Resources

Group/Cohort Intervention/treatment
Study group - MRI CO2 stress test
This is a pilot study to assess feasibility of using MRI CO2 stress testing to predict POD.
Procedure: MRI CO2 stress testing
Pre and post operatively

Primary Outcome Measures :
  1. Blue voxel count/whole brain voxel count [ Time Frame: Baseline ]
    the number and distribution of 'blue' voxels - those with reversed CO2 responsiveness to a controlled CO2 change with blood oxygen level dependent (BOLD) MRI.

  2. Incidence of post-op delirium [ Time Frame: Post-op out to discharge or maximum of 2 weeks post-surgery ]
    the incidence and severity of post-op delirium using the cognitive assessment method - intensive care unit (CAM-ICU) scoring approach twice a day.

Secondary Outcome Measures :
  1. Length of Stay (LOS) in hospital [ Time Frame: post-operatively to 2 weeks ]
    Length of stay in hospital - number of days from day of surgery up to a maximum of 2 weeks.

  2. Stroke [ Time Frame: Post-op until time of discharge up to 2 weeks ]
    Post-op stroke rate and severity will be assessed.

  3. Intra-operative blood pressure [ Time Frame: Intra-operative ]
    Blood pressure will be measured in mmHg at 60 hz. during the operative procedure. The nadir and time below 60 mmHg will be recorded.

Other Outcome Measures:
  1. Pre-op test for post-operative delirium (POD) [ Time Frame: up to 2 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients scheduled to undergo major surgery.

Inclusion Criteria:

  • major surgery
  • able to tolerate CO2 stress test

Exclusion Criteria:

  • diagnosed dementia
  • unable to have MRI
  • excessive claustrophobia
  • unstable angina, recent myocardial infarction (MI)
  • chronic obstructive pulmonary disease (COPD)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02126215

Contact: W. Alan Mutch, MD 2047893731
Contact: Linda Girling 2047871414

Canada, Manitoba
Kleysen Institute for Advanced Medicine - Health Sciences Centre Recruiting
Winnipeg, Manitoba, Canada, R3E 0Z2
Contact: W. Alan Mutch, MD    2047893731   
Contact: Linda Girling    2047871414   
Principal Investigator: W. Alan Mutch, MD         
Sponsors and Collaborators
University of Manitoba
Principal Investigator: W. Alan Mutch, MD University of Manitoba

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Manitoba Identifier: NCT02126215     History of Changes
Other Study ID Numbers: B2013:057-AAA
First Posted: April 29, 2014    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: January 2017

Keywords provided by University of Manitoba:
magnetic resonance imaging
carbon dioxide
abdominal aortic aneurysm
post-op delirium

Additional relevant MeSH terms:
Aortic Aneurysm
Aortic Aneurysm, Abdominal
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Vascular Diseases
Cardiovascular Diseases
Aortic Diseases