Clinical trial NCT03513757: Dexmedetomidine and Propofol for Pediatric MRI Sedation
Official title: An Observer-blinded Randomized Study of Propofol Infusion vs Bolus Dexmedetomidine and Propofol Sedation for Pediatric Magnetic Resonance Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Headache
Tumor
Seizure Disorder
Neurofibromatoses
Hydrocephalus
Abdominal Neoplasm
Spine Deformity
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2018-05-02
Enrollment: 40
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: observer blinded comparison of propofol with low-dose propofol and dexmedetomidine for pediatric MRI sedation
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficiency of Propofol Dexmedetomidine Sedation Compared With Propofol Infusion
timeFrame: through study completion, an average of 2 hours
Secondary outcomes:
measure: Total Propofol Administered
timeFrame: up to 90 minutes
measure: Dexmedetomidine Dose
timeFrame: up to 90 minutes
measure: Glycopyrrolate Dose
timeFrame: 5 minutes
measure: Lidocaine Dose
timeFrame: up to 90 minutes
measure: Nitrous Oxide
timeFrame: up to 10 minutes
measure: Sevoflurane
timeFrame: sevoflurane induction time up to 10 minutes
measure: Eye Opening
timeFrame: up to 90 minutes
measure: Oral/Enteral Intake
timeFrame: up to 2 hours
measure: Discharge Ready
timeFrame: up to 2 hours
measure: Sleep Pattern
timeFrame: up to 48 hours
measure: Irritability
timeFrame: up to 48 hours
measure: Delirium
timeFrame: up to 24 hours.
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Hospital and Health System Foundation, Wisconsin
name: Susan P Taylor, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andropoulos DB, Greene MF. Anesthesia and Developing Brains - Implications of the FDA Warning. N Engl J Med. 2017 Mar 9;376(10):905-907. doi: 10.1056/NEJMp1700196. Epub 2017 Feb 8. No abstract available.
citation: Vespasiano M, Finkelstein M, Kurachek S. Propofol sedation: intensivists' experience with 7304 cases in a children's hospital. Pediatrics. 2007 Dec;120(6):e1411-7. doi: 10.1542/peds.2007-0145.
citation: Emrath ET, Stockwell JA, McCracken CE, Simon HK, Kamat PP. Provision of deep procedural sedation by a pediatric sedation team at a freestanding imaging center. Pediatr Radiol. 2014 Aug;44(8):1020-5. doi: 10.1007/s00247-014-2942-z. Epub 2014 May 24.
citation: Mallory MD, Baxter AL, Kost SI; Pediatric Sedation Research Consortium. Propofol vs pentobarbital for sedation of children undergoing magnetic resonance imaging: results from the Pediatric Sedation Research Consortium. Paediatr Anaesth. 2009 Jun;19(6):601-11. doi: 10.1111/j.1460-9592.2009.03023.x.
citation: Mason KP, Zurakowski D, Zgleszewski SE, Robson CD, Carrier M, Hickey PR, Dinardo JA. High dose dexmedetomidine as the sole sedative for pediatric MRI. Paediatr Anaesth. 2008 May;18(5):403-11. doi: 10.1111/j.1460-9592.2008.02468.x. Epub 2008 Mar 18.
citation: Siddappa R, Riggins J, Kariyanna S, Calkins P, Rotta AT. High-dose dexmedetomidine sedation for pediatric MRI. Paediatr Anaesth. 2011 Feb;21(2):153-8. doi: 10.1111/j.1460-9592.2010.03502.x.
citation: Akpinar H, Naziroglu M, Ovey IS, Cig B, Akpinar O. The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels. Sci Rep. 2016 Nov 22;6:37196. doi: 10.1038/srep37196.
citation: Boriosi JP, Eickhoff JC, Klein KB, Hollman GA. A retrospective comparison of propofol alone to propofol in combination with dexmedetomidine for pediatric 3T MRI sedation. Paediatr Anaesth. 2017 Jan;27(1):52-59. doi: 10.1111/pan.13041. Epub 2016 Oct 25.
citation: Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology. 2004 May;100(5):1138-45. doi: 10.1097/00000542-200405000-00015.