Cerebral Palsy, Developmental Delay, Epilepsy
Conditions
Keywords
pediatrics, sedation, dexmedetomidine, propofol, MRI
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.
Interventions
DRUGDexmedetomidine 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.
DRUGDexmedetomidine 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.
DRUGDexmedetomidine 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.
Sponsors
Joseph Cravero
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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, |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Sedation Infusion Time | For the duration of the MRI scan - approximately one hour | The number of minutes that the patient was receiving dexmedetomidine infusion |
| 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), |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from 3.2.2017 and the final patient was enrolled 9.6.2022. Recruitment occurred after mail and phone contact approximately 2 weeks before the study and consent was obtained on the day of the study.
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine (High)-Propofol Arm 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 (2mg/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. | 13 |
| Dexmedetomidine (Low)-Propofol Arm The investigators will administer dexmedetomidine 1 mcg/kg over 5 minutes. Next, the investigators will begin an infusion at 0.5 mcg/kg/hour. At the 5 minute point, propofol will be given (2mg/kg bolus followed by 100 mcg/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 2 mg/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. | 14 |
| Dexmedetomidine (Bolus Only)-Propofol Arm The investigators will administer dexmedetomidine 1 mcg/kg over 5 minutes. At the 5 minute point, propofol will be given (2 mg/kg bolus followed by 100 mcg/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 2 mg/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. | 28 |
| Total | 55 |
Baseline characteristics
| Characteristic | Dexmedetomidine (Low)-Propofol Arm | Dexmedetomidine (Bolus Only)-Propofol Arm | Dexmedetomidine (High)-Propofol Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 28 Participants | 13 Participants | 55 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 4.6 years | 3.6 years | 2.6 years | 3.6 years |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United States | 14 participants | 28 participants | 13 participants | 55 participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 16 Participants | 10 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 | 0 / 28 |
| other Total, other adverse events | 0 / 13 | 0 / 14 | 0 / 28 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 | 0 / 28 |
Outcome results
Primary
Case Times
Number of minutes from the start of sedation medication administration to the time the patient is adequately sedated for the MRI scan,
Time frame: Timeframe immediately before the MRI scan while sedation medication is administered - approximately 10 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Case Times | 7 minutes |
| Dexmedetomidine (Low)-Propofol Arm | Case Times | 7 minutes |
| Dexmedetomidine (Bolus Only)-Propofol Arm | Case Times | 7 minutes |
Primary
Dosage/Consumption
Dosage and consumption of dexmedetomidine infusion
Time frame: Prior to beginning the MRI and throughout the MRI scan - approximately one hour.
Population: Patients who completed the study and received a dexmedetomidine infusion
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Dosage/Consumption | 0.36 mcg/kg/min |
| Dexmedetomidine (Low)-Propofol Arm | Dosage/Consumption | 0.25 mcg/kg/min |
Primary
Incidence of Adverse Events
arterial desaturation, airway obstruction, hypotension and bradycardia
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Incidence of Adverse Events | 1 incidents |
| Dexmedetomidine (Low)-Propofol Arm | Incidence of Adverse Events | 1 incidents |
| Dexmedetomidine (Bolus Only)-Propofol Arm | Incidence of Adverse Events | 3 incidents |
Primary
Incidence of Patient Movement and MRI Interruption
If patient moved during their MRI and caused an interruption of the scan.
Time frame: During the MRI scan, until completion, approximately one hour.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Incidence of Patient Movement and MRI Interruption | 2 patients |
| Dexmedetomidine (Low)-Propofol Arm | Incidence of Patient Movement and MRI Interruption | 3 patients |
| Dexmedetomidine (Bolus Only)-Propofol Arm | Incidence of Patient Movement and MRI Interruption | 2 patients |
Secondary
Case Duration
total number of minutes in the MRI scanner,
Time frame: Duration of the MRI scan - approximately one hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Case Duration | 52.8 minutes | Standard Deviation 21.2 |
| Dexmedetomidine (Low)-Propofol Arm | Case Duration | 53.3 minutes | Standard Deviation 16.8 |
| Dexmedetomidine (Bolus Only)-Propofol Arm | Case Duration | 40.1 minutes | Standard Deviation 17.4 |
Secondary
Incidence of Technique Failure
lack of adequate sedation for MRI scan in spite of the sedation as described above
Time frame: During the MRI scan until completion - approximately one hour
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Incidence of Technique Failure | 0 incidents |
| Dexmedetomidine (Low)-Propofol Arm | Incidence of Technique Failure | 0 incidents |
| Dexmedetomidine (Bolus Only)-Propofol Arm | Incidence of Technique Failure | 0 incidents |
Secondary
Recovery Time
number of minutes in the recovery area until the patient appeared awake (eye opening),
Time frame: from completion of the MRI scan until prepared for discharge - approximately 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Recovery Time | 63.5 minutes | Standard Deviation 22 |
| Dexmedetomidine (Low)-Propofol Arm | Recovery Time | 60.9 minutes | Standard Deviation 23.6 |
| Dexmedetomidine (Bolus Only)-Propofol Arm | Recovery Time | 42.5 minutes | Standard Deviation 22.4 |
Secondary
Sedation Infusion Time
The number of minutes that the patient was receiving dexmedetomidine infusion
Time frame: For the duration of the MRI scan - approximately one hour
Population: Patients who completed the study and received a dexmedetomidine infusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine (High)-Propofol Arm | Sedation Infusion Time | 43 minutes |
| Dexmedetomidine (Low)-Propofol Arm | Sedation Infusion Time | 50 minutes |