Sedation in pediatric dentistry: a review of the evidence

Introduction

Behavior management is considered the foundation of pediatric dentistry, it consists of pharmacological and non-pharmacological approaches (Ashley et al., 2018). Majority of the pediatric patients can be managed with conventional behavioral management (Jain et al., 2020), however, very young patients who cannot overcome their fear, are extremely anxious and have special needs may require a sedative agent. (AAPD, 2019). Diagnostic and minimal surgical procedures performed on pediatric patients has increased in the past several decades. (AAPD, 2019), along with the advancement and increased understanding of the significance of anxiolysis and analgesia, the need for sedation has raised. (AAPD, 2019), Nevertheless, pharmacological management is not a substitute for effective communication and persuasive ability of the dentist. (Hosey, 2002).

Definition and Goals of sedation

Sedation is a drug-induced depression of consciousness that allow reduction of physical discomfort and pain, accompanied by behavior modification. No need for interferences to support a patent airway, and involuntary breathing is adequate. (ASA, 2019). The patient is safely discharged from sedation unit after returning to the normal healthy state. (ASA, 2019).

Sedation encompasses a continuum of altered state of consciousness, varying from minimal sedation and anxiolysis to deep sedation and general anesthesia. (SASA, 2020).

• Minimal sedation is a state of anxiolysis where the patient can respond normally to verbal stimulus, and can maintain the airway. (SASA, 2020).
• Moderate sedation is a state of anxiolysis where the patient can only respond to a purposeful verbal stimulus and can maintain airway. (SASA, 2020).
• Deep sedation is a state of anxiolysis where the patient cannot respond normally to verbal stimulus but can respond to painful stimulus and may need assistance to maintain airway. (SASA, 2020).
• General anesthesia is a state of unconsciousness where the patient does not respond to any type of stimulation and have impaired ventilation which require ventilation under positive pressure. (SASA, 2020).

The response of pediatric patient to different sedation medication is different than adults, due to the physiological growth, smaller masses and lower weight (SASA, 2020), therefore, the tendency to go into deeper levels of sedation is high (AAPD, 2019), that’s why a health care professional trained in sedation must be trained in basic life support in case of emergency. (SASA, 2020).

Indications of sedation

Guidelines shared by the South African Society of Anesthesiologists included:

• Dental phobia, Anxiety and injection phobia. (SASA, 2020).
• Special needs patient with ability to communicate. (SASA, 2020).
• Patient with Uncooperative behaviour. (SASA, 2020).
• Increased Gag-reflex. (SASA, 2020).
• Patients 4 years of age and above. (SASA, 2020).
• Moderate extensiveness of dental treatment. (SASA, 2020).

Contraindications of sedation

This also may serve as the indications of general anesthesia (GA) vs. sedation.

• Prolonged and extensive treatment plan that require multiple sedation appointments. (SASA, 2020).
• Availability of theatre, personnel and equipments with consideration for the cost. (AAPD, 2019).
• Mouth breathers that need intubation. (SASA, 2020).
• ASA III or higher. (SASA, 2020).
• Mallampati class 3 & 4.
• Weight under 15Kg (SASA, 2020), it was shown that children with smaller bodies and weight have a higher tendency for adverse effects of medication including loss of consciousness. (SASA, 2020)
• Patient undergoing chemotherapy. (Silva et al., 2015).
• Obese children (SASA, 2020)
• Patients with no communication ability such as special needs children or children of very young age (under 4 years old) (Silva et al., 2015); (SASA, 2020).

However, if the patient had a slight ability to communicate, it is preferable to allow adequate behavioural management to establish cooperation at a young age by performing sedation (AAPD, 2019), In sedation the patient can respond to verbal stimulus and is conscious reduced anxiety. In conclusion general anesthesia should be reserved as the last resort. (SASA, 2020).

A study have shown that parents may prefer sedation over GA to avoid known consequences, however, dentists and anesthesiologists preferred GA as it is easier to monitor patients' vital signs and in maintaining safe airway. (Al Karaawi, 2019).

All patients scheduled for sedation should be assessed preoperatively and reviewed for risk factors prior to the start of procedure. (SASA, 2016).

Physical assessment

This include medical history questionnaire and recording of vital signs, which serve as a baseline measurement to the day of procedure. (SASA, 2020).

Medical questionnaire is filled by the patient/guardian and then revised in depth; it consists of;

Weight, current medications and allergies, previous sedations, general anesthesia, hospitalization, family history (SASA, 2020) and diseases or syndromes especially, central nervous system, cardiovascular system and respiratory system, these systems tend to be affected the most by the action of sedative agents (Jackson & Johnson, 2002).

A useful method of assessing the level of risk involved in treating a child is to assign a physical status classification to the child (Jackson & Johnson, 2002), such as the American Society of Anesthesiologists (ASA) Physical Status Classification (Figure 1)

ASA I & II are considered appropriate for sedation, including mild, moderate or even deep at the dental office (AAPD, 2019), however ASA II patients may become ASA III by the morning of the procedure, that is why children should be evaluated again immediately prior to the procedure. (SASA, 2020). ASA III & IV are not recommended for sedation particularly moderate and deep, although, if sedation is still indicated special considerations must be made and should be done in a hospital setting in presence of an anesthesiologist. (SASA, 2020).

Airway assessment

Regarded as the most vital aspects to assess the possibility of adverse events in sedation. (AAPD, 2019).

The frontal and lateral view of the face is observed for abnormalities or asymmetries in the mouth, nose and neck. (SASA, 2020). Mouth opening is also examined for loose teeth and enlarged tongue also known as macroglossia. (SASA, 2020). Examination of the pharynx for enlarged tonsils close to the medial side of the mouth is crucial along with Mallampati classification. (SASA, 2020).

Mallampati classification

Provides different classifications from I to IV (Figure 2) used to assess the patency of the airway and consist of a visual inspection space from the base of the tongue to the roof of the mouth (Malamed, 2010), it’s also used to provide a prediction for the ease of endotracheal intubation. (Malamed, 2010).

This technique is done when the patient is in sitting posture with maximal protrusion of the tongue with phonation. (Mallampati et al., 1985).

A high Mallampati score (class III or IV) indicates a higher chance of compromised airway and Sleep Apnea under sedation or GA. (Malamed, 2010). Sleep apnea is interrupted breathing caused by obstruction of the airway by the tongue and soft palate. (Young et al., 2004). It was shown that patients with rigorous obstructive sleep Apnea (OSA) and multiple incidence of desaturation will suffer from malformed Mu-Receptors (Brown et al., 2004), opioid analgesics primarily work on Mu-Receptors (Brown et al., 2004), so children with OSA become analgesic at opioid levels of half to one third that of a normal healthy patient (Moss et al., 2006), therefore, lower dosages of opioids must be utilized in these patients. (AAPD, 2019).

Facilities and Equipments

Part of providing safe and systematic approach for sedation procedure is following an easy to remember acronym which stands for the equipment in need, such as SOAPME;

• Suction: Appropriate suction catheters. (AAPD, 2019); (SASA, 2016).
• Oxygen: O2 supply, working flow meters and delivery devices. (AAPD, 2019); (SASA, 2016).
• Airway: Endotracheal tubes, oral & nasal airways, laryngoscope blades. (AAPD, 2019); (SASA, 2016).
• Pharmacy: Basic life saving drugs & antagonists as indicated. (AAPD, 2019); (SASA, 2016).
• Monitors: Pulse oximeter, BP monitors. (AAPD, 2019); (SASA, 2016).
• Equipment: Special equipment for the particular patient. (AAPD, 2019); (SASA, 2016).

Personnel

This include a sedationist who usually is a medical practitioner or an anaesthesiologist that only performs the sedation procedure (Piercy & Roelofse, 2010), operator-sedationist who performs the procedure and sedation (Piercy & Roelofse, 2010) and lastly, dental sedation nurse or sedation assistant that monitors the equipment and record vital signs, sometimes also called an observer. (Piercy & Roelofse, 2010).

Healthcare professionals involved must be competent and trained with the technique used. (SASA, 2020). Personnel trained must be trained with Basic life support (BLS) in case of emergency and Paediatric Advanced life support (PALS) training is also recommended. (AAPD, 2019).

Covers different parts of the procedure, it includes documents before sedation (Diagnosis appointment), immediately before sedation (Sedation appointment), during sedation (monitoring), after sedation and Discharge questionnaire. (SASA, 2020).

Documentation before sedation:

Medical history questionnaire should be completed in the first appointment and authorized by the child’s parent or guardian. (SASA, 2020).

Informed consent

This document must be in verbal and written format, signed before administration of any sedative or analgesic drug (AAPD, 2019), it consists of cost, explanation of the dental procedure, intended sedation medication, administration route, risks and benefits and lastly, any other appropriate alternatives. (SASA, 2020).

Pre-sedation instructions

Pre sedation instructions must be clearly explained to the parent before the day of the procedure some of the instructions include; child should wear comfortable loose clothes (AAPD, 2019), child taking chronic disease medication must take it on the day of the procedure with small sips of clear fluid, after discussing this with the doctor or dentist. (SASA, 2020). Make sure that the child doesn’t wear nail polish (Çiçek et al., 2011), it was shown that nail polish may interfere with the pulse oximetry measurements. (Çiçek et al., 2011).

Fasting Rule

Poor protective reflexes during sedation can lead to pulmonary aspiration (Mallory et al., 2011), that’s why fasting is recommended before sedation for; Formula milk or Solid food: six hours, Breast Milk: four hours and Clear fluids: two hours. (SASA, 2020).

In case of emergency and the patient has not fasted, the risk is clearly balanced with the urgency of the treatment and risk of delaying of procedure. (Treston, 2004).

Post-sedation instructions

Given to the parent in verbal and written format can include but not limited to; Avoid lip biting due to paresthesia by local anesthesia injection (SASA, 2020), monitor the child for at least 12 hours after the procedure without interfering with their activities if they need to rest quietly (SASA, 2020), introduce food slowly by starting with fluids then move to solids. (SASA, 2020).

Documentation Immediately before sedation

Pre-procedural checklist must be completed to minimize adverse effects of the procedure (SASA, 2020), in addition, measurements of the vital signs is taken and compared with the baseline measurements taken during history (AAPD, 2019), any changes must be recorded. (SASA, 2020).

Documentation during sedation (Monitoring)

This include a time-Based document which should be updated at least every 10 minutes. (SASA, 2020). Route and dose of sedation medication are recorded first, monitoring depth of sedation, airway patency, adverse events and complications must be then reported. (SASA, 2020); (AAPD, 2019). Behaviour monitoring can also provide a helpful tool to determine the depth of the sedation. (SASA, 2020). According to SASA the University of Michigan Sedation Scale (UMSS) is an easy, effective and credible scale that facilitates fast and reliable assessment of depth of sedation in children. (SASA, 2020); (Malviya et al., 2002).

Documentation after sedation (Recovery & Discharge)

Following the sedation procedure, the child needs to be observed in an adequately equipped recovery room. (Hosey, 2002). Observation must be done by a health professional trained with BLS (SASA, 2020) till there is no further risk of reduction in consciousness of the patient. (AAPD, 2019). To discharge the patient from the medical facility, this necessitates that the patient has no pain, is easily rousable, can take oral fluid, can talk & sit unaided and most importantly with a patent and uncompromised airway. (SASA, 2020).

This segment is going to cover the routes of administration with light to the advantages, disadvantages, patient selection for each, indications and contraindications.

It must be pointed out that intramuscular, submucosal and sublingual routes were rarely advocated for use in pediatric dentistry. (Baek, 2015).

Oral route

The most universally accepted and easiest method of administrating a sedative agent (Alzahrani et al., 2012), sedative drugs administered in the form of pills or syrups. (SASA, 2020). It is relatively safe, economic and requires no special equipment (SASA, 2020), however, it was shown to have a variability of effects which depends on intestinal absorption (Girdler, 2017), which means longer onset of action and inability to titrate the drug, therefore, reaching the desirable sedation level can be tricky and unpredictable sometimes. (Girdler, 2017).

A common issue encountered with oral sedation is that it depend on the patient compliance whether they accept swallowing the medication or not, some drugs may have bitter taste like oral midazolam. (Girdler, 2017).

Rectal route

With rectal routes studies have shown controversial absorption levels and exhibits the poorest sedation control compared to other forms of administration (Kupietzk, 1993), in addition, because of cultural sensitivities this route is not routinely used for dental sedation. (Dean & Cameron, 2016).

Intranasal route

Demonstrates direct absorption of sedative agent into the blood circulation through the nasal mucosa (ADA, 2016), it can avoid the first hepatic pass metabolism, hence, having increased bioavailability, faster onset and recovery compared to oral route. Its peak level of action is ten minutes and recovery time is 30 minutes. (SASA, 2020). Only mild cooperation is needed for this technique, in contrast to IV cannulation in intravenous route and nasal hood in inhalation sedation (Nelson & Xu, 2015), however, it is usually associated with burning sensation, tearing and crying. (SASA, 2020). Common cold and increased mucous secretions are contraindications since sedative drug uptake is highly dependent on the patency of the nasal passages (Kupietzk, 1993).

Bitter taste was reported to last for few hours after sedation with IN midazolam (Wood et al., 2011) however, a concentrated form of IN midazolam 25 mg/mL or 40 mg/mL with lidocaine can decrease bitter taste made with IN Midazolam. (Peerbhay & Elsheikhomer, 2016). Intranasal sedation is recommended only for short or emergency dental procedures. (Girdler, 2017).

Inhalation route

Gaseous or volatile agent introduced to the lung, becomes bioavailable through the blood/Air apparatus in the alveoli (ADA, 2016). Demonstrates fast onset of action and recovery from sedation, which indicates that the level of sedation can be easily manipulated or terminated.

Nitrous Oxide sedation

Nitrous oxide (N2O) is an inhalation sedation gas with analgesic characteristics (Attri et al., 2017); (SASA, 2020), known and proven to be safe when used in moderate sedation (Attri et al., 2017). N2O has a prompt absorption, rapid onset and recovery due to lack of solubility in the plasma and adipose tissue (Becker & Rosenberg, 2008), therefore, achieves equilibration most rapidly than any other inhalation agent. (Becker & Rosenberg, 2008). Nitrous oxide is indicated in moderately cooperative patients with anxiety but can understand and follow simple instructions (SASA, 2020) or patients suffering from extreme gag reflex that can hinder the procedure. (Attri et al., 2017). It is important to note that Nitrous oxide sedation is almost always indicated in extensive and lengthy procedures due to its safe applications and fast recovery. (AAPD, 2019).

Contraindications for nitrous oxide involve patients with anatomic or disease-induced airway obstructions such as upper respiratory tract infection (URTI), Chronic obstructive pulmonary diseases (Attri et al., 2017) and uncooperative child patient who refuses placement of the nasal hood because of mental or physical disability. (Attri et al., 2017). Recent surgery of the ear or infection of the middle ear also is contraindication for N2O sedation due to reported cases of ruptured tympanic membrane (Morgan et al., 2006).

Nitrous oxide is administrated after selection of nasal hood with the appropriate fit and size (SASA, 2020), then 100 percent oxygen is introduced for one to two minutes, followed by titration of N2O by 10% increments till the appropriate depth of sedation is achieved which shouldn’t exceed 50% in conscious sedation. (SASA, 2020). The flow rate should be from five to six litres per minute. (Attri et al., 2017). Constant monitoring of child eyes, general responses and level of consciousness is very important during induction of sedation until recovery. (AAPD, 2019)

The most frequently reported adverse effects of N2O are nausea, vomiting and diffusion hypoxia.

Diffusion hypoxia is a phenomenon that occur when N2O is released rapidly from the blood stream to the alveoli after nitrous oxide sedation (AAPD, 2019); (Cameron & Widmer, 2013), however, it is drastically reduced with administration of 100% oxygen for 3-5min after termination of nitrous oxide. (SASA, 2020)

Long term exposure of N2O was reported as an occupational safety hazard because it demonstrated; Reproductive system disturbances, bone marrow suppression and vitamin B metabolism disorders (Girdler, 2017), in addition, there is a considerable risk on pregnant staff specially in first trimester, where it can lead to abortion. (Girdler, 2017). Proper scavenging systems, adequate air circulation, ventilation and use of rubber dam can significantly reduce contamination and hazards of N2O (Holroyd, 2008)

Intravenous route

A method of sedation that involve direct administration of sedative agent to the blood stream through cannulation. (SASA, 2020). This can avoid first pass effect and allow lower doses when compared to oral sedation (AAPD, 2019). Intravenous sedation (IV) allow adequate titration and provides a fast onset of action, which means shorter procedure time with proper depth of sedation (Lourenço-Matharu et al., 2011), in addition, IV sedation can allow rapid access to drug antagonist in case of emergency. (AAPD, 2019).

Main disadvantage of this technique is patients with needle phobia can encounter a traumatic experience when inserting the needle cannula (Nelson & Xu, 2015), thus, EMLA/analgesic topical cream should be applied before procedure to reduce pain on the site of injection.

In general, short procedures that require approximately 30 min duration. (Cameron & Widmer, 2013)

Sedative agents

This section is going to include the most common sedative agents used in paediatric dentistry along with their properties, advantages, disadvantages and common adverse effects.

Midazolam is among the most popularly used sedative medication in dentistry (Attri et al., 2017), it’s a benzodiazepine (BDZ) that produce hypnosis and anxiolysis but doesn’t provide analgesia. (SASA, 2020). BDZ provides a wide margin of safety (Attri et al., 2017), with a rapid onset of action due to high solubility. (Attri et al., 2017). Midazolam is given in different routes of administration, most commonly in oral form a dose of 0.25mg-0.5mg/Kg. & Intravenous 0.025mg-0.1mg/Kg, when given in oral form, sweetened syrup is given with midazolam due to its bitter taste (Attri et al., 2017). Some patients may experience dental fear during treatment, midazolam produce anterograde amnesia which is an effective feature in these situations. (Shah et al., 2011). Al-Rakaf et al., (2001) & Peerbhay & Elsheikhomer, (2016) found that as the dose increase from 0.3 to 0.5 mg/kg, the anxiety reduce and there is improved behavior of the patient.

Marshall et al., (1999) found an improvement in Frankl behavior with increasing oral dose from 0.5 to 0.75 mg/kg, however, patients experienced increased adverse effects. Common side effects with midazolam include respiratory and cardiac depression, ataxia, dystonia, diplopia (double-vision) and paradoxical agitation which arises in 15% of patients (SASA, 2020); (Attri et al., 2017), in addition, various drugs such as, erythromycin, antidepressants, antipsychotics, antiepileptics and antihistamines can enhance the effects of midazolam and subsequently lead to over-sedation. (Attri et al., 2017). In case of uncontrolled depth of sedation and respiratory depression by midazolam (SASA, 2016), an antagonist to benzodiazepines such as Flumazenil can be given to reverse the action of BDZ, In case of emergency, if there is no IV access the same dose can be administered intranasally. (SASA, 2016). The duration of action of flumazenil is around 1 hour, if large dosages of midazolam were given, multiple administrations are required. (SASA, 2016). It must be noted that administration of flumazenil in purpose of rushing the discharge of the patient is inappropriate. (SASA, 2020).

Fentanyl and alfentanil are short-acting opioids, can yield varying levels of analgesic and sedative effects (SASA, 2020), usually given in either painless or painful procedures. (AAPD, 2019). Opioids are easily titratable and produce side-effects that are rapidly reversible, however, monitoring of depressant effects remains critical. (AAPD, 2019). While opioids have sedative action, it should not be primarily administered in sedation alone but in combination with another sedative agent. (SASA, 2020). Common side effects of using opioids include chest wall and glottic rigidity that leads to respiratory depression low gastrointestinal activity which can lead to nausea and vomiting. (Attri et al., 2017); (SASA, 2020).

According to SASA, when opioids are administered, an antagonist such as naloxone must be readily accessible. (SASA, 2016). Naloxone reverses respiratory depressant side effects and analgesia produced by opioids (Girdler, 2017), it must only be utilized for extreme cases of airway depression, as naloxone can lead to a major sympathetic action. (SASA, 2020). If IV access is not accessible, the dose may be given intramuscularly. (SASA, 2020).

Ketamine is a hallucinogenic agent that produce trance-like state that can lead to sedation, analgesia and amnesia (Attri et al., 2017); (SASA, 2020), ketamine restricted effect on the respiratory system and CVS stability is advantageous compared with other sedative agents (Attri et al., 2017), when used with patients with CV disease, it produce only minor effects on the heart rate (Attri et al., 2017). Common side effects of ketamine are increased salivary and tracheal mucus gland secretions (Heinz et al., 2006), which is particularly dangerous in patients with respiratory tract infections, where it can predispose to laryngospasm. (SASA, 2020)

Emergence delirium phenomenon one of the most commonly cited side effect of ketamine, found more in adults (5–50%) than children (0–5%). (Attri et al., 2017).

Propofol is a short acting sedation drug that lack analgesic characteristics (AAPD, 2019), it is promptly circulated to the peripheral tissue, and its effects, therefore, diminish drastically in half hour of administration (SASA, 2020), This, together with its fast onset of action as well as adequate amnesia it produces turns it to an “ideal” agent for intravenous sedation (Buck, 2000), however, margin of safety is narrow when compared to other sedative agents like e.g. midazolam and ketamine. (SASA, 2016). Common adverse events of propofol are increased incidence of respiratory depression and laryngospasm. (SASA, 2016).

It was frequently reported that deep sedation and obstructive apnea can occur rapidly and unpredictably with propofol, thus, propofol is recommended to be administered in the presence of capnography, along with an anesthesiologist trained with BLS. (SASA, 2016).

Combination of drugs

A polypharmacy comes with a high risk of complications; therefore, it should only be undertaken in the presence of qualified and well-trained personnel. (AAPD, 2019); (SASA, 2020)

Ketofol is made from ketamine and propofol as a combination (SASA, 2020). The synergy between propofol and ketamine meaning lower dosages for each agent can be used in combination, decreasing the likelihood of side effects. (SASA, 2016).

Several studies noted sedation and analgesia to be safe and effective. (Akin et al., 2005); (Willman et al., 2007).

Shah et al., (2011) showed less adverse effects with ketofol compared to ketamine alone.

Ketamine & Midazolam; Midazolam stabilize the hallucinogenic effects of ketamine, and ketamine reduce the depressive effect of midazolam. (SASA, 2020). When compared to ketamine alone, ketamine plus midazolam showed lower side effects and recovery difficulties (Girdler, 2017)

Midazolam & N2O; provides safe form of sedation in dentistry (Alzahrani et al., 2012), this combination provides the same sedative effects but with reduction in the dosage of midazolam, hence, less adverse effects. (Gowri & Kannan, 2017). Midazolam alone lack analgesic effects, however, with nitrous oxide the additive effects can produce analgesia, which is practical in painful procedures. (Averley et al., 2004).

A Cochrane library systematic review conducted to investigate the most ideal agent or method of sedation in dentistry determined that the evidence is inconclusive due to the poor quality of the established studies (Ashley et al., 2018), Which means more quality research is needed with controlled variables. (Ashley et al., 2018). however it was shown that Nitrous oxide and Midazolam regardless of the route, are the most widely studied, most commonly and safely used sedation drugs in dentistry. (Ashley et al., 2018).

Table below demonstrates the different application of each drug:

(SASA, 2020); (AAPD, 2019); (Girdler, 2017); (Ashley et al., 2018).

Airway can be obstructed by aspiration of foreign bodies while treating patients under sedation (Walker, 2013), this can happen due to reduction in gag reflex and lack of throat packing, as found in general anesthesia. (Girdler, 2017). however, proper utilization of rubber dam and high-volume suction during dental treatment can provide a physical barrier which can prevent the risk of aspiration. (Girdler, 2017).

Neurological damage post sedation is a serious side effect which can lead to permanent brain damage, this incident is related to respiratory depression during sedation and lack of oxygen which leads to death of the brain cells, this is avoided by proper monitoring, dosage and control of level of sedation. (Davydow et al., 2009); (Girdler, 2017).

Conclusion

Expertise in conscious sedation medications and the ability to manage adverse events of over sedation is critical for sound and efficient outpatient procedural sedation.

Adequate dispensing of conscious sedation drugs can allow painful and anxiety provoking treatment endurable, increase child acceptability to dental treatment and allow modification of the behavior for future dental visits.