Dexmedetomidine and Propofol for Pediatric MRI Sedation

Study Overview
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Brief Summary
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The purpose of this study is to compare the results of combining two anesthetic medications (dexmedetomidine and propofol) in low doses with a standard dose of a single drug that is commonly used to provide sedation/anesthesia for MRI studies in young children (propofol). The drugs used for the MRI scan in this study will be chosen randomly. Half the patients will receive small doses of propofol and dexmedetomidine. The other half will receive propofol administered constantly throughout the scan. Other drugs that may be used include sevoflurane and nitrous oxide at the start of the sedation (for placing an intravenous), lidocaine (to reduce the pain of propofol injection) and glycopyrrolate (to prevent the heart rate from decreasing too low. The investigators will record 5 additional blood pressures and heart rates. If additional medications are required to complete the scan, the investigators will administer whatever is necessary. At the end of the study, the investigators will have an observer record the time it takes for participants to spontaneously open eyes , to be able to drink liquids and/or eat and to behave as before the study. Also, it is very important that the investigators find out from participants about changes in behavior, or if eating or sleeping habits were unusual following completion of the study. For that reason, the investigators will call participants in a day or so following the MRI scan. The investigators expect to recruit 40 children between the ages of 12 and 72 months for the study and hope to have the study completed in December 2018.

Detailed Description
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The purpose of this study is to compare the results of combining two anesthetic medications (dexmedetomidine and propofol) in low doses with a standard dose of a single drug that is commonly used to provide sedation/anesthesia for MRI studies in young children (propofol). Recent studies and the FDA have raised concerns that anesthesia for longer than three hours may have effects on behavior and learning. Although investigators do not know if these effects are caused by drugs or the medical condition a child is being treated for, in December 2016, the FDA published the information below regarding anesthesia for children: General anesthetic and sedation drugs are used to put people into a deep sleep so they do not feel pain during surgery or procedures. These drugs are usually injected into a vein or breathed in through a mask. General anesthetic and sedation drugs are widely used to ensure the health, safety, and comfort of children and adults undergoing surgery or other procedures. Recent studies in children suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning. More research is still needed to fully understand how anesthetics might affect brain development, especially longer or repeated exposures and in more vulnerable children. Anesthetic and sedation drugs are necessary for infants, children, and pregnant women who require surgery or other painful and stressful procedures. https://www.fda.gov/Drugs/DrugSafety/ucm532356.htm Research in neonatal and infant animals has demonstrated that sedative and anesthetic agents, like propofol, produce adverse effects on brain development, including loss of brain cells resulting in long-term, possibly permanent changes in learning and behavior. These adverse effects appear to occur mostly after prolonged periods of sedation or anesthesia (generally greater than 3 hours) and when brain development is occurring at a rapid rate (which roughly occurs in children under 3 years of age). It is not known if similar adverse effects occur in humans. Study participants should be advised that the drugs used to accomplish the procedure may have the potential to increase the loss of nerve cells in the developing brain of young child and that the clinical significance of any such changes is not known. There are some animal studies that suggests dexmedetomidine may be better for a growing infant's brain. However, the effects of dexmedetomidine alone or in combination with propofol on the developing brain have not been thoroughly tested to date. The drugs used for the MRI scan in this study will be chosen randomly. Half the patients will receive small doses of propofol and dexmedetomidine. The other half will receive propofol administered constantly throughout the scan. Other drugs that may be used include sevoflurane and nitrous oxide at the start of the sedation (for placing an intravenous), lidocaine (to reduce the pain of propofol injection) and glycopyrrolate (to prevent the heart rate from decreasing too low. Investigators will record 5 additional blood pressures and heart rates. If additional medications are required to complete the scan, investigators will administer whatever is necessary. At the end of the study, an observer will record the time it takes for spontaneous eye opening, to be able to drink liquids and/or eat and to behave as before the study. Also, it is very important that investigators learn in the following day or two how the participant behaved at home; whether eating, behavior and sleeping were unusual. For that reason, the investigator will call the participant a day or so following the MRI scan. The investigators expect to recruit 70 children between the ages of 12 and 72 months for the study and hope to have the study completed in 2018.

Official Title
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An Observer-blinded Randomized Study of Propofol Infusion vs Bolus Dexmedetomidine and Propofol Sedation for Pediatric Magnetic Resonance Imaging

Conditions
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Headache, Tumor, Seizure Disorder, Neurofibromatoses, Hydrocephalus, Abdominal Neoplasm, Spine Deformity

Intervention / Treatment
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* Drug: propofol
* Drug: Dexmedetomidine
* Drug: Glycopyrrolate
* Drug: Lidocaine 1% Injectable Solution
* Drug: Nitrous Oxide
* Drug: Sevoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All children scheduled for outpatient MRI scans with expected duration of scan between 30 minutes and 75 minutes. Exclusion Criteria: Inpatient status, airway abnormalities, allergy to any study medications, eggs and soy, and mitochondrial disorders. All subjects with any cardiac disease or history of cardiac arrhythmias will be excluded.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 60 Months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: observer blinded comparison of propofol with low-dose propofol and dexmedetomidine for pediatric MRI sedation
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: propofol<br>Each patient will receive 1 mg/kg lidocaine followed by 2 mg/kg propofol IV once prior to continuous propofol infusion for MRI sedation at 200 mcg/kg/min. Dose will be increased by 50 mcg/kg/min up to 300 mcg/kg/min for movement and decreased to 150 mcg/kg/min if no movement after 30 minutes. Additional 1 mg/kg propofol bolus administered at time of each movement. Study to be terminated if movement persists despite above interventions. | Drug: propofol<br>* propofol 2 mg/kg at start of procedure; 2 mg/kg for movement, 150-300 mcg/kg/minute propofol infusion if movement persists<br>* Other names: diprivan;Drug: Lidocaine 1% Injectable Solution<br>* 1 mg/kg intravenous administration prior to propofol administration<br>* Other names: Xylocaine 1%;Drug: Nitrous Oxide<br>* Inhalation of nitrous oxide may be used for IV placement<br>Drug: Sevoflurane<br>* Inhalation of sevoflurane may be used for IV placement<br>* Other names: Ultane;|
| Experimental: propofol dexmedetomidine<br>Each patient will receive: 1 mg/kg lidocaine, 2 mg/kg propofol, 4 mcg/kg glycopyrrolate and single dose dexmedetomidine administered prior to scan. Dexmedetomidine dose is dependent on expected duration of scan and will be equal to 1 mcg/kg/hour x duration of scan in hours. 1 mg/kg propofol will be administered for movement up to 2 times. For continued movement after that, begin propofol infusion at 150 mcg/kg/min. Study to be terminated if movement persists despite above interventions. | Drug: propofol<br>* propofol 2 mg/kg at start of procedure; 2 mg/kg for movement, 150-300 mcg/kg/minute propofol infusion if movement persists<br>* Other names: diprivan;Drug: Dexmedetomidine<br>* single dose dexmedetomidine administered at start of sedation in the propofol-dexmedetomidine group. Dosing is based upon anticipated duration of scan from 30 - 75 minutes and will range from 0.5 mic/kg to 1.25 mcg/kg<br>* Other names: precedex;Drug: Glycopyrrolate<br>* 4 mcg/kg glycopyrrolate will be administered at the start of sedation in the propofol-dexmedetomidine group<br>* Other names: Robinul;Drug: Lidocaine 1% Injectable Solution<br>* 1 mg/kg intravenous administration prior to propofol administration<br>* Other names: Xylocaine 1%;Drug: Nitrous Oxide<br>* Inhalation of nitrous oxide may be used for IV placement<br>Drug: Sevoflurane<br>* Inhalation of sevoflurane may be used for IV placement<br>* Other names: Ultane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency of Propofol Dexmedetomidine Sedation Compared With Propofol Infusion | Time (minutes) from anesthesia start to readiness for discharge from the department to home or clinic. | through study completion, an average of 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Propofol Administered | total propofol administered (mg/kg) | up to 90 minutes | 
| Dexmedetomidine Dose | dexmedetomidine dose (mcg/kg) | up to 90 minutes | 
| Glycopyrrolate Dose | glycopyrrolate dose (mcg/kg) | 5 minutes | 
| Lidocaine Dose | lidocaine dose (mg/kg) | up to 90 minutes | 
| Nitrous Oxide | documentation of use | up to 10 minutes | 
| Sevoflurane | sevoflurane induction time of 5 minutes | sevoflurane induction time up to 10 minutes | 
| Eye Opening | minutes from completion of scan to spontaneous eye opening | up to 90 minutes | 
| Oral/Enteral Intake | minutes from completion of scan to oral/enteral intake | up to 2 hours | 
| Discharge Ready | minutes from completion of scan to discharge ready | up to 2 hours | 
| Sleep Pattern | parental observation of deviation from child's normal habit obtained through follow-up phone call | up to 48 hours | 
| Irritability | behavior deemed inappropriate and a deviation from child's normal though parental observation obtained through follow-up phone call | up to 48 hours | 
| Delirium | Pediatric Anesthesia Emergence Delirium (PAED) score greater than 12 as defined by Sikich and Lerman. 0 = no delirium, 20 = worst possible delirium; 5 categories scored from 0-4 additive for a maximum score of 20. Categories 1-3 are scored the same and categories ar scored inversely as described. 1. Child makes contact with caregiver, 2. child's actions are purposeful, 3. child is aware of his surroundings. For each of these category, score 0 for extremely, 1 for very much, 2 for quite a bit, 3 for just a little, 4 for not at all. The other 2 categories 4. Child is restless and 5 Child is inconsolable are scored as 0 for not at all, 1 for just a little, 2 for quite a bit, 3 for very much, 4 for extremely | up to 24 hours. |