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Clinical Trials/NCT03309917
NCT03309917CompletedNot Applicable

The Effect of Blood Pressure on Cerebral Blood Flow During Propofol Anesthesia

Rigshospitalet, Denmark1 site in 1 country30 target enrollmentStarted: December 27, 2017Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Not Applicable
Status
Completed
Enrollment
30
Locations
1
Primary Endpoint
Change in internal carotid artery blood flow when mean arterial pressure (MAP) is set to 80-85 and 60-65 mmHg

Study Overview

Brief Summary

General anesthesia often reduces blood pressure whereby blood flow to the brain and other vital organs may become insufficient. Thus, medicine is often administered to maintain blood pressure but it is unclear at what level blood pressure should be aimed at during anesthesia.

Thirty patients undergoing major abdominal surgery will be included. The study will start one hour after the start of surgery and lasts for approximately half an hour. The purpose of the study is to evaluate whether blood flow to the brain can be increased by maintaining blood pressure at a higher level than that used in clinical practice. In the study, MAP is adjusted to a high, moderate, and low level for a short time. The low level of blood pressure used in the study, corresponds to the level aimed at in clinical practice. The drug noradrenaline will be used to control blood pressure. Blood flow to the brain will be evaluated on the neck using ultrasound.

Detailed Description

Background Propofol anesthesia reduces cerebral blood flow (CBF) and mean arterial pressure (MAP) but it is unclear whether the decrease in CBF is accentuated by hypotension. Cerebral autoregulation is generally considered to maintain CBF when MAP is between 60-150 mmHg. Hence, vasoactive medication is administered if MAP decreases to below approximately 60 mmHg.

It is controversial whether there is a plateau for cerebral autoregulation. Thus, middle cerebral artery blood velocity (MCA Vmean), as an index of CBF, is associated to MAP during pharmacological changes in MAP between approximately 40-125 mmHg. Similarly, CBF is affected by pharmacological changes in MAP between 40-80 mmHg during hypothermic cardiopulmonary bypass surgery in propofol anesthesia. Arterial hypertension may increase the lower limit of cerebral autoregulation which can be mitigated by antihypertensive treatment.

Cognitive dysfunction and delirium are common following major surgery, particularly in the elderly, and may be related to hypotension and cerebral hypoperfusion. Further, hypotensive anesthesia is associated with an increase in markers of neuronal damage, but studies have been too small to detect any difference in incidence of cognitive dysfunction following hypotensive as compared to normotensive anesthesia.

In young healthy adults, propofol anesthesia causes limited reduction in blood pressure and decreases CBF by approximately 50% by a reduction in neuronal activity. An increase in MAP from approximately 80 to 100 mmHg during propofol anesthesia does not affect CBF but it is unknown whether CBF can be increased by an increase in MAP from approximately 60 to 80 mmHg. Propofol appears to maintain cerebral autoregulation but it is unknown whether the lower level of cerebral autoregulation is affected. The internal carotid artery supplies most of CBF and dilates during moderate hypotension with maintained blood flow which indicates that the vessel contributes to cerebral autoregulation. Further, central blood volume and cardiac output may be important factors for maintaining CBF.

The study will include thirty patients planned for major abdominal surgery in propofol-remifentanil anesthesia combined with epidural analgesia. Internal carotid artery blood flow will be evaluated on the neck using duplex ultrasound. The study will be conducted one hour after the start of surgery and lasts for approximately half an hour. In the study, MAP is set pharmacologically at 80-85, 70-75 and 60-65 mmHg for a short time in random order. The level of 60-65 mmHg corresponds to the level at which MAP is maintained in clinical practice. Control of MAP is by intravenous infusion of noradrenaline, an α- and β-adrenergic agonist.

Study Design

Study Type
Interventional
Allocation
Na
Intervention Model
Single Group
Primary Purpose
Basic Science
Masking
None

Eligibility Criteria

Ages
19 Years to — (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Patient planned for Whipple's surgery or total pancreatic resection
  • •Age > 18 years

Exclusion Criteria

  • •No informed consent
  • •Alcohol intake ≥ 420 g / week
  • •Beard on the neck
  • •Visualization of the internal carotid artery not possible, e.g. due to high placement of the bifurcation
  • •Stenosis that obstructs ≥ 16% of the internal carotid artery
  • •Cardiac disease, including congestive heart failure (NYHA II-IV), myocardial infarction, valvular heart disease or atrial fibrillation
  • •Neurologic disease considered to affect cerebral blood flow, including dementia, epilepsy, and apoplexy
  • •Intake of moclobemide, isocarboxazid or tricyclic antidepressants

Arms & Interventions

Changes in mean arterial pressure

Experimental

The study is conducted from one hour after incision and lasts for approximately half an hour. Measurements are conducted at three levels of mean arterial pressure:

  • MAP set at 80-85 mmHg for 5 min.
  • MAP set at 70-75 mmHg for 5 min.
  • MAP set at 60-65 mmHg for 5 min.

Blood pressure control is by infusion of noradrenaline. When the evaluations have been conducted blood pressure control is according to clinical practice. Measurements include internal carotid artery blood flow, mean arterial pressure, heart rate, stroke volume, frontal lobe and muscle oxygenation, depth of anesthesia, and arterial and central venous blood gas variables.

Intervention: MAP set at 80-85 mmHg for 5 min (Other)

Changes in mean arterial pressure

Experimental

The study is conducted from one hour after incision and lasts for approximately half an hour. Measurements are conducted at three levels of mean arterial pressure:

  • MAP set at 80-85 mmHg for 5 min.
  • MAP set at 70-75 mmHg for 5 min.
  • MAP set at 60-65 mmHg for 5 min.

Blood pressure control is by infusion of noradrenaline. When the evaluations have been conducted blood pressure control is according to clinical practice. Measurements include internal carotid artery blood flow, mean arterial pressure, heart rate, stroke volume, frontal lobe and muscle oxygenation, depth of anesthesia, and arterial and central venous blood gas variables.

Intervention: MAP set at 70-75 mmHg for 5 min (Other)

Changes in mean arterial pressure

Experimental

The study is conducted from one hour after incision and lasts for approximately half an hour. Measurements are conducted at three levels of mean arterial pressure:

  • MAP set at 80-85 mmHg for 5 min.
  • MAP set at 70-75 mmHg for 5 min.
  • MAP set at 60-65 mmHg for 5 min.

Blood pressure control is by infusion of noradrenaline. When the evaluations have been conducted blood pressure control is according to clinical practice. Measurements include internal carotid artery blood flow, mean arterial pressure, heart rate, stroke volume, frontal lobe and muscle oxygenation, depth of anesthesia, and arterial and central venous blood gas variables.

Intervention: MAP set at 60-65 mmHg for 5 min (Other)

Outcomes

Primary Outcomes

Change in internal carotid artery blood flow when mean arterial pressure (MAP) is set to 80-85 and 60-65 mmHg

Time Frame: Values are recorded during 2 min at 2 time points; when MAP is set to 80-85 and 60-65 mmHg during propofol anesthesia as part of the study. The evaluations are separated by approximately 30 min

Internal carotid artery blood flow \[ml/min\] assessed by duplex ultrasound when MAP is set to 80-85 and 60-65 mmHg for 5 min as part of the experiment during propofol anesthesia

Secondary Outcomes

  • Change in internal carotid artery blood flow when MAP is set to 70-75 and 60-65 mmHg(Values are recorded during 2 min at 2 time points; when MAP is set to 70-75 and 60-65 mmHg during propofol anesthesia as part of the study. The evaluations are separated by approximately 15 min)
  • Change in internal carotid artery blood flow when MAP is set to 80-85 and 70-75 mmHg(Values are recorded during 2 min at 2 time points; when MAP is set to 80-85 and 70-75 mmHg during propofol anesthesia as part of the study. The evaluations are separated by approximately 15 min)
  • Comparison of the slope of linear regression of MAP and internal carotid artery blood flow for the evaluations when MAP is set to 80-85 and 70-75 mmHg and that of the evaluations when MAP is set to 70-75 and 60-65 mmHg(Values are recorded during 2 min at 3 time points; when MAP is set to 80-85, 70-75, and 60-65 mmHg during propofol anesthesia as part of the study. The evaluations are separated by approximately 15 and 30 min)

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Niels Damkjær Olesen

Principal investigator

Rigshospitalet, Denmark

Study Sites (1)

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