DeliriumNCT03293550
Can a New EEG Based Tool Predict Post-operative Delirium and Cognitive Dysfunction?
An observational study of Delirium and Cognitive Dysfunction, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
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 and categorized into two distinct clinical entities… Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Delirium, Cognitive Dysfunction
- How many people
- 160 participants
- Where
- 1 siteIsrael
- Study dates
- 31 Dec 2017to 6 Sep 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 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Study population: Patients 65 years or older, ASA 1-4, undergoing elective cardiac surgery (CABG or valve replacement) or hip/knee replacement.
Who may be able to join
- Patients 65 years or older undergoing elective cardiac surgery (CABG or valve replacement) or hip/knee replacement.
Who cannot join
- inability or refusal to provide informed consent,
- significant visual impairment so that the pictures of the confusion assessment method could not be interpreted to accurately test to assess delirium,
- profound dementia or aphasia that interfered with the assessment of delirium,
- inability to speak Hebrew/ Russian or Arabic so that a language barrier was not confused with postoperative confusion.
- Any previously documented major neurologic or psychiatric dysfunction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Association Between Minor Brain Injuries and Level of Anesthesia Detected by a New EEG Based Tool, to Delirium and Post-operative Cognitive Dysfunction After Cardiac and Non-cardiac Surgery - a Proof of Concept Study
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 and categorized into two distinct clinical entities; Post-operative cognitive delirium (POD) and post-operative cognitive dysfunction (POCD).
Delirium is an acute and fluctuating deterioration in attention accompanied by either a change in cognition or arousal and is often diagnosed by criteria established in the Confusion Assessment Method (CAM). Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms. Age and the type of operation are the major risk factors.
Read more
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 an 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.
Despite its limitations over-anesthesia as monitored by BIS was at-least correlative with POD. 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. In POCD a major role has been assigned to hippocampal damage.
The investigators have recently demonstrated that temporary hippocampal interruptions are manifested by interhemispheric desynchronization, which are recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception.
The investigators have developed a unique algorithm for analyzing EEG based on the concept of monitoring perception and attention and their interhemispheric synchronization.
The aims of this proof of concept study are: (i) to find-out whether interhemispheric desynchronization of attentional processes is associated with POCD; (ii) to find out whether the level of anesthesia, is linked primary to POD and secondary to POCD.
Read the detailed description
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 and categorized into two distinct clinical entities; Post-operative cognitive delirium (POD) and post-operative cognitive dysfunction (POCD).
Delirium is an acute and fluctuating deterioration in attention accompanied by either a change in cognition or arousal and is often diagnosed by criteria established in the Confusion Assessment Method (CAM). Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms. Age and the type of operation are the major risk factors.
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 use of neuropsychological tests, including; visual verbal learning test, based on Rey's auditive recall of words, the concept shifting test, based on the trail- making test from Halstead and Reitan's neuropsychological test battery, the Stroop color word interference test , the letter-digit coding, based on the symbol-digit substitution task from the Wechsler adult intelligence scale and the four boxes test. 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. There are two main problems with the BIS device: (1) It analyzes EEG and EMG with no ability to differentiate the neuronal activity from the muscle activity. Thus, when neuromuscular blocking drugs (NMBDs) are used, scores produced by the BIS are influenced by the lack of muscle activity, and mistakenly indicate a state of unconsciousness (lack of neuronal activity) even if no hypnotic medications were used, and (2) The BIS is based solely on frontal electrodes and does not monitor posterior activity. Thus, anesthetic medications with more posterior effect (such as ketamine) receive a false score by the BIS device. Accordingly, the BIS system might be better used as a means of tracking specific anesthetic medications and not as a universal means for monitoring unconsciousness.
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. In POCD a major role has been assigned to hippocampal damage.
The investigators have recently demonstrated that temporary hippocampal interruptions are manifested by interhemispheric desynchronization, which are 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, comprised of 6 electrodes.
The aims of this proof of concept study are: (i) to find-out whether interhemispheric desynchronization of attentional processes is associated with POCD; (ii) to find out whether the level of anesthesia, is linked primary to POD and secondary to POCD. For both purposes the investigators use a novel EEG algorithm based on the concept of monitoring perception and attention and their interhemispheric synchronization.
- Conditions
- Delirium, Cognitive Dysfunction
- Medical subject headings
- Delirium, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| patients over 65 years undergoing elective surgery | patients over 65 years undergoing elective cardiac surgery or elective hip or knee surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of depth of anesthesia to post operative delirium
Correlation of depth of anesthesia, as measured by a new EEG based algorithm, to post operative delirium
Measured: The diagnosis of delirium is assessed two hours after the operation, when the patient is fully awake, in the post anesthesia care unit (PACU)
Correlation of intra operative EEG changes to early post operative cognitive dysfunction
Correlation of EEG changes as measured by a new EEG based algorithm to post operative cognitive dysfunction
Measured: The diagnosis of cognitive dysfunction is assessed post operative on day 7 and compared to baseline pre surgery cognitive function.
Correlation of intra operative EEG changes to 45 days post operative cognitive dysfunction
Correlation of EEG changes as measured by a new EEG based algorithm to post operative cognitive dysfunction
Measured: The diagnosis of cognitive dysfunction is assessed post operative on day 45 and is compared to baseline pre surgery cognitive function.
Correlation of intra operative EEG changes to late post operative cognitive dysfunction
Correlation of EEG changes as measured by a new EEG based algorithm to post operative cognitive dysfunction
Measured: The diagnosis of cognitive dysfunction is assessed post operative on day 90 and is compared to baseline pre surgery cognitive function.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start31 Dec 2017
- Primary completion6 Sep 2020
- Study completion6 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Neuroindex Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03293550
- Sponsor's protocol ID
- 185-17 rambam-CTIL
- Status last verified
- Sep 2020
- First submitted
- 31 Aug 2017
- Last updated
- 17 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28187050Avidan 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.
PubMed 18337600Brown C 4th, Deiner S. Perioperative cognitive protection. Br J Anaesth. 2016 Dec;117(suppl 3):iii52-iii61. doi: 10.1093/bja/aew361.
PubMed 27940456Casati 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.
PubMed 16824246Chan 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.
PubMed 23027226Glass 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.
PubMed 9105228Inouye 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.
PubMed 2240918Paredes 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.
PubMed 27027720Moller 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.
PubMed 9525362Radtke 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.
PubMed 23539235Short 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.
PubMed 27106988Shahaf 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.
PubMed 26536542Shahaf 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.
PubMed 25445244Shahaf 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.
PubMed 23805094Wildes 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.
PubMed 27311914
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Association Between Minor Brain Injuries and Level of Anesthesia Detected by a New EEG Based Tool, to Delirium and Post-operative Cognitive Dysfunction After Cardiac and Non-cardiac Surgery - a Proof of Concept Study
- ClinicalTrials.gov ID
- NCT03293550
- Acronym / sponsor ID
- 185-17 rambam-CTIL
- Conditions
- Delirium, Cognitive Dysfunction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Collaborators
- Neuroindex Ltd.
- Study start
- 31 Dec 2017 (actual)
- Primary completion
- 6 Sep 2020 (actual)
- Study completion
- 6 Sep 2020 (actual)
- First posted
- 26 Sep 2017 (actual)
- 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.
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 and categorized into two distinct clinical entities; Post-operative cognitive delirium (POD) and post-operative cognitive dysfunction (POCD).
Delirium is an acute and fluctuating deterioration in attention accompanied by either a change in cognition or arousal and is often diagnosed by criteria established in the Confusion Assessment Method (CAM). Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms. Age and the type of operation are the major risk factors.
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 an 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.
Despite its limitations over-anesthesia as monitored by BIS was at-least correlative with POD. 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. In POCD a major role has been assigned to hippocampal damage.
The investigators have recently demonstrated that temporary hippocampal interruptions are manifested by interhemispheric desynchronization, which are recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception.
The investigators have developed a unique algorithm for analyzing EEG based on the concept of monitoring perception and attention and their interhemispheric synchronization.
The aims of this proof of concept study are: (i) to find-out whether interhemispheric desynchronization of attentional processes is associated with POCD; (ii) to find out whether the level of anesthesia, is linked primary to POD and secondary to POCD.
Detailed description
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 and categorized into two distinct clinical entities; Post-operative cognitive delirium (POD) and post-operative cognitive dysfunction (POCD).
Delirium is an acute and fluctuating deterioration in attention accompanied by either a change in cognition or arousal and is often diagnosed by criteria established in the Confusion Assessment Method (CAM). Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms. Age and the type of operation are the major risk factors.
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 use of neuropsychological tests, including; visual verbal learning test, based on Rey's auditive recall of words, the concept shifting test, based on the trail- making test from Halstead and Reitan's neuropsychological test battery, the Stroop color word interference test , the letter-digit coding, based on the symbol-digit substitution task from the Wechsler adult intelligence scale and the four boxes test. 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. There are two main problems with the BIS device: (1) It analyzes EEG and EMG with no ability to differentiate the neuronal activity from the muscle activity. Thus, when neuromuscular blocking drugs (NMBDs) are used, scores produced by the BIS are influenced by the lack of muscle activity, and mistakenly indicate a state of unconsciousness (lack of neuronal activity) even if no hypnotic medications were used, and (2) The BIS is based solely on frontal electrodes and does not monitor posterior activity. Thus, anesthetic medications with more posterior effect (such as ketamine) receive a false score by the BIS device. Accordingly, the BIS system might be better used as a means of tracking specific anesthetic medications and not as a universal means for monitoring unconsciousness.
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. In POCD a major role has been assigned to hippocampal damage.
The investigators have recently demonstrated that temporary hippocampal interruptions are manifested by interhemispheric desynchronization, which are 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, comprised of 6 electrodes.
The aims of this proof of concept study are: (i) to find-out whether interhemispheric desynchronization of attentional processes is associated with POCD; (ii) to find out whether the level of anesthesia, is linked primary to POD and secondary to POCD. For both purposes the investigators use a novel EEG algorithm based on the concept of monitoring perception and attention and their interhemispheric synchronization.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients over 65 years undergoing elective surgery | – | –patients over 65 years undergoing elective cardiac surgery or elective hip or knee surgery |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
- Study population
- Patients 65 years or older, ASA 1-4, undergoing elective cardiac surgery (CABG or valve replacement) or hip/knee replacement.
Key inclusion criteria (1 listed)
- Patients 65 years or older undergoing elective cardiac surgery (CABG or valve replacement) or hip/knee replacement.
Key exclusion criteria (5 listed)
- inability or refusal to provide informed consent,
- significant visual impairment so that the pictures of the confusion assessment method could not be interpreted to accurately test to assess delirium,
- profound dementia or aphasia that interfered with the assessment of delirium,
- inability to speak Hebrew/ Russian or Arabic so that a language barrier was not confused with postoperative confusion.
- Any previously documented major neurologic or psychiatric dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation of depth of anesthesia to post operative delirium
Time frame: The diagnosis of delirium is assessed two hours after the operation, when the patient is fully awake, in the post anesthesia care unit (PACU)
Correlation of depth of anesthesia, as measured by a new EEG based algorithm, to post operative delirium
Correlation of intra operative EEG changes to early post operative cognitive dysfunction
Time frame: The diagnosis of cognitive dysfunction is assessed post operative on day 7 and compared to baseline pre surgery cognitive function.
Correlation of EEG changes as measured by a new EEG based algorithm to post operative cognitive dysfunction
Correlation of intra operative EEG changes to 45 days post operative cognitive dysfunction
Time frame: The diagnosis of cognitive dysfunction is assessed post operative on day 45 and is compared to baseline pre surgery cognitive function.
Correlation of EEG changes as measured by a new EEG based algorithm to post operative cognitive dysfunction
Correlation of intra operative EEG changes to late post operative cognitive dysfunction
Time frame: The diagnosis of cognitive dysfunction is assessed post operative on day 90 and is compared to baseline pre surgery cognitive function.
Correlation of EEG changes as measured by a new EEG based algorithm to post operative cognitive dysfunction
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Background: PubMed 28187050Aldecoa 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.
- Background: PubMed 18337600Avidan 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.
- Background: PubMed 27940456Brown C 4th, Deiner S. Perioperative cognitive protection. Br J Anaesth. 2016 Dec;117(suppl 3):iii52-iii61. doi: 10.1093/bja/aew361.
- Background: PubMed 16824246Casati 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.
- Background: PubMed 23027226Chan 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.
- Background: PubMed 9105228Glass 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.
- Background: PubMed 2240918Inouye 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.
- Background: PubMed 27027720Paredes 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.
- Background: PubMed 9525362Moller 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.
- Background: PubMed 23539235Radtke 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.
- Background: PubMed 27106988Short 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.
- Background: PubMed 26536542Shahaf 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.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Delirium and Cognitive Dysfunction, run by Rambam Health Care Campus at 1 site in Israel.
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 1 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: finished, as of the sponsor's last update on 17 Sep 2020. 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 Israel. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of depth of anesthesia to post operative delirium (time frame: The diagnosis of delirium is assessed two hours after the operation, when the patient is fully awake, in the post anesthesia care unit (PACU)). The study lists 4 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 NCT03293550, which also lists 15 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 17 Sep 2020.