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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.
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 32* 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(including myocardium, kidney, liver, spinal cord, organs supplied by the splanchnic circulation, muscle tissue and other 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 and 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.An MRI examination is performed 24 hours after surgery to detect any ischemic lesions possibly associated with the vasopressor infusion.
* The initial sample size of 40 patients was reduced to 32 patients in april 2024 (after inclusion of 4 patients). The change in sample size is due to unexpected limited scanner availability and unexpected difficuties with patient recruitment. These factors will be associated with a longer period of patient inclusion and consequently longer time before study completion which we find unacceptable.
** In a substudy including approximately half of the patients, we plan to describe the physiology of the circulatory system during the transition from wakefulness to general anesthesia. Specifically, we will present the absolute and relative changes in blood flow to the brain and selected non-cerebral organs. The analysis will also assess the redistribution of cardiac output during this transition.
This substudy is intended solely to describe physiological changes occurring during the transition from wakefulness to anesthesia. Only data obtained prior to the randomized part of the protocol will be used, and the substudy is independent of the randomized analyses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Noradrenaline | Experimental | Noradrenaline |
|
| Phenylephrine | Active Comparator | Phenylephrine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Noradrenalin | Drug | Infusion of noradrenaline during anesthesia and surgery |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rasmussen | Contact | 004529265713 | mads.rasmussen@vest.rm.dk |
| Name | Affiliation | Role |
|---|---|---|
| Mads Rasmussen, MD, PhD | Aarhus University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Recruiting | Aarhus | 8200 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40132839 | Derived | Faisal Mohamad N, Koch KU, Aanerud J, Meier K, Mikkelsen IK, Espelund US, Eriksen CF, Juul N, Alstrup KB, Jespersen B, Fries LM, Tankisi A, Dyrskog S, Cortnum SOS, Sindby AK, Borghammer P, Tolbod LP, Meng L, Korshoej AR, Rasmussen M. Impact of norepinephrine versus phenylephrine on brain circulation, organ blood flow and tissue oxygenation in anaesthetised patients with brain tumours: study protocol for a randomised controlled trial. BMJ Open. 2025 Mar 25;15(3):e095172. doi: 10.1136/bmjopen-2024-095172. |
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THe trial data may be shared upon request to the Investigator
Other researchers may request the data after publication of the primary results and for a period of 10 years
No specific criteria
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| ID | Term |
|---|---|
| D007022 | Hypotension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D009638 | Norepinephrine |
| D010656 | Phenylephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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Randomized, double blinded, clinical trial
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| Phenylephrine | Drug | Infusion of phenylephrine during anesthesia and surgery |
|
|
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) |
| D000588 |
| Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |