Comparison of Propofol With Pentobarbital/Midazolam/Fentanyl Sedation for Magnetic Resonance Imaging of the Brain in Children

 

Jay Pershad, Jim Wan and Doralina L. Anghelescu

 

Pediatrics 2007;120;e629-e636;

 

ABSTRACT

OBJECTIVE. Propofol and pentobarbital, alone or combined with other agents, are

frequently used to induce deep sedation in children for MRI. However, we are

unaware of a previous comparison of these 2 agents as part of a randomized,

controlled trial. We compared the recovery time of children after deep sedation

with single-agent propofol with a pentobarbital-based regimen for MRI and considered

additional variables of safety and efficacy.

METHODS. This prospective, randomized trial at a tertiary children’s hospital enrolled

60 patients 1 to 17 years old who required intravenous sedation for elective cranial

MRI. Patients were assigned randomly to receive a loading dose of propofol

followed by continuous intravenous infusion of propofol or to receive sequential

doses of midazolam, pentobarbital, and fentanyl until a modified Ramsay score of

_4 was attained. A nurse who was blind to group assignment assessed discharge

readiness (Aldrete score _ 8) and administered a follow-up questionnaire. We

compared recovery time, time to induction of sedation, total sedation time, quality

of imaging, number of repeat-image sequences, adverse events, caregiver satisfaction,

and time to return to presedation functional status.

RESULTS. The groups were similar in age, gender, race, American Society of Anesthesiology

physical status class, and frequency of cognitive impairment. No sedation

failure or significant adverse events were observed. Propofol offered significantly

shorter sedation induction time, recovery time, total sedation time, and

time to return to baseline functional status. Caregiver satisfaction scores were also

significantly higher in the patients in the propofol group.

CONCLUSIONS. Propofol permits faster onset and recovery than, and comparable efficacy

to, a pentobarbital/midazolam/fentanyl regimen for sedation of children for

OVER THE PAST decade, propofol-based sedation has

been used increasingly for procedures outside of

the traditional operating room setting.1–13 However,

there are few data from prospective, randomized, controlled

trials evaluating the use of single-agent propofol

to provide deep sedation of pediatric patients for MRI.14

The use of propofol with inhalational induction agents

or as the sole agent (total intravenous anesthesia) in

spontaneously breathing patients undergoing MRI has

been retrospectively studied.15–17 Pentobarbital, a shortacting

barbiturate, has a proven record of safety and

efficacy when used with midazolam or fentanyl for sedation

during pediatric diagnostic imaging.14,18–22 The

overall incidence of inadequate or failed sedation during

imaging procedures in children varies widely from 1% to

16%.21,23–25 We are not aware of any prospective, randomized

clinical trial comparing deep sedation with

propofol versus pentobarbital for pediatric MRI.

Propofol is an ultra–short-acting, nonbarbiturate,

nonbenzodiazepine sedative-hypnotic agent with an

arm-brain circulation time of 90 to 100 seconds. Sedation

is quickly induced by rapid distribution of the highly

lipophilic drug into the vessel-rich organs, including the

brain. Its rapid redistribution and clearance account for

its brief sedation effect and the need for repeated boluses

or continuous infusion to maintain the level of anesthesia

and sedation.26–28 Propofol induces dose-dependant

central nervous system depression. At the recommended

dose for induction in children 3 to 12 years old (2.5–3

mg/kg), a 21% incidence of transient apnea has been

reported.29 However, sedation regimens during imaging

procedures require lower doses and are associated with a

lower overall incidence of hypoxia or respiratory depression,

ranging from 0% to 10%.14,15,30 At subhypnotic

doses, propofol induces sedation, amnesia, and antiemetic

activity.31 The rapid titrability, brief pharmacologic

effect, and maintenance of spontaneous ventilation

make intravenous propofol an ideal agent for deep sedation

during pediatric MRI.

At our institution, pediatric patients are sedated for

diagnostic imaging with intravenous propofol or pentobarbital/

midazolam/fentanyl regimens. Pentobarbitalbased

regimens are usually used for MRI, whereas

propofol is preferred for the shorter-duration computed

tomography studies. All sedation in the radiology suite at

our institution is performed by a radiology sedation service

that is staffed and supervised exclusively by boardcertified

pediatric emergency physicians.32

The primary objective of this study was to compare

the recovery time (RT) after sedation with propofol versus

a pentobarbital-based regimen for cranial MRI studies

in children. Secondary outcome measures were induction

time (IT), total sedation time (TST), time to

return to baseline (TTB; presedation) functional status,

number of repeat imaging sequences, quality of images

obtained, caregiver satisfaction with sedation, and frequency

of immediate and delayed adverse events.

MATERIALS AND METHODS

Patients

Our study was a randomized, prospective, partially

blinded comparative trial of patients 1 to 17 years of age

who were scheduled for elective cranial MRI and who

required sedation. The study was conducted in the department

of radiology at an urban, tertiary-level pediatric

facility.

We excluded patients whose American Society of Anesthesiology

(ASA) physical status class was _3, those

requiring diagnostic imaging for trauma, and those for

whom any of the agents investigated were contraindicated.

A convenience sample of eligible patients was

given the opportunity to participate in this study, based

on the availability of the principal investigator. Our institutional

review board approved the study. Informed

consent was obtained from patients, parents, or guardians,

as appropriate, and Health Insurance Portability

and Accountability Act regulations were followed.

Sedation Protocol

Patients were assigned randomly to 1 of 2 groups by

using the method of randomly permuted blocks of size

10.33 The random allocation sequence was generated by

a biostatistician (Dr Wan) and provided in sealed numbered

envelopes. The sequence was concealed from the

sedating physician, until intervention was assigned. The

principal investigator enrolled participants and assigned

participants to 1 of 2 groups. Parents were present during

induction and recovery. Patients in the pentobarbital

group received midazolam, pentobarbital, and fentanyl

in sequential doses until the desired level of sedation was

achieved. Midazolam (0.1 mg/kg) was administered intravenously

up to a maximum dose of 5 mg, and pentobarbital

(2 mg/kg) was then given intravenously. Additional

doses of 1 mg/kg pentobarbital were then

administered until the desired level of sedation was

achieved, up to a maximum of 6 mg/kg. The cumulative

dose of pentobarbital was limited to 200 mg. If adequate

sedation was not achieved, fentanyl (1 _g/kg) was administered

intravenously, up to a maximum dose of 100_g.

Patients in the propofol group received an initial dose

of 0.5 mg/kg lidocaine mixed in the same syringe, to

decrease the pain associated with injection of intravenous

propofol. A loading dose of intravenous propofol

was administered in 1 mg/kg aliquots, each administered

over a period of 60 seconds, until loss of eyelid reflex was

observed. Supplemental doses of 0.5 mg/kg were administered

until the desired level of sedation was attained. A

maintenance infusion was initiated at 6 mg/kg per hour.

If the patient moved before or during the scan, addtional 0.5 mg/kg

propofol boluses were administered

and the infusion rate was incrementally increased by

10%, up to a maximum of 15 mg/kg per hour.

In accordance with our institution’s sedation policy,

all patients received continuous heart rate, pulse oximetry,

and nasal capnography monitoring, and respiratory

rate and blood pressure were assessed every 5 minutes.

Patients received preoxygenation with blow-by oxygen

via facemask to maintain oxygen saturation of _95%. A

registered nurse with specialized training in sedation

monitored the patient before, during, and after the procedure,

until the patient was ready for discharge. Because

MRI necessitated remote monitoring, close vigilance

was provided throughout the scanning procedure.

An attending pediatric emergency medicine physician

credentialed by our institution to provide procedural

sedation was present at all times to monitor the patient

and provide immediate intervention as needed.

While sedated, patients were closely observed for

signs of upper-airway obstruction, such as snoring, stridor,

decreasing hemoglobin oxygen saturation, loss of

exhaled carbon dioxide, or progressive hypercapnia, as

detected by the end-tidal capnographic wave form. Airway

rescue measures, including airway manipulation,

suction, and insertion of a nasal airway, were used sequentially

as needed. If the patient’s ventilatory status or

oxygenation did not improve, assisted ventilation was

initiated, and the procedure was aborted according to

the decision of the principal investigator.

After completion of the scans, a registered nurse not

associated with the study who was blind to the type of

medication received evaluated discharge readiness.

Standard discharge criteria (Aldrete score)34 were used.

Recovery was graded at 5-minute intervals. Patients met

discharge criteria when they reached an Aldrete score of

_8 or reached a score within 2 points of their presedation

score.

Assessment of Sedation Efficacy and Adverse Events

Sedation was considered efficacious if the patient lost

consciousness, underwent the procedure without movement,

and maintained spontaneous, adequate respiratory

effort. We used the Ramsay scale35 to measure the

level of sedation. Our goal was to achieve a level of _4

on the Ramsay scale.

Failure to achieve adequate sedation (ie, patient

awakened or moved, interfering with completion of the

MRI) despite maximal doses was considered a failure of

the sedation regimen, and the procedure was rescheduled.

Sedation was also considered to have failed if the

procedure was aborted because of a significant adverse

event.31

Possible “major” adverse events during sedation include

hypotension, hypoxemia, emesis, agitation, apnea,

respiratory depression, laryngospasm, and bradycardia.

Hypotension was defined as systolic blood pressure _70

plus twice the patient’s age in years, associated with

altered peripheral perfusion (delayed capillary refill

time). Hypotension was treated with a 20 mL/kg intravenous

bolus of crystalloids and a 10% reduction in the

propofol infusion rate. Hypoxemia was defined as a

pulse oximetry value _90% and prompted immediate

intervention. Emesis was defined as presence of stomach

contents in the pharynx, at any time after administration

of the sedation drugs. Agitation was defined as uncontrollable

distress or inconsolability despite parental presence.

Apnea was defined as cessation of respiration for

_20 seconds. Bradycardia was defined as a heart rate

below 50 beats per minute. Laryngospasm was identified

by the occurrence of airway obstruction or stridor with a

decline in pulse oximetry readings that was not relieved

by airway manipulation, suction and insertion of oral or

nasal airway, and required assisted ventilation or neuromuscular

blockade to achieve adequate ventilation.

“Immediate” adverse events were those that occurred

during sedation or before discharge. Delayed adverse

events were adverse effects that occurred after discharge,

as noted during the follow-up satisfaction survey. We

did not record “minor” adverse events that were selflimited

and typically associated with administration of

parenteral sedatives. These include pain or discomfort

during injection (usually observed with propofol), transient

myoclonus (usually noted with propofol), and facial

pruritis with fentanyl administration.

Assessment of Other Variables

The following data were collected for each patient: age,

gender, indication for diagnostic study, presence or absence

of cognitive impairment, sedation IT, scan time,

RT, TST, sedation efficacy or failure, frequency and timing

of adverse effects, imaging efficacy (quality of MRI

scan), and satisfaction of the caregiver with procedural

sedation. IT was defined as the time from initial administration

of the drug to achievement of sedation adequate

to perform the MRI. Scan time was defined as the

length of time between the patient’s placement on the

MRI table and completion of the imaging sequences. RT

was defined as the time that elapsed between scan completion

and meeting of discharge criteria. TST was defined

as the time between administration of the first dose

of drug and patient readiness for discharge. Quality of

images was rated on a 5-point Likert scale based on the

presence or absence of motion artifact, by an independent

radiologist, blind to the identity of the patient and

the sedation regimen. Scans were assigned quality ratings

of 1 (poor) through 5 (excellent). An independent

nurse blind to the sedation regimen made a follow-up

telephone call 24 to 48 hours after discharge to determine

the time at which the child returned to the baseline

level of function and whether delayed adverse events

were observed. During this telephone call, parents or

caregivers were asked to assign a score on a 5-point

Likert scale (5 being extremely satisfied and 1 being not

at all satisfied) assessing their satisfaction with the overall

sedation process.

Data Analysis

The primary outcome measure was RT. Secondary outcome

measures were IT, TST, quality of imaging, number

of repeat image sequences, frequency of immediate

and delayed adverse events, sedation success or failure,

caregiver satisfaction, and caregiver report of TTB. According

to Kienstra et al21 and Mason et al,20 the standard

deviation for the RT in the pentobarbital group was 32

minutes. From Hasan et al,30 the standard deviation for

the RT in the propofol group was 21 minutes. Assuming

a probability (P) of type I error of .05 and a power of

80%, the required sample size to detect a 20 minute

difference in RT was 30 subjects for each group. The

2-sample t test was used to test the difference in RT

between the 2 groups. For secondary outcomes, categorical

variables with small sample size, such as the frequency

of adverse events and sedation failures, were

compared between the 2 groups using Fisher’s exact test.

The Mantel 1-degree-of-freedom _2 test was used to

compare the Likert-scale variables. All analyses were

performed by using by SAS 9.1.3 statistical software

(SAS Institute Inc Cary, NC).

RESULTS

Sixty patients were assigned randomly to 1 of 2 groups

(Fig 1). The groups were similar in age, gender, race,

American Society of Anesthesiology physical status class,

and proportion of patients with cognitive impairment

(Table 1). The mean total dose of each drug is listed in

Table 2. No sedation failures or significant adverse

events were recorded. RT, sedation IT, TST, TTB functional

status, and caregiver satisfaction scores significantly

favored propofol over pentobarbital. No significant

differences were observed between the groups in

imaging quality or in the number of repeat images (Tables

3 and 4).

The adverse events that occurred were relatively minor.

We observed 11 immediate adverse events, 8 in the

propofol group, and 3 in the pentobarbital group. The

propofol-related immediate adverse events were transient

decreased blood pressure without signs of compromised

peripheral perfusion in 4 cases and respiratory

depression in 4 cases. The 4 cases of respiratory depression

occurred during induction. Two children developed

partial airway obstruction without desaturation, which

corrected with airway manipulation including chin lift

maneuver. Two patients experienced a decrease of oxygen

saturation into the 80s and 70s, respectively, that

lasted for _1 minute. One subject responded to airway

manipulation, readjustment of oxygen mask, and suction.

The other patient required brief (_60 seconds)

assisted ventilation with a bag mask and insertion of

nasal airway, after which adequate spontaneous ventilation

was observed. The nasal airway was maintained

for the duration of the scan. None of these cases received

tracheal intubation or escalation of care to warrant

aborting the procedure. The remainder of the scanning

procedures in these patients was uneventful. Pentobarbital

sedation was associated with 3 immediate adverse

events: 1 episode of transient decreased blood pressure

and 2 cases of emergence agitation. Seven delayed adverse

events were noted, all in the pentobarbital group.

These comprised 6 cases of prolonged sedation and 1

case of delayed agitation.

DISCUSSION

Our results demonstrate that propofol provided significantly

shorter recovery, sedation induction, TSTs, TTB

functional status, and better caregiver satisfaction scores

compared with a pentobarbital/midazolam/fentanyl regimen.

The differences in mean induction, recovery and

TSTs were 8, 17, and 20 minutes, respectively, in favor of

propofol. When extrapolated to multiple sedations, we

believe that these differences have clinical significance

and pharmacoeconomic impact by optimizing the use of

the MRI scanner. In a previous prospective trial, Bloomfield

et al14 noted propofol to be associated with a shorter

time to arousal and time to discharge then pentobarbital.

Our trial differed from theirs in that all participants were

assigned randomly to the treatment groups. In addition,

the nurse responsible for monitoring recovery and discharge

and for conducting the telephone follow-up in

our study was blind to the type of agent received. Although

subjects in both studies were preoxygenated,

end-tidal carbon dioxide monitoring was not part of the

protocol used by Bloomfield et al. In addition, pentobarbital

was used as a single agent in doses higher than

those used in our study (maximum total dose: 7.5 vs 6

mg/kg), and the details of pentobarbital dosing and the

incidence of adverse events were not described.

Our study has several limitations. This was a convenience

sample of eligible patients based on the availability

of the principal investigator. The physician investigator

responsible for administration of propofol and

supervision of procedural sedation in both groups was

not blind to the agent received. Although this factor may

have introduced some bias, the presence of the investigator

ensured strict adherence to the sedation protocol.

The fact that we restricted enrollment to patients scheduled

exclusively for cranial MRI may limit extrapolation

of our results to MRI studies of other body parts. However,

this restriction was designed to reduce variation in

scan time among the study subjects.

It could be argued that the use of midazolam as an

adjunct to pentobarbital may have prolonged the RT.20

Our institution currently leaves the choice of sedative

agent for MRI to the discretion of the practicing physician.

For more than a decade, the practice in our radiology

department has been to premedicate with midazolam.

Because of the success of this experience,

midazolam sedation was included in our trial in an attempt

to reduce the total dose of pentobarbital, an intermediate-

acting barbiturate.

The maximum allowed infusion rate of 15 mg/kg per

hour of propofol in our protocol was higher than the 9 to

10 mg/kg per hour cited in the literature, although our

starting rate of 6 mg/kg per hour is a standard approach.

14,15 Also, subsequent boluses for patient movement

during the scanning procedure were administered

in 0.5 mg/kg aliquots, with a 10% incremental adjustment

in drip rate. This was lower than the 1 to 2 mg/kg

doses of propofol for subsequent boluses used in previous

studies; therefore, our increments were more conservative.

14,15

The cumulative maximum dose of pentobarbital in

our study was 6 mg/kg (200 mg). This was consistent

with the dose used in 2 previous studies22,24 and higher

than the 5 mg/kg used in 2 other trials.21,36 In contrast, 1

previous study used a maximum dose of 6.5 mg/kg of

pentobarbital.37 Furthermore, the method of administration

of pentobarbital in our study was an initial bolus of

2 mg/kg followed by additional aliquots of 1 mg/kg until

adequate sedation was achieved. Previous studies used 2

mg/kg boluses for additional dosing.22,24 Others used a

smaller dose for subsequent boluses ranging from 1 to 2

mg/kg aliquots of pentobarbital.20,21 It is possible that the

relatively smaller incremental doses of pentobarbital

used in our study may have led to a bias in favor of the

propofol group.

Overall, the difference in frequency of adverse events

between the 2 groups in our study was not statistically

significant. However, given the small numbers, we were

unable to exclude the possibility of a type II error. Adverse

events of respiratory depression during induction

and hypotension, observed with propofol administration

in our study were similar to those previously reported.

14,15,29 We noted transient respiratory depression in 4

(13.3%) of 30 patients in the propofol group versus 0

(0%) of 30 in the pentobarbital group. This difference

was not statistically significant (P _ .11). The relatively

higher incidence of respiratory adverse events in the

propofol group highlights the importance of having a

physician trained in advanced airway management immediately

available. The pentobarbital regimen was associated

with prolonged sedation in 6 patients (20%)

and emergence agitation in 2 patients (6.7%). One subject

experienced delayed agitation after discharge from

the hospital. The incidence of emergence agitation noted

in our study is consistent with the incidence reported in

the literature. The incidence of paradoxical hyperactivity

for all drug regimens, including pentobarbital, as reported

by Rubin et al38 was 1.8%. Emergence agitation

noted with the use of pentobarbital alone varies greatly

between studies: 0% in Mason et al19 in 2004, 1.2% in

Karian et al,23 1.5% in Mason et al,20 7% in Greenberg et

al,24 12% in Kienstra et al,21 and 14% by Malviya et al.36

Furthermore, the incidence of paradoxical hyperactivity

with pentobarbital was comparable when considered

with and without adjunctive midazolam (1.6% vs

1.5%).20 The report of prolonged sedation in our study,

was based on subjective responses obtained from the

parents or caregivers, on the 24- to 48-hour postdischarge

follow-up survey. This may have led to some bias

against the subjects assigned to the pentobarbital medication

regimen.

CONCLUSIONS

Our results highlight the favorable induction and recovery

profile of propofol sedation, while showing comparable

efficacy to a pentobarbital-based regimen in pediatric

patients undergoing cranial MRI. Although

absolute reduction in induction and RT were relatively

small, when extrapolated to multiple encounters for a

busy sedation service, the time savings and potential

economic impact may be significant.

REFERENCES

1. Bassett KE, Anderson JL, Pribble CG, Guenther E. Propofol for

procedural sedation in children in the emergency department.

Ann Emerg Med. 2003;42:773–782

2. Godambe SA, Elliot V, Matheny D, Pershad J. Comparison of

propofol/fentanyl versus ketamine/midazolam for brief orthopedic

procedural sedation in a pediatric emergency department.

Pediatrics. 2003;112:116–123

3. Guenther E, Pribble CG, Junkins EP, Jr, Kadish HA, Bassett KE,

Nelson DS. Propofol sedation by emergency physicians for

elective pediatric outpatient procedures. Ann Emerg Med. 2003;

42:783–791

4. Havel CJ, Jr, Strait RT, Hennes H. A clinical trial of propofol vs

midazolam for procedural sedation in a pediatric emergency

department. Acad Emerg Med. 1999;6:989–997

5. Hertzog JH, Dalton HJ, Anderson BD, Shad AT, Gootenberg JE,

Hauser GJ. Prospective evaluation of propofol anesthesia in the

pediatric intensive care unit for elective oncology procedures in

ambulatory and hospitalized children. Pediatrics. 2000;106:

742–747

6. Mace SE, Barata IA, Cravero JP, et al. Clinical policy: evidencebased

approach to pharmacologic agents used in pediatric sedation

and analgesia in the emergency department. J Pediatr

Surg. 2004;39:1472–1484

7. Skokan EG, Pribble C, Bassett KE, Nelson DS. Use of propofol

sedation in a pediatric emergency department: a prospective

study. Clin Pediatr (Phila). 2001;40:663–671

8. Elitsur Y, Blankenship P, Lawrence Z. Propofol sedation for

endoscopic procedures in children. Endoscopy. 2000;32:

788–791

9. Taylor DM, O’Brien D, Ritchie P, Pasco J, Cameron PA. Propofol

versus midazolam/fentanyl for reduction of anterior shoulder

dislocation. Acad Emerg Med. 2005;12:13–19

10. Pershad J, Godambe SA. Propofol for procedural sedation in

the pediatric emergency department. J Emerg Med. Jul 2004;

27:11–14

11. Herman M, Godambe S, Pershad J. PEM physicians can safely

and effectively administer propofol. Pediatr Emerg Care. 2004;

20:648–649

12. Barbi E, Gerarduzzi T, Marchetti F, et al. Deep sedation with

propofol by nonanesthesiologists: a prospective pediatric experience.

Arch Pediatr Adolesc Med. 2003;157:1097–1103

13. Reeves ST, Havidich JE, Tobin DP. Conscious sedation of children

with propofol is anything but conscious. Pediatrics. Jul

2004;114(1). Available at: www.pediatrics.org/cgi/content/

full/114/1/e74

14. Bloomfield EL, Masaryk TJ, Caplin A, et al. Intravenous sedation

for MR imaging of the brain and spine in children: pentobarbital

versus propofol. Radiology. 1993;186:93–97

15. Frankville DD, Spear RM, Dyck JB. The dose of propofol required

to prevent children from moving during magnetic resonance

imaging. Anesthesiology. 1993;79:953–958

16. Keengwe IN, Hegde S, Dearlove O, Wilson B, Yates RW, Sharples

A. Structured sedation programme for magnetic resonance

imaging examination in children. Anaesthesia. 1999;54:

1069–1072

17. Burke A, Pollock J. Propofol and paediatric MRI. Anaesthesia.

Jul 1994;49:647

18. Mason KP, Sanborn P, Zurakowski D, et al. Superiority of

pentobarbital versus chloral hydrate for sedation in infants

during imaging. Radiology. 2004;230:537–542

19. Mason KP, Zurakowski D, Connor L, et al. Infant sedation for

MR imaging and CT: oral versus intravenous pentobarbital.

Radiology. 2004;233:723–728

20. Mason KP, Zurakowski D, Karian VE, Connor L, Fontaine PJ,

Burrows PE. Sedatives used in pediatric imaging: comparison

of IV pentobarbital with IV pentobarbital with midazolam

added. AJR Am J Roentgenol. 2001;177:427–430

21. Kienstra AJ, Ward MA, Sasan F, Hunter J, Morriss MC, Macias

CG. Etomidate versus pentobarbital for sedation of children for

head and neck CT imaging. Pediatr Emerg Care. 2004;20:

499–506

22. Connor L, Burrows PE, Zurakowski D, Bucci K, Gagnon DA,

Mason KP. Effects of IV pentobarbital with and without fentanyl

on end-tidal carbon dioxide levels during deep sedation of

pediatric patients undergoing MRI. AJR Am J Roentgenol. 2003;

181:1691–1694

23. Karian VE, Burrows PE, Zurakowski D, Connor L, Mason KP.

Sedation for pediatric radiological procedures: analysis of potential

causes of sedation failure and paradoxical reactions.

Pediatr Radiol. 1999;29:869–873

24. Greenberg SB, Adams RC, Aspinall CL. Initial experience with

intravenous pentobarbital sedation for children undergoing

MRI at a tertiary care pediatric hospital: the learning curve.

Pediatr Radiol. 2000;30:689–691

25. Malviya S, Voepel-Lewis T, Eldevik OP, Rockwell DT, Wong

JH, Tait AR. Sedation and general anaesthesia in children

undergoing MRI and CT: adverse events and outcomes. Br J

Anaesth. 2000;84:743–748

26. Smith I, White PF, Nathanson M, Gouldson R. Propofol. An

update on its clinical use. Anesthesiology. 1994;81:1005–1043

27. Fulton B, Sorkin EM. Propofol. An overview of its pharmacology

and a review of its clinical efficacy in intensive care sedation.

Drugs. 1995;50:636–657

28. Bryson HM, Fulton BR, Faulds D. Propofol: an update of its use

in anaesthesia and conscious sedation. Drugs. 1995;50:513–559

29. Hannallah RS, Baker SB, Casey W, McGill WA, Broadman LM,

Norden JM. Propofol: effective dose and induction characteristics

in unpremedicated children. Anesthesiology. 1991;74:

217–219

30. Hasan RA, Shayevitz JR, Patel V. Deep sedation with propofol

for children undergoing ambulatory magnetic resonance imaging

of the brain: experience from a pediatric intensive care

unit. Pediatr Crit Care Med. 2003;4:454–458

31. Reves JG GP, Lubarsky DA. Nonbarbiturate intravenous anesthetics.

In: Miller R, ed. Anesthesia. 5th ed. Philadelphia, PA:

Churchill Livingstone; 2000:251–254

32. Pershad J, Gilmore B. Successful implementation of a radiology

sedation service staffed exclusively by pediatric emergency

physicians. Pediatrics. 2006;117(3). Available at: www.

pediatrics.org/cgi/content/full/117/3/413

33. Zelen M. The randomization and stratification of patients to

clinical trials. J Chronic Dis. 1974;27:365–375

34. Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth

Analg. 1970;49:924–934

35. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled

sedation with alphaxalone-alphadolone. Br Med J. 1974;

2(5920):656–659

36. Malviya S, Voepel-Lewis T, Tait AR, et al. Pentobarbital vs chloral

hydrate for sedation of children undergoing MRI: efficacy and

recovery characteristics. Paediatr Anaesth. Jul 2004;14:589–595

37. Strain JD, Campbell JB, Harvey LA, Foley LC. IV Nembutal:

safe sedation for children undergoing CT. AJR Am J Roentgenol.

1988;151:975–979

38. Rubin JT, Towbin RB, Bartko M, Baskin KM, Cahill AM, Kaye

RD. Oral and intravenous caffeine for treatment of children

with post-sedation paradoxical hyperactivity. Pediatr Radiol.

2004;34:980–984