Clinical trial NCT02633241: A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
Official title: A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Epilepsy
Cerebral Palsy
Developmental Delay
Keywords: pediatrics
sedation
dexmedetomidine
propofol
MRI
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2015-12-17
Enrollment: 71
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dosage/Consumption
timeFrame: Prior to beginning the MRI and throughout the MRI scan - approximately one hour.
measure: Incidence of Patient Movement and MRI Interruption
timeFrame: During the MRI scan, until completion, approximately one hour.
measure: Incidence of Adverse Events
timeFrame: 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.
measure: Case Times
timeFrame: Timeframe immediately before the MRI scan while sedation medication is administered - approximately 10 minutes
Secondary outcomes:
measure: Incidence of Technique Failure
timeFrame: During the MRI scan until completion - approximately one hour
measure: Sedation Infusion Time
timeFrame: For the duration of the MRI scan - approximately one hour
measure: Case Duration
timeFrame: Duration of the MRI scan - approximately one hour
measure: Recovery Time
timeFrame: from completion of the MRI scan until prepared for discharge - approximately 90 minutes
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Joseph Cravero, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.