Awareness Under AnesthesiaNCT02938325
Monitoring Awareness and Pain Under Anesthesia Using a New EEG Based System
An observational study of Awareness Under Anesthesia, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
General anesthesia (GA) is the process of induction of unconsciousness in order to undergo surgery. Unlike sleep, a process of "anesthesia" is not related at all, 'Sleep' and does not include dreams - but is done by using drugs that cause a kind of "unconsciousness" control. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Awareness Under Anesthesia
- How many people
- 90 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jan 2017to Dec 2024
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients undergoing elective procedures under sedation, or patients undergoing surgery under general anesthesia. Another twenty volunteers will undergo elective EEG and BIS recording for 10 minutes, for comparison.
Who may be able to join
- ASA 1-3
- Patients for elective surgery under general anesthesia or elective procedures under sedation (such as cardiac electrical studies, liver chemo-embiolization, biliary tract drainage)
- The willing of the patient to fulfil the Modified Brice Questionnaire at the end of the procedure in recovery unit
- Healthy volunteers that will accept to be monitored with EEG and BIS for 10 minutes in supine position, as control.
Who cannot join
- Lack of consent
- Emergent surgery Emergent procedure (catheterization)
Trial locations and contacts
1 site in 1 country.
About this study
General anesthesia (GA) is the process of induction of unconsciousness in order to undergo surgery. Unlike sleep, a process of "anesthesia" is not related at all, 'Sleep' and does not include dreams - but is done by using drugs that cause a kind of "unconsciousness" control.
The induction of GA includes combination of drugs - for sleep (inhalation anesthesia or hypnotic drugs intravenously), analgesia (opiates) and muscle relaxants. Since most of our patients paralyzed during surgery, the anesthesiologists have no way of knowing whether our paralyzed patient is asleep or awake. If the patient is awake and paralyzed, a situation named "awareness under anesthesia" it can cause him a traumatic experience that would leave him a cripple for his whole life.
Read more
There are many stories about patients who lay paralyzed, awake, while been operated, who remembered every word of what happened during the operation and of course could not mark the anesthetist that they are awake. The anesthesiologist might suspect that his patient is awake and paralyzed through "signals" from the sympathetic nervous system - for example the increase in heart rate and blood pressure. But many of our patients receive different medications (eg, beta-receptor blockers that does not allow the rise of a pulse) obscuring the clinical signs, so that the patient is awake and paralyzed without being noticed by the anesthesiologist.
Some patients are at a higher risk to suffer from awareness under anesthesia, because the anesthesiologist cannot provide "enough" anesthesia, due to their medical condition, for example: women in caesarean section under GA, patients in cardiac surgery or injured trauma patients.
Twenty years ago, an EEG based tool, naming "BIS" was developed. Nowadays, BIS monitor's credibility is questionable 1. The effect of different hypnotic drugs is not uniform. 2. Recently it was shown that a paralyzed patient BIS index could fall mimicking a situation of a sleep - enabling a paralyzed patient being awake. Thus, it is not clear whether the calculation of the BIS monitor is based on physiological models that define what is consciousness, loss of consciousness and how consciousness arises. It seems that the BIS is only suitable for certain drugs - not as a general monitor for the level of anesthesia.
The purpose of the present study is to develop a universal system for determining awareness under GA using an innovative algorithm for analyzing EEG waves, based on the physiological processes of attention and perception underlying the basis for sedation and GA.
- Conditions
- Awareness Under Anesthesia
- Keywords
- Electroencephalogram, awareness
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 |
|---|---|---|
| No intervention: General Anesthesia | Thirty patients undergoing elective surgery under general anesthesia who will be monitored with standard ASA, BIS and EEG for comparisons. In recovery unit, at the end of the surgery, patients will be questioned for awareness under anesthesia by Modified Brice Questionnaire. There will be no intervention. Patients will be anesthetized with general anesthesia as they were supposed to be for their elective surgery. The EEG during the anesthesia will be assessed afterwards, and patients will be asked about their memory from the surgery. | |
| No intervention: Sedation | Fourty patients undergoing elective cardiac catheterization under conscious sedation who will be monitored with standard ASA, BIS and EEG for comparisons. In recovery unit, at the end of the procedure, patients will be questioned for awareness under sedation by Modified Brice Questionnaire. There will be no intervention. Patients will be anesthetized with sedation as they were supposed to be for their elective cardiac catheterization. The EEG during the anesthesia will be assessed afterwards, and patients will be asked about their memory from the surgery. | |
| No Intervention - Awake Volunteers | EEG and BIS will be recorded in twenty volunteers, for 10 minutes, in supine position, while their eyes are closed. This recording will be utilized as for positive control for recall. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Could a new EEG based Posteriorization/Anteriorization (P/A) index identify recall under sedation
Posteriorization/ Anteriorizatio index is analyzed at the end of the surgery, with no influence on the intraoperative treatment of the patient.
Measured: Immediately after surgery
Secondary outcomes (3)
The association between the P/A index to muscle activity
The correlation between the electromyelograph (EMG) activity, to the calculated index
Measured: Sub- analysis, within 6 months from the date the last patient was recruited for the study
The association between BIS to muscle activity
The correlation between the electromyelograph (EMG) activity, to BIS
Measured: Sub- analysis, within 6 months from the date the last patient was recruited for the study
Could Bis identify recall under sedation
BIS index is recorded during the procedure, but the anesthesiologists is blinded to its results. The association between BIS and recall is analyzed at the end of the surgery.
Measured: Immediately after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2016 (estimated)
- Study start1 Jan 2017
- Primary completionDec 2023 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Awareness Under AnesthesiaStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dana Baron Shahaf, MD PhD, Principal investigator, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02938325
- Sponsor's protocol ID
- 152-16 rambam-CTIL
- Status last verified
- Dec 2023
- First submitted
- 26 Sep 2016
- Last updated
- 8 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
White NS, Alkire MT. Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness. Neuroimage. 2003 Jun;19(2 Pt 1):402-11. doi: 10.1016/s1053-8119(03)00103-4.
PubMed 12814589Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia. Science. 2008 Nov 7;322(5903):876-80. doi: 10.1126/science.1149213.
PubMed 18988836Shalbaf R, Behnam H, Jelveh Moghadam H. Monitoring depth of anesthesia using combination of EEG measure and hemodynamic variables. Cogn Neurodyn. 2015 Feb;9(1):41-51. doi: 10.1007/s11571-014-9295-z. Epub 2014 May 9.
PubMed 26052361Osterman JE, Hopper J, Heran WJ, Keane TM, van der Kolk BA. Awareness under anesthesia and the development of posttraumatic stress disorder. Gen Hosp Psychiatry. 2001 Jul-Aug;23(4):198-204. doi: 10.1016/s0163-8343(01)00142-6.
PubMed 11543846Avidan MS, Palanca BJ, Glick D, Jacobsohn E, Villafranca A, O'Connor M, Mashour GA; BAG-RECALL Study Group. Protocol for the BAG-RECALL clinical trial: a prospective, multi-center, randomized, controlled trial to determine whether a bispectral index-guided protocol is superior to an anesthesia gas-guided protocol in reducing intraoperative awareness with explicit recall in high risk surgical patients. BMC Anesthesiol. 2009 Nov 30;9:8. doi: 10.1186/1471-2253-9-8.
PubMed 19948045Newton DE, Thornton C, Konieczko K, Frith CD, Dore CJ, Webster NR, Luff NP. Levels of consciousness in volunteers breathing sub-MAC concentrations of isoflurane. Br J Anaesth. 1990 Nov;65(5):609-15. doi: 10.1093/bja/65.5.609.
PubMed 2248835Dupont H. [Anesthesia awareness and the bispectral index]. Ann Fr Anesth Reanim. 2008 Dec;27(12):1042-3. doi: 10.1016/j.annfar.2008.10.013. No abstract available. French.
PubMed 19097272Short 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 27106988Suzuki M, Edmonds HL Jr, Tsueda K, Malkani AL, Roberts CS. Effect of ketamine on bispectral index and levels of sedation. J Clin Monit Comput. 1998 Jul;14(5):373. doi: 10.1023/a:1009975701184. No abstract available.
PubMed 9951765Voss L, Sleigh J. Monitoring consciousness: the current status of EEG-based depth of anaesthesia monitors. Best Pract Res Clin Anaesthesiol. 2007 Sep;21(3):313-25. doi: 10.1016/j.bpa.2007.04.003.
PubMed 17900011Chen Y, Cai A, Dexter F, Pryor KO, Jacobsohn EM, Glick DB, Willingham MD, Escallier K, Winter A, Avidan MS. Amnesia of the Operating Room in the B-Unaware and BAG-RECALL Clinical Trials. Anesth Analg. 2016 Apr;122(4):1158-68. doi: 10.1213/ANE.0000000000001175.
PubMed 26859877Brunner M, Vaughan D. Evoked potential monitoring in anaesthesia and analgesia. Anaesthesia. 2000 Aug;55(8):823-5. doi: 10.1046/j.1365-2044.2000.01629-27.x. No abstract available.
PubMed 10947725Shahaf 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 23805094Shahaf 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 25445244
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monitoring Awareness and Pain Under Anesthesia Using a New EEG Based System
- ClinicalTrials.gov ID
- NCT02938325
- Acronym / sponsor ID
- 152-16 rambam-CTIL
- Conditions
- Awareness Under Anesthesia
- Keywords
- Electroencephalogram, awareness
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 19 Oct 2016 (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.
General anesthesia (GA) is the process of induction of unconsciousness in order to undergo surgery. Unlike sleep, a process of "anesthesia" is not related at all, 'Sleep' and does not include dreams - but is done by using drugs that cause a kind of "unconsciousness" control.
The induction of GA includes combination of drugs - for sleep (inhalation anesthesia or hypnotic drugs intravenously), analgesia (opiates) and muscle relaxants. Since most of our patients paralyzed during surgery, the anesthesiologists have no way of knowing whether our paralyzed patient is asleep or awake. If the patient is awake and paralyzed, a situation named "awareness under anesthesia" it can cause him a traumatic experience that would leave him a cripple for his whole life.
There are many stories about patients who lay paralyzed, awake, while been operated, who remembered every word of what happened during the operation and of course could not mark the anesthetist that they are awake. The anesthesiologist might suspect that his patient is awake and paralyzed through "signals" from the sympathetic nervous system - for example the increase in heart rate and blood pressure. But many of our patients receive different medications (eg, beta-receptor blockers that does not allow the rise of a pulse) obscuring the clinical signs, so that the patient is awake and paralyzed without being noticed by the anesthesiologist.
Some patients are at a higher risk to suffer from awareness under anesthesia, because the anesthesiologist cannot provide "enough" anesthesia, due to their medical condition, for example: women in caesarean section under GA, patients in cardiac surgery or injured trauma patients.
Twenty years ago, an EEG based tool, naming "BIS" was developed. Nowadays, BIS monitor's credibility is questionable 1. The effect of different hypnotic drugs is not uniform. 2. Recently it was shown that a paralyzed patient BIS index could fall mimicking a situation of a sleep - enabling a paralyzed patient being awake. Thus, it is not clear whether the calculation of the BIS monitor is based on physiological models that define what is consciousness, loss of consciousness and how consciousness arises. It seems that the BIS is only suitable for certain drugs - not as a general monitor for the level of anesthesia.
The purpose of the present study is to develop a universal system for determining awareness under GA using an innovative algorithm for analyzing EEG waves, based on the physiological processes of attention and perception underlying the basis for sedation and GA.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| No intervention: General Anesthesia | – | –Thirty patients undergoing elective surgery under general anesthesia who will be monitored with standard ASA, BIS and EEG for comparisons. In recovery unit, at the end of the surgery, patients will be questioned for awareness under anesthesia by Modified Brice Questionnaire. There will be no intervention. Patients will be anesthetized with general anesthesia as they were supposed to be for their elective surgery. The EEG during the anesthesia will be assessed afterwards, and patients will be asked about their memory from the surgery. |
| No intervention: Sedation | – | –Fourty patients undergoing elective cardiac catheterization under conscious sedation who will be monitored with standard ASA, BIS and EEG for comparisons. In recovery unit, at the end of the procedure, patients will be questioned for awareness under sedation by Modified Brice Questionnaire. There will be no intervention. Patients will be anesthetized with sedation as they were supposed to be for their elective cardiac catheterization. The EEG during the anesthesia will be assessed afterwards, and patients will be asked about their memory from the surgery. |
| No Intervention - Awake Volunteers | – | –EEG and BIS will be recorded in twenty volunteers, for 10 minutes, in supine position, while their eyes are closed. This recording will be utilized as for positive control for recall. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing elective procedures under sedation, or patients undergoing surgery under general anesthesia. Another twenty volunteers will undergo elective EEG and BIS recording for 10 minutes, for comparison.
Key inclusion criteria (4 listed)
- ASA 1-3
- Patients for elective surgery under general anesthesia or elective procedures under sedation (such as cardiac electrical studies, liver chemo-embiolization, biliary tract drainage)
- The willing of the patient to fulfil the Modified Brice Questionnaire at the end of the procedure in recovery unit
- Healthy volunteers that will accept to be monitored with EEG and BIS for 10 minutes in supine position, as control.
Key exclusion criteria (2 listed)
- Lack of consent
- Emergent surgery Emergent procedure (catheterization)
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
Could a new EEG based Posteriorization/Anteriorization (P/A) index identify recall under sedation
Time frame: Immediately after surgery
Posteriorization/ Anteriorizatio index is analyzed at the end of the surgery, with no influence on the intraoperative treatment of the patient.
3 secondary outcomes
The association between the P/A index to muscle activity
Time frame: Sub- analysis, within 6 months from the date the last patient was recruited for the study
The association between BIS to muscle activity
Time frame: Sub- analysis, within 6 months from the date the last patient was recruited for the study
Could Bis identify recall under sedation
Time frame: Immediately after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2023.
- Background: PubMed 12814589White NS, Alkire MT. Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness. Neuroimage. 2003 Jun;19(2 Pt 1):402-11. doi: 10.1016/s1053-8119(03)00103-4.
- Background: PubMed 18988836Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia. Science. 2008 Nov 7;322(5903):876-80. doi: 10.1126/science.1149213.
- Background: PubMed 26052361Shalbaf R, Behnam H, Jelveh Moghadam H. Monitoring depth of anesthesia using combination of EEG measure and hemodynamic variables. Cogn Neurodyn. 2015 Feb;9(1):41-51. doi: 10.1007/s11571-014-9295-z. Epub 2014 May 9.
- Background: PubMed 11543846Osterman JE, Hopper J, Heran WJ, Keane TM, van der Kolk BA. Awareness under anesthesia and the development of posttraumatic stress disorder. Gen Hosp Psychiatry. 2001 Jul-Aug;23(4):198-204. doi: 10.1016/s0163-8343(01)00142-6.
- Background: PubMed 19948045Avidan MS, Palanca BJ, Glick D, Jacobsohn E, Villafranca A, O'Connor M, Mashour GA; BAG-RECALL Study Group. Protocol for the BAG-RECALL clinical trial: a prospective, multi-center, randomized, controlled trial to determine whether a bispectral index-guided protocol is superior to an anesthesia gas-guided protocol in reducing intraoperative awareness with explicit recall in high risk surgical patients. BMC Anesthesiol. 2009 Nov 30;9:8. doi: 10.1186/1471-2253-9-8.
- Background: PubMed 2248835Newton DE, Thornton C, Konieczko K, Frith CD, Dore CJ, Webster NR, Luff NP. Levels of consciousness in volunteers breathing sub-MAC concentrations of isoflurane. Br J Anaesth. 1990 Nov;65(5):609-15. doi: 10.1093/bja/65.5.609.
- Background: PubMed 19097272Dupont H. [Anesthesia awareness and the bispectral index]. Ann Fr Anesth Reanim. 2008 Dec;27(12):1042-3. doi: 10.1016/j.annfar.2008.10.013. No abstract available. French.
- 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 9951765Suzuki M, Edmonds HL Jr, Tsueda K, Malkani AL, Roberts CS. Effect of ketamine on bispectral index and levels of sedation. J Clin Monit Comput. 1998 Jul;14(5):373. doi: 10.1023/a:1009975701184. No abstract available.
- Background: PubMed 17900011Voss L, Sleigh J. Monitoring consciousness: the current status of EEG-based depth of anaesthesia monitors. Best Pract Res Clin Anaesthesiol. 2007 Sep;21(3):313-25. doi: 10.1016/j.bpa.2007.04.003.
- Background: PubMed 26859877Chen Y, Cai A, Dexter F, Pryor KO, Jacobsohn EM, Glick DB, Willingham MD, Escallier K, Winter A, Avidan MS. Amnesia of the Operating Room in the B-Unaware and BAG-RECALL Clinical Trials. Anesth Analg. 2016 Apr;122(4):1158-68. doi: 10.1213/ANE.0000000000001175.
- Background: PubMed 10947725Brunner M, Vaughan D. Evoked potential monitoring in anaesthesia and analgesia. Anaesthesia. 2000 Aug;55(8):823-5. doi: 10.1046/j.1365-2044.2000.01629-27.x. No abstract available.
- Individual participant dataSharing planned: No
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.
Dana Baron Shahaf, MD PhD principal investigator
Rambam Health Care Campus
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 Awareness Under Anesthesia, 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 4 inclusion and 2 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 8 Dec 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dana Baron Shahaf, MD PhD (972-4-7772487, dana_bs@rambam.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Could a new EEG based Posteriorization/Anteriorization (P/A) index identify recall under sedation (time frame: Immediately after surgery). 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 NCT02938325, which also lists 14 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 8 Dec 2023.