Postoperative DeliriumNCT02126215
An MRI Study of Post-operative Delirium in Patients Undergoing Major Surgery
An observational study of Postoperative Delirium, run by University of Manitoba at 1 site in Canada.
Trial 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. Blue CVR maps have also been recently documented with an O2 challenge. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Postoperative Delirium
- What is being tested?
- MRI CO2 and O2 stress testing
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2014to Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients scheduled to undergo major surgery.
Who may be able to join
- major surgery
- able to tolerate CO2 and O2 stress test
Who cannot join
- diagnosed dementia
- unable to have MRI
- excessive claustrophobia
- unstable angina, recent myocardial infarction (MI)
- chronic obstructive pulmonary disease (COPD)
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Kleysen Institute for Advanced Medicine - Health Sciences Centre
Winnipeg, Manitoba, R3E 0Z2
W. Alan Mutch, MD, 2047893731, amutch@cc.umanitoba.ca
Linda Girling, 2047871414, lgirling@hsc.mb.ca
About this study
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
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. Blue CVR maps have also been recently documented with an O2 challenge. The blue CVR maps 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. 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 and CAM-S) 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. Tighter control of ET respiratory gases may be indicated for both ET CO2 and ET O2 based on the results of this preliminary study.
Read the 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. A battery of neurocognitive tests will be undertaken for each subject prior to surgery. This test battery will include PHQ-9, GAD-7, Trails A and WAIS-IV Digit Span, Hopkins Verbal Learning Test Revised, Rey's Complex Figure, DKEFS, F-A-S, CLOX I and II. This will take 45-60 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 and CAM-S). Storage of anesthesia hemodynamics will be to digital data acquisition systems for later collation. End-tidal CO2 will be targeted at patient baseline values +/- 2.5 mmHg during the surgical procedure and if ventilated for any period post-operatively. Inspired O2 will be targeted to 0.3 - 0.6, based on pulse oximetry of greater than 95% with adequate arterial oxygenation confirmed by ABG. 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. Multiple CVR maps (650 studies) have been done at University Health Network in Toronto. As well over 150 studies have been conducted at the Health Sciences Centre at the University of Manitoba in the past 5 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. tighter control of end-tidal gases may be a consequence of the findings of this study.
- Conditions
- Postoperative Delirium
- Being tested
- MRI CO2 and O2 stress testing
- Keywords
- magnetic resonance imaging, carbon dioxide, abdominal aortic aneurysm, post-op delirium
- Medical subject headings
- Emergence Delirium, Aortic Aneurysm, Abdominal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI CO2 and O2 stress testingProcedure or surgery
Pre and post operatively
| Study group | Role | What they receive |
|---|---|---|
| Study group - MRI CO2 and O2 stress test | This is a pilot study to assess feasibility of using MRI CO2 and O2 stress testing to predict POD. Receives: Procedure: MRI CO2 and O2 stress testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blue voxel count/whole brain voxel count
the number and distribution of 'blue' voxels - those with reversed CO2 and O2 responsiveness to a controlled CO2 and O2 change with blood oxygen level dependent (BOLD) MRI.
Measured: Baseline
Incidence of post-op delirium
the incidence and severity of post-op delirium using the cognitive assessment method - intensive care unit (CAM-ICU) scoring approach twice a day.
Measured: Post-op out to discharge or maximum of 2 weeks post-surgery
Secondary outcomes (3)
Length of Stay (LOS) in hospital
Length of stay in hospital - number of days from day of surgery up to a maximum of 2 weeks.
Measured: post-operatively to 2 weeks
Stroke
Post-op stroke rate and severity will be assessed.
Measured: Post-op until time of discharge up to 2 weeks
Intra-operative blood pressure
Blood pressure will be measured in mmHg at 60 hz. during the operative procedure. The nadir and time below 60 mmHg will be recorded.
Measured: Intra-operative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Postoperative DeliriumStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- W. Alan Mutch, MD, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02126215
- Sponsor's protocol ID
- B2013:057-AAA
- Status last verified
- Jul 2019
- First submitted
- 22 Apr 2014
- Last updated
- 11 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Mutch WA, Mandell DM, Fisher JA, Mikulis DJ, Crawley AP, Pucci O, Duffin J. Approaches to brain stress testing: BOLD magnetic resonance imaging with computer-controlled delivery of carbon dioxide. PLoS One. 2012;7(11):e47443. doi: 10.1371/journal.pone.0047443. Epub 2012 Nov 5.
PubMed 23139743Mutch WAC, El-Gabalawy R. Anesthesia and postoperative delirium: the agent is a strawman - the problem is CO2. Can J Anaesth. 2017 Jun;64(6):678-680. doi: 10.1007/s12630-017-0859-3. Epub 2017 Mar 10. No abstract available.
PubMed 28283991El-Gabalawy R, Patel R, Kilborn K, Blaney C, Hoban C, Ryner L, Funk D, Legaspi R, Fisher JA, Duffin J, Mikulis DJ, Mutch WAC. A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management. Front Aging Neurosci. 2017 Aug 18;9:274. doi: 10.3389/fnagi.2017.00274. eCollection 2017.
PubMed 28868035Mutch WAC, El-Gabalawy RM, Graham MR. Postoperative Delirium, Learning, and Anesthetic Neurotoxicity: Some Perspectives and Directions. Front Neurol. 2018 Mar 20;9:177. doi: 10.3389/fneur.2018.00177. eCollection 2018.
PubMed 29615969Mutch WAC, El-Gabalawy R, Girling L, Kilborn K, Jacobsohn E. End-Tidal Hypocapnia Under Anesthesia Predicts Postoperative Delirium. Front Neurol. 2018 Aug 17;9:678. doi: 10.3389/fneur.2018.00678. eCollection 2018.
PubMed 30174647Mutch WAC, El-Gabalawy R, Ryner L, Puig J, Essig M, Kilborn K, Fidler K, Graham MR. Brain BOLD MRI O2 and CO2 stress testing: implications for perioperative neurocognitive disorder following surgery. Crit Care. 2020 Mar 4;24(1):76. doi: 10.1186/s13054-020-2800-3.
PubMed 32131878
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02126215
- Acronym / sponsor ID
- B2013:057-AAA
- Conditions
- Postoperative Delirium
- Keywords
- magnetic resonance imaging, carbon dioxide, abdominal aortic aneurysm, post-op delirium
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 29 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. Blue CVR maps have also been recently documented with an O2 challenge. The blue CVR maps 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. 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 and CAM-S) 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. Tighter control of ET respiratory gases may be indicated for both ET CO2 and ET O2 based on the results of this preliminary study.
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. A battery of neurocognitive tests will be undertaken for each subject prior to surgery. This test battery will include PHQ-9, GAD-7, Trails A and WAIS-IV Digit Span, Hopkins Verbal Learning Test Revised, Rey's Complex Figure, DKEFS, F-A-S, CLOX I and II. This will take 45-60 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 and CAM-S). Storage of anesthesia hemodynamics will be to digital data acquisition systems for later collation. End-tidal CO2 will be targeted at patient baseline values +/- 2.5 mmHg during the surgical procedure and if ventilated for any period post-operatively. Inspired O2 will be targeted to 0.3 - 0.6, based on pulse oximetry of greater than 95% with adequate arterial oxygenation confirmed by ABG. 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. Multiple CVR maps (650 studies) have been done at University Health Network in Toronto. As well over 150 studies have been conducted at the Health Sciences Centre at the University of Manitoba in the past 5 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. tighter control of end-tidal gases may be a consequence of the findings of this study.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study group - MRI CO2 and O2 stress test | – | Procedure: MRI CO2 and O2 stress testingThis is a pilot study to assess feasibility of using MRI CO2 and O2 stress testing to predict POD. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients scheduled to undergo major surgery.
Key inclusion criteria (2 listed)
- major surgery
- able to tolerate CO2 and O2 stress test
Key exclusion criteria (5 listed)
- diagnosed dementia
- unable to have MRI
- excessive claustrophobia
- unstable angina, recent myocardial infarction (MI)
- chronic obstructive pulmonary disease (COPD)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI CO2 and O2 stress testingPre and post operatively | Procedure or surgery | Study group - MRI CO2 and O2 stress test |
Primary outcome
Blue voxel count/whole brain voxel count
Time frame: Baseline
the number and distribution of 'blue' voxels - those with reversed CO2 and O2 responsiveness to a controlled CO2 and O2 change with blood oxygen level dependent (BOLD) MRI.
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.
3 secondary outcomes
Length of Stay (LOS) in hospital
Time frame: post-operatively to 2 weeks
Stroke
Time frame: Post-op until time of discharge up to 2 weeks
Intra-operative blood pressure
Time frame: Intra-operative
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2019.
- Background: PubMed 23139743Mutch WA, Mandell DM, Fisher JA, Mikulis DJ, Crawley AP, Pucci O, Duffin J. Approaches to brain stress testing: BOLD magnetic resonance imaging with computer-controlled delivery of carbon dioxide. PLoS One. 2012;7(11):e47443. doi: 10.1371/journal.pone.0047443. Epub 2012 Nov 5.
- Background: PubMed 28283991Mutch WAC, El-Gabalawy R. Anesthesia and postoperative delirium: the agent is a strawman - the problem is CO2. Can J Anaesth. 2017 Jun;64(6):678-680. doi: 10.1007/s12630-017-0859-3. Epub 2017 Mar 10. No abstract available.
- Background: PubMed 28868035El-Gabalawy R, Patel R, Kilborn K, Blaney C, Hoban C, Ryner L, Funk D, Legaspi R, Fisher JA, Duffin J, Mikulis DJ, Mutch WAC. A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management. Front Aging Neurosci. 2017 Aug 18;9:274. doi: 10.3389/fnagi.2017.00274. eCollection 2017.
- Background: PubMed 29615969Mutch WAC, El-Gabalawy RM, Graham MR. Postoperative Delirium, Learning, and Anesthetic Neurotoxicity: Some Perspectives and Directions. Front Neurol. 2018 Mar 20;9:177. doi: 10.3389/fneur.2018.00177. eCollection 2018.
- Background: PubMed 30174647Mutch WAC, El-Gabalawy R, Girling L, Kilborn K, Jacobsohn E. End-Tidal Hypocapnia Under Anesthesia Predicts Postoperative Delirium. Front Neurol. 2018 Aug 17;9:678. doi: 10.3389/fneur.2018.00678. eCollection 2018.
- Derived from this study: PubMed 32131878Mutch WAC, El-Gabalawy R, Ryner L, Puig J, Essig M, Kilborn K, Fidler K, Graham MR. Brain BOLD MRI O2 and CO2 stress testing: implications for perioperative neurocognitive disorder following surgery. Crit Care. 2020 Mar 4;24(1):76. doi: 10.1186/s13054-020-2800-3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
W. Alan Mutch, MD principal investigator
University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Postoperative Delirium, run by University of Manitoba at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact W. Alan Mutch, MD (2047893731, amutch@cc.umanitoba.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blue voxel count/whole brain voxel count (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02126215, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2019.