The Effect of Sevoflurane on Cerebral CO2 Sensitivity and Systemic Arteries

Sevoflurane Anesthesia Clinical Trial

Official title:

The Effect of Sevoflurane on Cerebral Vasoreactivity Ans Systemic Arteries

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054143
• Other study ID #: 17637-1/2012/EKU
• Secondary ID: DEOEC RKEB/IKEB:
• Status: Completed
• Phase: Phase 4
• First received: January 31, 2014
• Last updated: February 3, 2014
• Start date: November 2012
• Est. completion date: April 2013

Study information

• Verified date: February 2014
• Source: University of Debrecen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hungary: Scientific and Medical Research Council Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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)

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Sevoflurane Anesthesia

Intervention

Procedure:
• Partial pressure of CO2 at the end of an exhaled breath
Three previously defined EtCO2 levels (partial pressure of CO2 at the end of an exhaled breath) were adjusted during anesthesia.

Drug:
• Sevoflurane
Sevoflurane was administered to all patients at 1 minimal alveolar concentration (MAC) during the whole operation.

Locations

Country	Name	City	State
Hungary	University of Debrecen Medical and Health Science Center Department of Anesthesiology and Intensive Care	Debrecen

Sponsors (1)

Lead Sponsor	Collaborator
University of Debrecen

Country where clinical trial is conducted

Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in subendocardial viability ratio (SEVR)	From the derived central aortic pulse pressure, calculations can be made, using the area under the systolic and diastolic part of the curve.	Changes form baseline in SEVR at the 15th, 20th and 25th minutes of the operation	No
Primary	Blood flow velocity in the middle cerebral artery	Systolic, diastolic and mean blood flow velocities are measured with transcranial doppler device.	Changes from baseline in blood flow velocity at the 15th, 20th and 25th minutes of the operation	No
Secondary	Arterial wall stiffness of the radial artery	The stiffness of the radial artery is assessed. Stiffness rate is concluded from the augmentation pressure and augmentation index, from which both values are provided by the tonometry device.	Changes from baseline in arterial stiffness at the 15th, 20th and 25th minutes of the operation	No
Secondary	Changes in the central systolic and diastolic blood pressure	CEntral blood pressure values are measured by means of tonometry device on the radial artery.	Changes from baseline in central blood pressure at the 15th, 20th and 25th minutes of the operation	No