The Effect of Sevoflurane on Cerebral CO2 Sensitivity and Systemic Arteries
Condition: Sevoflurane Anesthesia
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 sevoflurane. Sevoflurane is a widely and commonly used
           inhalational anaesthetic, that is mainly used for the maintenance of general anesthesia.

        -  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
           sevoflurane 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:

      - Sevoflurane alters cerebral carbon-dioxide sensitivity and the stiffness of systemic
      arteries.
    

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 7.5 mg midazolam. Anaesthesia is induced
      using 2 mcg/kg fentanyl followed by 2 mg/kg propofol. Afterwards 0.6mg/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 and sevoflurane is adjusted to
      reach a constant 1minimal alveolar concentration (MAC) during examination. Anesthesia is
      maintained with sevoflurane and on demand fentanyl boluses.

      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; Sevoflurane
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.; Sevoflurane was administered to all patients at 1 minimal alveolar concentration (MAC) during the whole operation.
Other intervention name(s): EtCO2; Sevorane
Intervention MeSH terms: Sevoflurane
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: sevoflurane; cerebral vasoreactivity; arterial stiffness; Transcranial Doppler; SphygmoCor