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

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.

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 -