Conscious sedation service for geriatric and special-care dentistry: A health policy brief

Abstract

Background:

Geriatric and special care dentistry (GSD) involves oral health care for seniors and individuals with disabilities. Due to ethical issues, finances, waiting times, treatment versatility and so on, conscious sedation (CS) may have a place to optimise the delivery of care.

Objectives:

This article identifies considerations for implementing CS in GSD services in Singapore.

Methods:

Taking the form of a health policy brief, this review (a) defines the situation for patients with special-care needs and justified the need for dental CS, (b) makes reference to practices from countries with established dental CS services, (c) states and evaluates available CS techniques for the GSD centre in Singapore and (d) discusses action plans and considerations for implementation.

Results:

Demographic analysis revealed that 23.8% of the GSD patients could have benefitted from CS, or 44.7% of all patients who required behavioural management. The key advantages of CS included enhanced safety, more teeth saved and a reduction in general anaesthesia wait, amongst others. Conventional dental CS techniques included midazolam via various routes, nitrous oxide and ketamine. To establish a CS service, key points of consideration need to be conceptualised first, such as adequate training, perception of patients and providers, operational costs, facilities and developing guidance specific for oral health professionals.

Conclusion:

A local CS service will be beneficial for GSD patients in view of the challenges faced. A group of experts and stakeholders is needed to provide practical consensus.

Keywords

Conscious sedation special-care dentistry moderate sedation disability medicine Singapore

Introduction

The field of geriatric and special-care dentistry (GSD) are linked due to the similar barriers that they face, and they are tackled by the Ministry of Health Singapore as a single public-health predicament. This cohort will be collectively referred to as patients with special-care needs (PSCN).

A woman with severe intellectual disability presented at the GSD centre due to a painful lower right molar. A simple extraction was required. Being unsuitable for treatment under local anaesthesia (LA) due to challenging behaviours, the individual and family were presented with the option of dental treatment under general anaesthesia (GA). For a single tooth removal, dental treatment under GA is often not advised. Even with GA, many concerns arise, such as conservation of other decayed teeth, sustainable follow-ups, ward availability and waiting times.¹ Within the hospital policy, legal representatives are required for consent involving adults lacking mental capacity.² The application for court-appointed deputyship can take three to six months and costs between S$3000 and S$10,000.³ Due to unfamiliarity with the hospital environment, this woman previously had a difficult experience in the induction room and on the wards. Therefore, her family preferred chair-side management after weighing the risks and benefits. After three acclimatisation visits, extraction was attempted with physical restraint. However, the procedure had to be aborted due to profound difficulties faced. Such difficulties are commonly faced by dental PSCN. This experience also highlighted obstacles faced by the patient’s family, the dentist and the medical team.

Aims and objectives

This review is in the form of a health policy brief that identifies key considerations for implementing conscious sedation (CS) in GSD services for Singapore. A health policy brief consists of four steps: define the problem, make the case, state the policy and discuss the impact.⁴

Defining the problem

Background

The Ministry defines CS as ‘. . .a drug induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile simulation. No interventions are required to maintain a patent airway and spontaneous ventilation is adequate. Cardiovascular function is usually maintained’.⁵

Due to high-profile cases of mismanaged sedation in the 1980s and 1990s, the administration of CS (or moderate sedation) by dentists internationally further declined.^6–8 CS is only briefly covered in lectures in the local dental undergraduate curriculum.

There is also very limited education in postgraduate dental curricula.⁸ Currently, CS practice consists largely of nitrous-oxide sedation undertaken for children and intramuscular ketamine for oral and maxillofacial paediatric emergencies.⁹ Even in dental hospitals seeing PSCN, CS is not provided by dentists. Anaesthetists are called upon to administer sedation or GA in most private and public dental settings, which can add to the total treatment cost. Currently, there are only two studies investigating Singaporean dentists’ use of CS.^8,10

In the past few decades, regulative changes internationally refined the scope of dental sedation (disallowing anaesthesia), improved training outcomes and mandated emergency preparedness, raising safety in CS practice.^7,11–19 A large-scale UK audit of 1756 CS cases in 2016 reported minor complications rates of 2.3%.²⁰ These complications, such as desaturation, paradoxical reaction, tolerance, bradycardia or tachycardia, were defined as ‘no harm’ or ‘low harm’.²⁰ In terms of efficacy, CS has been shown to improve patient experience and chair-side cooperation, control gag reflex and enhance long-term attendance.¹¹ In fact, it could be more hazardous to practice dentistry for certain patients without any form of pharmacological anxiolysis or sedation.²¹ As a result, there has been a growing international enthusiasm to revise CS use in dentistry.^6,7

The need for CS for GSD

As a tertiary centre, Singapore’s only GSD centre sees PSCN who are medically complex and find more difficulty cooperating.²² The PSCN who require behavioural management are treated either under LA or under GA. The collated data of PSCN seen by a special-care dentist in 2017 revealed that 53.1% required varying levels of behavioural management (Table 1). The majority included younger individuals with learning disabilities (65.7%) and seniors with acquired cognitive disorders (18.8%). The British Dental Association case mix complexity index noted the group requiring behavioural management had a higher overall complexity.^22,23

Table 1.

Comparison of case-mix complexity and demographic profile of PSCN versus those requiring behavioural management.^a

	All PSCN in GSD centre	PSCN requiring behavioural management
	Average case mix weighted and average banded total score
Ability to communicate	2.95/8	5.06/8
Ability to cooperate	3.09/12	5.64/12
Medical status	6.09/12	4.16/12
Oral risk factor	6.61/12	6.99/12
Access to oral care	2.00/8	2.75/8
Legal and ethical barriers	1.93/8	3.32/8
Total banded score	22.7	27.9
	Demographic profile
Patients, n (%)	160 (100%)	85 (53.1%)
Average age, years (median)	50.2 (54)	39.8 (29)
25th–75th percentile of age (range)	28.3–68 (11–94)	23–61 (11–94)
Percentage ⩾65 years old	31.3%	21.2%
Male:female ratio	1:0.975	1:0.889

Data from a special-care dentist’s log in the GSD centre, where 160 PSCN were seen over 49 sessions in 2017. Patients not fulfilling the criteria of PSCN were not recorded.

PSCN: patients with special-care needs; GSD: geriatric and special needs/care dentistry.

Of 85 PSCN requiring behavioural management, 41.2% coped well with behavioural techniques, including tell-show-do, graded exposure, distraction techniques and light clinical holding. A fifth (21.2%) had dental treatment completed with significant difficulties, notably physical restraint, and would have been better managed with CS if it had been available, and 23.5% were unable to complete their dental treatment without any pharmacological management (CS or GA included). The remaining 14.1% presented extremely challenging behaviours and required dental GA rather than CS.

This analysis illustrated that 23.8% of all PSCN, or 44.7% of PSCN requiring behavioural management, could be presented with the option of CS. In reality, PSCN who do not qualify for GA and cannot cope with behavioural techniques were treated with significant physical restraint or placed on active surveillance (i.e. watchful waiting).

The importance of upholding human rights is outlined in the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) and Association of Southeast Asian Nations (ASEAN) Disability Forum.^24,25 Indeed, the ‘least restrictive option’ in the ‘best interests’ of PSCN should be employed, according to the statutory principles of the Mental Capacity Act.^26,27 Since extensive physical restraint has its risks (Table 2) and is often argued to be counterproductive, some PSCN are therefore placed on active surveillance, subjecting them to the chronic effects of untreated oral diseases.^21,28–30

Table 2.

Summary of points for the risk of excessive physical restraint.^21,28–30

Risks involved in physical restrain	Examples
Physical trauma	• Osteoporosis increasing risk of fracture• Collagen defect and tendency for dislocation• Hand pieces can lacerate tissues during aberrant movements• Sharps injury or needle breakage
Risk of anxiety-related emergencies	• Angina and acute coronary syndromes• Adrenal crisis with hypothalamus–pituitary–adrenal axis suppression• Asthma attack• Seizures• Stroke, especially in patients with high blood pressure
Hazard to health-care staff	• Biting the clinicians’ hands• Blunt injuries due to challenging behaviour, in stronger adults
Difficulty to execute competent dentistry	• Inability to use hand-pieces• Poor moisture control• Limitations in choice of treatment
Unpredictability in outcome	• Dependent on patient’s cooperation on the day
Psychological trauma	• Traumatic experience causes long-term aversion to dental environment• Loss of trust to people involved in physical restraint
Contrary to respect of human rights	• UN Convention on Rights of Persons with Disabilities• ASEAN Disability Forum• Human Rights 1998: Article 5 No torture, inhuman or degrading treatment (European Convention on Human Rights)

With modern techniques, the risk of morbidity in GA is low, and postoperative morbidity is reportedly similar between dental patients with and without disabilities.³¹ However, GA as the only option for pharmacological restraint consists of practical difficulties and demands thorough individual assessments.^32,33

One major consideration for dentistry under GA is that treatment planning undergoes a fundamental shift from a conservative to an invasive one. A service evaluation concluded that if inhalation sedation (IHS) was used, children could save 1.34 teeth for every GA session avoided.³⁴ Also, GA provides limited preventive dentistry.¹

On the operational aspect, various studies have concluded that CS can be more cost- effective than GA (Table 3).^35–37 These studies are, however, limited due to difficulty in conducting randomised trials ethically. Also, those that have been conducted were based on a paediatric population. No similar studies for PSCN were found.

Table 3.

Cost-effectiveness comparison of CS versus GA.^35–37

Study	Comparison	Cost-analysis parameter	Conclusion
Lee et al. 2001	Dental GA versus oral sedation in children	Using treatment and societal costs to evaluate dental relative-based value units	If more than three sessions of CS was required for same ‘units’ of treatment, GA may provide more cost savings
Lyratzopoulos and Blain 2003	Inhalation sedation with nitrous oxide versus GA in children	Staffing costs	Inhalation sedation estimated to cost one-third that of outpatient GA
Jameson et al. 2007	Hospital-based dental GA versus primary-care advanced CS in children	Fees, costs and treatment pathways used to calculate ‘average cost per child treated’	GA was 46.6% more expensive than advanced CS

CS: conscious sedation; GA: general anaesthesia.

A summary of practical concerns regarding dental GA in the GSD centre is outlined in Table 4, where the introduction of a CS service could create more options to overcome these barriers.

Table 4.

Summary of practical concerns of dental GA for PSCN in GSD centre.^1–3,33,38

Medical concerns	• Longer recovery in individuals with hepatic or renal impairment• Risk of postoperative delirium in the elderly• Fasting• Other medical complexities complicating GA
Dental concerns	• Treatment decision under GA involves more extractions than restorations• Indication for dental GA must include significant work to be indicated; examination under GA is seldom warranted without prior signs and symptoms
Consent	• People who lack capacity are required to have a legal representative to agree to elective GA procedures in some services• Best interest decision alone is not sufficient
Cost	• Surgical and hospitalisation fees have varying levels of subsidy, on top of dental procedure fees• CS is generally more cost effective than GA• Application of CAD takes three to six months, with legal fees of S$3000–$10,000
Environment	• People with difficulty cooperating are required to have access to ward facilities on recovery not in the dental hospital• Medical GA suites do not stock the full range of dental inventory, where the focus is for surgeries rather than fillings, periodontal therapy, root canal treatment or prosthodontic work• Unfamiliar environment on admission can upset patients with intellectual disability
GSD specialty in GA	• GSD has yet to be recognised as a specialty in Singapore, and may pose operational difficulties within institutional policies• PSCN in GA are often treated by oral surgery or paediatric dental specialists, where they have to work outside their preferred scope of specialty (i.e. for oral surgeons to do fillings or periodontal therapy, or for paediatric dental specialists to see adults)

GSD: geriatric and special needs/care dentistry; CAD: court-appointed deputyship.

Make the case

Singaporean guidelines and hospital policies

Within the Ministry of Health and Singapore General Hospital databases, three guidelines and three policies relevant to CS in GSD centre were obtained (Table 5). The various points raised from the above six guidelines and policies are evaluated.

Table 5.

Documents from Singapore’s Ministry and hospital databases relevant to conscious sedation practice in Singapore.^2,5,39–42

Ministry of Health guidelines	• Guidelines on Safe Sedation Practice for Non-Anaesthesiologists in Medical Clinics⁵ • Guidelines on Safe Sedation Practice for Investigation and Intervention Procedures³⁹ • Clinical Practice Guidelines on the Prescription of Benzodiazepines, Ministry of Health⁴⁰
Singapore General Hospital policies	• Sedation for Diagnostic and Therapeutic Procedures by Non-Anaesthetist (MB-COP-016)⁴¹ • Care of Patient Post Surgery/Procedure with Sedation, Version 13 (NU- OPS-404)⁴² • Informed and Written Consent, Revision 02 (CP-PP-07)²

Comparing Singapore and international practices

The Singapore guidelines and policies were compared to international publications of CS practice (Table 6). Areas of comparison include the level of statement, targeted audience, specifications or restrictions in techniques and various operational differences. These are incorporated into the detailed discussion of proposed CS techniques below (some details have been left out for brevity).

Table 6.

Documents relevant to conscious sedation practice internationally with regards to dentistry.^12–19

Australia and New Zealand	• Guidelines on Sedation and/or Analgesia for Diagnostic and Interventional Medical, Dental or Surgical Procedures. Australian and New Zealand College of Anaesthetists¹² • Australian Dental Association Policy Statement 6.17 – Conscious Sedation in Dentistry¹³
Canada	• Alberta Dental Association and College: Standards for the Use of Sedation in Non-Hospital Dental Practice¹⁴ • Guidelines to the Practice of Anesthesia: Appendix 6: Position Paper on Procedural Sedation: An Official Position Paper of the Canadian Anesthesiologists’ Society¹⁵
South Africa	• South African Society of Anaesthesiologists (SASA) Guidelines for the safe use of procedural sedation and analgesia for diagnostic and therapeutic procedures in adults: 2015¹⁶
UK	• Standards for Conscious Sedation in the Provision of Dental Care – Report of the Intercollegiate Advisory Committee for Sedation in Dentistry¹⁷ • Scottish Dental Clinical Effectiveness Programme. Conscious Sedation in Dentistry – Dental Clinical Guidance 3rd Edition¹⁸
USA	• Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report by the American Society of Anesthesiologists Task Force on Moderate Procedural Sedation and Analgesia, the American Association of Oral and Maxillofacial Surgeons, American College of Radiology, American Dental Association, American Society of Dentist Anesthesiologists, and Society of Interventional Radiology¹⁹

State policy

List of available techniques for GSD centre

With an understanding of the patient demographics (Table 1), an evaluation of the guidelines and policies (as above), an understanding of the established international practices of CS a and discussion with the Head of Department and Clinical Head at the GSD centre, the following CS techniques were selected for literature review and proposal: regimen in intravenous(i.v.) midazolam administration, nitrous-oxide inhalation, oral and intra-nasal midazolam, combination of nitrous oxide with oral or intra-nasal midazolam, and ketamine.

Regimen in i.v. midazolam administration

Administration of i.v. midazolam is widely practised internationally with very different dosing regimens across different medical specialties. As a result, many medical guidelines and policies seldom specify dosing regimens to provide flexibility on indication. From the documents, a dosing regimen was specified in the Singapore General Hospital policy and South African Society of Anaesthesiologists guidelines. They were compared to other regimens recommended in Craig and Boyle, the National Institute for Health and Care Excellence (NICE) and Medscape (Table 7).^{11,16,41,43,44}

Table 7.

Comparison of administration of midazolam for conscious sedation.^{11,16,41,43,44}

	Adults				Elderly
	Loading	Titration	Time to reach a dose of		Loading	Titration	Time to reach a dose of
			5 mg	10 mg			2 mg	5 mg
Singapore General Hospital policy	0.5–2 mg over 2 minutes	1 mg/5 minutes to effect	17 minutes	42 minutes	0.5–1 mg over 2 minutes	0.5 mg/5 minutes to effect	12 minutes	42 minutes
South African guideline	0.05–0.1 mg/kg (maximum 2 mg) every 10 minutes or when maximum recommended dose of 3 mg is reached		N.A. Maximum recommended dose is 3 mg		Not specified		10 minutes	N.A.
Craig and Boyle	2 mg over 30 seconds, wait 90 seconds	1 mg/30 seconds to effect	3.5 minutes	6 minutes	1 mg over 30 seconds, wait 4 minutes	0.5 mg/2 minutes to effect	8.5 minutes	20.5 minutes
NICE	2–2.5 mg at a rate of 2 mg/minute	Add 1 mg slowly to effect	At least 3.5 minutes	N.A. Maximum dose 7.5 mg	0.5–1 mg at a rate of 2 mg/minute	Add 0.5–1 mg slowly to effect	At least 2 minutes	N.A. Maximum dose 3.5 mg
Medscape	0.5–1 mg (maximum 2.5 mg) over 2 minutes	Repeat dose every 2–3 minutes to effect	At least 6 minutes	At least 14 minutes	1–1.5 mg in 2 minutes	Repeat 1 mg every 2–3 minutes to effect	At least 4 minutes

The South African regimen has a maximum recommended midazolam dose of 3 mg, making it less feasible for use as a single agent in dentistry.¹⁶ The regimens of NICE and Medscape are similar, with little variability compared to the regimen proposed in Craig and Boyle.^11,43,44 The Singapore General Hospital’s regimen, with an intermission of five minutes between increments, is suited for medical uses, that is, premedication for GA, anxiolysis in long-term care facilities or as an adjunct in multi-drug sedation.⁴¹ Titrating midazolam alone at this speed may not be effective in reaching therapeutic sedation for dental procedures. In adults, where distribution half-life is 6–15 minutes, redistribution of midazolam from the GABA_A receptor sites will occur before clinical sedation can occur, particularly at higher doses (Table 7).¹¹ For example, it will take 17 minutes to administer only 5 mg. In addition, the slower administration would require an overall higher dose to reach comparable therapeutic depth. The cumulative dose is increased, resulting in prolonged recovery, side effects and more profound respiratory depression.¹¹ While the longer intermission appears to provide a safety net against over-sedating, by considering the indications, ease and predictability in using single drug sedation, this regimen may limit efficacy in dentistry.

Following the National Patient Safety Agency Rapid Response Report 2008, changes were made for titration in elderly patients due to their susceptibility to over-sedation.^11,45,46 It was suggested halving the increment dose and doubling the intermission duration.⁴⁷ At the GSD centre, where 21.2% of PSCN who required behavioural management were aged ⩾65 years (Table 1), there is a need to clarify techniques used for seniors. Interestingly, the most similar regimen for Singapore General Hospital, South African and Craig and Boyle was the ‘elderly’ sedation at low doses.^11,16,41 For 2 mg, they take 12, 10 and 8.5 minutes, respectively. Indeed, seniors may sometimes require as little as 2 mg i.v. midazolam, which may provide adequate sedation for more than 30 minutes.¹¹

Practising i.v. midazolam within medical clinics (outside public hospitals) is not restricted by this policy. Instead, the Ministry’s guidelines are followed. However, ASA III patients should only be sedated in secondary or tertiary institutions.⁵ Other considerations for sedationists include advanced life-support training, fasting parameters and monitoring vital signs every five minutes.⁵ A clinical and haemodynamic monitoring frequency of five minutes is also recommended in the ASA Task Force Guidelines, ‘unless such monitoring interferes with the procedure’.¹⁹ Other guidelines broadly specify to monitor ‘continuously’, ‘intermittently’ or ‘throughout the procedure’.^13,14,16

Few studies to date have established which regimen is most suitable for dental CS. However, titrating to response is highly recommended to confer safety.^5,11–19 The regimen for i.v. midazolam required by the GSD centre would be more feasible for seniors requiring doses around 2 mg. Other techniques have to be considered to meet the needs of other PSCN.

Nitrous oxide in dentistry for PSCN

IHS with nitrous oxide is safe, as it is inhaled and exhaled unchanged, minimally metabolised by the body. Nitrous oxide antagonises the presynaptic N-methyl D-aspartate receptors in the central nervous system. It is also postulated to work on the β-subunit of the nicotinic acetylcholine receptors and 5-HT3 receptors, and possibly mimics nitric oxide to confer its classical vasodilative, anxiolytic and analgesic properties.⁴⁸

IHS is regarded as the first-choice sedation for children and those with early dementia, obesity or haemoglobinopathies.^47–51 It is suggested that nitrous oxide can reduce the need for GA and the number of teeth extracted.³⁴ While its success in dentistry reportedly exceeds 90%, there is a need to re-evaluate for PSCN or seniors aged >65 years.

Another review describes its use in the elderly with dementia for anxiety and involuntary movements, recommending a 50% premixed gas, no more than 30 minutes of usage and at least three minutes of 100% oxygen recovery.⁵² For the elderly, adequate IHS can be achieved with as little as 25% because of age-related changes in lung gaseous exchange and the sensitivity of neuronal receptors.^11,52 Craig and Boyle recommends titration to response to avoid dose-related side effects.¹¹ The benefits and contraindications for PSCN are summarised in Table 8.

Table 8.

Summary of benefits and contraindications of nitrous oxide in dentistry for PSCN.^{11,29,30,34,48–67}

Benefits
Sickle-cell anaemia	• Low oxygen tension or acidosis as a result of anxiety or respiratory depression or anxiety can precipitate a sickling crisis• IHS is more ideal than i.v. sedation⁵¹
Morbid obesity	• Most sedatives mask arousal mechanisms and reduce respiratory effort and pharyngeal muscular tone^49,56 • Sleep apnoea was found to reduce oxyhaemoglobin saturation by 4%⁵⁶ • Adiposity increases benzodiazepine distribution up to 2.8×, prolonging recovery⁵⁸
Elderly	• Higher prevalence of anxiety: 6% of people aged 74–90 years had a Modified Dental Anxiety Score of >19 (extremely anxious)⁵⁷ • Prolonged recovery with other sedatives: the elimination half-life of midazolam in the elderly is 5.6 hours compared to 2.1 hours in adults⁵⁶
Chronic pulmonary disease	• Supplement of oxygen in IHS can be beneficial to patients with chronic hypoxia, such as chronic obstructive pulmonary disease or chronic bronchitis^29,30 • Caution to achieve an oxygen saturation of 88–92% is advised to reduce the ‘Haldane effect’ and less respiratory acidosis⁵⁸
Liver and kidney impairment	• Most sedatives are excreted through the hepatic cytochrome P450 3A4 isoenzymes, such as opioids, benzodiazepines, propofol and ketamine⁵⁹ • A combination of hypoalbuminaemia (hepatic impairment), chronic renal failure, increased GABA_A receptor sensitivity raises the risk of over-sedation⁶⁰
Disability	• More predictable recovery for individuals with learning disabilities• Faster recovery of physical ability and mobility^11,29,30 • Reported efficacy in movement disorders, e.g. cerebral palsy or Parkinson’s^52,61
Contraindications
Nasal obstruction and difficulties	• Anatomical abnormalities and nasal obstruction prevents entry of gases• Unrepaired cleft palate or obvious oral-antra communication results in leakage of gas, limiting efficacy• Inability to breathe through the nose with mouth open¹¹
Pregnancy	• Organogenesis in the first trimester can be disrupted as a result of haemopoietic suppression^62,63 • As little as 3 hours of 50% nitrous-oxide mixture resulted in detectable deoxyuridine suppression in 30% of subjects⁶⁴
Demyelinating disease	• Nitrous oxide long-term use (1280 L of 50% N₂O a week) caused failure of basic protein methylation in myelin sheaths due to impaired methionine synthesis⁵⁸ • Avoid in multiple sclerosis and autoimmune-related nerve demyelination^11,29 • Effects on myasthenia gravis are inconclusive; two professional bodies for myasthenia gravis stated there is ‘no contraindication’ and can be beneficial for individuals with some apprehension^65,66
Drug reaction	• Inactivation of cobalamin vitamin B12 raises toxicity of methotrexate^26,58 • Isocarboxazid, phenelzine, selegiline, tranylcypromine⁶⁷
Intraocular and intracranial surgeries	• Nitrous oxide is thought to contribute to vasodilation and increase intracranial and intraocular pressure• IHS is best avoided if there is recent ocular or cranial surgeries.¹¹
Care-resistant behaviours	• Intolerance to nasal hood• Inability to accept any form of dentistry even with nitrous oxide• Disinhibition¹¹

IHS: inhalation sedation; i.v.: intravenous.

Overall, IHS can be effective, particularly for the elderly where age-related neurological changes increase psycho-emotional needs. Despite inherent limitations for individuals with intellectual disabilities, irrespective of the low potency, risk of disinhibition, inability to accept the nasal hood or inability to comprehend instructions, nitrous oxide’s safety often presents as a viable consideration for PSCN.^52–56

The Ministry and hospital instructs sedationists to be qualified in advanced life support if >50% nitrous oxide is given.⁴ IHS is also an operator sedationist technique, unlike i.v. sedation. Given that its use is already established in paediatric dentistry, nitrous oxide can be readily implemented in most centres.

Oral and intra-nasal midazolam

Both oral and intra-nasal administration of benzodiazepines are indicated for individuals who are not amenable to IHS or i.v. procedures due to intellectual disabilities, needle phobia, claustrophobia and so on.^11,29,30 These two techniques are non-titratable, and a bolus dose (even if weight is used) is an estimate of optimal dose. Attempts to titrate oral doses may augment respiratory depression and extend recovery.¹¹ A comparison of midazolam’s actions via various routes are presented in Table 9.

Table 9.

Comparison of midazolam’s actions via various routes.^11,16

	Onset	Duration of action^a	Bioavailability	Dose	α-T_1/2	β-T_1/2
i.v.	3–4 minutes	20–60 minutes	100%	• Titrated to effect (1 mg/mL or 2 mg/mL)
Intra-nasal	5–10 minutes	20–60 minutes	70–90%	• Bolus 12 mg^b: 0.3 mL of 40 mg/mL
Oral	10–20 minutes	60 minutes	41–50%	• Bolus 30 mg^b: 2.5 mg/mL AmSed^® • i.v. formulation added to drink	6–15 minutes	1.5–2 hours

Dose dependent.

Dose adjusted accordingly for children and the elderly.

In ageing individuals, pharmacokinetic changes elevate susceptibility to benzodiazepines. Early studies of midazolam suggested that the oral bioavailability of midazolam is 20% higher in seniors (aged >74 years) than in adults.⁵⁶ First-pass metabolism correspondingly reduces by 1% every year after the age of 40 years.⁶⁰ In addition, liver function reduces by 30–40% with age, particularly in cytochrome P450 3A4 complex.⁵⁹ This retards benzodiazepine’s metabolism and excretion time, increasing the circulatory and distribution time within the body. For example, the elimination half-life of diazepam is regarded as 43–72 hours. In the elderly, this can extend up to 96 hours.⁵⁶ Overall, these changes hasten onset and lengthen recovery time for oral midazolam.

Pharmacodynamic changes in the elderly are also known to occur. Indeed, the National Patient Safety Agency Rapid Response Report called for a review of elderly benzodiazepine dosing. Yet, the scientific evidence regarding its exact cause is inconclusive.^45,47 Biochemical studies suggest changes in GABA_A receptor subunit composition.⁶⁸ For example, subunit α3 is up-regulated, while α2 and α5 are down-regulated, altering their neurological effects.⁶⁸

Oral sedation is intended to sedate, dissimilar to premedication doses aimed for anxiolysis. This can be prepared by adding the i.v. formulation to a sweet drink to mask its bitterness. Otherwise, a syrup formulation such as AmSed^® is acceptable to most children and individuals with intellectual disabilities, especially when well fasted (Table 9).¹¹

For intra-nasal sedation, the nasal Mucosal Atomiser Device™ atomises the solution into a fine mist of 30–100 µ.⁶⁹ Transmucosal membrane absorption of midazolam into the nasal capillary (Kiesselbach’s plexus) circumnavigates the first pass and theoretically enters the brain within a few seconds.⁶⁹ The resultant bioavailability is thus around 80%.⁴⁰ As midazolam has a pH of 3.5, this produces a stinging sensation on contact with the nasal mucosa. Lidocaine (20 mg/mL) may be added to this formula.¹¹

The instructions on oral and intra-nasal (or transmucosal) sedation do not differ much from i.v. routes because they can all result in a similar depth of sedation. Establishing venous access is recommended for safety.^11,13,17,18 Monitoring instruction includes pre- and postoperative blood pressure, mandatory perioperative pulse oximetry and continuous clinical monitoring of vital signs.^17,18

In Singapore under the Ministry’s and hospital’s instructions, the requirement for venous access is not specified for oral or intra-nasal sedation.^5,41 To achieve sedation at the ‘moderate’ level, intra-operative monitoring is compulsory.⁴¹ No other specific instructions are outlined except for paediatric sedation.⁵ Considering the limitations in the available regimen for administering i.v. sedation (Table 7), these two non-titratable methods have become comparatively important.

Combination of nitrous oxide with bolus midazolam via oral or intra-nasal routes

The combination technique of IHS and bolus midazolam was proposed, as there were concerns raised regarding the appropriateness of cannulating a patient in the dental surgery. Additionally, some PSCN may not accept venous access well.

Whilst this combination is occasionally used for children, very few studies, if any, were carried out in adult dental patients, much less PSCN. A 2010 guideline by the National Clinical Guideline Centre and commissioned by NICE provides a systematic review-like analysis of the available randomised controlled trials for this combination technique in children and young adults.⁵⁰ The summary of the trials demonstrates equivalent safety in the combination compared to a single midazolam intra-nasal or oral dose (Table 10). There is also expectedly a longer induction and recovery in the oral IHS combination compared to intra-nasal IHS.⁵⁰

Table 10.

RCTs of nitrous oxide and oral/intra-nasal midazolam combination from NCGC guidelines.^50,70–75

RCTs	Intervention	Comparison	Summary of findings (quality of evidence)
Fuks 1994• 20–42 months old	Intra-nasal 0.3 mg/kg+N₂O 50%+Papoose Board^®	Intra-nasal 0.2 mg/kg+ N₂O 50%+Papoose Board^®	• All patients completed procedure (moderate)• No vomiting reported (moderate)
Fukuta 1994• 5–20 years old• ‘mentally disabled’ and combative	Intra-nasal 0.3 mg/kg+N₂O	Intra-nasal 0.2 mg/kg+N₂O	• No reported events of assisted respiration or vomiting (moderate)• No significant differences in completion, duration, desaturation, vomiting (low to very low)
Hartgraves 1994• 1.5–6 years old• ‘recalcitrant’	Oral 0.5 mg/kg+N₂O 40–45%	Intra-nasal 0.2 mg/kg+N₂O 40–45%	• No significant difference in completion or oxygen desaturation (low to very low)
Lee-Kim 2004• 2–6 years old• Frankl 3–4	Oral 0.7 mg/kg+N₂O 40–45%	Intra-nasal 0.3 mg/kg+N₂O 40–45%	• Significantly longer induction time (3×) for oral group (moderate)• Significantly longer working time (+10 minutes; low)
Luhman 2001• 2–6 years old	Oral 0.5 mg/kg+N₂O 50%	Oral placebo+N₂O 50%	• All procedure completed (moderate)• No events of aspiration and respiratory interventions (moderate)• No significant difference in vomiting (low)
Al-Zahrani 2009• 4–6 years old	Oral 0.6 mg/kg	Oral 0.6 mg/kg+N₂O 30–50%	• All procedures completed (low)• No significant differences in induction time and duration of procedure (low to very low)

RCT: randomised controlled trial.

The Standards by Alberta Dental Association and College in Canada specifically acknowledge the combined use of a single oral sedative (benzodiazepines or antihistamines) with nitrous oxide and oxygen.¹⁴ There are four ‘modalities of sedation’, each with increasing difficulty and hence with corresponding logistical, personnel and training requirements. Combination techniques are modality 3, positioned between ‘oral administration of a single dose of a single sedative drug’ (modality 2) and ‘parenteral and parenteral-like sedation’ (modality 4).¹⁴ Fasting to standards are expected, but no dosing regimen is specified. The Standards outline that dentists using modality 3 should be at least trained in utilising ‘supplementary’ sedatives, and those who qualify to administer modality 4 sedation (and GA) are automatically permitted to perform this.¹⁴ This suggests that i.v. sedation under modality 4 may be viewed as more complex, requiring a higher level of training than the oral IHS combination.

While combined IHS and bolus midazolam theoretically provides a deeper level of sedation than either single drug methods, it is yet to be determined if the midazolam/nitrous oxide combination is more effective in improving cooperation in PSCN. Analysing lower-quality clinical studies for combination techniques in PSCN provides another perspective (Table 11). A clinical trial by Collado et al.⁷⁶ reported that people with intellectual disabilities accept non-cannulation modules better and were 6.5 times more ‘disturbed by cannulation’.⁷⁶ The results of these studies should be analysed with caution due to considerable heterogeneity.^76–79

Table 11.

Summary of non-RCTs with inhalation sedation and oral/intra-nasal midazolam.^76–79

Non-RCTs	Intervention	Comparison	Summary of findings
Fukuta 1993• Uncontrolled trial• 4–21 years old• Combative and mentally handicapped	Intra-nasal 0.2 mg/kg+N2O titrated	No control group	Good/effective behaviour shown in:• 69.2% of patients receiving infiltration• 93.8% receiving rubber dam• 76.2% having cavity prep done• 84.2% having restoration placed• 87.5% having pulpotomy done
Wood 2010• Audit• 3–13 years old	Intra-nasal midazolam+N₂O titrated	No control group	• 96% patients referred for dental GA accepted treatment under this technique• 93% of parents found this acceptable• 50% of children found intra-nasal acceptable• No clinically relevant oxygen desaturation
Collado 2013• Non-RCT• 7–66 years old	Intellectual disability group^a i.v. midazolam with:• 50% N₂O or• oral or rectal midazolam 0.3–0.5 mg/kg or• nil	Dental anxiety group^a i.v. midazolam with:• 50% N₂O or• oral or rectal midazolam • 0.3–0.5 mg/kg or• nil	• 25.4% of the ID versus 3.9% DA group were ‘disturbed by cannulation’• 58.9% of ID versus 90.3% DA were ‘relaxed after induction’• 31% ID versus 3% DA had ‘oral or rectal midazolam’• The above differences were found to be significant
Musani 2015• Crossover trial• 4–10 years old	Oral 0.2 mg/kg+N₂O	Intra-nasal 0.1 mg/kg+N₂O	• Significant difference in average onset (oral: 20.1 minutes vs. intra-nasal: 12.1 minutes)• Significant difference in difference in (recovery) alertness between groups (higher for intranasal)

For i.v. midazolam, the patients required for cannulation nitrous oxide or oral/rectal premedication or no additional preparations.

ID: intellectual disability; DA: dental anxiety.

A systematic review of nitrous oxide with i.v. midazolam use in dentistry did not report significantly improved efficacy either.⁸⁰ Nonetheless, the studies suggest that these combination techniques possess a good safety profile, similar to either drugs administered alone.^76–79 In the case of PSCN and the elderly, no single route is strictly better than another. A repertoire should be available to individualise treatment accordingly. With adequate staff training, emergency preparedness and audit of service, this technique can be proposed.

Ketamine sedation

Ketamine is a N-methyl D-aspartate glutamate receptor antagonist with various complex neurological effects postulated. It is a versatile sedative and analgesic that can be administered via oral, intramuscular, intra-nasal or i.v. routes.¹⁶ While ketamine is widely tested in paediatrics, its use in the GSD field is less researched.^81–84 A literature search specifying ‘adults’, ‘disability’, ‘dentistry’ and ‘ketamine’ revealed few studies, including a non-randomised double-blinded trial and three case reports (Table 12).

Table 12.

Summary of studies of ketamine’s use for adults with disabilities in dentistry.^81–84

Study	Patient group	Treatment rendered	Summary of findings
Green 1999	• 17 ‘mentally disabled’ adults• 17–49 years old	Sedation:Ketamine i.m.(2.9–4.7 mg/kg) or i.v. (1.0 mg/kg)Treatment:Laceration repair (10)Exodontia (1)Pelvic examination and dislocation (6)	• All procedures competed• Median time from induction to discharge 130 minutes (range 50–260 minutes)• Side effects: emesis, airway repositioning, seizures/myoclonus• No reported hallucinations• Atropine (antisialogue) and midazolam provided
Petros 1991	• 4 ‘mentally retarded and extremely difficult’ adults• 16–38 years old	Sedation:Ketamine oral 500–700 mg with sweet drinkTreatment: Dental exam, LA, amalgam fillings, scale or polish	• Treatment started in 30–60 minutes• Postop to discharge: 4–6 hours• Oral dose provided: 8–10 mg/kg
Rosenberg 1991	• 1 ‘extremely combative’ and strong (96 kg)• 16 years old	Sedation:Ketamine oral 700 mg (6–8 mg/kg)Treatment: Dental exam, x-rays, pelvic exam	• Sedated ‘deeply’ within 15 minutes• Postop to discharge: 70 minutes• Had diazepam and nitrous oxide (50%)
Horacek 2012	• 29 ‘intellectually disabled’ patients• Average age 36 years• Double-blinded trial	Sedation:Either:• Oral ketamine (5 mg/kg)+clonidine (2 µg/kg)+midazolam (0.3 mg/kg) or• Oral ketamine (5 mg/kg)+midazolam (0.3 mg/kg)	• 2 patients (1 from each group) required more complex management (propofol/etomidate)• No significant differences in behaviour measured• No significant differences for onset (all within 25 minutes)• No significant differences in ‘interaction scale’ and ‘calmness score’

Oral ketamine remains a popular choice for patients with learning disabilities, and treatment can indeed be successfully rendered in almost all cases.^81–84 Recovery from oral administration, however, can take four to six hours, and recovery facilities suitable for this length of stay are required.^16,83 In addition, ketamine produces a state of dissociative consciousness separate from the spectrum known for other sedatives such as nitrous oxide, benzodiazepines or propofol.¹¹ This ‘trance-like cataleptic state’, though not exactly loss of consciousness, can cause difficulties in assessing sedation level.¹⁶

Ketamine’s non-specific inhibition of catecholamine uptake might induce sympathomimetic effect, and may cause significant ischaemia in cardiac disorders.^16,85 The manufacturer’s instructions also discourage ketamine use in adults aged >40 years and in patients with coronary artery disease.⁸⁶ At the level of CS, however, low bolus doses (Table 12) are said to be safe, with preservation of protective reflexes and spontaneous ventilation and no induction of sympathetic effects of heart rate and blood pressure.¹⁶ Chudrofsky et al.⁸⁷ also demonstrated the possibility of using ketamine (with midazolam) safely for adults up to the age of 68 years. As for patients with developmental disorders, such as Down’s syndrome carrying a one-third risk for cardiac anomalies, excluding underlying cardiac defects remains the crux.^29,30,85 Therefore, specific training is required to assess, monitor and address complications such as laryngospasm, hallucinations or emesis.¹¹

Both the Ministry’s guidelines and the hospital’s policy do not specify ketamine use, although there is still a need for assessment, monitoring and recovery pursuant to instructions.^5,39 The operator and sedationist should be separate individuals, although the administration and monitoring can be undertaken by a trained and dedicated member of staff such as an enrolled or registered nurse.³⁹

Ketamine, as a procedural sedative, is already widely used in Singapore for dental-related procedures in children. In a review of 500 emergency cases in Singapore, as much as 54.4% of all i.v. and intramuscular ketamine sedation was used for paediatric laceration repairs, mostly in the oral facial region.⁹ Despite longer recovery and infrequent side effects, ketamine’s sedation profile is unique, which can be invaluable for achieving cooperation in PSCN.^11,81–84 This CS technique has the potential to be further explored in the GSD centre.

Discuss impact

The provision of CS service in a GSD centre is about safely optimising the patient’s treatment options in view of the barriers currently faced. At this point, the safety perceptions of CS amongst local dentists can be actively improved through education.¹⁰ Comprehensive training for CS in dentistry is not yet available locally, and this is critical to ensure the safety and efficacy of the techniques. This sentiment is also reflected by special needs dental specialists in Malaysia.⁸⁸

This paper highlighted the possibility of using nitrous oxide and oral or intra-nasal midazolam either separately or as a combination, using i.v. midazolam and also using ketamine for PSCN. There is a wider range of techniques, such as dexmedetomidine, which has been gaining popularity in dentistry.^16,89–91 Practical considerations of the centre’s set-up may still dictate the choice of technique to be accepted. These can include: emergency preparedness, including advanced life-support training and facility set-up; specific training for dental dentists and supporting staff; acceptability of CS by the institution’s authorities and anaesthetists; acceptability of CS by patients and families; ethical consideration and consent processes;^2,27 cost of procurement; spatial requirements (e.g. floor plan for recovery, wheelchair, etc.);^39,40 and recalibration of guidance and policies.^2,5,39

Conclusion

Taking the form of a health policy brief, this review (a) defined the situation for PSCN and justified the need for dental CS, (b) made reference to practices from countries with established dental CS services, (c) stated and evaluated available CS techniques for the GSD centre in Singapore and (d) discussed action plans and considerations for implementation.

Pursuant to article 25 in UNCRPD to which Singapore is committed, ‘persons with disabilities have the right to the enjoyment of the highest attainable standard of health without discrimination on the basis of disability’.²⁵ A focused group of experts and stakeholders is required to amalgamate ideas and align directions. This CS service in the GSD centre will unfold a new chapter in disability and oral health in Singapore.

Footnotes

Authors’ contributions

Lim GXD and Boyle CA planned the format and articles to be included. Lim GXD researched literature, gained ethical approval, data analysis, and produced the first draft of the manuscript. Both authors reviewed, edited, and approved the final version of the manuscript.

Availability of data and materials

The datasets generated from the author’s log are available from the corresponding author. Clinic data is subjected to Legal Aspect of Medical Confidentiality within Singapore and the National Dental Centre Singapore’s specific ethical board.

Ethical approval

The dataset generated from the author’s log was done in accordance to Declaration of Helsinki and Personal Data Protection Act (Singapore). Written approval was sought and accepted in 2017 by the National Dental Centre Singapore’s Ethics Review Board. No approval number was issued.

Informed consent

Not applicable.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

ORCID iD

Guang Xu David Lim

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