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

Phase 4

Completed

• Conditions: Epilepsy; Cerebral Palsy; Developmental Delay
• Interventions: Drug: Dexmedetomidine bolus and high infusion-Propofol; Drug: Dexmedetomidine bolus and low infusion-Propofol; Drug: Dexmedetomidine bolus only - Propofol

• Registration Number: NCT02633241
• Lead Sponsor: Joseph Cravero

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.

Study Timeline

• Study First Submitted: 2015-12-11
• Study First Submitted QC: 2015-12-14
• Study First Posted: 2015-12-17
• Study Start: 2017-03-02
• Results First Submitted: 2019-05-15
• Results First Submitted QC: 2019-08-15
• Results First Posted: 2019-08-28
• Primary Completion: 2022-09-06
• Study Completion: 2022-09-06
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-23
• Last Update Posted: 2023-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine (bolus and high infusion)-Propofol arm	Dexmedetomidine bolus and high infusion-Propofol	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.
Dexmedetomidine (bolus and low infusion)-Propofol arm	Dexmedetomidine bolus and low infusion-Propofol	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.
Dexmedetomidine (bolus only)-Propofol arm	Dexmedetomidine bolus only - Propofol	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

Primary Outcome Measures

Name	Time	Method
Dosage/Consumption	Prior to beginning the MRI and throughout the MRI scan - approximately one hour.	Dosage and consumption of dexmedetomidine infusion
Incidence of Patient Movement and MRI Interruption	During the MRI scan, until completion, approximately one hour.	If patient moved during their MRI and caused an interruption of the scan.
Incidence of Adverse Events	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.	arterial desaturation, airway obstruction, hypotension and bradycardia
Case Times	Timeframe immediately before the MRI scan while sedation medication is administered - approximately 10 minutes	Number of minutes from the start of sedation medication administration to the time the patient is adequately sedated for the MRI scan,

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States