Use of Electrophysiological Markers to Predict Post-operative Cognitive Dysfunction
NCT ID: NCT04512989
Last Updated: 2023-12-08
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Total Enrollment
100 participants
Study Classification
OBSERVATIONAL
Study Start Date
2020-10-01
Study Completion Date
2024-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
As the population ages and medical progress is made, many elderly patients that previously would not have been candidates for surgery are now undergoing operations. In this group of older patients, brain dysfunction after anesthesia and surgery, naming post-operative cognitive dysfunction, is well known.
Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. It was previously found that the presence of cognitive dysfunction 3 months after non-cardiac surgery was associated with increased mortality. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors are related to patient characteristics, type of operation and anesthetic management.
The investigators have recently shown that using different electrophysiological markers, they can monitor attention and perception which might be associated with brain frailty and brain injury.
The aims of this proof of concept study are: (i) to find-out whether attention processes might be in association with brain frailty. (ii) to find our whether brain injury which is expressed by interhemispheric synchronization is is associated with POCD; (iii) to find out whether the level of anesthesia, as measured electrophysiological by perception might be linked primary to POCD.
Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. It was previously found that the presence of cognitive dysfunction 3 months after non-cardiac surgery was associated with increased mortality. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors are related to patient characteristics, type of operation and anesthetic management.
The investigators have recently shown that using different electrophysiological markers, they can monitor attention and perception which might be associated with brain frailty and brain injury.
The aims of this proof of concept study are: (i) to find-out whether attention processes might be in association with brain frailty. (ii) to find our whether brain injury which is expressed by interhemispheric synchronization is is associated with POCD; (iii) to find out whether the level of anesthesia, as measured electrophysiological by perception might be linked primary to POCD.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
As the population ages and medical progress is made, many elderly patients that previously would not have been candidates for surgery are now undergoing operations. In this group of older patients, brain dysfunction after anesthesia and surgery is well recognized, naming post-operative cognitive dysfunction.
Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. The reported incidence figures for postoperative cognitive dysfunction vary depending on the group of patients studied, the definition of POCD used, the tests used to establish the diagnosis and their statistical evaluation, the timing of testing, and the choice of control group. The diagnosis of POCD relies on the availability of the neuropsychological tests. In a large prospective multicenter cohort study, it was found that the presence of cognitive dysfunction 3 months after noncardiac surgery was associated with an increased mortality. Furthermore, patients with cognitive decline at 1 week had an increased risk of leaving the labor market prematurely and a higher prevalence of time receiving social transfer payments. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors for developing POCD are related to patient characteristics, type of operation and anesthetic management.
Cardiovascular, respiratory, hepatic, and renal insufficiency are all associated with impaired brain performance. It is theoretically obvious that an adequate intraoperative oxygen supply for all vital organs is essential if postoperative cerebral dysfunction is to be avoided. Casai et al found that brain desaturation (rSO2 decrease \<75% of baseline) occurred in 40% of elderly patients after noncardiac surgery, and the cerebral desaturation was linked with a high incidence of POCD. A recent systematic review shows that reductions in cerebral oxygen saturation (rSO2) during cardiac surgery may indicate CPB cannula malposition, particularly during aortic surgery. However, only weak evidence links low rSO2 during cardiac surgery to POCD.
POCD is a well-recognized clinical phenomenon of multifactorial origin; emboli, hypoperfusion, inflammation, and patient's preoperative cerebral dysfunction. Meticulous surgical and anesthesiological techniques are important for preventing complications and keeping the risk of POCD to a minimum.
The EEG is an electrophysiological monitoring method used to record electrical activity of the brain, including normal and abnormal activity. In recent years, numerous clinical studies were performed to evaluate whether the use in intraoperative electroencephalography (EEG) to control the depth of anesthesia has any effect on POCD.
Recently it was confirmed that intraoperative neuro-monitoring for depth of anesthesia is associated with a lower incidence of delirium. However it is unrelated to the incidence of POCD. The most common available monitor for depth of anesthesia is the Bispectral index, developed more than 20 years ago. The device's output is based on electroencephalographic (EEG) signals from the frontal lobe (monitors brain activity) in combination with electromyographic (EMG) waves (monitors muscle activity). The BIS produces a number ranging from 0 -100, which matches the patient's level of consciousness (awake, sedated or unconscious) under GA.
Despite its limitations, over-anesthesia as monitored by BIS, was at-least correlative with POD (but not with POCD). Therefore, it is hopeful that an even more precise evaluation of the level of anesthesia will improve POD prediction (and thereby prevention) even further. On the other hand the measure of depth of anesthesia by itself does not provide sufficient prediction for POCD.
The investigators have recently that brain injury is demonstrated by interhemispheric desynchronization, which is recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception. This algorithm was based on a previous set of studies, which showed the ability to decompose the entire multi-electrode EEG/ ERP sample to a superposition of attention and perception processes, spread in space (over the scalp) and time (hundreds of milliseconds). Our algorithm is unique in the ability to extract the needed perceptual and attentional information indicating depth of anesthesia and hemispheric damage (manifested by interhemispheric desynchronization) in real time every 30 seconds and with a minimal electrodes' setup.
The aims of this proof of concept study are: (i) to find-out whether attention processes might be in association with brain frailty. (ii) to find our whether brain injury which is expressed by interhemispheric synchronization is is associated with POCD; (iii) to find out whether the level of anesthesia, as measured electrophysiological by perception might be linked primary to POCD.
Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. The reported incidence figures for postoperative cognitive dysfunction vary depending on the group of patients studied, the definition of POCD used, the tests used to establish the diagnosis and their statistical evaluation, the timing of testing, and the choice of control group. The diagnosis of POCD relies on the availability of the neuropsychological tests. In a large prospective multicenter cohort study, it was found that the presence of cognitive dysfunction 3 months after noncardiac surgery was associated with an increased mortality. Furthermore, patients with cognitive decline at 1 week had an increased risk of leaving the labor market prematurely and a higher prevalence of time receiving social transfer payments. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors for developing POCD are related to patient characteristics, type of operation and anesthetic management.
Cardiovascular, respiratory, hepatic, and renal insufficiency are all associated with impaired brain performance. It is theoretically obvious that an adequate intraoperative oxygen supply for all vital organs is essential if postoperative cerebral dysfunction is to be avoided. Casai et al found that brain desaturation (rSO2 decrease \<75% of baseline) occurred in 40% of elderly patients after noncardiac surgery, and the cerebral desaturation was linked with a high incidence of POCD. A recent systematic review shows that reductions in cerebral oxygen saturation (rSO2) during cardiac surgery may indicate CPB cannula malposition, particularly during aortic surgery. However, only weak evidence links low rSO2 during cardiac surgery to POCD.
POCD is a well-recognized clinical phenomenon of multifactorial origin; emboli, hypoperfusion, inflammation, and patient's preoperative cerebral dysfunction. Meticulous surgical and anesthesiological techniques are important for preventing complications and keeping the risk of POCD to a minimum.
The EEG is an electrophysiological monitoring method used to record electrical activity of the brain, including normal and abnormal activity. In recent years, numerous clinical studies were performed to evaluate whether the use in intraoperative electroencephalography (EEG) to control the depth of anesthesia has any effect on POCD.
Recently it was confirmed that intraoperative neuro-monitoring for depth of anesthesia is associated with a lower incidence of delirium. However it is unrelated to the incidence of POCD. The most common available monitor for depth of anesthesia is the Bispectral index, developed more than 20 years ago. The device's output is based on electroencephalographic (EEG) signals from the frontal lobe (monitors brain activity) in combination with electromyographic (EMG) waves (monitors muscle activity). The BIS produces a number ranging from 0 -100, which matches the patient's level of consciousness (awake, sedated or unconscious) under GA.
Despite its limitations, over-anesthesia as monitored by BIS, was at-least correlative with POD (but not with POCD). Therefore, it is hopeful that an even more precise evaluation of the level of anesthesia will improve POD prediction (and thereby prevention) even further. On the other hand the measure of depth of anesthesia by itself does not provide sufficient prediction for POCD.
The investigators have recently that brain injury is demonstrated by interhemispheric desynchronization, which is recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception. This algorithm was based on a previous set of studies, which showed the ability to decompose the entire multi-electrode EEG/ ERP sample to a superposition of attention and perception processes, spread in space (over the scalp) and time (hundreds of milliseconds). Our algorithm is unique in the ability to extract the needed perceptual and attentional information indicating depth of anesthesia and hemispheric damage (manifested by interhemispheric desynchronization) in real time every 30 seconds and with a minimal electrodes' setup.
The aims of this proof of concept study are: (i) to find-out whether attention processes might be in association with brain frailty. (ii) to find our whether brain injury which is expressed by interhemispheric synchronization is is associated with POCD; (iii) to find out whether the level of anesthesia, as measured electrophysiological by perception might be linked primary to POCD.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Cognitive Dysfunction
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
cognitive dysfunction
EEG
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Observational Model Type
COHORT
Study Time Perspective
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Patients undergoing cardiac surgery
Cognitive assesment using MOCA test
Intervention Type
DIAGNOSTIC_TEST
Cognitive assesment using MOCA test
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Cognitive assesment using MOCA test
Cognitive assesment using MOCA test
Intervention Type
DIAGNOSTIC_TEST
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients 18 years and older undergoing elective cardiac surgery (CABG or valve replacement).
Exclusion Criteria
1. inability or refusal to provide informed consent,
2. significant visual impairment so that the pictures of the cognitive tests could not be interpreted accurately.
3. profound dementia or aphasia that interfered with the cognitive assessment.
4. inability to speak Hebrew/ Russian or Arabic so that a language barrier was not confused with postoperative cognitive dysfunction.
5. . Any previously documented major neurologic or psychiatric dysfunction
2. significant visual impairment so that the pictures of the cognitive tests could not be interpreted accurately.
3. profound dementia or aphasia that interfered with the cognitive assessment.
4. inability to speak Hebrew/ Russian or Arabic so that a language barrier was not confused with postoperative cognitive dysfunction.
5. . Any previously documented major neurologic or psychiatric dysfunction
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Rambam Health Care Campus
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Dana Baron Shahaf
Role: PRINCIPAL_INVESTIGATOR
Rambam Health Care Campus
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Rambam Health Care Campus
Haifa, , Israel
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
Israel
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Audisio R, Borozdina A, Cherubini A, Jones C, Kehlet H, MacLullich A, Radtke F, Riese F, Slooter AJ, Veyckemans F, Kramer S, Neuner B, Weiss B, Spies CD. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. 2017 Apr;34(4):192-214. doi: 10.1097/EJA.0000000000000594.
Reference Type
BACKGROUND
Avidan MS, Zhang L, Burnside BA, Finkel KJ, Searleman AC, Selvidge JA, Saager L, Turner MS, Rao S, Bottros M, Hantler C, Jacobsohn E, Evers AS. Anesthesia awareness and the bispectral index. N Engl J Med. 2008 Mar 13;358(11):1097-108. doi: 10.1056/NEJMoa0707361.
Reference Type
BACKGROUND
Brown C 4th, Deiner S. Perioperative cognitive protection. Br J Anaesth. 2016 Dec;117(suppl 3):iii52-iii61. doi: 10.1093/bja/aew361.
Reference Type
BACKGROUND
Casati A, Fanelli G, Pietropaoli P, Proietti R, Tufano R, Montanini S; Collaborative Italian Study Group on Anaesthesia in Elderly Patients; Danelli G, Nuzzi M, Mentegazzi F, Torri G, Martani C, Spreafico E, Fierro G, Pugliese F, De Cosmo G, Aceto P, Servillo G, Monaco F. Monitoring cerebral oxygen saturation in elderly patients undergoing general abdominal surgery: a prospective cohort study. Eur J Anaesthesiol. 2007 Jan;24(1):59-65. doi: 10.1017/S0265021506001025. Epub 2006 Jul 7.
Reference Type
BACKGROUND
Chan MT, Cheng BC, Lee TM, Gin T; CODA Trial Group. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol. 2013 Jan;25(1):33-42. doi: 10.1097/ANA.0b013e3182712fba.
Reference Type
BACKGROUND
Glass PS, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology. 1997 Apr;86(4):836-47. doi: 10.1097/00000542-199704000-00014.
Reference Type
BACKGROUND
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8. doi: 10.7326/0003-4819-113-12-941.
Reference Type
BACKGROUND
Paredes S, Cortinez L, Contreras V, Silbert B. Post-operative cognitive dysfunction at 3 months in adults after non-cardiac surgery: a qualitative systematic review. Acta Anaesthesiol Scand. 2016 Sep;60(8):1043-58. doi: 10.1111/aas.12724. Epub 2016 Mar 29.
Reference Type
BACKGROUND
Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0.
Reference Type
BACKGROUND
Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth. 2013 Jun;110 Suppl 1:i98-105. doi: 10.1093/bja/aet055. Epub 2013 Mar 28.
Reference Type
BACKGROUND
Short TG, Campbell D, Leslie K. Response of bispectral index to neuromuscular block in awake volunteers. Br J Anaesth. 2016 May;116(5):725-6. doi: 10.1093/bja/aew089. No abstract available.
Reference Type
BACKGROUND
Shahaf DB, Shahaf G, Mehta J, Venkatraghavan L. Intracarotid Etomidate Decreases the Interhemispheric Synchronization in Electroencephalogram (EEG) During the Wada Test. J Neurosurg Anesthesiol. 2016 Oct;28(4):341-6. doi: 10.1097/ANA.0000000000000241.
Reference Type
BACKGROUND
Shahaf G, Fisher T, Aharon-Peretz J, Pratt H. Comprehensive analysis suggests simple processes underlying EEG/ERP - demonstration with the go/no-go paradigm in ADHD. J Neurosci Methods. 2015 Jan 15;239:183-93. doi: 10.1016/j.jneumeth.2014.10.016. Epub 2014 Nov 1.
Reference Type
BACKGROUND
Shahaf G, Pratt H. Thorough specification of the neurophysiologic processes underlying behavior and of their manifestation in EEG - demonstration with the go/no-go task. Front Hum Neurosci. 2013 Jun 24;7:305. doi: 10.3389/fnhum.2013.00305. eCollection 2013.
Reference Type
BACKGROUND
Wildes TS, Winter AC, Maybrier HR, Mickle AM, Lenze EJ, Stark S, Lin N, Inouye SK, Schmitt EM, McKinnon SL, Muench MR, Murphy MR, Upadhyayula RT, Fritz BA, Escallier KE, Apakama GP, Emmert DA, Graetz TJ, Stevens TW, Palanca BJ, Hueneke R, Melby S, Torres B, Leung JM, Jacobsohn E, Avidan MS. Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial. BMJ Open. 2016 Jun 15;6(6):e011505. doi: 10.1136/bmjopen-2016-011505.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
542-20
Identifier Type: -
Identifier Source: org_study_id