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

Cognitive Change Clinical Trial

Official title:

Neurobiological, Cognitive-affective and Behavioral Changes Following Exposure to Either Sevoflurane- or Propofol-based Anesthesia in Children Undergoing MRI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03022240
• Other study ID #: REB16-0104
• Status: Completed
• Phase: Phase 3
• Start date: January 2017
• Est. completion date: September 2019

Study information

• Verified date: April 2019
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 5 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Behavior
• Cognitive Change

Intervention

Drug:
• Propofol
The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)
• Sevoflurane
The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)
• Ametop
Each patient will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction.
• Ondansetron
Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)	The BRIEF-P is the first standardized rating scale designed to specifically measure executive function in preschool-aged children (ages 2-5).	Change from baseline within 1 week after randomization
Other	The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)	The BRIEF-P is the first standardized rating scale designed to specifically measure executive function in preschool-aged children (ages 2-5).	Change from baseline within 2-3 weeks after randomization
Other	The Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P)	The BRIEF-P is the first standardized rating scale designed to specifically measure executive function in preschool-aged children (ages 2-5).	Change from baseline within 12-13 weeks after randomization
Other	The Post Hospital Behavior Questionnaire (PHBQ)	The PHBQ asks parents to rate their child's behavior on 27 items concerning sleep, eating, internalizing and externalizing behaviors. For each item parents must compare their child's current behavior with their behavior one week prior to hospitalization.	Within 1 week after randomization
Other	The Post Hospital Behavior Questionnaire (PHBQ)	The PHBQ asks parents to rate their child's behavior on 27 items concerning sleep, eating, internalizing and externalizing behaviors. For each item parents must compare their child's current behavior with their behavior one week prior to hospitalization.	Within 2-3 weeks after randomization
Other	The Modified Yale Preoperative Anxiety Scale (mYPAS)	The mYPAS is the current "gold standard" for assessing anxiety during induction of anesthesia for children ages 2-16 years.	On the day of randomization, obtained just prior to the intervention
Other	Pediatric Anesthesia Emergence Delirium (PAED) Scale	Validated tool to measure emergence delirium in children.	On the day or randomization, obtained immediately after the intervention
Other	Nuclear Magnetic Resonance Spectroscopy (NMRS)	Glucose, lactate, choline and NAA values will be obtained from the parietal cortex	On the day of randomization, obtained during the intervention
Other	Resting State Functional Magnetic Resonance Imaging (rfMRI)	Resting functional brain networks will be identified and compared between groups	On the day of randomization, obtained during the intervention
Other	Inflammatory Markers	Concentrations of plasma IL-1b, TNF-a, IL-6, IL-10 will be quantified	On the day of randomization, change from baseline, obtained immediately after the intervention
Other	Blood metabolites	Concentrations of plasma proteins, peptides and metabolites will be quantified	On the day of randomization, change from baseline, obtained immediately after the intervention
Primary	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	The Child Behavior Checklist (CBCL) 1.5 to 5 years	The CBCL is widely used for identifying problem behaviors in children ages 1.5 to 5 years	Change from baseline at 12-13 weeks after randomization