The Effect of Sevoflurane on Cerebral CO2 Sensitivity and Systemic Arteries

NCT ID: NCT02054143

Last Updated: 2014-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2013-04-30

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.

Conditions

Sevoflurane Anesthesia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Sevoflurane

Sevoflurane was administered to all patients at 1 minimal alveolar concentration (MAC) after the intubation occured until the patient was extubated.

Group Type: EXPERIMENTAL

Partial pressure of CO2 at the end of an exhaled breath

Intervention Type: PROCEDURE

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

Sevoflurane

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: PROCEDURE

Sevoflurane

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

Intervention Type: DRUG

Other Intervention Names

EtCO2; Sevorane

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Debrecen

OTHER

Sponsor Role: lead

Responsible Party

Tamas Vegh, MD

assistant lecturer anesthesiologist and intensive care specialist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Csilla Molnár, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

University of Debrecen Medical and Health Science Center Department of Anesthesiology and Intensive Care

Debrecen, , Hungary

Countries

Hungary

References

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.

Reference Type: DERIVED

PMID: 31215448 (View on PubMed)

Other Identifiers

DEOEC RKEB/IKEB:3584-2012

Identifier Type: OTHER

Identifier Source: secondary_id

17637-1/2012/EKU

Identifier Type: -

Identifier Source: org_study_id