Clinical Sedation Regimens

Dental needs
Child temperament
Drugs (all oral administration supplemented with N2O/O2)
Ultrashort (e.g., extract of maxillary central incisors)
Easy
Nitrous alone (40–50); midazolam alone (0.5 mg/kg)
Difficult
Midazolam (1.0 mg/kg) + nitrous (50 %)
Short (e.g., 1 quadrant of pulps/crowns)
Easy
Midazolam (0.5 mg/kg) + meperidine (1.0 mg/kg)
Difficult
Chloral hydrate (15–20 mg/kg) or midazolam (0.3–0.5 mg/kg) + meperidine (2 mg/kg) + hydroxyzine (0.5–1.0 mg/kg)
Long (e.g., two or more quadrants of dentistry
Easy
Chloral hydrate (15–25 mg/kg) + meperidine (2 mg/kg) + hydroxyzine (0.5–1.5 mg/kg)
Difficult
Recommend general anesthesia

Single Agents

Characteristics of the agents described below can be seen in Table 6.2. Midazolam may be one of the few agents that are commonly used alone in children. Furthermore, it is the most frequently used sedative agent in pediatric dentistry (other than nitrous oxide). It is generally indicated for children who require ultrashort or short procedures lasting less than 20 min of working time. It is relatively safe when administered orally in children whose risk status is ASA I. The dose range is from 0.3 to 1.0 mg/kg administered by the oral route. Therapeutic end points (i.e., “low” and “high” ends of therapeutic dose) in dosing can be associated with extremes in temperament (viz., lower doses for “easy” and higher doses for “difficult” children). Hiccups can occur shortly after consumption but usually resolve within 20–30 min after administration. Another prominent effect seen in a smaller proportion of patients is a paradoxical excitement or “angry child syndrome.” Anecdotally, the paradoxical excitement or “angry child syndrome” seems to occur more often in higher doses, regardless of temperament. Attempts to reason with the child during this effect are generally fruitless, but the effect can be reversed with a benzodiazepine reversal agent (i.e., Romazicon [flumazenil]). Reversing this hyperexcited state can be done, but the reversal effect is only temporary with reemergence of the state possibly occurring once the child has returned home. Consequently, it is advisable that when a reversal agent is administered, the patient should remain at the facility for a longer period of time to manage any issues associated with reemergence of the sedative agent.

Table 6.2

Characteristics of common drug combinations used in pediatric dentistry
Drug combinations
Individual drug Dose – oral (mg/kg)
Combo dose:
Characteristics
Warnings
Sedation considerations (timing)a
Likelihood of unconsciousness
+++ – high
++ – medium
+ – low
Reversibility
Choral hydrate
+ hydroxyzine
CH (15–50)
H (1–2)
Combo dose:
CH (20–40)
H (1–2)
Hyperexcitable
Agitation
Drowsiness
Sleep
Loss of consciousness
AIRWAY blockage!!!!!
Onset: 20 min
Separation time: 45 min
Work: 1–1.5 h
+++
None
Chloral hydrate + meperidine + hydroxyzine (called “triple” combo)
CH (15–50)
M (1–2)
H (1–2)
Combo doses:
“Low dose”
CH (15–25)
M (2)
H (2)
Euphoric
Mellow
Dysphoric
Agitated
Drowsiness
Sleep
AIRWAY blockage!!!!!
Deep sedation possible
Respiratory depression
Onset: 20 min
Separation time: 45 min
Work: 1–1.5 h
++
Only M is reversible in these combinations
Narcan (0.1 mg/kg)
“High dose”
CH (40–50)
M (1)
H (1)
     
+++
 
Meperidine
+ hydroxyzine
Combo dose:
M (1–2)
H (1–2)
Euphoria
Dysphoria
More sensitive to stimuli than “triple” combo
Respiratory depression, rare
Onset: 20–30 min
Separation time: 30 min
Work: 1 h???
+
Only M
Narcan (0.1 mg/kg)
Meperidine
+ midazolam
Combo dose:
M (1–1.5)
Mid (0.3–0.5)
Same as above
Angry child reaction
Fussy
Respiratory depression; loss of head right reflex
Onset: 20–30 min
Separation time: 30 min
Work: 1 h???
++
Both M and mid are reversible
Meperidine
+ hydroxyzine
+ midazolam
Combo dose:
M (1)
H (1)
Mid (0.3–0.5)
Initially relaxation;
Same as above
Same as above
Onset: 20–30 min
Separation time: 30 min
Work: 1 h???
+++
Only H is not reversible
Midazolam
+ hydroxyzine
Combo dose:Mid (0.3–0.7)
H (1–2)
Initial relaxation;
Same as above
Respiratory depression; loss of head right reflex
Onset: 10 min
Separation time: 20 min
Work: 30–45 min???
+
Only mid flumazenil (0.01 mg/kg)
aFor best results with any combination: “Settle” child with nitrous oxide (40–70 %) 5–10 min before proceeding. Remember to reset your nitrous to lower concentration after child is settled. If nitrous fails, expect poor sedation results. Inject local anesthesia very, very slowly
The working time, usually 20–30 min at most, can be increased by adding another agent with sedative properties such as hydroxyzine or meperidine or both; however, the depth of sedation also increases and a reduction in the dose of both agents is necessary. When combining agents, the latency time will usually vary depending on the mix of agents and their properties. For instance, the latency with midazolam alone is usually 10–15 min, hydroxyzine with 15–20 min, and meperidine with 20–25 min. When all three agents are used, latency time varies from 20 to 30 min.
Typically, midazolam initially causes a quieting of the child and obvious relaxation. The child must be watched carefully once relaxation occurs; otherwise, a traumatic fall could occur because of imbalance and weakness of the limbs. The child temporarily responds to distraction, storytelling, and quiet activities such as coloring during the first 15 min after its administration. Provoking or painful stimulation (e.g., injections) after the first 20–25 min following its administration can elicit disruptive behaviors and even initiate the angry child syndrome. Once these behaviors are “unleashed,” they are hard to control and “retrieve” the child back into a state of cooperation.
When administered by parenteral routes (e.g., intranasal), the dose must be decreased compared to the oral dose (0.2–0.3 mg/kg versus 0.5–1.0 mg/kg, respectively). The onset is slightly more rapid, but the long-term effects on behavior via this route are not much different than that of the oral route. Sometimes, delivery of midazolam by the intranasal route provokes the child causing agitation, but this usually diminishes in intensity as the child succumbs to the sedative’s effects.
Antihistamines such as hydroxyzine are very popular for mild sedation when used alone and tend to be relatively safe for children [3, 4]. Next to nitrous oxide, they are the most frequently used adjuncts to oral sedative agents during sedations for pediatric patients undergoing dental procedures. They have beneficial effects including antiemetic and drying properties, mild sedation adding slightly to the effects of other agents, and prolongation of the sedation working time. Onset time usually occurs in 15–30 min, and working time varies considerably depending on the child’s age and other characteristics (e.g., temperament).
Studies evaluating the addition of hydroxyzine with other sedatives have shown mixed results [59]. This inconsistency may be due to differences in methodology in the studies (e.g., dose). Nonetheless, it remains a popular agent whether beneficial or not.
Meperidine or chloral hydrate may be used as independent, single agents. Meperidine does not appear to cause as much sedation in the dental clinic, but can impact the mood of the child. If the mood change is beneficial which is often the case, this effect is referred to as euphoria. If, like can occur with midazolam, agitation dominates, the effect is known as dysphoria. The euphoric effect dominates in the majority of cases, in the author’s opinion, particularly when meperidine is mixed with midazolam, hydroxyzine, or chloral hydrate.
Meperidine has a bitter taste typical of narcotics and, like most other agents, requires some masking with a flavoring agent. The onset time is 20–30 min with a working time approximating 45 min to an hour. The submucosal route is another popular means of administering meperidine [6, 1013]. It is necessary to reduce the dose whenever any parenteral route is used (compared to the dose of the oral route). Its onset time is usually 10–15 min. Usually, the effect noted (after an initial expression of agitation, crying, and momentary struggling at the time of its administration) is more quietness, euphoric mood change, and increased likelihood of positive interaction between the patient and dental team.
In terms of behavioral management, there does not appear to be any differences based on the route of administration [13]. As stated, the time of onset of meperidine effects when administered submucosally is less compared to oral administrations. One drawback of the submucosal administration of meperidine is that it can cause itching over the facial area where the injection was given, and often a reddening and slight swelling of the skin is seen (i.e., wheal). These effects are caused by the histamine release from local mast cells and even direct vascular effects when exposed to meperidine [1416].
Another potential side effect of administering meperidine submucosally is the possibility of injecting meperidine into a large venous complex (i.e., pterygoid plexus) which exists just distal to the maxillary tuberosity in children. When appropriately administered via this route, the patient becomes sedate and ready for the start of dental procedures within 10–15 min. Working time is usually 30–45 min. Nonetheless, meperidine causes a sharp, intense sting when administered immediately eliciting struggling and crying behaviors in most children. Often in aiding to minimize the intensity of the disruptive behaviors, the child is sedated with hydroxyzine given orally approximately 30 min before the meperidine injection. It should be noted that the rapid, almost IV-like administration of meperidine into the venous supply can cause a rapid onset of hypotension. Advanced airway management and knowledge of reversal agent therapy (i.e., naloxone) are highly recommended if using this route of administration.
Considering these issues, it seems more prudent to administer meperidine in therapeutic doses via the oral route which tends to eliminate the occurrence of the submucosal effects. Another serious concern is potential interaction between local anesthetics and some narcotics including meperidine which when either or both are used in excessive amounts can result in seizures and/or death [17].
Chloral hydrate when used alone is unpredictable. Paradoxical reactions resulting in hyperactivity and disruptive behaviors can occur after its administration in children. In low doses, this reaction may predominate as the primary behavior in the dental setting, whereas in higher doses, the reaction may only be temporary before sleep is induced when the child is not stimulated.
The normal sequence of observed behaviors after the administration of chloral hydrate is as follows. Typically, disinhibition or excitement occurs in 15–25 min after the oral administration of chloral hydrate. Signs of this disinhibition which is similar to consumption of alcohol in some individuals include increased social interaction and talkativeness, exploratory hyperactivity in the environment, general silliness, but occasionally frank agitation. This phase is usually followed by drowsiness or sleepiness and can result in sleep itself. One must be cautioned however that this early phase of apparent sleep is not generally sufficient to begin the patient separation from the parent to start dental procedures. Thus, the immediate phases of apparent sleep should not lure the practitioner into thinking the patient is ready for dental procedures, but does require confirmation of airway patency and careful and appropriate monitoring depending on the growing depth of sedation. In other words, it is best to wait approximately 45 min to allow the attainment of adequate blood levels of chloral hydrate during which time the child must be monitored for airway and respiratory sufficiency. Starting too quickly can result in a highly agitated child who is hard to console (i.e., similar to a “bad” drunk). If one does start too early with the separation and procedural process and significant relentless agitation occurs, one can stop the process (i.e., a failed sedation) and return the child to the parent. In more cases than not, the child will return to a comfortable sleep in the arms of the parent and should be monitored appropriately. It is highly advisable that one does not reattempt to start the procedure again even if the child looks well sedated as experience shows the agitation will likely return frustrating the parent and dental team.
The working time, depending on whether other drugs are used in combination; the patient’s level of fatigue which can be increased if struggling occurs in the early phase of treatment; and child characteristics such as temperament and cognitive development is usually 60 or more minutes.
Anderson reported in 1960 on the use of chloral hydrate for 300 of his child patients. Other studies using chloral hydrate as the single agent or with nitrous oxide have also been reported [1821]. Most of the studies indicate that chloral hydrate produces good to excellent sedations. However, chloral hydrate currently is rarely used as a single agent for children during dental procedures.
At least 20 studies have documented the use of choral hydrate in combination with other sedatives, particularly antihistamines. The dosage range used in these studies for chloral hydrate and hydroxyzine is 40–75 mg/kg and 1–2 mg/kg, respectively. There is some support to the expectation that the addition of hydroxyzine to chloral hydrate improves patient behavior compared to chloral hydrate alone [5]; on the contrary, others have found no improvement in this comparison [22].

Combinations of Agents

Many of the “common” agents such as midazolam, chloral hydrate, meperidine, hydroxyzine, and other antihistamines can and are often combined in various combinations. Studies support these combinations for somewhat effective clinical alternatives to standard non-pharmacological behavioral guidance techniques; however, there are no systematic studies to aid in selecting definitive outcomes when combinations are used. Combinations of agents can be seen in Table 6.2.
Midazolam and meperidine with or without nitrous oxide may be considered as a combination. This combination produces both sedation and adds some analgesia into the mix based on the characteristics of the two drugs. One prospective study suggests that little difference in behavior is seen comparing midazolam at a higher dose to midazolam in a lower dose and combined with meperidine [23]. Hiccups occurred less frequently with the combination than when midazolam was used alone. Another retrospective study indicated different behavioral effects occurred by varying the doses of the two drugs [24]. Although this may be a useful combination, more prospective, randomized, and controlled dosage studies involving a much larger sample size may be beneficial in discriminating optimal dose ranges for children of different temperamental styles.
This combination may prolong the working time. Furthermore, both can increase the depth of sedation possibly changing monitoring requirements as well as affect the mood of the patient. Nitrous oxide initially may be helpful with this combination especially during “settling” of the child early in the procedural process (see Chap. 8), but if and once the child becomes agitated and behaviorally noncompliant, its effectiveness is minimal at best. It is conceivable that midazolam could be used in combination with chloral hydrate, but caution is advised due to the increased likelihood of unconsciousness.
Given orally with the characteristic slower onset of action of the drugs and in downwardly modified therapeutic doses, there is less likelihood of adverse events occurring. However, if respiratory depression or unconsciousness occurs, both agents are reversible (i.e., midazolam-flumazenil and meperidine-naloxone). Should this situation occur, the question becomes which agent should first be reversed. There is no definitive answer based on evidence, but empirically meperidine, as a narcotic, is likely to cause respiratory depression and thus would logically be reversed first. Either way, the primary means of managing any respiratory depression before the onset of effects of reversal agents is via an open airway, a bag-valve-mask, and 100 % oxygen.
Chloral hydrate is rarely used alone or even in combination today in dental practices primarily due to its lack of availability in large volumes from a manufacturer. However, it can be made available by individual dose per a prescription via a compounding pharmacist. It can be combined with almost any other common agent. But its effects of causing sleep and unconsciousness as well as hypotonia of the tongue and increased likelihood of airway blockage must be weighed carefully before using it in combinations. Certainly, appropriate training to include advanced airway management techniques is indicated whenever it is used.
Chloral hydrate combined with meperidine and hydroxyzine has been shown to be an effective combination, especially when longer working times are desirable [2528]. This “triple” combination can be partitioned either into a “high” chloral hydrate or “low” chloral hydrate combination. The likelihood of unconsciousness or deep sedation is great in the former and less likely in the latter. Typically, the dose of the “high” triple when administered orally is 40–50 mg/kg, 1 mg/kg, and 1–2 mg/kg or less of chloral hydrate, meperidine, and hydroxyzine, respectively. Deep sedation can occur and may be more notable when nitrous oxide is used with this combination.
The best “low-dose” triple combination is 10–20 mg/kg, 2 mg/kg, and 1–2 mg/kg or less of chloral hydrate, meperidine, and hydroxyzine, respectively. The low-dose triple usually causes moderate sedation but occasionally can also induce deep sedation. The latency time for this combination is usually 40–50 min, but the working time typically is 60 min or longer assuming good local anesthetic technique. Unfortunately, only one of the three agents (i.e., meperidine) is reversible. A frequent and interesting observation of the low-dose triple combination is the rapid rate of alertness and apparent readiness to be discharged immediately following dental procedures. Nonetheless, sleep can occur fairly often once the patient is home and in a less challenging setting. This napping can occur with other sedatives as well.
Another triple combination is one that substitutes midazolam for chloral hydrate. The “midazolam” triple combination (midazolam, meperidine, and hydroxyzine) also could use variable dosages for each agent. Examples might include a dose range of 0.3–0.75, 1.0–1.5, and 1.0 mg/kg of midazolam, meperidine, and hydroxyzine, respectively. One study compared the two “high-dose” triple combinations (i.e., chloral versus midazolam) and found little difference in behaviors [29]. Yet the rate of quiet behaviors was relatively high suggesting a good sedation outcome. Desaturation did occur in the triple combination involving chloral hydrate in two patients that was resolved by a chin lift procedure, but this maneuver emphasizes that deep sedation occurred. This triple combination also has an advantage in that it contains two of the three sedatives that can be reversed (i.e., midazolam and meperidine with flumazenil and naloxone, respectively) compared to the chloral hydrate triple which only has one reversible agent (i.e., meperidine).
Nitrous oxide can be used with any of these sedatives or combinations given orally. The effect of nitrous oxide can be adjusted via altering the concentration that is inhaled, so it is the only agent in these oral inhalation combinations that can be titrated. Higher concentrations of nitrous oxide (i.e., 40 % and higher) can deepen the level of sedation; thus, caution is advised. Likewise, a patient who is more deeply sedated can be stimulated and the nitrous oxide reduced or shut off allowing the patient to drift into lighter levels of sedation.
In the future, other agents are likely to become popularized should any of the current commonly used agents fade in popularity, cease to be produced, or taken off the market by regulatory agencies. For example, should the marketplace not support continued production of meperidine as the primary narcotic used as a sedative for children during dental procedures, fentanyl may emerge as a possible front-runner when administered nasally or submucosally, despite its potent respiratory depressing properties. Tables 6.3 and 6.4 summarize relatively recent and older representative studies, respectively, showing different routes and combinations of agents.

Table 6.3

Recent studies involving multiple agents
Routes and agents
Routes
Oral versus submucosal
Meperidine, midazolam, and hydroxyzine
Toomarian, L., et al. (2013). “Assessing the sedative effect of oral vs. submucosal meperidine in pediatric dental patients.” Dent Res J (Isfahan) 10(2): 173-179
PURPOSE: Compare behavioral and physiological effects of three sedative drug regimens: oral meperidine (OM), submucosal meperidine (SM), and oral midazolam (M) in healthy pediatric patients
METHODS: This study sample consisted of 30 children aged 24–72 months (mean = 41.1) exhibiting definitely negative behavior. Three sedative regimens: oral meperidine/hydroxyzine, oral midazolam/hydroxyzine, and submucosal meperidine/oral hydroxyzine were administered randomly during three consecutive appointments with a crossover design. Houpt behavioral scale was employed for evaluating the sedation effect of each regimen by a calibrated independent pediatric dentist. Physiological parameters were also recorded including blood oxygen saturation and pulse rate. Data was analyzed using Wilcoxon signed-rank test, Mc-Nemar, GEE Logistic regression, Friedman, Fisher exact, and Cochran tests for significance
RESULTS: Overall success rates were 50, 46.7, and 26.7 % for submucosal meperidine, oral meperidine, and oral midazolam, respectively (p = 0.03). The probability of achieving a success in behavior control was more in 48–72 month olds. Child’s age and drug type were the two main predictors of altered behavior. Evaluating the differences between the effects of three tested regimens on recorded physiological parameters showed no significant differences
CONCLUSION: All three regimens were proved safe within the limits of the current study. Meperidine sedation in both routes was considered to be more effective. Although there was less sleep and more head/oral resistance in midazolam group, the difference between groups was not significant
Oral versus submucosal route
Meperidine and hydroxyzine
Cathers, J. W., et al. (2005). “A comparison of two meperidine/hydroxyzine sedation regimens for the uncooperative pediatric dental patient.” Pediatr Dent 27(5): 395-400
PURPOSE: The purpose of this study was to compare the safety and efficacy of submucosal-administered meperidine (SM) and oral-administered meperidine (OM). Both regimens were used in conjunction with oral hydroxyzine for the sedation of children for dental treatment
METHODS: Twenty preschool-age children, with previous histories of uncooperative behavior, were randomly assigned to first receive a sedation regimen of either SM (0.5 mg/lb), or OM (1 mg/lb), both with oral hydroxyzine (0.5 mg/lb). A crossover design was utilized so that each child received both regimens. Safety was monitored through vital signs and side effects. Efficacy was measured with Houpt and Frankl behavior ratings
RESULTS: Vital signs remained stable during both treatments. Differences noted were clinically insignificant. The major side effects reported during submucosal injection included pain (58 %) and edema (26 %). All blinded behavior ratings, in both sedation regimens, significantly improved from presedation Frankl ratings. No significant differences existed between treatments. Success was 63 % in the SM group and 80 % in the OM group. The percentages were not statistically significant (p = .219)
CONCLUSIONS: Both methods of administration were found to be safe and effective for sedating uncooperative pediatric dental patients. Neither was significantly more effective or safer than the other
Intranasal
Midazolam and lidocaine
Chiaretti, A., et al. (2011). “Intranasal lidocaine and midazolam for procedural sedation in children.” Arch Dis Child 96(2): 160-163
PURPOSE: To evaluate the safety and efficacy of a sedation protocol based on intranasal lidocaine spray and midazolam (INM) in children who are anxious and uncooperative when undergoing minor painful or diagnostic procedures, such as peripheral line insertion, venipuncture, intramuscular injection, echocardiogram, CT scan, audiometry testing, and dental examination and extractions
METHOD: Forty-six children, aged 5–50 months, received INM (0.5 mg/kg) via a mucosal atomizer device. To avoid any nasal discomfort, a puff of lidocaine spray (10 mg/puff) was administered before INM. The child’s degree of sedation was scored using a modified Ramsay sedation scale. A questionnaire was designed to evaluate the parents’ and doctors’ opinions on the efficacy of the sedation. Statistical analysis was used to compare sedation times with children’s age and weight
RESULTS: The degree of sedation achieved by INM enabled all procedures to be completed without additional drugs. Premedication with lidocaine spray prevented any nasal discomfort related to the INM. The mean duration of sedation was 23.1 min. The depth of sedation was 1 on the modified Ramsay scale. The questionnaire revealed high levels of satisfaction by both doctors and parents. Sedation start and end times were significantly correlated with age only. No side effects were recorded in the cohort of children studied
CONCLUSIONS: This study has shown that the combined use of lidocaine spray and atomized INM appears to be a safe and effective method to achieve short-term sedation in children to facilitate medical care and procedures
Oral versus intranasal
Midazolam
Johnson, E., et al. (2010). “The physiologic and behavioral effects of oral and intranasal midazolam in pediatric dental patients.” Pediatr Dent 32(3): 229-238
PURPOSE: The purpose of this study was to compare the safety and effectiveness of oral and intranasal midazolam in healthy children by evaluating their physiological and behavioral responses
METHODS: Regimen A patients received 0.5 mg/kg oral midazolam with an intranasal saline spray placebo at their first appointment and 03 mg/kg intranasal midazolam with an oral midazolam placebo at their second appointment. Regimen B patients received the medications in the reverse order at each appointment. Physiological parameters and behavioral ratings were recorded
RESULTS: There were no significant differences in physiological parameters in the two treatment groups, except for significantly lower oxygen saturation in the oral group at t = 20 min (p = .03) The oral group showed significantly lower crying scores at t = 5 min (p = .02) and lower overall behavioral scores at t = papoose and t = 5 min (p = .04 and .03, respectively). Oral sedations were given ratings by providers of “effective” and “very effective” significantly more than intranasal sedations (p < .05)
CONCLUSIONS: Both regimens have similar behavioral outcomes, with the oral group having improved crying and overall behavior early in the appointment. Oral sedations were considered to be more effective by providers than intranasal sedations. Clinically significant desaturations occur in both regimens, indicating the need for operators to recognize and respond to the need for airway correction according to American Academy of Pediatric Dentistry guidelines
Oral versus nasal
Midazolam
Lee-Kim, S. J., et al. (2004). “Nasal versus oral midazolam sedation for pediatric dental patients.” J Dent Child (Chic) 71(2): 126-130
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Oct 18, 2015 | Posted by in General Dentistry | Comments Off on Clinical Sedation Regimens
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