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

NCT ID: NCT02633241

Last Updated: 2023-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-02
• Study Completion Date: 2022-09-06

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.

Conditions

Epilepsy; Cerebral Palsy; Developmental Delay

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Dexmedetomidine bolus and high infusion-Propofol

Intervention Type: DRUG

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.

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.

Group Type: OTHER

Dexmedetomidine bolus and low infusion-Propofol

Intervention Type: DRUG

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.

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

Group Type: OTHER

Dexmedetomidine bolus only - Propofol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Dexmedetomidine-Propofol; Dexmedetomidine-Propofol; Dexmedetomidine-Propofol

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).

Exclusion Criteria

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

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Joseph Cravero

OTHER

Sponsor Role: lead

Responsible Party

Joseph Cravero

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joseph Cravero, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Boston Children's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25714157 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24814202 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17683409 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12006795 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB-P00019084

Identifier Type: -

Identifier Source: org_study_id