Dexmedetomidine and Propofol for Pediatric MRI Sedation

NCT ID: NCT03513757

Last Updated: 2020-02-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-04

Study Completion Date

2018-10-21

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.

Conditions

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Headache Tumor Seizure Disorder Neurofibromatoses Hydrocephalus Abdominal Neoplasm Spine Deformity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

observer blinded comparison of propofol with low-dose propofol and dexmedetomidine for pediatric MRI sedation
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
The patients and their parents/guardians as well as the blinded observer or investigator who participates in outcomes assessment will be blinded to the drug or drugs administered.

Study Groups

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propofol

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.

Group Type ACTIVE_COMPARATOR

propofol

Intervention Type DRUG

propofol 2 mg/kg at start of procedure; 2 mg/kg for movement, 150-300 mcg/kg/minute propofol infusion if movement persists

Lidocaine 1% Injectable Solution

Intervention Type DRUG

1 mg/kg intravenous administration prior to propofol administration

Nitrous Oxide

Intervention Type DRUG

Inhalation of nitrous oxide may be used for IV placement

Sevoflurane

Intervention Type DRUG

Inhalation of sevoflurane may be used for IV placement

propofol dexmedetomidine

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.

Group Type EXPERIMENTAL

propofol

Intervention Type DRUG

propofol 2 mg/kg at start of procedure; 2 mg/kg for movement, 150-300 mcg/kg/minute propofol infusion if movement persists

Dexmedetomidine

Intervention Type DRUG

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

Glycopyrrolate

Intervention Type DRUG

4 mcg/kg glycopyrrolate will be administered at the start of sedation in the propofol-dexmedetomidine group

Lidocaine 1% Injectable Solution

Intervention Type DRUG

1 mg/kg intravenous administration prior to propofol administration

Nitrous Oxide

Intervention Type DRUG

Inhalation of nitrous oxide may be used for IV placement

Sevoflurane

Intervention Type DRUG

Inhalation of sevoflurane may be used for IV placement

Interventions

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propofol

propofol 2 mg/kg at start of procedure; 2 mg/kg for movement, 150-300 mcg/kg/minute propofol infusion if movement persists

Intervention Type DRUG

Dexmedetomidine

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

Intervention Type DRUG

Glycopyrrolate

4 mcg/kg glycopyrrolate will be administered at the start of sedation in the propofol-dexmedetomidine group

Intervention Type DRUG

Lidocaine 1% Injectable Solution

1 mg/kg intravenous administration prior to propofol administration

Intervention Type DRUG

Nitrous Oxide

Inhalation of nitrous oxide may be used for IV placement

Intervention Type DRUG

Sevoflurane

Inhalation of sevoflurane may be used for IV placement

Intervention Type DRUG

Other Intervention Names

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diprivan precedex Robinul Xylocaine 1% Ultane

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.
Minimum Eligible Age

12 Months

Maximum Eligible Age

60 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical College of Wisconsin

OTHER

Sponsor Role lead

Responsible Party

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Susan Taylor

Associate Professor, Department of Pediatric Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Susan P Taylor, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital and Health System Foundation, Wisconsin

Locations

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Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 28177852 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18055659 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24859263 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19645979 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18363626 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21210884 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27872485 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27779360 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15114210 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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CHW 959242-5

Identifier Type: -

Identifier Source: org_study_id

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