Cerebral Blood Supply During Cardiopulmonary Bypass
Condition: Postoperative Delirium
MeSH terms: Delirium; Emergence Delirium
Study type: Observational

Summary: 
      Postoperative delirium is an acute and fluctuating state of confusion and disorientation with
      an incidence of 25-70% after cardiac surgery. Possible reasons for this multifactorial
      complication are hypoperfusion, cerebral microembolization and inflammatory response, which
      eventually lead to regional or global imbalance between cerebral oxygen demand and supply.
      Adequate cerebral blood supply depends sufficient blood supply via the vertebral arteries and
      the internal carotid arteries. The aim of this preliminary study is to investigate if
      patients who develop delirium after open-heart surgery show differences in their cerebral
      blood flow during cardiopulmonary bypass (CPB) in extracerebral arterial vessels compared to
      those patients without delirium.
    

Detailed description: 
      Postoperative delirium is an acute and fluctuating state of confusion and disorientation,
      characterized by changes in attention, cognition, consciousness, and perception, with an
      incidence of 25-70% after cardiac surgery. Possible reasons for this multifactorial
      complication are hypoperfusion, cerebral microembolization and inflammatory response, which
      eventually lead to regional or global imbalance between cerebral oxygen demand and supply.
      This frequent cerebral injury has detrimental and long-lasting consequences and remains a
      serious healthcare burden, particularly due to its association with higher medical costs,
      increased morbidity, long-term cognitive deficits, and greater mortality. Progress in
      reducing the incidence of delirium has been hindered by the lack of a full understanding of
      its pathophysiology.

      Adequate cerebral blood supply depends sufficient blood supply via the vertebral arteries and
      the internal carotid arteries. Whereby the blood supply of the brain by the carotid arteries
      is two-thirds and is easily accessable for blood flow examination with Doppler ultrasound.

      The aim of this preliminary study is to investigate if patients who develop delirium after
      open-heart surgery show differences in their cerebral blood flow during cardiopulmonary
      bypass (CPB) in extracerebral arterial vessels compared to those patients without delirium.
      Additionally we want to investigate the influence of cerebral microembolisation and CPB
      associated inflammation in those patients. As secondary outcome measure we also want to
      determine differences in length of stay (LOS) in the intensive care unit (ICU) as well as in
      hospital LOS and 30-day mortality.

      Methods:

      Design:

      Prospective observational study

      Population:

      Elective cardiac surgical patients undergoing valve replacement/reconstruction surgery on
      cardiopulmonary bypass.

      Procedure:

      Patients will be enrolled the day before surgery by one physician of the study group.

      Anaesthesia will be induced with propofol (1.0-1.5 mg/kg), fentanyl (3-10 μg/kg), and
      cisatracurium (0.2 mg/kg). It will be maintained with sevoflurane (target BIS value 40-50)
      11, and fentanyl (0.05-0.1 μg/kg/min). Patients will receive tranexamic acid (10 mg/kg after
      anaesthesia induction plus the same dosage in the CPB prime), depending on their kidney
      function.

      Anticoagulation will be achieved with heparin (400 IE/kg) to an activated clotting time (ACT)
      >400 s.

      CPB will be performed using non-pulsatile target flow of 100% calculated cardiac output. Mean
      arterial pressure will be maintained between 60 to 70 mmHg throughout CPB.

      To standardize the intraoperative course of our patients we will limit the intraoperative
      haematocrit to 22% and the PaCO2-concentration between 30 and 40 mmHg.12 Blood glucose levels
      will be held between 80-150 mg/dl intra- and postoperatively. Sedation on ICU will be
      performed using propofol until extubation

      Carotis duplex sonography for perfusion flow will be evaluated at the following timepoints:

        1. Before induction of anaesthesia

        2. Before going on CBP

        3. During CPB, 5 min after aortic cross clamping

        4. After CPB

        5. 24 hours after CPB Blood flow will be derived from the product of the vessels'
           cross-sectional area and the intensity-weighted mean blood flow velocity through the
           vessel using a pulsed-wave Doppler in ml/min. Because the sample volume will be adjusted
           to the width of the vessel at the point where the diameter width will be measured, the
           measurement can be performed independent of flow conditions (laminary or pulsatile).
           Imaging of the vessel will be performed in the longitudinal plane, the cross-sectional
           area will be assumed to be circular.

      To diagnose postoperative delirium two delirium assessement tests will be used:

        -  Confusion Assessment method for the ICU (CAM-ICU) and

        -  The Intensive Care Delirium Screening Checklist (ICDSC)

      Delirium Scores will be measured at the following timepoints:

        1. Postoperative day (POD) 1

        2. POD 2

        3. POD 5

      The CAM-ICU will be assessed twice a day (in the morning and in the evening). The Confusion
      Assessment Method (CAM) will be performed after discharge from the ICU.

      Transcranial Doppler ultrasound (TCD) for detection and differentiation of high-intensity
      transient signals (HITS) in both middle cerebral arteries (MCAs) into artefacts, solid, and
      gaseous cerebral microemboli (CME) will be performed at the following timepoints:

        1. During cannulation of the ascending aorta

        2. After aortic cross-clamp

        3. During decannulation All collected data will be saved password-protected in an
           electronic database on the department's server after data collection has been finished.
           Only studyteam-members will have access to this data. After completion of the study the
           results are to be published according to GCP-standards.
    

Intervention name(s): Delirium Scores; Carotis duplex sonography; TCD for detection of HITS
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): Confusion Assessment method for the ICU (CAM-ICU) and
The Intensive Care Delirium Screening Checklist (ICDSC)
Delirium Scores will be measured at the following timepoints:
Postoperative day (POD) 1
POD 2
POD 5; Carotis duplex sonography for perfusion flow will be evaluated at the following timepoints:
Before induction of anaesthesia
Before going on cardiopulmonary bypass (CBP)
During CPB, 5 min after aortic cross clamping
After CPB
24 hours after CPB; Transcranial Doppler ultrasound (TCD) for detection and differentiation of high-intensity transient signals (HITS) in both middle cerebral arteries (MCAs) into artefacts, solid, and gaseous cerebral microemboli (CME) will be performed at the following timepoints:
During cannulation of the ascending aorta
After aortic cross-clamp
After opening of the aortic cross-clamp
During decannulation
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Elective cardiac surgical patients undergoing valve replacement/reconstruction surgery on
        cardiopulmonary bypass.
      
Keywords: cerebral blood supply; cardiopulmonary bypass; open-heart cardiac surgery