1. health and fitness
2. dental care

JJOD-1030; No of Pages 19
journal of dentistry xxx (2006) xxx–xxx
available at www.sciencedirect.com
journal homepage: www.intl.elsevierhealth.com/journals/jden
Review
What is the evidence for paediatric dental sedation?
L.L. Matharu a,*, P.F. Ashley b
a
b
Unit of Paediatric Dentistry, King’s College London, Dental Institute Bessemer Road, London SE5 9RW, United Kingdom
Unit of Paediatric Dentistry, UCL Eastman Dental Institute, 256 Gray’s Inn Road, London WC1X 8LD, United Kingdom
article info
abstract
Article history:
Background and rationale: Sedation can be used to relieve anxiety and manage behaviour in
Received 7 June 2006
children, unfortunately it is difficult to determine from published research which agents,
Accepted 8 August 2006
dosages and techniques are effective.
Objective: To evaluate the relative efficacy of the various conscious sedation techniques and
dosages for behaviour management in paediatric dentistry.
Keywords:
Design and key methods: Relevant databases and reference lists from articles were searched
Systematic review
up to December 2005. Studies were selected if they met the following criteria: randomised
Sedation
controlled trials of conscious sedation comparing two or more drugs/techniques/placebo
Children
undertaken by the dentist or one of the dental team in anxious children up to 16 years of age.
Results: Sixty-five studies were included with 3372 subjects in total. Overall quality of
studies was found to be disappointing with poor reporting often the main problem.
Conclusions: Authors were not able to reach any definitive conclusion on which was the
most effective drug or method of sedation used for anxious children due to issues with the
quality and validity of published studies to date.
# 2006 Elsevier Ltd. All rights reserved.
1.
Introduction
Caries levels of children living in industrialised nations have
dropped substantially over the last few decades. Unfortunately a significant proportion of children still have dental
decay and much of it remains untreated.1,2 Reasons for this
lack of treatment are complex, one significant barrier will be
fear of the treatment itself.
Historically this has been overcome in children by use of
general anaesthetic (GA). It is now recognised that GA should
be avoided wherever possible due to the associated rare risk of
death. General anaesthesia is also costly as it requires the use
of specialist facilities and staff such as anaesthetists and
specialist nurses.
An alternative is for individuals to have treatment under
local anaesthesia and sedation. Views of what constitutes
sedation differ between clinicians, however any definition
should seek to differentiate sedation from general anaesthesia. A widely used definition of sedation is as follows.3
‘‘a state of depression of the central nervous system which
reduces anxiety thus enabling treatment to be carried out
satisfactorily. During sedation the patient will be able to
independently maintain an open mouth, and respond sensibly
to verbal commands. In addition, the patient will retain
adequate function of protective reflexes such as the laryngeal
reflex. The drugs used should carry a margin of safety
sufficient to render unintended loss of consciousness extremely unlikely’’. It is important to distinguish this from so
called deep sedation3 which brings with it the risk of
unintended loss of consciousness.
Sedation is a widely used technique to facilitate provision
of dentistry for children and adolescents so like any other
* Corresponding author. Tel.: +44 20 7737 4000x2417.
E-mail address: [email protected] (L.L. Matharu).
0300-5712/$ – see front matter # 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jdent.2006.08.002
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
JJOD-1030; No of Pages 19
2
journal of dentistry xxx (2006) xxx–xxx
clinical procedure high quality evidence is required. Therefore,
we carried out a Cochrane review of the literature4 to determine
which sedative agents were effective for behaviour management in children receiving dental care. This highlighted
significant issues with the research to date and a summary of
this review is presented below. This paper is based on a
Cochrane review most recently substantively amended in The
Cochrane Library 2006, issue 1 (see http://www.thecochranelibrary.com for information). Cochrane reviews are regularly
updated as new evidence emerges and in response to
comments and criticisms, and The Cochrane Library should
be consulted for the most recent version of the review.
2.
Materials and methods
2.1.
Types of studies
Randomised controlled clinical trials.
2.2.
2.3.
Types of interventions
2.3.1.
Test group
Any sedative agent via any route of admission. Studies that
reported induction of deep sedation were excluded.
Control group
Placebo (including no intervention) or alternative sedation
agent or different dosage of the same agent.
2.4.
Types of outcome measures
(1) Completion of treatment (yes/no);
(2) Difference in behaviour between test and control groups;
(3) Adverse events.
2.5.
2.6.
Methods of the review
Selection of papers suitable for inclusion was carried out by
two assessors (LM and PA). Disagreements were resolved by
discussion.
2.7.
Assessment of methodological quality
All studies meeting the selection criteria were included in this
review regardless of quality.
Data extraction was carried out on a specially designed
form independently by two assessors (LM and PA) blinded to
each other’s data. Disagreements were resolved by discussion.
Assessors were not blinded to the journal of publication or the
author’s names on the papers.
Types of participants
Children and adolescents aged 0–16 years of age having
restorative treatment or extractions with local anaesthesia.
2.3.2.
were also contacted for any unpublished data. The search
attempted to identify all relevant studies irrespective of
language. Non-English papers were translated.
Search strategy for identification of studies
Detailed search strategies were developed for each database.
Databases searched were: The Cochrane Central Register of
Controlled Trials (CENTRAL) (The Cochrane Library, December
2005); MEDLINE (OVID) (up to December 2005). EMBASE (OVID)
(up to December 2005); system for information on grey
literature in Europe (SIGLE) (up to December 2005).
World Wide Web (Google) and the Community of Science
Database were also searched for additional relevant trials.
The following journals were handsearched by the authors
for the period 2000–2005: International Journal of Paediatric
Dentistry; Dental Update; Pediatric Dentistry; Journal of
Dentistry for Children; American Academy of Pediatric
Dentistry; Journal of American Dental Association; British
Dental Journal.
The reference lists of all eligible trials were checked for
additional studies. Specialists in the field known to authors
3.
Results
3.1.
Description of studies
One hundred and forty-eight studies potential studies were
identified and 65 of these fulfilled the criteria of the review.
Lindsay and Yates5 paper was classified as two separate studies,
Lindsay 1985a and 1985b. Reasons for exclusion were mainly
because non-relevant outcome variables were used or the study
was not a prospective randomised trial. Only one study could be
excluded because deep sedation was stated as being used.6
Dates of publication ranged from 1966 to 2005. Studies were
from 15 different countries with the greatest proportion of
studies (n = 32, 49%) from the USA. The majority of studies
(34%) were published in Pediatric Dentistry. Age of patients
ranged from 1 to 16 years but in at least 27 of the studies all
subjects were 6 or under (only 40 studies gave minimum and
maximum age ranges). Mean age (approximation) for all
studies was 4.6 years. The mean number of participants was
51.9 (standard deviation (S.D.) = 96.3) with 3372 in total.
A total of 35 different drugs or combinations of drugs were
used and delivered orally, intranasally, intravenously, rectally,
intramuscularly, submucosally or by inhalation depending on
the type of drug and experimental aims. In 24 of the studies
(37%) all participants were administered supplemental nitrous
oxide/oxygen and papoose boards were used in 31 of the
studies (48%). Sixteen of the studies (25%) compared a drug
regimen to a placebo, 11 of the studies (17%) looked at the
effect of varying dosages or mode of delivery of the same agent
and the remainder compared different drugs or combinations
of drugs (58%).
Dental treatment was poorly described and all subjects
appeared to have some sort of restoration under rubber dam or
extraction with local anaesthetic.
Outcome measures varied widely with measures of
behaviour or level of sedation most commonly used (Houpt
or modified Houpt Scale used most frequently (n = 30, 46%)).
Thirty-four different types of measurement scales for behaviour or sedation were used.
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
JJOD-1030; No of Pages 19
Study ID
Sample size
and age (years)
Intervention and
mode delivery
Outcomes
Results
Did all patients
complete treatment?
Evans et al.36
n = 75
Group 1 chloral
hydrate 15 mg/lb;
group 2 placebo; all oral
No significant difference
between groups for manageability
or emotionality ( p > 0.05)
All participants
completed treatment
Flaitz et al.37
n = 12; mean age
(age range) 3.75 (2–6)
Group 1 placebo; group 2
diazepam 0.6 mg/kg;
all rectal
Significantly less
interfering responses in diazepam
group ( p < 0.0001)
All participants
completed treatment
Gallardo et al.38
n = 60; age range = 4–8
Group 1 flunitrazepam
0.5 mg/kg; group 2
diazepam 0.5 mg/kg;
group 3 placebo; all oral
Change in
manageability and
emotionality
categories between
first and second visits
Interfering and
non-interfering
responses.
Total patient
vocalisations
and operator
commands
Overall sedation;
mental attitude;
hypnotic effects.
Motor activity;
ease of treatment
All participants
completed treatment
Gallardo et al.39
n = 32; age range = 4–10
Group 1 midazolam 7.5 mg;
group 2 placebo; all oral
Flunitrazepam significantly better
than placebo ( p < 0.001) in all
categories. No significant difference
between diazepam and placebo
( p > 0.05) except for ease of treatment
category (dental treatment
more difficult in placebo
group, p < 0.001)
Midazolam significantly better
than placebo ( p < 0.001) in all categories
Houpt et al.40
n = 19; mean age
(age range) 2.49 (1.6–3.4)
Group 1 chloral hydrate
50 mg/kg + nitrous
oxide/oxygen 50:50%;
group 2 placebo; all oral
All participants
completed treatment
Kapur et al.41
n = 40; age: younger than 4
Group 1 midazolam
0.5 mg/kg
oral/transmucosal;
group 2 placebo
(same volume)
Significantly less movement
( p < 0.05) in chloral hydrate
group at 60 min point. Significantly
less crying ( p < 0.05) in chloral
hydrate group when mouth
prop inserted, rubber
dam placed and at
60 min point. Significantly
more ( p < 0.05) patients
drowsy/asleep in chloral
hydrate group. Overall
evaluation of sedation
significantly better
( p < 0.05) for chloral
hydrate group
Significantly better sedation
in group 1 compared to group 2
( p < 0.01). Eight completed
group 1 vs. seven group 2 ( p < 0.01)
Overall sedation;
mental attitude;
hypnotic effects;
motor activity;
ease of treatment
Houpt
Sedation score,
treatment
completion, time
All participants
completed treatment
journal of dentistry xxx (2006) xxx–xxx
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 1 – Summary of placebo studies
All participants
completed treatment
3
Intervention and
mode delivery
Outcomes
Results
Did all patients
complete treatment?
Lima et al.7
n = 11; mean age
(age range) 3.3
(1.66–4.9)
Group 1 placebo; group
2 midazolam 1 mg/kg;
group 3 midazolam
0.75 mg/kg +
hydroxyzine
2 mg/kg; all oral
Houpt
All participants
completed treatment
Lindsay and Roberts8
n = 24; mean age
(S.D.) 8.6 (3.8)
Group 1, 50:50 nitrous
oxide/oxygen;
group 2 placebo;
all inhalation
Child’s obstructive
activities;
clinician supporting
activities
Lindsay and Yates5
n = 27; mean age
(age range) 7.9 (4–12)
Group 1 diazepam
0.2 mg/kg;
group 2 placebo; all oral
All participants
completed treatment
Lindsay and Yates5
n = 17; mean age
(age range) 8.7 (4–13)
Group 1 diazepam 2 mg
given evening before,
0.2 mg/kg morning
of procedure,
0.2 mg/kg given 1 h before
procedure (pm);
group 2 placebo; all oral
No significant differences
( p > 0.05) between groups
All participants
completed treatment
McKee et al.42
n = 60, 15 each group;
mean age (S.E.)
from 3 (0.2) to 3.7 (0.2)
Group 1 placebo;
group 2 meperidine
0.25 mg/lb;
group 3 meperidine
0.50 mg/lb;
group 4 meperidine
1 mg/lb;
all intramuscular
Co-operation and
stress rating;
disruptiveness
of child;
clinician management
activities;
amount of work
completed
Co-operation and
stress rating;
disruptiveness
of child;
clinician management
activities;
amount of work
completed
Modified Houpt;
dichotomous
behaviour scale;
10-point
behaviour scale.
Global rating scale
Significantly more sleep in
group 3 compared to placebo
( p = 0.018). Significantly less
movement in group 1 compared
to group 2 ( p = 0.018), significantly
less crying in group 2 compared
to group 3 or 1
( p = 0.025). Overall
group 2 significantly
better than 3 or 1
Total number of obstructive
activities and time to complete
treatment significantly less in
nitrous oxide group. Clinicians
supporting activities less
frequent per minute and less
numerous throughout whole
session for nitrous oxide ( p < 0.01)
No significant differences
( p > 0.05) between groups
All doses of meperidine were
significantly better than placebo
( p < 0.05) for values of global
sedation scale. All three
scales significantly
contributed to
overall MANCOVA
One participant
from 0.25 mg/lb
group and one
from 0.5 mg/lb
group became
unmanageable
and treatment
was not completed
All participants
completed treatment
journal of dentistry xxx (2006) xxx–xxx
Sample size
and age (years)
JJOD-1030; No of Pages 19
4
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 1 (Continued )
Study ID
Nathan et al.20
n = 35; age range = 4–6
Primosch et al.31
n = 27; mean age
(age range) 7.3 (5–9.7)
Veerkamp et al.19
n = 56; group 1 n = 27;
group 2 n = 29;
age range all
subjects 6–11 years
Yanase et al.13
n = 25; mean age
(S.D.) 3.7 (1.25)
Group 1 placebo;
group 2 chloral
hydrate 20 mg/kg;
group 3 chloral
hydrate 40 mg/kg;
group 4 chloral hydrate
60 mg/kg; all oral
Group 1 no intervention;
group 2 placebo; group 3,
20–50:50 nitrous
oxide/oxygen; inhalation
Group 1 placebo; group 2,
40:60 nitrous oxide/oxygen;
all inhalation
Behaviour
evaluations;
completion of
treatment
Significant difference
( p < 0.05) seen between
placebo and 60 mg/kg chloral
hydrate group. No significant
differences between placebo
and other groups
All participants
completed treatment
Venham; parental
questionnaire;
behavioural
screening instrument
Ohio State University
behaviour
rating scale (OSUBR)
Significantly lower anxiety
and behaviour ratings in
nitrous oxide group ( p < 0.05)
All participants
completed treatment
All participants
assumed to have
completed treatment
Group 1 behaviour
management;
group 2 up to
40:60 nitrous
oxide/oxygen; inhalation
Group 1 diazepam
0.3 mg/kg;
group 2 placebo; all oral
Venham scale
Use of nitrous oxide
significantly reduces the
risk of adverse patient
behaviours and increased
the incidence of quiet,
co-operative behaviour ( p < 0.001)
Significantly less anxiety
( p < 0.05) in nitrous oxide group
Significantly lower behavioural
scores ( p < 0.01) in diazepam group
All participants
completed treatment
Behaviour score
All participants
completed treatment
JJOD-1030; No of Pages 19
n = 60, 15 each group;
mean age from 3.3 to 3.9
journal of dentistry xxx (2006) xxx–xxx
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Moore et al.43
5
Study ID
Sample
Intervention and mode delivery
Outcomes
Outcome results
Did all patients
complete treatment?
Al-Rakaf et al.44
n = 38; group 1 (n = 12),
group 2 (n = 13),
group 3 (n = 13);
mean age (S.D.) 3.75
(0.75)–4.3 (0.65)
n = 50, 25 per group;
mean age (S.D.)
group 1: 5.4 years
(1.7); group 2: 5 years (1.5)
Group 1 midazolam 0.3 mg/kg;
group 2 midazolam 0.4 mg/kg;
group 3 midazolam
0.5 mg/kg; all intranasal
Houpt
Seventy-nine percent of
0.3 mg/kg, 96% 0.4 mg/kg
and 100% 0.5 mg/kg
completed treatment
Group 1 midazolam
(oral) 0.5 mg/kg;
group 2 midazolam
(rectal) 0.35 mg/kg
Acceptance application
sedation and LA, operating
conditions, amnesia
Group 1 temazepam
0.3 mg/kg;
group 2 temazepam
0.5 mg/kg; all oral
Group 1 midazolam
0.2 mg/kg;
group 2 midazolam
0.3 mg/kg; all intranasal
Houpt
Significant difference in
general behavioural scores
between groups ( p = 0.0001)
with behaviour improving
with increased dose of midazolam
Poorer acceptance application
sedation in group 2
(8% poor group 2 vs. none poor
group 1, p < 0.05). No other
significant differences
between groups
No significant differences
in behaviour between groups
Group 1 chloral hydrate
75 mg/kg;
group 2 chloral hydrate
50 mg/kg + promethazine 25 mg;
group 3 chloral hydrate
50 mg/kg; all oral
Group 1 chloral hydrate
50 mg/kg;
group 2 chloral hydrate
75 mg/kg; all oral
Houpt
Aydintug et al.21
n = 22; mean age
(age range) 4.1 (2–4)
Fuks et al.46
n = 30; mean age
(age range) 2.7 (1.7–3.5)
Houpt et al.47
n = 21; mean age
(age range) 2.7 (1.2–3.7)
Houpt et al.48
n = 17; mean age
(age range) 2.6 (1.7–3.8)
Houpt
Houpt
Treatment abandoned
in three participants in
low dose group
No significant differences
in overall behaviour
between groups
(mean scores general
behaviour group
1 = 4.4 S.D. 1.0;
group
2 = 4.66 S.D. 1.1; p > 0.05)
No significant
differences between
groups (mean overall evaluation
group 1 = 4.71; group 2 = 4.76;
group 3 = 4.63; p > 0.05)
All participants
completed treatment
Less crying (mean rating group
1 = 2.15; group 2 = 2.82) and
movement (mean rating group
1 = 2.57; group 2 = 3.48) in the
higher dosage group, however
this was reported as being
significant at the 0.5 (?) level.
Eighty-two percent of low
dose administrations rated
bad or very bad, 75% high
dose administrations rated
good or very good. Reported
as being significant at the 0.5 level?
Four participants from
the low dose group
did not complete
compared to one
participant in the
high dose group
All participants
completed treatment
journal of dentistry xxx (2006) xxx–xxx
El Magboul et al.45
All participants
completed treatment
JJOD-1030; No of Pages 19
6
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 2 – Summary of dosage comparison studies
Group 1 midazolam
0.2 mg/kg intra-muscular;
group 2 midazolam
0.2 mg/kg intranasal
Houpt
Lee-Kim et al.17
n = 40 (20 per group);
mean age (S.D.)
group 1 = 3.4 (0.9);
group 2 = 3.2 (0.8)
n = 37;
age range 1.5–7 years
Group 1 midazolam
0.7 mg/kg oral;
group 2 midazolam
0.3 mg/kg intranasal
Group 1 midazolam
0.5 mg/kg;
group 2 midazolam
0.6 mg/kg;
group 3 midazolam
0.75 mg/kg; all oral
Houpt
Sullivan et al.32
n = 25; mean age
(age range)
group 1 = 4.1 (2.5–5.5)
Sleep, body movement,
head/oral resistance,
crying, verbal,
overall behaviour
Wilson49
n = 20; mean age
(age range)
2.5 (1.7–3.2)
Group 1 ketamine
8 mg/kg + diazepam
0.1 mg/kg;
group 2 ketamine
10 mg/kg + diazepam
0.1 mg/kg; all oral
Group 1 chloral
hydrate 25 mg/kg; group
2 chloral hydrate 50 mg/kg;
group 3 chloral
hydrate 70 mg/kg; all oral
Marshall et al.24
Frankl and modified
behaviour scale
Ohio State University
behaviour rating scale
Level of sedation deeper for
group 1 (2 vs. 1.45, p = 0.015)
however significant
differences for global
evaluation of sedation
only seen for one observer
(5.08 vs. 3.91—individual
values for two observers
not given, p = 0.04 for
observer 1, p = 0.056 for
observer 2)
No differences in sleep,
movement or crying
All participants
completed treatment
Significant correlation
between an increase
in Frankl scores and
dosages greater than
0.5 mg/kg and success
of treatment in most
cases (mean change
in Frankel scale group
1 = 1.18, group
2 = 1.55, group 3 = 1.28)
No significant differences
in any behavioural
category or overall
behaviour (success
rate group 1 = 24%;
group 2 = 43%)
Significant differences in
crying and quietness
between 25 and 70 mg/kg
(mean % crying group
1 = 45.7 S.D. 23.6,
group 2 = 34.9 S.D. 23.2,
group 3 = 18.6 S.D. 21.7,
mean % quiet
group 1 = 47.6 S.D. 26.5,
group 2 = 54.3 S.D. 25.4,
group 3 = 74.2 S.D. 29.2)
Treatment abandoned
in three participants
in low dose group
JJOD-1030; No of Pages 19
n = 23; group 1 n = 12;
group 2 n = 11;
mean age
(range) 5.13 (2.9)
All participants
completed treatment
Nine aborted treatments
per group
Treatment completed in
all participants
journal of dentistry xxx (2006) xxx–xxx
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Lam et al.16
7
Sample
Intervention and
mode delivery
Outcomes
Outcome results
Did all patients
complete treatment?
Abrams et al.50
n = 30 (10 per group);
age range = 1.4–5.1
Group 1 ketamine 3 mg/kg;
group 2 midazolam 0.4 mg/kg;
group 3 sufentanil 1 mg;
group 4 sufentanil
1.5 mg; all intranasal
Sedation scoring
criteria
Groups 1–3 had sedation
score of 4 (acceptable
sedation), group 4 had
sedation score of 7
(heavy sedation)
Alfonzo-Echeverri et al.51
n = 40 (20 per group);
mean age (S.D.)
group 1 = 3.4 (0.8);
group 2 = 3.1 (0.9)
Modified Houpt
No significant difference
between groups ( p = 0.07).
Data reported as individual
frequencies
Avalos-Arena et al.52
n = 40 (20 per group);
mean age (S.D.)
group 1 = 2.3 (0.2);
group 2 = 2.4 (0.3)
Group 1 ketamine
6 mg/kg;
group 2 meperidine
2.0 mg/kg + promethazine
0.5 mg/kg; all oral
Group 1 chloral hydrate
70 mg/kg; group 2 chloral
hydrate 70 mg/kg + hydroxyzine
2 mg/kg; all oral
One participant
untreatable in
midazolam group,
one participant
untreatable from
sufentanil 1.5 mg group
Dental treatment
aborted in four
children receiving
meperidine
Houpt
All participants
completed treatment
Averley et al.28
n = 65 (20 group 1,
22 group 2, 23 group 3);
mean age (S.D.)
9.3 (2.2) years
to 9.9 (2.2) years
Primary: completion of
treatment; secondary:
level of co-operation
during treatment,
recovery time,
perception of anxiety
and pain and parent’s
satisfaction
Averley et al.29
n = 697 (174 group 1,
256 group 2,
267 group 3);
mean age 9.1 (2.7)
years to 9.6 (2.5) years
Group 1 midazolam (IV)
0.5 mg/min + air (nasal
inhalation); group 2
midazolam (IV)
0.5 mg/min + nitrous oxide
40% (nasal inhalation);
group 3 midazolam (IV)
0.5 mg/min + nitrous oxide
40% (nasal inhalation) +
sevoflurane 0.3%
(nasal inhalation)
Group 1 midazolam
(IV) 0.5 mg/min + air
(nasal inhalation);
group 2 midazolam (IV)
0.5 mg/min + nitrous
oxide 40%
(nasal inhalation);
group 3 midazolam (IV)
0.5 mg/min + nitrous
oxide 40%
(nasal inhalation) +
sevoflurane 0.3%
(nasal inhalation)
No significant difference
( p > 0.05) for overall
behaviour evaluation
(mean values reported
at seven different time
intervals). Crying and
movement evaluations
significantly better ( p < 0.05)
at 45–60 min after application
of rubber dam for group 1
Significantly more
completed ( p = 0.07)
in group 3 (group 1:
10, group 2: 16,
group 3: 19)
Significantly more
completed
( p < 0.001) in
group 3 (group 1: 54%,
group 2: 80%,
group 3: 93%)
Fifty-four percent
completed group 1,
80% group 2, 93%
group 3
Primary: completion
of treament; secondary:
level of co-operation
during treatment,
recovery time,
perception of anxiety
and pain and parent’s
satisfaction
Ten completed group 1,
16 group 2, 19 group 3
journal of dentistry xxx (2006) xxx–xxx
Study ID
JJOD-1030; No of Pages 19
8
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 3 – Summary of drug comparison studies
Group 1 chloral
hydrate 50 mg/kg;
group 2 diazepam
0.3 mg/kg or diazepam
0.6 mg/kg; all oral
Houpt
Bui et al.54
n = 22 (11 per group);
mean age (S.D.) group 1 = 2.8 (0.5);
group 2 = 2.7 (0.6)
Group 1 ketamine
(10 mg/kg) + promethazine
(1.1 mg/kg); group 2 ketamine
(10 mg/kg); all oral
Houpt
Dallman et al.55
n = 31; mean age (S.D.) 3.5 (0.9)
Group 1 midazolam
0.2 mg/kg intranasal;
group 2 chloral hydrate
62.5 mg/kg + promethazine
12.5 mg; oral
Houpt
Downs et al.56
n = 10; age range = 2–4
Group 1 midazolam
0.2 mg/kg;
group 2 meperidine
2 mg/kg + promethazine
1 mg/kg;
all intramuscular
Houpt
Haas et al.57
n = 23; mean age
(age range) 6.8 (3.5–10.7)
Group 1 midazolam
0.6 mg/kg;
group 2 chloral hydrate
50 mg/kg; all oral
Modified Houpt
No difference in overall
behaviour between groups.
Significantly more children
( p < 0.05) were asleep in the
chloral hydrate group when
compared to both diazepam
groups
Behaviour significantly
better in group 2 (mean
score 4.27 S.D. 0.5) than
in group 1 (mean score
3.12 S.D. 0.29) ( p < 0.05)
Significantly more
participants were asleep
in the chloral hydrate/
promethazine group
(no p value given). No
significant differences
between groups for any
other measure ( p value
reported as p < 0.05,
21 subjects good or
excellent in group
1 and 22 in group 2)
Significantly less sleep
( p = 0.001),
more movement ( p = 0.0268)
and more crying ( p = 0.0251)
in midazolam group. No
significant difference
for overall rating of
behaviour (mean rating
overall behaviour group
1 = 3.9, group 2 = 4.6, p = 0.31)
Significantly increased
level of sedation prior to
administration local
anaesthetic in midazolam
group ( p < 0.015). No
significant differences
between groups for any
other parameters
(mean overall behaviour
group 1 = 4.4 S.D. 0.28,
group 2 = 4.27 S.D. 0.35)
JJOD-1030; No of Pages 19
n = 30; mean age
(age range) 2.8 (1.7–4)
All participants
completed treatment
Dental treatment
aborted in one
participant from
group 1 due to
violent physical
movement and crying
All participants
assumed to have
completed treatment
All participants
completed treatment
journal of dentistry xxx (2006) xxx–xxx
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Badalaty et al.53
All participants
assumed to have
completed treatment
9
Intervention and
mode delivery
Outcomes
Outcome results
Did all patients
complete treatment?
Hartgraves and
Primosch22
n = 100 (50 per group);
mean age (age range);
group 1 3.1 (1.5–5.7);
group 2 3.2 (1.5–5.9)
Presence or absence of
sedative effect; completion
of treatment
No significant differences
between groups. Relevant
data not given
Two participants
did not complete
treatment in each group
Hasty et al.58
n = 10; mean age
(S.D.) 3.1 (0.5)
North Carolina
behaviour
rating scale (NCRBS)
More favourable
behaviour
for chloral
hydrate/meperidine/
hydroxyzine regimen
( p < 0.01)
All participants
assumed to have
completed treatment
Houpt et al.59
n = 24; mean age
(age range) 2.6 (2.1–3.7)
Houpt
No significant
differences between
groups
All participants
completed treatment
Jensen et al.60
n = 90 (45 per group);
median age (age range);
group 1 = 2.7 (1.5–3.7);
group 2 = 2.4 (1.2–3.6)
Group 1 midazolam
0.2 mg/kg nasal;
group 2 midazolam
0.5 mg/kg + hydroxyzine
25 mg; oral
Group 1 chloral hydrate
50 mg/kg + hydroxyzine
25 mg;
group 2 meperidine
1.5 mg/kg + chloral hydrate
50 mg/kg + hydroxyzine
25 mg; all oral
Group 1 diazepam
0.5 mg/kg + 50:50 nitrous
oxide for the first 20 min
treatment; group
2 diazepam
0.5 mg/kg + 50:50
nitrous oxide after 20 min
treatment; diazepam oral;
nitrous oxide inhalation
Group 1 diazepam
0.7 mg/kg; group
2 midazolam
0.3 mg/kg; all rectal
Wilton’s sedation scale;
acceptance of
treatment (Holst)
Lahoud and Averley23
n = 411 (170 group 1,
241 group 2);
mean age (S.D.)
group 1 = 6.2 (1.9);
group 2 = 6 (1.7)
Group 1, 40:60 nitrous
oxide/oxygen; group 2,
40:60 nitrous
oxide/oxygen + 0.1–0.3%
sevoflurane; all
inhalation
Venham scale level of
sedation and failure rate
No difference in
acceptance of dental
procedures ( p = 0.07). At 1 h
significantly more
children agitated in
the diazepam group
( p = 0.006)
Sevoflurane significantly
better ( p < 0.0001) than
nitrous oxide as
recorded by Venham
scale (% relaxed group
1 = 32, group 2 = 67).
Significantly less failure
in group 2 (11% failed
compared with 48% group 1,
p < 0.0001)
Some children did
not complete
treatment however
it is not possible to
extract exact numbers
as this data was only
presented as bar chart
Eighty-nine percent
sevoflurane group
completed treatment
compared to 52% of
nitrous oxide group
journal of dentistry xxx (2006) xxx–xxx
Sample
JJOD-1030; No of Pages 19
10
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 3 (Continued )
Study ID
Lo¨kken et al.61
n = 24; mean age
(S.D.) 4.4 (1.4)
McCann et al.62
n = 20; mean age
(age range) 3.7 (3–4.6)
Group 1 chloral hydrate
50 mg/kg + meperidine
1.5 mg/kg + hydroxyzine
25 mg oral;
group 2 chloral
hydrate
50 mg/kg + meperidine
1.5 mg/kg + hydroxyzine
25 mg
(all oral) + 50:50 nitrous
oxide/oxygen inhalation
Group 1 midazolam
0.3 mg/kg;
group 2 midazolam
0.3 mg/kg + ketamine
1 mg/kg; all rectal
Level of sedation.
Sedation outcome
Group 1 chloral hydrate
40 mg/kg + hydroxyzine
2 mg/kg (oral) + 50:50
nitrous oxide/oxygen
(inhalation);
group 2 chloral hydrate
40 mg/kg + hydroxyzine
2 mg/kg (oral)
Ohio State University
behaviour rating scale
(OSUBR)
Feasibility of dental
treatment; anxiety;
drowsiness; pain;
dentist preference
Sedation significantly
‘deeper’ in nitrous oxide
group (mean level of
sedation group 1 =
2.2 S.D. 0.6, group 2 =
2.9 S.D. 0.8, p < 0.04).
Significantly better sedation
outcome in nitrous oxide
group (data presented as
individual frequencies
p = 0.035)
Sedation was difficult in
five participants in
midazolam group
compared to one
participant in
midazolam/ketamine
group. No significant
difference in anxiety
or pain (e.g. mean change
in anxiety from baseline at
30 min group 1 = 23 S.D. 40,
group 2 = 8 S.D. 47, p = 0.08,
mean pain on injection
with local anaesthetic
group 1 = S.D. 9, group
2 = 8 S.D. 17, p = 0.21).
Significantly more
patients ( p = 0.04) drowsy in
midazolam/ketamine
group at 15 min time point
(mean change in drowsiness
from baseline group
1 = 21 S.D. 15,
group 2 = 31 S.D. 12).
No significant difference
in dentist preference
No significant
differences between
groups (multiple values
for crying, movement,
quiet, struggle
reported at eight
different time points)
JJOD-1030; No of Pages 19
n = 19; mean age
(age range) 3.4 (2.2–4.6)
Three patients
aborted treatment
at first visit however
treatment groups
not specified
All participants
completed treatment
journal of dentistry xxx (2006) xxx–xxx
All participants
assumed to have
completed treatment
11
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Leelataweewud et al.30
Sample
Intervention and
mode delivery
Outcomes
Outcome results
Did all patients
complete treatment?
Meyer et al.18
n = 40 (20 per group);
mean age
(age range)
group 1 = 3.7 (1.7–6.1);
group 2 = 3.5 (1.9–5.3)
Group 1 triazolam
0.02 mg/kg;
group 2 chloral
hydrate
40 mg/kg + hydroxyzine
25 mg; all oral
Houpt
All participants
assumed to have
completed treatment
Moody et al.25
n = 30 (10 per group);
mean age 3.2–3
Modified Barker
overall quality
sedation
Musial et al.63
n = 20; mean age
(S.D.) 3.8 (0.7)
Myers et al.9
n = 20; mean age (S.D.) 4 (0.7)
Quiet, crying,
struggling and
movement (similar
to OSUBR)
Mean percent behaviour
significantly different
( p < 0.0001) between
groups (group 1: quiet 62,
crying 5, movement 6,
struggling 27; group 2:
quiet 84, crying 2,
movement 4, struggling 10)
Twenty completed
group 1, 19 group 2
Pisalchaiyong et al.10
n = 13; mean age
(range) 8.68 (5.8–14.7)
Group 1 chloral
hydrate 50 mg/kg oral;
group 2 chloral hydrate
50 mg/kg rectal; group
3 chloral hydrate
30 mg/kg + 25 mg
hydroxyzine oral
Group 1 midazolam
1 mg/kg; group
2 midazolam
0.5 mg/kg + meperidine
1 mg/kg; all oral
Group 1 chloral
hydrate (oral)
50 mg/kg + placebo
(oral submucosal
injection);
group 2 chloral
hydrate (oral)
50 mg/kg + midazolam
(oral submucosal injection)
0.2 mg/kg
Group 1 diazepam
0.3 mg/kg; group 2
midazolam
0.5 mg/kg; all oral
No significant
differences between
groups (mean overall
behaviour group
1 and group 2 the
same with a value
of 4.3 S.E. 0.4354)
Forty percent chloral
hydrate (oral) group
classified as good or
excellent compared
to 70% of chloral
hydrate (rectal) or
chloral hydrate/hydroxyzine
Data presented
graphically,
no p values given.
No differences reported
Houpt
All completed treatment
Poorman et al.11
n = 40 (20 per group); mean age
(age range) group 1 = 3.5 (2–5);
group 2 = 3.2 (2–5)
Group 1 chloral hydrate
40 mg/kg + hydroxyzine
25 mg/kg; group 2 chloral
hydrate
40 mg/kg + hydroxyzine
25 mg/kg + meperidine
0.5 mg/kg; all oral
Houpt
Overall value for
sedation was 77%
good/very good in
group 1 and 100%
good or very good
in group 2 ( p < 0.02)
No significant
differences
between groups
(mean overall
behaviour
group 1 = 4.3 S.E. 0.3032;
group 2 = 5 S.E. 0.3032)
All completed treatment
All participants
assumed to have
completed treatment
journal of dentistry xxx (2006) xxx–xxx
Modified OSUBR
All participants
assumed to have
completed treatment
JJOD-1030; No of Pages 19
12
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 3 (Continued )
Study ID
Group 1 metoclopramide
5 mg/kg + hydroxyzine
3.7 mg/kg; group 2 hydroxyzine
3.7 mg/kg; all oral
Houpt
Reeves et al.14
n = 40 (20 per group);
mean age (age range)
group 1 = 4 (2.7–6.1);
group 2 = 3.5 (2.2–5.8)
Modified Houpt
Roelofse et al.64
n = 100 (50 per group);
mean age (S.D.)
group 1 = 4.3 (1);
group 2 = 4.3 (1.1)
Group 1 chloral hydrate
50 mg/kg + hydroxyzine
25 mg; group 2 midazolam
0.5 mg/kg + acetaminophen
10 mg/kg; all oral
Group 1 ketamine
5 mg/kg + midazolam
0.35 mg/kg; group
2 midazolam
1 mg/kg; all rectal
Roelofse et al.65
n = 60 (30 per group);
mean age (S.D.)
group 1 = 4.8 (1.3);
group 2 = 4.9 (1.3)
Anxiety level of
sedation movement
crying overall
behaviour
Roelofse et al.66
n = 100 (50 per group);
mean age
(S.D.) = 4.1 (1.3);
group 2 = 4 (1.2)
Group 1 0.5 ml/kg of
trimeprazine 6 mg/ml +
physeptone 0.4 mg/ml;
group 2 ketamine
12.5 mg/kg; all oral
Group 1 ketamine
5 mg/kg + midazolam
0.35 mg/kg;
group 2 trimeprazine
3 mg/kg + methadone
0.2 mg/kg; all oral
Sams et al.67
n = 24
(13 group 1,
11 group 2);
mean age (S.D.)
group 1 = 2.6 (0.7);
group 2 = 3 (0.9)
Group 1 chloral hydrate
50 mg/kg + promethazine
1 mg/kg; group
2 meperidine
1 mg/kg + promethazine
1 mg/kg; all oral
Modified Houpt
Ramsay sedation
score movement
crying.
Overall sedation and
behaviour
Modified Houpt,
Ramsay sedation
score
No significant differences
between groups (mean
overall behaviour group
1 = 4.4, group
2 = 4.6, p > 0.05)
Subjects in chloral
hydrate/hydroxyzine
group were in
a significantly
deeper sleep ( p < 0.05)
Significant differences
in level of sedation
with 71% subjects
in group 2 ‘orientated
and calm’ compared to
14% group 1. Significantly
less movement and
crying ( p < 0.05) in group
1 (58% no movement at all
compared to 14% group 2)
Sedation was significantly
‘better’ in the group 2
(10% rated as poor
compared to 33% in group 2)
All participants
completed treatment
Significant differences
( p < 0.05) in level of sedation
with 48% participants in
group 1 ‘orientated and calm’
30 min after drug
administration compared to
88% in group 2. Sedation
rated as poor in
significantly more
children in group 2
(24%) than group 1 (6%)
Chloral hydrate/
promethazine group
significantly ‘better’
( p < 0.05) for overall
evaluation at 4 of the 10
measured time intervals
(e.g. mean overall behaviour
15 min post-injection
group 1 = 5.2 S.D. 1.1, group
2 = 4.4 S.D. 1.3, p < 0.05)
All participants
completed treatment
JJOD-1030; No of Pages 19
n = 30; mean age
(age range) 2.4 (1.6–3.3)
Dental treatment
aborted in one
participant from
chloral hydrate/
hydroxyzine group
Dental treatment
aborted in two
participants from
ketamine/midazolam
group
All participants
completed treatment
journal of dentistry xxx (2006) xxx–xxx
All participants
completed treatment
13
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Ram et al.12
Intervention and
mode delivery
Outcomes
Outcome results
Did all patients
complete treatment?
Shapira et al.68
n = 19; mean age
(age range) 3.1
(2.1–3.7)
Crying alertness
No significant
difference between
‘‘success’’ and ‘‘failure’’
within groups (mean
overall behaviour group
1 = 5.4 S.D. 0.83, group
2 = 4.7 S.D. 1.06, group
3 = 5.1 S.D. 0.99, p > 0.07)
Dental treatment
aborted in four
participants from
hydroxyzine/oxygen
group, one from
hydroxyzine/nitrous
oxide group and one
from nitrous oxide group
Shapira et al.15
n = 29;
age range = 2–4
Group 1 hydroxyzine
50 mg/kg oral + 50:50
nitrous oxide/oxygen
inhalation; group 2
hydroxyzine 50 mg/kg
oral + oxygen inhalation;
group 3 placebo oral + 50:50
nitrous oxide/oxygen
inhalation
Group 1 hydroxyzine
3.7 mg/kg oral; group
2 midazolam
0.2 mg/kg nasal
Modified Houpt
One patient aborted
in midazolam group
Shapira et al.69
n = 28; mean age
(age range)
3.0 (1.7–4.6)
Singh et al.70
n = 90 (30 per group);
age range 3–9 years
Group 1 midazolam
0.5 mg/kg; group
2 midazolam
0.3 mg/kg + hydroxyzine
3.7 mg/kg; all oral
Group 1 midazolam
0.5 mg/kg; group
2 triclofos 70 mg/kg;
group 3 promethazine
1.2 mg/kg; all oral
Modified Ohio State
University behaviour
rating scale (OSUBR);
overall behaviour
(similar to Houpt)
Degree of sedation.
Ease of treatment
completion
No difference in
general mean
behaviour evaluation
(group 1 = 4.44 S.D. 1.47,
group 2 = 4.62 S.D. 1.37)
No difference in general
behaviour. No p value,
data presented graphically
All participants
assumed to have
completed treatment
Songvasin and Pasavorakul71
n = 14; mean
age = 3.9 years
Houpt
Tsinidou et al.72
n = 20; mean age
(age range) 3.2 (1.7–5)
Group 1 chloral hydrate
50 mg/kg + promethazine
1 mg/kg; group
2 hydroxyzine
1 mg/kg + diazepam
0.25 mg/kg; all oral
Group 1 chloral hydrate
50 mg/kg + hydroxyzine
25 mg; group
2 temazepam
0.3 mg/kg; all oral
Sedative scores ‘‘best’’
for group 1 (mean 4.7
S.E. 0.12), followed by 2
(mean 4.93 S.E. 0.11)
and 3 (mean 5.27 S.E. 0.09)
p < 0.001 between groups
1 and 2, p < 0.05 between
groups 2 and 3. Treatment
most ‘‘convenient’’ for group
1, then group 2 and group 3.
Data presented graphically.
p < 0.01 between groups
1 and 3, p < 0.05 between
groups 2 and 3
Significantly less ( p < 0.05)
crying and movement
and ‘better’ overall sedation
in group 2
No significant
differences between
groups
(rated as ‘‘good’’
or ‘‘excellent’’ for
11 cases group 1 and
12 cases group 2)
Dental treatment
aborted in five
participants in
temazepam group
and three in chloral
hydrate/hydroxyzine
group
Houpt
All completed treatment
All participants
assumed to have
completed treatment
journal of dentistry xxx (2006) xxx–xxx
Sample
JJOD-1030; No of Pages 19
14
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
Table 3 (Continued )
Study ID
JJOD-1030; No of Pages 19
journal of dentistry xxx (2006) xxx–xxx
All participants
completed treatment
Group 1 nitrous oxide
30% nasal inhalation;
group 2 midazolam 0.5
mg/min (max 5 mg) IV
n = 40; mean age
(age range) 13.2 (12–16)
Wilson et al.27
Houpt sedation level
(Britkopf + Buttner);
Frankl patient
preference
Group 1 midazolam
0.5 mg/kg oral; group 2,
30:70 nitrous
oxide/oxygen inhalation
n = 46; mean age
(age range) 12.5 (10–16)
Wilson et al.26
Houpt Frankl
level of sedation;
level of behaviour;
patient preference
No difference
in overall behaviour
(Houpt) and treatment
outcome
(no p value given,
data presented graphically).
Fifty-four percent of
participants preferred
midazolam
More sedated in group
2 but not significant
(no data or p values
reported, data presented
graphically)
Dental treatment
aborted in one child
from each group
3.2.
15
Methodological quality of included studies
Twenty-eight of the studies used a parallel design (43%) with
the remainder being cross-over trials. Only 19 studies were
scored as adequate with regards to allocation concealment. In
the majority of studies (n = 51) method of randomisation was
not recorded. In the remainder it appeared to be adequate
(random number table, computer generated, tossed coin,
sealed unmarked envelopes).
Blinding was complicated in studies of this due to the
nature of the equipment and drugs involved. Data regarding
blinding are presented in the following hierarchy (best
possible combination is first, worst is last).
(1) Operator/outcome assessor and patient blind (n = 44);
(2) Outcome assessor and patient blind, operator aware7–13
(n = 7);
(3) Outcome assessor and operator blind14,15 (n = 2);
(4) Outcome assessor only blind16–19 (n = 4);
(5) Patient only blind20 (n = 1);
(6) No blinding21–27 (n = 7).
Intention-to-treat analysis was used in only two studies,28,29 one of these was a pilot to calculate a sample size
for the other.29 There were no sample size calculations given
in any of the other studies. Outcome variables were
predominantly ordinal (e.g. five-point scale for increasing
movement) or categorical in nature (e.g. success/failure).
Methods used for statistical analysis included both nonparametric (x2, Wilcoxon matched pairs, Kruskal–Wallis,
Mann–Whitney U, Fishers Exact test, non-parametric two
factor ANOVA, McNemar test, sign test) and parametric tests
(t-test, ANOVA, Tukey’s range test, Friedman two-way
analysis, method of least squares).
Drop outs were poorly reported and it was difficult to
determine whether or not they had occurred. In the majority
of studies it was assumed that all subjects completed the
treatment regimen. Seven studies did explicitly state that
there were drop outs28–30,5,31,32,27 with reasons given being
patient refusal.
In the majority of studies (n = 51, 84%) subjects were
reported as being unco-operative or anxious at the beginning
of the study (only measured in 19 studies (32%) using the
Frankl scale).
3.3.
Study outcomes
Meta-analysis of the available data was not possible for several
reasons. The variety of drug regimens compared made it
difficult to isolate classes of drugs that were sufficiently
similar to allow comparison. Where groups of studies were
isolated, then differing outcome measures made their metaanalysis impossible. Results of individual studies are presented in Tables 1–3. Studies have been separated into three
groups; placebo studies (any drug versus a placebo); dosage
comparison studies (same drug, different dosage); drug
comparison studies (any drug or combination of drugs versus
any drug or combination of drugs).
Data on adverse effects was poorly reported, vomiting and
nausea (31%) and sleep and drowsiness (44%) were the most
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
JJOD-1030; No of Pages 19
16
journal of dentistry xxx (2006) xxx–xxx
common adverse effects reported. The most serious adverse
effect was obstructive hypoxaemia which was seen in three
studies involving chloral hydrate. There did not appear to be a
clear association with any particular drug and any particular
side effect, most drugs were involved with most side effects at
some point.
4.
Discussion
The results of a Cochrane review can be interpreted
differently, depending on people’s perspectives and circumstances. Please consider the discussion and conclusions
presented below carefully. They are the opinions of review
authors, and are not necessarily shared by The Cochrane
Collaboration.
In common with the findings from many other systematic
reviews, reporting was poor with data such as method of
allocation and randomisation frequently not recorded. Samples were poorly described with important information such
as gender, weight or baseline anxiety often missing and little
information provided on types of dental treatment.
Numbers of subjects were small and studies likely to be
underpowered, sample size calculations were the exception
rather than the norm, this will have had an adverse effect on
quality.33 Cross-over designs were frequently used, whilst this
may have overcome some problems such as recruitment of
sufficient numbers, etc., the effect of ‘‘carryover’’ is unknown.
It is possible that anxiety and behaviour could be influenced by
previous treatment and experience of sedation. Age ranges
were broad with no obvious attempt to classify patients into
age bands (as recommended by the British National Formulary
(BNF) when prescribing drugs to children; groups are: from 1 to
6, from 6 to 12 and over 12) to establish which sedative might
be more effective for a given age group.
Statistical methods used varied widely between studies
even though outcome measures were sometimes similar. In
some instances these tests were arguably inappropriate for
the type of ordinal data usually produced by these studies.
Blinding was appropriate in the majority of studies however in
eight of them the outcome assessor was aware of the agent in
use, this must be considered a powerful source of bias.34
Interpretation of outcome data related to behaviour was
difficult. Over half of the studies used the Houpt or modified
Houpt scoring system to record behaviour (the remaining
studies used a wide variety of methodologies), however even
within the Modified Houpt Scale there was a variation in
scores used from three up to six. Behaviour was recorded in
some studies for the whole episode and in others at a series of
discrete points, e.g. application of local anaesthetic. Furthermore, many of the outcome measures used relied on
observations of movement, yet in a large proportion of studies
patients were restrained in a papoose board. This variation in
outcome measurement greatly complicated the analyses of
the data and was one of the reasons why a meta-analysis
could not be carried out. Interestingly participants often
completed treatment regardless of which group they were
assigned to (n = 43, 66%). This might reflect a lack of baseline
anxiety in all participants which then begs the question as to
why they were included in the study. Alternatively given the
use of papoose boards and supplemental nitrous oxide oxygen
perhaps it is not surprising.
Supplemental nitrous oxide/oxygen was used frequently,
particularly in studies from North America and would be
expected to increase the overall level of sedation. Whilst there is
nothing inherently wrong in using supplemental nitrous oxide/
oxygen very few studies explicitly stated it was used either in
the title, introduction or aims. Papoose boards were also used
often but again there use was often not specified clearly from
the outset. This has the potential to mislead as results from a
study comparing (for example) chloral hydrate to midazolam
may be very different if in one case supplemental nitrous oxide/
oxygen and a papoose board used and in another it is not.
Only one paper was excluded because it described the use
of deep sedation, however in many of the included studies
participants were reported as falling asleep and mouth props
were used, suggesting deep sedation was occurring. This
highlights the importance of reaching a consensus definition
of conscious sedation, or at the very least using the definitions
already available. Without this information it is impossible for
researchers or clinicians in countries where the existing
regulatory framework does not permit deep sedation to make
appropriate use of published data. Alternatively the definition
of deep sedation should be abandoned, as it is not used.
The initial aim of this review was determine those sedative
agents that had the greatest effectiveness with regard to
behaviour management. Due to the strength of evidence
presented and multiplicity of agents investigated, a clear
statement of implications for practice is difficult, we would
refer those interested in further information on individual
studies to the Cochrane review.4 It could be argued that
evidence supporting the use of these sedative agents exists
within the medical literature, however medical and dental
procedures are clearly very different and the requirements
from sedative agents therefore different also. There are safety
issues to consider as well, what might be considered
appropriate delivered by an anaesthetist in a hospital
environment would be highly inappropriate delivered by a
dentist in his surgery.
What were our conclusions? Aside from being unable to
recommend a specific drug or drugs for dental sedation in
children, there were two clear issues with studies selected for
this review: quality and validity. Quality of study reporting,
and to an extent conduct, was on the whole poor with perhaps
one exception.29 As stated previously this is a common finding
of systematic reviews, it is hoped that greater awareness and
use of the CONSORT guidelines35 will go some of the way to
resolving this. Other issues with regard to quality that need to
be tackled include the use of predominantly small trials33 and
ensuring that at least the outcome assessor is blind to the
intervention.34 Issues of validity may be more difficult to
address, of particular concern though are the wide variety of
outcome measures used in these studies and there relevance
to successful outcome of treatment.
Acknowledgements
The authors would like to thank the two translators,
Pati Pungchanchaikul and Jens Poppen, and the help and
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
JJOD-1030; No of Pages 19
journal of dentistry xxx (2006) xxx–xxx
assistance of the Cochrane Oral Health Group—in particular
Sylvia Bickley.
references
1. National Centre for Health Statistics (NCHS). Third national
health and nutrition examination survey (NHANES III) reference
manuals and reports [CD-ROM]. Hyattsville, MD: NCHS, US
Department of Health and Human Services, Public
Health Services, Centers for Disease Control and
Prevention; 1996.
2. Pitts NB, Evans DJ, Nugent ZJ. The dental caries experience
of 5-year-old children in the United Kingdom. Surveys
coordinated by the British Association for the Study of
Community Dentistry in 1999/2000. Community Dental Health
2001;18:49–55.
3. American Academy of Pediatrics Committee on Drugs.
Guidelines for monitoring and management of pediatric
patients during and after sedation for diagnostic and
therapeutic procedures. Pediatrics 1992;6:1110–5.
4. Matharu L, Ashley P. Sedation of anxious children
undergoing dental treatment. Cochrane Library )2006;(1).
5. Lindsay SJ, Yates JA. The effectiveness of oral diazepam in
anxious child dental patients. British Dental Journal
1985;159(5):149–53.
6. Veerkamp JSJ, Porcelijn T, Gruythuysen RJ. Intravenous
sedation for outpatient treatment of child dental patients:
an exploratory study. ASDC Journal of Dentistry for Children
1997;64(1):48–54.
7. Lima ARA, Costa LRRS, Costa PSS. A randomized controlled
crossover trial of oral midazolam and hydroxyzine for
pediatric dental sedation. Pesqui Odontol Bras 2003;17(3):
206–11.
8. Lindsay SJ, Roberts GJ. Methods for behaviour research on
dentally anxious children. British Dental Journal
1980;149(6):175–9.
9. Myers GR, Maestrello CL, Mourino AP, Best AM.
Effect of submucosal midazolam on behaviour and
physiologic response when combined with oral chloral
hydrate and nitrous oxide sedation. Pediatric Dentistry
2003;26(1):37–43.
10. Pisalchaiyong T, Trairatvorakul C, Jirakijja J, Yuktarnonda
W. Comparison of the effectiveness of oral diazepam and
midazolam for the sedation of autistic patients during
dental treatment. Pediatric Dentistry 2005;27:198–206.
11. Poorman TL, Farrington FH, Mourino AP. Comparison of a
chloral hydrate/hydroxine combination with and without
meperidine in the sedation of pediatric dental patients.
Pediatric Dentistry 1990;12(5):288–91.
12. Ram D, Mamber E, Chosack A, Fuks AB. The effect of
metoclopramide and hydroxyzine in sedation of infants
undergoing dental treatment. ASDC Journal of Dentistry for
Children 1999;66(1):49–52.
13. Yanase H, Braham RL, Fukuta O, Kurosu K. A study of the
sedative effect of home-administered oral diazepam for the
dental treatment of children. International Journal of Paediatric
Dentistry 1996;6(1):13–7.
14. Reeves ST, Wiedenfeld KR, Wrobleski J, Hardin CL, Pinosky
ML. A randomized double-blind trial of chloral hydrate/
hydroxyzine versus midazolam/acetaminophen in the
sedation of pediatric dental outpatients. ASDC Journal of
Dentistry for Children 1996;63(2):95–100.
15. Shapira J, Holan G, Botzer E, Kupieztky A, Tal E, Fuks AB. The
effectiveness of midazolam and hydroxyzine as sedative
agents for young pediatric dental patients. ASDC Journal of
Dentistry for Children 1996;63(6):421–5.
17
16. Lam C, Udin RD, Malamed SF, Good DL, Forrest JL.
Midazolam premedication in children: a pilot study
comparing intramuscular and intranasal administration.
Anesthesia Progress 2005;52:56–61.
17. Lee-Kim SJ, Fadavi S, Punwani I, Koerber A. Nasal versus
oral midazolam sedation for pediatric dental patients.
Journal of Dentistry for Children 2004;71:126–30.
18. Meyer M, Mourino AP, Farrington FH. Comparison of
triazolam to a chloral hydrate/hydroxyzine combination in
the sedation of pediatric dental patients. Pediatric Dentistry
1990;12(5):283–7.
19. Veerkamp JSJ, Gruythuysen RJM, van Amerongen.
Hoogstraten J. Dental treatment of fearful children using
nitrous oxide. Part 3. Anxiety during sequential visits. ASDC
Journal of Dentistry for Children 1993;60(3):175–82.
20. Nathan JE, Venham LL, West MS, Werboff J. The effects of
nitrous oxide on anxious young pediatric patients across
sequential visits: a double blind study. ASDC Journal of
Dentistry for Children 1988;55(3):220–30.
21. Aydintug YS, Okcu KM, Guner Y, Gunaydin Y, Sencimen M.
Evaluation of oral or rectal midazolam as conscious
sedation for pediatric patients in oral surgery. Military
Medicine 2004;169:270–3.
22. Hartgraves PM, Primosch R. An evaluation of oral and nasal
midazolam for pediatric dental sedation. ASDC Journal of
Dentistry for Children 1994;61(3):175–8.
23. Lahoud GY, Averley PA. Comparison of sevoflurane and
nitrous oxide mixture with nitrous oxide alone for
inhalation conscious sedation in children having dental
treatment: a randomised controlled trial. Anaesthesia
2002;57(5):446–50.
24. Marshall WR, Weaver BD, McCutcheon P. A study of the
effectiveness of oral midazolam as a dental pre-operative
sedative and hypnotic. Special Care in Dentistry
1999;19(6):259–66.
25. Moody Jr EH, Mourino AP, Campbell RL. The therapeutic
effectiveness of nitrous oxide and chloral hydrate
administered orally, rectally, and combined with
hydroxyzine for pediatric dentistry. ASDC Journal of Dentistry
for Children 1986;53(6):425–9.
26. Wilson KE, Welbury RR, Girdler NM. A randomised,
controlled, crossover trial of oral midazolam and nitrous
oxide for paediatric dental sedation. Anaesthesia
2002;57(9):860–7.
27. Wilson KE, Girdler NM, Welbury RR. Randomized,
controlled, cross-over clinical trial comparing intravenous
midazolam sedation with nitrous oxide sedation in children
undergoing dental extractions. British Journal of Anaesthesia
2003;91(6):850–6.
28. Averley PA, Lane I, Sykes J, Girdler NM, Steen N, Bond S. An
RCT pilot study to test the effects of intravenous midazolam
as a conscious sedation technique for anxious children
requiring dental treatment—an alternative to general
anaesthesia. British Dental Journal 2004;197(9):553–8.
29. Averley PA, Girdler NM, Bond S, Steen N, Steele J. A
randomised controlled trial of paediatric conscious sedation
for dental treatment using intravenous midazolam
combined with inhaled nitrous oxide or nitrous oxide/
sevoflurane. Anaesthesia 2004;59:844–52.
30. Leelataweewud P, Vann WF, Dilley DC, Lucas WJ. The
physiological effects of supplemental oxygen versus nitrous
oxide/oxygen during conscious sedation of pediatric dental
patients. Pediatric Dentistry 2000;22(2):125–33.
31. Primosch RE, Buzzi IM, Jerrell G. Effect of nitrous oxideoxygen inhalation with scavenging on behavioral and
physiological parameters during routine pediatric dental
treatment. Pediatric Dentistry 1999;21(7):417–20.
32. Sullivan DC, Wilson CF, Webb MD. A comparison of two oral
ketamine–diazepam regimens for the sedation of anxious
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
JJOD-1030; No of Pages 19
18
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
journal of dentistry xxx (2006) xxx–xxx
pediatric dental patients. Pediatric Dentistry 2001;23(3):
223–31.
Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ.
Quantitative systematic review of topically applied
non-steroidal anti-inflammatory drugs. BMJ
1998;316(7128):333–8.
Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical
evidence of bias. Dimensions of methodological quality
associated with estimates of treatment effects in controlled
trials. JAMA 1995;273:408–12.
Moher D, Schulz KF, Altman DG. The CONSORT statement:
revised recommendations for improving the quality of
reports of parallel-group randomised trials. Lancet
2001;357(9263):1191–4.
Evans WO, Tannenbaum K, Turek B, Alling EF. A method for
evaluating the use of premedicating agents in difficult
pedodontic patients. Journal of Dentistry for Children 1966:
317–23.
Flaitz CM, Nowak AJ, Hicks MJ. Double blind comparison of
rectally administered diazepam to placebo for pediatric
sedation: the cardiovascular response. Anesthesia Progress
1985;32(6):232–6.
Gallardo F, Cornejo G, Auil B. Premedication with
flunitrazepam, diazepam and placebo in the apprehensive
child. ASDC Journal of Dentistry for Children 1984;51(3):208–10.
Gallardo F, Cornejo G, Borie R. Oral midazolam as
premedication for the apprehensive child before dental
treatment. Journal of Clinical Paediatric Dentistry
1994;18(2):123–7.
Houpt M, Manetas C, Joshi A, Desjardins P. Effects of chloral
hydrate on nitrous oxide sedation of children. Pediatric
Dentistry 1989;11(1):26–9.
Kapur A, Chawla HS, Goyal A, Gauba K, Bhardwaj N. Efficacy
and acceptability of oral-transmucosal midazolam as a
conscious sedation agent in pre-school children. Journal of
the Indian Society of Pedodontics and Preventive Dentistry
2004;22(3):109–13.
McKee K, Nazif MM, Jackson DL, Barnhart DC, Close J, Moore
PA. Dose–responsive characteristics of meperidine sedation
in preschool children. Pediatric Dentistry 1990;12(4):222–7.
Moore PA, Mickey EA, Hargreaves JA, Needleman HL.
Sedation in pediatric dentistry: a practical assessment
procedure. Journal American Dental Association
1984;109(4):564–9.
Al-Rakaf H, Bello LL, Turkustani A, Adenubi JO. Intranasal
midazolam in conscious sedation of young paediatric dental
patients. International Journal of Paediatric Dentistry
2001;11(1):33–40.
El Magboul KM, O’Sullivan EA, Curzon ME. A clinical trial
comparing two doses of oral temazepam for sedation of
paediatric dental patients. International Journal of Paediatric
Dentistry 1995;5(2):97–102.
Fuks AB, Kaufman E, Ram D, Hovav S, Shapira J. Assessment
of two doses of intranasal midazolam for sedation of young
pediatric dental patients. Pediatric Dentistry 1994;16(4):
301–30.
Houpt MI, Weiss NJ, Koenigsberg SR, Desjardins PJ.
Comparison of chloral hydrate with and without
promethazine in the sedation of young children. Pediatric
Dentistry 1985;7(1):41–6.
Houpt MI, Sheskin RB, Koenigsberg SR, Desjardins PJ, Shey
Z. Assessing chloral hydrate dosage for young children.
ASDC Journal of Dentistry for Children 1985;52(5):364–9.
Wilson S. Facial electromyography and chloral
hydrate in the young dental patient. Pediatric Dentistry
1993;15(5):343–7.
Abrams R, Morrison JE, Villasenor A, Hencmann D, Fonseca
M, Mueller W. Safety and effectiveness of intranasal
administration of sedative medications (ketamine,
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
midazolam, or sufentanil) for urgent brief pediatric dental
procedures. Anesthesia Progress 1993;40(3):63–6.
Alfonzo-Echeverri EC, Berg JH, Wild TW, Glass NL. Oral
ketamine for pediatric outpatient dental surgery sedation.
Pediatric Dentistry 1993;15(3):182–5.
Avalos-Arena V, Moyao-Garcia D, NavaOcampo AA, ZayazCarranza REZ, Fragoso-Rios R. Is chloral hydrate/hydroxyzine
a good option for paediatric dental outpatient sedation?
Current Medical Research and Opinion 1998;14(4):219–26.
Badalaty MM, Houpt M, Koenigsberg SR, Maxwell KC,
Desjardins PJ. A comparison of chloral hydrate and
diazepam sedation in young children. Pediatric Dentistry
1990;12(1):33–7.
Bui T, Redden RJ, Murphy S. A comparison study between
ketamine and ketamine–promethazine combination for oral
sedation in pediatric dental patients. Anesthesia Progress
2002;49(1):14–8.
Dallman JA, Ignelzi Jr MA, Briskie DM. Comparing the safety,
efficacy and recovery of intranasal midazolam vs. oral
chloral hydrate and promethazine. Pediatric Dentistry
2001;23(5):424–30.
Downs T, Dembo J, Ferreti G, Lyons TD, Pelphery A. A
comparative study of midazolam to meperidine/
promethazine as an IM sedative technique for the pediatric
dental patient. ASDC Journal of Dentistry for Children
1997;64(3):197–200.
Haas DA, Nenninger SA, Yacobi R, Magathan JG, Grad H,
Copp PE, et al. A pilot study of the efficacy of oral midazolam
for sedation in pediatric dental patients. Anesthesia Progress
1996;43(1):1–8.
Hasty MF, Vann WF, Dilley DC, Anderson J. Conscious
sedation of pediatric dental patients: an investigation of
chloral hydrate, hydroxyzine pamoate, and meperidine vs.
chloral hydrate and hydroxyzine pamoate. Pediatric Dentistry
1991;13(1):10–9.
Houpt MI, Kupietzky A, Tofsky NS, Koenigsberg SR. Effects
of nitrous oxide on diazepam sedation of young children.
Pediatric Dentistry 1996;18(3):236–41.
Jensen B, Schroder U, Mansson U. Rectal sedation with
diazepam or midazolam during extractions of traumatized
primary incisors; a prospective, randomized, double-blind
trial in Swedish children aged 1.5–3.5 years. Acta
Odontologica Scandinavia 1999;57(4):190–4.
Lo¨kken P, Bakstad OJ, Fonnelop E, Skogedal N, Hellsten K,
Bjerkelund CE, et al. Conscious sedation by rectal
administration of midazolam or midazolam plus ketamine
as alternatives to general anesthesia for dental treatment of
uncooperative children. Scandinavian Journal of Dental
Research 1994;102(5):274–80.
McCann W, Wilson S, Larsen P, Stehle B. The effects of
nitrous oxide on behavior and physiological parameters
during conscious sedation with a moderate dose of chloral
hydrate and hydroxyzine. Pediatric Dentistry 1996;18(1):35–41.
Musial KM, Wilson S, Preisch J, Weaver J. Comparison of the
efficacy of oral midazolam alone vs midazolam and
meperidine in the paediatric dental patient. Pediatric
Dentistry 2003;25(5):468–74.
Roelofse JA, Joubert JJ, Roelofse PG. A double-blind
randomized comparison of midazolam alone and
midazolam combined with ketamine for sedation of
pediatric dental patients. Journal of Oral and Maxillofacial
Surgery 1996;54(7):838–44.
Roelofse JA, Joubert JJ, Swart LC, Stander I, Roelofse PG.
An evaluation of the effect of oral ketamine and standard
oral premedication in the sedation of paediatric dental
patients. Journal of the Dental Association of South Africa
1996;51(4):197–201.
Roelofse JA, Louw LR, Roelofse PG. A double-blind
randomized comparison of midazolam alone and
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002
JJOD-1030; No of Pages 19
journal of dentistry xxx (2006) xxx–xxx
midazolam combined with ketamine for sedation of
pediatric dental patients. Anesthesia Progress 1998;45(1):3–11.
67. Sams DR, Cook EW, Jackson JG, Roebuck BL. Behavioral
assessments of two drug combinations for oral sedation.
Pediatric Dentistry 1993;15(3):186–90.
68. Shapira J, Holan G, Guelmann M, Cahan S. Evaluation of the
effect of nitrous oxide and hydroxyzine in controlling the
behavior of the pediatric dental patient. Pediatric Dentistry
1992;14(3):167–70.
69. Shapira J, Kupietzky A, Kadari A, Fuks AB, Holan G.
Comparison of oral midazolam with and without
hydroxyzine in the sedation of pediatric dental patients.
Pediatric Dentistry 2004;26(6):492–6.
19
70. Singh N, Pandey RK, Saksena AK, Jaiswal JN. A comparative
evaluation of oral midazolam with other sedatives as
premedication in pediatric dentistry. Journal of Clinical
Pediatric Dentistry 2002;26(2):161–4.
71. Songvasin C, Pasavorakul A. A comparison of the child’s
behavior between two groups of oral sedative drugs.
Journal of the Dental Association of Thailand 1990;40(6):
237–45.
72. Tsinidou KG, Curzon ME, Sapsford DJ. A study to compare
the effectiveness of temazepam and a chloral hydrate/
hydroxyzine combination in sedating paediatric dental
patients. International Journal of Paediatric Dentistry
1992;2(3):163–9.
Please cite this article as: L.L. Matharu, P.F. Ashley, What is the evidence for paediatric dental sedation?, Journal of Dentistry (2006),
doi:10.1016/j.jdent.2006.08.002