Gastrointestinal NeoplasmsNCT02951273
Cerebral Blood Flow During Propofol Anaesthesia
An observational study of Gastrointestinal Neoplasms, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
General anaesthesia often reduces blood pressure whereby blood flow to the brain and other vital organs may become insufficient. Thus, medicine is often administered during anaesthesia to maintain blood pressure. However, it is unclear at what level blood pressure should be aimed at during anaesthesia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Neoplasms
- What is being tested?
- Study of cerebral blood flow
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 8 Dec 2016to 6 Jul 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Thirty patients planned for oesophageal- or ventricular resection at Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark
Who may be able to join
- Patients planned for major abdominal surgery that require placement of an arterial line and central venous catheter, including oesophageal- or ventricular resection
- Age ≥ 18 years.
Who cannot join
- No informed consent
- Robotic assisted procedures
- Treatment with anti-inflammatory medication, including NSAID and corticosteroids
- Atherosclerosis of the internal carotid artery that obstructs ≥ 30% of the vessel lumen
- Neurologic disease considered to affect cerebral blood flow, including dementia, epilepsy, and apoplexy
Trial locations and contacts
1 site in 1 country.
About this study
General anaesthesia often reduces blood pressure whereby blood flow to the brain and other vital organs may become insufficient. Thus, medicine is often administered during anaesthesia to maintain blood pressure. However, it is unclear at what level blood pressure should be aimed at during anaesthesia.
Several factors may affect blood flow to the brain during anaesthesia. During surgery on the internal organs, a hormone may be released that dilates blood vessels and causes a so-called mesenteric traction syndrome characterised by a decrease in blood pressure and flushing. This reaction lasts for approximately thirty minutes and is observed in about half of the patients who undergo surgery on the stomach and intestines. It is unknown whether a mesenteric traction syndrome affects blood flow to the brain. Ventilation is also of importance for blood flow to the brain. Thus, blood flow to the brain is reduced by hyperventilation and increases if breathing is slower. It is unclear whether the relation between blood flow to the brain and ventilation is affected during anaesthesia.
Read more
This study will evaluate how blood flow to the brain is affected by anaesthesia and standard treatment of a possible reduction in blood pressure. Further, the study will assess whether blood flow to the brain is affected by development of a mesenteric traction syndrome. Lastly, the project will evaluate blood flow to the brain during short-term changes in the patient's ventilation by adjustments on the ventilator.
Thirty patients planned for major abdominal surgery will be included in the project. The study will take place from the patient's arrival at the operation room and until two hours after the start of surgery. Placement of catheters and anaesthesia are according to standard care. Blood flow to the brain will be evaluated using ultrasound. Oxygenation of the brain, skin and muscle will be evaluated by probes that emit light. Depth of anaesthesia is assessed by recording the electrical activity of the brain. Blood pressure is measured by a catheter placed in an artery at the wrist and blood samples will be drawn from the catheter.
Read the detailed description
Background General anaesthesia reduces blood pressure, but cerebral autoregulation is considered to maintain its blood flow if mean arterial pressure (MAP) is between 60-150 mmHg. Thus, vasoactive medication is administered to treat anaesthesia-induced hypotension if MAP decreases to below approximately 60 mmHg. In young healthy adults, propofol anaesthesia, with limited reduction in blood pressure, decreases cerebral blood flow by approximately 50% by a decrease in neuronal activity. However, it is unknown whether the anaesthesia-induced reduction in cerebral blood flow is affected by a marked decrease in MAP and whether propofol anaesthesia affects the lower level of cerebral autoregulation.
If central blood volume is maintained, cerebral oxygenation may be unaffected by a decrease in MAP to ~40 mmHg whereas a reduction in central blood volume and cardiac output (CO) during orthostasis or bleeding, reduces cerebral oxygenation when MAP is lower than approximately 80 mmHg. Thus, CO may affect cerebral blood flow and the ability to increase CO is likely of importance for maintaining a sufficient cerebral blood flow.
During anaesthesia, cerebral blood flow and MAP may be affected by various factors including release of vasoactive substances. Manipulation of the abdominal organs may induce a so-called mesenteric traction syndrome (MTS) encompassing a triad of flushing, hypotension, and tachycardia in about half of the patients who undergo major abdominal surgery. MTS typically develops 15-20 min after the start of surgery and the haemodynamic manifestations, that appear to be mediated by prostaglandin I2, last for approximately 30 min. The effect of MTS on cerebral blood flow is unknown. Prostaglandin I2 dilates cerebral arteries in vitro but does not affect cerebral blood flow when administered to healthy subjects. In a previous study we found that MTS increases near-infrared spectroscopy determined frontal lobe oxygenation possibly due to an increase in extracranial circulation while there was no effect on middle cerebral artery mean flow velocity as an index of changes in cerebral blood flow.
Propofol anaesthesia appears not to affect the CO2 reactivity of the middle cerebral artery as determined by transcranial Doppler ultrasonography, but the CO2 reactivity of the internal carotid artery during propofol anaesthesia is unknown.
Objective The purpose of this study is to evaluate how internal carotid artery blood flow is affected by propofol anaesthesia and related hypotension, and by administration of phenylephrine as standard care to treat anaesthesia-induced hypotension. Further, the study will assess whether internal carotid artery blood flow is affected by development of MTS and whether propofol anaesthesia affects the CO2 reactivity of the internal carotid artery.
Hypotheses
- Propofol anaesthesia and related anaesthesia-induced hypotension (MAP < 65 mmHg) reduces internal carotid artery blood flow
- Treatment of anaesthesia-induced hypotension by administration of phenylephrine increases internal carotid artery blood flow
- Development of MTS increases near-infrared spectroscopy determined frontal lobe oxygenation due to an increase in forehead skin blood flow and oxygenation with no effect on internal carotid artery blood flow
- Propofol anaesthesia lowers the CO2 reactivity of the internal carotid artery
Methods The study will include thirty patients undergoing oesophageal- or ventricular resection. The study lasts from when the patient arrives to the operating room and until two hours after the start of surgery. As part of standard care all patients will be instrumented with arterial and central venous catheters. Anaesthesia will be induced by propofol and maintained by propofol and remifentanil combined with epidural anaesthesia. Development of MTS is defined by flushing within the first 60 min of surgery. Measurements include unilateral internal carotid artery blood flow evaluated by duplex ultrasound, MAP and heart rate as recorded by a transducer connected to the arterial line, central haemodynamics (stroke volume, CO, and total peripheral resistance) evaluated by pulse contour analysis of the arterial pressure curve, frontal lobe and muscle oxygenation as determined by near-infrared spectroscopy, forehead skin blood flow, haemoglobin concentrations, and oxygenation assessed by laser Doppler flowmetry, and depth of anaesthesia determined by Bispectral Index. At each time point 2 measurements of internal carotid artery blood flow are collected and the mean is taken. Arterial blood will be drawn for analysis of the arterial CO2 tension (PaCO2).
During the study PaCO2 will be maintained at the value before induction of anaesthesia by ventilator adjustments. Internal carotid artery CO2 reactivity before induction of anaesthesia will be determined by evaluations of blood flow and PaCO2 during normoventilation and during hyperventilation to reduce PaCO2 by 1.5 kPa as guided by end-tidal CO2 tension (PetCO2) and measurements will be conducted when PetCO2 has been stable for 5 min. The CO2 reactivity during anaesthesia will be determined by evaluations of internal carotid artery blood flow and PaCO2 at a PaCO2 at the value before induction of anaesthesia and 1.5 kPa above and below that value as guided by PetCO2 and measurements will be conducted when PetCO2 has been stable for 5 min. The CO2 reactivity before and during anaesthesia is calculated as the percentage change in internal carotid artery blood flow per kPa change in PaCO2. Analysis of internal carotid blood flow will be after correction for CO2 reactivity.
Blood samples for analysis of markers of MTS (6-keto-prostaglandin-F1, pro-ANP, ACTH, cortisone, IL-1, IL-6, and TNF-α) will be drawn before induction of anaesthesia and 20 and 60 min after the start of surgery. Total amount of blood samples will be no more than 75 ml. Patients will be excluded if the planned surgery is cancelled and excluded patients will be replaced.
Measurements will be conducted and arterial blood drawn at the following time points:
- Before induction of anaesthesia during normoventilation and hyperventilation
- After induction of anaesthesia
- During anaesthesia-induced hypotension (MAP < 65 mmHg)
- After treatment of anaesthesia-induced hypotension by administration of phenylephrine
- 5 min before and after incision and 0, 20, 40 and 70 min after development of MTS and 20, 40, 60 and 90 min after the start of surgery in patients who did not develop MTS
- During normo-, hyper-, and hypocapnia during anaesthesia in random order
Statistics Trial size: The minimal clinically important difference in internal carotid artery blood flow by treatment of anaesthesia-induced hypotension is considered to be 10%, corresponding to approximately 24 ml/min, and twenty-seven patients were considered required assuming a 42 ml/min SD with a 5% significance level and a power of 80%.
- Conditions
- Gastrointestinal Neoplasms
- Being tested
- Study of cerebral blood flow
- Keywords
- abdominal surgery, blood pressure, cardiac output, cerebral blood flow, cerebral oxygenation, CO2 reactivity, duplex ultrasound, general anaesthesia, mesenteric traction syndrome, near-infrared spectroscopy, upper gastrointestinal cancer surgery
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Study of cerebral blood flowOther
Measurements are conducted from before induction of anaesthesia and until 2 hours after the start of surgery and include internal carotid artery blood flow, mean arterial pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, forehead skin blood flow and haemoglobin concentrations, depth of anaesthesia, and frontal lobe, skin, and muscle oxygenation. Further measurements are conducted during hyperventilation before induction of anaesthesia and during hypo-, normo- and hypercapnia during anaesthesia.
Blood samples are obtained from the arterial line for evaluation of the arterial CO2 tension and markers of mesenteric traction syndrome. Total volume of blood sampled is less than 75 ml.
| Study group | Role | What they receive |
|---|---|---|
| Study of cerebral blood flow | Patients undergoing oesophageal- or ventricular resection (n=30) Receives: Other: Study of cerebral blood flow |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Internal Carotid Artery Blood Flow by Treatment of Anaesthesia-induced Hypotension
Unilateral internal carotid artery blood flow [ml/min] assessed by duplex ultrasound.
Measured: Two measurements; one measurement during anaesthesia-induced hypotension (mean arterial pressure < 65 mmHg) before administration of phenylephrine and one measurement 3-5 min after administration of phenylephrine.
Secondary outcomes (11)
Changes in Internal Carotid Artery Blood Flow by Induction of Anaesthesia.
Unilateral internal carotid artery blood flow [ml/min] assessed by duplex ultrasound.
Measured: Two measurements; one measurement 5-10 min before induction of anaesthesia and one measurement 5-20 min after induction of anaesthesia.
Association by Multiple Regression Between Changes in Internal Carotid Artery Blood Flow, Mean Arterial Pressure and Cardiac Output by Treatment of Anaesthesia-induced Hypotension.
Association by multiple regression between changes in unilateral internal carotid artery blood flow [ml/min] as outcome variable and changes in mean arterial pressure [mmHg] and cardiac output [l/min] as covariates.
Internal carotid artery blood flow [ml/min] was assessed by duplex ultrasound. Mean arterial pressure [mmHg] was recorded by a transducer connected to an arterial line. Cardiac output [l/min] was evaluated by pulse contour analysis (Modelflow) that estimates cardiac output by analysis of the arterial pressure curve taking age, gender, height and weigth into account.
Measured: Two measurements; one measurement during anaesthesia-induced hypotension (mean arterial pressure < 65 mmHg) before administration of phenylephrine and one measurement 3-5 min after administration of phenylephrine.
Changes in Frontal Lobe Oxygenation by Development of Mesenteric Traction Syndrome (MTS).
Near-infrared spectroscopy determined frontal lobe oxygenation [%] as compared between those patients who develop a MTS (defined as flushing within 60 min after the start of surgery) and those who do not. An effect of a MTS was evaluated by a repeated measure mixed model with the fixed effects time point, group according to development of MTS, and interaction between time and group. The reported result is the interaction factor for the time point 0 min after flushing and 20 min after the start of surgery in patients who did not develop MTS.
Measured: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in Forehead Skin Blood Flow by Development of Mesenteric Traction Syndrome (MTS).
Forehead skin blood flow [PU] assessed by laser Doppler flowmetry as compared between those patients who develop mesenteric traction syndrome (defined as flushing within 60 min after the start of surgery) and those who do not. Laser Doppler flowmetry applies a laser placed on the forehead that penetrates the skin and is scattered with a Doppler shift by the red blood cells and return to a detector that evaluates the amount of backscattered light and Doppler shift. An effect of a MTS was evaluated by a repeated measure mixed model with the fixed effects time point, group according to development of MTS, and interaction between time and group. The reported result is the interaction factor for the time point 0 min after flushing and 20 min after the start of surgery in patients who did not develop MTS.
Measured: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in Forehead Skin Oxygenation by Development of Mesenteric Traction Syndrome (MTS).
Forehead skin oxygenation [%] assessed by laser Doppler flowmetry as compared between those patients who develop a MTS (defined as flushing within 60 min after the start of surgery) and those who do not. An effect of a MTS was evaluated by a repeated measure mixed model with the fixed effects time point, group according to development of MTS, and interaction between time and group. The reported result is the interaction factor for the time point 0 min after flushing and 20 min after the start of surgery in patients who did not develop MTS.
Measured: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in Internal Carotid Artery Blood Flow by Development of Mesenteric Traction Syndrome (MTS).
Unilateral internal carotid artery blood flow [ml/min] assessed by duplex ultrasound as compared between those patients who develop a MTS (defined as flushing within 60 min after the start of surgery) and those who do not. An effect of a MTS was evaluated by a repeated measure mixed model with the fixed effects time point, group according to development of MTS, and interaction between time and group. The reported result is the interaction factor for the time point 0 min after flushing and 20 min after the start of surgery in patients who did not develop MTS.
Measured: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in the CO2 Reactivity of the Internal Carotid Artery From Before to After Induction of Anaesthesia.
Unilateral internal carotid artery blood flow [ml/min] assessed by duplex ultrasound and arterial CO2 tension (PaCO2) [kPa] was evaluated by gas analysis. Changes in PaCO2 are guided by evaluation of end-tidal CO2 tension.
The CO2 reactivity to hypocapnia when awake and during anaesthesia is calculated as the percentage change in internal carotid artery blood flow per kPa change in PaCO2. The CO2 reactivity when awake and when anaesthetized is compared.
Measured: Four measurements; before induction of anaesthesia during normoventilation and during hyperventilation to reduce PaCO2 by 1.5 kPa and during anaesthesia at a PaCO2 at the value before induction of anaesthesia and 1.5 kPa below that value.
Changes in Heart Rate From Baseline Before Induction of Anaesthesia.
Heart rate [bpm] as recorded continuously by a transducer connected to an arterial line.
Measured: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Changes in Mean Arterial Pressure From Baseline Before Induction of Anaesthesia.
Mean arterial pressure [mmHg] as recorded continuously by a transducer connected to an arterial line.
Measured: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Changes in Cardiac Output From Baseline Before Induction of Anaesthesia.
Cardiac output [l/min] as evaluated continuously by pulse contour analysis of the arterial pressure curve (Modelflow).
Measured: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Changes in Stroke Volume From Baseline Before Induction of Anaesthesia.
Stroke volume [ml] as evaluated continuously by pulse contour analysis of the arterial pressure curve (Modelflow).
Measured: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study start8 Dec 2016
- Primary completion6 Jul 2017
- Study completion6 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Niels Damkjær Olesen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Niels H. Secher, MD, D.M.Sc., Study director, Department of Anaesthesia, Rigshospitalet 2043, DK-2100 Copenhagen Ø, DenmarkNiels D. Olesen, MD, Principal investigator, Department of Anaesthesia, Rigshospitalet 2043, DK-2100 Copenhagen Ø, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02951273
- Sponsor's protocol ID
- H-16036250
- Status last verified
- Dec 2017
- First submitted
- 26 Oct 2016
- Last updated
- 17 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Fujimoto Y, Nomura Y, Hirakawa K, Hotta A, Nakamoto A, Yoshikawa N, Ohira N, Tatekawa S. Flurbiprofen axetil provides a prophylactic benefit against mesenteric traction syndrome associated with remifentanil infusion during laparotomy. J Anesth. 2012 Aug;26(4):490-5. doi: 10.1007/s00540-012-1368-8. Epub 2012 Mar 2.
PubMed 22382665Jorgensen LG, Perko M, Perko G, Secher NH. Middle cerebral artery velocity during head-up tilt induced hypovolaemic shock in humans. Clin Physiol. 1993 Jul;13(4):323-36. doi: 10.1111/j.1475-097x.1993.tb00333.x.
PubMed 8370233Kaisti KK, Metsahonkala L, Teras M, Oikonen V, Aalto S, Jaaskelainen S, Hinkka S, Scheinin H. Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography. Anesthesiology. 2002 Jun;96(6):1358-70. doi: 10.1097/00000542-200206000-00015.
PubMed 12170048Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, Hert SD, Ford I, Gonzalez-Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luscher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Sousa-Uva M, Voudris V, Funck-Brentano C; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014 Sep 14;35(35):2383-431. doi: 10.1093/eurheartj/ehu282. Epub 2014 Aug 1. No abstract available.
PubMed 25086026LASSEN NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959 Apr;39(2):183-238. doi: 10.1152/physrev.1959.39.2.183. No abstract available.
PubMed 13645234Matta BF, Lam AM, Strebel S, Mayberg TS. Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression. Br J Anaesth. 1995 Feb;74(2):159-63. doi: 10.1093/bja/74.2.159.
PubMed 7696064Meng L, Hou W, Chui J, Han R, Gelb AW. Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans. Anesthesiology. 2015 Nov;123(5):1198-208. doi: 10.1097/ALN.0000000000000872.
PubMed 26402848Nissen P, van Lieshout JJ, Nielsen HB, Secher NH. Frontal lobe oxygenation is maintained during hypotension following propofol-fentanyl anesthesia. AANA J. 2009 Aug;77(4):271-6.
PubMed 19731845Ogoh S, Sato K, Okazaki K, Miyamoto T, Secher F, Sorensen H, Rasmussen P, Secher NH. A decrease in spatially resolved near-infrared spectroscopy-determined frontal lobe tissue oxygenation by phenylephrine reflects reduced skin blood flow. Anesth Analg. 2014 Apr;118(4):823-9. doi: 10.1213/ANE.0000000000000145.
PubMed 24651237Takada M, Taruishi C, Sudani T, Suzuki A, Iida H. Intravenous flurbiprofen axetil can stabilize the hemodynamic instability due to mesenteric traction syndrome--evaluation with continuous measurement of the systemic vascular resistance index using a FloTrac(R) sensor. J Cardiothorac Vasc Anesth. 2013 Aug;27(4):696-702. doi: 10.1053/j.jvca.2012.11.019. Epub 2013 May 3.
PubMed 23648081Torella F, McCollum CN. Regional haemoglobin oxygen saturation during surgical haemorrhage. Minerva Med. 2004 Oct;95(5):461-7.
PubMed 15467521Uski T, Andersson KE, Brandt L, Edvinsson L, Ljunggren B. Responses of isolated feline and human cerebral arteries to prostacyclin and some of its metabolites. J Cereb Blood Flow Metab. 1983 Jun;3(2):238-45. doi: 10.1038/jcbfm.1983.32.
PubMed 6341384Wienecke T, Olesen J, Oturai PS, Ashina M. Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain. 2008 Sep 30;139(1):106-116. doi: 10.1016/j.pain.2008.03.018. Epub 2008 May 2.
PubMed 18450380
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebral Blood Flow During Propofol Anaesthesia
- ClinicalTrials.gov ID
- NCT02951273
- Acronym / sponsor ID
- H-16036250
- Conditions
- Gastrointestinal Neoplasms
- Keywords
- abdominal surgery, blood pressure, cardiac output, cerebral blood flow, cerebral oxygenation, CO2 reactivity, duplex ultrasound, general anaesthesia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- 8 Dec 2016 (actual)
- Primary completion
- 6 Jul 2017 (actual)
- Study completion
- 6 Jul 2017 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Posted 17 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
General anaesthesia often reduces blood pressure whereby blood flow to the brain and other vital organs may become insufficient. Thus, medicine is often administered during anaesthesia to maintain blood pressure. However, it is unclear at what level blood pressure should be aimed at during anaesthesia.
Several factors may affect blood flow to the brain during anaesthesia. During surgery on the internal organs, a hormone may be released that dilates blood vessels and causes a so-called mesenteric traction syndrome characterised by a decrease in blood pressure and flushing. This reaction lasts for approximately thirty minutes and is observed in about half of the patients who undergo surgery on the stomach and intestines. It is unknown whether a mesenteric traction syndrome affects blood flow to the brain. Ventilation is also of importance for blood flow to the brain. Thus, blood flow to the brain is reduced by hyperventilation and increases if breathing is slower. It is unclear whether the relation between blood flow to the brain and ventilation is affected during anaesthesia.
This study will evaluate how blood flow to the brain is affected by anaesthesia and standard treatment of a possible reduction in blood pressure. Further, the study will assess whether blood flow to the brain is affected by development of a mesenteric traction syndrome. Lastly, the project will evaluate blood flow to the brain during short-term changes in the patient's ventilation by adjustments on the ventilator.
Thirty patients planned for major abdominal surgery will be included in the project. The study will take place from the patient's arrival at the operation room and until two hours after the start of surgery. Placement of catheters and anaesthesia are according to standard care. Blood flow to the brain will be evaluated using ultrasound. Oxygenation of the brain, skin and muscle will be evaluated by probes that emit light. Depth of anaesthesia is assessed by recording the electrical activity of the brain. Blood pressure is measured by a catheter placed in an artery at the wrist and blood samples will be drawn from the catheter.
Detailed description
Background General anaesthesia reduces blood pressure, but cerebral autoregulation is considered to maintain its blood flow if mean arterial pressure (MAP) is between 60-150 mmHg. Thus, vasoactive medication is administered to treat anaesthesia-induced hypotension if MAP decreases to below approximately 60 mmHg. In young healthy adults, propofol anaesthesia, with limited reduction in blood pressure, decreases cerebral blood flow by approximately 50% by a decrease in neuronal activity. However, it is unknown whether the anaesthesia-induced reduction in cerebral blood flow is affected by a marked decrease in MAP and whether propofol anaesthesia affects the lower level of cerebral autoregulation.
If central blood volume is maintained, cerebral oxygenation may be unaffected by a decrease in MAP to ~40 mmHg whereas a reduction in central blood volume and cardiac output (CO) during orthostasis or bleeding, reduces cerebral oxygenation when MAP is lower than approximately 80 mmHg. Thus, CO may affect cerebral blood flow and the ability to increase CO is likely of importance for maintaining a sufficient cerebral blood flow.
During anaesthesia, cerebral blood flow and MAP may be affected by various factors including release of vasoactive substances. Manipulation of the abdominal organs may induce a so-called mesenteric traction syndrome (MTS) encompassing a triad of flushing, hypotension, and tachycardia in about half of the patients who undergo major abdominal surgery. MTS typically develops 15-20 min after the start of surgery and the haemodynamic manifestations, that appear to be mediated by prostaglandin I2, last for approximately 30 min. The effect of MTS on cerebral blood flow is unknown. Prostaglandin I2 dilates cerebral arteries in vitro but does not affect cerebral blood flow when administered to healthy subjects. In a previous study we found that MTS increases near-infrared spectroscopy determined frontal lobe oxygenation possibly due to an increase in extracranial circulation while there was no effect on middle cerebral artery mean flow velocity as an index of changes in cerebral blood flow.
Propofol anaesthesia appears not to affect the CO2 reactivity of the middle cerebral artery as determined by transcranial Doppler ultrasonography, but the CO2 reactivity of the internal carotid artery during propofol anaesthesia is unknown.
Objective The purpose of this study is to evaluate how internal carotid artery blood flow is affected by propofol anaesthesia and related hypotension, and by administration of phenylephrine as standard care to treat anaesthesia-induced hypotension. Further, the study will assess whether internal carotid artery blood flow is affected by development of MTS and whether propofol anaesthesia affects the CO2 reactivity of the internal carotid artery.
Hypotheses
- Propofol anaesthesia and related anaesthesia-induced hypotension (MAP < 65 mmHg) reduces internal carotid artery blood flow
- Treatment of anaesthesia-induced hypotension by administration of phenylephrine increases internal carotid artery blood flow
- Development of MTS increases near-infrared spectroscopy determined frontal lobe oxygenation due to an increase in forehead skin blood flow and oxygenation with no effect on internal carotid artery blood flow
- Propofol anaesthesia lowers the CO2 reactivity of the internal carotid artery
Methods The study will include thirty patients undergoing oesophageal- or ventricular resection. The study lasts from when the patient arrives to the operating room and until two hours after the start of surgery. As part of standard care all patients will be instrumented with arterial and central venous catheters. Anaesthesia will be induced by propofol and maintained by propofol and remifentanil combined with epidural anaesthesia. Development of MTS is defined by flushing within the first 60 min of surgery. Measurements include unilateral internal carotid artery blood flow evaluated by duplex ultrasound, MAP and heart rate as recorded by a transducer connected to the arterial line, central haemodynamics (stroke volume, CO, and total peripheral resistance) evaluated by pulse contour analysis of the arterial pressure curve, frontal lobe and muscle oxygenation as determined by near-infrared spectroscopy, forehead skin blood flow, haemoglobin concentrations, and oxygenation assessed by laser Doppler flowmetry, and depth of anaesthesia determined by Bispectral Index. At each time point 2 measurements of internal carotid artery blood flow are collected and the mean is taken. Arterial blood will be drawn for analysis of the arterial CO2 tension (PaCO2).
During the study PaCO2 will be maintained at the value before induction of anaesthesia by ventilator adjustments. Internal carotid artery CO2 reactivity before induction of anaesthesia will be determined by evaluations of blood flow and PaCO2 during normoventilation and during hyperventilation to reduce PaCO2 by 1.5 kPa as guided by end-tidal CO2 tension (PetCO2) and measurements will be conducted when PetCO2 has been stable for 5 min. The CO2 reactivity during anaesthesia will be determined by evaluations of internal carotid artery blood flow and PaCO2 at a PaCO2 at the value before induction of anaesthesia and 1.5 kPa above and below that value as guided by PetCO2 and measurements will be conducted when PetCO2 has been stable for 5 min. The CO2 reactivity before and during anaesthesia is calculated as the percentage change in internal carotid artery blood flow per kPa change in PaCO2. Analysis of internal carotid blood flow will be after correction for CO2 reactivity.
Blood samples for analysis of markers of MTS (6-keto-prostaglandin-F1, pro-ANP, ACTH, cortisone, IL-1, IL-6, and TNF-α) will be drawn before induction of anaesthesia and 20 and 60 min after the start of surgery. Total amount of blood samples will be no more than 75 ml. Patients will be excluded if the planned surgery is cancelled and excluded patients will be replaced.
Measurements will be conducted and arterial blood drawn at the following time points:
- Before induction of anaesthesia during normoventilation and hyperventilation
- After induction of anaesthesia
- During anaesthesia-induced hypotension (MAP < 65 mmHg)
- After treatment of anaesthesia-induced hypotension by administration of phenylephrine
- 5 min before and after incision and 0, 20, 40 and 70 min after development of MTS and 20, 40, 60 and 90 min after the start of surgery in patients who did not develop MTS
- During normo-, hyper-, and hypocapnia during anaesthesia in random order
Statistics Trial size: The minimal clinically important difference in internal carotid artery blood flow by treatment of anaesthesia-induced hypotension is considered to be 10%, corresponding to approximately 24 ml/min, and twenty-seven patients were considered required assuming a 42 ml/min SD with a 5% significance level and a power of 80%.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study of cerebral blood flow | – | Other: Study of cerebral blood flowPatients undergoing oesophageal- or ventricular resection (n=30) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Thirty patients planned for oesophageal- or ventricular resection at Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark
Key inclusion criteria (2 listed)
- Patients planned for major abdominal surgery that require placement of an arterial line and central venous catheter, including oesophageal- or ventricular resection
- Age ≥ 18 years.
Key exclusion criteria (5 listed)
- No informed consent
- Robotic assisted procedures
- Treatment with anti-inflammatory medication, including NSAID and corticosteroids
- Atherosclerosis of the internal carotid artery that obstructs ≥ 30% of the vessel lumen
- Neurologic disease considered to affect cerebral blood flow, including dementia, epilepsy, and apoplexy
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 |
|---|---|---|
| Study of cerebral blood flowMeasurements are conducted from before induction of anaesthesia and until 2 hours after the start of surgery and include internal carotid artery blood flow, mean arterial pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, forehead skin blood flow and haemoglobin concentrations, depth of anaesthesia, and frontal lobe, skin, and muscle oxygenation. Further measurements are conducted during hyperventilation before induction of anaesthesia and during hypo-, normo- and hypercapnia during anaesthesia. Blood samples are obtained from the arterial line for evaluation of the arterial CO2 tension and markers of mesenteric traction syndrome. Total volume of blood sampled is less than 75 ml. | Other | Study of cerebral blood flow |
Primary outcome
Changes in Internal Carotid Artery Blood Flow by Treatment of Anaesthesia-induced Hypotension
Time frame: Two measurements; one measurement during anaesthesia-induced hypotension (mean arterial pressure < 65 mmHg) before administration of phenylephrine and one measurement 3-5 min after administration of phenylephrine.
Unilateral internal carotid artery blood flow [ml/min] assessed by duplex ultrasound.
11 secondary outcomes
Changes in Internal Carotid Artery Blood Flow by Induction of Anaesthesia.
Time frame: Two measurements; one measurement 5-10 min before induction of anaesthesia and one measurement 5-20 min after induction of anaesthesia.
Association by Multiple Regression Between Changes in Internal Carotid Artery Blood Flow, Mean Arterial Pressure and Cardiac Output by Treatment of Anaesthesia-induced Hypotension.
Time frame: Two measurements; one measurement during anaesthesia-induced hypotension (mean arterial pressure < 65 mmHg) before administration of phenylephrine and one measurement 3-5 min after administration of phenylephrine.
Changes in Frontal Lobe Oxygenation by Development of Mesenteric Traction Syndrome (MTS).
Time frame: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in Forehead Skin Blood Flow by Development of Mesenteric Traction Syndrome (MTS).
Time frame: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in Forehead Skin Oxygenation by Development of Mesenteric Traction Syndrome (MTS).
Time frame: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in Internal Carotid Artery Blood Flow by Development of Mesenteric Traction Syndrome (MTS).
Time frame: Six measurements during anaesthesia; 5 min before and after incision and 0, 20, 40, and 70 min after flushing and 20, 40, 60, and 90 min after the start of surgery in those patients who do not develop mesenteric traction syndrome.
Changes in the CO2 Reactivity of the Internal Carotid Artery From Before to After Induction of Anaesthesia.
Time frame: Four measurements; before induction of anaesthesia during normoventilation and during hyperventilation to reduce PaCO2 by 1.5 kPa and during anaesthesia at a PaCO2 at the value before induction of anaesthesia and 1.5 kPa below that value.
Changes in Heart Rate From Baseline Before Induction of Anaesthesia.
Time frame: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Changes in Mean Arterial Pressure From Baseline Before Induction of Anaesthesia.
Time frame: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Changes in Cardiac Output From Baseline Before Induction of Anaesthesia.
Time frame: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Changes in Stroke Volume From Baseline Before Induction of Anaesthesia.
Time frame: Continuous measurements from before induction of anaesthesia and until 2 hours after start of surgery.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22382665Fujimoto Y, Nomura Y, Hirakawa K, Hotta A, Nakamoto A, Yoshikawa N, Ohira N, Tatekawa S. Flurbiprofen axetil provides a prophylactic benefit against mesenteric traction syndrome associated with remifentanil infusion during laparotomy. J Anesth. 2012 Aug;26(4):490-5. doi: 10.1007/s00540-012-1368-8. Epub 2012 Mar 2.
- Background: PubMed 8370233Jorgensen LG, Perko M, Perko G, Secher NH. Middle cerebral artery velocity during head-up tilt induced hypovolaemic shock in humans. Clin Physiol. 1993 Jul;13(4):323-36. doi: 10.1111/j.1475-097x.1993.tb00333.x.
- Background: PubMed 12170048Kaisti KK, Metsahonkala L, Teras M, Oikonen V, Aalto S, Jaaskelainen S, Hinkka S, Scheinin H. Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography. Anesthesiology. 2002 Jun;96(6):1358-70. doi: 10.1097/00000542-200206000-00015.
- Background: PubMed 25086026Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, Hert SD, Ford I, Gonzalez-Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luscher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Sousa-Uva M, Voudris V, Funck-Brentano C; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014 Sep 14;35(35):2383-431. doi: 10.1093/eurheartj/ehu282. Epub 2014 Aug 1. No abstract available.
- Background: PubMed 13645234LASSEN NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959 Apr;39(2):183-238. doi: 10.1152/physrev.1959.39.2.183. No abstract available.
- Background: PubMed 7696064Matta BF, Lam AM, Strebel S, Mayberg TS. Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression. Br J Anaesth. 1995 Feb;74(2):159-63. doi: 10.1093/bja/74.2.159.
- Background: PubMed 26402848Meng L, Hou W, Chui J, Han R, Gelb AW. Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans. Anesthesiology. 2015 Nov;123(5):1198-208. doi: 10.1097/ALN.0000000000000872.
- Background: PubMed 19731845Nissen P, van Lieshout JJ, Nielsen HB, Secher NH. Frontal lobe oxygenation is maintained during hypotension following propofol-fentanyl anesthesia. AANA J. 2009 Aug;77(4):271-6.
- Background: PubMed 24651237Ogoh S, Sato K, Okazaki K, Miyamoto T, Secher F, Sorensen H, Rasmussen P, Secher NH. A decrease in spatially resolved near-infrared spectroscopy-determined frontal lobe tissue oxygenation by phenylephrine reflects reduced skin blood flow. Anesth Analg. 2014 Apr;118(4):823-9. doi: 10.1213/ANE.0000000000000145.
- Background: PubMed 23648081Takada M, Taruishi C, Sudani T, Suzuki A, Iida H. Intravenous flurbiprofen axetil can stabilize the hemodynamic instability due to mesenteric traction syndrome--evaluation with continuous measurement of the systemic vascular resistance index using a FloTrac(R) sensor. J Cardiothorac Vasc Anesth. 2013 Aug;27(4):696-702. doi: 10.1053/j.jvca.2012.11.019. Epub 2013 May 3.
- Background: PubMed 15467521Torella F, McCollum CN. Regional haemoglobin oxygen saturation during surgical haemorrhage. Minerva Med. 2004 Oct;95(5):461-7.
- Background: PubMed 6341384Uski T, Andersson KE, Brandt L, Edvinsson L, Ljunggren B. Responses of isolated feline and human cerebral arteries to prostacyclin and some of its metabolites. J Cereb Blood Flow Metab. 1983 Jun;3(2):238-45. doi: 10.1038/jcbfm.1983.32.
- Individual participant dataSharing planned: No
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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.
Niels H. Secher, MD, D.M.Sc. study director
Department of Anaesthesia, Rigshospitalet 2043, DK-2100 Copenhagen Ø, Denmark
Niels D. Olesen, MD principal investigator
Department of Anaesthesia, Rigshospitalet 2043, DK-2100 Copenhagen Ø, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gastrointestinal Neoplasms, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 2 inclusion and 5 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 17 Jan 2018. 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 Denmark. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Internal Carotid Artery Blood Flow by Treatment of Anaesthesia-induced Hypotension (time frame: Two measurements; one measurement during anaesthesia-induced hypotension (mean arterial pressure < 65 mmHg) before administration of phenylephrine and one measurement 3-5 min after administration of phenylephrine.). 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 NCT02951273, which also lists 13 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 17 Jan 2018.