Delirium Reduction by Volatile Anesthesia in Cardiac Surgery

NCT03729011 | Completed Phase 4

• 1 other identifier: 18
• Study Type: interventional
• Target: 405
• Locations: 1 country
• Sites: 5

Brief Summary

Parallel group, prospective, randomized, controlled, single-blinded trial. The aim of our study is to test the hypothesis that volatile anesthesia would reduce the incidence of early postoperative delirium in patients undergoing cardiac surgery with CPB as compared to TIVA.

Conditions

Delirium

Keywords

delirium; Cardiac surgery; Cardiopulmonary bypass; Cognitive dysfunction

Outcome Measures

Primary Outcomes (1)

• Postoperative delirium

  Postoperative delirium detection will be managed with Confusion Assessment Method for the ICU (CAM-ICU)

  5 days after surgery

Secondary Outcomes (14)

• Early postoperative cognitive dysfunction

  7 days after surgery

• Delirium duration

  10 days after surgery

• Duration of ICU stay

  30 days

• Duration of hospital stay

  60 days

• 30-day all-cause mortality

  30 days

Study Arms (2)

Volatile anesthesia group

ACTIVE COMPARATOR

Drug: Volatile agent

TIVA group

ACTIVE COMPARATOR

Drug: Propofol

Interventions

Volatile agent DRUG

Patients will receive volatile agent to provide general anaesthesia, including CPB period. Volatile agents will be administered from anesthesia induction to the end of surgery. Concentration (MAC) of volatile agent will be selected by anaesthesiologist according to clinical situation and patient features.

Also known as: Sevoflurane, Desflurane, Isoflurane

Volatile anesthesia group

Propofol DRUG

Patients will receive propofol and no volatile agent. Propofol will be used for induction and maintenance of anesthesia.

TIVA group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Males and females \> 65 years
• Written informed consent
• Cardiac surgery with CPB

You may not qualify if:

• Emergency surgery
• Surgery on aorta
• Known allergy to components of anaesthesia
• Pregnancy
• Hemodynamically significant stenosis of carotid arteries
• Parkinson's disease
• Liver cirrhosis (Child B or C)
• Current enrollment into another RCT (in the last 30 days)
• Previous enrollment and randomization into the DELICATE trial
• Poor language comprehension
• Preoperative Medications: Anticholinergics (dimedrol, atropine, dramina), antidepressants, antiepileptics, antiparkinson drugs, chemotherapeutic agents

Sponsors & Collaborators

• Meshalkin Research Institute of Pathology of Circulation: lead

Study Sites (5)

National Medical Research Center for Surgery named after A.V. Vishnevsky, Ministry of Health of the Russian Federation

Moscow, 117997, Russia

Location

M.F. Vladimirsky Moscow Regional Research and Clinical Institute (MONIKI)

Moscow, Russia

Location

Meshalkin Research Institute of Pathology of Circulation

Novosibirsk, 630055, Russia

Location

Saint Petersburg State University Hospital

Saint Petersburg, Russia

Location

Tomsk National Research Medical Center of the Russian Academy of Sciences

Tomsk, Russia

Location

Related Publications (24)

• Brown CH. Delirium in the cardiac surgical ICU. Curr Opin Anaesthesiol. 2014 Apr;27(2):117-22. doi: 10.1097/ACO.0000000000000061.

  PMID: 24514034 BACKGROUND

• Martin BJ, Buth KJ, Arora RC, Baskett RJ. Delirium: a cause for concern beyond the immediate postoperative period. Ann Thorac Surg. 2012 Apr;93(4):1114-20. doi: 10.1016/j.athoracsur.2011.09.011. Epub 2011 Dec 24.

  PMID: 22200370 BACKGROUND

• Gottesman RF, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Selnes OA, McKhann GM. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol. 2010 Mar;67(3):338-44. doi: 10.1002/ana.21899.

  PMID: 20373345 BACKGROUND

• Rudolph JL, Inouye SK, Jones RN, Yang FM, Fong TG, Levkoff SE, Marcantonio ER. Delirium: an independent predictor of functional decline after cardiac surgery. J Am Geriatr Soc. 2010 Apr;58(4):643-9. doi: 10.1111/j.1532-5415.2010.02762.x. Epub 2010 Mar 22.

  PMID: 20345866 BACKGROUND

• Franco K, Litaker D, Locala J, Bronson D. The cost of delirium in the surgical patient. Psychosomatics. 2001 Jan-Feb;42(1):68-73. doi: 10.1176/appi.psy.42.1.68.

  PMID: 11161124 BACKGROUND

• Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1092-7. doi: 10.1164/rccm.200904-0537OC. Epub 2009 Sep 10.

  PMID: 19745202 BACKGROUND

• Bickel H, Gradinger R, Kochs E, Forstl H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement Geriatr Cogn Disord. 2008;26(1):26-31. doi: 10.1159/000140804. Epub 2008 Jun 24.

  PMID: 18577850 BACKGROUND

• Li YW, Li HJ, Li HJ, Feng Y, Yu Y, Guo XY, Li Y, Zhao BJ, Hu XY, Zuo MZ, Zhang HY, Wang MR, Ji P, Yan XY, Wu YF, Wang DX. Effects of two different anesthesia-analgesia methods on incidence of postoperative delirium in elderly patients undergoing major thoracic and abdominal surgery: study rationale and protocol for a multicenter randomized controlled trial. BMC Anesthesiol. 2015 Oct 13;15:144. doi: 10.1186/s12871-015-0118-5.

  PMID: 26459347 BACKGROUND

• Nguyen Q, Uminski K, Hiebert BM, Tangri N, Arora RC. Midterm outcomes after postoperative delirium on cognition and mood in patients after cardiac surgery. J Thorac Cardiovasc Surg. 2018 Feb;155(2):660-667.e2. doi: 10.1016/j.jtcvs.2017.09.131. Epub 2017 Oct 20.

  PMID: 29132782 BACKGROUND

• Cerejeira J, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. The neuroinflammatory hypothesis of delirium. Acta Neuropathol. 2010 Jun;119(6):737-54. doi: 10.1007/s00401-010-0674-1. Epub 2010 Mar 24.

  PMID: 20309566 BACKGROUND

• Caplan JP, Chang G. Refeeding syndrome as an iatrogenic cause of delirium: a retrospective pilot study. Psychosomatics. 2010 Sep-Oct;51(5):419-24. doi: 10.1176/appi.psy.51.5.419.

  PMID: 20833941 BACKGROUND

• Siepe M, Pfeiffer T, Gieringer A, Zemann S, Benk C, Schlensak C, Beyersdorf F. Increased systemic perfusion pressure during cardiopulmonary bypass is associated with less early postoperative cognitive dysfunction and delirium. Eur J Cardiothorac Surg. 2011 Jul;40(1):200-7. doi: 10.1016/j.ejcts.2010.11.024. Epub 2010 Dec 18.

  PMID: 21168339 BACKGROUND

• Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci. 2008 Jul;63(7):764-72. doi: 10.1093/gerona/63.7.764.

  PMID: 18693233 BACKGROUND

• Wimmer-Greinecker G, Matheis G, Brieden M, Dietrich M, Oremek G, Westphal K, Winkelmann BR, Moritz A. Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting. Thorac Cardiovasc Surg. 1998 Aug;46(4):207-12. doi: 10.1055/s-2007-1010226.

  PMID: 9776494 BACKGROUND

• Chen F, Duan G, Wu Z, Zuo Z, Li H. Comparison of the cerebroprotective effect of inhalation anaesthesia and total intravenous anaesthesia in patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis. BMJ Open. 2017 Oct 11;7(10):e014629. doi: 10.1136/bmjopen-2016-014629.

  PMID: 29025825 BACKGROUND

• Morimoto Y, Yoshimura M, Utada K, Setoyama K, Matsumoto M, Sakabe T. Prediction of postoperative delirium after abdominal surgery in the elderly. J Anesth. 2009;23(1):51-6. doi: 10.1007/s00540-008-0688-1. Epub 2009 Feb 22.

  PMID: 19234823 BACKGROUND

• Sagara Y, Hendler S, Khoh-Reiter S, Gillenwater G, Carlo D, Schubert D, Chang J. Propofol hemisuccinate protects neuronal cells from oxidative injury. J Neurochem. 1999 Dec;73(6):2524-30. doi: 10.1046/j.1471-4159.1999.0732524.x.

  PMID: 10582614 BACKGROUND

• Wang H, Lu S, Yu Q, Liang W, Gao H, Li P, Gan Y, Chen J, Gao Y. Sevoflurane preconditioning confers neuroprotection via anti-inflammatory effects. Front Biosci (Elite Ed). 2011 Jan 1;3(2):604-15. doi: 10.2741/e273.

  PMID: 21196338 BACKGROUND

• McAuliffe JJ, Loepke AW, Miles L, Joseph B, Hughes E, Vorhees CV. Desflurane, isoflurane, and sevoflurane provide limited neuroprotection against neonatal hypoxia-ischemia in a delayed preconditioning paradigm. Anesthesiology. 2009 Sep;111(3):533-46. doi: 10.1097/ALN.0b013e3181b060d3.

  PMID: 19672176 BACKGROUND

• Bilotta F, Stazi E, Zlotnik A, Gruenbaum SE, Rosa G. Neuroprotective effects of intravenous anesthetics: a new critical perspective. Curr Pharm Des. 2014;20(34):5469-75. doi: 10.2174/1381612820666140325110113.

  PMID: 24669972 BACKGROUND

• Young Y, Menon DK, Tisavipat N, Matta BF, Jones JG. Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol. 1997 May;14(3):320-6. doi: 10.1046/j.1365-2346.1997.00130.x.

  PMID: 9202922 BACKGROUND

• Ergun R, Akdemir G, Sen S, Tasci A, Ergungor F. Neuroprotective effects of propofol following global cerebral ischemia in rats. Neurosurg Rev. 2002 Mar;25(1-2):95-8. doi: 10.1007/s101430100171.

  PMID: 11954772 BACKGROUND

• Van Aken H, Van Hemelrijck J. Influence of anesthesia on cerebral blood flow and cerebral metabolism: an overview. Agressologie. 1991;32(6-7):303-6.

  PMID: 1843831 BACKGROUND

• Lingehall HC, Smulter NS, Lindahl E, Lindkvist M, Engstrom KG, Gustafson YG, Olofsson B. Preoperative Cognitive Performance and Postoperative Delirium Are Independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery: A Longitudinal Cohort Study. Crit Care Med. 2017 Aug;45(8):1295-1303. doi: 10.1097/CCM.0000000000002483.

  PMID: 28481752 BACKGROUND

MeSH Terms

Conditions

Delirium; Cognitive Dysfunction

Interventions

Sevoflurane; Desflurane; Isoflurane; Propofol

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Ethyl Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Patients will be randomly allocated to receive either inhalation anaesthesia or TIVA. Permuted-block randomization will be used to allocate subjects to one of the study groups. Sequentially numbered sealed opaque envelopes will contain the treatment code, to be opened in the morning of surgery. Patients will be unaware of group assignment. All the statistical analyses will be performed by the biostatistician not involved in treatment allocation.

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: November 2, 2018
• Study Start: January 9, 2019
• Primary Completion: January 11, 2024
• Study Completion: January 11, 2024
• Last Updated: May 15, 2025

Record last verified: 2024-01

Locations

RU (5)