Dexmedetomidine and Propofol for Pediatric MRI Sedation

Headache Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03513757
• Other study ID #: CHW 959242-5
• Status: Completed
• Phase: Phase 4
• Start date: March 4, 2018
• Est. completion date: October 21, 2018

Study information

• Verified date: February 2020
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 21, 2018
• Est. primary completion date: August 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 60 Months

Eligibility

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.

Related Conditions & MeSH terms

• Abdominal Neoplasm
• Abdominal Neoplasms
• Epilepsy
• Headache
• Hydrocephalus
• Neurofibromatoses
• Seizure Disorder
• Seizures
• Spine Deformity
• Tumor

Intervention

Drug:
• propofol
propofol 2 mg/kg at start of procedure; 2 mg/kg for movement, 150-300 mcg/kg/minute propofol infusion if movement persists
• 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
• Glycopyrrolate
4 mcg/kg glycopyrrolate will be administered at the start of sedation in the propofol-dexmedetomidine group
• Lidocaine 1% Injectable Solution
1 mg/kg intravenous administration prior to propofol administration
• Nitrous Oxide
Inhalation of nitrous oxide may be used for IV placement
• Sevoflurane
Inhalation of sevoflurane may be used for IV placement

Locations

Country	Name	City	State
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (9)

Akpinar H, Naziroglu M, Övey IS, Çig 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. Erratum in: Sci Rep. 2018 Jul 04;8:47002. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology. 2004 May;100(5):1138-45. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Total Propofol Administered	total propofol administered (mg/kg)	up to 90 minutes
Secondary	Dexmedetomidine Dose	dexmedetomidine dose (mcg/kg)	up to 90 minutes
Secondary	Glycopyrrolate Dose	glycopyrrolate dose (mcg/kg)	5 minutes
Secondary	Lidocaine Dose	lidocaine dose (mg/kg)	up to 90 minutes
Secondary	Nitrous Oxide	documentation of use	up to 10 minutes
Secondary	Sevoflurane	sevoflurane induction time of 5 minutes	sevoflurane induction time up to 10 minutes
Secondary	Eye Opening	minutes from completion of scan to spontaneous eye opening	up to 90 minutes
Secondary	Oral/Enteral Intake	minutes from completion of scan to oral/enteral intake	up to 2 hours
Secondary	Discharge Ready	minutes from completion of scan to discharge ready	up to 2 hours
Secondary	Sleep Pattern	parental observation of deviation from child's normal habit obtained through follow-up phone call	up to 48 hours
Secondary	Irritability	behavior deemed inappropriate and a deviation from child's normal though parental observation obtained through follow-up phone call	up to 48 hours
Secondary	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.