EEG-based Depth of Anesthesia-monitoring, Effects on Dosage and Cognition

NCT04529304 | Completed DMC

• 1 other identifier: 2019/32173
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Depth of anesthesia-monitoring based on EEG changes demands knowledge about the effects of the different anesthetic medications on EEG waveforms. The investigators want to investigate the use of the raw-EEG waveform in addition to indexes (BIS) and EEG spectrogram analyses for depth of anesthesia monitoring. The investigators hypothesize that with the use of this monitoring, anaesthesia providers will be able to better individualize the dosage of anesthetic drugs, and that this will reduce the total consumption of anesthetic medication , thus reducing time to wake-up after surgery. Some studies have indicated that too deep anesthesia, confirmed by "burst-suppression" or isoelectric-EEG , is associated with increased postoperative cognitive dysfunction (POCD). The investigators will therefore assess the patients with the Cambridge Neuropsychological Test Automated Battery tests in mild cognitive impairment (CANTAB-MCI) cognitive function assessment tool.

Conditions

Postoperative Complications; Delayed Emergence From Anesthesia; Cognitive Dysfunction

Keywords

Depth of Anesthesia Monitoring; Post operative cognitive dysfunction (POCD)

Outcome Measures

Primary Outcomes (4)

• EEG-based Depth of anesthesia-monitoring and dosage of anesthetic medications

  Summarizing the total amount of anesthetic drugs used, mg/kg/hr

  24 hours

• EEG-based Depth of anesthesia-monitoring and dosage of vasopressor medications during anesthesia

  Summarizing the total amount of vasopressor drugs used, micg/kg/min

  24 hours

• EEG-based Depth of anesthesia-monitoring and time to wake-up after surgery

  Time from the end of intravenous infusion of anesthetic - to motoric and verbal response.

  24 hours

• Evaluation of cognitive function using CANTAB-MCI

  Baseline assessment 1 day preoperatively, assessment 2-3 hours after wake-up, and 24 hours after wake-up using CANTAB-MCI

  1 day preoperatively to 24 hours after wake-up

Study Arms (2)

Visual EEG

EXPERIMENTAL

Individual dosing of anesthetic medications based on EEG AND other standardized clinical observations (BP, HR)

Device: Bilateral Bispectral Index and EEG

Blinded EEG

EXPERIMENTAL

Individual dosing of anesthetic medications based on standardized clinical observations (BP, HR).

Device: Bilateral Bispectral Index and EEG

Interventions

Bilateral Bispectral Index and EEG DEVICE

raw-EEG and spectrographic EEG-visualization based on the Medtronic Device "Bilateral BiSpectral Index"

Blinded EEG; Visual EEG

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Age
• Participant must be above the age of 18 years , at the time of signing the informed consent.
• Sex
• Male and/or female
• Informed Consent
• Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Psychiatric disorders
• Pregnancy
• Breast feeding
• Using antiepileptic drugs.
• Central neurological disease
• Unable to complete baseline CANTAB-test.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, Oslo County, 0124, Norway

Location

Related Publications (46)

• Gibbs FA, Gibbs LE, Lennox WG. Effects on the electroencephalogram of certain drugs which influence nervous activity. Arch Intern Med. 1937;60:154-66

  BACKGROUND

• KIERSEY DK, BICKFORD RG, FAULCONER A Jr. Electro-encephalographic patterns produced by thiopental sodium during surgical operations; description and classification. Br J Anaesth. 1951 Jul;23(3):141-52. doi: 10.1093/bja/23.3.141. No abstract available.

  PMID: 14848401 BACKGROUND

• Tinker JH, Sharbrough FW, Michenfelder JD. Anterior shift of the dominant EEG rhytham during anesthesia in the Java monkey: correlation with anesthetic potency. Anesthesiology. 1977 Apr;46(4):252-9. doi: 10.1097/00000542-197704000-00005.

  PMID: 402870 BACKGROUND

• John ER, Prichep LS, Kox W, Valdes-Sosa P, Bosch-Bayard J, Aubert E, Tom M, di Michele F, Gugino LD. Invariant reversible QEEG effects of anesthetics. Conscious Cogn. 2001 Jun;10(2):165-83. doi: 10.1006/ccog.2001.0507.

  PMID: 11414713 BACKGROUND

• Gugino LD, Chabot RJ, Prichep LS, John ER, Formanek V, Aglio LS. Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane. Br J Anaesth. 2001 Sep;87(3):421-8. doi: 10.1093/bja/87.3.421.

  PMID: 11517126 BACKGROUND

• Feshchenko VA, Veselis RA, Reinsel RA. Propofol-induced alpha rhythm. Neuropsychobiology. 2004;50(3):257-66. doi: 10.1159/000079981.

  PMID: 15365226 BACKGROUND

• Cimenser A, Purdon PL, Pierce ET, Walsh JL, Salazar-Gomez AF, Harrell PG, Tavares-Stoeckel C, Habeeb K, Brown EN. Tracking brain states under general anesthesia by using global coherence analysis. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8832-7. doi: 10.1073/pnas.1017041108. Epub 2011 May 9.

  PMID: 21555565 BACKGROUND

• Purdon PL, Pierce ET, Mukamel EA, Prerau MJ, Walsh JL, Wong KF, Salazar-Gomez AF, Harrell PG, Sampson AL, Cimenser A, Ching S, Kopell NJ, Tavares-Stoeckel C, Habeeb K, Merhar R, Brown EN. Electroencephalogram signatures of loss and recovery of consciousness from propofol. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1142-51. doi: 10.1073/pnas.1221180110. Epub 2013 Mar 4.

  PMID: 23487781 BACKGROUND

• Ching S, Cimenser A, Purdon PL, Brown EN, Kopell NJ. Thalamocortical model for a propofol-induced alpha-rhythm associated with loss of consciousness. Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22665-70. doi: 10.1073/pnas.1017069108. Epub 2010 Dec 13.

  PMID: 21149695 BACKGROUND

• Supp GG, Siegel M, Hipp JF, Engel AK. Cortical hypersynchrony predicts breakdown of sensory processing during loss of consciousness. Curr Biol. 2011 Dec 6;21(23):1988-93. doi: 10.1016/j.cub.2011.10.017. Epub 2011 Nov 17.

  PMID: 22100063 BACKGROUND

• Chauvette S, Crochet S, Volgushev M, Timofeev I. Properties of slow oscillation during slow-wave sleep and anesthesia in cats. J Neurosci. 2011 Oct 19;31(42):14998-5008. doi: 10.1523/JNEUROSCI.2339-11.2011.

  PMID: 22016533 BACKGROUND

• Lewis LD, Weiner VS, Mukamel EA, Donoghue JA, Eskandar EN, Madsen JR, Anderson WS, Hochberg LR, Cash SS, Brown EN, Purdon PL. Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness. Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):E3377-86. doi: 10.1073/pnas.1210907109. Epub 2012 Nov 5.

  PMID: 23129622 BACKGROUND

• Li D, Voss LJ, Sleigh JW, Li X. Effects of volatile anesthetic agents on cerebral cortical synchronization in sheep. Anesthesiology. 2013 Jul;119(1):81-8. doi: 10.1097/ALN.0b013e31828e894f.

  PMID: 23508217 BACKGROUND

• Wang K, Steyn-Ross ML, Steyn-Ross DA, Wilson MT, Sleigh JW. EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory. Front Syst Neurosci. 2014 Oct 29;8:215. doi: 10.3389/fnsys.2014.00215. eCollection 2014.

  PMID: 25400558 BACKGROUND

• Vizuete JA, Pillay S, Ropella KM, Hudetz AG. Graded defragmentation of cortical neuronal firing during recovery of consciousness in rats. Neuroscience. 2014 Sep 5;275:340-51. doi: 10.1016/j.neuroscience.2014.06.018. Epub 2014 Jun 18.

  PMID: 24952333 BACKGROUND

• Purdon PL, Sampson A, Pavone KJ, Brown EN. Clinical Electroencephalography for Anesthesiologists: Part I: Background and Basic Signatures. Anesthesiology. 2015 Oct;123(4):937-60. doi: 10.1097/ALN.0000000000000841.

  PMID: 26275092 BACKGROUND

• Lee JM, Akeju O, Terzakis K, Pavone KJ, Deng H, Houle TT, Firth PG, Shank ES, Brown EN, Purdon PL. A Prospective Study of Age-dependent Changes in Propofol-induced Electroencephalogram Oscillations in Children. Anesthesiology. 2017 Aug;127(2):293-306. doi: 10.1097/ALN.0000000000001717.

  PMID: 28657957 BACKGROUND

• Iwakiri H, Nishihara N, Nagata O, Matsukawa T, Ozaki M, Sessler DI. Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening. Anesth Analg. 2005 Jan;100(1):107-110. doi: 10.1213/01.ANE.0000139358.15909.EA.

  PMID: 15616062 BACKGROUND

• Avidan MS, Jacobsohn E, Glick D, Burnside BA, Zhang L, Villafranca A, Karl L, Kamal S, Torres B, O'Connor M, Evers AS, Gradwohl S, Lin N, Palanca BJ, Mashour GA; BAG-RECALL Research Group. Prevention of intraoperative awareness in a high-risk surgical population. N Engl J Med. 2011 Aug 18;365(7):591-600. doi: 10.1056/NEJMoa1100403.

  PMID: 21848460 BACKGROUND

• Palanca BJ, Mashour GA, Avidan MS. Processed electroencephalogram in depth of anesthesia monitoring. Curr Opin Anaesthesiol. 2009 Oct;22(5):553-9. doi: 10.1097/ACO.0b013e3283304032.

  PMID: 19652597 BACKGROUND

• Constant I, Sabourdin N. The EEG signal: a window on the cortical brain activity. Paediatr Anaesth. 2012 Jun;22(6):539-52. doi: 10.1111/j.1460-9592.2012.03883.x.

  PMID: 22594406 BACKGROUND

• Gibert S, Sabourdin N, Louvet N, Moutard ML, Piat V, Guye ML, Rigouzzo A, Constant I. Epileptogenic effect of sevoflurane: determination of the minimal alveolar concentration of sevoflurane associated with major epileptoid signs in children. Anesthesiology. 2012 Dec;117(6):1253-61. doi: 10.1097/ALN.0b013e318273e272.

  PMID: 23103557 BACKGROUND

• Fritz BA, Kalarickal PL, Maybrier HR, Muench MR, Dearth D, Chen Y, Escallier KE, Ben Abdallah A, Lin N, Avidan MS. Intraoperative Electroencephalogram Suppression Predicts Postoperative Delirium. Anesth Analg. 2016 Jan;122(1):234-42. doi: 10.1213/ANE.0000000000000989.

  PMID: 26418126 BACKGROUND

• Soehle M, Dittmann A, Ellerkmann RK, Baumgarten G, Putensen C, Guenther U. Intraoperative burst suppression is associated with postoperative delirium following cardiac surgery: a prospective, observational study. BMC Anesthesiol. 2015 Apr 28;15:61. doi: 10.1186/s12871-015-0051-7.

  PMID: 25928189 BACKGROUND

• Samarkandi AH. The bispectral index system in pediatrics--is it related to the end-tidal concentration of inhalation anesthetics? Middle East J Anaesthesiol. 2006 Feb;18(4):769-78.

  PMID: 16749571 BACKGROUND

• Tirel O, Wodey E, Harris R, Bansard JY, Ecoffey C, Senhadji L. Variation of bispectral index under TIVA with propofol in a paediatric population. Br J Anaesth. 2008 Jan;100(1):82-7. doi: 10.1093/bja/aem339.

  PMID: 18070785 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.

  PMID: 18337600 BACKGROUND

• Hajat Z, Ahmad N, Andrzejowski J. The role and limitations of EEG-based depth of anaesthesia monitoring in theatres and intensive care. Anaesthesia. 2017 Jan;72 Suppl 1:38-47. doi: 10.1111/anae.13739.

  PMID: 28044337 BACKGROUND

• Chhabra A, Subramaniam R, Srivastava A, Prabhakar H, Kalaivani M, Paranjape S. Spectral entropy monitoring for adults and children undergoing general anaesthesia. Cochrane Database Syst Rev. 2016 Mar 14;3(3):CD010135. doi: 10.1002/14651858.CD010135.pub2.

  PMID: 26976247 BACKGROUND

• Juel, Bjørn Erik; Romundstad, Luis Georg; Kolstad, Frode; Storm, Johan Frederik; Larsson, Pål Gunnar. Changes in EEG captured by Directed Transfer Function is sufficient to accurately classify the state of wakefulness in patients undergoing sevoflurane anesthesia in accordance with the clinician's judgement. FENS; 2018

  BACKGROUND

• Juel, Bjørn Erik; Kusztor, Aniko; Nilsen, Andre Sevenius; Farnes, Nadine; Larsson, Pål Gunnar; Romundstad, Luis Georg; Storm, Johan Frederik. Changes in electrophysiological markers of consciousness in response to various anesthetics. Nordic Neuroscience; 2017

  BACKGROUND

• Juel BE, Romundstad L, Kolstad F, Storm JF, Larsson PG. Distinguishing Anesthetized from Awake State in Patients: A New Approach Using One Second Segments of Raw EEG. Front Hum Neurosci. 2018 Feb 20;12:40. doi: 10.3389/fnhum.2018.00040. eCollection 2018.

  PMID: 29515381 BACKGROUND

• Nadine Farnes, Bjørn Erik Juel, André Sevenius Nilsen, Luis Romundstad, Johan Fredrik Storm Increased signal diversity/complexity of spontaneous EEG in humans given sub-anaesthetic doses of ketamine. bioRXiv 2019 508697; doi: https://doi.org/10.1101/508697

  BACKGROUND

• Messner M, Beese U, Romstock J, Dinkel M, Tschaikowsky K. The bispectral index declines during neuromuscular block in fully awake persons. Anesth Analg. 2003 Aug;97(2):488-491. doi: 10.1213/01.ANE.0000072741.78244.C0.

  PMID: 12873942 BACKGROUND

• Egerhazi A, Berecz R, Bartok E, Degrell I. Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):746-51. doi: 10.1016/j.pnpbp.2007.01.011. Epub 2007 Jan 16.

  PMID: 17289240 BACKGROUND

• Punjasawadwong Y, Phongchiewboon A, Bunchungmongkol N. Bispectral index for improving anaesthetic delivery and postoperative recovery. Cochrane Database Syst Rev. 2014 Jun 17;2014(6):CD003843. doi: 10.1002/14651858.CD003843.pub3.

  PMID: 24937564 BACKGROUND

• Masuda T, Yamada H, Takada K, Sagata Y, Yamaguchi M, Tomiyama Y, Oshita S. [Bispectral index monitoring is useful to reduce total amount of propofol and to obtain immediate recovery after propofol anesthesia]. Masui. 2002 Apr;51(4):394-9. Japanese.

  PMID: 11995347 BACKGROUND

• Struys MM, De Smet T, Versichelen LF, Van De Velde S, Van den Broecke R, Mortier EP. Comparison of closed-loop controlled administration of propofol using Bispectral Index as the controlled variable versus "standard practice" controlled administration. Anesthesiology. 2001 Jul;95(1):6-17. doi: 10.1097/00000542-200107000-00007.

  PMID: 11465585 BACKGROUND

• Tufano R, Palomba R, Lambiase G, Giurleo LG. [The utility of bispectral index monitoring in general anesthesia]. Minerva Anestesiol. 2000 May;66(5):389-93. Italian.

  PMID: 10965722 BACKGROUND

• Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet. 2000 Feb 26;355(9205):707-11. doi: 10.1016/S0140-6736(99)11010-9.

  PMID: 10703802 BACKGROUND

• Sebel PS, Bowdle TA, Ghoneim MM, Rampil IJ, Padilla RE, Gan TJ, Domino KB. The incidence of awareness during anesthesia: a multicenter United States study. Anesth Analg. 2004 Sep;99(3):833-839. doi: 10.1213/01.ANE.0000130261.90896.6C.

  PMID: 15333419 BACKGROUND

• Orser BA, Mazer CD, Baker AJ. Awareness during anesthesia. CMAJ. 2008 Jan 15;178(2):185-8. doi: 10.1503/cmaj.071761. Epub 2007 Dec 11. No abstract available.

  PMID: 18073268 BACKGROUND

• Pollard RJ, Coyle JP, Gilbert RL, Beck JE. Intraoperative awareness in a regional medical system: a review of 3 years' data. Anesthesiology. 2007 Feb;106(2):269-74. doi: 10.1097/00000542-200702000-00014.

  PMID: 17264720 BACKGROUND

• Errando CL, Sigl JC, Robles M, Calabuig E, Garcia J, Arocas F, Higueras R, Del Rosario E, Lopez D, Peiro CM, Soriano JL, Chaves S, Gil F, Garcia-Aguado R. Awareness with recall during general anaesthesia: a prospective observational evaluation of 4001 patients. Br J Anaesth. 2008 Aug;101(2):178-85. doi: 10.1093/bja/aen144. Epub 2008 May 30.

  PMID: 18515816 BACKGROUND

• Xu L, Wu AS, Yue Y. The incidence of intra-operative awareness during general anesthesia in China: a multi-center observational study. Acta Anaesthesiol Scand. 2009 Aug;53(7):873-82. doi: 10.1111/j.1399-6576.2009.02016.x. Epub 2009 Jun 3.

  PMID: 19496761 BACKGROUND

• Lewis SR, Pritchard MW, Fawcett LJ, Punjasawadwong Y. Bispectral index for improving intraoperative awareness and early postoperative recovery in adults. Cochrane Database Syst Rev. 2019 Sep 26;9(9):CD003843. doi: 10.1002/14651858.CD003843.pub4.

  PMID: 31557307 BACKGROUND

MeSH Terms

Conditions

Postoperative Complications; Delayed Emergence from Anesthesia; Cognitive Dysfunction

Interventions

Electroencephalography

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Luis G Romundstad, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Patient is blinded to intervention. Outcome assessoring done by patient/IPAD-solution from CANTAB, patient status assessed by blinded care-provider (nurse)
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Medical Doctor

Model Details: Two groups with 50 participants in each group. We want to compare one group with visible EEG-monitor with a group where the EEG monitor is invisible to the anesthetic team.

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: August 27, 2020
• Study Start: January 8, 2021
• Primary Completion: March 12, 2026
• Study Completion: March 13, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After end of study, 2025, and 5 years.
• Access Criteria: Access through application to study contactpersons.

Locations

NO (1)