TYPE Review

PUBLISHED 26 April 2023

DOI 10.3389/fmed.2023.1186823

Procedural sedation in pediatric

OPEN ACCESS dentistry: a narrative review
EDITED BY
Diansan Su,
Shanghai Jiao Tong University, China
Feng Gao 1,2,3 and Yujia Wu 1,2,3*
REVIEWED BY
1
Department of Anesthesiology, Stomatological Hospital of Chongqing Medical University, Chongqing,
Xudong Yang, China, 2 Chongqing Key Laboratory of Laboratory of Oral Diseases and Biomediacal Sciences,
Peking University Hospital of Stomatology, Chongqing, China, 3 Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher
China Education, Chongqing, China
Na Xing,
Hospital of Zhengzhou University, China
Procedural sedation and analgesia are now considered standard care for
*CORRESPONDENCE
Yujia Wu managing pain and anxiety in pediatric dental patients undergoing diagnostic
[email protected] and therapeutic procedures outside of the operating room. Anxiolysis, which
RECEIVED 15March 2023 combines both pharmacologic and non-pharmacologic approaches, plays a
ACCEPTED 05 April 2023 significant role in procedural sedation. Non-pharmacologic interventions such as
PUBLISHED 26 April 2023
Behavior Management Technology can help reduce preprocedural agitation, ease
CITATION
the transition to sedation, reduce the required amount of medication for effective
Gao F and Wu Y (2023) Procedural sedation in
pediatric dentistry: a narrative review. sedation, and decrease the occurrence of adverse events. As the introduction of
Front. Med. 10:1186823. novel sedative regimen and methods in pediatric dentistry, the potential role of
doi: 10.3389/fmed.2023.1186823 mainstay sedatives administered by new routes, for new indications, and with new
COPYRIGHT delivery techniques, should be considered. The purpose of this paper is to examine
© 2023 Gao and Wu. This is an open-access
and discuss the current state of sedation techniques in pediatric dentistry.
article distributed under the terms of the
Creative Commons Attribution License (CC BY).
The use, distribution or reproduction in other KEYWORDS
forums is permitted, provided the original
author(s) and the copyright owner(s) are procedural sedation, pediatric dentistry, behavior management technology, drug
credited and that the original publication in this delivery, medications
journal is cited, in accordance with accepted
academic practice. No use, distribution or
reproduction is permitted which does not
comply with these terms.

1. Introduction
Dental phobia and dental anxiety are both terms used to describe fear and anxiety related
to dental procedures, but they differ in their severity. Dental phobia refers to an enduring and
excessive fear of dental stimuli and procedures that results in avoidance or significant distress.
Dental anxiety, on the other hand, is a heightened fear of dental procedures that may or may not
meet the complete criteria for a diagnosis of phobia. Children and adolescents who suffer from
odontophobia or dental anxiety may exhibit disruptive behaviors during examinations and
treatment, ranging from restlessness to full-blown tantrums (1); In the most extreme cases,
young individuals with dental anxiety may refuse treatment, even when they are experiencing
significant pain that could be relieved with proper care (2). Prevalence estimates of dental
anxiety in youth are somewhat variable, with estimates ranging from around 5 to 20%. However,
this is likely to be an underestimate in the general population since children and adolescents
with the most severe dental anxiety may avoid dental treatment entirely or seek care only at
specialty clinics (3). Dental anxiety and fear vary across a continuum from very mild anxiety
and fear to severe and debilitating dental phobia (4). A child’s capability to regulate their own
behavior and cooperate during a procedure relies on their chronological age as well as their
cognitive and emotional development. Children who have low or moderate levels of fear or
anxiety can be effectively managed by establishing a trusting relationship, utilizing good
communication skills, showing empathy, providing careful treatment, and using some basic
non-pharmacological techniques. Conversely, highly anxious/fearful or phobic children may
necessitate targeted pharmacological support in addition to the utilization of behavior guidance
strategies, such as behavioral guidance techniques, nitrous oxide sedation, intravenous sedation,

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TABLE 1 Terminology to describe levels of procedural sedation.

Level of sedation Description

Minimal Also called anxiolysis; the patient is awake and relaxed, and is able to respond normally to verbal stimuli.

Moderate Also called conscious sedation, the patient experiences a state of depressed consciousness while remaining responsive to verbal requests or tactile
stimuli. Spontaneous breathing remains unimpaired, and no respiratory support is required.

Deep The patient displays a decreased level of arousal but responds intentionally to painful stimulation, potentially requiring assistance to maintain
airway patency and adequate ventilation. Cardiovascular function is usually maintained.

Dissociative The patient is in a trance-like and cataleptic state, experiencing deep analgesia and anesthesia. Despite this, the patient retains protective airway
reflexes, spontaneous ventilation, and cardiovascular function.

and general anesthesia (5). The selection of sedative agents and the degree of sedation, with the Ramsey scale being the most
approach is typically influenced by factors such as the type of commonly used. This scale scores on eight characteristics, with scores
procedure, the patient’s comorbidities and temperament, and the indicating anxiolysis (2 to 3), moderate sedation (4 to 5), deep
clinician’s preference. The primary objectives of sedation usually sedation (6), and general anesthesia (7 to 8) (16) (Table 1).
include providing anxiolysis, analgesia, amnesia, safety, efficacy, and Choosing the minimal number of medications and ensuring that
the ability to facilitate the completion of the procedure (6). Numerous the drug selection aligns with the type and objectives of the procedure
short procedures may be conducted using distraction and guided are crucial for safe practice. Dental sedation is unique in that it
imagery techniques in conjunction with the application of topical or remains, along with emergency medicine, the area of procedural
local anesthetics, and minimal sedation if necessary (7). However, sedation where the proceduralist can also be supervising the
lengthier procedures that demand immobility involving children administration of sedation (17).
younger than six years or those with developmental delays often The perfect sedative substance would alleviate anxiety and
demand a greater level of sedation to gain control of their behavior (8). enhance conduct, thus facilitating the execution of dental procedures
A dental practice environment presents several additional and offering a pleasant experience for the patient. It ought to
challenges, such as the use of the low-speed drill, continuous vibration, be administered safely in the primary care sector and possess a
constant suction, and the administration of local anesthesia injections. generous margin of safety (12). The purpose of this paper is to discuss
All of these concurrent stimuli may cause the child to remain in a the current state of pediatric dental sedation.
heightened state of alertness (9). Because of the significant levels of
anxiety and fear experienced by young children during dental
procedures, conventional non-pharmacological methods are often 3. Goals and safety of procedural
considered inadequate (10). Due to dental fear and/or dental behavior sedation
management problems, some children may not be able to cooperate
for treatment using local anesthesia and psychological support alone, As per the American Academy of Pediatric Dentistry (AAPD) and
and passive restraint was ranked as the least desirable technique. the American Association of Pediatrics (AAP),the objectives of
Parents have reported concerns that protective stabilization may sedation encompass: (1) to guard the patient’s safety and welfare; (2)
increase their child’s fear and be stressful for them (11). Although to minimize physical discomfort and pain; (3) control anxiety,
treatment can be performed under general anesthesia, it is generally minimize psychological trauma, and maximize the potential for
recommended to avoid it whenever possible due to the need for amnesia; (4) to modify behavior and/or movement to allow the safe
specialized resources and the potential risks, including the risk of completion of the procedure; and (5) to return the patient to a state in
death (12). which discharge from medical/dental supervision is safe, as
determined by recognized criterial (8). All of these objectives must
be attained while ensuring that the patient retains airway control,
2. Definition of procedural sedation oxygenation, and hemodynamic stability. The endeavors of the
Pediatric Sedation Research Consortium have significantly enhanced
The International Committee for the Advancement of Procedural our understanding of procedural sedation, and have demonstrated the
Sedation provides the following definition for the practice of remarkable safety of procedural sedation when administered by
procedural sedation: The practice of procedural sedation is the proficient and enthusiastic practitioners from various disciplines,
administration of one or more pharmacological agents to facilitate a employing the aforementioned modalities and skills that prioritize a
diagnostic or therapeutic procedure while targeting a state during culture of sedation safety. Nonetheless, these pioneering investigations
which airway patency, spontaneous respiration, protective airway also reveal a persistent but low incidence of potential life-threatening
reflexes, and hemodynamic stability are preserved, while alleviating events induced by sedation, such as apnea, airway obstruction,
anxiety and pain (13). In order to meet the need for pain control, laryngospasm, pulmonary aspiration, desaturation, and others, even
analgesics can be combined with sedative agents, a technique referred when administered by a dedicated team of specialists. These studies
to as procedural sedation analgesia (PSA) (14). Procedural sedation is have helped to establish the essential competencies required to rescue
categorized as a state of minimal or moderate sedation in accordance children experiencing adverse events while under sedation (8).
with the American Society of Anesthesiologists (ASA) classification Consequently, the provider must possess a thorough understanding
(15). Various evaluation methods have been developed to determine of the available pharmacologic agents to administer the most

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appropriate medication required for a specific procedure at the lowest psychological and behavioral approaches are effective (27).
dose and highest therapeutic index. Furthermore, for each Non-pharmacologic interventions, such as behavioral and cognitive
pharmacologic agent selected, the medical professional must be aware approaches, may prevent the need for procedural sedation in many
of the drug’s peak response, onset, and duration of action (18). children. Their use has been shown to ease the transition into a state
of sedation, reduce the amount of medication required, and
subsequently, the depth of sedation, and decrease the frequency of
4. Patient selection and assessment adverse events (28). The American Academy of pediatric Dentistry
(AAPD) recommended concentrating more on non-pharmacologic
Patient evaluation should encompass a comprehensive medical, intervention in future studies (29). To date, there are many behavior
dental, and social history. The American Society of Anesthesiologists management techniques (BMTs) available to dental practitioners,
Physical Status (ASA-PS) classification is an appraisal performed by including tell-show-do (TSD), relaxation, distraction, systematic
an anesthesia provider prior to anesthesia administration, with the desensitization, modeling, audio analgesia, hypnosis, and behavior
sole objective of evaluating the patient’s physical condition (18). rehearsal. Among these, TSD and modeling are the most commonly
Patients classified as ASA Class I or Class II may be regarded as used BMTs by pediatric dentists (30). Two literature reviews have
suitable candidates for outpatient conscious sedation. Patients in ASA suggested that distraction techniques are effective in reducing anxiety
Class III and Class IV present unique challenges necessitating and pain during dental procedures, but the level of evidence
personalized consideration and are optimally managed in a hospital supporting this is low (31, 32). The effectiveness of listening to music
setting (19). during dental procedures in reducing anxiety and pain is not clear, as
there are conflicting results in the literature. Some studies suggest that
music can be helpful in reducing anxiety and pain, while others do not
5. Selection of procedural sedation find significant benefits (33). The use of virtual reality headsets to
intervention in children provide a calming and distraction-inducing environment has shown
promising results in reducing anxiety and stress levels in patients
Sedation exists on a continuum, and the physiologic effects may undergoing dental procedures. This technology works by creating an
vary significantly depending on various factors, including the immersive environment that distracts the patient from the dental
medication, dosage, delivery route, and patient characteristics (20). procedure, which can help to decrease pain and anxiety levels (34, 35).
When selecting pharmacologic or non-pharmacologic interventions Communication with parents or legal guardians is crucial for effective
for sedation, the child’s developmental status, clinical circumstances, guidance of a child’s behavior during dental procedures. Maintaining
and overall condition must be taken into account (21). The open communication with parents can help ensure the child’s safety
invasiveness of a medical procedure may affect the perceived degree and comfort during the procedure, and it can also help alleviate any
of sedation. As the invasiveness of a procedure increases, a deeper anxiety or concerns that the parents may have (36) (Table 2).
level of sedation is typically required, necessitating higher doses of Research indicates that modern parents may be less tolerant of
medication and potentially increasing the risk of adverse events physical and attentional behavior guidance than previous generations,
during or after the procedure. The expected duration of the procedure and may be more inclined to accept or request procedural sedation or
is another essential factor to consider, in addition to invasiveness. A general anesthesia for their child’s dental treatment (37). As a result,
more extended procedure will necessitate a greater quantity of sedative pharmacological behavior guidance is now commonly employed in
drugs than a shorter intervention (22). Almost all non-dissociative the dental profession (38). The use of pediatric sedation outside of the
drugs used for procedural sedation and analgesia can induce a state of operating room is a growing trend in the field of anesthesiology.
general anesthesia, resulting in the loss of protective airway reflexes. However, few new sedatives have been introduced in the last decade,
Therefore, continuous monitoring is crucial, and clinicians must highlighting the need for further development of new routes and
be prepared to rescue patients from levels of sedation deeper than methods for delivering existing anesthetic agents (39).
intended (23). Achieving adequate sedation requires both anxiety
reduction and pain control, making excellent local anesthesia critical
(24). Guidelines for procedural sedation in the USA and Europe 7. The method of drug delivery
suggest selecting an appropriate sedative agent based on the procedure
and patient characteristics or for its ease of dosing to achieve and 7.1. PO
maintain sedation while minimizing adverse events (25, 26).
In the pediatric setting, it is generally advised to circumvent
aversive routes of administration, such as intravenous (IV)
6. Behavior management technology administration, and instead opt for the oral route of administration.
Among pediatric dentists, oral sedation is the preferred and most
Ideally, only children who suffer from high dental anxiety or fear, commonly utilized method of administration (24). Oral sedation is
or those with diagnosed dental phobia, should be referred to general not only cost-effective but also straightforward to administer, and is
anesthesia. The National Consensus Development Conference on generally well-received by most children. Importantly, it does not
Anesthesia and Sedation in the Dental Office recognizes that require injection or cannula insertion, which adds to its appeal as a
“behavioral approaches are often overlooked as effective mechanisms safe and convenient method of sedation (40). Oral medications are
for relieving patient apprehension” and suggests that sedation and particularly well-suited for inducing minimal to moderate sedation in
general anesthesia may be unnecessary in situations when the dental setting. While these medications can lead to mild

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TABLE 2 Brief description of different BMTs.

Technique Brief description

Tell-show-do The tell-show-do technique involves verbal explanations of procedures in phrases appropriate to the developmental level of the patient (tell),
followed by demonstrations of the visual, auditory, olfactory, and tactile aspects of the procedure in a non-threatening setting (show), and
finally, completion of the procedure without deviating from the explanation and demonstration (do)
Positive rein-forcement an efficacious method for rewarding desired behaviors and reinforcing their recurrence
Nonverbal communication Nonverbal communication entails reinforcing and guiding behavior through suitable physical contact, posture, facial expression, and body
language
Effective communication It is vital in establishing a relationship with the child and fostering a positive attitude toward dental health
Modeling Modeling is based on the psychological principle that children learn by observing the behavior of others. Therefore, by modeling appropriate
behavior, the dentist can capture the child’s attention, promote compliance, and prevent negative attitudes or behaviors
Voice control Voice control refers to the intentional modification of voice volume, tone, or pace to influence and guide the patient’s behavior
Parental separation Involves utilizing the presence or absence of parents to obtain cooperation for treatment
Distraction Distraction is a technique used to redirect the patient’s attention from a potentially unpleasant procedure
Hand-over-mouth technique The technique of hand-over-mouth is employed to redirect inappropriate behavior that cannot be modified by basic behavioral management
techniques. In this technique, the dentist gently places their hand over the child’s mouth while calmly explaining the behavioral expectations,
all while ensuring that the child’s airways remain open
Protective stabilization Partial or complete immobilization of the child may be necessary to protect them from injury, particularly in cases where the child is
uncooperative or disabled
Hypnosis Hypnotic induction may be utilized to help relax a child during dental procedures, as it has been shown to be effective in reducing anxiety in
children

impairment of cognitive function and coordination, they do not blood concentration. Nonetheless, a significant drawback of IV
typically affect ventilatory or cardiovascular functions (41). When administration, particularly in pediatric dental procedural sedation,
drugs are administered orally, they undergo significant reduction in is the requirement for continuous venous access and the associated
concentration due to hepatic first-pass metabolism. As a result, oral puncturing of the vein (46).
sedation may have certain drawbacks, such as the inability to titrate
the dose to achieve the desired effect, as well as the need for a single-
bolus dosing regimen (8). 8. Anesthesia technology
8.1. Total intravenous anesthesia
7.2. Intranasal and inhalation sedation
Total intravenous anesthesia (TIVA) is a general anesthesia
One of the major advantages of transmucosal administration is technique that employs a blend of intravenous anesthetics without the
that it allows for direct absorption of drugs into the systemic administration of any inhalation anesthetics. The primary objectives
circulation, bypassing hepatic first-pass metabolism and resulting in of this approach are to achieve a seamless induction and safe
increased bioavailability and faster onset of action compared to oral maintenance of anesthesia, along with swift emergence. Over the last
sedation. In addition, transmucosal administration typically causes few years, TIVA has gained immense popularity among pediatric
less discomfort than intravenous sedation, making it a more favorable anesthesiologists (47). In contrast to inhalation anesthetics, Lauder
option for patients (42). The extensively vascularized nasal mucosa et al. reported several advantages of TIVA during anesthesia in
and the olfactory tissue in direct proximity to the central nervous pediatric patients. According to their findings, significant reductions
system expedite swift transportation into the bloodstream and brain, in laryngospasm, nausea/vomiting, emergence delirium, airway
with onsets of action comparable to that of intravenous therapy (43). reactivity, stress hormone release, and pain were observed in pediatric
Despite its simplicity, relative painlessness, and the need for less patients undergoing TIVA (48). In the case of TIVA, it is necessary to
patient cooperation, intranasal administration has been linked with establish IV access before administering IV drugs. However, most
mucosal irritation (44). When comparing the administration of children worldwide dread the thought of an ‘IV’. To alleviate this fear,
intranasal midazolam via drops and aerosolized forms, aerosolization anesthesia is commonly induced via a mask. Once an appropriate
was better tolerated and resulted in less aversive behavior (45). In depth of anesthesia has been attained, IV access can then
dentistry, the intranasal route is regarded as parenteral and hence, may be obtained (49).
necessitate a more comprehensive sedation license.

8.2. New techniques for sedation delivery

7.3. Intravenous sedation
Target-controlled infusions (TCI) have the potential to become
Intravenous administration is the swiftest way for a drug to take the future of pediatric sedation. Advancements in computer
effect and the optimal method for titrating a drug to achieve a specific technology, pharmacokinetic modeling, and IV infusion delivery

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TABLE 3 Characteristics of several types of sedation.

Advantages Disadvantages
PO Economical, easily manageable from a technical standpoint, Decrease in concentration resulting from hepatic first-pass
widely embraced by the majority of children, and devoid of metabolism; inadequate ability to adjust the dosage to achieve
the need for injections or cannula insertion. desired effects, reliance on a single bolus administration, and
notable inter-individual variations.

Intranasal (IN) and inhaled routes Prevention of hepatic first-pass metabolism, leading to lower Mucosal irritation; may require a more comprehensive sedation
levels of discomfort compared to intravenous sedation and license.
greater acceptance among patients.

Intravenous (IV), TIVA, TCI and The most rapid method for a drug to produce an effect and Significant investment in both personnel and equipment, the
‘closed-loop system’ the optimal approach for tailoring drug dosage to achieve a requirement for continuous venous access, and the associated
specific blood concentration. venipuncture procedure.

devices have facilitated the development of TCI. TCI devices deliver a effectiveness of nitrous oxide-oxygen procedural sedation is
bolus, followed by exponentially declining infusions to quickly achieve diminished in cases of severe anxiety or fear. Additionally, due to their
and sustain a stable drug concentration in the plasma or at the site of inherently uncooperative nature, children may not readily accept the
drug effect. In pediatrics, a significant challenge for TCI is identifying nasal mask or may exhibit uncontrolled movements during the initial
models that are most suitable for children across various age ranges stages of sedation (59). Considering its significant diffusibility,
(50). Although there is insufficient evidence to provide definitive administration of nitrous oxide ought to be avoided in patients who
recommendations regarding the use of TCI versus MCI (manually have the potential for closed-space diseases, such as bowel obstruction,
controlled infusion) in clinical anesthesia practice, it has been middle ear disease, pneumothorax, or pneumocephalus.
reported that the use of TCI led to fewer interventions than MCI. This
discovery provides impetus for further research to develop pediatric
models for TCI and assess their practical applicability (51). 9.2. Midazolam
A more recent development in this field is the concept of
modifying TCI to a ‘closed-loop system.’ Closed-loop delivery systems Midazolam is a short-acting benzodiazepine that rapidly produces
provide the advantage of giving feedback to the delivery system, which anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant
can then adjust the delivery. Various procedures require different effects, and often leads to anterograde amnesia. The drug binds to the
depths of sedation, and each procedure has different demands for the benzodiazepine receptor in the central nervous system (CNS) and
level of sedation over its duration. With precise pharmacokinetic and augments the inhibitory effects of the neurotransmitter gamma-
pharmacodynamic studies tailored to different procedures, it may aminobutyric acid (GABA). The inhibitory effects of GABA are
be feasible to target TCI and closed-loop delivery more effectively to generated by augmenting the influx of chloride ions through the nerve
the procedure (52) (Table 3). cell’s ion channels, thereby decreasing the cell’s capacity to initiate an
action potential (60). The reliable and consistent sedative and amnestic
effects of benzodiazepines render them an appealing class of drugs for
9. Medications utilization in pediatric procedural sedation (61). Benzodiazepine
sedatives, with midazolam being regarded as the standard of care, have
9.1. Nitrous oxide been used extensively for procedural sedation in pediatric
patients (26).
Nitrous oxide is one of the top choices for mild sedation during Midazolam is a frequently used sedative agent in pediatric
dental procedures (53). For numerous years, a combination of nitrous dentistry due to its swift sedative action, anxiolytic properties, and
oxide and oxygen, featuring diverse concentrations, has been amnestic effects (62). The European Association of Pediatric Dentistry
efficaciously utilized to furnish analgesia during various painful (EAPD) recommends the use of oral midazolam for sedation of
procedures in children (54). The utilization of nitrous oxide for children requiring dental treatment. The administration of oral
minimal sedation entails the delivery of nitrous oxide at concentrations midazolam for dental sedation in pediatric patients is supported by
of ≤50%, blended with oxygen, and without any concurrent moderate-quality evidence and is deemed safe at appropriate dosages
administration of other sedatives, opioids, or depressant medications, while being well-tolerated by children (63). However, there have been
to an otherwise healthy patient belonging to ASA class I or II. During reports of paradoxical reactions in a small number of cases, such as
the procedure, the patient retains the capacity for verbal hyperactivity, aggressive behavior, inconsolable crying, and
communication (55). Research investigating nitrous oxide as a sole psychomotor disorders. These reactions are typically mild and self-
therapeutic agent has demonstrated that dental procedures were limiting, but healthcare providers should be aware of the possibility
accomplished in 52% of cases with a 40% concentration, and up to and monitor patients closely during and after the administration of
85% with an equimolar combination, with no reported adverse effects midazolam (64). Oral sedation with midazolam does not allow for the
(56, 57). According to a systematic review and meta-analysis, the same degree of titration as intravenous methods, which makes it
estimated efficacy rates of nitrous oxide-oxygen procedural sedation important to exercise caution when anticipating potential
in pediatric populations was 91.9% (95% CI:82.5 ~ 98.2%) (58). The pharmacodynamic interactions with other drugs. For example,

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combining midazolam with other sedative drugs, such as opioids or averting respiratory depression. Its capacity to maintain spontaneous
barbiturates, can lead to excessive sedation or respiratory depression. ventilation, spare respiratory effects, and uphold upper airway tone
Similarly, the use of midazolam with antipsychotics, H1 renders DEX an appealing option for procedural sedation in children,
antihistamines, or centrally acting antihypertensive drugs can result particularly those who are susceptible to apnea, hypoventilation, or
in additive sedative effects, which may increase the risk of adverse respiratory depression (71). DEX is an exceptional drug when the
events. Therefore, it is essential to review a patient’s medical history primary objective is to achieve sedation and immobility in children.
and medication profile before administering midazolam or any other It can be employed as a safe and effective option and is the preferred
sedative medication (65). Flumazenil can reverse respiratory drug for inducing sedation in diagnostic imaging procedures (72).
depression or apnea and paradoxical reactions. However, it should not Intranasal DEX helps overcome the challenge of obtaining
be administered to patients with seizure disorders or those receiving intravenous access in pediatric patients who are undergoing various
chronic benzodiazepine treatment due to the potential risk of diagnostic studies. This practice is becoming increasingly popular
precipitating seizures or withdrawal symptoms. The oral route of among sedation providers outside of the operating room owing to
midazolam administration (PO) is preferable, particularly in children, the reduction in emotional stress that children experience with the
as it is less traumatic. Oral midazolam can be administered 20 to intranasal administration route (73). The effects of DEX resemble
30 min before the procedure. The standard dosage of oral midazolam those of natural sleep, and it is known to be a safe and neuroprotective
for moderate sedation in children typically ranges from 0.25 to 1 mg/ agent in anesthetic neurotoxicity (74, 75). DEX has a slightly longer
kg (66). onset time (15 to 30 min) and a more prolonged duration of action
(55 to 100 min) when compared to midazolam (76).
Dexmedetomidine is an excellent sedative premedication option for
9.3. Ketamine uncooperative children and can be utilized as a sole agent for
sedation. However, current evidence suggests that it may not offer
Ketamine is a noncompetitive antagonist of the N-methyl-D- significant benefits when routinely administered as an adjunct to
aspartate receptor that impedes the discharge of the excitatory general anesthesia in children undergoing simple day case
neurotransmitter glutamate. It exerts its anesthetic, amnesic, and procedures (77). As Lee-Archer et al. comment, their current
analgesic effects by lowering central sensitization and the “wind-up” standard of care without dexmedetomidine is appropriate and no
phenomenon. Due to its efficacy and widespread use, Ketamine is a change in practice is needed. Until, or unless, further larger trials are
popular choice for painful procedures (67). At present, Ketamine is performed there is no reason to expose children to unnecessary
the solitary dissociative sedative agent employed in clinical practice. additional drug exposure when there is no clear evidence of its
It can be utilized as a sole pharmacological intervention for efficacy in these clinical situations.
painful procedures.
When administering procedural sedation to pediatric patients,
Ketamine can be administered via various routes such as intravenous, 9.5. Fentanyl
intramuscular, and intranasal. The use of Ketamine, either alone or in
combination with other agents, can safely, effectively, and promptly Fentanyl is a potent and highly selective opioid agonist with a
induce sedation in pediatric patients, regardless of the chosen route of rapid onset and short duration of action. Unlike other opioids, it lacks
administration (68). There exists a “dissociative threshold” of roughly histamine release and has fewer cardiovascular effects. It is primarily
1–1.5 mg/kg intravenously or 3–4 mg/kg intramuscularly for used for immediate relief of severe pain. The nasal spray formulation
Ketamine, beyond which increasing dosages do not lead to heightened of fentanyl is a safe alternative and eliminates the need for needle use
effects. Horizontal nystagmus is a characteristic outcome of Ketamine (78). However, the safety profile of oral transmucosal fentanyl citrate
administration, and parents should be apprised that this is a normal is poor, with complications in up to 46 percent of patients and a high
consequence of Ketamine use to avoid undue anxiety. rate of emesis (79). This has led to the recommendation that it not
Esketamine, a dextrorotatory enantiomer of Ketamine, has a lower be used for procedural sedation (80).
incidence of psychotropic side effects than racemic Ketamine. This Alfentanil is a synthetic, short-acting μ-opioid agonist that is
leads to lesser impairment in concentration capacity and primary associated with fewer adverse events, including less respiratory
memory, as well as faster recovery. Esketamine has the potential depression and postoperative nausea and vomiting (PONV), than
clinical advantage of a shorter recovery time and quicker orientation fentanyl. When compared to fentanyl, alfentanil has a shorter half-life
recovery time compared to racemic Ketamine (69). It can be given in and faster recovery time, which provides significant clinical advantages
a variety of ways, including nasal administration. during outpatient anesthesia (81).

9.4. Dexmedetomidine 9.6. Propofol

Dexmedetomidine (DEX) is a selective alpha-2 adrenergic Propofol has been a revolutionary anesthetic agent ever since
receptor agonist that can be employed for pediatric sedation via its inception four decades ago, and is still regarded as a nearly
intranasal, oral, or buccal routes of administration (70). There has perfect anesthetic agent. Its outstanding performance in clinical
been an upward trend in the utilization of dexmedetomidine, settings can be attributed to its prompt onset, brief duration of
particularly via the intranasal route. Unlike other sedative agents, action, and negligible adverse effects (82). Sub-anesthetic dosages
DEX does not interact with opioid and GABA receptors, thereby of propofol administered through intravenous conscious sedation

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infusion have eased dental procedures for apprehensive children. hydroxyzine hydrochloride or hydroxyzine pamoate, this drug has
Moreover, it can be injected toward the conclusion of an a wide safety margin and is frequently used in pediatric conscious
examination or procedure to mitigate the occurrence and intensity sedation. It can be administered as a sole agent or in conjunction
of emergence agitation (83). However, intravenous propofol with other medications such as midazolam. However, when used
induction remains problematic due to the challenges involved in concurrently with other central nervous system depressants,
obtaining vascular access in distressed and alert children (84). The hydroxyzine can increase the depressant effects. Several pediatric
most critical adverse effect of propofol is its potent respiratory sedation studies have utilized doses ranging from 1 to 2 mg/kg
depression, which may lead to sudden apnea. when combined with other sedative medications (90). The sedative
effect of hydroxyzine may appear somewhat delayed, but it endures
for a sufficient duration, making it suitable for lengthy
9.7. Etomidate dental procedures.

Etomidate is an imidazole-based agonist of the γ-aminobutyric

acid type A (GABAA) receptor used for the induction of general 9.11. Sevoflurane
anesthesia and sedation. It produces a rapid onset of hypnotic effect
similar to barbiturates and propofol but does not possess any analgesic Sevoflurane, a fluorinated methyl-propyl ether, functions as an
properties. A notable advantage of etomidate is its minimal impact on inhaled anesthetic that acts on the gamma-aminobutyric acid
the cardiovascular system. It causes negligible systemic changes in (GABA)-A receptor. It is a reliable anesthetic medication that has a
blood pressure and heart rate, making it an ideal drug for patients who rapid onset and recovery time. Additionally, it offers a quick
are hemodynamically unstable. Additionally, etomidate causes adjustment of anesthetic depth and has a high safety profile concerning
minimal respiratory depression and does not trigger histamine release, the cardiovascular system. One advantage of using sevoflurane for
rendering it a highly favorable agent (85). Etomidate may cause sedation, particularly in pediatric patients with needle phobia or
adrenocortical suppression by inhibiting the cytochrome P450 intellectual disabilities who are unable to cooperate with venous
enzyme 11β-hydroxylase, which renders it unsuitable for use as a catheterization, is that it is easy to administer compared to sedation
maintenance drug for anesthesia or sedation. Consequently, etomidate using intravenous drug injection. Due to these benefits, there is an
is primarily reserved for inducing anesthesia in patients who are expectation that the demand for sedation in dental treatment using
hemodynamically unstable (86). sevoflurane will continue to grow (91). When carrying out dental
procedures on pediatric or disabled patients, sevoflurane sedation is a
more cost-effective option compared to general anesthesia because of
9.8. Chloral hydrate its quicker induction and recovery times. However, sevoflurane
sedation does have some drawbacks. The distinctive odor of the
Chloral hydrate is a non-opiate, non-benzodiazepine sedative- sedative may be challenging to tolerate for some patients, and there
hypnotic drug. Although the liquid formulation of chloral hydrate is may be a need to secure the airway in cases of excessive sedation.
no longer available commercially, some hospital pharmacies are now Additionally, the anesthetic gas may spread to the treatment
compounding their own formulations. In pediatric dental practice, room (92).
low-dose chloral hydrate (10–25 mg/kg), in combination with other
sedating medications, is frequently employed. However, we have
observed a decline in the use of chloral hydrate, which is appropriate 9.12. Melatonin
considering its narrow therapeutic index and the lack of an antidote
for toxicity (87). Melatonin is an indoleamine that functions as an effective oral
sleep aid. Its primary function is to modulate the circadian rhythm of
sleep. Melatonin has been shown to have optimal efficacy as an initial
9.9. Pentobarbital anxiolytic agent for pediatric patients scheduled for surgical
procedures (93). However, the efficacy of melatonin and the
Pentobarbital is a barbiturate that does not possess any inherent appropriate dosage for children have yet to be clearly defined. The
analgesic properties, but induces deep sedation, hypnosis, amnesia, optimal dose of 0.5 mg/kg was established for melatonin based on
and anticonvulsant activity in a dose-dependent manner. When earlier reports (94). Ansari et al.’s research indicates that premedication
administered intravenously, sedation becomes noticeable in 3–5 min with oral midazolam in pediatric patients is superior to that with
and persists for approximately 30–40 min (88). However, the duration melatonin, with higher levels of satisfaction reported by both parents
of sedation with pentobarbital can be prolonged, which makes it a less and operators (95).
feasible option for high-volume outpatient pediatric dental services
that depend on swift patient turnover (89).
9.13. Reversal agents

9.10. Hydroxyzine Reversal drugs should not be administered routinely, but rather
should be reserved for instances of oversedation or respiratory
Hydroxyzine is a psychosedative medication that exerts depression that persist beyond a transient period and when the patient
antihistaminic, antiemetic, and antispasmodic effects. Available as fails to respond to verbal or tactile stimulation (23).

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TABLE 4 Properties of procedural sedation agents used in pediatrics.

Medications Dose Onset time Duration

Nitrous oxide Inhaled starting at 100% O2 and increasing concentration nitrous oxide to effect. 30 s (peak effect 3 to 5 min) 3–5 min

Midazolam PO 0.25-1 mg/kg (maximum dose 15 mg) 15–20 min 30–50 min

IN 0.3–0.5 mg/kg (maximum dose 10 mg) 10–15 min 30 min

IV 0.05–0.1 mg/kg (0.5–5 years) (maximum0.6 mg/kg) 2–3 min 30–50 min

IV 0.025–0.05 mg/kg (6–12 years) (maximum 0.4 mg/kg) 10–20 min 60–120 min

IM 0.1–0.5 mg/kg

Ketamine IV 1 mg/kg, given over 1 min; repeat dose (0.5 mg/kg) every 10 min as needed 1 min 15 min

IM4mg/kg; repeat dose (2 mg/kg) after 10 min if needed 3–5 min 15–30 min

Dexmedetomidine IN 1-4ug/kg (max 100ug) 15–30 min 55–100 min

IV 1–3 ug/kg loading dose (max 100ug) over 10 min, followed by 0.5–1 ug/kg/h continuous 5–10 min 15 min
infusion

Fentanyl IV 1–1.5 mcg/kg as initial dose and titrated 1 mcg/kg every 3 min 1–3 min 30–60 min

Maximum dose 4 mcg/kg

IN 1–3 mcg/kg 10 min 20 min

Propofol IV 1–3 mg/kg; may be repeated at half-doses as needed 15–30 s 5–15 min

Etomidate IV 0.2–0.3 mg/kg 1 min 5–15 min

Chloral hydrate PO 25–100 mg/kg, after 30 min can repeat 25–50 mg/kg. Maximum dose:2 g or 100 mg/kg 15–30 min 60–120 min

Pentobarbital IV 1–6 mg/kg, titrated in 1–2 mg/kg increments every 3–5 min to desired effect 3–5 min 30–40 min

IM 2–6 mg/kg, maximum 100 mg 10–15 min 60–120 min

PO 3–6 mg/kg maximum 100 mg(<4 years) 15–60 min 60–240 min

PO 1.5-3 mg/kg, maximum 100 mg (>4 years)

Naloxone IV or IM 0.1 mg/kg/dose up to maximum of 2 mg/dose, may repeat every 2 min as needed 2 min 20–40 min

Flumazenil IV 0.02 mg/kg/dose, may repeat every 1 min up to 1 mg 1–2 min 30–60 min
PO, per os (buccal); IV, intravenous; IM, intramuscular; IN, intranasal.

9.13.1. Naloxone 9.14.1. Remimazolam

Naloxone is an opioid-receptor antagonist used to treat opioid Remimazolam is a rapidly metabolized intravenously
overdose and reverse the respiratory and central nervous system administered benzodiazepine sedative that induces sedation by
depressant effects of opioids (96). It is available in both parenteral and binding to specific neurotransmitter receptors in the brain (99). It like
intranasal formulations, and has a relatively rapid onset of action remifentanil, has organ-independent elimination and acts on the same
(approximately 2 min) with a duration of approximately receptor as midazolam - γ-aminobutyric acid. As such, remimazolam
20–40 min (97). is classified as a “soft drug,” which has been investigated for the
creation of fast-acting sedatives with predictable recovery (100).
9.13.2. Flumazenil Randomized controlled trials of procedural sedation have shown that
Flumazenil is a benzodiazepine reversal agent that competes with remimazolam has a quicker onset and offset of hypnotic effect than
benzodiazepines for receptor sites through competitive inhibition. It midazolam. Remimazolam exhibits the cardiorespiratory stability
is used to reverse central nervous system and respiratory depressant typical of benzodiazepines, and its effects can be fully reversed by
effects and decrease recovery time. Flumazenil possesses a short half- flumazenil (101). Remimazolam does not produce injection site pain,
life, resulting in a short duration of action. It is important not to which is a common side effect in propofol use (observed in 18.7% of
hesitate to use flumazenil if you are having difficulty getting patients cases) (102). The incidence of intraoperative hypotension events is
to respond to verbal commands or if constant physiological lower with remimazolam (22%) compared to propofol (49.3%) (102).
monitoring indicates a trend toward non-manageable oxygen There is no requirement for unscheduled mechanical ventilation when
desaturation (98) (Table 4). administering procedural sedation with the use of remimazolam
(103). Propofol sedation has limitations such as pain at the injection
site and potential respiratory and hemodynamic depression without a
9.14. New innovation in drug development reversal agent. In contrast, remimazolam does not cause injection site
pain and has a reversal agent, which makes it a potential candidate for
Recent and evolving drug innovations are primarily focused on primary sedation medication in pediatric sedation in the future (104).
modifying the chemical structures of existing drugs or drug classes The continuous infusion of remimazolam could prove to be a
with the intention of improving their pharmacodynamic, valuable sedative option during dental procedures. Regarding general
pharmacokinetic, and side effect properties (82). anesthesia in adults, the recommended induction dose of remimazolam

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to achieve unconsciousness is 12 mg/kg/h, while a maintenance dose of However, these unfavorable events can be mitigated by combining
1 mg/kg/h is utilized in Japan and South Korea (105). In the ketamine with propofol. Propofol effectively mitigates the emetogenic
United States, a recommended dose of 5 mg of remimazolam and psycho-cognitive effects of ketamine, while the combined effect
administered via an IV push injection over 1 min is suggested for of ketamine decreases the likelihood of propofol-induced respiratory
inducing procedural sedation. If necessary, additional IV doses of depression and hypotension (109).
remimazolam of 2.5 mg over 15 s may be given with a minimum interval
of 2 min between doses. In the European Union, for patients not 9.15.2. Midazolam+ketamine
receiving a concurrent opioid, an initial dose of 7 mg of remimazolam Studies have indicated that premedication regimens combining
is recommended for inducing procedural sedation (106). the anxiolytic properties of midazolam with the analgesic properties
Despite remimazolam appearing to be an excellent sedative, only of ketamine resulted in superior pediatric behavior compared to the
a limited number of studies have evaluated its use for sedation in the administration of these drugs separately (110).
pediatric population. In order to enhance patient safety and comfort
during dental procedures, further studies on the use of remimazolam 9.15.3. Midazolam+fentanyl
for dental sedation in pediatric patients are necessary. The combination of fentanyl and midazolam is a commonly
employed regimen for procedural sedation and analgesia in
9.14.2. ADV6209 pediatric patients, with a robust safety profile when both drugs are
ADV6209, which has received approval as a pediatric anxiolytic meticulously titrated to effect. Fentanyl yields desirable effects,
in Europe, could potentially replace midazolam. One of the benefits including analgesia, sedation, enhanced mood, and extended
of ADV6209 is that it is a 0.2% aqueous midazolam formulation duration of action, which are not typically observed with other
combined with a gamma-cyclodextrin complex that masks the bitter frequently utilized sedatives. Moreover, opioids possess the
taste and improves solubility, with the addition of sucralose and potential benefit of decreasing the incidence of disinhibitory
orange aroma (107). Over 75% of the drug is absorbed within 30 min paradoxical reactions. Co-administration of an opioid alongside a
of oral administration, and in adults, it has a half-life of 2.66 h and a benzodiazepine appears to reduce the frequency of restlessness and
duration of 48.5 min (17). agitation, which are more commonly encountered with high doses
of benzodiazepines (40).
9.14.3. ABP-700
Cyclopropyl-methoxycarbonyl metomidate, also known as 9.15.4. DEX+ketamine
ABP-700, is a second-generation etomidate that binds to the same site Although procedural sedation using dexmedetomidine is
on the GABAA receptor as etomidate. ABP-700 is designed with an generally safe, bradycardia caused by this medication could be a
ester bond that undergoes rapid hydrolysis in the body by non-specific potential issue. However, it is worth noting that ketamine has a unique
tissue esterases, producing an inactive carboxylic acid metabolite. This ability to stimulate the cardiovascular system. Therefore, combining
potent anesthetic agent has minimal hemodynamic effects and adrenal low doses of ketamine with dexmedetomidine could lead to a more
suppression in animal studies. ABP-700 is a novel, potent, positive stable cardiorespiratory profile (111).
allosteric modulator of the GABAA receptor and is currently being
developed for general anesthesia and procedural sedation (85).
10. Fasting
9.15. Multi-drug delivery for pediatric The need for fasting prior to PSA is a controversial topic. Current
dental sedation ASA guidelines for fasting prior to PSA recommend 2-h clear,4-h
breast milk,6-h formula, and 8-h solids. However, there is little
Acknowledging that a singular pharmaceutical agent does not evidence that this approach actually prevents aspiration. The updated
provide optimal sedative outcomes, it is customary for pediatric dental Practice Guidelines for Moderate Procedural Sedation and Analgesia,
professionals to amalgamate various medications. This polypharmacy released in 2018, recommends a slightly different approach. According
technique offers cumulative, mutually augmenting, and intensified to these guidelines, patients should fast for 2 h if they have had clear
sedative effects, thereby allowing for decreased dosages of each liquids, 4 h if they have had breast milk, 6 h if they have had formula,
individual medication. Furthermore, medicines can be combined to and 6 h if they have had ‘light foods’ (112). Lowering the fasting time
introduce effects that are not innately present in a single agent (40). for clear liquids can improve the patient’s experience by reducing the
However, an analysis of case reports in the United States concerning duration of fasting. According to the updated 2023 ASA guidelines on
severe neurological impairment and fatalities revealed that these fasting, include the use of oral midazolam, it is recommended to
accidents were caused by the combination of more than three minimize fasting duration in children. Therefore, every effort should
medications, excessive dosages, and insufficient training (89). Limited be made to permit clear liquids in healthy children up to 2 h before
research, with available studies using mixed methodological medical procedures (113), and that early eating is safe as long as the
approaches, has made it difficult to judge either regimen as being patients have recovered from anesthesia and swallowing function
superior to the other (108). evaluation is done (114). It’s important to note that following the ASA
fasting guidelines is recommended for patients undergoing moderate
9.15.1. Propofol+ketamine sedation, where the child may not be able to maintain verbal contact
Ketamine poses the potential risks of undesired adverse effects or may undergo deep sedation. The use of nitrous oxide for sedation
such as emergence phenomenon, vomiting, and laryngospasm. does not require fasting.

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TABLE 5 Necessary equipment for safe administration of pediatric

sedation “SOAPME.”
EEG parameters to provide a numeric measure of the hypnotic effect
of anesthetic or sedative drugs on brain activity. The utility of the BIS
S = Size Appropriate suction catheters and a functioning suction monitor during general anesthesia has been validated in multiple
apparatus pediatric studies.
O = Oxygen An adequate oxygen supply and flow meters or devices to allow It is crucial for the clinical team to be able to identify signs of a
for delivery deteriorating patient and respond appropriately. While monitoring
A = Airway Size-appropriate bag-valve-mask, nasopharyngeal and equipment is essential, there is no single piece of equipment that can
oropharyngeal airways, laryngeal-mask-airway, laryngoscope replace the role of a capable and vigilant sedation provider who is
blades, endotracheal tubes and stylet, face mask responsible for monitoring the patient during the sedation procedure
(Table 5).
P = Pharmacy All basic drugs needed for life support during an emergency,
including antagonists

M = Monitors Functioning pulse oximeters, size-appropriate oximeter probes,

12. Conclusion
end-tidal carbon dioxide monitor, other monitors as appropriate
for the procedure
Pediatric dental providers should exercise caution in case selection
E = Equipment Special equipment or drugs as needed and customize the route, medication, and dosage based on the patient
From “Pediatric Procedural Sedation, Analgesia, and Anxiolysis” by B. Klick, A. Serrette, and and procedure. Patient safety should be the top priority, and providers
J.M. Clingenpeel, 2017, Emergency Medicine, 49, pp. 352–362. should adhere to established best practices for sedation. The key to
safe sedation lies in the early detection and management of potential
adverse events. The continued development and safety of pediatric
11. Monitoring sedation will depend on a thorough pre-sedation assessment and a
willingness to explore both traditional and new sedatives, either alone
Over the last three decades, sedation has become a commonly or in combination. Several important questions remain unanswered,
used alternative to general anesthesia. However, it is worth noting that such as the potential benefits and risks of using combination sedatives
almost 80% of sedation-related emergencies initially present as during a sedation procedure and their impact on
respiratory compromise (89). As the level of sedation deepens, the neurocognitive outcomes.
airway protective reflex decreases, and the likelihood of airway
obstruction or foreign body aspiration increases. Therefore,
appropriate respiratory monitoring and airway management are Author contributions
essential during sedation procedures. Various organizations, including
the Joint Commission on Accreditation of Healthcare Organizations FG: conceptualization, visualization, writing—original draft, and
(JCAHO), the American Society of Anesthesiologists (ASA), the polishing the manuscript. YW: conceptualization, funding acquisition,
American Academy of Pediatrics (AAP), and the American Academy and writing—last draft. All authors contributed to the article and
of Pediatric Dentistry (AAPD), have published guidelines aimed at approved the submitted version.
reducing the risks associated with sedation in children and ensuring
safe patient monitoring. These guidelines are mostly consistent and
follow the principles set out by the ASA. All guidelines for respiratory Funding
function monitoring recommend the following (115):
The present study was supported by Chongqing Medical
1. Continuous monitoring of oxygenation through pulse oximetry University 2022 Future Medical Youth Innovation Team Development
is necessary. Support Program (grant: w0147).
2. Ventilation should Be monitored periodically during moderate
sedation and continuously during deep sedation and
general anesthesia. Conflict of interest
Monitoring equipment typically includes cardiac, blood pressure, The authors declare that the research was conducted in the
pulse oximetry, and respiratory monitors. The use of an EtCO2 absence of any commercial or financial relationships that could
monitor is highly desirable. be construed as a potential conflict of interest.
Continual evaluation of the extent of sedation is of paramount
importance in detecting the patient’s transition into profound
sedation and the concomitant risk of impaired protective reflexes. Publisher’s note
The guidelines established by the American Academy of Pediatrics
(AAPD) and the American Society of Anesthesiologists (ASA) All claims expressed in this article are solely those of the authors
dictate that the depth of sedation be persistently monitored and do not necessarily represent those of their affiliated organizations,
throughout the procedure. In this regard, the BIS monitor can or those of the publisher, the editors and the reviewers. Any product
furnish an additional, objective criterion for measuring the depth of that may be evaluated in this article, or claim that may be made by its
sedation and thereby enhancing patient safety. It gathers processed manufacturer, is not guaranteed or endorsed by the publisher.

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Gao and Wu 10.3389/fmed.2023.1186823

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