Effects of Dexmedetomidine on Cognitive Outcome and Brain Injury Markers

NCT03585452 | Completed

• 1 other identifier: Cardiodex
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Dexmedetomidine is a drug with sedative, anxiolytic, and analgesic properties. Benefits of its use covers good sedations without respiratory suppression, reduced circulating catecholamines due to decreased sympathetic transmission and nociceptive transmission blocking resulting in lower needs for postoperative pain management. All these features are beneficial for cardiac surgery patients. What is more, it was find as an anesthesia agent. Recently some protective effects were find, like reduced postoperative delirium occurrence with cardiac surgery dexmedetomidine sedated patients. Other study revealed that patient receiving dexmedetomidine during cardiac surgery and in the first 24 h postoperatively showed significant reductions in in-hospital and 30-day mortality as well as postsurgical delirium. Although dexmedetomidine appears to reduce postoperative delirium, its role in prevention of neurological injury has not been well studied. To fulfil this gap we designed the study to investigate effects of dexmedetomidine use during cardiac surgery (with cardiopulmonary bypass - CPB) and in the first hours postoperatively on biomarkers of brain injury and cognitive function.

Conditions

Cognitive Dysfunction

Keywords

dexmedetomidine; cardiac surgery; brain injury biomarkers; cognitive examination

Outcome Measures

Primary Outcomes (1)

• Cognitive function

  Cognitive function assessment with Addenbrooke's Cognitive Examination - ACE-III

  at discharge - 7 days after surgery

Study Arms (2)

Group C

ACTIVE COMPARATOR

Patients with typical anesthetic regimen: premedication: 2 mg estazolam p.o. and 10 mg morphine s.c. - 1 hour before procedure. Preoxygenation and induction of anaesthesia: remifentanyl 1 µg/kg, etomidate 0.3 mg/kg, pancuronium 0.1 mg/kg and intubation. Maintenance of the anesthesia: remifentanyl 0.2-0.5 µg/kg/min and propofol 2-4 mg/kg/min infusions. Ventilation with Air/O2. Additionally: nitroglycerine infusion or phenylephrine 0.05-0.1 mg boluses will be used for normotension maintenance at demanding doses. Subsequently typical CABG procedure with normothermic CPB will be performed. Weaning from CPB will be performed with inotropic support (dobutamine) and vasodilator (nitroglycerine) administration - with patients dependent doses. Routine recovery after surgery.

Drug: Propofol based general anesthesia

Group D

EXPERIMENTAL

Regimen will be the same with additional dexmedetomidine infusion: with loading dose: 0.5 µg/kg/h through 1 hour and then dose will be reduced to 0.25 µg/kg/h and infusion will be continued during surgery and postoperative period to the total dose of 200 µg. Anesthetics and opioids doses will be adjusted under hemodynamic and eeg sensor - SedLine Masimo.

Drug: Dexmedetomidine Infusion

Interventions

Dexmedetomidine Infusion DRUG

Patients with additional dexmedetomidine infusion

Also known as: Dexdor

Group D

Propofol based general anesthesia DRUG

Patients with typical anaesthetic regimens

Also known as: Control

Group C

Eligibility Criteria

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

You may qualify if:

• all adult patients qualified for elective coronary artery bypass grafts (CABG), (with CPB) with good ejection fraction - above 40%.

You may not qualify if:

• diabetic patients, neurological diseases, any autoimmune diseases, any internal carotid or vertebral artery obstruction, myocardial infarction, ejection fraction \< 40%.

Sponsors & Collaborators

• Michał Kowalczyk: lead

Study Sites (1)

Michał Kowalczyk

Lublin, Lublin Voivodeship, 20-867, Poland

Location

Related Publications (12)

• McDonagh DL, Berger M, Mathew JP, Graffagnino C, Milano CA, Newman MF. Neurological complications of cardiac surgery. Lancet Neurol. 2014 May;13(5):490-502. doi: 10.1016/S1474-4422(14)70004-3. Epub 2014 Apr 2.

  PMID: 24703207 BACKGROUND

• Brandao PG, Lobo FR, Ramin SL, Sakr Y, Machado MN, Lobo SM. Dexmedetomidine as an Anesthetic Adjuvant in Cardiac Surgery: a Cohort Study. Braz J Cardiovasc Surg. 2016 May-Jun;31(3):213-218. doi: 10.5935/1678-9741.20160043.

  PMID: 27737403 BACKGROUND

• Chen S, Hua F, Lu J, Jiang Y, Tang Y, Tao L, Zou B, Wu Q. Effect of dexmedetomidine on myocardial ischemia-reperfusion injury. Int J Clin Exp Med. 2015 Nov 15;8(11):21166-72. eCollection 2015.

  PMID: 26885050 BACKGROUND

• Cheng H, Li Z, Young N, Boyd D, Atkins Z, Ji F, Liu H. The Effect of Dexmedetomidine on Outcomes of Cardiac Surgery in Elderly Patients. J Cardiothorac Vasc Anesth. 2016 Dec;30(6):1502-1508. doi: 10.1053/j.jvca.2016.02.026. Epub 2016 Mar 3.

  PMID: 27435836 BACKGROUND

• Gong Z, Ma L, Zhong YL, Li J, Lv J, Xie YB. Myocardial protective effects of dexmedetomidine in patients undergoing cardiac surgery: A meta-analysis and systematic review. Exp Ther Med. 2017 May;13(5):2355-2361. doi: 10.3892/etm.2017.4227. Epub 2017 Mar 13.

  PMID: 28565849 BACKGROUND

• Ji F, Li Z, Young N, Moore P, Liu H. Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2014 Apr;28(2):267-73. doi: 10.1053/j.jvca.2013.06.022. Epub 2013 Oct 29.

  PMID: 24182835 BACKGROUND

• Perez-Zoghbi JF, Zhu W, Grafe MR, Brambrink AM. Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats. Br J Anaesth. 2017 Sep 1;119(3):506-516. doi: 10.1093/bja/aex222.

  PMID: 28969317 BACKGROUND

• Wang Y, Han R, Zuo Z. Dexmedetomidine-induced neuroprotection: is it translational? Transl Perioper Pain Med. 2016;1(4):15-19.

  PMID: 28217717 BACKGROUND

• van Dijk D, Keizer AM, Diephuis JC, Durand C, Vos LJ, Hijman R. Neurocognitive dysfunction after coronary artery bypass surgery: a systematic review. J Thorac Cardiovasc Surg. 2000 Oct;120(4):632-9. doi: 10.1067/mtc.2000.108901.

  PMID: 11003741 BACKGROUND

• Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR. The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry. 2006 Nov;21(11):1078-85. doi: 10.1002/gps.1610.

  PMID: 16977673 BACKGROUND

• Ottens AK, Golden EC, Bustamante L, Hayes RL, Denslow ND, Wang KK. Proteolysis of multiple myelin basic protein isoforms after neurotrauma: characterization by mass spectrometry. J Neurochem. 2008 Mar;104(5):1404-14. doi: 10.1111/j.1471-4159.2007.05086.x. Epub 2007 Nov 22.

  PMID: 18036155 BACKGROUND

• Chelluboina B, Warhekar A, Dillard M, Klopfenstein JD, Pinson DM, Wang DZ, Veeravalli KK. Post-transcriptional inactivation of matrix metalloproteinase-12 after focal cerebral ischemia attenuates brain damage. Sci Rep. 2015 May 8;5:9504. doi: 10.1038/srep09504.

  PMID: 25955565 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michał Kowalczyk, M.D., Ph.D.

  Medical University of Lublin, Poland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients were not aware of the fact into which group they were divided
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients were randomly divided into two groups by simple 1:1 randomisation using opaque envelopes: the control group (group CON; patients with typical anaesthetic regimens) and the dexmedetomidine group (group DEX; those with additional dexmedetomidine infusion).

Study Record Dates

• First Submitted: July 1, 2018
• First Posted: July 13, 2018
• Study Start: August 1, 2018
• Primary Completion: December 30, 2018
• Study Completion: March 31, 2019
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will become available after article publication.
• Access Criteria: Available for everybody.

Locations

PL (1)