A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging

This is a pilot study to determine if a standard bolus dose and infusion of dexmedetomidine can significantly decrease the dose of propofol (infusion) required for accomplishing an MRI. The investigators studied three arms to examine the effectiveness of dexmedetomidine. Arm 1 was a single bolus of 1.0 mcg/kg with 1.0 mcg/kg/hr infusion followed by propofol infusion. Arm 2 was a bolus of 1.0 mcg/kg with 0.5 mcg/kg/hr infusion followed by propofol infusion. Arm 3 was only a single bolus of 1.0 mcg/kg with no infusion followed by propofol infusion.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Cerebral Palsy; Developmental Delay
• Intervention / Treatment: Drug: Dexmedetomidine bolus only - Propofol; Drug: Dexmedetomidine bolus and high infusion-Propofol; Drug: Dexmedetomidine bolus and low infusion-Propofol

Detailed Description

A recent publication in the New England Journal of Medicine highlighted the accumulating evidence for neurotoxic effects of anesthetics in animal models and a collection of epidemiologic studies in humans. Recent studies of anesthesia in fetal and neonatal primates are yielding more evidence of neurotoxicity associated with many common anesthesia and sedation techniques (e.g. propofol, etomidate, sevoflurane, desflurane and isoflurane). On the other hand, the data suggests that some alternative sedative agents, such as Dexmedetomidine, may not have the same neurotoxic effect.

Children routinely undergo sedation for MRI scanning with large doses of propofol and other sedatives. Many of these scans occur at young ages when these children may be at risk of neurological injury from sedative exposure. In addition, these scans do not involve any stimulation - which could be protective against neurodegeneration.

The investigators propose a pilot study to determine if a standard bolus dose and infusion of dexmedetomidine can significantly decrease the dose of propofol (infusion) required for accomplishing an MRI. Based on previous work with the combination of propofol with dexmedetomidine for other procedures, the investigators propose a standard dose of dexmedetomidine (1 mcg/kg bolus followed by an infusion at 1.0 mcg/kg/hour, 0.5 mcg/kg/hour, or no infusion). The investigators will augment this sedation with propofol 2-3 mg/kg titrated bolus followed by 100 mcg/kg/min infusion which can also be titrated up or down to a maximum of 300 mcg/kg/min to keep the blood pressure and heart rate within 30% of baseline levels).

The investigators hypothesize that the use of low dose propofol with dexmedetomidine will be effective undergoing MRI while sparing exposure to the high dose of the sedative.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 8 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects presenting as out-patients, scheduled to receive an anesthetic for MRI of body (spine, chest, abdomen, and/or pelvis) and/or extremity (arm and/or leg).
2. The subject must be a candidate for the sedation technique described in this study with a natural airway (see exclusion criteria described below). This decision will be made by a staff member of the Department of Anesthesiology.
3. The subjects must be 1 and 12 years.
4. The subject's legally authorized representative has given written informed consent to participate in the study.
5. American Society of Anesthesiologist status I, II, or III

Exclusion Criteria:

1. The subject is residing in the Pediatric Intensive Care Unit, the Cardiac Intensive Care Unit, or Neonatal Intensive Care Unit.
2. Diagnosis of a difficult airway or severe obstructive sleep apnea that is not compatible with spontaneous ventilation in a supine position.
3. Congenital heart disease or history of dysrhythmia.
4. Patient taking digoxin or beta-blocker
5. Anxiolytic medication is ordered before the MRI (e.g., midazolam or ketamine).
6. The subject has a history or a family (parent or sibling) history of malignant hyperthermia.
7. The subject is allergic to or has a contraindication to propofol or dexmedetomidine.
8. The subject has previously been treated under this protocol.
9. The subject has a tracheostomy or other mechanical airway device.
10. The subject has received within the past 12 hours an oral or intravenous alpha-adrenergic, beta-adrenergic agonist, or antagonist drugs (e.g., clonidine, propranolol, albuterol).
11. The subject is not scheduled to receive anesthesia-sedation care for the MRI.
12. The subject received one of the anesthetic regimens for the same MRI during the past six months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Dexmedetomidine (bolus only)-Propofol arm; Patients in this cohort will receive dexmedetomidine 1mcg/kg over 5 minutes and then propofol 2-3mg/kg titrated bolus followed by 100mcg/kg/min infusion to accomplish MRI	Drug: Dexmedetomidine bolus only - Propofol; First, the investigators will begin by administering dexmedetomidine 1mcg/kg over 5 minutes. When this is completed, they will administer propofol 2-3mg/kg titrated bolus followed by 100mcg/kg/min infusion which can also be titrated up or down to a maximum of 300mcg/kg/min to keep the blood pressure and heart rate within 30% of baseline levels.; Other Names: Dexmedetomidine-Propofol
Other: Dexmedetomidine (bolus and high infusion)-Propofol arm; Patients in this cohort will receive a combination of Dexmedetomidine 1mcg/kg bolus, Dexmedetomidine 1 mcg/kg/hour infusion, and Propofol 100mcg/kg/minute to accomplish an MRI examination.	Drug: Dexmedetomidine bolus and high infusion-Propofol; First, the investigators will administer dexmedetomidine 1mcg/kg over 5 minutes. Next, the investigators will begin an infusion at 1mcg/kg/hour. At the 5 minute point, propofol will be given (2-3mg/kg bolus followed by 100mcg/kg/min infusion). The attending clinician will determine whether or not the child is in an adequate state to begin the MRI scan. If the sedative effect of the dexmedetomidine-propofol does not produce a sufficiently sedated state within 10 minutes, a repeat bolus of propofol 2mg/kg will be administered. The dose of Dexmedetomidine will not be changed. The dose will be repeated if the child is not adequately sedated in 2 more minutes. At this time infusion rate of propofol will be increased to 200 mcg/kg/minute. If the child is not sedated in 5 more minutes, the outcome will be recorded as a technique failure and sedation will continue at the discretion of the anesthesiologist.; Other Names: Dexmedetomidine-Propofol
Other: Dexmedetomidine (bolus and low infusion)-Propofol arm; Patients in this cohort will receive a combination of Dexmedetomidine 1mcg/kg bolus, Dexmedetomidine 0.5 mcg/kg/hour infusion, and Propofol 100mcg/kg/minute to accomplish an MRI examination.	Drug: Dexmedetomidine bolus and low infusion-Propofol; First, the investigators will administer dexmedetomidine 1mcg/kg over 5 minutes. Next, the investigators will begin an infusion at 0.5mcg/kg/hour. At the 5 minute point, propofol will be given (2-3mg/kg bolus followed by 100mcg/kg/min infusion). The attending clinician will determine whether or not the child is in an adequate state to begin the MRI scan. If the sedative effect of the dexmedetomidine-propofol does not produce a sufficiently sedated state within 10 minutes, a repeat bolus of propofol 2mg/kg will be administered. The dose of Dexmedetomidine will not be changed. The dose will be repeated if the child is not adequately sedated in 2 more minutes. At this time infusion rate of propofol will be increased to 200 mcg/kg/minute. If the child is not sedated in 5 more minutes, the outcome will be recorded as a technique failure and sedation will continue at the discretion of the anesthesiologist.; Other Names: Dexmedetomidine-Propofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Patient Movement and MRI Interruption	If patient moved during their MRI and caused an interruption of the scan.	During the MRI scan, until completion, approximately one hour.
Incidence of Adverse Events	arterial desaturation, airway obstruction, hypotension and bradycardia	From the time the medication is initiated just (5 minutes) prior to the MRI scan and during the MRI scan and immediately during recovery - approximately one hour and twenty minutes in total.
Case Times	Number of minutes from the start of sedation medication administration to the time the patient is adequately sedated for the MRI scan,	Timeframe immediately before the MRI scan while sedation medication is administered - approximately 10 minutes
Dosage/Consumption	Dosage and consumption of dexmedetomidine infusion	Prior to beginning the MRI and throughout the MRI scan - approximately one hour.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Technique Failure	lack of adequate sedation for MRI scan in spite of the sedation as described above	During the MRI scan until completion - approximately one hour
Case Duration	total number of minutes in the MRI scanner,	Duration of the MRI scan - approximately one hour
Recovery Time	number of minutes in the recovery area until the patient appeared awake (eye opening),	from completion of the MRI scan until prepared for discharge - approximately 90 minutes
Sedation Infusion Time	The number of minutes that the patient was receiving dexmedetomidine infusion	For the duration of the MRI scan - approximately one hour

Collaborators and Investigators

• Sponsor: Joseph Cravero
• Investigators: Principal Investigator: Joseph Cravero, MD, Boston Children's Hospital

Publications and helpful links

General Publications

• Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. Anesthetic neurotoxicity--clinical implications of animal models. N Engl J Med. 2015 Feb 26;372(9):796-7. doi: 10.1056/NEJMp1414786.
• Wu J, Mahmoud M, Schmitt M, Hossain M, Kurth D. Comparison of propofol and dexmedetomedine techniques in children undergoing magnetic resonance imaging. Paediatr Anaesth. 2014 Aug;24(8):813-8. doi: 10.1111/pan.12408. Epub 2014 May 12.
• Heard CM, Joshi P, Johnson K. Dexmedetomidine for pediatric MRI sedation: a review of a series of cases. Paediatr Anaesth. 2007 Sep;17(9):888-92. doi: 10.1111/j.1460-9592.2007.02272.x.
• Triltsch AE, Welte M, von Homeyer P, Grosse J, Genahr A, Moshirzadeh M, Sidiropoulos A, Konertz W, Kox WJ, Spies CD. Bispectral index-guided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study. Crit Care Med. 2002 May;30(5):1007-14. doi: 10.1097/00003246-200205000-00009.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2017
• Primary Completion (Actual): September 6, 2022
• Study Completion (Actual): September 6, 2022

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: MRI; pediatrics; dexmedetomidine; sedation; propofol
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: IRB-P00019084

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No