The Effect of Dexmedetomidine Infusion on Post-operative Cognitive Function and Oxidative Stress in Cardiac Surgery

Objective: The aim of this study was to determine the effect of dexmedetomidine in reducing postoperative cognitive dysfunction (POCD) in cardiac surgical patients which use cardiopulmonary bypass machine (CPB).

Materials and Methods: This study was double-blinded, randomized controlled trial. Patients scheduled for elective CPB facilitated cardiac surgery were randomly assigned in two groups, dexmedetomidine group (DEX) or control group. The cognitive tests (MoCA test and Short bless test) were done before the operation, 48 hours, and 7 days postoperatively. POCD was defined as a decline of 1SD of baseline score in any test. Arterial blood sample were analyzed for IL-6, IL-10, TNF-alpha and hs-CRP before induction (T0), after separation from CPB (T1), arrival at ICU (T2) and 24-hour after surgery (T3). Primary outcome was the incidence of POCD and the secondary outcomes were inflammatory response, other postoperative complications, ICU and hospital stay.

After the patients were enrolled in the study, they were allocated into Dexmedetomidine group or control group by computer-based randomization. Patients, surgeons, anesthesiologists and researchers who performed the cognitive test were all blinded to the study groups.

General anesthesia was induced with intravenously midazolam 0.1-0.2 mg/kg and fentanyl 5-10 mcg/kg or Thiopental 3-5 mg/kg or Propofol 2 mg/kg. Patients were intubated with pancuronium 1 mg/kg or rocuronium 0.6-1 mg/kg. Anesthesia was maintained with nitrous oxide in oxygen, isoflurane, fentanyl, and pancuronium or rocuronium as required. Standard monitoring was provided including an indwelling radial artery catheter and central venous catheter. Bispectral index (BIS) monitoring was applied and maintained between 40-60 through the operation. Cerebral oximetry was monitored both sides of the brain by non-invasive oximeters at forehead area and the data were recorded.

After skin incision, the Dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation.The control group received a loading dose and continuous IV infusion of normal saline at the same rate.

During the cardiopulmonary bypass, mean arterial pressure was maintained at 60-80 mmHg or 20% from baseline. If hypertension was detected, Nicardipine 0.2 mg was given intravenously. Ephedrine 6 mg or norepinephrine 4 mcg were given within 5 minutes and repeated every 5 minutes if hypotension was presented. Atropine 0.6 mg was administered for bradycardia (heart rate less than 50 beats per minute). After the operation, patients were transferred to Cardio-thoracic intensive care unit and received standard postoperative cardiac surgery care.

2 neuropsychological tests were used to evaluate patients' cognitive function; Montreal Cognitive Assessment (MoCA) and Short blessed test (SBT). These tests were chosen by King Chulalongkorn Memorial Hospital's psychiatrist based on previous studies and the statement consensus on assessment of neurobehavioral outcomes after cardiac surgery published in 1995. All patients were evaluated their cognitive function for 3 points of time, 1st time was at preoperative period (T1), 2nd time was at 48 hours postoperatively (T2) and the last one was at 7 days postoperatively or the day at discharge from the hospital (T3). POCD was defined as a decline of 1 standard deviation (1SD) of baseline score in any test.

Blood samples were taken through the radial artery catheter, and sampling times were chosen as follows: before the induction of anaesthesia (T0); after separated from CPB (T1); arrival at intensive care unit (ICU) (T2); 24 hr after surgery (T3). Plasma Tissue Necrotic Factor-Alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) levels were measured by Magnetic Luminex Performance Assay. High sensitivity C-reactive protein (CRP) level were also measured by nephelometry.

Eligibility Criteria:
Inclusion Criteria:

* American Society of Anesthesiologists (ASA) physical status I-III.

Exclusion Criteria:

* patients who were allergy to medication in the research regimen
* preoperative left ventricular ejection fraction less than 30%
* body mass index more than 35 kg/m2
* preoperative mean arterial pressure less than 60 mmHg
* preoperative heart rate less than 45/min
* patients with impaired renal function (serum creatinine more than 1.5 mg/dl in female and 2 mg/dl in male)
* active liver disease, and who had history of symptomatic cerebrovascular disease
* psychiatric problem and other neurological diseases
* patients who cannot read