Anesthetics Impact on Brain Blood Flow During Surgery

Overseen By Jason Chui, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Jason Chui

Disqualifiers: Neurological conditions, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how different anesthesia and blood pressure medications affect brain blood flow during surgery. Researchers use a new light-based neuromonitoring tool to track changes in the brain's blood flow and energy use. Patients will be divided into groups to assess how various drugs impact brain health during surgery. The trial includes those undergoing surgery lasting over an hour with no history of neurological issues. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping researchers understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the research staff or your doctor.

What is the safety track record for these treatments?

Research has shown that both sevoflurane and propofol, used to help patients sleep during surgery, are generally safe when administered in the right amounts. Sevoflurane is effective and easy to control. It is widely used and considered safe, but it is crucial to avoid excessive doses due to its narrow safe range.

When combined with ephedrine, sevoflurane can be used safely, as ephedrine helps maintain stable blood pressure during surgery. Sevoflurane is also often paired with phenylephrine, which increases blood pressure and blood flow to the brain, although it may reduce cardiac output in some cases.

Propofol is valued for its quick recovery time and fewer side effects, such as nausea and vomiting. When used with phenylephrine, it helps stabilize blood pressure during surgery. Ephedrine, when combined with propofol, aids in maintaining blood pressure, which is crucial for brain function during surgery.

Overall, previous studies have shown that both sevoflurane and propofol, along with their partners ephedrine and phenylephrine, are safe. These medicines are already approved for use in anesthesia, supporting their safety in humans. ^{1 2 3 4 5}

Why are researchers enthusiastic about this trial?

Researchers are excited about this trial because it explores how different anesthetic combinations affect brain blood flow during surgery, a critical factor in ensuring patient safety and optimal outcomes. Unlike standard anesthetic protocols, which may not specifically consider variations in vasopressor use, this trial examines the impact of using either ephedrine or phenylephrine alongside sevoflurane or propofol. By testing these combinations, the trial aims to uncover the most effective regimen for maintaining stable brain blood flow, potentially leading to improved surgical practices. This could offer more personalized anesthesia plans, enhancing patient care and safety during surgery.

What evidence suggests that this trial's treatments could be effective for maintaining brain blood flow during surgery?

This trial will compare different anesthetic and vasopressor combinations to study their impact on brain blood flow during surgery. Research shows that sevoflurane, an anesthetic used in this trial, can alter brain blood flow by widening or narrowing blood vessels. Phenylephrine, a vasopressor option in this trial, raises both blood pressure and brain blood flow. Propofol, another anesthetic under study, typically reduces brain blood flow but maintains a balance in the brain's oxygen and energy use. Ephedrine, another vasopressor being tested, helps keep brain blood flow steady during anesthesia. Each treatment affects brain blood flow and metabolism, which is crucial during surgery to ensure the brain receives enough oxygen and nutrients. ^{6 7 8 9 10}

Who Is on the Research Team?

Jason Chui, MD

Principal Investigator

Western University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need general anesthesia for surgery lasting more than an hour. It's not for those with neurological conditions, substance abuse history, skin issues on the forehead, or allergies to certain anesthesia drugs.

Inclusion Criteria

ASA I-IV

I am scheduled for surgery under general anesthesia lasting over an hour at a specified hospital.

I am over 18 years old.

Exclusion Criteria

I cannot communicate with the research team.

History of substance abuse such as heavy cannabis use

I have a history of stroke, TIA, neurodegenerative disease, or carotid stenosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Anesthesia Induction

Preoperative baseline cerebral hemodynamic and metabolic parameters are measured, followed by anesthesia induction and monitoring of cerebral hemodynamics and metabolism.

Approximately 5-10 minutes

1 visit (in-person)

Surgery and Treatment

Participants undergo surgery with randomized anesthetic maintenance and vasopressor agents. Continuous monitoring of cerebral blood flow and metabolism using trNIRS/DCS.

Duration of surgery

Post-Anesthesia Care

Patients are extubated and transferred to the PACU. Neurological outcomes are collected via routine physical exam.

Immediate post-surgery period

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ephedrine
• Light-based neuromonitoring
• Phenylephrine
• Propofol
• Sevoflurane

Trial Overview The study tests how different anesthetics and blood pressure drugs affect brain blood flow and energy use during surgery. Patients are randomly assigned to receive Propofol, Phenylephrine, Sevoflurane, or Ephedrine while being monitored with a new light-based device.

How Is the Trial Designed?

Group I: Sevoflurane-based anesthetic maintenance with phenylephrine used as the vasopressor Experimental Treatment 2 Interventions

Sevoflurane-based anesthetic maintenance with phenylephrine used as the vasopressor. Patient's anesthesia will be maintained with 1 MAC of sevoflurane during surgery. Patient will receive phenylephrine infusion as the primary vasopressor of choice. The typical dose of phenylephrine infusion is 10-40 mcg/min (dilution 100 mcg/ml).

Group II: Sevoflurane-based anesthetic maintenance with ephedrine used as the vasopressor Experimental Treatment 2 Interventions

Sevoflurane-based anesthetic maintenance with ephedrine used as the vasopressor. Patient's anesthesia will be maintained with 1 MAC of sevoflurane during surgery. The patient will receive ephedrine infusion as the primary vasopressor of choice. The typical dose of ephedrine infusion is 10-50 mg/hr (dilution 2 mg/ml).

Group III: Propofol-based anesthetic maintenance with phenylephrine used as the vasopressor Experimental Treatment 2 Interventions

Propofol-based anesthetic maintenance with phenylephrine used as the vasopressor. Patient will receive propofol as their maintenance agent during surgery. The typical dose is 150-200 mg/kg/min. Patient will receive phenylephrine infusion as the primary vasopressor of choice. The typical dose of phenylephrine infusion is 10-40 mcg/min (dilution 100 mcg/ml).

Group IV: Propofol-based anesthetic maintenance with ephedrine used as the vasopressor Experimental Treatment 2 Interventions

Propofol-based anesthetic maintenance with ephedrine used as the vasopressor. Patient will receive propofol as their maintenance agent during surgery. The typical dose is 150-200 mg/kg/min. The patient will receive ephedrine infusion as the primary vasopressor of choice. The typical dose of ephedrine infusion is 10-50 mg/hr (dilution 2 mg/ml).

Ephedrine is already approved in United States, Canada for the following indications:

Approved in United States as Ephedrine for:

• Hypotension
• Bronchial asthma
• Narcolepsy
• Myasthenia gravis
• Allergic disorders

Approved in Canada as Ephedrine for:

• Nasal decongestant
• Asthma
• Bronchitis

Who Is Running the Clinical Trial?

Jason Chui

Lead Sponsor

Trials

1

Recruited

80+

Published Research Related to This Trial

In a study involving 10 healthy males, phenylephrine significantly reduced oxygenation levels in both the forehead and cerebral regions while increasing blood flow to the internal carotid artery, indicating a complex effect on cerebral oxygenation despite overall stable oxygen levels.

Conversely, ephedrine maintained forehead oxygenation and increased blood flow to extracerebral tissues, while slightly decreasing cerebral oxygenation, suggesting it may be a safer option for preserving oxygen levels in the brain during blood pressure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External carotid artery flow maintains near infrared spectroscopy-determined frontal lobe oxygenation during ephedrine administration. Sørensen, H., Rasmussen, P., Sato, K., et al.[2022]

A study of 56 concentrated powder products in Taiwan revealed that many Chinese herbal formulae containing Herba Ephedrae could exceed World Anti-Doping Agency (WADA) thresholds for Ephedra alkaloids, particularly ephedrine and norpseudoephedrine.

The analysis showed that a significant percentage of these products could lead to violations of WADA regulations, highlighting the need for athletes and medical personnel to be cautious when using herbal remedies alongside other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephedra alkaloid contents of Chinese herbal formulae sold in Taiwan. Chang, CW., Hsu, SY., Huang, GQ., et al.[2018]

In a study involving six healthy Welsh Mountain ponies, ephedrine significantly increased heart rate, arterial blood pressure, cardiac index, and intramuscular blood flow during halothane anesthesia, particularly after a higher dose of 0.2 mg/kg.

While ephedrine improved hemodynamic parameters, one pony experienced an arrhythmia, highlighting a potential safety concern despite the overall positive effects on blood flow and circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of ephedrine on intramuscular blood flow and other cardiopulmonary parameters in halothane-anesthetized ponies. Lee, YL., Clarke, KW., Alibhai, HI., et al.[2019]

In a study of 70 elderly orthopedic patients, immediate infusion of either ephedrine or phenylephrine after spinal anesthesia effectively maintained blood pressure and prevented significant hemodynamic changes compared to a saline control group.

Ephedrine not only maintained blood pressure but also increased cardiac index and heart rate, demonstrating its potential advantages over phenylephrine in managing hemodynamics post-anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of the infusion of ephedrine and phenylephrine on the hemodynamic stability after subarachnoid anesthesia in senior adults - a controlled randomized trial. Žunić, M., Krčevski Škvarč, N., Kamenik, M.[2020]

Ephedrine significantly accelerates psychomotor recovery from anesthesia in rhesus monkeys, reducing recovery time from an average of 80.4 minutes to about 14.8 minutes.

The administration of ephedrine also improved oxygen saturation and systolic blood pressure, while causing a notable decrease in pulse rate shortly after administration, indicating its potential benefits and effects on cardiorespiratory functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephedrine accelerates psychomotor recovery from anesthesia in macaque monkeys. Hess, L., Votava, M., Slíva, J., et al.[2013]

An ephedrine alkaloid-free extract of Ephedra Herb (EFE) demonstrated analgesic, anti-influenza, and anticancer activities similar to the standard extract (EHE) but without the adverse effects associated with ephedrine alkaloids, such as excitation and insomnia.

In a safety evaluation involving healthy volunteers, EFE showed fewer adverse events compared to the standard extract EHE, suggesting that EFE is a safer alternative for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Adverse Effects of Ephedra Herb and the Safety of Ephedrine Alkaloids-free Ephedra Herb Extract (EFE)]. Odaguchi, H., Hyuga, S., Sekine, M., et al.[2020]

In a study of over 103,000 patients undergoing general anesthesia, the use of phenylephrine was linked to a higher risk of postoperative delirium compared to ephedrine, with an adjusted odds ratio of 1.35.

The risk of delirium increased with higher doses of phenylephrine, suggesting a dose-dependent relationship, which indicates that using ephedrine may be a safer option to reduce the incidence of delirium after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative use of phenylephrine versus ephedrine and postoperative delirium: A multicenter retrospective cohort study. Ma, H., Ahrens, E., Wachtendorf, LJ., et al.[2023]

Thiopental and propofol are both favorable anesthetics for brain-injured patients due to their positive effects on cerebral blood flow and metabolism, but neither has been shown to improve outcomes in head injury cases.

Isoflurane is recommended as the best inhalational agent for neuroanesthesia because it has minimal impact on cerebral blood flow and intracranial pressure, while nitrous oxide remains popular despite variable effects, as its impact can be mitigated by other agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrovascular and cerebral metabolic effects of commonly used anaesthetics. Chong, KY., Gelb, AW.[2020]

A new sensitive and validated LC-MS/MS method was developed to detect and quantify multiple phenalkylamines, including ephedrine and cathinone, in plasma, demonstrating high accuracy and precision across a range of concentrations (10 to 1000 ng/ml).

The method effectively distinguished between alkaloids from cold medications and those from herbal sources, showing that ingestion of an Ephedra extract resulted in the detection of multiple ephedrines, highlighting the potential for abuse and the importance of monitoring these substances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection and validated quantification of nine herbal phenalkylamines and methcathinone in human blood plasma by LC-MS/MS with electrospray ionization. Beyer, J., Peters, FT., Kraemer, T., et al.[2019]

The study used HPLC-MS to analyze the pharmacokinetics and tissue distribution of five Ephedra alkaloids in rats, revealing that the compatibility of Ephedrae Herba with Atractylodis Macrocephalae Rhizoma alters their distribution in plasma and tissues.

This compatibility may enhance the therapeutic efficacy of Ephedra alkaloids while simultaneously reducing their toxicity, suggesting a potential for safer and more effective herbal treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacokinetic and Tissue Distribution Study of Ephedrae Herba and Herbal Pair of Ephedrae Herba-Atractylodis Macrocephalae Rhizoma in Rats]. Zhu, ZM., Li, HC., Luo, JB.[2018]

A network meta-analysis of 9 randomized controlled trials involving adult surgical patients found that dopamine and ephedrine are more effective at preserving cerebral oxygen saturation (ScO2) during treatment for intraoperative hypotension compared to norepinephrine and phenylephrine.

The study suggests a rank order for maintaining ScO2, with dopamine and ephedrine being the best options, while phenylephrine was associated with the greatest reduction in ScO2, indicating potential risks in its use during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Regional Cerebral Oxygen Saturation Effect of Inotropes/Vasopressors Administered to Treat Intraoperative Hypotension: A Bayesian Network Meta-analysis. Bombardieri, AM., Singh, NP., Yaeger, L., et al.[2023]

Ephedra, traditionally used for thousands of years, has become controversial in the U.S. due to concerns about its composition, particularly regarding the levels of ephedrine and related alkaloids in dietary supplements.

The review highlights potential health risks associated with Ephedra, especially for sensitive individuals or those abusing it for its stimulant effects, raising important questions about its safety and regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephedra in perspective--a current review. Abourashed, EA., El-Alfy, AT., Khan, IA., et al.[2013]

In a study of 24 anesthetized brain tumor patients, ephedrine was found to significantly improve cerebral blood flow and brain tissue oxygenation compared to phenylephrine, which worsened microcirculation as indicated by increased capillary transit time heterogeneity.

Despite both drugs achieving similar mean arterial pressure, ephedrine demonstrated superior effects on cerebral macro- and microcirculation, suggesting it may be a better choice for maintaining cerebral oxygen levels during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging. Koch, KU., Mikkelsen, IK., Espelund, US., et al.[2022]

In a study of 24 patients undergoing spine surgery, the infusion of ephedrine helped maintain core body temperature during anesthesia, while the control group experienced a significant drop in temperature.

Ephedrine also stabilized hemodynamic variables like blood pressure and heart rate, suggesting it effectively prevents core-to-peripheral heat redistribution during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of ephedrine on intraoperative hypothermia. Jo, YY., Kim, JY., Kim, JS., et al.[2021]

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