Cerebral Flow-metabolism Coupling During Adult Surgery

NCT05941494 | Unknown Phase 4

• 1 other identifier: CHEM FACT
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The brain is a highly active organ that requires a large blood flow to function properly. Normally, blood flow is tightly linked to the brain's energy demands. However, during surgery, anesthesia can affect this relationship in different ways. Some types of anesthesia can decrease blood flow to the brain, while others can increase it. Anesthesiologists need to be careful to maintain adequate blood flow to the brain during surgery, especially when blood pressure drops. Drugs may be used to increase blood pressure, but some of these drugs can also affect blood flow to the brain. It is still unclear how to best maintain blood flow to the brain during surgery and how different types of anesthesia and drugs affect this process. The study aims to assess the clinical utility of a new technique that uses light-based neuromonitoring to measure changes in cerebral blood flow and metabolism. The investigators will recruit 80 adult patients undergoing surgery under general anesthesia and randomize them into one of four groups to evaluate the effects of different anesthetic agents and vasopressors on brain hemodynamics and metabolism. The study will include patients over 18 years of age with no history of neurological conditions, substance abuse, or contraindications to cerebral oximetry devices or specific anesthetic agents. The patients will receive standard anesthesia care and be monitored with our light-based neuromonitoring system. This study aims to demonstrate the device's ability to detect changes in cerebral hemodynamic parameters related to anesthesia induction and systemic hypotension. This study will also evaluate the effects of anesthetic maintenance agents and vasopressors on cerebral hemodynamics and neurovascular coupling.

Conditions

Anesthesia

Keywords

Anesthesia Drugs; Vasopressors; Neuromonitoring

Outcome Measures

Primary Outcomes (1)

• Effects of anesthetic maintenance agents and vasopressors on cerebral hemodynamics and metabolism.

  Differences in CMRO2 during surgery between sevoflurane and propofol groups will be analyzed by repeated measures ANOVA. Next, differences in CMRO2 during surgery between the phenylephrine and ephedrine groups will be compared by repeated measures ANOVA. To explore any interaction, we will examine whether the effect of one independent variable depends on the level of the other independent variable by conducting a two-way ANOVA. A two-way ANOVA will allow us to examine the main effects of each independent variable and the interaction effect. The interaction effect can be examined by looking at the F-value and p-value associated with the interaction term in the ANOVA output. If the p-value is significant (i.e., less than the alpha level), then there is evidence of an interaction effect.

  Duration of surgery

Secondary Outcomes (1)

• Effects of anesthetic maintenance agents and vasopressors on cerebral hemodynamics and metabolism during induction

  Anesthesia induction

Study Arms (4)

Propofol-based anesthetic maintenance with phenylephrine used as the vasopressor

EXPERIMENTAL

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).

Drug: Propofol; Drug: Phenylephrine

Propofol-based anesthetic maintenance with ephedrine used as the vasopressor

EXPERIMENTAL

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).

Drug: Propofol; Drug: Ephedrine

Sevoflurane-based anesthetic maintenance with phenylephrine used as the vasopressor

EXPERIMENTAL

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).

Drug: Sevoflurane; Drug: Phenylephrine

Sevoflurane-based anesthetic maintenance with ephedrine used as the vasopressor

EXPERIMENTAL

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).

Drug: Sevoflurane; Drug: Ephedrine

Interventions

Propofol DRUG

Patient will receive propofol as their maintenance agent during surgery. The typical dose is 150-200 mg/kg/min.

Also known as: Propofol for anesthesia maintenance

Propofol-based anesthetic maintenance with ephedrine used as the vasopressor; Propofol-based anesthetic maintenance with phenylephrine used as the vasopressor

Sevoflurane DRUG

Patient's anesthesia will be maintained with 1 MAC of sevoflurane during surgery.

Also known as: Sevoflurane for anesthesia maintenance

Sevoflurane-based anesthetic maintenance with ephedrine used as the vasopressor; Sevoflurane-based anesthetic maintenance with phenylephrine used as the vasopressor

Ephedrine DRUG

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).

Also known as: Ephedrine as a vasopressor

Propofol-based anesthetic maintenance with ephedrine used as the vasopressor; Sevoflurane-based anesthetic maintenance with ephedrine used as the vasopressor

Phenylephrine DRUG

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).

Also known as: Phenylephrine as a vasopressor

Propofol-based anesthetic maintenance with phenylephrine used as the vasopressor; Sevoflurane-based anesthetic maintenance with phenylephrine used as the vasopressor

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients over the age of 18 years old.
• ASA I-IV
• Undergoing surgery under general anesthesia at London Health Sciences Centre or St. Joseph's Healthcare that is scheduled to last longer than 1 hour.

You may not qualify if:

• Had any neurological conditions such as history of stroke, TIA, neurodegenerative disease, or carotid stenosis
• Had a history of substance abuse such as heavy cannabis users
• Have a contraindication of applying the cerebral oximetry device (e.g., skin lesions in the forehead)
• Have contraindications to receive specific anesthetic agents or vasopressors such as malignant hyperthermia or an allergy.
• Unable to communicate with the research staff

Sponsors & Collaborators

• Jason Chui: lead

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

Related Publications (13)

• Murkin JM. Cerebral oximetry: monitoring the brain as the index organ. Anesthesiology. 2011 Jan;114(1):12-3. doi: 10.1097/ALN.0b013e3181fef5d2. No abstract available.

  PMID: 21178667 BACKGROUND

• Jonsson M, Lindstrom D, Wanhainen A, Djavani Gidlund K, Gillgren P. Near Infrared Spectroscopy as a Predictor for Shunt Requirement During Carotid Endarterectomy. Eur J Vasc Endovasc Surg. 2017 Jun;53(6):783-791. doi: 10.1016/j.ejvs.2017.02.033. Epub 2017 Apr 19.

  PMID: 28431821 BACKGROUND

• Khozhenko A, Lamperti M, Terracina S, Bilotta F. Can Cerebral Near-infrared Spectroscopy Predict Cerebral Ischemic Events in Neurosurgical Patients? A Narrative Review of the Literature. J Neurosurg Anesthesiol. 2019 Oct;31(4):378-384. doi: 10.1097/ANA.0000000000000522.

  PMID: 30001276 BACKGROUND

• Khan JM, McInnis CL, Ross-White A, Day AG, Norman PA, Boyd JG. Overview and Diagnostic Accuracy of Near Infrared Spectroscopy in Carotid Endarterectomy: A Systematic Review and Meta-analysis. Eur J Vasc Endovasc Surg. 2021 Nov;62(5):695-704. doi: 10.1016/j.ejvs.2021.08.022. Epub 2021 Oct 6.

  PMID: 34627675 BACKGROUND

• Milej D, Shahid M, Abdalmalak A, Rajaram A, Diop M, St Lawrence K. Characterizing dynamic cerebral vascular reactivity using a hybrid system combining time-resolved near-infrared and diffuse correlation spectroscopy. Biomed Opt Express. 2020 Jul 23;11(8):4571-4585. doi: 10.1364/BOE.392113. eCollection 2020 Aug 1.

  PMID: 32923065 BACKGROUND

• Milej D, He L, Abdalmalak A, Baker WB, Anazodo UC, Diop M, Dolui S, Kavuri VC, Pavlosky W, Wang L, Balu R, Detre JA, Amendolia O, Quattrone F, Kofke WA, Yodh AG, St Lawrence K. Quantification of cerebral blood flow in adults by contrast-enhanced near-infrared spectroscopy: Validation against MRI. J Cereb Blood Flow Metab. 2020 Aug;40(8):1672-1684. doi: 10.1177/0271678X19872564. Epub 2019 Sep 9.

  PMID: 31500522 BACKGROUND

• Abdalmalak A, Milej D, Diop M, Shokouhi M, Naci L, Owen AM, St Lawrence K. Can time-resolved NIRS provide the sensitivity to detect brain activity during motor imagery consistently? Biomed Opt Express. 2017 Mar 13;8(4):2162-2172. doi: 10.1364/BOE.8.002162. eCollection 2017 Apr 1.

  PMID: 28736662 BACKGROUND

• Durduran T, Yodh AG. Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement. Neuroimage. 2014 Jan 15;85 Pt 1(0 1):51-63. doi: 10.1016/j.neuroimage.2013.06.017. Epub 2013 Jun 14.

  PMID: 23770408 BACKGROUND

• Selb J, Boas DA, Chan ST, Evans KC, Buckley EM, Carp SA. Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia. Neurophotonics. 2014 Jul;1(1):015005. doi: 10.1117/1.NPh.1.1.015005.

  PMID: 25453036 BACKGROUND

• Verdecchia K, Diop M, Lee A, Morrison LB, Lee TY, St Lawrence K. Assessment of a multi-layered diffuse correlation spectroscopy method for monitoring cerebral blood flow in adults. Biomed Opt Express. 2016 Aug 24;7(9):3659-3674. doi: 10.1364/BOE.7.003659. eCollection 2016 Sep 1.

  PMID: 27699127 BACKGROUND

• Rajaram A, Milej D, Suwalski M, Kebaya L, Kewin M, Yip L, de Ribaupierre S, Han V, Diop M, Bhattacharya S, St Lawrence K. Assessing cerebral blood flow, oxygenation and cytochrome c oxidase stability in preterm infants during the first 3 days after birth. Sci Rep. 2022 Jan 7;12(1):181. doi: 10.1038/s41598-021-03830-7.

  PMID: 34996949 BACKGROUND

• Rajaram A, Milej D, Suwalski M, Yip LCM, Guo LR, Chu MWA, Chui J, Diop M, Murkin JM, St Lawrence K. Optical monitoring of cerebral perfusion and metabolism in adults during cardiac surgery with cardiopulmonary bypass. Biomed Opt Express. 2020 Sep 29;11(10):5967-5981. doi: 10.1364/BOE.404101. eCollection 2020 Oct 1.

  PMID: 33149999 BACKGROUND

• Kaya K, Zavriyev AI, Orihuela-Espina F, Simon MV, LaMuraglia GM, Pierce ET, Franceschini MA, Sunwoo J. Intraoperative Cerebral Hemodynamic Monitoring during Carotid Endarterectomy via Diffuse Correlation Spectroscopy and Near-Infrared Spectroscopy. Brain Sci. 2022 Aug 2;12(8):1025. doi: 10.3390/brainsci12081025.

  PMID: 36009088 BACKGROUND

MeSH Terms

Interventions

Propofol; Sevoflurane; Ephedrine; Phenylephrine

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Phenethylamines; Ethylamines; Ethanolamines

Study Officials

• Jason Chui, MD

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Chui, MD

CONTACT

5196858500; jason.chui@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcomes assessors will be blinded to the combination of anesthetic maintenance agents (propofol or sevoflurane) and vasopressors (phenylephrine or ephedrine) that were used during surgery.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Anesthesiologist, Associate Professor

Model Details: This is a prospective, 2x2 factorial design, blinded, randomized controlled study. Written informed consent will be obtained from all participants. We will recruit 80 adult patients (age \>18 years old), who are ASA I-III and are scheduled for surgery under general anesthesia. We will randomize these patients into one of the four groups in 1:1:1:1 ratio for one of two choices of anesthetic maintenance agents and vasopressors.

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: July 12, 2023
• Study Start: October 3, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)