Conscious Sedation Procedures Using Intravenous
Midazolam for Dental Care in Patients with Different
Cognitive Profiles: A Prospective Study of Effectiveness
Vale ´rie Collado1,2*, Denise Faulks1,2, Emmanuel Nicolas1,2, Martine Hennequin1,2
1Clermont Universite ´, Universite ´ d’Auvergne, EA4847, Centre de Recherche en Odontologie Clinique, BP 10448, F-63000 Clermont-Ferrand, France, 2CHU Clermont-
Ferrand, Service d’Odontologie, Ho ˆtel-Dieu, F-63000 Clermont-Ferrand, France
The use of midazolam for dental care in patients with intellectual disability is poorly documented. This study aimed to
evaluate the effectiveness and safety of conscious sedation procedures using intravenous midazolam in adults and children
with intellectual disability (ID) compared to dentally anxious patients (DA). Ninety-eight patients with ID and 44 patients
with DA programmed for intravenous midazolam participated in the study over 187 and 133 sessions, respectively.
Evaluation criteria were success of dental treatment, cooperation level (modified Venham scale), and occurrence of adverse
effects. The mean intravenous dose administered was 8.864.9 mg and 9.864.1 mg in ID and DA sessions respectively (t-
test, NS). 50% N2O/O2was administered during cannulation in 51% of ID sessions and 61% of DA sessions (NS, Fisher exact
test). Oral or rectal midazolam premedication was administered for cannulation in 31% of ID sessions and 3% of DA sessions
(p,0,001, Fisher exact test). Dental treatment was successful in 9 out of 10 sessions for both groups. Minor adverse effects
occurred in 16.6% and 6.8% of ID and DA sessions respectively (p=0.01, Fisher exact test). Patients with ID were more often
very disturbed during cannulation (25.4% ID vs. 3.9% DA sessions) and were less often relaxed after induction (58.9% ID vs.
90.3% DA) and during dental treatment (39.5% ID vs. 59.7% DA) (p,0.001, Fisher exact test) than patients with DA. When
midazolam sedation was repeated, cooperation improved for both groups. Conscious sedation procedures using
intravenous midazolam, with or without premedication and/or inhalation sedation (50% N2O/O2), were shown to be safe
and effective in patients with intellectual disability when administered by dentists.
Citation: Collado V, Faulks D, Nicolas E, Hennequin M (2013) Conscious Sedation Procedures Using Intravenous Midazolam for Dental Care in Patients with
Different Cognitive Profiles: A Prospective Study of Effectiveness and Safety. PLoS ONE 8(8): e71240. doi:10.1371/journal.pone.0071240
Editor: Michael Glogauer, University of Toronto, Canada
Received February 11, 2013; Accepted June 27, 2013; Published August 5, 2013
Copyright: ? 2013 Collado et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was financed by a 2004 local hospital medical research fund (Projet Hospitalier de Recherche Clinique). The funders had no role in study
design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org
A large minority of the population does not possess the cognitive
capacity and adaptive skills required to cope with dental treatment
and therefore cannot access therapeutic or preventive care. These
difficulties particularly concern patients with cognitive impairment
but other non-cognitively impaired patients, such as very young
children or dentally anxious children and adults, also present
behavioural difficulties during dental care leaving them vulnerable
to poor oral health or undiagnosed problems . For these
patients, conscious sedation may improve the treatment experi-
ence whilst avoiding the use of physical restraint and thus may
influence long-term levels of anxiety . Numerous studies report
the use of midazolam (HypnovelH, VersedH), a short acting
benzodiazepine, alone or with other drugs during dental treatment
or other invasive outpatient care [3–6]. The UK definition of
conscious sedation in dentistry is used in this article: ‘‘A technique
in which the use of a drug or drugs produces a state of depression
of the central nervous system enabling treatment to be carried out,
but during which verbal contact with the patient is maintained
throughout the period of sedation. The drugs and techniques used
to provide conscious sedation for dental treatment should carry a
margin of safety wide enough to render loss of consciousness
Published studies investigating the effectiveness and tolerance of
midazolam used as a single agent for dental treatment are
heterogeneous in their evaluation criteria, use different means of
administration, concern different populations and are carried out
in different settings [3,4,8–12]. In anxious adults without disability,
the drug is usually administered intravenously. This route has
many advantages. The presence of continuous venous access
improves safety as it enables rapid injection of the antagonist
flumazenil if necessary. Moreover, the intravenous route allows
incremental titration of midazolam (usually 1 mg/min) and this
limits the risk of respiratory depression . Titration also reduces
the risk of under- or over- sedation by allowing the clinician to
obtain the desired level of sedation for each individual patient and
for the type of treatment planned. Studies using intravenous
midazolam in anxious patients have reported high success rates
(evaluated by the percentage of planned dental treatment
performed) without serious complication during oral surgery and
PLOS ONE | www.plosone.org1August 2013 | Volume 8 | Issue 8 | e71240
dental treatment [3,14,15]. However, the level of cooperation or
anxiety of the patient over the sessions has never been reported.
For young or anxious children, as for patients with intellectual
disability, little specific data are available in these populations [16–
22]. Midazolam is usually reported as being administered using an
intranasal, intrarectal or oral route [23–27] because of potential
better acceptability of these routes. Indeed, the acceptability of
intravenous midazolam may be poor in patients that are often
anxious about needles and failure of planned sedation may occur
on cannulation in young children . In a study comparing
nitrous oxide to intravenous midazolam sedation for orthodontic
extractions in adolescents, the main reason evoked for not
participating in the trial was fear of cannulation (24% of 55
patients approached) . However, the technique showed good
effectiveness and safety when the IV midazolam protocol was
accepted and IV midazolam was even preferred to nitrous oxide
most of the time. One recent study also reported very good or
excellent behaviour during dental treatment under IV sedation for
83% of 365 patients aged 7 to 16 years . In adults with
learning disability and challenging behaviour, two consecutive
audits have investigated the use of intravenous titration to the
sedation endpoint after intranasal midazolam premedication to
facilitate cannulation [30,31]. This technique allowed dental
treatment to be carried out without major interference from the
patient in 78.8% of cases . Minor adverse events occurred in
6% of cases in these patients, of whom many had associated
medical conditions. Unfortunately, neither the behaviour of the
patients, nor the evolution of the psychological state of the patient
over the session, were detailed.
The present study aimed to evaluate the effectiveness and safety
of conscious sedation procedures using intravenous midazolam for
dental care undertaken by trained hospital dentists in adults and
children with intellectual disability (ID) compared with adults and
children with dental anxiety (DA).
Three dental practitioners with postgraduate training in
midazolam conscious sedation conducted this study at a University
Hospital. All have ten to twenty years of experience of the routine
use of conscious sedation using both 50% nitrous oxide/oxygen
and midazolam IV, IR and PO, in populations with intellectual
disability and/or anxiety. All are postgraduate teachers in
conscious sedation at the Dental University and University
Hospital of Clermont-Ferrand (France).
Approval was obtained from the local ethical comity (CCPPRB
Auvergne i.e. ‘‘Comite ´ Consultatif de Protection des Personnes se
pre ˆtant a ` la Recherche Biome ´dicale’’) under registration number
AU-571, and from the French National Drugs Agency (AFF-
SAPS), for an initial clinical trial entitled ‘‘Conscious sedation with
midazolam in patients with dental anxiety: Impact of administra-
tion route (oral versus intravenous)’’. The registration number on
the ‘‘Clinical Trials’’ website for this study was NCT 01874717.
However, oral administration was refused by patients or carers
most of the time after IV administration or in some cases, an
additional intravenous dose was necessary after oral administra-
tion. Consequently, in order to respect patients’ choice, the
objectives of the study were changed and aimed at comparing
patients with different cognitive profiles requiring IV sedation with
midazolam for dental care. The Regional Clinical Research
Division was immediately informed of this change and there was
no additional requirement to resume the study. Furthermore, after
update in the French ethical laws related to human research,
global approval from the local ethical committee (nuCE-CIC-
GREN-11/17) was obtained for all observational studies evaluat-
ing the quality of dental treatment performed in the dental
university hospital of Clermont-Ferrand (France). This new text
clearly stated that dental care under sedation or general
anaesthesia was covered by this approval. The agreement specified
that all patients visiting the unit should receive oral and written
information mentioning that data obtained during dental care
could be used anonymously for research purposes unless the
patient specifically stated in writing otherwise (tacit agreement).
All children and adults programmed for dental treatment under
intravenous sedation with midazolam over a period of 50 months
were considered for inclusion in the study. Exclusion criteria were:
i) patients in the American Society of Anesthesiologists (ASA)
category III, IV or V ; ii) patients having accepted dental
treatment without premedication or sedation, and without
declaring dental anxiety, during the month prior to the
appointment; iii) Any medical contraindication to the use of
midazolam. All patients were referred to the Unit of Special Care
Dentistry by a general dental practitioner, a physician or member
of the medical staff of a special institution. Conscious sedation with
intravenous midazolam was planned if the patient could not be
approached for more than a very brief examination, following
failure to treat under inhalation sedation (50% N2O/O2), or
following poor cooperation during treatment under inhalation
sedation (50% N2O/O2). Poor cooperation was defined as a score
of 3 or more on the French modified version of the Venham scale
[33,34] (Table 1).
Patients were assigned to two groups. Patients in the dental
anxiety group (DA) expressed dental anxiety but had no
intellectual disability. Patients in the intellectual disability group
(ID) had an appropriate medical diagnosis or attended a special
school, home or work placement. The children and adults in the
ID group showed anxiety and/or poor cooperation due to
difficulty interpreting the dental situation and due to functional
and physical barriers to care.
A medical, dental and social evaluation of each patient was
undertaken prior to intravenous sedation. This assessment
confirmed the absence of a medical contraindication to the use
of midazolam and revealed possible problems for intravenous
cannulation (anatomical difficulties, difficulty coping with nee-
dles…). Patients were informed that an appropriate escort should
be present from the start of the sedation session and remain with
the patient over the following 24 hours. Oral and written pre- and
post- operative instructions were given. When difficulties of
anxiety or cooperation linked to the use of a needle were
expressed by the patient or his/her carer, topical anaesthesia was
prescribed (EMLAH5% cream: lidocaı ¨ne/prilocaı ¨ne 50/50) to be
applied to the site of cannulation one hour before the appoint-
ment. Fasting was not required prior to intravenous sedation, but
light meals only were recommended . Treatment planning was
also discussed with the patient and/or the carer, and consent to
treat was obtained.
On attending for treatment under intravenous sedation,
adherence to the preoperative instructions was verified and the
escort was made fully aware of his or her postoperative role.
Medical history and consent were confirmed. If necessary and
possible, inhalation sedation (50% N2O/O2) was administered
during cannulation in order to reduce anxiety and provide surface
analgesia. When it was anticipated that inhalation sedation (50%
IV Midazolam in Dental Patients with Disability
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N2O/O2) would be inadequate or impossible, an oral or rectal
premedication was given. Commonly, oral midazolam was
administered 10 to 20 minutes before cannulation (midazolam
for injection at 5 mg/ml, (PanpharmaH) mixed with sweetened
syrup at the dose of 0.3 to 0.5 mg/kg). In certain patients, used to
the administration of suppositories, intrarectal midazolam was
occasionally administered (midazolam for injection at 5 mg/ml,
(PanpharmaH) given intra-rectally with a commercially available
adapted syringe). In a few cases, oral hydroxyzine was prescribed
1K hours before the appointment (AtaraxH, 2 mg/kg). In one
case, alprazolam was given to a patient with DA before
implantology treatment (XanaxH, 0.25 mg the day before at
bedtime and 0.25 mg one hour before dental treatment). If
necessary, inhalation sedation (50% N2O/O2) was used in
addition to premedication for cannulation but was removed
during titration of midazolam in order to be able to gauge the
sedative effect of the drug on behaviour and the physiological
parameters. During dental treatment under IV midazolam,
inhalation sedation (50% N2O/O2) was added if required in
relation to the behaviour and to the physiological state of the
patient. In particular, this technique was used to increase the level
of sedation without further increasing the risk of respiratory
depression. Oxygen was not systematically administered during
The patient was monitored clinically from the moment of their
arrival in the Unit. For most patients, a baseline physiological
assessment was established before the administration of any drugs.
For certain patients with marked opposition, sedation was
commenced and the pulse oxymeter and blood pressure cuff
placed as soon as physically possible. Systolic and diastolic blood
pressure (SBP and DBP), heart rate (HR) and oxygen saturation
(SpO2) were recorded throughout the sedation session and the
recovery period (Monitor: DINAMAP ProCare 300). Following
cannulation, intravenous midazolam (5 ml ampoules, 1 mg/ml,
PanpharmaH) was titrated (slow injection of 2 mg, wait 90 s, then
titration in increments of 1 mg at 1 minute intervals) until a level
of sedation was obtained that was sufficient for dental care to be
performed in comfortable conditions for the patient.
From arrival at the hospital, and throughout the session and
recovery period, behavioural management techniques were used
continuously (e.g. maintenance of physical and verbal contact,
positive reinforcement, reassurance, positive suggestion etc.).
These techniques were adapted to the age and communication
skills of the patient. Time was taken to introduce the patients to the
different steps of the procedure and stress reducing strategies were
used continually during care. Local anaesthesia was used
systematically if there was the least risk of pain during treatment
(including subgingival scaling or rubber dam clamp placement…).
1) The first objective was to study the effectiveness of the
procedure. The three criteria used to assess effectiveness were the
success of the treatment session, the level of cooperation during the
session, and any positive change on repeat sedation.
N Success: The session was considered a ‘total success’ if the
intended dental treatment was completed under intravenous
sedation. It was a ‘partial success’ if only part of the planned
dental care could be performed. ‘Failure’ was recorded if no
dental treatment was possible. The type of treatment
undertaken was also recorded.
N Level of cooperation: This was assessed using the French
modified Venham scale [33,34] (Table 1). This scale offers a
good description of behaviour and anxiety in one score (from 0
and 5). The intra- and inter- examiner reliability of this scale
has been previously confirmed . Inter-investigator variabil-
ity for the French modified Venham scale was controlled for
the three dentists participating in the current study and was
not statistically significant (General Linear Models procedure).
The French modified Venham scale was applied at the
following periods during the sedation session: Ti: At first
contact with the dentist; T0: During venous cannulation; T1:
At the end of the induction; T2: During the first injection of
local anaesthesia; T3: At the moment of least cooperation
during initial dental treatment.
Table 1. English translation of the French modified Venham Scale.
0 Relaxed, smiling, willing, able to converse, best possible working conditions; displays the behaviour desired by the dentist spontaneously, or immediately
upon being asked
1 Uneasy, concerned; eye contact but tense facial expression; suspicious of environment; sits spontaneously back in the chair; hands remain down or partially
raised to signal discomfort; during a stressful procedure may briefly and rapidly protest to demonstrate discomfort; the patient is willing and able to
describe experience as requested; breath is sometimes held; capable of cooperating well with treatment.
2 Tense; tone of voice, questions and answers reflect anxiety; multiple requests for information; hands clench armrests or may be tense or raised without
interfering with treatment; sits back spontaneously in chair but head and neck tense; accepts handholding; eye contact; during stressful procedure verbal
protest, quiet crying; patient interprets situation with reasonable accuracy and continues to work to cope with his/her anxiety; protests more troublesome;
patient still complies with request to cooperate; continuity is undisturbed
3Reluctant; tends to reject the treatment situation, difficulty in assessing situational threat; frequent sighs; pronounced protest, crying; only sits back in chair
after being asked several times, the head and neck remain tense; slight movements of avoidance; tense hands, avoids eye contact; accepts handholding;
minor attempts to use hands to stop procedure; wriggling; protest out of proportion to threat or is expressed well before the threat; copes with situation
with great reluctance; treatment proceeds with difficulty
4 Very disturbed by anxiety and unable to assess situation; physically very tense, wrinkled eyebrows, eye contact avoided or eyes shut; general crying not
related to treatment; prominent avoiding movements, needing physical restraint on occasion; places hands over mouth or on dentist’s arm to prevent
treatment, but eventually allows care to progress; pinches lips together but ends up by opening mouth; regularly lifts head from chair; rejects physical
contact but may still accept handholding; patient can be reached through oral communication and eventually with reluctance and great effort begins to
work to cope; dissociation is only partial; protest regularly disrupts procedure
5 Out of contact, fails to grasp the reality of the threat; inaccessible to oral and visual communication; rejects physical contact; clenches mouth and lips; closes
mouth and clenches teeth whenever possible; violent head movements; screaming, shouting, swearing, fighting, aggressive; regardless of age, reverts to
primitive flight responses; actively involved in escape behaviour; physical restraint required
IV Midazolam in Dental Patients with Disability
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Repeat sedation: The group of sessions corresponding to a first
experience of intravenous sedation with midazolam was compared
with the group of repeat sedation sessions. The success rate, the
level of cooperation, the rate of adverse effects, and the dose of
intravenous midazolam required were compared.
2) The second objective was to study the safety of the procedure.
The criteria used to assess safety were: the incidence of adverse
events during the sedation and recovery periods, the values of the
recorded physiological parameters and the Ramsay score of level
N Adverse events: These were pre-listed according to 5
categories: respiratory problems (hyper or hypoventilation,
desaturation), digestive problems (nausea, vomiting), neuro-
logical problems (convulsions, epileptic fit…), behavioural
events (euphoria, hyper-excitability…), vaso-vagal effects
(sweating, pallor, faint…).
N Physiological parameters: The minimal level of oxygen
saturation (SpO2), the minimal and maximal values of heart
rate (HR), and systolic and diastolic blood pressure (SBP and
DBP respectively) were recorded for each session. Normative
values for physiological parameters were established (Table 2).
The percentage of sessions with values outlying the normative
range was analysed.
N Ramsay scores: The level of sedation was recorded applying
Ramsay scale on first opening the mouth for examination after
induction (T4), at the start of actual dental treatment (after
local anaesthesia if necessary) (T5) and at the end of dental
treatment (T6)  (Table 3). In order to meet the definition of
conscious sedation, the Ramsay score should not exceed 3.
The statistical analysis was designed to study any potential
differences between patients with DA and patients with ID as
regards: age, gender, success rate, Venham scores, adverse events,
Ramsay scores and percentage of sessions with physiological
parameters out of the normal range. Statistical significance was set
N Characteristics of the patients and progress of conscious
sedation sessions: Age difference between the two groups was
assessed by t-test. Gender distribution was compared by
Fisher-exact test. Comparison of the mean duration of the
conscious sedation sessions and of recovery time between the
two groups, and comparison of the mean dose of intravenous
midazolam, were undertaken using a t-test (a=0.05). The
frequency of the use of inhalation sedation (50% N2O/O2)
and/or of premedication for cannulation, were compared
between DA and ID groups using Fisher’s exact test.
N Success rate and adverse events: The Fisher’s exact test was
used to compare the success rate and the percentage of adverse
events between the two groups. The type of dental treatment
performed was compared using the Pearson chi square test.
N Level of cooperation: The distribution of Venham scores at Ti,
T0, T1, T2 and T3 was assessed for DA and ID groups. Three
levels of cooperation were defined: i) Venham score 0: patient
totally relaxed; ii) Venham score 1 to 3: moderate difficulties
with cooperation; iii) Venham score 4 or 5: very disturbed
patient, restraint necessary for treatment. Analysis of the
distribution of the extreme levels (0 on one hand and 4–5 on
the other) between patients with DA and with ID was
undertaken using the Fisher exact test.
N Influence of repeat sessions: The group of sessions correspond-
ing to a first experience of intravenous sedation with
midazolam was compared with the group of repeat conscious
sedation sessions. The success rate and the rate of adverse
effects were compared with a Fisher exact test for DA and ID
groups. The distribution of the extreme scores on the modified
Venham scale (0 vs 4–5) at each time (Ti, T0, T1, T2, T3) was
compared similarly. The dose of intravenous midazolam was
also compared applying an independent t-test.
N Physiological parameters: Normative values for physiological
parameters were established (Table 3). The percentage of
sessions with SpO2, HR, SBP and DBP respectively outlying
the normal range in the two groups was compared using the
Fisher exact test.
N The distribution of Ramsay scores at T4, T5, and T6 was
compared between groups using a Pearson chi square test.
Characteristics of the Patients and Progress of Conscious
Ninety-eight patients with ID and 44 patients with DA were
included in the study over 187 and 133 sessions of dental care
under intravenous midazolam respectively. Demographic charac-
teristics for DA and ID groups are given in Table 4. Both groups
were similar in age (t-test) and gender (Fisher exact test). Thirty-
eight sessions were performed in patients under 16 years. Thirty-
three children with ID were included in the study with a mean age
of 12.862.4 years (min: 8, max: 15). Five children with DA were
included (7, 8, 13, 14 and 15 years old).
The average duration of the sedation sessions from administra-
tion of premedication to the end of treatment was 72628 min
(min: 20, max: 160) and 103636 min (min: 25, max: 258) for
patients with ID and DA respectively (p,0.05, t-test). Inhalation
sedation (50% N2O/O2) was administered during intravenous
cannulation in 51.1% (94/184) of sessions for the ID group and
61.4% (81/132) of sessions for the DA group (NS, Fisher exact
test). Inhalation sedation (50% N2O/O2) was administered during
all or part of dental treatment in 50.0% (39/78) sessions performed
Table 2. Normative values of physiological parameters considered for this study.
Heart Rate (beats/min) Systolic Blood Pressure (mmHg) Diastolic Blood Pressure (mmHg)
Normative range Standards Normative rangeStandardsNormative range
119065, .1609570, .12055 40, . , .100
12–1870 60, .160110 70, .1305845, ., .110
Adult7550, ., .160122 70, . , .1457550, . , .120
IV Midazolam in Dental Patients with Disability
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in the ID group and 67.1% (47/70) sessions in the DA group. The
mean dose of midazolam given intravenously was 8.8 mg
64.9 mg (min: 3 mg, max: 27 mg) for the ID group and 9.8 mg
64.1 mg (min: 2 mg, max: 28 mg) for the DA group (NS, t-test).
The duration of titration of intravenous midazolam was correlated
to the dose administrated (p,0.05, Pearson correlation). Premed-
ication was given before cannulation in 58/187 (31%) sessions for
patients with ID (midazolam: n=55, hydroxyzine: n=3) and in 4/
133 (3%) sessions for patients with DA (oral midazolam: n=2,
hydroxyzine: n=1, alprazolam: n=1). Oral midazolam was the
most common premedication for patients with ID (49/55). Rectal
administration was used for 8 sessions in 8 different patients with
ID. Recovery time was not different between the groups:
54636 min (min: 10, max: 180) for patients with ID and
44630 min (min: 0, max: 150) for patients with DA.
Planned dental treatment was successfully performed in 90.6%
of sessions in patients with DA and 89.1% in patients with ID, with
no difference between groups (chi square test, NS). 7.1% of
sessions in patients with DA and 10.3% of sessions in patients with
ID were a ‘partial success’ (only part of the planned treatment
completed). A total failure, or abandon of treatment, was recorded
in 3 patients (2 with DA and 1 with ID), and these were
subsequently referred for general anaesthesia. Of these patients,
one 18 year old woman with DA received 0.5 mg/kg of oral
midazolam and 8 mg of IV midazolam. She exhibited Venham
scores of 5 throughout the session from the moment of
cannulation. One 14 year old girl with DA received 6 mg of IV
midazolam. She needed endodontic treatment for a first mandib-
ular molar but she presented Venham scores of 3 or 4 throughout
the session. One 13 year old boy with autistic disorder received
0.3 mg/kg of oral midazolam (but refused to drink all the
preparation) and then 6 mg of IV midazolam. He also needed
endodontic treatment for a first mandibular molar and exhibited
scores of 3 or 4 throughout the session.
The type of dental treatment for which midazolam sedation was
indicated was different between the groups (p,0,001, Pearson chi
square test). More sessions for oral hygiene and scaling were
undertaken in the group with ID and more conservative
procedures (restorative or endodontic treatments) were performed
for patients with DA (Table 5).
Level of Cooperation
The distribution of the three levels of Venham score, at each
time point and for each group, is presented in Figure 1. When
comparing only the extreme Venham scores (0 or 4–5), the
following differences were demonstrated between patients with DA
and those with ID: At T0, there were significantly more sessions
with Venham scores of 4 or 5 for patients with ID (45/177, 25.4%)
than for patients with DA (5/128, 3.9%) (p,0.001, Fisher exact
test). At T1, significantly more sessions for patients with DA scored
0 than for patients with ID (112/124 (90.3%) vs. 99/168 (58.9%))
(p,0.001, Fisher exact test). At T3, in patients with ID, 70/177
(39.5%) sessions were undertaken with a totally relaxed patient
(score 0), whereas in patients with DA 77/129 (59.7%) sessions
were performed with a score of 0 (p,0.001, Fisher exact test).
Statistical analysis of scores of 4 and 5 at Ti, T1, T2 and T3 was
impossible because of the very low rates of these scores in patients
No major adverse event was recorded during the study. Minor
side effects were recorded for 16.6% (31/187) of sessions in
patients with ID and 6.8% (9/133) of sessions in patients with DA
(p=0.01, Fisher exact test) (Table 6). These rates were not
influenced by concomitant psychotropic treatment when present
(NS, Fisher exact test). The distribution of the type of adverse
events was not different between groups. Minor adverse events
were recorded in children under 16 years of age in 11 sessions, all
in patients with ID (1 episode of desaturation, 2 of hiccups, 3 of
nausea and 5 of hyperexcitability).
A print-out of physiological parameters was available for 110
sessions in patients with DA and 160 sessions in patients with ID.
In 53 sessions, the poor level of cooperation of patients with ID did
not allow baseline physiological assessment before initial induction
with IV midazolam.
In 34 sessions the recorded SpO2fell below 90%. Of these
sessions, 8/110 (7.3%) were in patients with DA and 26/160
(16.3%) concerned patients with ID (p,0.05 Fisher exact test). In
half of these sessions, low SpO2was recorded in the induction
period. In some cases, low recorded SpO2was related to loss of the
pulse oxymeter sensor from the finger. In all cases, low recorded
SpO2was corrected clinically by repositioning the sensor and by
using simple airway management techniques (repositioning the
patient to facilitate ventilation). Oxygen was administered (2l/min)
in three sessions (for two patients with ID and one patient with
DA), during 17 minutes in one case and 10 minutes in the others.
Flumazenil was administered at the end of the session for one
patient with intellectual disability in order to facilitate behaviour
management during the return journey to his special home. It was
never necessary to summon additional medical assistance.
In 17 sessions (12/110 in patients with DA and 5/160 in
patients with ID), the HR fell below the minimal normative value
in relation to the age of the patient (Table 3) (NS, Fisher Exact
test). In 4 sessions (1/110 in patients with DA and 3/160 in
patients with ID), it rose above over the maximal normative value
(NS, Fisher Exact test).
The SBP was below the minimal normative value at some point
for 3 sessions (all in patients with ID) and was above the maximal
Table 3. Ramsay sedation scale (Ramsay et al. 1974).
1Anxious and agitated or restless, or both
2 Cooperative, oriented, and tranquil
3 Responsive to commands only
4 Exhibiting a brisk response to light glabellar tap or loud auditory stimulus
5 Exhibiting a sluggish response to light glabellar tap or loud auditory stimulus
IV Midazolam in Dental Patients with Disability
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normative value at some point for 72 sessions: 17/110 (15.5%) in
patients with DA and 55/160 (34.4%) in patients with ID
(p,0.001, Fisher Exact test). The DBP was below the minimal
normative value at some point for 27 sessions (11/110 in patients
with DA and 16/160 in patients with ID) (Non Significant, Fisher
Exact test) and was over the maximal normative value at some
point for 12 sessions (all in patients with ID).
Level of Sedation
The distribution of Ramsay scores at T4, T5 and T6 was
different between patients with DA and patients with ID (p,0.001
at T4 and T6, and p,0.05 at T5, Pearson chi-square test)
(Table 7). On opening the mouth for initial examination after
induction (T4), the patients exhibited a Ramsay score of 1 to 3 in
all cases and so did not exceed the limit of conscious sedation. At
the start of actual dental treatment (T5), the Ramsay score was
over 3 in 2 sessions in two patients with ID and 1 session in a
patient with DA. At the end of treatment, when the stimulation of
treatment was over, there were 4 sessions in the ID group with a
Ramsay score of 4.
All patients subsequently recovered spontaneously without need
for the use of flumazenil for reversal or additional medical
assistance. However, all of these patients were contra-indicated for
IV midazolam for future treatment as it was considered that the
level of sedation necessary for treatment was over and above that
of the self-imposed limit of conscious sedation .
Influence of Repeat Conscious Sedation
More sessions in the DA group were undertaken in patients with
previous experience of the technique than for the group with ID
(66.9% vs. 47.6%) (p,0.001, Pearson chi square test). The mean
number of sessions per patient was 3.763.2 (min. 1, max. 16) for
patients with DA and 2.362.4 (min. 1, max. 15) for patients with
ID (p,0.001, t-test). When the sedation with intravenous
midazolam was repeated, the rate of total and partial success
combined increased significantly in patients with DA (from 92 to
99%, p,0.01 Fisher exact test) and remained statistically
unchanged in patients with ID (from 96 to 99%). No influence
of repetition on adverse events was found in either group. No
influence of repetition on the dose of midazolam administered was
found for either group (repeated measure procedure). For the
repeated sessions in patients with DA, more sessions were
conducted with a totally relaxed patient (Venham score of 0) at
Ti (37.1% repetition vs. 14.6% first experience, p,0.01, Fisher
exact test) and T1 (94.1% vs. 82.1%, p,0.05, Fisher exact test)
(Figure 2). Statistical analysis was not possible for Venham scores
of 4 or 5 because there were too few sessions with such scores. In
patients with ID, more repeat sessions reported a Venham score of
0 at T0 (33.3% repetition vs. 15.6% first experience, p,0.01,
Fisher exact test) and at T3 (51.2% vs. 28.6%, p,0.001, Fisher
exact test). At T0, the patients were also less often very disturbed
or out of contact (Venham scores of 4 or 5) when the procedure
was repeated (19.5% vs. 31%, p,0.01, Fisher exact test). At T1,
very few sessions were conducted with a Venham score of 4 or 5 so
no statistical analysis was possible.
Discussion and Conclusions
Conscious sedation procedures using intravenous midazolam
administered with or without inhalation sedation (50% N2O2) or
premedication were shown to be safe and effective in patients with
intellectual disability as well as patients with dental anxiety
disorder. This study is the first prospective clinical trial giving
comparative data of conscious sedation for dental care in patients
Table 4. Demographic characteristics of the DA (dental anxiety) and ID (intellectual disability) groups.
Male/Female n (%)
Age in years Mean (± SD)
No. Sessions in
patients , ,16 years
Type of patients
Patients with Dental
27.0 (69.5) [7–66]
Associated medical condition
(epilepsy, heart disorder, cancer,
30.5 (611.6) [8–57]
Rare genetic syndrome
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with intellectual disability and no influence of routine psychotropic
treatment on the effectiveness or safety of the procedures used was
found. In this study, thirty-eight sessions were performed in
children and adolescents. More sessions would be necessary to
allow a separate analysis of the young population.
The effectiveness of the conscious sedation could be partly
explained by the flexibility of the approach used in order to
address individual patient needs. In the vast majority of patients
requiring premedication, the drug given was midazolam (per os or
intrarectal) in order not to introduce multiple pharmacological
effects (55/58 sessions). Inhalation sedation (50% N2O2) was used
Table 5. Main dental treatment performed under intravenous midazolam sedation for patients with dental anxiety disorder (DA)
and patients with intellectual disability (ID).
Patients with DAPatients with ID
No. sessions (%)No. sessions (%)
Clinical assessment Clinical examination and radiographs0 (0%) 1 (0.6%)
Impression taking4 (3.3%)9 (5.2%)
Hygiene and periodontal treatmentScaling without local anaesthesia0 (0%)13 (7.5%)
Scaling with local anaesthesia1 (0.6%) 12 (6.9%)
Conservative treatment Restorative treatment without local anaesthesia 0 (0%)1 (0.6%)
Restorative treatment with local anaesthesia 33 (27.5%)33 (19%)
Root canal treatment with local anaesthesia 37 (30.8%)32 (18.4%)
Prosthetics Prosthetic treatment without local anaesthesia6 (5%)13 (7.5%)
Prosthetic treatment with local anaesthesia 9 (7.5%)9 (5.2%)
Oral surgeryExtraction (with local anaesthesia)24 (20%) 46 (26.4%)
Minor oral surgery (with local anaesthesia)6 (5%) 5 (2.9%)
Total no. sessions120 174
Figure 1. Comparison of cooperation scores between both groups during dental treatment. The distribution of the three levels of
Venham score, at each time point and for each group. Ti: At first contact with the dentist; T0: During venous cannulation; T1: At the end of the
induction; T2: During the first injection of local anaesthesia; T3: At the moment of least cooperation during initial dental treatment. DA: Group of
patients with Dental anxiety disorder; ID: group of patients with Intellectual Disability. ***=significant difference between the two groups of patients
(p,0.001, Fisher exact test).
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to allow cannulation and/or to deepen sedation without additional
respiratory depression. The technique used was chosen in relation
to each individual, in order to enable treatment with minimal
distress at each step, from the beginning to the end of the care
session. Effectiveness of the procedures also therefore depended on
the ability of the operator/sedationist to evaluate and anticipate
patient difficulties and behaviour prior to the session, according to
the treatment required. The success rate of 89% showed that this
procedure may be considered as an alternative to general
anaesthesia for these patients, allowing comprehensive dental
treatment and regular maintenance, as reported previously for this
population [30,31]. Three failures recorded during the study in
two patients with DA and one patient with ID were related to very
poor cooperation (Venham scores of 3 and more over the session,
Table 6. Safety of the technique. Distribution of the different types of minor adverse events. DA=dental anxiety; ID=intellectual
DA GroupID Group
Total no. sessions: 133type187 type
Type of adverse
Respiratory (hyper- or hypo- ventilation;
1 1 apnoea (5 seconds)8 8 desaturation lasting .30
Neurological (convulsions, epilepsy…)1 1 hiccups8 6 hiccups,1 epileptic fit,1
Digestive (nausea, vomiting…)6 3 vomiting (all in one woman
with severe gag reflex) and
3 episodes of nausea
7 2 vomiting and 5 nausea
Behavioural (euphoria, excitability…)1 1 panic attack8 6 hyperexcitability and 1
episode of lip-biting under
Vasovagal (sweating, pallor, faint…)00
Total no. events:9 (6.8%) 31 (16.6%)
Table 7. Level of sedation. Distribution of the Ramsay scores recorded over the sessions (T4: on first opening of the mouth for
examination after induction; T5: at the start of actual dental treatment; T6: at the end of dental treatment).
Patients with Dental AnxietyPatients with Intellectual Disability
Ramsay scale Score No. sessions (%)No. sessions (%)
T4 No. sessions 123 172
1 20 (16.3)60 (34.9)
2 96 (78)83 (48,3)
3 7 (5.7) 29 (16,9)
4 0 (0)0 (0)
5 0 (0)0 (0)
6 0 (0) 0 (0)
T5No. sessions 121167
1 15 (12.4)43 (25.7)
2 92 (76) 91 (54.5)
3 13 (10.7) 31 (18.6)
4 1 (0.8) 1 (0.6)
5 0 (0) 1 (0.6)
6 0 (0) 0(0)
T6 No. sessions122169
1 11 (9.0)52 (30.8)
2 99 (81.1)87 (51.5)
3 12 (9.8)26 (15,4)
40 (0) 4 (2.4)
5 0 (0) 0 (0)
6 0 (0)0 (0)
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even with oral premedication) and to technical difficulties (molar
endodontic treatment in young patients).Conscious sedation aims
to reduce anxiety and improve cooperation for treatment. For this
reason, the cooperation level was analysed by studying Venham
scores in both groups. Patients with a dental anxiety disorder were
significantly more often relaxed than patients with intellectual
disability during actual dental treatment under intravenous
midazolam sedation. Very few patients with dental anxiety
exhibited very high Venham scores (4 or 5: very disturbed or
out of contact). Similarly, a previous study showed that the
sedative effect of 50% nitrous oxide in oxygen inhalation was more
marked in patients with dental phobia compared with patients
with intellectual disability . These results suggest the difficulty
in dealing with the very heterogeneous behavioural profiles
present in the population of patients with intellectual disability
. Moreover, the average duration of sessions in this study was
higher for anxious patients. It may be hypothesised that the
relaxing psychological effect of the drug outlasts its pharmacolog-
ical effect in patients without intellectual impairment. Subsequent
cognitive restructuration was shown in anxious patients by their
improvement in cooperation over repeat conscious sedation
sessions before administration of the drug, even when anxiety
was recorded on arrival in the surgery. When the protocol was
repeated, patients with intellectual disability were also more often
relaxed during the first steps of the session, in particular during
cannulation. On repetition, fewer patients with ID had a Venham
score of 4 or 5 (i.e fewer needed some type of physical restraint).
During actual dental treatment, behaviour improved in patients
with intellectual disability at repeat sessions and reached levels
similar to that seen in persons with dental anxiety disorder. This
confirmed the results of a previous study showing the educative
and anxiolytic effects of repeat sessions of sedation by inhalation of
50% nitrous oxide in oxygen in patients with special needs .
The nature of this improvement needs to be determined by further
Figure 2. Influence of IV midazolam repetition on cooperation scores in both groups. The distribution of the three levels of Venham score,
at each time point and for each group, in relation to the session being a first experience of sedation (First exp.) or a repeat session (Reit.). Ti: At first
contact with the dentist; T0: During venous cannulation; T1: At the end of the induction; T2: During the first injection of local anaesthesia; T3: At the
moment of least cooperation during initial dental treatment. DA: Group of patients with Dental Anxiety disorder; ID: group of patients with
Intellectual Disability. Significant difference between the two groups of patients, Fisher exact test: ***=p,0.001, **=p,0.01, *=p,0.05.
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In over half of the sessions, inhalation sedation (50% N2O2) was
used to reduce anxiety and nociception during cannulation, and
then used throughout dental treatment if necessary. Previous
studies conducted in children also showed that the association of
nitrous oxide/oxygen with intravenous or oral midazolam
enhances the effectiveness of the procedure [6,28,39–41]. Indeed,
in one study, 80% of sessions were successfully conducted in
cooperative patients responsive to verbal commands using a
combination of nitrous oxide and midazolam versus 54% with
midazolam alone . The analgesic properties of nitrous oxide
are particularly useful when combined with midazolam, especially
during venous cannulation and injection of local anaesthesia.
Moreover, nitrous oxide gives a supplemental sedative effect
during treatment without respiratory depression. This is useful for
those patients who respond more markedly to the hypnotic and
depressive effects of midazolam than to its anxiolytic effects.
Accordingly, some authors showed that when nitrous oxide was
associated with midazolam for oral surgery there was a significant
reduction in the amount of midazolam required, a significant
reduction in recovery time, and a significant improvement in
cooperation and arterial oxygen saturation .
In this study, the adequate dose of intravenous midazolam, not
counting any premedication, was close to that reported in other
recent articles [30,31], and it was not different between groups.
Some authors using midazolam plus propofol sedation found that
higher doses were necessary for patients with intellectual disability
. However in the current study, premedication was given to
31% of patients with intellectual disability (midazolam in 94.8% of
cases), to allow venous access or to allow placement of a mask for
inhalation sedation. If these patients had been able to accept
cannulation without premedication, it can be assumed that they
would have required a greater quantity of IV midazolam to reach
a suitable level of conscious sedation. Other authors have also
reported that premedication is useful to increase acceptability of
inhalation sedation . The present study showed the safety of
using inhalation sedation (50% N2O2) and/or premedication in
association with intravenous midazolam sedation. This comple-
ments previous observations of the use of intranasal midazolam as
premedication before cannulation in patients with intellectual
disability . The intranasal route of administration is not yet
available in France but this technique is promising. It seems that
the ability to associate different procedures is extremely important
and allows for flexibility in relation to the needs of an individual
patient and to the clinical context.
In the present study, as in that undertaken by Ransford et al.
, the type of dental treatment performed was different between
patients with a dental anxiety disorder and those with intellectual
disability. This suggests that the main role of this procedure in the
population with intellectual disability may be to enable simple
regular maintenance and prevention and/or to enable examina-
tion for the most reluctant patients. For these patients, general
anaesthesia may still be indicated if complex treatment is required.
For patients with dental anxiety alone, intravenous midazolam
sedation seems sufficient to be able to undertake all types of dental
No major adverse event occurred during the study and no
relationship was found between the incidence of minor adverse
events and concomitant psychotropic treatment when present.
However, more minor adverse events occurred in patients with ID
than in patients with DA (16.6% versus 6.8% respectively). In a
previous study in adults with disability using intranasal plus
intravenous midazolam, 6.0% of adverse events were reported
. In another study of children and adolescents during
conscious sedation with oral or rectal midazolam, 15.4% of minor
adverse effects were observed . Other authors report a rate of
24.6% of minor adverse events during sedation with intranasal
midazolam in children and adolescents . The disparity
between these results is in part due to differences in defining
and recording minor adverse events.
Particular attentiveness is required for patients with disability as
regards their physiological state during sedation. This study
showed that the physiological parameters (minimal SpO2,
maximal SBP and DBP) were outside of the normal range more
often in these patients than in patients with dental anxiety
disorder. The risk of serious complication is therefore higher in this
population . In particular, patients with motor difficulties or
poor muscle tonicity (such as persons with Down syndrome) are at
greater risk of respiratory depression than others. Moreover, the
variations in blood pressure recorded here may suggest a higher
level of stress during dental care in patients with intellectual
disability despite sedation. This is related to greater problems with
cooperation and the higher frequency of minor adverse events
observed in this population . Moreover, in this study, conscious
sedation was surpassed on the Ramsay scale for 5 patients over 7
sessions (6 of which occurred in 4 patients with ID). The risk of
over-sedation in this population should therefore not be underes-
timated. It is true that the inadequacy of the Ramsay scale for
patients with communication deficiencies has been discussed by
other authors, as verbal responsiveness cannot be considered a
valid criterion to assess level of consciousness for these patients
. However, in the present study, the level of consciousness was
evaluated according to the usual means of communication with
the patient. Physiological parameters were monitored accurately
during the period of loss of verbal contact and any variation
managed appropriately. Although the boundary of conscious
sedation was exceeded briefly in all cases, it was never necessary to
reverse the sedation with flumazenil. All patients with ID and
over-sedation were subsequently referred for general anaesthesia if
further treatment was required. All these results concerning the
safety of sedation suggest that particular attention should be paid
in conscious sedation training to ensure that operator/sedationists
are able to adapt to the behavioural, as well as physiological,
particularities of each patient and to react adequately in case of
over-sedation. Sufficient clinical training, ideally by mentoring, is
required to ensure the effectiveness and safety of the procedure.
The authors wish to thank Genevie `ve Traverse and Danie `le Giral, nurses
in the special dental care unit where this project was undertaken, for their
assistance during the sedation sessions and Caroline Eschevins for her
technical assistance during the manuscript production.
Conceived and designed the experiments: VC MH. Performed the
experiments: VC MH DF. Analyzed the data: EN VC. Wrote the paper:
VC MH EN DF.
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