Neurobiological and Cognitive Changes Following Exposure to Either Sevoflurane- or Propofol-based Anesthesia in Children

NCT03022240 | Completed Phase 3 DMC

• 1 other identifier: REB16-0104
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The demand for magnetic resonance imaging (MRI) in pediatric patients is increasing due to its use in medical diagnosis and surveillance. Pediatric patients often require general anesthesia (GA) for MRI due to the need for prolonged immobility during the scanning process to obtain high quality images. Two widely used anesthetic techniques for pediatric MRIs are volatile-based anesthesia using sevoflurane and total intravenous anesthesia (TIVA) using propofol. Concerns have been raised regarding the potential neurotoxic effects of anesthetics on the developing brain. Within the animal literature, there is emerging evidence to suggest that both sevoflurane and propofol may cause inflammation, impacting brain cell survival and connections, thereby contributing to possible cognitive dysfunction. However, given the challenges in extrapolating the animal data to humans, and the relatively limited human cohort studies examining the long-term effects of anesthesia exposure, there is inadequate information available to make informed clinical decisions regarding the choice of optimal anesthetic agents for MRI in children. Therefore, this study will uniquely examine the mechanisms of two widely used anesthetics and their short and long-term impact on developmental outcomes in healthy children.

Conditions

Cognitive Change; Behavior

Outcome Measures

Primary Outcomes (1)

• Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV)

  The WPPSI - IV is designed for children aged 2.5 to 7.5 years, and is used to assess general intelligence.

  12-15 weeks from date of randomization

Secondary Outcomes (1)

• The Child Behavior Checklist (CBCL) 1.5 to 5 years

  Change from baseline at 12-13 weeks after randomization

Other Outcomes (11)

• The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)

  Change from baseline within 1 week after randomization

• The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)

  Change from baseline within 2-3 weeks after randomization

• The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)

  Change from baseline within 12-13 weeks after randomization

Study Arms (2)

Inhalational Technique

EXPERIMENTAL

All patients will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction. After inhalation induction of anesthesia with sevoflurane (in 100% O2), an IV will be obtained. Anesthesia will be maintained with sevoflurane (in a mixture of air:oxygen) with a minimum alveolar concentration of 1.0-1.3, titrated to effect. No long acting opioids or nitrous oxide will be used. Airway management will be at the discretion of the anesthesiologist. Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.

Drug: Sevoflurane; Drug: Ametop; Drug: Ondansetron

Total Intravenous Anesthetic Technique

EXPERIMENTAL

All patients will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to IV insertion. Once an IV is established, patients will receive an IV bolus of propofol (2-6mg/kg). Anesthesia will be maintained with a propofol infusion starting at 250 mcg/kg/min and titrated to effect. Airway management will be at the discretion of the anesthesiologist. Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.

Drug: Propofol; Drug: Ametop; Drug: Ondansetron

Interventions

Propofol DRUG

The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)

Total Intravenous Anesthetic Technique

Sevoflurane DRUG

The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)

Inhalational Technique

Ametop DRUG

Each patient will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction.

Inhalational Technique; Total Intravenous Anesthetic Technique

Ondansetron DRUG

Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.

Inhalational Technique; Total Intravenous Anesthetic Technique

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Those between the ages 2 to 5 years who require general anesthesia for MRI Brain and have an American Society of Anesthesiologists' physical status of I to II

You may not qualify if:

• Emergency cases
• Intubated prior to MRI
• Allergies/contraindication to anesthetics
• Requirement of a painful procedure with MRI
• Significant developmental delay
• Autism or suspected autism
• History of extreme prematurity \<28 wks gestational age
• Sedation or general anesthesia in the last 14 days
• Receiving chemotherapy or radiation

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

MeSH Terms

Conditions

Behavior

Interventions

Propofol; Sevoflurane; Tetracaine; Ondansetron

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Tiffany Rice, PhD, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: January 16, 2017
• Study Start: January 1, 2017
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: March 26, 2020

Record last verified: 2019-04

Locations

CA (1)