Clinical trial NCT02054143: The Effect of Sevoflurane on Cerebral CO2 Sensitivity and Systemic Arteries
Official title: The Effect of Sevoflurane on Cerebral Vasoreactivity Ans Systemic Arteries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sevoflurane Anesthesia
Keywords: sevoflurane
cerebral vasoreactivity
arterial stiffness
Transcranial Doppler
SphygmoCor
Lead sponsor: University of Debrecen
Sponsor class: OTHER
First posted: 2014-02-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Above the age 18
* American Society of Anesthesiologists (ASA) physical classification I. or II.
* Patients undergoing elective varicotomy or inguinal hernioplasty in general anesthesia

Exclusion Criteria:

* Patients with cerebral, cardiac or systemic vascular disorders (hypertension, diabetes)
* Patients receiving medication that affects the blood vessels (antihypertensive, antidiabetic, antiarrhythmic medications)

Primary outcomes:
measure: Blood flow velocity in the middle cerebral artery
timeFrame: Changes from baseline in blood flow velocity at the 15th, 20th and 25th minutes of the operation
Secondary outcomes:
measure: Arterial wall stiffness of the radial artery
timeFrame: Changes from baseline in arterial stiffness at the 15th, 20th and 25th minutes of the operation
measure: Changes in the central systolic and diastolic blood pressure
timeFrame: Changes from baseline in central blood pressure at the 15th, 20th and 25th minutes of the operation
Other outcomes:
measure: Changes in subendocardial viability ratio (SEVR)
timeFrame: Changes form baseline in SEVR at the 15th, 20th and 25th minutes of the operation
Locations:
city: Debrecen
country: Hungary
facility: University of Debrecen Medical and Health Science Center Department of Anesthesiology and Intensive Care
Study officials:
affiliation: University of Debrecen Medical and Health Science Center Department of Anesthesiology and Intensive Care 4032-Debrecen, Nagyerdei krt 98. Hungary Tel/fax: +36-52-255-347
name: Csilla Molnár, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Juhasz M, Molnar L, Fulesdi B, Vegh T, Pall D, Molnar C. Effect of sevoflurane on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity. BMC Anesthesiol. 2019 Jun 19;19(1):109. doi: 10.1186/s12871-019-0784-9.