Pediatric Anesthesiology

Section Editor: Peter J. Davis

A Comparison of Dexmedetomidine-Midazolam with

Propofol for Maintenance of Anesthesia in Children
Undergoing Magnetic Resonance Imaging
Christopher Heard, MBChB,
FRCA*
Frederick Burrows, MD†
Kristin Johnson, PharmD‡
Prashant Joshi, MD§
James Houck, MD储
Jerrold Lerman, MD, FRCPC,
FANZCA¶#
BACKGROUND: Dexmedetomidine is an ␣2 agonist that is currently being investigated
for its suitability to provide anesthesia for children. We compared the pharmaco-
dynamic responses to dexmedetomidine-midazolam and propofol in children
anesthetized with sevoflurane undergoing magnetic resonance imaging (MRI).
METHODS: Forty ASA 1 or 2 children, 1–10 yr of age, were randomized to receive
either dexmedetomidine-midazolam or propofol for maintenance of anesthesia for
MRI after a sevoflurane induction. Dexmedetomidine was administered as an
initial loading dose (1 ␮g/kg) followed by a continuous infusion (0.5
␮g 䡠 kg⫺1 䡠 h⫺1). Midazolam (0.1 mg/kg) was administered IV when the infusion
commenced. Propofol was administered as a continuous infusion (250 –300
␮g 䡠 kg⫺1 䡠 min⫺1). Recovery times and hemodynamic responses were recorded by
one nurse who was blinded to the treatments.
RESULTS: We found that the times to fully recover and to discharge from the
ambulatory unit after dexmedetomidine administration were significantly greater
(by 15 min) than those after propofol. Analysis of variance demonstrated that heart
rate was slower and systolic blood pressure was greater with dexmedetomidine
than propofol. Respiratory indices for the two treatments were similar. During
recovery, hemodynamic responses were similar. Cardiorespiratory indices during
anesthesia and recovery remained within normal limits for the children’s ages. No
adverse events were recorded.
CONCLUSION: Dexmedetomidine-midazolam provides adequate anesthesia for MRI
although recovery is prolonged when compared with propofol. Heart rate was
slower and systolic blood pressure was greater with dexmedetomidine when
compared with propofol. Respiratory indices were similar for the two treatments.
(Anesth Analg 2008;107:1832–9)

G eneral anesthesia or sedation is usually required

for children who require radiological studies such as
From the *Department of Anesthesiology and Division of Pedi-
atric Critical Care, State University of New York at Buffalo, Women
and Children’s Hospital of Buffalo, Buffalo, New York; †Depart-
ment of Anesthesiology, State University of New York at Buffalo,
Women and Children’s Hospital of Buffalo, Buffalo, New York;
‡Department of Pharmacy, Women and Children’s Hospital of
Buffalo, Buffalo, New York; §Division of Pediatric Critical Care,
State University of New York at Buffalo, Women and Children’s
Hospital of Buffalo, Buffalo, New York; 储Department of Anesthesi-
ology, Women and Children’s Hospital of Buffalo, Buffalo, New
York; ¶State University of New York at Buffalo and University of
Rochester, Rochester, New York; and #Department of Anesthesiol-
ogy, Women and Children’s Hospital of Buffalo, Buffalo and Strong
Memorial Hospital, Rochester, New York.
Accepted for publication July 2, 2008.
Supported by Departmental Funds.
Presented, in part, at the Annual meeting of the American
Society of Anesthesiologists, San Francisco, CA, October 15th, 2007.
Reprints will not be available from the author.
Address correspondence to Dr. Christopher Heard, Department
of Anesthesiology, Women and Children’s Hospital of Buffalo, 219
Bryant St., Buffalo, NY 14222. Address e-mail to heardop1@
verizon.net.
Copyright © 2008 International Anesthesia Research Society
DOI: 10.1213/ane.0b013e31818874ee
magnetic resonance imaging (MRI). Although many
healthy young children have been managed by radi-
ologists and nursing with oral or IV sedation, the
efficiency of this technique is poor and the failure rate,
particularly in children who are cognitively chal-
lenged, is substantial.1,2 Those who are most in need
of general anesthesia include children who are young
(⬍6 yr of age), those who are unable or unwilling to
remain still during the scan and those who are devel-
opmentally or cognitively challenged. The most widely
used general anesthetics for MRI are propofol and
sevoflurane, although more recently there has been
growing interest in dexmedetomidine for this purpose.
Dexmedetomidine has been investigated as an an-
esthetic for ambulatory radiological procedures in
children, including MRI.3– 8 Most of these reports have
been case series with wide variations in the dosing
regimens and success rates. Dexmedetomidine was
compared with midazolam and propofol for MRI in
children in randomized, controlled trials.5,7 In the
comparison with propofol, the failure rates (as
evidenced by movement during the scan) with dexme-
detomidine and propofol were 16% and 10%, respec-
tively, the scan times were uncharacteristically brief

1832 Vol. 107, No. 6, December 2008

(25 min) and hemoglobin desaturation occurred in the
perioperative period.7 As a result of the scan failures
with dexmedetomidine, the scans had to be resched-
uled.3,5,7 The results of these studies suggested that
when dexmedetomidine was administered in accor-
dance with these study protocols, it did not provide
adequate anesthesia for MRI in children.
To address the substantial failure rates during MRI
scans, larger doses of dexmedetomidine have been
studied for MRI in children.9 However, many clini-
cians have been hesitant to administer large doses of
dexmedetomidine for these outpatient surgeries as the
elimination half-life of dexmedetomidine in children
is prolonged, approximately 2 h,10 and there is con-
cern of hypotension and bradycardia. Nonetheless,
large initial loading doses of dexmedetomidine (2–3
␮g/kg) combined with increased infusion rates (up to
2 ␮g 䡠 kg⫺1 䡠 h⫺1) were recently reported in children
for MRI and found to be effective in reducing the scan
failure rates.9
In a pilot study, we investigated several strategies
to optimize the anesthetic, i.e., prevent movement,
using standard doses of dexmedetomidine. Our pre-
liminary data indicated that, after a brief inhaled
induction, a single IV dose of midazolam combined
with dexmedetomidine provided not only effective
and reliable anesthesia for MRI without movement,
but provided rapid recovery and stable cardiorespira-
tory responses that appeared to be comparable with
our experience with propofol.8 Accordingly, we de-
signed this study to compare the recovery charac-
teristics and pharmacodynamics (cardiorespiratory
responses) of dexmedetomidine (combined with mi-
dazolam) with those of propofol during and after
anesthesia for ambulatory MRI in children.
METHODS
With local IRB approval and informed written
consent from the Children and Youth Institutional
Review Board, Woman and Children’s Hospital of
Buffalo, 40 children, ages 1–10 yr, scheduled for
elective MRI under anesthesia were recruited. Exclu-
sion criteria were: age ⬍1 yr, the presence of congenital
heart disease, a recent upper respiratory infection,
pneumonia or episode of acute asthma in the preced-
ing 2 wk, behavioral problems (i.e., attention deficit
hyperactivity disorder), gastroesophageal reflux dis-
ease requiring treatment, recent use of digoxin, ␤
blockers, ␣2 agonists, anticonvulsants or psychotropic
medications, allergies to ␣2 agonists or propofol, sleep
apnea, difficult airway or one that required tracheal
intubation or laryngeal mask airway, body mass index
(BMI) ⬍5% or ⬎95% or a scan expected to last more
than 90 min.
After application of electrocardiogram, noninvasive
arterial blood pressure and pulse oximeter, anesthesia
was induced with 8% inspired sevoflurane, 60% ni-
trous oxide in oxygen by facemask in the MRI scan
Vol. 107, No. 6, December 2008
room. With loss of consciousness, IV access was
established and a balanced salt solution was adminis-
tered according to standard fluid guidelines. The
facemask was then replaced with baffled nasal prongs
through which supplemental oxygen was delivered at
2 L/m via one prong, and the carbon dioxide (CO2)
tension was monitored via the second prong (Pediatric
ETCO2 Divided Sampling Cannula, Salter Labs®,
Arvin, CA). The child was positioned with a soft roll
under the shoulder and the neck extended. A stable
capnogram was established before proceeding. If
evidence of airway obstruction was present, supple-
mental airway maneuvering and interventions were
instituted. Electrocardiogram, pulse oximetry, and
CO2 were monitored continuously throughout the
anesthetic. Noninvasive arterial blood pressure
was monitored at 5 min intervals throughout the
anesthetic.
After induction of anesthesia, the children were
randomly assigned to receive either a dexmedetomi-
dine or propofol by infusion. Randomization was
determined in advance of the study using random
number tables to assign the numbers between 1 and 40
to the 2 groups. The randomization assignment was
concealed until the parents consented to the study.
For those who were assigned to receive dexmedeto-
midine, an initial loading dose of dexmedetomidine, 1
␮g/kg, was infused IV over 10 min followed by a
continuous infusion at 0.5 ␮g 䡠 kg⫺1 䡠 h⫺1. For those
who were scheduled to receive propofol, propofol was
infused IV at 300 ␮g 䡠 kg⫺1 䡠 min⫺1 for the first 10 min
and then at 250 ␮g 䡠 kg⫺1 䡠 min⫺1 for the remainder of
the MRI. At the 10 min mark, 0.1 mg/kg midazolam
was given IV to children in the dexmedetomidine
group and a similar volume of saline was given IV to
those in the propofol group. All infusions were at-
tached to the clave in the IV tubing set closest to the
child. Once the infusion of dexmedetomidine (initial
loading dose) or propofol was established, the child
entered the MRI scanner.
The infusions were discontinued when the scan
was completed. The child was then transferred to the
postanesthesia care unit (PACU) while breathing
supplemental oxygen administered by a facemask and
monitored by pulse oximetry. After recovery from
anesthesia in the PACU, the children were transferred
to the ambulatory unit until discharge.
A single observer, who was blinded to the treat-
ment assignment, was present throughout the MRI
and recovery periods. Blinding was assured by con-
cealing the infusion pump and tubing using green
towels and by standardizing the two infusion proto-
cols such that each required only one adjustment, at 10
min after they were started. At the completion of the
anesthetic, the IV tubing was flushed with saline to
eliminate any residual propofol to maintain observer
blinding.
© 2008 International Anesthesia Research Society 1833
 The observer recorded the heart rate, systolic and
diastolic blood pressures, respiratory rate, hemoglo-
bin oxygen saturation, and CO2 tension (via the nasal
cannula) every 5 min during the anesthetic and heart
rate, systolic and diastolic blood pressures, respiratory
rate, and hemoglobin oxygen saturation every 5 min
in the PACU. The observer also recorded all compli-
cations and side effects during or after the anesthetic.
The times from the application of the facemask until
start of the infusion (a measure of the sevoflurane
exposure), from the beginning to the end of the
treatment infusion and the total time in the MRI scan
suite were recorded. The time intervals from the
termination of the anesthetic until spontaneous eye
opening, recovery of full responsiveness (based on a
modified Aldrete score of 10/10) and discharge from
PACU were recorded. The time intervals from PACU
discharge until hospital discharge and from end of the
scan until hospital discharge were also determined.
Discharge criteria from the ambulatory unit were
based on standard discharge criteria used at our
institution regardless of the anesthetic administered.
A follow-up phone call was completed within 72 h of
completion of anesthesia to determine if there were
any adverse events or sequelae noted by the parents
after discharge.
Sample size was estimated based on pilot and
published data of the recovery times after dexmedeto-
midine and propofol in children undergoing MRI.7,8
With a difference between the mean recovery times of
25 min and a standard deviation of 13 min, two tailed
␣ 0.05 and power of 0.8, only 6 children were required
in each group. For MRI scanning at our institution, we
use large doses of propofol to reduce the risk of
movement (i.e., failed scans), a practice that could
increase the recovery time after propofol administra-
tion. To account for an anticipated smaller difference
in the recovery times between the dexmedetomidine
and propofol, 20 children were enrolled in each treat-
ment arm.
The primary outcome variable was the time interval
from discontinuation of the infusion until full recov-
ery of responsiveness after anesthesia as defined by
the modified Aldrete score (Appendix). Secondary
outcome variables included the times in the PACU to
eye opening, and to discharge from the PACU and
the ambulatory unit, as well as heart rates, systolic
and diastolic blood pressure responses, respiratory
rates, end-tidal CO2 tensions, and the incidence of
complications.
Demographic data (age, weight), anesthesia and
MRI scan times and recovery times were compared
between treatments using the Student’s t-test. Con-
tinuous measurements (heart rate, systolic and dia-
stolic blood pressures, respiratory rate, and ETCO2
tension) during anesthesia and in the PACU were
analyzed using a two-factor (treatment and time)
repeated-measures analysis of variance model with
the Student-Newman-Keuls test for post hoc multiple
1834 Comparison of Dexmedetomidine-Midazolam with Propofol
Table 1. Demographic Data
Dexmedetomidine Propofol
Number 20 20
Age (yr) 4.3 ⫾ 1.4 3.8 ⫾ 1.7
Weight (kg) 17 ⫾ 3.4 16.6 ⫾ 4.0
BMI percentile 51.5 ⫾ 25.4 45.3 ⫾ 31.2
Gender (M/F) 13/7 12/8
MRI head 13 13
MRI spine 6 7
MRI extremity 0 1
Continuous data are means ⫾ SD; remainder are numbers of children.
BMI ⫽ body mass index; MRI ⫽ magnetic resonance imaging.
comparisons. All data were evaluated using Bartlett’s
test for homogeneity of variances and Kolmogorov-
Smirnov test for normalcy of data distribution. Effects
of treatment, time and the interaction, treatment ⫻
time are reported as F values for each analysis of
variance and P values for each post hoc comparison.
P ⬍ 0.05 was accepted.
RESULTS
Forty children completed this study, 20 in each
group. Demographic data for the two groups were
similar (Table 1). The number of children who were
taking medications before the study (three children
required asthma medications, three required seizure
medications, two required laxatives) was similar in the
two groups. The reasons for the MRI scans were
developmental delay (n ⫽ 11), tethered cord (n ⫽ 8),
seizures (n ⫽ 5), cerebral palsy (n ⫽ 3), tumor (n ⫽ 2),
headache (n ⫽ 3), syrinx (n ⫽ 2), and others (n ⫽ 6).
All children completed their scans using the anesthetic
regimen to which they had been randomized. The
average overall doses of dexmedetomidine and propo-
fol infused were 1.7 ␮g/kg ⫾ 0.25 and 9.3 mg/kg ⫾
3.1, respectively.
The time interval from application of the facemask
until start of the infusions, the duration of the infu-
sions and the time in the MRI suite were similar for the
two treatments (Table 2). Although the times to eye
opening after the two treatments were similar, the
primary outcome variable, the time to recovery of full
responsiveness, was significantly greater after dexme-
detomidine administration than it was after propofol
by 50% or 15 min (P ⬍ 0.05). The time to PACU
discharge after dexmedetomidine exceeded that after
propofol by almost 50%, or 15 min (P ⬍ 0.05). The
times in the ambulatory unit (post-PACU discharge)
was similar for the two treatments. The total time
interval between completion of the scan and hospital
discharge after dexmedetomidine was significantly
greater than that after propofol, with virtually all of
the excess time occurring in the PACU (Table 2).
Heart rates for both treatments at baseline were
similar (Fig. 1). During the MRI, heart rate differed
significantly between the two treatments. Heart rate
changes during the MRI were dependent on both the
treatment (F0.05 (1) 1,38 ⫽ 4.2, P ⬍ 0.048) and the
ANESTHESIA & ANALGESIA
Table 2. Procedure and Recovery Times
Dexmedetomidine Propofol
Time from mask 3.9 ⫾ 1.5 4.7 ⫾ 1.1
application to start of
infusion (min)
Duration of infusion 33.4 ⫾ 9.3 35.6 ⫾ 14.7
(min)
Time in MRI suite 37.4 ⫾ 9.4 40.3 ⫾ 14.7
(min)
Time to eye opening 34.0 ⫾ 18.9 26.9 ⫾ 12.6
(min)
Time to full 44.2 ⫾ 18.0* 29.7 ⫾ 11.1 Figure 2. Blood pressure during magnetic resonance imaging
responsivenessa (min) (MRI). Systolic and diastolic blood pressure responses to
Time to PACU 50.3 ⫾ 18.2* 36.5 ⫾ 9.2 dexmedetomidine-midazolam (Dex) and propofol during
discharge (min) MRI scans. Treatment and the interaction, treatment ⫻ time,
Time from PACU 45.4 ⫾ 20.6 42.9 ⫾ 22.2 yielded significant differences for both systolic and diastolic
discharge to hospital blood pressures (see Results for significance levels). Data are
discharge (min) means ⫾ sd. *P ⬍ 0.0003; **P ⬍ 0.00003 between dexme-
Time from end of scan 95.7 ⫾ 26.5* 79.4 ⫾ 24.3 detomidine and propofol. †P ⬍ 0.02; ⽤P ⬍ 0.0035; ††P ⬍
until hospital 0.048 compared with baseline.
discharge (min)
Data are means ⫾ SD.
PACU ⫽ postanesthesia care unit; MRI ⫽ magnetic resonance imaging.
a
Systolic blood pressures in the two treatments were
Based on a modified Aldrete score of 10/10 (Appendix).
* P ⬍ 0.05 compared with propofol.
similar at baseline (Fig. 2). Treatment (F0.05 (1) 1,38 ⫽
15.5, P ⬍ 0.0003) and the interaction, treatment ⫻ time,
(F0.05, (1) 5,190 ⫽ 7.1, P ⬍ 0.000004) yielded significant
effects on systolic blood pressure, whereas time did
not. Systolic blood pressure in the dexmedetomidine
group at 20 min was significantly greater than baseline
(P ⬍ 0.02), whereas those in the propofol group at 20
and 25 min were less than baseline (P ⬍ 0.02). Systolic
blood pressures in the dexmedetomidine group were
greater than those in the propofol group at 10 min
(P ⬍ 0.0003) and at 15, 20, and 25 min (P ⬍ 0.00003).
The minimum systolic blood pressure recorded in the
dexmedetomidine group was 70 mm Hg (n ⫽ 2) and in
the propofol group, 64 mm Hg (n ⫽ 2). Diastolic blood
pressures in the two treatments were similar at
Figure 1. Heart rate during magnetic resonance imaging baseline (Fig. 2). Treatment (F0.05 (1) 1,38 ⫽ 29.1, P ⬍
(MRI). Heart rate responses to dexmedetomidine- 0.000004) and the interaction, treatment ⫻ time
midazolam (Dex) and propofol during MRI scans. Treat- (F0.05 (1) 1,38 ⫽ 9.2, P ⬍ 0.0000001) yielded significant
ment (P ⬍ 0.048) and the interaction, treatment ⫻ time, (P ⬍ effects on diastolic blood pressure. Diastolic blood
0.00006) yielded significant effects on heart rate. Heart rate
in the dexmedetomidine group was significantly less than
pressures at 15, 20 and 25 min in both groups were
the baseline value at all times (P ⬍ 0.00004) whereas heart significantly different from baseline. Diastolic blood
rate in the propofol group did not differ significantly from pressures in the propofol group were significantly less
the baseline value at any time. Data are means ⫾ sd. *P ⬍ than those in the dexmedetomidine group at 5 min
0.00007 compared with dexmedetomidine. †P ⬍ 0.00004 (P ⬍ 0.006) and at 10, 15, 20, and 25 min (P ⬍ 0.00003).
compared with baseline value.
Respiratory rate decreased significantly with time
(F0.05, (1) 5,190 ⫽ 8.7, P ⬍ 0.0000002), although treatment
interaction, treatment ⫻ time, (F0.05 (1) 5,190 ⫽ 5.7, P ⬍ and the interaction, treatment ⫻ time, did not. During
0.00006); time did not affect heart rate. Heart rate at all the MRI, respiratory rate for both treatments de-
times in the dexmedetomidine group was significantly creased at 10 min (P ⬍ 0.009), at 15 min (P ⬍ 0.03), at
less than baseline (P ⬍ 0.00004), whereas heart rate in 20 min (P ⬍ 0.0003), and 25 min (P ⬍ 0.00002) (Fig. 3).
the propofol group did not differ significantly from The slowest respiratory rate detected was 14 breaths
baseline at any time. Heart rate in the dexmedetomi- per minute (n ⫽ 1) in the dexmedetomidine group and
dine group at 5 and 10 min was significantly less than 10 in the propofol group (n ⫽ 1). There were no
that in the propofol group (P ⬍ 0.00007). At no time episodes of apnea. ETCO2 tension did not differ
was the heart rate ⬍60 bpm in either group. The within or between the groups at any time (Fig. 4). The
slowest heart rate in the dexmedetomidine group was maximum ETCO2 tension detected was 57 mm Hg in
64 bpm (n ⫽ 3) and that in the propofol group was 66 the dexmedetomidine group (n ⫽ 1) and 52 mm Hg in
bpm (n ⫽ 1). the propofol group (n ⫽ 1).

Vol. 107, No. 6, December 2008 © 2008 International Anesthesia Research Society 1835
Figure 3. Respiratory rate during magnetic resonance imaging
(MRI) scan. Respiratory rate responses to dexmedetomidine-
midazolam (Dex) and propofol during MRI scans. Time exerted a
significant effect on respiratory rate. In both groups, the respira-
tory rate at 10 min (P ⬍ 0.009), 15 min (P ⬍ 00026), 20 min (P ⬍
0.0003) and 25 min (P ⬍ 0.00002) decreased compared with
baseline. Data are means ⫾ sd.
Figure 4. End-tidal CO2 during magnetic resonance imag-
ing (MRI) scan. End-tidal carbon dioxide tension to
dexmedetomidine-midazolam (Dex) and propofol during MRI
scanning. Carbon dioxide tensions did not differ between or
within the treatments at any time. Data are means ⫾ sd.
There were no episodes of desaturation or airway
obstruction in either group.
The mean heart rates after dexmedetomidine and
propofol administration were similar in PACU (Fig.
5). Heart rate did not change significantly within or
between the two treatments at any time. The slowest
heart rates with dexmedetomidine were 66 (n ⫽ 1), 67
(n ⫽ 1), and 68 bpm (n ⫽ 1) and with propofol were 58
(n ⫽ 1) and 62 bpm (n ⫽ 1).
The mean systolic and diastolic blood pressures
changed significantly after dexmedetomidine and
propofol administration in the PACU (Fig. 6). For
systolic blood pressure, the interaction term, treatment ⫻
time, yielded significant differences (F0.05, (1) 5,190 ⫽
3.54, P ⬍ 0.0044), whereas treatment and time did not.
The minimum systolic blood pressure in the dexme-
detomidine (n ⫽ 1) and propofol groups (n ⫽ 2) was
72 mm Hg. For diastolic blood pressure, treatment
(F0.05, (1) 1.38 ⫽ 10.5, P ⬍ 0.0025) and the interaction,
treatment ⫻ time, (F0.05, (1) 5,190 ⫽ 2.99, P ⬍ 0.013)
yielded significant differences (Fig. 6). Diastolic blood
pressures after dexmedetomidine administration were
1836 Comparison of Dexmedetomidine-Midazolam with Propofol
Figure 5. Heart rate in postanesthesia care unit (PACU).
Heart rate responses to dexmedetomidine (Dex) and propo-
fol in the PACU. The interaction, treatment ⫻ time, yielded
significant differences in heart rate. All error bars for propo-
fol are upright and for dexmedetomidine downward. Data
are means ⫾ sd. *Compared with dexmedetomidine (P ⬍
0.013). †Compared with baseline (P ⬍ 0.005).
Figure 6. Blood pressure in postanesthesia care unit (PACU).
Systolic and diastolic blood pressures after dexmedetomi-
dine (Dex) and propofol anesthesia in PACU. Systolic blood
pressure changed significantly with the interaction, treat-
ment ⫻ time (P ⬍ 0.0044); there was no independent effect
of treatment or time. Diastolic blood pressure changed
significantly with treatment (P ⬍ 0.0025) and the interac-
tion, treatment ⫻ time (P ⬍ 0.013). Data are means ⫾ sd.
*P ⬍ 0.00005; **P ⬍ 0.0013; †P ⬍ 0.02 compared with
dexmedetomidine.
significantly greater than those after propofol at base-
line and 5 min (P ⬍ 0.000048) as well as at 10 and 15
min (P ⬍ 0.0013).
There were no cardiorespiratory complications dur-
ing the MRI or in the PACU with either treatment.
One child who received dexmedetomidine was agi-
tated in the PACU but required no treatment. The
same child was also mildly agitated in the day surgical
unit but was discharged without any delay and with-
out sequelae. No child who received propofol devel-
oped agitation. During follow-up phone calls, all of
the parents expressed satisfaction with their child’s
anesthetic. There were no complaints or complications
reported after discharge.
The cost of dexmedetomidine and propofol was the
number of vials (no splitting of the contents among
children) required to deliver the total infusion dose
plus the dose required to prime the infusion circuit.
Based on these assumptions, the cost to sedate with
ANESTHESIA & ANALGESIA
propofol, $19.50, was $33.00 less than with dexme-
detomidine, $52.40. The pharmacy acquisition cost for
dexmedetomidine-midazolam per child based on the
mean dose of dexmedetomidine infused, 29 ␮g, and
midazolam, 1.9 mg, was $10.80 and $1.86, respectively
or a combined cost of $12.66. The pharmacy acquisi-
tion cost for the mean dose of propofol infused, 202
mg, was $10.10, similar to that of dexmedetomidine.
DISCUSSION
The purpose of this study was to compare the
recovery characteristics and pharmacodynamics of a
dexmedetomidine-midazolam combination with those
of propofol for maintenance of anesthesia in children
undergoing elective MRI. We found that the time to
recovery of full responsiveness, the primary outcome
variable, after dexmedetomidine-midazolam was sig-
nificantly greater than that after propofol by 50% or 15
min (P ⬍ 0.05). This accounted for the excess time in
the PACU after dexmedetomidine-midazolam admin-
istration compared with propofol. Once discharged
from the PACU though, the times to discharge from
the hospital for both treatment groups were similar.
We also noted that 100% of the children in both
treatments completed their MRI scans without inter-
ruption or interventions (i.e., no failures) and without
complications. Heart rate and systolic blood pressure
changes were transient and statistically significant,
but not of sufficient magnitude to warrant interven-
tions. Respiratory responses to both dexmedetomidine-
midazolam and propofol were similar and unchanged
over time.
In previous studies of dexmedetomidine, the failure
rates to complete the MRI, 16% to 20%, were attrib-
uted to movement during the scans.3,5–7 These rates
are similar to those reported with other sedatives for
MRI in children.1,2 However, larger doses of dexme-
detomidine have recently been shown to reduce the
failure rate of MRI scans.9 The combination of stan-
dard doses of dexmedetomidine and a single IV dose
of 0.1 mg/kg midazolam attenuated the rate of move-
ment and failed scans substantively, to 7% in a pre-
liminary report,8 and to 0% in the current study. The
external validity of our 0% incidence of failed scans,
however, must be tempered by the small sample size
in this study. With only 20 children receiving dexme-
detomidine in the current study, the long-run risk of
zero failed scans after dexmedetomidine-midazolam
administration in the entire population of healthy
children is only 85%.11 Nonetheless, these data are
very encouraging and suggest that larger studies
are warranted to confirm the effectiveness of a
dexmedetomidine-midazolam combination for main-
tenance of anesthesia for children undergoing MRI.
At our institution, IV access is usually established
after a sevoflurane and nitrous oxide inhaled induc-
tion. The infusions of dexmedetomidine or propofol
are commenced after discontinuing the inhaled anes-
thetic. This practice precludes determining the precise
Vol. 107, No. 6, December 2008
onset time of the maintenance anesthetics, but does
provide a smooth transition from inhaled induction to
IV maintenance in unpremedicated children who do
not have IV access established preoperatively.
To facilitate ambulatory radiological procedures in
children, the anesthetic prescription should facilitate
rapid recovery. Recovery after administration of
propofol for MRI in children is rapid, complete and
associated with few complications.12–15 However,
there is growing concern regarding the use of propofol
infusions in children. First, federal regulatory agen-
cies have expressed concerns regarding the risk of
developing propofol infusion syndrome in children.*
Second, preliminary evidence suggests that subclinical
metabolic acidosis may occur after even a brief expo-
sure to a propofol infusion.16,17 In an effort to present
an alternative strategy to propofol, it has become
important to investigate the use of alternative anes-
thetics, such as dexmedetomidine, for procedures in
children.
Recent pharmacokinetic data for dexmedetomidine
in children indicated that the elimination half-life after
a single bolus, 2 h,10 although similar to that in adults,
far exceeds that of propofol (approximately 25
min).18,19 Consequently, one might expect that recov-
ery after receiving dexmedetomidine may be delayed
compared with propofol. In the current study, the
times to full recovery after dexmedetomidine and to
discharge from the PACU were statistically signifi-
cantly greater than those after propofol, although the
differences (15 min) were of minor clinical import.
One might be tempted to attribute the delay in recov-
ery after dexmedetomidine in this study to the single
dose of midazolam, although this is unlikely to be the
case as a single dose of midazolam did not delay
recovery after dexmedetomidine in a previous study.8
Both dexmedetomidine-midazolam and propofol fa-
cilitated rapid recovery and discharge after MRI.
The hemodynamic responses to dexmedetomidine
and propofol have been documented.4,7,10 Decreases
in heart rate have been reported over time with
dexmedetomidine in children.4,7,10 Our results are
consistent with those data. However, there were no
instances of bradycardia with either treatment in this
study. Whether the absence of bradycardia is the
result of a type II statistical error (adverse hemody-
namic responses were not the primary outcome vari-
able) or to the brevity of the anesthetic is unclear. A
review of all prospective case reports and studies that
included dexmedetomidine in infants and children
yielded only one instance of bradycardia in 251 chil-
dren.3–5,7,10,20 –22 Because that single instance included
the use of digoxin, which likely interacted with
dexmedetomidine and that it occurred in a very young
infant,21 we presumed that that single instance did not
*www.fda.gov/medwatch/safety/2001/safety01.htm#dipriv
(accessed on November 12, 2007).
© 2008 International Anesthesia Research Society 1837
represent the true incidence of bradycardia that would
otherwise occur in the population of healthy children
without heart disease (and who were not receiving
digoxin). Excusing that single report because of a drug
interaction, the upper 95% confidence interval of the
long-run risk of developing bradycardia in children who
received dexmedetomidine, based on zero episodes in
250 children, is 1.2%.11 In contrast, the incidence of
bradycardia during administration of larger doses of
dexmedetomidine, in some cases combined with pento-
barbital, was 16%.9 Heart rates as slow as 40 bpm were
reported in that study. Bradycardia remains a potentially
serious side effect associated with the use of dexmedeto-
midine in children, the severity of which depends on the
dose of dexmedetomidine.
Respiratory rate and ETCO2 tensions remained
clinically unchanged during the two treatments. This,
together with the absence of any episodes of apnea or
bradypnea, suggests that neither dexmedetomidine
nor propofol depresses respiration excessively in chil-
dren when used in the dose range and manner used in
this study. Inducing anesthesia with sevoflurane and
after that with an initial loading dose and an infusion
of dexmedetomidine or an infusion of propofol sup-
ports adequate respiration in spontaneously breathing
children during MRI.
No side effects or complications were attributed to
either anesthetic in this study. Nausea and vomiting did
not occur after either treatment during the hospital stay
or after discharge. The lack of nausea and vomiting after
receiving propofol is consistent with its antiemetic ac-
tion. Whether dexmedetomidine prevents nausea and
vomiting cannot be established with any certainty given
the small number of children in each group.
Among the limitations of this study, the time to
onset of the anesthesia with dexmedetomidine could
not be evaluated because we induced anesthesia with
an inhaled induction with sevoflurane. We do not
believe that sevoflurane affected the success rate of the
MRI scans as the exposure to sevoflurane was brief
(⬍5 min) and the solubility of sevoflurane is very
small. The advantages of inducing anesthesia by inha-
lation in children include the ability to establish IV
access after the child is anesthetized and that the
residual sevoflurane could bridge the interval be-
tween recovery from the initial loading dose of
dexmedetomidine and start of the infusion.9 In addi-
tion, residual sevoflurane may have bridged the need
for an induction dose of propofol, thereby reducing
the risk of apnea during transition to the propofol
infusion.9 Disadvantages of this technique include the
exclusion of nonanesthesiology practitioners from us-
ing it as they are not qualified to administer inhaled
anesthesia. The external validity of this study is lim-
ited, in part, because of the broad exclusion criteria for
patient recruitment. Children with recent upper respira-
tory infections, asthma and those with behavior difficul-
ties (i.e., cognitively impaired, autism) are common
co-morbidities in children who require anesthesia.
1838 Comparison of Dexmedetomidine-Midazolam with Propofol
Whether the responses to dexmedetomidine-midazolam
and propofol in that population would mirror those
obtained in this study remain to be established.
CONCLUSION
After induction of anesthesia with sevoflurane,
dexmedetomidine supplemented with a single IV dose
of midazolam provided adequate conditions for MRI
without failures in this small study. However, when
compared with propofol, recovery to full responsiveness
after dexmedetomidine was statistically, although not
clinically, prolonged. Heart rate and systolic blood pres-
sure changes were transient and of limited clinical
import at the doses of anesthetic treatments studied. Respi-
ratory indices were similar with the two treatments.
Appendix A
Category Score Description
Activity 2 Able to move four extremities
voluntarily or on command
1 Able to move two extremities
voluntarily or on command
0 Unable to move extremities
voluntarily or on command
Respiratory 2 Able to breath deeply and
cough freely
1 Dyspnea or limited breathing
0 Apneic
Circulation 2 Blood pressure ⫹ 20%
preanesthetic level
1 Blood pressure ⫹ 20%–49%
preanesthetic level
0 Blood pressure ⫹ 50%
preanesthetic level
Consciousness 2 Fully awake
1 Arousable on calling
0 Not responsive
Oxygen saturation 2 Able to maintain saturation of
95% on room air
1 Needs oxygen
supplementation to
maintain saturation of 95%
0 Oxygen saturation ⬍95% on
supplemental oxygen
Pediatric anesthesia recovery scale modified from Aldrete. Maximum score is 10.
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