Vasopressor Impact on Brain Circulation, Organ Blood Flow and Tissue Oxygenation During Anesthesia

Study Overview
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Brief Summary
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The optimal vasopressor for ensuring organ blood flow and tissue oxygen delivery during surgery remains undetermined. This study aim to compare the effects of noradrenaline vs. phenylephrine infusion on blood flow and oxygen delivery to the brain and various other organs in anesthetized neurosurgical patients.

Detailed Description
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The brain and other blood flow sensitive organs are vulnerable to hypotension during neurosurgery. As a countermeasure, vasopressor agents are often administered to increase blood pressure. The ultimate goal of the vasopressor is to secure perfusion of vital organs and fulfill their metabolic demand. However, the optimal vasopressor for ensuring organ blood flow and tissue oxygen delivery during surgery remains undetermined.The aim of this study is to compare the effects of noradrenaline vs. phenylephrine infusion on blood flow and oxygen consumption in the brain and various other organs in anesthetized neurosurgical patients. The project constitutes a clinical randomized study involving 40 patients diagnosed with brain tumors. The study is conducted on the same day as their scheduled brain tumor surgery. The study is designed as a randomized, double-blinded clinical trial, with two distinct groups: Group 1 receives phenylephrine, while Group 2 receives noradrenaline. PET exams of blood flow and oxygen consumption in brain and organs are performed using a PET scanner with a wide field of view. The wide field of view allow for simultaneous multiorgan blood flow and oxygen consumption measurements. Four positron emission tomography (PET) examinations are performed prior to the surgical procedure. The first PET examination (PET 1) is performed on the awake patient. The patient is then anesthetized, and the PET exam is repeated (PET 2). Vasopressor infusion is initiated and titrated to increase mean arterial blood pressure(MABP) above 60 mmHg, or by 10% relative to baseline(baseline MABP is measured prior to PET 2). The PET exam is repeated (PET 3). MABP is further increased to above 70 mmHg or by 20 % relative to the baseline level. The PET exam is repeated (PET 4). The anesthetized patient is then transported to the surgical theatre and surgery is initiated. During the surgical procedure, MABP is maintained between 70-80 mmHg according to institutional guidelines. The vasopressor infusion is terminated after completion of the surgery.. Invasive blood pressure, cardiac output (CO),depth of anesthesia (bispectral index) and brain tissue oxygen saturation(near infrared spectroscopy) are continuously measured.

Official Title
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Vasopressor Impact on Brain Circulation, Organ Blood Flow and Tissue Oxygenation During Anesthesia in Neurosurgical Patients

Conditions
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Hypotension

Intervention / Treatment
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* Drug: Noradrenalin
* Drug: Phenylephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of supratentorial malignant or non-malignant brain tumors. Preferably 3 cm or larger( measured as the largest diameter in any plane on MRI). Scheduled for elective supratentorial craniotomy. Patients aged between 18 and 75 years. American Society of Anesthesiologists status 1-3 Exclusion Criteria: History of allergy or intolerance to one of the study medications. Active treatment with monoamine oxidase inhibitors. An American Society of Anesthesiologists (ASA)physical status IV-VI. Pregnancy or breastfeeding. Inability to provide written informed consent -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double blinded, clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noradrenaline<br>Noradrenaline | Drug: Noradrenalin<br>* Infusion of noradrenaline during anesthesia and surgery<br>* Other names: Noradrenaline;|
| Active Comparator: Phenylephrine<br>Phenylephrine | Drug: Phenylephrine<br>* Infusion of phenylephrine during anesthesia and surgery<br>* Other names: metaoxedrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral blood flow | Blood flow measured in milliliters per minute through selected regions of the brain as determined by Positron Emission Tomography | Up to 3 hours (measured on the day of surgery prior to the surgical procedure) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral metabolic rate of oxygen | Cerebral oxygen consumption in selected regions of the brain as determined by Positron Emission Tomography | Up to 4 hours (measured on the day of surgery prior to the surgical procedure) | 
| Blood flow through body organs in milliliters per minute as determined by Positron Emission Tomography | Blood flow in various body organs supplied by the systemic circulation | Up to 4 hours (measured on the day of surgery prior to the surgical procedure) | 
| Blood pumped out by the heart per minute (cardiac output) | Cardiac output as determined by Positron Emission Tomography and/or by beat-to-beat determination by analysis of the arterial blood pressure waveform | Up to one day | 
| Ischemic lesions | Ischemic lesions possibly associated with vasopressor use as detected on the postoperative MRI examination | Up to 3 days | 
| Cerebral tissue oxygen saturation | Cerebral tissue oxygen saturation as measured with near infrared spectroscopy (NIRS) | Up to one day | 
| Bispectral Index (BIS) | Depth of anesthesia as measured by BIS | Up to one day | 
| Organ metabolic rate of Oxygen | Oxygen consumption in various organs as measured by Positron Emission Tomography | Up to 3 hours (measured on the day of surgery prior to the surgical procedure) |