The Effect of Different End-tidal Carbon-dioxide Levels on Cerebral CO2 Vasoreactivity and the Stiffness of Systemic Arteries During Propofol Anesthesia
Condition: Propofol-anaesthesia Via Target-controlled Infusion
Study type: Interventional
Phase: Phase 4

Summary: 
      Purpose:

      The purpose of this study is to examine the effect of different carbon-dioxide concentrations
      on cerebral CO2 sensitivity and the resistance and stiffness of systemic arteries during
      anesthesia with target-controlled infusion anesthesia using intravenous propofol. Propofol is
      a widely and commonly used intravenous anaesthetic, that is mainly used for the induction of
      general anesthesia and the maintenance of total intravenous anaesthesia (TIVA).

      Changes in the velocity of cerebral blood flow and arterial stiffness due to the different
      exhaled carbon-dioxide concentrations will allow us to conclude how propofol affects these
      parameters during the course of the narcosis.

      Instruments:

      An ultrasound device called transcranial doppler (TCD) is used to measure the velocity of
      blood flow within a main artery located inside the skull.

      A tonometry device named SphygmoCor is used to assess the pressure wave proceeding in the
      radial artery, from which the stiffness of the systemic vessels can be concluded.

      Measurements:

      - Examinations with the ultrasound and tonometry devices are carried out once before the
      operation, three times during the intervention, with different exhaled CO2 values and once
      after the operation is completed.

      Hypothesis:

      - Propofol alters cerebral carbon-dioxide sensitivity and the stiffness of systemic arteries
      during TCI anaesthesia.
    

Detailed description: 
      Study protocol:

      - The study is conducted in four stages: in the first stage, measurements are performed
      preoperatively in awake patients. Patients are placed in supine position and mean arterial
      blood pressure (MAP), heart rate, oxygen saturation are measured. The transcranial doppler
      (TCD) probe is fixed in place by applying a headband to maintain a constant angle of
      insonation. Mean blood flow velocity (MBFV) and pulsatility index (PI) in the middle cerebral
      artery (MCA) are obtained. MCA is insonated through the right temporal window by using pulsed
      2 megahertz TCD ultrasound probe. Identification of the MCA is confirmed by using standard
      criteria, at a depth of 45-55 mm. Cerebral CO2 vasoreactivity is calculated as the percentage
      change in MBFV or PI for mmHg change in end-tidal CO2 (ETCO2).

      SphygmoCor is placed on the left radial artery to obtain data about the central aortic blood
      pressure, augmentation pressure (AP) and augmentation index normalised to a 75 beat per
      minute heart rate (Alx75). From the derived aortic pulse, calculations can be made, using the
      area under the systolic and diastolic part of the curve, to determine the heart's ratio of
      oxygen supply and demand, it is called the subendocardial viability ratio (SEVR).

      As part of the premedication each patient receives 100 mg diclofenac per os 30 minutes and
      500 ml Lactated-Ringer infusion 60 minutes prior to the operation.

      Anesthesia is induced and maintained with target-controlled infusion anesthesia (TCI) using
      intravenous propofol at 4 mcg/ml constant plasma concentration. Analgesia is provided by
      using 2 ug/kg sufentanyl bolus dose at the time of induction. Afterwards 0.6 mg/kg rocuronium
      is given for muscle paralysis and subsequently patients were intubated with a suitable
      intratracheal tube. After induction of anaesthesia, the patients are placed on a mechanical
      ventilation system, using a volume-controlled setting with an air and oxygen mixture set to
      0.4 fraction of inspired oxygen (FiO2) , the fresh gas flow rate to 2 l/min. .

      Differences in the depth of anesthesia could influence cerebral activity, thereby cerebral
      metabolism and blood flow. Bispectral index is placed onto every patient in order to assure
      constant depth of anaesthesia during the intervention.

      The second series of TCD and SphygmoCor measurements are performed 20 minutes after the
      respiratory rate is set to maintain end-tidal CO2 at 40 mmHg in order to allow sufficient
      time for equilibrium to be reached and the effect of drugs used for the induction of
      anesthesia to be terminated. Subsequently the examinations are repeated twice again at 35 and
      30 mmHg ETCO2. The measurements were carried out 5-5 minutes after adjusting the minute
      ventilation to reach target ETCO2 values.

      Statistical methods:

      - Comparisons between the preoperative and three intraoperative stages of the study are made
      using repeated measures ANOVA with the Bonferroni post hoc correction. The relationship
      between MBFV, PI and ETCO2 is assessed using linear regression, while the connection between
      SEVR, pulse and Alx75 is calculated with bivariate correlation.
    

Intervention name(s): Partial pressure of CO2 at the end of an exhaled breath; Propofol
Intervention type(s): Procedure; Drug
Intervention description(s): Three previously defined EtCO2 levels (partial pressure of CO2 at the end of an exhaled breath) were adjusted during anesthesia.; Propofol is administered to all patients via target-controlled infusion (TCI) to reach 4 mcg/ml constant plasma concentration according to the Schneider model during the course of the narcosis.
Other intervention name(s): EtCO2; Diprivan
Intervention MeSH terms: Propofol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Target controlled infusion; propofol; cerebral vasoreactivity; arterial stiffness; Transcranial Doppler; SphygmoCor