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Indian Pediatr 2013;50: 233-235 |
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Oral Chloral Hydrate vs. Intranasal
Midazolam for Sedation During Computerized Tomography
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*Razieh Fallah,
#Mohammad
Hosein Ataee Nakhaei, †Shekofah
Behdad, $Reza Nafisi
Moghaddam and **Ali Shamszadeh
From the *Department of Pediatrics, Research Center
of Pain and #Department of Pediatrics, Shahid Sadoughi University of
Medical Sciences, Yazd, Iran; †Anesthesia and Intensive Care and
**Department of Computer Engineering, Engineering and Basic Sciences
Faculty, Islamic Azad University, Sari Branch, Sari, Iran.
Correspondence to: Mohammad Hosein Ataee Nakhaei,
Shahid Sadoughi Hospital, Ave - Sina Blvd,
Shahid Ghandi Blvd, Yazd, IR Iran.
Email: [email protected]
Received: February 06, 2012;
Initial review: March 05, 2012:
Accepted: May 29, 2012.
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We conducted this single blind randomized clinical trial to compare
the efficacy and safety of oral chloral hydrate and intranasal
midazolam for induction of sedation for computerized tomography scan
of brain in children. Participants aged 1-10 years (n=60)
were randomized to receive 100 mg/kg chloral hydrate orally with
intra nasal normal saline OR intranasal midazolam 0.2 mg/kg with
oral normal saline. Adequate sedation (Ramsay sedation score of
four) was obtained and CT scan completed successfully in 76.7% of
chloral hydrate group and in 40% of midazolam group (P=0.004).
No significant difference was seen for side effects frequency
between the two drugs (10% in chloral hydrate , 3.3% in midazolam
group; P= 0.34). We conclude that oral chloral hydrate can be
considered as a safe and effective drug for sedation in children
undergoing CT scan of brain.
Key words: Chloral hydrate, Computerized tomography,
Intranasal midazolam.
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Good quality CT scan needs sufficient immobility of
children during the procedure and sedation and anesthesia is often used
for this purpose [1]. Different sedation regimens are used for sedation.
Chloral hydrate is a non-opiate, non-benzodiazepines sedative-hypnotic
drug which has been used for pediatric sedation induction [2]. But ,
there are concerns about its long duration of action, obstruction of
airway, respiratory depression, oxygen desaturation and its potential
for carcinogenicity [3].
Midazolam is a water-soluble benzodiazepine which can
be used by different routes (oral, intravenous, intramuscular, rectal,
sublingual, aerosolized buccal and intranasal) for pediatric sedation
induction [4-7]. Intranasal midazolam is a nonparenteral route that does
not cause pain of injection and is a useful and effective alternative to
oral route in children [6]. We conducted this study to compare the
efficacy of oral chloral hydrate and intranasal midazolam in children
for sedation during an elective brain CT scan.
Methods
We followed a randomized single-blind study design.
Thirty children were required in clinical, open-label, parallel group
study conducted on the each group to detect a 20% difference in efficacy
between the two drugs with type one error (alpha) of 0.05 and 80% power.
Eligible participants included children aged 1-10
years , referred to CT center for elective brain CT scan. These children
were in American Society of Anesthesiology (ASA) class 1 (a normally
healthy patient) or 2 (a patient with mild systemic disease eg, mild
asthma, controlled diabetes mellitus) [8]. Exclusion criteria consisted
of presence of gastritis or any other serious systemic disease, severe
systemic reaction, head injury and receiving a sedative hypnotic agent
within the past 48 hours.
The trial used computer generated equal randomization
and allocation ratio was 1:1 for the two groups. Randomisation and
blinding was done by an investigator with no clinical involvement in the
trial. Data collectors, outcome assessors and data analysts were all
kept blinded to the allocation.
The children were randomized to receive either single
dose of 100 mg/kg oral chloral hydrate with one milliliter of intranasal
normal saline as placebo (Group I) or 0.2 mg/kg intranasal midazolam
with oral normal saline as placebo (Group II). Ramsay sedation scale was
used for assessment of sedation level [9]. A score of four was
considered as adequately sedated. The primary outcomes were efficacy in
adequate sedation and completing of CT scan.
Secondary outcomes included clinical side effects ,
serious adverse events (hypotension, hypoxia and cyanosis, severe
vomiting, intractable irritability and agitation , apnea, laryngospasm,
and bradycardia), time from administration of the drug to adequate
sedation, caregiver’s satisfaction on a likert scale (1-5), and total
stay time in CT center. Respiratory depression requiring assisted
ventilation, oxygen saturation of less than 90%, or a 25% or greater
decrease in pre sedation mean arterial blood pressure were considered as
serious side effects.
Failure to achieve adequate sedation (patient
awakened or moved, interfered with completion of CT scan, inadequate
sedation and need to administration of other sedative drug) and
procedure abortion due to serious adverse events, were considered as
failure of sedation regimen. The developmental status of the patient was
assessed by a pediatric neurologist based on Denver II Developmental
screening test.
The data were analyzed using SPSS 15 statistical
software. Chi-square test or Fisher exact test was used for data
analysis of qualitative variables and mean values were compared using
independent t-test. Differences were considered significant at P<
0.05. Informed consent was taken from patients ,
parents and the study has been approved by the Ethics Committee of
Shahid Sadoughi University of Medical Sciences, Yazd, Iran. This study
is registered in Iranian clinical trials with registration number
IRCT201107082639N4.
Results
Sixteen children (24 girls) with mean age of 2.75±
2.3 years were evaluated (Table I). Ramsay sedation score
of four was achieved in 12 children (40%) in intranasal midazolam and in
28 children (93.3%) in CH groups, respectively (P<0.001).
Brain CT scan was successfully completed in 40 % of Group II (95% CI.
0.23- 0.57) and in 76.7% of Group I (95% CI: of 0.62- 0.92) (P<0.05).
TABLE I Demographic Characteristics of Children in Study Subjects
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Chloral hydrate |
Midazolam
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P value |
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(n = 30) |
(n = 30) |
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Female
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11 |
13 |
0.59 |
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Delayed development |
18 |
14 |
0.30 |
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Age (y)*
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2.68 ± 1.62 |
2.81 ± 1.63 |
0.83 |
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Weight (kg*) |
12.08 ± 5.7 |
11.66 ± 4.34 |
0.29 |
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* (mean ±SD); #midazolam by
intranasal route. |
Table II shows comparison between the outcome
in the two groups. Mild side effects such as vomiting occurred in 3
(10%) children in Group I and transient agitation in 3.3% of Group II.
No serious adverse events were seen in any of the study subject.
TABLE II Comparison of Outcome Variables (Mean ±SD) in the Two groups
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Characteristics |
Chloral hydrate
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Intranasal Midazolam
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P value |
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Acquired Ramsay sedation
score
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4.53 ± 1.19 |
2.93 ± 2.21 |
0.0001 |
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Time from drug administration
to adequately sedated (min)
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23.75 ± 15.09 |
10.92 ± 4.23 |
0.02 |
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Time after taking the drug
to completing CT scan (min)
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35.01 ± 12.6 |
35.14 ± 14.05 |
0.929 |
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Caregiver’s satisfaction scale |
4.1 ± 1.28 |
2.4 ± 1.62 |
0.001 |
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Total stay time in
CT center (min) |
56.06 ± 23.05 |
50.8 ± 15.3 |
0.56 |
Discussion
Oral chloral hydrate was more effective than
intranasal midazolm in sedation induction in uncooperative children
undergoing CT scan. Dallman, et al. [7] in an earlier study,
could not demonstrate any significant differences in behavior
assessments (crying, movement, sleep) of 0.2 mg/kg intranasal midazolam
and 62.5 mg/kg chloral hydrate with 12.5 mg promethazine. Layangool,
et al. [10] demonstrated a comparable success rate of 99.2% for
echocardiography with 50 mg/kg chloral hydrate or 0.3 mg/kg of
sublingual midazolam. Our results are in agreement with another study
with oral midazolam [11].
However, Schulte-Uentrop concluded that in sedation induction for MRI,
chloral hydrate, pentobarbital and midazolam are not proper and
dexmedetomidine may be a more effective drug in sedation induction in
children without cardiac risk [12].
The lower efficacy of midazolam in sedation induction
of children in present study may be related to the low dose of 0.2
mg/kg. Effectiveness of intranasal midazolam in dose of 0.5 mg/kg in
conscious sedation of Iranian children was reported in another study
[13]. Therefore, further boluses of intranasal midazolam, upto its
maximum dose and its combination with other sedative drugs may be more
effective in sedation of Iranian children and its usage as a
premedication before anesthesia may be logical.
The limitations of this study were its small sample
size and short duration of follow up. Therefore, it is suggested that
further studies be conducted with larger sample sizes, longer follow up
periods and different dosages of the drugs.
Contributors: RF: Writing the manuscript; MHAN:
Resident of research; SB:Editing the manuscript; NM: Gathering the data
and AS: Data analysis.
Funding: Research Deputy of Shahid Sadoughi
University of Medical Sciences, Yazd, Iran.
Competing interests: None stated.
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What This Study Adds?
• Chloral hydrate is more effective than intranasal midazolam
in sedation induction of uncooperative children undergoing CT
scan.
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References
1. Wachtel RE, Dexter F, Dow AJ. Growth rates in
pediatric diagnostic imaging and sedation. Anesth Analg.
2009;108:1616-21.
2. Avlonitou E, Balatsouras DG, Margaritis E,
Giannakopoulos P, Douniadakis D, Tsakanikos M. Use of chloral
hydrate as a sedative for auditory brainstem response testing in a
pediatric population. Int J Pediatr Otorhinolaryngol. 2011;75:760-3.
3. Haselkorn T, Whittemore AS, Udaltsova N,
Friedman GD. Short-term chloral hydrate administration and cancer in
humans. Drug Saf. 2006;29:67-77.
4. Chiaretti A, Barone G, Rigante D, Ruggiero A,
Pierri F, Barbi E, et al. Intranasal lidocaine and midazolam
for procedural sedation in children. Arch Dis Child. 2011;96:160-3.
5. Singh R, Kumar N, Vajifdar H. Midazolam as a
sole sedative for computed tomography imaging in pediatric patients.
Paediatr Anaesth. 2009;19:899-904.
6. Klein EJ, Brown JC, Kobayashi A, Osincup D,
Seidel K. A randomized clinical trial comparing oral, aerosolized
intranasal, and aerosolized buccal midazolam. Ann Emerg Med.
2011;58:323-9.
7. Dallman JA, Ignelzi MA Jr, Briskie DM.
Comparing the safety, efficacy and recovery of intranasal midazolam
vs. oral chloral hydrate and promethazine. Pediatr Dent.
2001;23:424-30.
8. Cote CJ, Wilson S. Guidelines for monitoring
and management of pediatric patients during and after sedation for
diagnostic and therapeutic procedures: an update. Pediatrics.
2006;118: 2587-602.
9. Ramsay MA, Savege TM, Simpson BR, Goodwin R.
Controlled sedation with alphaxalone-alphadolone. Br Med J.
1974;2:656-9.
10. Layangool T, Sangtawesin C, Kirawittaya T,
Prompan W, Attachoo A, Pechdamrongsakul A, et al. A
comparison of oral chloral hydrate and sublingual midazolam sedation
for echocardiogram in children. J Med Assoc Thai. 2008;91:S45-52.
11. D’Agostino J, Terndrup TE. Chloral hydrate
versus midazolam for sedation of children for neuroimaging: a
randomized clinical trial. Pediatr Emerg Care. 2000;16:1-4.
12. Schulte-Uentrop L, Goepfert MS. Anaesthesia
or sedation for MRI in children. Curr Opin Anaesthesiol.
2010;23:513-7.
13. Mazaheri R, Eshghi A, Bashardoost N, Kavyani N. Assessment of
intranasal midazolam administration with a dose of 0.5 mg/kg in behavior
management of uncooperative children. J Clin Pediatr Dent. 2008;32:95-9
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