A Comparison of Oral Sedation-related Events of Three Multiagent Oral Sedation Regimens in Pediatric Dental Patients

This study will compare the post sedation events from three different multi-drug oral sedation regimens in order to help pediatric dentists determine the best course of action for their patients and prepare parents appropriately and caution them about the expected effects. Patients will be evaluated for adverse effects within two time periods at 8 and 24 hours post oral sedation procedure using surveys.

Study Overview

• Status: Completed
• Conditions: Dental Decay; Anxiety, Dental
• Intervention / Treatment: Combination product: Regimen 1; Combination product: Regimen #2; Combination product: Regimen #3

Detailed Description

Inclusion criteria included patients of record who were scheduled to undergo oral sedation at Loma Linda University Pediatric Dentistry clinic for dental treatment. Children ages ranged from 3 to 6 years old with no medical issues, ASA-1. The reason for oral sedation was situational anxiety in the dental operatory. Exclusion criteria included children who presented with a history of: (1) acute illness; (2) upper respiratory tract infection within two weeks of treatment; (3) taking any medication within the two weeks prior to scheduled dental treatment; and (4) a body mass index (BMI) greater than the 95th percentile for their age and gender. A total sample of 60 healthy pediatric patients were included in this study with were no gender, race, or ethnic significant difference.

The included patients were randomly allocated into one of three sedation groups by drawing a concealed folded paper from an opaque randomization bag after obtaining parent consent. All papers that were used in the randomization had the same size and texture. The pediatric dental resident and attending faculty were informed with medication combination once randomized allocation had been made.

The study groups were as follows: Group 1 received Midazolam (0.5- 0.75 mg/kg), Meperidine (1.5-2.0 mg/kg), and Hydroxyzine (1.5- 2.0 mg/kg), Group 2 received Meperidine (1.5-2 mg/kg) and Hydroxyzine (1.5- 2.0 mg/kg). Group 3 received Midazolam (0.5- 0.75 mg/kg) and Hydroxyzine (1.5- 2mg/kg).

Clinical Procedure Calculations based on the child's weight of maximum local anesthetic delivery, oral sedation medication dosages, and reversal agents were completed prior to delivery of medication. The reversal agent used for benzodiazepines was Flumazenil, 0.01mg/Kg with a maximum of 0.2 mg/dose. While the reversal agent for Meperidine was Naloxone, calculated as 0.1 mg/Kg up to 2 mg.

After obtaining proper consents, all patients were placed in passive protective stabilization (Joey Board®, Joey Board, Queen Creek, AZ) in the event the child was to become uncooperative and to maintain patient stability during treatment, as coordination could be impaired. Nitrous oxide/Oxygen (N2O/O2) was used in all sedations and administered at a flow rate of four to six L/minute (30-50% N2O/ 10-50% O2) with 100% O2 given for five minutes pre- and postoperatively. All operating dentists followed standard sedation protocol at standard sedation protocol in Loma Linda University Pediatric Dentistry Clinic adapted from the American Academy of Pediatric Dentistry (AAPD) guidelines.8 Routine dental care was provided with local anesthesia with rubber dam or isolite® isolation. Xylocaine (2% lidocaine with 1:100,000 epinephrine) was used for local anesthesia in all cases and did not exceed 4 mg/kg lidocaine. Once AAPD discharge criteria8 were met, the patient was released to the parent. At that time, postoperative care instructions, including emergency contact numbers and recommendation for over-the-counter pain medications, if needed, were provided both verbally and in written form.

The dentist performing each sedation was asked to complete a detailed questionnaire that provided details about the patient's behavior from the time of drug administration to the time of discharge (Survey 1). In addition, parents received two telephone interviews regarding events that occurred after the sedation session. An investigator conducted all phone interviews. These phone interviews took place at eight hours (Survey 2) and 24 hours (Survey 3) after discharge.

For all three of the surveys, questions were designed to elucidate patient physical signs and/or behaviors that fell into the following categories: (1) sleep disturbances; (2) gastrointestinal side effects; (3) non-aggressive behavior changes; (4) residual central nervous system alterations; (5) respiratory depression; (6) musculoskeletal effects; (7) physical reactions; (8) existence of a paradoxical reaction; and (9) amnesic effects. Information on the pre-sedation cooperation level and overall effectiveness of the sedation (rated as ineffective, effective, very effective, or overly sedated) were obtained from the procedural sedation record (adopted from AAPD) corresponding to each case.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 6 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients scheduled to undergo oral sedation appointments in Loma Linda University Pediatric dental clinic for operative procedures.
• Age 3-7 years old, Healthy ( ASA-1 )
• No gender, race or ethnic restrictions.
• Reason for conscious oral sedation is situational anxiety in the dental operatory

Exclusion Criteria:

• Children with a history of acute illness
• History upper respiratory tract infection within two weeks of treatment
• Children taking any medication within the two weeks prior to scheduled dental treatment
• Sedation within the last six months
• Body mass index (BMI) greater than the 95th percentile for their age and sex
• Failing to drink the entire amount of sedation medications dispensed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Regimen 1; Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration - Meperidine (1.5 -2 mg/kg) Oral administration - Midazolam (0.5- 0.75 mg/kg) Inhalation - Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2)	Combination product: Regimen 1; Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5- 2mg/kg) + Meperidine (1.5 -2 mg/kg) + Midazolam (0.5- 0.75 mg/kg) In combination with oral drugs stated above, administeration via inhalation of Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.
Experimental: Regimen 2; Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration- Meperidine (1.5 -2 mg/kg) Inhalation - Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) -	Combination product: Regimen #2; Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5 - 2mg/kg) + Meperidine (1.5 -2 mg/kg). Administer Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.
Experimental: Regimen 3; Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration - Midazolam (0.5- 0.75 mg/kg) Inhalation- Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2)	Combination product: Regimen #3; Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5 - 2mg/kg) + Midazolam (0.5- 0.75 mg/kg). Administer Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Sedation-Related Events in Musculoskeletal System During Sedation	Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge Musculoskeletal system reaction during sedation scale: This is the result for Musculoskeletal related questions, it is a sum of 3 yes or no questions. (minimum=0, maximum=3) The higher the worse.	during sedation
Incidence of Adverse Sedation-Related Events in Musculoskeletal in 8 Hours	Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. Musculoskeletal system reaction at 8 hours scale: This is the result for Musculoskeletal related questions, it is a sum of 2 yes or no questions. (minimum=0, maximum=2) The higher the worse.	Change 8 (eight) hours post oral sedation medication administration
Incidence of Adverse Sedation-Related Events in Musculoskeletal at 24 Hours After Sedation	Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. Musculoskeletal system reaction at 24 hours scale: This is the result for Musculoskeletal related questions, it is a sum of 2 yes or no questions. (minimum=0, maximum=2) The higher the worse.	Change between 24 (twenty-four) hours post oral sedation
Compare Incidence of Adverse Effect Related to Gastrointestinal Reaction During Sedation	Compare the number and type of adverse effect related gastrointestinal reactions. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. GI effect for during sedation score; This is a summary of 3 yes/no questions, Minimum = 0 Maximum =3, the higher means more GI reactions, the worse outcome	During sedation
Compare Incidence of Adverse Effect Related to Gastrointestinal Reaction 8 Hours After Sedation	Compare the number and type of adverse effect related gastrointestinal reactions Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty four) hours (Survey 3) after discharge. GI effect 8 hours after sedation score; This is a summary of 5 yes/no questions, Minimum = 0 Maximum =5, the higher means more GI reactions, the worse outcome.	8 hours after sedation
Compare Incidence of Adverse Effect Related to Gastrointestinal Reaction 24 Hours After Sedation	Compare the number and type of adverse effect related gastrointestinal reactions Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty four) hours (Survey 3) after discharge. Long term effect for 24 hours after sedation score; This is a summary of 5 yes/no questions, Minimum = 0 Maximum =5, the higher means more GI reactions, the worse outcome	24 hours after sedation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare incidence of adverse effect related to the use of three medications versus two medications	Compare the number and type of adverse effect related (Amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) to the use of three medications versus two medications. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty four) hours (Survey 3) after discharge	24 (twenty-four) hours post oral sedation medication administration (composite measurement)

Collaborators and Investigators

• Sponsor: Loma Linda University
• Investigators: Principal Investigator: Jung-Wei Chen, DDS,MS,PhD, Loma Linda University

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): April 11, 2023
• Study Completion (Actual): April 12, 2023

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: September 9, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Pediatric; Dental
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Demineralization; Tooth Diseases; Dental Caries
• Other Study ID Numbers: 5190213

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes