Effects of Dexmedetomidine on Cognitive Outcome and Brain Injury Markers

Cognitive Dysfunction Clinical Trial

Official title:

Effects of Dexmedetomidine on Cognitive Outcome and Brain Injury Markers After General Anesthesia for Cardiac Surgery on Cardiopulmonary Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03585452
• Other study ID #: Cardiodex
• Status: Completed
• Phase: N/A
• Start date: August 1, 2018
• Est. completion date: March 31, 2019

Study information

• Verified date: October 2022
• Source: Medical University of Lublin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

All adult patients qualified for elective coronary artery bypass grafts (CABG), (with CPB), under general anesthesia with good ejection fraction - above 40% will be eligible for the study. Patients will be sampling by simple 1:1 sampling into 2 groups:

1. Control group (group C): patients with typical anesthetic regimen.

2. Dexmedetomidine group (group D): regimen will be the same with additional dexmedetomidine infusion.

In both groups typical monitoring will be applied: heart rate (HR), mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), pulse oximetry (SpO2), central vein pressure (CVP), hemodynamic monitoring with Swan-Ganz thermodilution pulmonary artery catheter, end tidal carbon dioxide (ET CO2), typical inhaust and exhaust gases analysis, eeg sensor - SedLine with patient state index (PSI), (Masimo technology) and regional cerebral oximetry (Masimo technology) with estimation of area under curve defined as time of the low brain oximetry value below 80% of initial value.

Blood for bio-markers analysis will be collected in the following points:

1. initially, before anesthesia induction

2. At the end of the procedure

3. 24 hours after procedure

4. 72 hours after procedure Biochemical measures will cover: biomarkers of brain injury:

myelin basic protein (MBP) and matrix metalloproteinase 12 (MMP12).

Cognitive function will be assessed using Addenbrooke's Cognitive Examination - ACE-III, at three time points: initially, one day before surgery, at discharge time and 3 months after discharge.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: March 31, 2019
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Brain Injuries
• Cognitive Dysfunction

Intervention

Drug:
• Dexmedetomidine Infusion
Patients with additional dexmedetomidine infusion
• Propofol based general anesthesia
Patients with typical anaesthetic regimens

Locations

Country	Name	City	State
Poland	Michal Kowalczyk	Lublin	Lubelskie

Sponsors (1)

Lead Sponsor	Collaborator
Michal Kowalczyk

Country where clinical trial is conducted

Poland, 

References & Publications (12)

Brandão 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2007 Nov 22. — View Citation

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. — View Citation

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. Review. — View Citation

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

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive function	Cognitive function assessment with Addenbrooke's Cognitive Examination - ACE-III	at discharge - 7 days after surgery