Clinical trial NCT02633241
Conditions: Epilepsy Cerebral Palsy Developmental Delay
Keywords: pediatrics sedation dexmedetomidine propofol MRI
Sponsor: Joseph Cravero
Start date: 2017-03-02; Completion date: 2022-09-06
Enrollment: 71 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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
Interventions: intervention 1: Dexmedetomidine bolus and high infusion-Propofol intervention 2: Dexmedetomidine bolus and low infusion-Propofol intervention 3: Dexmedetomidine bolus only - Propofol
Intervention descriptions: intervention 1: 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 2: 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 3: 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.

Protocol documents:
Prot_SAP_001.pdf: 
 
Title: A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic 
Resonance Imaging 
NCT02633241 
July 14, 2021 
 
 


Part B: Experimental Design and Protocol 
Human Subjects Protocol Application:  
Title: A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic 
Resonance Imaging 
PI: Joseph Cravero, MD 
 
Please provide a brief Summary or abstract of this research protocol.  
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.  Many of these studies are supported by the group Strategies for Mitigating 
Anesthesia-Related Neurotoxicity (SMARTTOTS). 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 suggest that some alternative sedative agents, such as 
Dexmedetomidine, may not have the same neurotoxic effect.  Funding agencies and advocacy 
groups such as SmartTots along with the FDA and the American Academy of Pediatrics have 
concluded that the current data from these animal studies are  sufficiently convincing that large 
scale clinical studies are warranted[1] .  
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.   
We 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.  
Review of intra-procedural records reveals that the standard infusion rate for propofol at BCH 
for MRI scans is 250mcg/kg/min after a 2-4mg/kg bolus.  Based on previous work with the 
combination of propofol with dexmedetomidine for other procedures, we propose a standard 
dose of dexmedetomidine (1 mcg/kg bolus followed by an infusion at 0.5 mcg/kg/hour).  We will 
augment this sedation with 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.). We are adding a second arm to this 
study to examine the effectiveness of dexmedetomidine (single) bolus dose (with no infusion) 
followed by propofol infusion to accomplish MRI. Outcome metrics will include: 1) Percentage 
of patients where this combination yields a quiet sedated state compatible with accomplishing an 
MRI scan (eyes closed and no movement) 2) MRI pauses from patient movement 3) incidence of 


adverse events such as airway obstruction, desaturation in spite of supplemental O2, bradycardia, 
hypotension, hypertension 4) time required for induction, time for emergence and recovery.  
Because we are testing these techniques in patients undergoing MRI, the outcomes are free of 
confounders related to surgical techniques, which is often a problem in anesthesia and 
perioperative research.  
We hypothesize that the use of low dose propofol with dexmedetomidine will be effective in 
patients undergoing MRI while sparing exposure to the high dose of the sedative.  
1. Specific Aim/Objective 
Determine if the combination of dexmedetomidine (1mcg/kg followed by 0.5 
mcg/kg/hour with propofol 2-3mg/kg titrated bolus followed by 100mcg/kg/min) is 
effective for sedation in pediatric patients undergoing a magnetic resonance imaging 
(MRI) scan.  
 
Determine if the combination of dexmedetomidine (1mcg/kg DEX bolus followed by 
propofol 2-3mg/kg titrated bolus followed by propofol infusion at 100mcg/kg/min) is 
effective for sedation in pediatric patients undergoing a magnetic resonance imaging 
(MRI) scan.  
 
Amendment 2021: This is essentially a dose ranging study. We have looked at bolus plus 
two infusion doses of DEX. Since bolus plus NO infusion is the most common option for 
this procedure, it would seem logical to look at this combination and compare outcomes 
to the other options. 
 
2. Background and Significance 
The Food and Drug Administration and the International Anesthesia Research Society 
have formed a public-private partnership called SmartTots to address concerns about 
potential adverse effects of general anesthesia in young children. Along with other 
nonclinical studies, research on the use of propofol in fetal and neonatal macaque 
monkeys suggests that it causes apoptosis of neurons and oligodendrocytes. In contrast, 
dexmedetomidine has not been shown to be neurotoxic in the studies. Factors influencing 
the extent of injury include age at the time of drug exposure, and cumulative anesthetic 
dose. The group concluded that the evidence available from these animal models is 
“sufficiently convincing to warrant large scale clinical studies”.   The report also offers 
some fundamental questions that might be answered through further study including how 
much injury risk is attributable to the anesthesia as opposed to inflammatory processes or 
underlying disease and to consider whether strategies or interventions can be developed 
to reduce harm. [1] 
 


Propofol and dexmedetomidine are both routinely used for sedation in children 
undergoing MRI. Wu compared each and found that while dexmedetomidine did not 
perform as well as propofol in terms of timeliness, effectiveness, it has been shown to be 
sufficiently effective [2]. Compared to other GABA inhibitors, propofol has a shorter 
induction time, shorter emergence, fewer interruptions during the scan, and shorter 
duration of stay in the PACU. Heard and colleagues did a series of case reviews of 
dexmedetomidine in pediatric MRI scans and similarly found that cases where 
dexmedetomidine was used alone, it was unpredictable with respect to adequate dosing or 
the duration of recovery but also noted that the addition of propofol to dexmedetomidine 
control inadequate sedation with no side effects, and even suggested the combination 
significantly increased the duration of effect than the use of propofol alone [3]. Triltsch et 
al. studied the ability of dexmedetomidine to reduce propofol requirements in adult ICU 
patients and found it to be effective in that respect [4].  
 
Current practice in MRI is generally to give bolus a of dexmedetomidine and small 
 
propofol bolus followed by a propofol infusion. Dexmedetomidine is given at 0.5-
 
1.0mcg/kg. 
 
 
Reports of dexmedetomidine use exist in the literature, but none describing 
 
dexmedetomidine use exactly as we are doing in this trial. However, doses exceeding 
 
what we propose in this study have been used safely in multiple retrospective analyses. 
 
Prospective data will be much more objective and detailed in order to help us understand 
 
the study aims. 
 
We believe that by studying the use of propofol-dexmedetomidine in children undergoing 
MRI scans we can shed light on some of the fundamental questions raised in the 
SmartTots report. Primarily we hope to explore whether a combination of propofol-
dexmedetomidine is effective for sedation in pediatric patients undergoing a magnetic 
resonance imaging (MRI) scan. Because MRI scans are painless and non-invasive, 
sedation outcomes can be observed independent of any effects of pain or “inflammatory 
processes”. 
 
Amendment 2021: There is no absolute standard in the MRI scanner at Boston Children’s 
Hospital. The preliminary results of the first part of this study showed no issues with the 
combination of propofol and dexmedetomidine. In fact, this exact technique is the most 
commonly used combination and dosing in the MRI scanner right now. We published a 
report of our experience in Pediatric Anesthesia – including thousands of cases done with 
this combination – last year, and the results showed NO issues. The addition of this arm 
is a minor modification to an approved study with results reported in our interim reports 
previously. The addition of DEX to the sedation is probably a benefit over propofol alone 
since it may be neuroprotective. It is hard to say for sure if this is a benefit over not being 


part of the study since it is likely that if the patient does not participate, they would likely 
get this same anesthetic/sedative.  
 
3. Design and Methods 
3a. Patient Selection and Inclusion/Exclusion Criteria 
Inclusion Criteria: 
1. Subjects presenting as out-patients, scheduled to receive an anesthetic for MRI of 
brain, 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 between 1 and 12 years of age. 
4. The subject's legally authorized representative has given written informed consent 
to participate in the study. 
5. ASA status I, II, or III  
Exclusion Criteria: 
1. The subject is an in-patient at BCH. 
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/family is not able to understand/speak English.  
3b.Recruitment Methods 
We plan to offer participation to patients aged between 1 and 12 years, who are scheduled 
for MRI at Boston Children’s Hospital.  Potentially eligible subjects will be identified 
through a review of the schedule of upcoming MRI scans, by age and scheduled 
procedure type. Potentially eligible patients will be sent (either by email or postal mail) a 
brochure describing our methodologies in lay language as well as a copy of the consent 
form, up to 1 month prior to their scheduled MRI. This brochure will include a link to a 
web-based, informational Power Point presentation.  Potential participating families will 
be encouraged to view the presentation.   Up to two weeks prior to the scheduled MRI 
scan, we will contact each potential participant by telephone to gauge their interest in 
participation and answer any questions concerning participation and/or the informational 
Power Point presentation. If the family agrees to participate a member of the study team 
will discuss the consent form and study process in further detail. If a family has not yet 
had an opportunity to view the informational slide show, and would like to do so, they 
will be able to view it at this time.  
If a family agrees to participate in the study, their anesthesia team will be sent an email 
from the research team in advance of the MRI scan informing them of their patient’s 
participation in the study.  
3c. Description of Study Treatments or Exposures/Predictors 
This is a prospective observational study of the use of propofol-dexmedetomidine for general 
anesthesia in pediatric patients undergoing an MRI scan. Eligible patients undergoing MRI 
scans, aged between 1 and 12 years, will be recruited from the MRI clinic at BCH and followed 
for the duration of their scan.  
Based on previous work with the combination of propofol with dexmedetomidine for other 
procedures: 
DEX bolus and infusion cohort: we will begin by administering dexmedetomidine 1mcg/kg over 
5 minutes.  When this is completed, we will begin an infusion at 0.5 mcg/kg/hour. At the 5 
minute point propofol will be given (2-3mg/kg titrated bolus followed by 100mcg/kg/min 
infusion).  


DEX bolus only (with propofol infusion) cohort: we will begin by administering 
dexmedetomidine 1mcg/kg over 5 minutes.  When this is completed, we 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. 
Sedation will be scored as ‘yes’ or ‘no’ by the attending clinician depending on whether or not 
the child is in an adequate state to begin the MRI scan by ten minutes after starting this regimen. 
If the sedative effect of the dexmedetomidine-propofol does not produce a sedated state 
compatible with completing the MRI scan within 10 minutes, a repeat bolus of propofol 1-
2mg/kg will be administered.  The dose of DEX will not be changed.  The 1-2mg/kg propofol 
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. 
A member of the research team will be present for the induction of the anesthesia. Either they or 
a second member of the clinical team will verify the doses and pump settings of the research 
medications specified above. 
On the day of the participant’s scan, before the scan begins, demographic data will be collected – 
including age, weight, diagnosis, and coexisting medical conditions. This data will be obtained 
from the electronic medical record after enrollment in the study.   
During the scan we will collect information on time to sufficient sedation, sedative consumption, 
the number of scan interruptions, hemodynamic information, the number and nature of any 
adverse events during the scan, length of scan. Per hospital standard of care, subjects will have 
blood pressure monitored by non-invasive blood pressure cuff every three minutes. End-tidal 
CO2, pulse-oximetry, and 3-lead-ECG monitoring will be monitored continuously and recorded 
every 5 minutes. Heart rate and respiratory rate will be continuously monitored and recorded 
every minute. Temperature will be recorded every 15 minutes. 
Many safe-guards will be in place to protect patients while they are receiving sedation with 
dexmedetomidine and propofol. Subjects will receive standard anesthesia-level care, just as they 
would if they were not participating in the study. Board certified pediatric anesthesiologists will 
provide the care in the MRI suite at Boston Children’s Hospital along with a Certified Nurse 
Anesthetist, anesthesia resident, or pediatric anesthesia fellow. Per hospital standard operating 
protocol, patients will receive supplemental oxygen. There are anesthesia carts and code-carts 
fully stocked with a complete array of “code” medications as well as additional anesthetics, 
muscle relaxants etc. 
After the scan is complete, when the participant is in the post anesthesia care unit (PACU) we 
will collect data on the number and nature of any adverse events (including any from the start of 


the study), emergence time, time to discharge criteria. Per hospital standard, patients are called 
the day after their procedure to assess for adverse events. Study staff will review the charts 
following this phone call to assess for adverse events following discharge from the hospital. 
3d. Retention/Incentives  
 
 All participants will receive a thank you postcard from the study.  
3e. Definition of Primary and Secondary Outcomes/Endpoints 
 
Primary outcomes:  
 Dosage/ consumption 
o Incidence of technique failure defined as lack of adequate sedation for 
MRI scan in spite of the sedation as described above.  
 Incidence of patient movement and MRI interruption. 
 Incidence of adverse events defined as: arterial desaturation, airway obstruction, 
hypotension and bradycardia. 
 Incidence of agitation on emergence as defined by a PAED score of 10 or greater 
at any point during PACU stay. 
 Times: Time from initiation of DEX infusion to meeting sedation criteria for MRI 
scan, duration of infusions of DEX and propofol, time in MRI suite, time to eye 
opening, time to full responsiveness, time to “ready for PACU discharge”.  
 
3f. Data Collection Methods, Assessments, Interventions, and Schedule 
Data will be collected from several resources:  
1. Data on safety outcomes and Dexmedetomidine-Propofol consumption will be collected 
from the AIMS record (during the scan) and the electronic medical record (during 
recovery) and entered into an InForm database by members of the research team.  
2. Data on incidence of MRI scan interruption will be observed directly by designated 
members of the research team and documented on a CRF  
3. Time data for time to produce sedation, drug administration, duration of infusion, time to 
emergence, agitation (yes/no), time to ready for PACU discharge will be recorded by 
members of the research team and entered into the InForm database.  
3g. Study Timeline 
For the purpose of this pilot observational study, 60 eligible patients undergoing MRI scans, 
aged between 1 and 12 years, will be recruited from the MRI clinic at BCH and followed for the 
duration of their scan. It is expected that recruitment will be completed within 12 months from 
the start of the study.  


4. Adverse Event Criteria and Reporting Procedures 
Amendment 2021: Per our previous results, being in the study likely will not change the nature 
of the sedation at all. If anything, adding Dexmedetomidine has clearly been shown in our study 
and many others to decrease the total dose of propofol required to accomplish MRI scan 
sedation/anesthesia. 
Adverse or unanticipated events will be reported as required to the Boston Children’s Hospital 
IRB according to institutional reporting requirements. A case report form will be used to 
document adverse events. Dexmedetomidine in the doses used in this study is not associated with 
adverse respiratory events.  We believe that the only adverse events that could reasonably be 
attributed to dexmedetomidine would be cardiovascular in nature. Adverse events will be 
evaluated using the WHO-UMC causality assessment system. Moderate adverse events will be 
defined as abnormal cardiovascular parameters including: 1) bradycardia greater than 30% below 
age-defined criteria, 2) hypertension of greater than 30% above age-defined criteria, or 3) 
hypotension greater than 30% below age-defined criteria, as defined by the values in the 
following tables [5].  
 
 
 
 
 
Normal Heart Rate by Age (beats/minute) 
Age 
Awake 
Rate 
Sleeping Rate 
Neonate (<28 d) 
100-205 
90-160 
Toddler (1-2 y) 
98-140 
80-120 
Preschool (3-5 y) 
80-120 
65-100 
School-age (6-11 y) 
75-118 
58-90 
Adolescent (12-15 y) 60-100 
50-90 
 
If any of these hemodynamic profiles occur for a sustained period of more than one minute 
during the bolus or infusion of dexmedetomidine, the patient will be immediately withdrawn 
from the study and care will proceed at the discretion of the board-certified anesthesiologist after 
stopping dexmedetomidine. If adverse events occur after the infusion of dexmedetomidine is 
completed, the patient will be closely monitored and cared for at the discretion of the 
anesthesiologist.  
Severe adverse effects will be considered life-threatening arrhythmias or loss of spontaneous 
circulation. If three moderate adverse events or one severe adverse event occur, the study will be 
stopped and the event will be reported to all necessary officials. 
Normal Blood Pressure by Age (mmHg) 
Age 
Systolic 
Pressure 
Diastolic 
Pressure 
Systolic Hypotension 
Toddler (1-2 y) 
86-106 
42-63 
<70 + (age in years x 2) 
Preschooler (3-5 y) 
89-112 
46-72 
<70 + (age in years x 2) 
School-age (6-9 y) 
97-115 
57-76 
<70 + (age in years x 2) 
Preadolescent (10-11 
y) 
102-120 
61-80 
<90 
Adolescent (12-15 y) 
110-131 
64-83 
<90 


5. Data Management and Statistical Analysis 
5a. Data Management Methods 
Each subject will be assigned a unique identifier.   An InForm database will be created to store 
data captured on case report forms and to collect survey data. InForm is a secure, web-based 
application designed to support electronic data capture for research.  Only authorized users are 
permitted access to the data files, and daily server back-up activities are executed to ensure data 
recovery. The data capture screens will mimic the case report forms to promote accurate data 
entry. Paper files will be stored in locked cabinets in the office of the PI.  Procedures to ensure 
accurate and reliable data collection will include well designed data forms and training in data 
collection methods. 
 
5b. Quality Control Method 
  
Data quality control will be assured through automated and manual methods. The study database 
enhances data quality through required entry fields for critical data and automatic flags for 
missing or out-of-range data. Case report forms are designed to closely mirror the format of data 
entry fields in the database to reduce risk of data transfer errors.  
 
5c. Data Analysis Plan 
 Patient characteristics—frequency-gender, types of scan, mean/SD ages and 
weight, mean/SD length of scan, changes in hemodynamics (baseline against 
lowest recorded).  
 Raw data will be recorded on the number of children in the study who have to 
stop the scan will be recorded. Furthermore, if a child’s scan is stopped, the 
number of times their scan must be stopped and duration of scan delay will also 
be recorded.  
 Raw data will be recorded on the number of children who experience a 
complication or adverse event during the MRI scan and/ or recovery. Raw data 
will be collected on the number of each type of complication. 
 Raw data will be recorded for dosage and summary statistics will be reported for 
dosage. 
 Compare patient characteristics, scan interruptions, complications against 
dosage/consumption. 
5d. Statistical Power and Sample Considerations 
This is a pilot study. As such, we are not performing a power analysis to determine a 
required sample size. We plan to enroll 60 subjects for this pilot study.  
5e. Study Organization 


 The principal investigator for this study is Dr. Joseph Cravero in the Department of 
Anesthesiology, Perioperative and Pain Medicine at Boston Children’s Hospital. 
5f. Data and Safety Monitoring Plan 
The Data and Safety Monitoring Plan will focus on adequacy of data collection, and 
occurrence of serious adverse events. Subjects will be monitored by the Principal 
Investigator (Dr. Cravero). Any serious adverse events that occur will be promptly 
reported to the Institutional Review Board at Children’s Hospital Boston according to 
IRB guidelines. A case report form will be used to document adverse events. The PI will 
review the safety and progress of this study on a regular basis. All data that is to be 
released to investigators will be reviewed prior to release to ensure maintenance of 
confidentiality. An interim analysis will be performed following the enrollment of the 
first 15 participants. 
6. Risk and Discomfort  
The use of propofol-dexmedetomidine is used as part of standard care at Boston Children’s 
Hospital. There are no additional risks to standard care to participants in this research study, as 
study participants will have an MRI done with sedation regardless of study participation or non-
participation. While some concerns have been raised regarding propofol the possibility of neural-
apoptosis, the exposure to this medication will not be different based on a choice of participation 
or non-participation.  In addition, dexmedetomidine has been suggested (in animal models) to 
confer some protection from neural–apoptosis and therefore participation may actually represent 
some benefit.. Although dexmedetomidine is not FDA approved for use in children, if parents 
choose not to have their children participate in this study it is still possible that their child may 
receive dexmedetomidine. In neonatal and infant animals, sedative and anesthetic agents, like 
propofol, produce adverse effects on brain development, including loss of brain cells resulting in 
long-term, possibly permanent changes in learning and behavior.  These adverse effects appear 
to occur mostly after prolonged periods of sedation or anesthesia (generally greater than 3 hours) 
and when brain development is occurring at a rapid rate (which roughly occurs in children under 
3 years of age).  It is not known if similar adverse effects occur in humans.  As a study 
participant you should be advised that the drugs we must provide to accomplish the procedure 
your child needs may have the potential to increase the loss of nerve cells in the developing brain 
of your child and that the clinical significance of any such changes is not known.  There are 
some animal studies that suggest dexmedetomidine may be better than other anesthetics for a 
growing infant’s brain.  However, the effects of dexmedetomidine alone or in combination with 
propofol on the developing brain have not been thoroughly tested to date. 
 
Patients will be removed from the study at any point if the attending physician feels that 
treatment with propofol-dexmedetomidine may be inappropriate to that patient’s care at that time 
or they develop any of the exclusion criteria. If a patient enrolled in the study should have an 


adverse event and the reaction is severe or life-threatening, then the patient will be withdrawn 
from the study. If the adverse event is felt to be caused by the dexmedetomidine or propofol-
dexmedetomidine combination, then the IRB and FDA will be notified of the adverse event.  
 
 
7. Potential Benefits 
 
We believe that by studying the use of propofol-dexmedetomidine in children undergoing MRI 
scans we can shed light on some of the fundamental questions raised in the SmartTots report. 
Primarily we hope to explore whether a combination of propofol-dexmedetomidine is effective 
for sedation in pediatric patients undergoing a magnetic resonance imaging (MRI) scan. The 
potential benefits of this study include a reduction in propofol dose and the opportunity to protect 
neurocognitive development in the pediatric population.  
8. Privacy Provisions 
Information will only be made available to individuals who are part of the research team. 
Any results from tests performed for research purposes will not be placed in the medical 
record. Medical information collected for this study will only become part of the child’s 
medical record if the information is determined to be pertinent to the care the child 
receives at Boston Children’s Hospital. Disclosure of personal information may occur 
only when required by law.    
9. Confidentiality Provisions 
All paper records are kept in locked cabinet with access restricted to the investigators. The study 
tablet is encrypted, password protected, and compliant with Boston Children’s Hospital policies. 
When not in use it will be stored in a locked cabinet with access restricted to the investigators. 
No data will be stored directly on the device.  
 All identifying information such as dates of birth, names or medical record numbers, will 
be removed from the Anesthesia Oracle database instance. All patients will be assigned to 
an ID number that will be not linked to any patient identifying information. Research 
related data will not be entered in to patients’ medical records. All data will be 
electronically secured in a private folder and password protected. Only research 
investigators and personnel affiliated with the study will have access to patient 
information.  
An InForm database will be created to store data captured on case report forms and to collect 
remote survey data. InForm is a secure, web-based application designed to support electronic 
data capture for research.  Only authorized users are permitted access to the data files, and daily 
server back-up activities are executed to ensure data recovery.  
10. References 


1. 
Rappaport, B.A., et al., Anesthetic Neurotoxicity — Clinical Implications of Animal 
Models. New England Journal of Medicine, 2015. 372(9): p. 796-797. 
2. 
Wu, J., et al., Comparison of propofol and dexmedetomedine techniques in children 
undergoing magnetic resonance imaging. Paediatr Anaesth, 2014. 24(8): p. 813-8. 
3. 
Heard, C.M., P. Joshi, and K. Johnson, Dexmedetomidine for pediatric MRI sedation: a 
review of a series of cases. Paediatr Anaesth, 2007. 17(9): p. 888-92. 
4. 
Triltsch, A.E., et al., Bispectral index-guided sedation with dexmedetomidine in intensive 
care: a prospective, randomized, double blind, placebo-controlled phase II study. Crit 
Care Med, 2002. 30(5): p. 1007-14. 
5.  
2015 American Heart Association Guidelines: Update for Cpr and Ecc. Dallas, Texas: 
American Heart Association, 2015. Accessed August 8, 2016