Oral Surgery ISSN 1752-2471

ORIGINAL ARTICLE ors_1125 115..123

Administration of oral midazolam in surgical dentistry

A. Parsa
Department of Oral and Maxillofacial Surgery, Falun Lasarett, Falun, Sweden

Key words: Abstract

dentistry, Falun lasarett, methods, midazolam,
oral sedation, surgical dentistry Objectives: Many patients experience fear, anxiety and strain during den-
to-alveolar surgeries which aggravate more complex procedures such as
Correspondence to: fixation of implants, difficult extractions. Many studies have in the past
Dr A Parsa
presented and assessed different methods of conscious sedation on patients
C/O 11 the Triangle
Bournemouth BH2 5RY
who suffer from anxiety and fear. Primary aims of this retrospective study
UK were to assess the suitability of using oral midazolam in surgical dentistry on
Tel.: +44 1202 291292 patients with anxiety and to present a guideline on the required dosage of
Fax: +44 1202 291293 oral midazolam in order to achieve good, subjective conscious sedation. Our
email: Parsadental@btinternet.com hypothesis is that oral midazolam is a safe and efficient conscious sedation
method with few complications and side effects that can be administered on
Accepted: 12 May 2011
patients with anxiety during dento-alveolar surgeries or those who find
doi:10.1111/j.1752-248X.2011.01125.x
long surgical procedures challenging.
Material and methods: This study is retrospective, and the method was
applied to 1549 patients who were sedated with oral midazolam. This study
was performed for 14 years (1989–2003), of which the majority were
treated for dental implants and surgical extractions. For each patient, the
following was documented: gender, age, patient’s weight, surgical proce-
dure, total dosage, dosage/kg, time between administration and opera-
tion, effect of sedation, and complications and awakening time after the
procedure.
Results: Patients experienced a positive and relaxed surgical session after
being sedated with oral midazolam. The sedative effect was good in most of
the cases except 152 (9, 8%), where an additional dosage was given. All of
those who required an additional dose did achieve a good subjective conscious
sedation after one additional dose. The additional dose was calculated as
50% of the original administered dose.
Conclusion: The sedative effect of oral midazolam was found effective in
this study and patients described the course of treatment positive and
relaxing. Using midazolam as conscious sedation for dento-alveolar surger-
ies on patients with fear and anxiety is a feasible, easily administered and
efficient method with low-rate complications. This study has presented a
figure as a guideline for the recommended dose of oral midazolam based on
patient’s age and weight to achieve a good, subjective conscious sedation.
On few occasions, an additional dose has been required if a subjective, good
conscious sedation has not been accomplished. The additional dose in this
study has been 50% of the original dose. The findings in this study indicate
that using oral midazolam is efficacious in inducing conscious sedation in
dentistry.

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© 2011 John Wiley & Sons A/S
Oral midazolam in surgical dentistry
Clinical relevance
Scientific rationale
Many patients experience surgical procedures per-
formed in the mouth as very unpleasant. This can
result in avoidance of dental treatment, which is one
of the major reasons for the provision of conscious
sedation.
Sedation allows a patient, with fear and anxiety, to
be calmer and more relaxed, and also reduces the per-
ception of discomfort1.
Primary aims of this retrospective study were to
assess the suitability of using oral midazolam in surgical
dentistry on patients with anxiety and to present a
guideline on the required dosage of oral midazolam to
achieve subjective, good conscious sedation.
Principle findings
This study found that the sedative effect of oral mida-
zolam is effective, and patients describe the course of
treatment as positive and relaxing.
Practical implications
We would encourage all oral surgeons to use oral
midazolam as a conscious sedation method for dento-
alveolar surgeries on patients with fear and anxiety, as
this method is feasible, easily administered, cost effec-
tive and efficient with low-rate complications.
Introduction
As it is well known, many patients regard dental treat-
ment as uncomfortable and potentially painful. Their
reactions range from normal apprehension through
various degrees of anxiety, or even phobia.
This can result in avoidance of dental treatment,
which is one of the major reasons for the provision of
conscious sedation.
These patients experience surgical procedures per-
formed in the mouth as very unpleasant. Administra-
tion of local anaesthesia on these patients is not
sufficient as local anaesthesia only deals with elimina-
tion of sensation or pain, whereas sedation refers to
consciousness and awareness. Sedation allows a
patient with fear and anxiety to be calmer and more
relaxed and also reduces the perception of discomfort1.
Analgesia refers to the relief of pain, and anaesthesia
refers to elimination of sensation and pain, so what is
sedation?
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Parsa
The Department of Health (DoH), UK defines con-
scious sedation as2 ‘a technique in which the use of
drug or drugs produces a state of depression of the
central nervous system (CNS) enabling treatment to be
carried out, but during which verbal contact is main-
tained throughout the period of sedation. The drugs
and techniques used to provide conscious sedation
should carry a margin of safety wide enough to render
loss of consciousness unlikely. The level of conscious-
ness must be such that the patient remains conscious,
retains protective reflexes, and is able to understand
and respond to verbal commands.’
There are four types of sedation according to the
American Society of Anesthesiologists (ASA)3:
● Minimal sedation or anxiolysis
● Moderate sedation
● Deep sedation
● General anaesthesia
In minimal sedation, you will feel relaxed, and you
may be awake. You can understand and answer ques-
tions and will be able to follow your physician’s
instructions.
In moderate sedation, you will feel drowsy and may
even sleep through much of the procedure, but will be
easily awakened when spoken to or touched. You may
or may not remember being in the procedure room.
In deep sedation, you will sleep through the proce-
dure with little or no memory of the procedure room.
You will have purposeful response to repeated or
painful stimulation, your breathing can slow and you
might be sleeping until the medications wear off. With
deep sedation, supplemental oxygen is often given.
There are five ranges of sedation techniques:
● Inhalation
● Intravenous
● Oral sedation
● Intranasal
● Rectal
Extensive research from Teo H. Sternbaches devel-
oped syntheses of chlordiazpoxide during late 1950s.
The drug showed complex abilities of anxiolysis, seda-
tive, hypnotic and amnesic.
Continued research in 1960 developed the more
potent substance within the benzodiazepine group,
diazepam. Midazolam was introduced in 1976 and was
registered in Sweden in 2 May 1985.
Positive clinical effects of benzodiazepines are the
following:
● Anxiolysis
● Anti-convulsive
● Sedating
● Hypnotic
● Amnesia
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Parsa
Negative clinical effects of benzodiazepines are the
following:
● Vomiting
● Restlessness
● Agitation
● Anxiety
● Aggressive behaviour
Midazolam is a benzodiazepine derivative with
sedative and hypnotic abilities, amnesia and with few
side effects. However, this pre-medication is metabo-
lised via hydroxylation by hepatic microsomal oxida-
tive enzymes. The imidazole ring in midazolam
oxidises faster than the diazepine ring does with diaz-
epam; therefore, midazolam has a shorter distribution
and elimination half-life.
Midazolam is a drug which is part of a group of
medicines called benzodiazepines. Benzodiazepines
belong to those medicines that have several effects on
the body. These effects include: anxiety relief, hypnotic,
anticonvulsant, skeletal muscle relaxant causing
sleepiness, muscle relaxing, stopping and impairing
short-term memory, and sedative properties. This
unique drug can be used before or during surgeries and
in medical or dental procedures. All medicines in this
category have these effects to some degree, depending
on which specific benzodiazepine is being taken. They
affect the brain by enhancing the effects of gamma-
amino butyric acid (GABA), a brain chemical that is
naturally calming. GABA can stop or slow down certain
nerve signals in the brain, which is why midazolam and
other benzodiazepines are known as mild tranquillis-
ers, sedatives or CNS depressants1.
With its introduction into anaesthesia over 25 years
ago, midazolam has been considered as a short-acting
benzodiazepine with a short elimination half-life of
about 2 h (1.5–2.4), and is therefore a very useful drug
for short, minor procedures such as dental extractions.
When midazolam is administered intravenously,
distribution half-life is approximately 15 min with
an elimination half-life of 2, 5 h4. This compares to
diazepam’s distribution half-life of approximately
30–60 min and elimination half-life of greater than
24 h5. It takes approximately 45–90 min for the diaz-
epam to reach the maximum effect when administered
orally, while midazolam reaches the maximum effect
after only 30 min.
At the Oral and Maxillofacial Department in Falun,
midazolam was previously used as an IV sedative with
good results. But a simpler form of administration such
as per oral was desired. Studies have initially demon-
strated that the advantages of midazolam include less
incidence of thrombophlebitis and also a greater level
of amnesia compared to diazepam6,7. Patients under-
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Oral midazolam in surgical dentistry
going dental treatment who received midazolam had a
more complete amnesia of intra-operative events than
those who had received diazepam. Shorter clinical
recovery rates have not been demonstrated despite
the more rapid clearance and lower plasma levels of
midazolam.
According to studies, midazolam has a better bio-
availability when administered intravenously com-
pared to per orally. (1.0 respectively 0.4)8.
Midazolam was first synthesised in 1976 by Fryer
and Walser9. Midazolam is sold in Sweden under
the names of Dormicum (Roche, Basel, Switzerland)
or midazolam alpharma (Dumex-Alpharma, Copen-
hagen, Denmark) and is delivered in glass ampules of
1 mL with a strength of 5 mg/mL.
The drug is the only water soluble benzodiazepine-
antagonist available. The water solubility allows for an
unproblematic galenic preparation for painless injec-
tion or mixture with common infusion solutions.
Crossing the blood-brain barrier demands lipid solu-
bility which also was found in this drug.
It is important to know that midazolam is not an
analgesic, but it exerts an effect on central nociception,
which sometimes makes it difficult to tell the difference
to analgesia.
Midazolam’s most useful property is its ability to
cause amnesia for a few hours. This can be very useful
when patients need to be awake and responsive during
a procedure or surgery that may be uncomfortable or
stressful. This is called conscious sedation, when a
patient is sedated but conscious. Typically, patients do
not remember anything about the procedure and think
that they were ‘out’ the whole time. Midazolam gives
patients the sensation of being under general anaes-
thesia without the risks of general anaesthesia or need
for any hospital setting. Once this medicine was
approved for marketing, experience showed that it also
was useful for gagging and other medical conditions
such as epilepsy10.
As already mentioned, oral midazolam can be used
for conscious sedation in dentistry. The uncooperative
paediatric or even adolescent patient may be among
the most difficult to treat in dentistry11–14. Behavioural
management alone is, unfortunately, not sufficient for
some patients who can be more easily managed with
sedation or general anaesthesia15–17.
Primarily, diazepam (benzodiazepines) have been
investigated as potentially more effective and safe for
use in oral sedation18,19. The advantages of this drug
group are for being efficacious in conscious sedation
and for having a good therapeutic index. Diazepam
has an extended duration of action, whereas mida-
zolam, used widely as a parenteral agent in general
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anaesthesia and sedation, has a rapid onset and a
shorter duration of action.
Studies have shown that oral midazolam was more
effective in inducing satisfactory sedation, increasing
the acceptance of mask induction and decreasing
separation anxiety in children20–23.
Plasma concentration
In the blood, midazolam is 96–98% bound to protein,
mainly serum albumin. The free fraction is normally up
to 2–4%. In patients with lower plasma protein, the
free fraction is higher (5–6%), which causes a faster
and stronger effect of the midazolam to the CNS.
Midazolam has a fast plasma clearance (250–
500 mL/min). It is metabolised via hydroxylation by
hepatic microsomal oxidative enzymes.
Distribution volume
Distribution volume for midazolam is higher in
women, elderly and obese than in men. All these
patients have, relatively, a higher amount of fat tissue.
As midazolam has a high affinity for lipids, it will divide
itself in this increased amount of fat tissue. This results
to a delay of the initial effect from midazolam but con-
siderably a longer half-life.
Interaction
● Inhibiting the metabolism
Calcium blocker (Isoptin, Cardicem)
Antibiotic (Abboticin, Ery-Max)
Antimycotica (Fungoral, Diflucan)
● Increasing the metabolism
Antiepileptica (Tegretol, Fenantoin)
Allergy to any benzodiazepine represents an abso-
lute contraindication.
With regard to the use of orally administered mida-
zolam in dentistry, using this medicine with any of fol-
lowing medical conditions is not recommended:
● Hypersensitivity
● Acute narrow angle glaucoma
● Shock
● Hypotension
● Head injury
● Drug or alcohol use
● Heart, kidney or liver diseases
● Elderly patients
Elderly patients are especially sensitive to the effect
of midazolam and should not be treated with this
medication. This is because there is an increased chance
for side effects during the use of this medicine (Table 1).
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Table 1 Indication for sedations
Conditions where Anxiety, gagging issues, poor cooperation at
sedation is pediatric, prolonged procedures, angina,
beneficial: controlled hypertension, asthma, epilepsy,
movement disorder
Conditions where Controlled heart failure
technique may Chronic anemia
require Chronic airway disease
modifications: Controlled diabetes
Conditions where Severe respiratory disease
caution is Hepatic disease
required: Severe physiological illness
Drug or alcohol use
Pregnancy and during breast feeding
Doubts about the ability to provide a suitable escort
Table 2 ASA classifications
Score Description
1 Normal, healthy patients
2 A patient with mild systemic disease
3 A patient with severe systemic disease
4 A patient with severe systemic disease that is constant threat to life
5 A moribund patient who is not expected to survive without
operation
6 A declared brain-dead patient whose organs are being removed
for donor purposes
Also, the recovery time for the elderly may be slower
after midazolam is given than in younger adults.
Studies in pregnant women has demonstrated that
midazolam crosses the human placenta and is a risk to
the foetus, but at least, after oral and intramuscular use,
these transfers appear to be slower than other benzodi-
azepines such as diazepam24. However, the benefits of
therapy in a life-threatening situation may outweigh
the potential risk. In deciding to use midazolam in
breastfeeding women, studies have shown that mida-
zolam is excreted in the breast milk25. The American
Academy of Pediatrics considers the effects of mida-
zolam to be unknown on nursing babies, but they may
be of concern26.
According to the ASA, midazolam should only be
administered to healthy people or patients with only
mild systemic disease27 (Table 2).
Side effects
This medication, along with its needed effects, may
cause some unwanted effects28; most of these side
effects will go away as the effects of midazolam wear off
(Table 3).
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Table 3 Side-effects for midazolam
Side effects: Nausea
Vomiting
Dizziness
Drowsiness
Serious side effects: Slow or shallow breathing
Slow/fast heartbeat
Mental/mood changes
Fainting
Muscle tremor
Allergic reactions: Rash, itching, dizziness, trouble breathing
For reversal of midazolam sedation, flumazenil is
used28. Flumazenil reverses the sedative, cardiovascu-
lar and respiratory depressant effects but not intra-
operative amnesia. Elective reversal with flumazenil
may occasionally be indicated. Flumazenil has a shorter
half-life time than midazolam. Flumazenil is sold in
Sweden under the name Lenoxat (Lanexat, Sweden).
The National Patient Safety Agency (NPSA), UK has
issued a Rapid Response Report on the use of midazolam
in conscious sedation. In this report, it is recommended
that where midazolam is used for conscious sedation,
practitioners should take the following precautions:
● Ensure that storage and use of high strength mida-
zolam are replaced with low strength midazolam;
● Review therapeutic protocols to ensure that guid-
ance on use of midazolam are clear and that the risks,
particularly for the elderly or frail are fully assessed;
● Ensure that all health-care practitioners involved
directly or participating in sedation techniques have
the necessary knowledge, skills and competence;
● Ensure that stocks of flumazenil are available where
midazolam is used and that the use of flumazenil is
regularly audited as a marker of excessive dosing of
midazolam; and
● Ensure that sedation is covered by an organisational
policy and that overall responsibility is assigned to a
senior clinician29.
A current problem with midazolam in England has
been brought to the attention of those who works in
health care in a report from the NPSA29. These prob-
lems are mainly the dose that has not been correctly
administered to the individual patient’s clinical needs,
taking into account age, weight, concurrent medica-
tion and clinical conditions. Problems can arise when
drug combinations are used, for example, when mida-
zolam is used with sedatives and analgesics.
Objective
At the Oral and Maxillofacial Department in Falun
Lasarett, diazepam was used as a sedative, but because
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Oral midazolam in surgical dentistry
of its long half-life, a desire has always been to find a
medication with a shorter pharmacological half-life.
Thus, the main aim of this study was to investigate if
oral midazolam could be used for conscious sedation. A
secondary aim was to provide a guideline for adequate
doses.
Hypothesis
This study set out to test the hypothesis that oral
midazolam is a safe and efficient conscious sedation
method with few complications and side effects that
can be administered on patients with anxiety during
dento-alveolar surgeries or those who find long surgi-
cal procedures challenging.
Materials and methods
At the Oral and Maxillofacial Department in Falun,
there are about 4000 patient visits per year. At this
department during 1989–2003 Midazolam was given
per-orally to 1549 patients. Oral midazolam was
chosen as it was found easier to administer than intra-
venous (IV) sedation, and presented with shorter half-
life than diazepam.
In this study, oral midazolam was only considered for
those patients who scored within ASA group I & II after
thorough assessment of the patient’s medical history
and for those who complied with the study’s indication
criteria.
The sedation level to achieve on patients in this study
was set as mild sedation which was described as ‘patient
been awake but calm with good subjective conscious
sedation’.
The indications for administrating midazolam were:
(1) patients who suffered from fear and anxiety at the
dentist and (2) those who found long and extensive
surgical sessions uncomfortable and challenging.
Dr Jan Rune, consultant at the Oral and Maxillofacial
Department was in charge of sedating with midazolam
per orally during surgical dentistry and was collecting
the data of the exact dose given to each individual for
achieving the sedation criteria for each patient. All this
data were then used to create a table as shown (Fig. 1)
to demonstrate the advised dosage per orally based on
age and weight. The prescribed amount of midazolam
for each patient was evaluated based upon their age
and body weight. Most of the patients in this study
were older than 18 years. The highest dosage was given
to the age group 18–55 years.
Between October 1989 and July 2003, 1549 patients
were given midazolam per orally, preoperative during
oral and maxillofacial procedures.
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For each patient, the following was documented:
gender, age, patient’s weight, surgical procedure, total
dosage, dosage/kg, time between administration and
operation, effect of sedation, complications and awak-
ening time after the procedure. This procedure was
performed by Dr Jan Rune. All patients were instructed
not to have any solid food after midnight but clear
liquid 2 h pre-sedation was allowed.
The amount of midazolam with the strength of
5 mg/mL was based on individual data and was mixed
with approximately 20 mL concentrated strawberry
squash, due to its bitter taste. The ordination was based
on patient’s weight and age. Patients below the age of
56 demanded a larger dose than the older patients.
(Fig. 1) The decided amount of midazolam was
ingested in a resting room, where the patients after
administration were given the time to rest lying on
their side or on their stomach with a median time of
45 min to obtain good subjective conscious sedation.
The good sedation in this study was assessed by the
following factors:
● General muscle relaxation;
● Relief of anxiety;
● Slowed responses;
● Slurred speech;
● Acceptance of local anaesthesia;
● Not remembering their Swedish identity number;
and
● Overall clinical impression (most important factor).
Patients were monitored clinically and by a pulse
oximeter throughout the period of sedation, dental
treatment and recovery. The clinical signs included
respiration rate, pulse and level of responsiveness.
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Parsa
Figure 1 Shows administered dose (mg) to
the four different age groups in relation to
bodyweight.
Each patient’s pre-sedation oxygen saturation was
measured and served as the control value. Continuous
pulse oximetry was used during and after the dental
treatments. Normal saturation rate was set as >95% in
this study. There was no need to use any antagonist
drug of the sedatives if the saturation rate would fall
below 95%. They were just stimulated to deep breaths
and supplemental oxygen was offered.
Xylocain adrenalin 1.8 mL (2%) was then adminis-
tered, and the amount was dependent on the treat-
ment. Once this was achieved the actual treatment
could begin. If patients did not fulfil the criteria set in
this study for subjective good conscious sedation, an
additional dose of oral midazolam would be adminis-
tered. This would be calculated based on 50% of the
original given dose. On completion of treatment,
patients were transferred to recovery and allowed to
recover for at least 20 min. Patients were supervised by
their relatives and a nurse. At the end of that period,
the patient’s fitness were assessed by the operator. Full
written and verbal postoperative instructions were
given. Operator’s assessment criteria included: physi-
ological status such as blood pressure, pulse and respi-
ration rate and behaviour during treatment and
outcome of treatment. Flumazenil was used intrave-
nously for reversal of the oral sedative midazolam. This
could be due to paradoxical reactions. They were also
stimulated to deep breaths and supplemental oxygen
was given followed by a member of sedation-trained
staff supervising the patient until they were fit for dis-
charge. Paradoxical reactions are characterised by rest-
lessness, agitation, anxiety and sometimes aggressive
behaviour.
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Results
The prescribed dosage of midazolam given to different
patient groups has been in accordance to Figure 1. The
data from this figure have been calculated from each
patient’s weight and age who have been involved in
this study. As shown in the figure, the largest doses
were given to the age group 18–55.
Of the 1549 patients 66% were female and 34%
were male with a median age of 47 years (9–85 years).
In between these, 1549 patients that were adminis-
tered with oral midazolam, age group 18–55 years was
the dominating group with 52%, followed by age
group 56–70 years (25.9%), age group over 70 years
(18.5%) and the minority was age group under 18
years with 3.6%.
Implant fixation dominated the surgical procedures
(51%), followed by surgical extraction of the third
molar of the lower jaw (38%).
The success rate of achieving subjective good con-
scious sedation assessed by the criteria set out in this
study was 90.2% in between the groups.
Figure 1 shows administered dose (mg) to the four
different age groups in relation to bodyweight.
The period of ingested sedative and start of procedure
was in the median time of 45 min. Post-operative
awakening median time was 90 min. The sedative
effect was good in most of the cases except 152 (9.8%),
where an additional dosage was given.
All of the procedures were performed as planned
without any complications except in 47 cases where
flumazenil was used intravenously for a reversal effect
of the sedative midazolam due to patients demonstrat-
ing signs of paradoxical reactions. The main side effect
that was presented by patients in this study was
aggressive behaviour in sense of kicking and punching.
The initial dosage for administering flumazenil was
0.2 mg intravenously, and if sufficient consciousness
was not achieved, then 1 min later, an additional dose
of 0.1 mg would be given. This could be repeated up to
the maximal dose of 1 mg.
The result of the study was promising with regard to
the use of midazolam per orally for conscious sedation
in surgical dentistry.
Discussion
The importance of creating a calm and painless envi-
ronment has always been an important goal in den-
tistry. There are many alternative forms of pain and
anxiety control for dental treatment to achieve this
goal. Such alternatives include the use of conscious
sedation technique.
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Oral midazolam in surgical dentistry
Benzodiazepines have been used extensively world-
wide, but little work has been carried out to consider
the use of oral midazolam in dentistry. This study was
to assess the safety and effectiveness of using oral
midazolam in surgical dentistry on patients with fear
and anxiety and also to create a guideline for recom-
mended dose to be administered per oral for subjective
good conscious sedation.
The administration of midazolam per-orally has been
shown to be very effective in adult and pediatric dental
patients11–17. This study was therefore designed to
establish such evidence within surgical dentistry.
The advantages with sedating worried and fright-
ened patients are great, in where the surgical procedure
can be performed in a faster and safer way10. The
patient will experience the procedure more comfort-
able and sedation in some cases is a necessity in order to
carry out the procedure2.
This study presents a large number of oral sedations
during oral surgical procedures.
The greatest advantage with oral sedation is that it is
easy to administer and dentists in primary care can
perform this method of conscious sedation if he or she
feels confident about their skills in this area.
A negative factor could be that the time spent at the
clinic will be longer and that the sedated person is not
safe to drive during the whole day of the treatment.
The findings in this study indicate that using oral
midazolam is efficacious for inducing conscious seda-
tion in dentistry. In this study, the additional dose of
oral midazolam was calculated as 50% of the primary
administered dose by the dentist who performed the
surgical procedure.
Some of the patients demonstrated a re-bound effect
(worried) postoperative but satisfied with the treat-
ment, which is very likely due to the amnesia effect.
There were 47 patients who showed signs of
aggression after being sedated with oral midazolam,
and no other intra-operative or post-operative com-
plications were associated with administration of the
drug in this study. The main side effects that were
presented by patients in this study were aggressive
behaviour in sense of kicking and punching and
demonstration of re-bound effect (worries) post-
operative. The importance of this study is based on
the belief that oral midazolam is a safe drug, admin-
istered orally and would allow for a much wider use
in dentistry.
Using midazolam as conscious sedation for dental
treatment on patients with fear and anxiety is a feasible
and efficient method with low-rate complications.
Midazolam gives patients the sensation of being under
general anaesthesia, without the risks and need for a
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Oral midazolam in surgical dentistry
hospital setting. It can probably reduce the need for
dental treatment under general anaesthesia29.
In a randomised controlled trial to evaluate the effec-
tiveness of midazolam in reducing anxiety during
dental treatments, Dionne et al. reported adverse effect
at 19.7% for the midazolam by including drowsiness
and lack of co-ordination. This study stated that
numbers of individual side effects were too low to
provide reliable data on adverse effects30.
In this study, the patients rarely developed para-
doxical reactions characterised by restlessness, agitation,
anxiety and aggressive behaviour. In this study, fluma-
zenil was used on 47 patients of 1549 (3%). The
reported incidence of paradoxical reactions with mida-
zolam appears to be small31,32.
There has not been many studies of this kind that
extend to evaluate oral midazolam in surgical den-
tistry and to demonstrate a guideline of required
dosage.
This study confirmed that oral midazolam is a safe
and efficient conscious sedation method with low
complications and side effects and which can be
administered on patients with anxiety during dento-
alveolar surgeries or those who find long surgical
procedures challenging. Another important aspect of
sedating worried and frightened patients that we
found in this study was the fact that the surgical pro-
cedure can be performed in a faster and safer way.
This is based on the fact that patients with anxiety
and fear for surgical dentistry are present with a lack
of cooperation.
Conclusions
Members of the dental team providing treatment under
conscious sedation must have received appropriate
training in form of theoretical as well as supervised
practical and clinical training before undertaking inde-
pendent clinical practice33. They should be trained in
the management of complications related to conscious
sedation in addition to the standard requirement for
proficiency in life-support techniques and the man-
agement of medical emergencies33.
For oral sedation, the sedationist needs to be trained
in other techniques of conscious sedation and skilled in
performing venous cannulation.
The recommendations of the Dental Sedation
Teachers Group (DSTG) state ‘that the use of oral and
intranasal sedation techniques by practitioners who are
already competent in IV sedation requires very little
additional training’33. Although that training has not
been detailed, it must include supervised clinical
practice.
122
Parsa
Using midazolam as a conscious sedative for dento-
alveolar surgeries on patients with fear and anxiety
is a feasible and efficient method with low rate
complications.
This study has presented a figure as a guideline for
the recommended dose of oral midazolam based on
patient’s age and weight to achieve a subjective good
conscious sedation. On few occasions, an additional
dose has been required if a subjective good conscious
sedation has not been accomplished. This additional
dose in this study has been 50% of the original dose.
Our hypothesis has been approved by the findings in
this study, which indicate that oral midazolam is a safe
and efficient conscious sedation method with low
complications and side effects, which can be adminis-
tered on patients with anxiety during dento-alveolar
surgeries or those who find long surgical procedures
challenging.
The success for a safe sedation is based on a thorough
assessment of patient’s medical history, indications for
sedation, competent dental team in sedation and
patient-management during and post sedation.
Acknowledgements
Hereby, I would like to sincerely thank: Dr Jan Rune for
making this study possible by providing the materials,
his great support and wisdom in oral surgery; Professor
Anders Gustafsson for being my supervisor, giving me
his support in writing this study; and Associate profes-
sor Tulay Lindberg who kindly supported me and
helped me in the right direction in completing this study,
and last but not least, Dr Shadi Parsa, my wonderful
wife, for her tremendous support, understanding,
enthusiasm and infinite help throughout this study.
References
1. Donaldson M, Gizzarelli G, Chanpong B. Oral sedation:
a primer on anxiolysis for the adult patient. Anesth Prog
2007;54:118–29. American Dental Society of
Anesthesiology.
2. Craig D. Compendium Conscious Sedation. London:
Department of Sedation and Special Care Dentistry,
2008.
3. Standards For Conscious Sedation In Dentistry:
Alternative Techniques. A Report From The Standing
Committee On Sedation For Dentistry. Faculty of
Dental Surgery, The Royal College of Surgeons of
England & The Royal College of Anaesthestists, 2007.
4. Ziegler WH, Schalch E, Leiman B, Ecker M. Comparison
of the effect of intravenously administered midazolam,
triazolam and their hydroxy metabolites. Br J Clin
Pharmacol 1983;16:63–9.
Oral Surgery 4 (2011) 115–123.
© 2011 John Wiley & Sons A/S
Parsa
5. Reves JG. Benzodiazepines. In: Prys-Roberts C, Hug CC,
editors: Pharmacokinetic of Anaesthesia. Oxford:
Blackwell Scientific Publications, 1984:157–86.
6. McGimpsey JG, Kawar P, Gamble JAS, Browne ES,
Dundee JW. Midazolam in dentistry. Br Dent J
1983;155:47–50.
7. Ann C, Flynn PJ, Richards J, Major E. A comparison of
midazolam and diazepam for intravenous sedation in
dentistry. Anesthesia 1984;39:589–93.
8. Greenblatt DJ, Harmatz JS, von Moltke LL, Wright CE,
Shader RI. Age and gender effects on the
pharmacokinetics and pharmacodynamics of triazolam,
a cytochrome P450 3A substrate. Clin Pharmacol Ther
2004;76:467–79.
9. Bartosikova L, Necas J, Bartosik T, Frana P, Pavlik M.
Changes in biomechanical parameters during heart
perfusion and after midazolam premedication. Biomed
Pap Med Fac Univ Palacky Olomouc Czech Repub
2008;152:79–82.
10. Skelly AM, Craig DC, Debuse D. Lecture Notes on
Conscious Sedation for Dentistry. London: Kings
Collage, 2003.
11. Chanpong B, Haas DA, Locker D. Need and demand for
sedation or general anesthesia in dentistry: a national
survey of the Canadian population. Anesth Prog
2005;52:3–11.
12. Ingersoll B. Behavioral Aspects in Dentistry. New York:
Appleton Century Crofts, 1982:107–27.
13. Eeinstein P, Domoto PK, Getz T. Difficult children: the
practical experience of 145 private practitioners. Pediatr
Dent 1981;3:303–5.
14. Jw H, Stricker G. Child patient response to various
dental procedures. J Am Dent Assoc 1965;70:70–4.
15. Needleman HL. Concious sedastion for pediatric
outpatient dental procedures. Int Anesthesiol Clin
1982;27:239–65.
16. Houpt M. Project USAP; the use of sedative agents in
pediatric dentistry. 1991 update. Pediatr Dent 1993;
15:36–40.
17. Moore PA, Houpt M. Sedaive drug therapy in pediatric
dentistry. In: Dionne RA, Phero JC, editors:
Management of Pain and Anxiety in Dental Practice.
New York: Elsevier, 1991:239–65.
18. Banality MM, Houpt M, Koenigsberg SR, Maxwell KC,
DesJardins PJ. A comparison of chloral hydrate
diazepam sedation in young children. Pediatr Dent
1990;12:33–7.
19. Gallardo F, Cornejo G, Auil B. Premedication with
flunitrazepam, diazepam and placebo in the
apprehensive child. J Dent Child 1984;41:208–10.
Oral Surgery 4 (2011) 115–123.
© 2011 John Wiley & Sons A/S
Oral midazolam in surgical dentistry
20. Feld LH, Negus JB, White PF. Oral midazolam
pre-anaesthetic medication in pediatric outpatients.
Anaesthesiol 1990;73:831–4.
21. McMillan CO, Spahr-Schopfer IA, Sikich N, Hartley E,
Lerman J. Premedication of children with oral
midazolam. Can J Anaesth 1992;39:545–50.
22. Weldon BG, Watcha MF, White PF. Oral midazolam in
children: effect of time and adjunctive therapy. Anaesth
Analg 1992;75:51–5.
23. Levine MF, Spahr-Schopfer IA, Hartley E, Lerman J,
McPerson B. Oral midazolam premedication in
children: the minimum time interval for separation
from parents. Can J Anaesth 1993;40:726–9.
24. Kanto J, Sjovall S, Erkkola R, Himberg J-J, Kangas L.
Placental transfer and maternal midazolam kinetics.
Clin Pharmacol Ther 1983;33:786–91.
25. Matheson I, Lunde PKM, Bredesen JE. Midazolam and
nitrazepam in the maternity ward: milk concentration
and clinical effect. Br J Clin Pharmacol 1990;30:
787–93.
26. Committee on drugs, The American Academy of
pediatrics. The transfer of drugs and other chemicals
into human milk. Pediatrics 1994;93:137–50.
27. Wolters U, Wolf T, Stutzer H, Schroder T. ASA
classification and perioperative variables as predictors
of postoperative outcome. British Journal Anaesthesia
1996;77:212–22.
28. Cienki JJ, Burkhart KK, Donovan JW. Zopiclone
overdose responsive to flumazenil. Clin Toxicol
2005;43:385–6.
29. National Patient Safety Agency. Rapid Response
Report. Reducing risk of overdose with midazolam
injections in adults. NPSA/2008/RRR011. 2008.
Available at: http://www.npsa.nhs.uk/rrr (accessed
14 June 2011).
30. Dionne RA, Yaqiela JA, Moore PA, Gonty A, Zuniga J,
Beirne OR et al. Comparing efficacy and safety of four
intravenous sedation regimens in dental outpatients.
J Am Dent Assoc 2001;132:740–51.
31. Mancuso C, Tanzi M, Gabay M. Paradoxical reactions
to benzodiazepines: literature review and treatment
options. Pharmacotherapy 2004;24:1177–85.
Pharmacotherapy Publications.
32. Wilson K, Welbury R, Girdler N. A study of the
effectiveness of oral midazolam sedation for
orthodontic extraction of permanent teeth in children:
a prospective, randomised, controlled, crossover trial.
Br Dent J 2002;192:457–62.
33. Dental Sedation Teachers Group. Training in Conscious
Sedation for Dentistry. 2005.
123
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