Enhanced CPD DO C Sedation

Stephanie Fenesan

Sadie Hughes and Neha Patel

An Alternative Sedation Option

for Special Care Patients:
Combined Inhalation Sedation
with Nitrous Oxide and Oxygen
and Intravenous Sedation
with Midazolam
Abstract: This article highlights an alternative sedation technique by providing inhalation sedation with nitrous oxide and oxygen
alongside intravenous sedation with midazolam as an additional option for patients within special care dentistry. Two case reports are
described, as well as a short overview of the available literature on this technique and the indications, advantages and disadvantages.
This technique should be considered alongside other sedation techniques. As with all treatment for which sedation is provided, each case
needs to be considered on an individual basis and the most appropriate option selected following discussion with the patient.
CPD/Clinical Relevance: Although single sedation techniques provide a good level of sedation to facilitate dental treatment for the
majority of patients, it is desirable to have an awareness of alternative sedation options that may be available for patients.
Dent Update 2021; 48: 533–538

Conscious sedation has become dental treatment for those who are unable combination of these factors.1 These factors
indispensable in the dental management to accept routine dental care due to can make it difficult for patients to accept
of patients in special care dentistry. Special physical, intellectual, medical, emotional, dental treatment without additional anxiety
care dentistry includes the provision of sensory, mental or social impairment, or a management techniques, such as behaviour
management techniques, conscious
sedation or general anaesthesia (GA).
Stephanie Fenesan, BDS Dip SCD RCS(Ed) MJDF RCS(Eng) BSc (Hons) AKC, Specialty The Intercollegiate Advisory Committee
Trainee in Special Care Dentistry, Department of Sedation and Special Care Dentistry, for Sedation in Dentistry (IACSD) defines
Guy’s Dental Institute, Guys and St Thomas’ NHS Foundation Trust. Sadie Hughes, BDS conscious sedation as: 'A technique in
MFDSRCPS MSc, Specialist in Special Care Dentistry, Hertfordshire Special Care Dental which the use of a drug or drugs produces
Service, Hertfordshire NHS Community Trust, Hoddesdon Health Centre, Hoddesdon, a state of depression of the central nervous
Hertfordshire. Neha Patel, BDS MFDS RCS(Ed) Dip DSed BSc (Hons), Senior Dental system enabling treatment to be carried
Officer Hertfordshire Special Care Dental Service, Hertfordshire NHS Community Trust, out, but during which verbal contact with
Marlowes Health and Well Being Centre, Hemel Hempstead, Hertfordshire.
the patient is maintained throughout
email: stephaniefenesan@nhs.net
the period of sedation. The drugs and
July/August 2021 DentalUpdate 533
 Sedation
techniques used to provide conscious
sedation for dental treatment should carry
a margin of safety wide enough to render
loss of consciousness unlikely.'2 While this
principle is applicable to most patients, it is
with the caveat that for some special care
patients, verbal contact might not be the
primary form of communication.
Techniques widely used in the provision
of conscious sedation in the UK include:
 Inhalation sedation;
 Transmucosal (for example, intranasal);
 Oral;
 Intravenous (IV).
The Scottish Dentistry Clinical Effectiveness
Programme (SDCEP) guidelines ‘Conscious
sedation in dentistry: dental clinical
guidance’ and ‘Standards for conscious
sedation in the provision of dental care’,
published by IACSD, advise that each
patient should be individually assessed and
appropriately treatment planned according
to their needs.1,3
The use of conscious sedation can
obviate the need for GA with implications
including risk assessment and cost. Manley
et al reported that 20% of patients with
a disability need a GA to receive dental
treatment.4 McGeown et al carried out a
cost analysis and estimated the average
cost per patient to be £1914.96 for a day-
stay GA case for an adult with additional
needs, which presents a significant cost
to the NHS.5 Irrespective of cost, for some
patients, GA remains a necessary treatment
option regardless of the associated rare,
but serious risks. This article suggests that
the following combined conscious sedation
technique can be a useful alternative to GA
for some patients.
Nitrous oxide
Nitrous oxide and oxygen is commonly
used for conscious sedation in dentistry,
particularly in paediatric dentistry.
Administered via a specially designed
inhalation sedation machine, it is a
colourless and virtually odourless gas, with
a low blood/gas solubility coefficient (0.47)
and a minimum alveolar concentration
(MAC) of 105%. MAC is defined as the
minimum alveolar concentration of
anaesthetic at 1 atmosphere (atm),
which produces immobility in 50% of
subjects exposed to a noxious stimulus,
usually a skin incision.6 MAC decreases by
534 DentalUpdate July/August 2021
approximately 6–7% every decade after the
age of 20 years and so, caution should be
exercised when administering nitrous oxide
to elderly people.7 Inhaled nitrous oxide at
concentrations of 50% have been compared
to a 10-mg dose of parenteral morphine in a
70-kg adult.8
In that regard, nitrous oxide is a low
potency, non-irritant, non-invasive agent
with rapid induction and recovery. These
properties, alongside the ability to rapidly
alter the depth of sedation, and the
machine's inability to deliver an oxygen
concentration below 30%, ensures a
wide safety margin and makes the state
of unconsciousness unlikely. Since it is
excreted virtually unchanged, this can
be ideal for patients with kidney or liver
disease, and for patients where other
sedation methods might be deemed
unsafe, such as those with obesity.9 It
has analgesic, muscle relaxation and
anxiolytic properties, which can be
controlled by administering a titrated
dose while maintaining communication.
A high proportion of patients experience
a euphoric, positive, relaxed demeanour,
which is ideal for the concurrent use of
semi-hypnotic suggestion.
Midazolam
Midazolam, introduced in 1983, is
currently the intravenous drug of choice
for dental conscious sedation. It is a rapid
onset, short-acting, water soluble, high-
potency benzodiazepine with no active
metabolites.10 Slow titration to a recognized
end point, through the small incremental
administration, while assessing the
patient’s response, avoids oversedation.
It is impossible to predict what dose is
needed for any individual patient.11 If the
effects of midazolam need to be reversed,
then the reversal agent, flumazenil, can be
used, for example in the event of a medical
emergency, or if recovery is prolonged. The
use of flumazenil is not a never event.
An advantage of using nitrous oxide
alongside midazolam is that the level
of nitrous oxide can be adjusted during
the procedure to adjust the overall level
of sedation experienced by the patient.
Midazolam can cause a decrease in blood
pressure and bradycardia, as well as
respiratory depression, and additionally
has no analgesic qualities.12 Using nitrous
oxide alongside IV midazolam can help
to combat these shortfalls, and can be
advantageous because it has the added
benefit of administered oxygen, as well as
having anxiolytic and analgesic qualities.
Additionally, administering nitrous oxide
prior to midazolam can help to reduce
anxiety and provide a degree of analgesia
during cannulation.
The use of nitrous oxide with
intravenous midazolam
Nitrous oxide is widely used for facilitating
cannulation, being discontinued once the
cannula is in situ. Many sedative drugs
given concurrently have synergistic effects,
which, while potentiating the sedation,
can also potentiate the risk of respiratory
depression, particularly in medically
compromised individuals. Nitrous oxide
used concurrently with IV midazolam has
been explored for use in anxious patients,
but there are no studies demonstrating the
use of this combined technique with special
care patients. Nitrous oxide administration
on a designated dental inhalation sedation
machine is always in conjunction with
oxygen and it is impossible to administer
a hypoxic mixture. The level of sedation
is also easily altered. This makes its use
with intravenous midazolam ideal for
many dental treatments where the level of
sedation a patient needs varies throughout
the procedure. Patients like the euphoria
provided by nitrous oxide and the anxiolysis
afforded by the benzodiazepine. This is
particularly useful in individuals where
the combination of other sedatives is
inappropriate, such as ASA III/IV (American
Society of Anaesthesiologists classification
system) patients, those with high anxiety
and a susceptibility to nausea, or patients
with a level of tolerance to certain drugs.
From the authors' clinical experience,
using this technique is an area that merits
further exploration.
The combined technique facilitates a
lower dose of midazolam while providing
a good level of sedation, which can be
beneficial for a range of patients including:
 Chronic pain syndrome (individuals
who are already taking high-dose
benzodiazepines);
 Reduced liver and/or kidney function;
 Multitude of medications, such as
chronic opioid use;
 Sedation

 Decreased respiratory function; a c

 Cerebral palsy where the euphoria of
nitrous oxide and the muscle relaxant
properties of midazolam creates a
good sedation;
 Failed IV midazolam as a single agent
but where nitrous oxide was well
tolerated for less invasive treatment;
 Where advanced IV sedation techniques
are contra-indicated, eg adverse
reaction to opioids such as fentanyl;
 Longer procedures where the effects
of midazolam may be beneficial for b d
the more invasive initial stages of
dental treatment, but a longer sedation
window is desirable, such as endodontic
treatment or implant placement.
In these examples certain parts of the
procedures such as canal instrumentation
or temporary crowns may be tolerated
during the midazolam recovery, thus using
the effects of nitrous oxide sedation and
decreasing the need for midazolam top ups,
which may lengthen the recovery time. Figure 1. (a–d) Case A: pre-operative radiographs.

Technique for administering

combined nitrous oxide and
intravenous midazolam
Nitrous oxide induction with increments
titrated slowly to induce a state of anxiolysis
and relaxation
The standard procedure for sedation
with nitrous oxide is to start with 100%
oxygen and then add 10% nitrous oxide
for 1 minute while assessing patient
response, before adding a further 10% for
a further 1 minute, and then increasing the
increments by 5% at 1-minute intervals until
the patient appears relaxed.
Cannulation and intravenous midazolam
administration titrated to the patient’s
sedation end point
The standard titration procedure for
midazolam is to start with 2 mg midazolam
over 30 seconds and then wait 90 seconds
while assessing the patient's response,
and then administer further increments of
1 mg every 30 seconds until the desired
sedation end point is observed, while
maintaining verbal contact with the patient,
or appropriate patient interaction if the
patient is non-verbal, such as in the case
of some patients seen within special care
dentistry. This regimen should be adjusted
July/August 2021 DentalUpdate 535
accordingly in response to individual
patient factors – patient age, presence of
comorbidities or multiple medications.
Throughout the treatment nitrous oxide
can be increased or decreased as required.
At the end of the procedure
At the end of the procedure, after ceasing
nitrous oxide administration, a minimum
of 2 minutes of 100% oxygen should be
administered. This is to prevent diffusion
hypoxia, although in most healthy
individuals this is a theoretical risk, and to
decrease pollution in the immediate area.
Case studies
Case A
A 24-year-old male student attended the
Hertfordshire Special Care Dental Service
(HSCDS) for a new patient assessment.
He complained of pain in the upper right
and left quadrants. Medically, a diagnosis
of autistic spectrum condition (ASC),
dyspraxia, anxiety and depression was
noted, with sertraline taken for the latter.
Access to dental treatment in his
university town proved challenging due
to the patient’s high anxiety and the lack
of understanding towards his condition
by the dental practitioners he visited.
This prompted the patient to return to his
family home to access dental treatment,
and a referral by the family GDP was made
to a general sedation clinic. Owing to his
medical history, this referral was redirected
to the HSCDS.
At the initial assessment appointment
within the HSCDS, despite his high anxiety,
an examination and radiographs were
completed. Dietary analysis revealed a
highly cariogenic diet with the patient
drinking fizzy drinks and grazing on food
with a high sugar content throughout
the day. He reported brushing twice
daily with an electric toothbrush and
fluoride toothpaste.
Extra-oral examination was normal.
Intra-oral examination revealed poor
oral hygiene with generalized plaque
associated gingival inflammation, and the
presence of caries, which was confirmed
radiographically (Figure 1). Gross caries
was present in the UR5–7, and UL4–7,
which all responded positively to thermal
vitality testing.
Following discussions about treatment
and anxiety management options,
treatment was planned under intravenous
sedation to help reduce his anxiety and
 Sedation
Visit Treatment
Visit 1 Restore UL5,7
Visit 2 Restore UR5–7
Visit 3 Restore UL4,6 and
place definitive
restoration UL7
Visit 4 Supragingival
ultrasonic scale
Visit 5 Definitive
restoration UL5
Table 1. Summary of treatment and visits for Case A.
allow acceptance of dental treatment. The
treatment plan consisted of preventive
advice and oral health education and the
restoration of UR5–7 and UL4–7 with the
adjunct of intravenous sedation. Treatment
was staged over five appointments.
Preventative advice was provided on
the use of a high-fluoride toothpaste
(5000ppm), along with dietary analysis,
dietary and oral hygiene advice.
On the first treatment appointment,
IV sedation was administered and 4 mg
of midazolam was titrated to the patient’s
response, maintaining verbal contact
throughout the procedure. He initially
sedated well during treatment where UL5
and UL7 were treated and stabilized with
Biodentine (Septodont, France). Towards
the end of the treatment, and as the effects
of the midazolam lessened, the patient
became agitated, upset and distressed and
an escalation in challenging behaviour
was observed. Behaviour management
techniques were used during the recovery
period to de-escalate the negative
emotional response and attempt to keep
the patient as calm as possible. However, a
gross hypersensitivity to the environment,
light and sounds was observed, particularly
the high-pitched noise made by the
washer-disinfector in an adjacent room,
which exacerbated his distress. This led
to an increased time in recovery as the
patient was tearful, distressed and unable
to leave the building for a prolonged
536 DentalUpdate July/August 2021
Sedation Outcome
Intravenous sedation Poor response at
end of sedation and
prolonged recovery
Combined intravenous Good outcome
sedation and
inhalation sedation
Combined intravenous Good outcome
sedation and
inhalation sedation
Inhalation sedation Good outcome
Inhalation sedation Good outcome
period following the discontinuation of the
invasive treatment phase.
Following this appointment, it was
discussed whether it would be appropriate
to continue treatment with intravenous
sedation due to the patient’s response.
An alternative technique combining
IV sedation with midazolam alongside
inhalation sedation with oxygen and
nitrous oxide was discussed as an
appropriate option.
On the second treatment appointment,
a combined sedation approach was used.
Inhalation sedation with nitrous oxide
and oxygen was initiated and titrated
to response, with 30% nitrous oxide
administered via a Porter MXR 3000 (Parker
Hannifin Corporation, USA) flow meter
alongside the use of active scavenging
equipment. The patient was observed
to be calm and relaxed at this point.
Successful cannulation was followed by the
administration of IV midazolam, titrated to
2 mg, in line with the patient’s response,
and while maintaining verbal contact
throughout the procedure. The patient
responded very well to the combined
technique, with successful treatment of
UR5,6, with recovery being smoother, more
gradual and, therefore, pleasant for the
patient. This was a successful appointment
and it was agreed with the patient to
continue to use this method to complete
the remainder of their dental treatment.
Two further appointments were needed to
successfully complete restorations on UR7
and UL4,6 using the combined technique.
The patient became acclimatized
to having dental treatment and felt less
anxious. At the penultimate appointment,
he felt confident enough to trial having
a supragingival scale using inhalation
sedation with oxygen and nitrous oxide
alone. Following the success of this
appointment and after discussion, the
patient felt confident to have the final
treatment, which included occlusal
reduction of Biodentine and placement of
definitive composite restoration on UL5.
This was successfully carried out by titrating
the level of nitrous oxide to 30%, in line
with the patient response.
Case B
A 38-year-old female patient attended
for a routine check-up complaining of a
fractured tooth in the lower right quadrant.
Medically, she had cerebral palsy with
left-sided hemiplegia and associated
dystonia affecting her left arm, a mild
learning disability and was medicated with
baclofen, cetirizine and trihephenidyl. Also
reported were an allergy to codeine and an
adverse reaction to tramadol. The patient
lived independently with limited support,
and was supported by her mother for her
dental appointments.
She presented with a heavily restored
dentition and a high caries rate. Preventive
advice was given, which included oral
hygiene advice, use of a high-fluoride
toothpaste and dietary analysis and advice.
Her oral hygiene and diet have improved,
but are not yet at an optimal level.
After discussion of treatment options,
it was decided to attempt IV sedation
with midazolam and although initially, the
patient appeared well sedated, she had
a very short treatment window and her
involuntary movements increased when
active treatment was attempted. Further
midazolam was titrated; however, this was
not helpful in reducing her involuntary
movements, which continued. As such, it
was very difficult to safely and effectively
continue treatment.
Further treatment options were
discussed, which included the option of
GA; however, owing to her high caries
rate, treatment would have needed
to be more radical to avoid repeat GA
sessions. The patient was informed that

posterior teeth, which may have been
suitable for endodontic treatment under
sedation would be extracted, in addition
to those with a poor/guarded prognosis in
accordance to local policy and as per BSDH
guidelines.13 The patient was keen to try and
keep as many teeth as possible and on this
basis, avoid a GA. Sedation with midazolam
and fentanyl was not appropriate because
of the patient’s previous adverse reaction
to opiates. It was decided to try combined
inhalation sedation with nitrous oxide and
IV sedation with midazolam, alongside
behaviour management techniques.
In the subsequent appointment using
the combined technique; nitrous oxide
was administered first and titrated to
45/55% nitrous oxide/oxygen followed
by IV midazolam titrated to 3 mg, in
conjunction with behaviour management
techniques. This combined technique was
helpful in reducing involuntary movements
and lengthening the treatment window
allowing treatment. Using this combined
method, the patient was able to avoid
GA and undergo more conservative
treatment, including endodontic treatment,
which would not have been viable under
GA because of day-case anaesthesia
time constraints.
Discussion
The combined technique is useful as an
additional sedation tool for patients for
whom basic single sedation techniques
have not been successful. However, there is
limited discussion of this method available
in the literature.
Venchard et al carried out a prospective
randomized controlled trial in an oral
surgery setting comparing sedation with
inhaled nitrous oxide, IV midazolam and
the combined technique with nitrous oxide
and midazolam.14 They found a significant
reduction in the amount of midazolam
administered and a reduction in recovery
time with the combined technique when
compared to using the single agents. It was
also found that the operating conditions
were improved with the combined
technique, and the mean lowest oxygen
saturation recorded was higher with the
combined technique.
A meta-analysis that examined studies
that compared the combined use of nitrous
oxide and midazolam sedation with their
July/August 2021 DentalUpdate 537
individual use found only four studies that
met their inclusion criteria, while only three
met their inclusion criteria for quantitative
meta-analysis.15 Of the four studies
systematically reviewed, two looked at
adults and two at children. All four assessed
patient cooperation between single agent
and combination sedation techniques. They
found no statistically significant reduction
in cooperation scores overall. Additionally,
there was no significant difference between
adult and child cooperation. However,
Averley et al and Venchard et al found the
total dose of midazolam administered was
significantly less in the combined group.14,16
Consequently, the recovery time was found
to be less because of the lower doses
of midazolam.
Lipp et al investigated the use of IV
midazolam and pentazocine with the
additional administration of nitrous oxide
and found that the combined technique
was regarded as the best technique
by patients, resulting in a reduction in
anxiety and lower pain scores. However,
nitrous oxide was administered after the
administration of IV midazolam.17 The
benefits of nitrous oxide were still delivered
for the duration of treatment, but there
would have been no anxiolytic effects at the
beginning during cannulation. Furthermore,
the nitrous oxide benefits can only be seen
after the midazolam sedation end point
had been reached, potentially resulting
in oversedation.
Following the systematic review,
Sivaramakrishnana and Sridharan
recommended: ‘the use of the nitrous oxide–
midazolam combination technique rather
than the individual use of either drug due
to the advantage of reducing the total dose
of midazolam used’.15 It can be argued that
if a lower dose of midazolam is used, safety
can be increased, and this complies with the
principle of giving the minimum amount of
drug necessary to achieve the desired effect.2
Critically, all patients included in
these studies were ASA I and ASA II.
Clinicians must be vigilant, especially when
combined sedation techniques are used,
to ensure that underlying medical issues
and comorbidities are not exacerbated
because of the sedation. Monitoring the
patient’s respiratory status is paramount,
particularly as there is a risk that the
additional oxygen administered could mask
initial respiratory depression. The IACSD
Sedation
standards state that: ‘no one technique is
suitable for all patients. However, adopting
the principle of minimum intervention, the
simplest and safest technique that is likely
to be effective, based on robust patient
assessment and clinical need, should
be used’.2 It might be argued that the
technique described can fulfil this aim more
effectively than other more commonly used
multidrug techniques.
In addition to the advantages discussed,
a further benefit of this particular technique
is that, for most sedation clinics, no extra
equipment is needed.
A more commonly used combined
technique is IV midazolam with fentanyl.
In the authors’ experience, patients have
responded more favourably with combined
nitrous oxide and IV midazolam rather than
fentanyl and midazolam. Fentanyl often
causes nausea and longer-lasting unwanted
effects compared to the pleasant euphoric
feeling of nitrous oxide; however, it has been
shown that there are benefits of opioid use
in sedation.18 Future studies to compare the
use of fentanyl or nitrous oxide as an adjunct
to IV midazolam would be useful.
Environmental impact of nitrous oxide
Increasingly, the medical profession
is required to justify the sustainability
of the equipment and resources used.
Nitrous oxide is extremely stable with
an atmospheric lifetime of 100–150
years. It is degraded by ultraviolet
radiation, producing nitrogen oxide as a
by-product which, by means of various
chain reactions, destroys ozone. Nitrous
oxide is used commercially as a propellant
in food aerosols, it is produced during
the combustion of fossil fuels, found in
nitrogen-containing fertilizers, and used as
an anaesthetic and sedative agent.
Owing to its ability to reflect heat
energy back to the surface of the earth,
nitrous oxide is labelled a greenhouse
gas. Maskell et al stated that nitrous oxide
contributes to the greenhouse effect by
approximately 6%; however, it has been
estimated that only 1% of this is due to
anaesthetic use.19,20
Training needs
Although there is no evidence to show
that this combined technique causes
a higher risk of respiratory depression,
 Sedation
multidrug techniques are for experienced
sedationists. Multidrug sedation is
categorized as an advanced technique in
the UK.2,3 There is no specific mention in
existing documentation or guidance in
the UK of nitrous oxide with oxygen and
IV midazolam being administered as a
combined technique, or whether this is
specifically an ‘advanced’ or ‘basic’ sedation
technique. However, sedationists wishing
to use it should be experienced and
skilled in using both techniques as single
agents before attempting to use them
concurrently. As this technique is not well
recognized in the UK or routinely taught
on sedation courses, there is no minimum
recommended number of supervised cases
stipulated in contemporaneous sedation
guidance documentation. However, in an
environment where treating individuals
with comorbidities or additional needs, it
would be prudent to undertake supervised
cases initially. This is an area that needs
further clarification and local policies
may need to be revised and updated to
reflect this if clinicians intend to use this
combined technique.
Conclusion
In theory, nitrous oxide with IV midazolam
for dental conscious sedation could be one
of the most accessible and safe combined
techniques for experienced sedationists
to learn, when compared to other
advanced techniques.
Any current single sedation technique
will have limitations and, undoubtedly, as
with all sedation cases, patient selection
is key. Although single-agent techniques
provide a good level of sedation to facilitate
dental treatment for the majority of patients,
they do not provide adequate sedation for
all. When single-agent sedation has failed,
GA is often considered the only other
available treatment option. For a minority
of patients, combined techniques offer a
safe, effective alternative and should be
included in the experienced sedationist’s
armamentarium. As medicine evolves,
our anxiety management techniques and
options should also. These case studies
illustrate patients for whom GA or IV
midazolam alone would not have been in
their best interests, and it is important that
alternative techniques are studied to prove
their efficacy.
538 DentalUpdate July/August 2021
Compliance with Ethical Standards
Conflict of Interest: The authors declare that
they have no conflict of interest.
Informed Consent: Informed consent was
obtained from all individual participants
included in the article.
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