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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.
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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine Infusion | Drug | Patients with additional dexmedetomidine infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive function | Cognitive function assessment with Addenbrooke's Cognitive Examination - ACE-III | at discharge - 7 days after surgery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michał Kowalczyk, M.D., Ph.D. | Medical University of Lublin, Poland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Michał Kowalczyk | Lublin | Lublin Voivodeship | 20-867 | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24703207 | Background | 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. | |
| 27737403 | 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. |
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We plan to attach row data as supplemental data during publishing process.
Data will become available after article publication.
Available for everybody.
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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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).
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Patients were not aware of the fact into which group they were divided
| Propofol based general anesthesia | Drug | Patients with typical anaesthetic regimens |
|
|
| 26885050 | 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. |
| 27435836 | 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. |
| 28565849 | 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. |
| 24182835 | 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. |
| 28969317 | 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. |
| 28217717 | Background | Wang Y, Han R, Zuo Z. Dexmedetomidine-induced neuroprotection: is it translational? Transl Perioper Pain Med. 2016;1(4):15-19. |
| 11003741 | 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. |
| 16977673 | 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. |
| 18036155 | 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. |
| 25955565 | 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. |