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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hypotension
• Intervention / Treatment: Drug: Noradrenalin; Drug: Phenylephrine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Rasmussen; Phone Number: 004529265713; Email: mads.rasmussen@vest.rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Mads Rasmussen, MD, PhD; Phone Number: +4529265713; Email: mads.rasmussen@vest.rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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).
2. Scheduled for elective supratentorial craniotomy.
3. Patients aged between 18 and 75 years.
4. American Society of Anesthesiologists status 1-3

Exclusion Criteria:

1. History of allergy or intolerance to one of the study medications.
2. Active treatment with monoamine oxidase inhibitors.
3. An American Society of Anesthesiologists (ASA)physical status IV-VI.
4. Pregnancy or breastfeeding.
5. Inability to provide written informed consent -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phenylephrine	Drug: Phenylephrine; Infusion of phenylephrine during anesthesia and surgery; Other Names: metaoxedrin
Experimental: Noradrenaline	Drug: Noradrenalin; Infusion of noradrenaline during anesthesia and surgery; Other Names: Noradrenaline

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Mads Rasmussen, MD, PhD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: IMPACT study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: THe trial data may be shared upon request to the Investigator
• IPD Sharing Time Frame: Other researchers may request the data after publication of the primary results and for a period of 10 years
• IPD Sharing Access Criteria: No specific criteria
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No