Dexmedetomidine and Propofol for Pediatric MRI Sedation

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.

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.