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

Study Overview
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Brief Summary
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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.

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

Conditions
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Behavior, Cognitive Change

Intervention / Treatment
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* Drug: Propofol
* Drug: Sevoflurane
* Drug: Ametop
* Drug: Ondansetron


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhalational Technique<br>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<br>* The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)<br>Drug: Ametop<br>* Each patient will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction.<br>Drug: Ondansetron<br>* Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.<br>|
| Experimental: Total Intravenous Anesthetic Technique<br>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<br>* The child will be randomized via a block design to receive either a volatile anesthetic (induction: sevoflurane), or total intravenous anesthetic technique (induction: propofol)<br>Drug: Ametop<br>* Each patient will receive Ametop local anesthetic to the dorsum of both hands 30-45 minutes prior to induction.<br>Drug: Ondansetron<br>* Each patient will receive the antiemetic ondansetron 0.1mg/kg IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |