Association Between Burst Suppression During Anesthetic Induction With Postoperative Delirium in Cardiac Surgery

Postoperative Delirium Clinical Trial

Official title:

Study of the Association Between Burst Suppression During Anesthetic Induction With Propofol in Cardiac Surgery in Patients Over 65 Years of Age With Postoperative Delirium

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04713644
• Other study ID #: 200923005
• Status: Recruiting
• Start date: March 1, 2021
• Est. completion date: January 31, 2022

Study information

• Verified date: January 2021
• Source: Pontificia Universidad Catolica de Chile
• Contact: Juan C Pedemonte, MD
• Phone: +56223543270
• Email: jcpedemo[@]uc.cl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The population over 65 years of age will be increasingly exposed to surgical procedures that require general anesthesia. Postoperative delirium is one of the main causes of preventable postoperative morbidity in the elderly population and is a frequent event after cardiac surgery with extracorporeal circulation. The excess administration of anesthetics that potentiate the Gamma Aminobutyric A receptor, such as propofol, are related to an intraoperative electroencephalographic pattern called burst suppression that has been associated with postoperative delirium. It is unknown whether this pattern is secondary to a relative overdose of anesthetics or rather corresponds to a characteristic of a vulnerable brain that is suppressed at doses at which other patients are not. Our objective will be to determine whether burst suppression in people over 65 years of age during a standardized anesthetic induction with propofol for cardiac surgery with extracorporeal circulation is associated with postoperative delirium compared to older people who do not present it.

Description:

Perioperative neurocognitive disorders, including postoperative delirium (POD), are the leading cause of preventable postoperative morbidity in the elderly population. POD is an acute brain dysfunction characterized by changes in attention and cognition usually within of the first week after surgery and anesthesia. Its appearance triggers a series of events that often end in loss of independence, increased morbidity and mortality and increased health costs. It has been associated with the development of long-term cognitive impairment, including persistent dementia. Its nature is multifactorial and its pathophysiology is not yet fully elucidated.

Over administration of anesthetics that potentiate the Gamma Amino Butyric A (GABAA) receptor, such as barbiturates or propofol, is related to an intraoperative electroencephalographic (EEG) pattern called burst suppression that has been associated with POD. It is a common event after cardiac surgery with an incidence ranging from 15% to 50%. Given its adverse impact on functioning and quality of life, delirium has enormous social implications for the individual, family, community, and health care systems.

Burst suppression is a pattern observed in the EEG characterized by quasi-periodic alternations between isoelectricity (flat EEG) and brief bursts of electrical activity such as spikes, sharp waves, or slow waves. It reflects a brain state of relative cortical inactivity that is not observed during normal waking states or sleeping behaviors. This pattern can be observed associated with coma due to diffuse anoxic damage, induced hypothermia and Ohtahara syndrome epilepsy. In addition, the administration of high-dose anesthetics that potentiate the GABAA receptor produce burst suppression followed by isoelectricity. Burst suppression during maintenance of general anesthesia with anesthetics that enhance the GABAA receptor has previously been associated with POD. When propofol is administered as a bolus during anesthetic induction, older patients, can suffer burst suppression in seconds. However, it is unknown whether this pattern is secondary to a relative overdose of anesthetics or rather corresponds to a characteristic of the vulnerable brain that is suppressed at doses to which other patients do not present this pattern. At present, it is not known whether burst suppression is a modifiable risk factor for POD or an epiphenomenon or marker of other factors that cause POD. A randomized controlled clinical trial studied an EEG-guided anesthetic protocol that reduced the administration of anesthetic, diminished the incidence of burts suppression during the intraoperative period, but not the incidence of POD. Therefore, the association between bursts suppression induced by anesthetics and POD appears not to be causal.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 100 Years

Eligibility

Inclusion Criteria:

• Patients = 65 years of age

• Undergoing elective cardiac surgery requiring extracorporeal circulation (coronary artery bypass, univalvular replacement, bivalvular and coronary artery bypass plus univalvular replacement)

• American Society of Anesthesiologists Physical Status II-III.

Exclusion Criteria:

• Body Mass Index > 35 and <18 Kg / m2

• Severe ventricular dysfunction (EF < 30% or severe dysfunction measured in ventriculography)

• Emergency surgery

• Chronic use of alcohol or drug abuse

• History of Stroke

• Neurological diseases

• Endocarditis

• Positive screening for preoperative delirium.

Related Conditions & MeSH terms

• Delirium
• Postoperative Delirium

Intervention

Drug:
• Standardized Propofol Administration
Intravenous bolus propofol administration of 0.5 mg/Kg dose, plus 0.5 mg/Kg extra if necessary

Locations

Country	Name	City	State
Chile	Hospital Clínico Pontificia Universidad Católica de Chile	Santiago	Región Metropolitana

Sponsors (1)

Lead Sponsor	Collaborator
Pontificia Universidad Catolica de Chile

Country where clinical trial is conducted

Chile, 

References & Publications (18)

Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology. 2018 Oct;129(4):829-851. doi: 10.1097/ALN.0000000000002194. Review. — View Citation

Besch G, Liu N, Samain E, Pericard C, Boichut N, Mercier M, Chazot T, Pili-Floury S. Occurrence of and risk factors for electroencephalogram burst suppression during propofol-remifentanil anaesthesia. Br J Anaesth. 2011 Nov;107(5):749-56. doi: 10.1093/bja/aer235. Epub 2011 Aug 8. — View Citation

Boone MD, Sites B, von Recklinghausen FM, Mueller A, Taenzer AH, Shaefi S. Economic Burden of Postoperative Neurocognitive Disorders Among US Medicare Patients. JAMA Netw Open. 2020 Jul 1;3(7):e208931. doi: 10.1001/jamanetworkopen.2020.8931. — View Citation

Brown CH 4th, Max L, LaFlam A, Kirk L, Gross A, Arora R, Neufeld K, Hogue CW, Walston J, Pustavoitau A. The Association Between Preoperative Frailty and Postoperative Delirium After Cardiac Surgery. Anesth Analg. 2016 Aug;123(2):430-5. doi: 10.1213/ANE.0000000000001271. — View Citation

Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. Review. — View Citation

Deiner S, Westlake B, Dutton RP. Patterns of surgical care and complications in elderly adults. J Am Geriatr Soc. 2014 May;62(5):829-35. doi: 10.1111/jgs.12794. Epub 2014 Apr 14. — View Citation

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. — View Citation

Fritz BA, Maybrier HR, Avidan MS. Intraoperative electroencephalogram suppression at lower volatile anaesthetic concentrations predicts postoperative delirium occurring in the intensive care unit. Br J Anaesth. 2018 Jul;121(1):241-248. doi: 10.1016/j.bja.2017.10.024. Epub 2018 Jan 17. — View Citation

Goldberg TE, Chen C, Wang Y, Jung E, Swanson A, Ing C, Garcia PS, Whittington RA, Moitra V. Association of Delirium With Long-term Cognitive Decline: A Meta-analysis. JAMA Neurol. 2020 Jul 13. doi: 10.1001/jamaneurol.2020.2273. [Epub ahead of print] — View Citation

Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. doi: 10.1016/S0140-6736(13)60688-1. Epub 2013 Aug 28. Review. — View Citation

Oh ES, Akeju O, Avidan MS, Cunningham C, Hayden KM, Jones RN, Khachaturian AS, Khan BA, Marcantonio ER, Needham DM, Neufeld KJ, Rose L, Spence J, Tieges Z, Vlisides P, Inouye SK; NIDUS Writing Group. A roadmap to advance delirium research: Recommendations from the NIDUS Scientific Think Tank. Alzheimers Dement. 2020 May;16(5):726-733. doi: 10.1002/alz.12076. Epub 2020 Apr 14. — View Citation

Oh ES, Fong TG, Hshieh TT, Inouye SK. Delirium in Older Persons: Advances in Diagnosis and Treatment. JAMA. 2017 Sep 26;318(12):1161-1174. doi: 10.1001/jama.2017.12067. Review. — View Citation

Pedemonte JC, Plummer GS, Chamadia S, Locascio JJ, Hahm E, Ethridge B, Gitlin J, Ibala R, Mekonnen J, Colon KM, Westover MB, D'Alessandro DA, Tolis G, Houle T, Shelton KT, Qu J, Akeju O. Electroencephalogram Burst-suppression during Cardiopulmonary Bypass in Elderly Patients Mediates Postoperative Delirium. Anesthesiology. 2020 Aug;133(2):280-292. doi: 10.1097/ALN.0000000000003328. — View Citation

Plummer GS, Ibala R, Hahm E, An J, Gitlin J, Deng H, Shelton KT, Solt K, Qu JZ, Akeju O. Electroencephalogram dynamics during general anesthesia predict the later incidence and duration of burst-suppression during cardiopulmonary bypass. Clin Neurophysiol. 2019 Jan;130(1):55-60. doi: 10.1016/j.clinph.2018.11.003. Epub 2018 Nov 16. — View Citation

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. Review. — View Citation

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. — View Citation

Søreide K, Wijnhoven BP. Surgery for an ageing population. Br J Surg. 2016 Jan;103(2):e7-9. doi: 10.1002/bjs.10071. — View Citation

Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, Kronzer A, McKinnon SL, Park D, Torres BA, Graetz TJ, Emmert DA, Palanca BJ, Goswami S, Jordan K, Lin N, Fritz BA, Stevens TW, Jacobsohn E, Schmitt EM, Inouye SK, Stark S, Lenze EJ, Avidan MS; ENGAGES Research Group. Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial. JAMA. 2019 Feb 5;321(5):473-483. doi: 10.1001/jama.2018.22005. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative Delirium	Positive Confusion Assessment Method (CAM), Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), or structured chart review	Up to 72 hours after surgery (3 postoperative days), CAM or CAM-ICU assessed twice daily (AM/PM)
Secondary	Burst suppression during anesthesia induction	Burst suppression incidence after standardized propofol induction in patients = 65 years scheduled for cardiac surgery with cardiopulmonary bypass	20 minutes after standardized propofol administration
Secondary	Burst suppression during cardiopulmonary bypass	Burst suppression incidence during cardiopulmonary bypass in patients = 65 years scheduled for cardiac surgery with cardiopulmonary bypass	Through Cardiopulmonary bypass time defined as time between connection to pump to disconnection, an average of 120 minutes
Secondary	Preoperative Cognitive Status	Preoperative cognitive assessment using MiniCog, minimum value: 0 - maximum value:5 , higher scores meaning better outcomes. If MiniCog = 2, MoCA (Montreal Cognitive Assessment) exam will be performed.	Preoperative anesthetic evaluation
Secondary	Preoperative Frailty	Preoperative frailty evaluation using Clinical Frailty Scale (CFS), minimum value: 1(Very Fit) - maximum value: 9 (Terminally Ill), higher scores meaning worse outcomes	Preoperative anesthetic evaluation
Secondary	Electroencephalogram (EEG) Alpha Power/Total Power	Electroencephalogram power between 8 to 12 Hz (Alpha) and 0.1 to 35 Hz (Total)	Stable anesthetic period before cardiopulmonary bypass and 20 minutes after propofol induction
Secondary	CRP (C Reactive Protein)	Serum C Reactive Protein	Blood sample collection during arterial line insertion, before anesthetic induction