Clinical trial NCT04068948: Comparing Pediatric Dental Oral Sedation Outcomes With and Without Meperidine in Children Aged 3-7 Years
Official title: Comparing Pediatric Oral Sedation Outcomes Using Midazolam and Hydroxyzine With and Without Meperidine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dental Caries in Children
Pediatric Dental Sedation
Meperidine
Hydroxyzine
Midazolam
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2019-08-28
Enrollment: 37
Sex: ALL
Minimum age (years): 3
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized clinical trial where participants are assigned randomly to receive a sedation regimen of either midazolam+hydroxyzine+meperidine or midazolam+hydroxyzine.
Primary purpose: TREATMENT

Brief summary: The primary objective of this randomized controlled trial is to assess the effects of oral sedation using midazolam and hydroxyzine with and without meperidine (a narcotic) on sedation outcomes in pediatric dental patients undergoing dental treatment at the University of Washington Center for Pediatric Dentistry. Procedural sedation can be offered as an option for dental treatment for a young, potentially uncooperative pediatric patient to safely and effectively complete dental restorative needs. Both sedation regimens are already regularly used for patients at the UW CPD. The goal of this study is to assess if removing a narcotic from the regimen will produce the same behavioral success outcomes as a regimen with a narcotic. Our hypothesis is that patients who receive oral sedation using midazolam, hydroxyzine, and meperidine will experience fewer behavioral failures than those who receive oral sedation using midazolam and hydroxyzine without meperidine.

The secondary objective of this project is to evaluate the relationship between child temperament and sedation outcome in each treatment group.

Detailed description: Young children in the dental setting can pose significant behavioral challenges. These patients may have dental anxiety or lack the effortful control (self-regulation) to successfully navigate the dental experience. Oral procedural sedation is an advanced pharmacological behavior guidance technique that can be used as part of the pediatric dentist's armamentarium when basic behavior guidance techniques are likely to be ineffective. Oral sedation can be a valuable tool, not only to facilitate dental treatment, but also to protect a young child's psyche, reduce dental fear, and ensure safety of both the patient and the dental team.

Case selection is crucial to optimizing sedation outcomes. In addition to biological factors like age, gender, and weight, temperament must also be carefully evaluated for the pediatric oral sedation candidate. Compared with children with high levels of effortful control, children who exhibit high levels of impulsivity may be more likely to respond poorly to uncomfortable or unfamiliar procedures, exhibit uncooperative behavior during sedation, and ultimately experience more sedation failures.

There is no standard drug regimen or protocol for oral sedation. Medications used for sedation studies often have a wide therapeutic range, and dosages used in the literature vary widely. Varying drug regimens can also be used depending on operator preference and the extent of the procedure. Benzodiazepines, opioids, and antihistamines are commonly used drug options that can be used alone or in combination to achieve desired sedative effects and minimize potential side effects of counterpart drugs. For example, midazolam is a rapid-onset, short acting benzodiazepine that offers a sedative effect with some degree of amnesia. These qualities make midazolam an ideal sedative for relatively minor or quick operative procedures in young children. An opioid such as meperidine can be added to potentiate the sedative effect and offer analgesia for lengthier, more complex procedures. Additionally, an antihistamine like hydroxyzine can be added for additional sedative effects as well as an antiemetic effect to counter potential nausea from the use of an opioid. The use of supplemental nitrous oxide/oxygen (N2O/O2) in conjunction with a chosen sedation regimen has been shown to further potentiate sedation effects and improve sedation outcomes.

Despite proving to be an effective behavior management technique, procedural sedation poses its own set of risks. Compared with intravenous or intranasal methods of drug delivery, oral delivery of sedation medications can be challenging due to longer and more variable onset to sedation, unpredictable hepatic first-pass absorption and bioavailability, and an inability to titrate the medications. Sedation effects may linger long after the procedure is completed and affect post-discharge outcomes. Additionally, the use of multiple medications has been shown to increase the risk of adverse outcomes compared with single or dual-combination drug regimens.

The majority of adverse events during sedation can be avoided with careful case selection, medication dosing, and proper intra-operative monitoring. When adverse events do occur, they are typically due to respiratory depression, and can include laryngospasm, neurologic injury, and death. Thus, to avoid oversedation and subsequent adverse sequelae, multi-drug regimens (especially those that contain opioids like meperidine) must be used judiciously.

The midazolam/meperidine/hydroxyzine regimen is a popular combination of medications for pediatric dental sedation. The increase in the use of meperidine has been associated with a movement away from utilization of chloral hydrate (another sedative with no reversal agent, previously frequently used in conjunction with a combination of the aforementioned drugs or other drugs). While there are studies comparing sedation regimens that include both chloral hydrate and meperidine used together, meperidine is an increasingly preferred option over chloral hydrate for procedural sedation, especially with the availability of a reversal agent for the opioid in the instance of oversedation, as well as a shorter half-life compared with chloral hydrate. While narcotic-containing regimens are popular, there are still inherent risks in utilization of an opioid in any sedation regimen. Several studies have been published comparing sedation regimens that include meperidine, but to date, there are no studies comparing the efficacy of midazolam and hydroxyzine with and without meperidine. Additionally, many studies compare side effects of different regimens (for example, post-operative drowsiness, nausea, time spent asleep, crying), but few utilize the Houpt Behavior Rating that we plan to use to categorize sedation outcomes.

Eligibility criteria: Inclusion Criteria:

1. Are between 36-95 months of age and are planned for dental treatment at the University of Washington Center for Pediatric Dentistry,
2. Are ASA I or II, (healthy, or have mild, well-controlled systemic disease)
3. Are under the 95th weight for age BMI (body mass index) percentile,
4. Are able to take diagnostic bitewing dental radiographs,
5. Are able to take medications by mouth,
6. Have Brodsky scores of II or less (tonsil sizes take up less than 50% of the oropharyngeal opening at the back of the throat),
7. Are planned to receive operative treatment under local anesthesia,
8. Can understand and communicate with providers in English.

Exclusion Criteria:

1. Are diagnosed with autism, ADHD, or any other psychiatric or behavioral diagnosis,
2. Are ASA III or higher (severe systemic disease),
3. Are above the 95th weight for age BMI percentile,
4. Are unable to take diagnostic radiographs,
5. Will not tolerate taking medications by mouth,
6. Have Brodsky scores of greater than II (tonsil sizes take up more than 50% of the oropharyngeal opening at the back of the throat),
7. Have undergone oral sedation at a previous dental appointment,
8. Cannot understand or communicate with providers in English.

Primary outcomes:
measure: Number of Participants With Successful Sedation
timeFrame: At completion of procedure
Secondary outcomes:
measure: Child Temperament According to CBQ-SF and Association With Sedation Outcomes
timeFrame: During procedure
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Center for Pediatric Dentistry
state: Washington
Study officials:
affiliation: University of Washington
name: Travis M Nelson, DDS
role: PRINCIPAL_INVESTIGATOR
References:
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