The Effect of Dexmedetomidine Infusion on Post-operative Cognitive Function and Oxidative Stress in Cardiac Surgery
Condition: Oxidative Stress; Cognition Disorders
MeSH terms: Cognition Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Dexmedetomidine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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 volume and rate as in the dexmedetomidine group
Other intervention name(s): Dex
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention