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Original Article

Comparison of oral midazolam with oral

tramadol, triclofos and zolpidem in the sedation
of pediatric dental patients: An in vivo study
Abstract
Objective: oral sedation is the simplest and most convenient
sedation method for managing uncooperative child patients
because it is easy to administer and there is no need for nasal
hood or injection. Oral midazolam is the most commonly used
preanesthetic medication for children. When given in amounts
between 0.5 and 0.75 mg/kg of body weight, oral midazolam
has been found to be an effective sedative agent for pediatric
outpatients. Tramadol is a synthetic, centrally acting analgesic
indicated for moderate to severe pain. Chloral hydrate is one of
the sedatives most commonly used, has excellent absorption,
fast induction, and exert minimal effects on respiration. zolpidem
is the most commonly prescribed hypnotic due to its clinical
efficacy, safety, and ability to be well tolerated with patients.
Materials and Methods: 60 anxious and fearful children who
reported to the department were treated under conscious
sedation for the accomplishment of dental treatment. Patients
were randomly assigned to four groups. Statistical analysis was
done using Kruskal Wallis Test and decision criterion was to reject
the null hypothesis if the P-value is less than 0.05. Results: it
was observed that there is a statistically significant difference in
median scores recorded for the level of sedation between the
different groups (P < 0.001). Conclusion: this study concluded
that midazolam is the best drug for producing conscious
sedation followed by tramadol and triclofos. Zolpidem was not
able to produce a sufficient level of sedation and it cannot be
supported as a sedative agent at the present dosage.

Key words
Conscious sedation, midazolam, tramadol, triclofos, zolpidem

Introduction
The field of pediatric dentistry beholds the greatest
challenge among the various other branches of dentistry
in providing dental care without inflicting any adverse

Bhatnagar S, Das UM1, Bhatnagar G2

Departments of Pedodontics and Preventive Dentistry, Jodhpur

Dental College General Hospital, Rajasthan, 1Department of
Pedodontics and Preventive Dentistry, VS Dental College &
Hospital, Bangalore, 2Department of Periodontics, Jodhpur
Dental College General Hospital, Rajasthan, India
Correspondence:
Dr. Sudhanshu Bhatnagar, 40 Hospital Road, C-Scheme,
Jaipur, Rajasthan 302 001, India.
E-mail: sudhanshubhatnagar@yahoo.com
Access this article online
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Website:
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DOI:
10.4103/0970-4388.99980
PMID:
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psychological impact upon the child.[1] Uncooperative

children present a unique problem for practitioners.
Wide variation seems to exist among practitioners
with respect to personality and management styles.
Perception of what constitutes the most appropriate
modality for a given situation will vary from clinician
to clinician and region to region. Some clinicians are
more authoritarian in persona and demeanour. Such
individuals hold high expectation for child cooperation,
require minimal or no need for pharmacological
agents, and report considerable success managing
difficult and challenging child behaviors, even among
preschoolers.[2] For most patients, acceptable behavior
can be achieved by traditional nonpharmacological
management techniques; however, for a small number,
conscious sedation is used. The primary use of
pharmacological sedation is to modify or eliminate
negative behavior and allow the child to cooperate,[3]

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Bhatnagar, et al.: Comparison of oral midazolam with oral tramadol, triclofos & zolpidem in sedation of pediatric dental patients

improve the patients behavior, reduce apprehension,

minimize the negative psychological response toward
treatment by reducing anxiety, and maximize amnesia
potential so as to control behavior during dental
procedure.[4] Sedative drugs may be administered by
oral, inhalation, rectal, submucosal, intramuscular, or
intravenous routes. The selection of techniques is often
made as a matter of clinical judgment. Oral sedation
is regarded by many dentists to be the simplest and
most convenient sedation method for managing uncooperative child patient since it is easy to administer
and there is no need for nasal hood or injection.[5]
Oral midazolam is the most commonly used preanaesthetic
medication for children. [6] The pharmacological
actions of midazolam are identical to those of other
benzodiazepines including sleep induction, sedation,
anxiolysis, and amnesia.[7] Midazolam is rapidly absorbed
in the gastrointestinal tract and produces its peak effect
in 30 min, and has a short half-life of 1.5 h. This makes
it a desirable drug for short procedures.[8] Tramadol is a
synthetic, centrally acting analgesic indicated for moderate
to severe pain. It has two complementary mechanisms of
action: it binds with low affinity to m-opioid receptors and
inhibits reuptake of nor-epinephrine and serotonin.[9]
Oral chloral hydrate or triclofos is easy to administer and
has a low incidence of adverse effects.[10] The normal oral
dose is 50 mg/kg of body weight with a suggested range
of 40 to 60 mg/kg. Following oral administration the
onset of action of chloral hydrate is rapid, drowsiness or
a rousable sleep usually developing within 30 to 45min.
Duration of action is 2 to 5 h.[11]
Introduced into clinical practice in the United States in
1992, zolpidem is now the most commonly prescribed
hypnotic due to its clinical efficacy, safety, and ability
to be well tolerated with patients.[12] Following oral
administration; zolpidem is rapidly absorbed from the
GI tract, having an onset of action of 45 min and a peak
effect seen in 1.5 h. It is metabolized in the liver, with an
elimination half life of 2.5 h. Zolpidem is converted into
inactive metabolites eliminated primarily through renal
clearance. Zolpidem is one of a few CNS depressants that
is recommended for administration during pregnancy.[13]

Materials and Methods

The study was conducted out on anxious and
fearful children who reported to the Department
of Pedodontics and Preventive Dentistry. The
Institutional review board approval was obtained
for the study. Informed consent was obtained
110

from the parents before starting any treatment or

administration of the drug. Patients with physical
status ASA-I and aged between 3-9 years were selected
for the study. A controlled clinical trial was done. Sixty
patients were treated under conscious sedation for the
accomplishment of dental treatment. Patients were
randomly assigned to four groups.
GROUP I- Patients receiving Midazolam (0.5 mg/kg
body weight) orally.
GROUP II- Patients receiving Tramadol (2 mg/kg
body weight) orally.
GROUP III- Patients receiving Triclofos (70 mg/kg
body weight) orally.
GROUP IV- Patients receiving Zolpidem (0.4 mg/kg
body weight) orally.

Inclusion criteria
1. Patients between the age group of 3-9 years.
2. Patients who exhibited fearful or refractory behavior
at previous dental appointments, as documented by
Frankls behavior rating scale.
3. Patients are in good health with physical status in
accordance with ASA-I.
4. Patients undergoing dental procedures like
extraction, restoration, and endodontic treatment
with or without anesthesia.

Exclusion criteria
1. Patients who are allergic to drugs used for sedation.
2. Patients with hepatic, respiratory, cardiac, endocrine,
or metabolic impairment.
3. Special children or patients with psychological needs,
including mental retardation.
An anesthetist was always present during the procedure
to monitor the vitals of the children. To mask their
bitter taste and maintain uniformity the drugs were
mixed with chilled fruit juice. The vehicle and quantity
was kept same for each group in order to avoid
any fallacy in observation. No additional drug was
administered if the children had spat the drug out or
vomited. The number of children who spat out the drug
was not recorded. The time of drug administration
was noted. After administration of the drug child was
shifted to a calm room where he/she was kept under
continuous observation. When sedative effect started
to appear the time of onset was recorded and treatment
was started. Two more readings were recorded of vital
signs at the interval of 10 min intraoperatively.
The operating and supervising dentists evaluated the
overall level of sedation for each session based on a

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Bhatnagar, et al.: Comparison of oral midazolam with oral tramadol, triclofos & zolpidem in sedation of pediatric dental patients

rating scale consisting of scale ranging from 1 to 8

[Table 1].
The ease of treatment completion was rated as 0
(excellent), 1 (satisfactory), 2 (unsatisfactory), and 3
(aborted).
Once the treatment was completed patient was shifted
in a quiet room free from disturbances for recovery. The
time of recovery was noted. Patient was discharged
after cardiovascular function was stable with patent
airway and state of hydration adequate. Patient is well
oriented to the surroundings, sit and stand unaided or
with minimal assistance. Discharge of the children were
done only after an anesthetist evaluation and time of
discharge was noted.

Results
Statistical analysis was done using the Kruskal Wallis
Test and decision criterion was to reject the null
hypothesis if the P-value is less than 0.05. Otherwise
we accept the null hypothesis. If there is a significant
difference between the groups we carry out Mann
Whitney test to find out among which pair of groups
there exists a significant difference.

Comparison of level of sedation

We observe that there is a statistically significant
difference in median scores recorded for the level of
sedation between the different groups (P < 0.001)
[Table 2]. Higher mean and median score is recorded
in Zolpidem group followed by Triclofos. Tramadol has
a higher mean score compared to Midazolam but the
median scores between the two are equal. The difference
in median scores between the groups is found to be
statistically significant [Figure 1].
Table 1: Rating scale consisting of scale ranging from 1 to 8
Score 1
Score 2

Score 3
Score 4
Score 5
Score 6
Score 7
Score 8

Sleeping, no response to patting the

shoulder.
Sleeping, no response to calling by name
two or three times, responds to patting on
shoulder.
Eyes closed, dull reaction. responds to verbal
stimulus
Eyes open and closed by turns, dull reaction
responds to verbal stimulus.
Eyes open, dull reaction responds to verbal
stimulus
Normal reaction
Irritable with body movement.
Hghly irritable with considerable body
movement

Asleep
Asleep

It was observed that there is no significant difference

between Midazolam and Tramadol with respect to the
level of sedation (P > 0.05). The median score between
them is equal.
Statistically significant difference is observed between
Midazolam and Triclofos with respect to the level of
sedation (P < 0.05). Triclofos has a higher median
score compared to Midazolam and this difference is
statistically significant.
Statistically significant difference is noticed between
Midazolam and Zolpidem (P < 0.001). The median
score for the level of sedation is found to be higher in
Zolpidem compared to Midazolam and this difference
is highly significant.
The difference in median score between Tramadol and
Triclofos with respect to the level of sedation is found
to be statistically significant (P < 0.001). The median
score for the level of sedation was higher in Triclofos
compared to Tramadol.
Higher median score for the level of sedation is
noticed in Zolpidem compared to Tramadol and the
difference in median scores between them is found to
be statistically significant (P < 0.001).
The difference in median score with respect to level
of sedation is found to be statistically significant
between Ticlofos and Zolpidem (P < 0.01). Higher
median score is recorded in Zolpidem compared to
Triclofos.

Comparison of ease of treatment

We observe that there is a statistically significant
difference in median scores recorded for the ease of
treatment between the different groups (P < 0.01)
[Table 3]. Higher mean and median score is recorded
in Zolpidem group followed by Triclofos. Tramadol has
a higher mean score compared to Midazolam but the
median scores between the two are equal. The difference

Drowsy
Sedated
Sedated
Normal
Excited
Excited
Figure 1: Mean sedation levels in the groups

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Bhatnagar, et al.: Comparison of oral midazolam with oral tramadol, triclofos & zolpidem in sedation of pediatric dental patients

in median scores between the groups is found to be

statistically significant [Figure 2].

Ticlofos and Zolpidem (P < 0.01). Higher median score

is recorded in Zolpidem compared to Triclofos.

MannWhitney test was carried out to found out the

significant difference among the various groups.

Discussion
The oral route of administration is the most popular
choice by pediatric dentists[14] for sedation. Haas[15]
and colleagues compared the acceptance of oral chloral
hydrate with oral midazolam for children 3 to 10 years
of age, finding no difference in acceptance when both
drugs were mixed with syrup and orange juice. The
Chloral hydrate Midazolam Hydroxyzine oral regimen
is a well-tolerated mixture, and they found that 91%
of the children drank all their medicines from the
cup at their first sedation visit. Keeping these facts in
consideration we chose the oral route for administration
of drug mixed in orange juice, since needle and nasal
hood evoke anxiety and apprehension in majority of
children. The level of sedation and the onset of action
can be unpredictable at times because of the variability
in absorption and metabolism.[16] considering this fact
patients were monitored during the course of treatment.
The success of sedation here was defined as achieving
the restorative treatment planned even though there
might have been some crying or movement. Everyone
would not agree with this definition as it is argued
that only if there is no crying or movement should the
sedation be considered successful.

No statistically significant difference is observed

between Midazolam and Tramadol with respect to the
ease of treatment (P > 0.05). The median score between
them is equal.
No statistically significant difference is observed
between Midazolam and Triclofos with respect to the
ease of treatment (P > 0.05). The median score between
them is equal.
Statistically significant difference is noticed between
Midazolam and Zolpidem (P < 0.001). The median
score for ease of treatment is found to be higher in
Zolpidem compared to Midazolam and this difference
is highly significant.
The difference in median score between Tramadol and
Triclofos with respect to the level of sedation is not
statistically significant (P > 0.05). The median score
for the ease of treatment was equal in both Triclofos
and Tramadol.
Higher median score for the ease of treatment is
noticed in Zolpidem compared to Tramadol and the
difference in median scores between them is found to
be statistically significant (P < 0.001).

Davies and Waters[17] showed that a dose of 0.5 mg/kg

is safe and effective in producing anxiolysis and amnesia
for a wide range of accident and emergency procedures.
They also stated that children remained more anxious
in procedures involving the face. The results obtained
for midazolam in this study are same as compared to
studies done earlier. Midazolam was able to produce
sufficient amount of sedation in all the patients in which
the drug was administered.

The difference in median score with respect to ease of

treatment is found to be statistically significant between

Liebig first introduced chloral hydrate into practice

in 1832 and it is the oldest and best studied sedativehypnotic used in pediatric dentistry. Its primary
pharmacological effect is CNS depression. Singh
etal.[18] used triclofos (70 mg/kg) as a sedative agent
and concluded that midazolam gave better results as

Figure 2: Mean Score for ease of treatment in the groups

Table 2: Comparison of the level of sedation

Group
Midazolam
Tramadol
Triclofos
Zolpidem

112

Mean

Std dev

Median

Min

Max

KruskalWallis Chi-square

P-value

4.27
4.07
5.00
6.47

0.46
0.88
0.85
1.06

4.00
4.00
5.00
7.00

4.00
3.00
4.00
5.00

5.00
6.00
6.00
8.00

33.146

<0.001

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Bhatnagar, et al.: Comparison of oral midazolam with oral tramadol, triclofos & zolpidem in sedation of pediatric dental patients

Table 3: Comparison of ease of treatment

Group

Midazolam
Tramadol
Triolofos
Zolpidem

Mean Std dev Median Min Max

0.80
1.13
1.20
1.80

0.68
0.64
0.56
0.56

1.00
1.00
1.00
2.00

0.00
0.00
0.00
1.00

2.00
3.00
2.00
3.00

Kruskal P-value
Wallis Chisquare
17.234

0.001

compared to triclofos in producing sedation. This study

showed that there is statistically significant difference
observed between midazolam and triclofos with
respect to the level of sedation (P < 0.05). Although
no significant difference was observed regarding ease
of treatment among the two groups. Two of the
patients slept off during the treatment, their vitals
were monitored and were kept under observation till
the time they recovered completely.
Tramadols mode of action is not completely understood,
at least two complementary mechanisms contribute to its
effect. Tramadols opioid activity results from low affinity
binding of the parent compound to opioid receptors
and higher binding of the M1 (0-desmethylated)
metabolite.[19] Tramadol is an effective opiod analgesic
that binds with low affinity to m-opioid receptors.[9]
The drug is most commonly used as an analgesic and
less commonly as sedative agent. Koirala et al.[1] used
the drug as a sedative in combination with midazolam
and zolpidem separately in their study. This study took
tramadol (2mg/kg) as a sedative agent. The results
obtained were significantly different from previous
studies. Earlier studies and literature state tramadol as
an analgesic with lesser sedative potential. In this study
the tramadol produced level of sedation as equivalent
to midazolam and triclofos. Tramadol was as effective
as midazolam in producing the same level of sedation.
The ease of treatment was also as good as midazolam
and triclofos. No statistically significant difference
was observed among the vitals before and after the
completion of the treatment. This kind of a result calls
for further research and studies to evaluate and prove
tramadol as an effective sedative agent.
Zolpidem 10 or 20 mg when used as an oral premedication
was found to be superior to placebo in causing sedation
and reducing the anesthetic dose.[20] It was used by
Koirala et al.[1] as a sedative alone and in a combination
with tramadol in their study. In this study, zolpidem was
taken alone as a sedative. The results obtained by us
were similar to the study conducted by Koirala etal.[1]
The children were not sedated up to the threshold

where any treatment can be done on them. Children

receiving zolpidem showed sedative effect in an hours
time which is significantly different from the results
obtained by Langtry and Benfield.[21] They showed
that effect of the drug takes place in 15 to 20 min. In
this study, drowsiness in some patients were observed
whereas some remain active throughout the stay in the
clinic. Some of the patients after administration of drug
started speaking irrelevant things to their parents or
to the operating dentist. Two patients were excluded
from the study as they vomited the drug out in 30 min
time after administration.

Conclusion
In conclusion, within the limits of the present study
it can be stated. Midazolam(0.5 mg/kg) is the most
effective drug in producing sedation for the pediatric
dental patients. Tramadol (2 mg/kg) has produced the
sedation level equivalent to midazolam and further studies
are required to clearly establish this result specifically for
the use of conscious sedation in pediatric dental patients.
Triclofos (70 mg/kg) has shown good results during the
treatment but it has not shown the same level of sedation
as midazolam. Zolpidem a strong hypnotic has not given
satisfactory result as a conscious sedation agent. Further
studies at higher dosage have to be done to support this
drug as a sedative agent in pediatrics dental patients.

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How to cite this article: Bhatnagar S, Das UM, Bhatnagar G.

Comparison of oral midazolam with oral tramadol, triclofos and
zolpidem in the sedation of pediatric dental patients: An in vivo
study. J Indian Soc Pedod Prev Dent 2012;30:109-14.
Source of Support: Nil, Conflict of Interest: None declared.

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