Effects of Dexmedetomidine on Cognitive Outcome and Brain Injury Markers

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

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: Control group (group C): patients with typical anesthetic regimen. 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: initially, before anesthesia induction At the end of the procedure 24 hours after procedure 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.

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).

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.

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.

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%.

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