Propofol-anaesthesia Via Target-controlled InfusionPhase 4NCT02203097
The Effect of Different End-tidal Carbon-dioxide Levels on Cerebral CO2 Vasoreactivity and the Stiffness of Systemic Arteries During Propofol Anesthesia
A Phase 4 study testing Partial pressure of CO2 at the end of an exhaled breath and Propofol in people with Propofol-anaesthesia Via Target-controlled Infusion, run by University of Debrecen at 1 site in Hungary.
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 target-controlled infusion anesthesia using intravenous propofol. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Propofol-anaesthesia Via Target-controlled Infusion
- What is being tested?
- Partial pressure of CO2 at the end of an exhaled breath and Propofol
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteHungary
- Study dates
- Jan 2014to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Above the age 18
- American Society of Anesthesiologists (ASA) physical classification I. or II.
- Patients undergoing elective varicotomy, inguinal hernioplasty or breast surgery in general anesthesia
Who cannot join
- Patients with cerebral, cardiac or systemic vascular disorders (hypertension, diabetes)
- Patients receiving medication that affects the blood vessels (antihypertensive, antidiabetic, antiarrhythmic medications)
Trial locations and contacts
1 site in 1 country.
Hungary1 site
University of Debrecen Medical and Health Science Center Department of Anesthesiology and Intensive Care
Debrecen, 4032
About this study
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).
Read more
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.
Read the 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.
- Being tested
- Partial pressure of CO2 at the end of an exhaled breath, Propofol
- Keywords
- Target controlled infusion, propofol, cerebral vasoreactivity, arterial stiffness, Transcranial Doppler, SphygmoCor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Partial pressure of CO2 at the end of an exhaled breathProcedure or surgery
Also called EtCO2
Three previously defined EtCO2 levels (partial pressure of CO2 at the end of an exhaled breath) were adjusted during anesthesia.
PropofolDrug
Also called Diprivan
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.
| Study group | Role | What they receive |
|---|---|---|
| Propofol | Experimental | 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. Receives: Procedure: Partial pressure of CO2 at the end of an exhaled breath; Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood flow velocity in the middle cerebral artery
Systolic, diastolic and mean blood flow velocities are measured with transcranial doppler device.
Measured: Changes from baseline in blood flow velocity at the 15th, 20th and 25th minutes of the operation
Secondary outcomes (2)
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.
Measured: Changes from baseline in arterial stiffness at the 15th, 20th and 25th minutes of the operation
Changes in the central systolic and diastolic blood pressure
Central blood pressure values are measured by means of tonometry device on the radial artery.
Measured: Changes from baseline in central blood pressure at the 15th, 20th and 25th minutes of the operation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2014 (estimated)
- Study startJan 2014
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Propofol-anaesthesia Via Target-controlled InfusionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Debrecen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tamas Vegh, MD, University of Debrecen
- Investigators
- Csilla Molnár, MD, PhD, 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203097
- Sponsor's protocol ID
- 030167-006/2014/OTIG
- Other IDs
- 2345
- Status last verified
- Mar 2017
- First submitted
- 25 Jul 2014
- Last updated
- 9 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fulesdi B, Limburg M, Bereczki D, Kaplar M, Molnar C, Kappelmayer J, Neuwirth G, Csiba L. Cerebrovascular reactivity and reserve capacity in type II diabetes mellitus. J Diabetes Complications. 1999 Jul-Aug;13(4):191-9. doi: 10.1016/s1056-8727(99)00044-6.
PubMed 10616858McCulloch TJ, Thompson CL, Turner MJ. A randomized crossover comparison of the effects of propofol and sevoflurane on cerebral hemodynamics during carotid endarterectomy. Anesthesiology. 2007 Jan;106(1):56-64. doi: 10.1097/00000542-200701000-00012.
PubMed 17197845Lan YC, Shen CH, Kang HM, Chong FC. Pulse transit time reveals drug kinetics on vascular changes affected by propofol. Comput Methods Biomech Biomed Engin. 2012;15(9):949-52. doi: 10.1080/10255842.2011.567981. Epub 2011 May 24.
PubMed 21547779Strebel S, Kaufmann M, Guardiola PM, Schaefer HG. Cerebral vasomotor responsiveness to carbon dioxide is preserved during propofol and midazolam anesthesia in humans. Anesth Analg. 1994 May;78(5):884-8. doi: 10.1213/00000539-199405000-00009.
PubMed 8160985Holzer A, Winter W, Greher M, Reddy M, Stark J, Donner A, Zimpfer M, Illievich UM. A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity. Anaesthesia. 2003 Mar;58(3):217-22. doi: 10.1046/j.1365-2044.2003.03041.x.
PubMed 12603451Previgliano IJ. Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2004 Dec 28;63(12):2457-8; author reply 2457-8. No abstract available.
PubMed 15630765Juhasz M, Pall D, Fulesdi B, Molnar L, Vegh T, Molnar C. The effect of propofol-sufentanil intravenous anesthesia on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity: a case series. Braz J Anesthesiol. 2021 Sep-Oct;71(5):558-564. doi: 10.1016/j.bjane.2021.04.002. Epub 2021 Apr 23.
PubMed 33901551
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Different End-tidal Carbon-dioxide Levels on Cerebral CO2 Vasoreactivity and the Stiffness of Systemic Arteries During Propofol Anesthesia
- ClinicalTrials.gov ID
- NCT02203097
- Acronym / sponsor ID
- 030167-006/2014/OTIG
- Keywords
- Target controlled infusion, propofol, cerebral vasoreactivity, arterial stiffness, Transcranial Doppler, SphygmoCor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of DebrecenUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 29 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Propofol | Experimental | Procedure: Partial pressure of CO2 at the end of an exhaled breath, Drug: PropofolPropofol 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Above the age 18
- American Society of Anesthesiologists (ASA) physical classification I. or II.
- Patients undergoing elective varicotomy, inguinal hernioplasty or breast surgery in general anesthesia
Key exclusion criteria (2 listed)
- Patients with cerebral, cardiac or systemic vascular disorders (hypertension, diabetes)
- Patients receiving medication that affects the blood vessels (antihypertensive, antidiabetic, antiarrhythmic medications)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Partial pressure of CO2 at the end of an exhaled breathAlso: EtCO2Three previously defined EtCO2 levels (partial pressure of CO2 at the end of an exhaled breath) were adjusted during anesthesia. | Procedure or surgery | Propofol |
| PropofolAlso: DiprivanPropofol 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. | Drug | Propofol |
Primary outcome
Blood flow velocity in the middle cerebral artery
Time frame: Changes from baseline in blood flow velocity at the 15th, 20th and 25th minutes of the operation
Systolic, diastolic and mean blood flow velocities are measured with transcranial doppler device.
2 secondary outcomes
Arterial wall stiffness of the radial artery
Time frame: Changes from baseline in arterial stiffness at the 15th, 20th and 25th minutes of the operation
Changes in the central systolic and diastolic blood pressure
Time frame: Changes from baseline in central blood pressure at the 15th, 20th and 25th minutes of the operation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2017.
- Results publication: PubMed 10616858Fulesdi B, Limburg M, Bereczki D, Kaplar M, Molnar C, Kappelmayer J, Neuwirth G, Csiba L. Cerebrovascular reactivity and reserve capacity in type II diabetes mellitus. J Diabetes Complications. 1999 Jul-Aug;13(4):191-9. doi: 10.1016/s1056-8727(99)00044-6.
- Results publication: PubMed 17197845McCulloch TJ, Thompson CL, Turner MJ. A randomized crossover comparison of the effects of propofol and sevoflurane on cerebral hemodynamics during carotid endarterectomy. Anesthesiology. 2007 Jan;106(1):56-64. doi: 10.1097/00000542-200701000-00012.
- Results publication: PubMed 21547779Lan YC, Shen CH, Kang HM, Chong FC. Pulse transit time reveals drug kinetics on vascular changes affected by propofol. Comput Methods Biomech Biomed Engin. 2012;15(9):949-52. doi: 10.1080/10255842.2011.567981. Epub 2011 May 24.
- Results publication: PubMed 8160985Strebel S, Kaufmann M, Guardiola PM, Schaefer HG. Cerebral vasomotor responsiveness to carbon dioxide is preserved during propofol and midazolam anesthesia in humans. Anesth Analg. 1994 May;78(5):884-8. doi: 10.1213/00000539-199405000-00009.
- Results publication: PubMed 12603451Holzer A, Winter W, Greher M, Reddy M, Stark J, Donner A, Zimpfer M, Illievich UM. A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity. Anaesthesia. 2003 Mar;58(3):217-22. doi: 10.1046/j.1365-2044.2003.03041.x.
- Results publication: PubMed 15630765Previgliano IJ. Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2004 Dec 28;63(12):2457-8; author reply 2457-8. No abstract available.
- Derived from this study: PubMed 33901551Juhasz M, Pall D, Fulesdi B, Molnar L, Vegh T, Molnar C. The effect of propofol-sufentanil intravenous anesthesia on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity: a case series. Braz J Anesthesiol. 2021 Sep-Oct;71(5):558-564. doi: 10.1016/j.bjane.2021.04.002. Epub 2021 Apr 23.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Csilla Molnár, MD, PhD 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Partial pressure of CO2 at the end of an exhaled breath and Propofol in people with Propofol-anaesthesia Via Target-controlled Infusion, run by University of Debrecen at 1 site in Hungary.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood flow velocity in the middle cerebral artery (time frame: Changes from baseline in blood flow velocity at the 15th, 20th and 25th minutes of the operation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02203097, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2017.