Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment

Ketamine

Brief Summary

Randomised clinical trial to test the efficacy, safety and cost-effectiveness of sedatives; masked, controlled, parallel design with three arms, phase 4.

Intervention / Treatment

  • Intranasal ketamine (DRUG)
    Ketamine injectable solution in a concentration of 50.0 mg/mL administered into the nose with an atomizer; dose of 4.0 mg/kg, maximum 100.0 mg
  • Oral ketamine (DRUG)
    Ketamine injectable solution in a concentration of 50.0 mg/mL via oral route; dose of 4.0 mg/kg maximum 100.0 mg
  • Intranasal midazolam (DRUG)
    Midazolam injectable solution in a concentration of 5.0 mg/mL administered into the nose with an atomizer; dose of 0.2 mg/kg, maximum 5.0 mg
  • Oral midazolam (DRUG)
    Midazolam oral solution in a concentration of 2.0 mg/mL via oral route; dose of 0.5 mg/kg, maximum 5.0 mg when associated with ketamine; dose of 1.0 mg/kg, maximum 20.0 mg when give as a solely agent

Condition or Disease

  • Child Behavior
  • Dental Caries

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 2 Years to 6 Years
    Enrollment: 84 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: May 21, 2015 ACTUAL
    Primary Completion: Oct 11, 2016 ACTUAL
    Completion Date: Oct 18, 2016 ACTUAL
    Study First Posted: May 18, 2015 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Apr 26, 2018

    Sponsors / Collaborators

    Lead Sponsor: Universidade Federal de Goias
    Responsible Party: N/A

    Location

    Goias, Brazil
    Goiania, Goias, Brazil

    About 10% of children may have behavioral problems during dental treatment, but the evidence for sedative protocols that benefit the care in pediatric dentistry are still weak. This randomized, masked, controlled, parallel design study aims to evaluate the efficacy, safety and cost-effectiveness of intranasal sedation with ketamine / midazolam in healthy children aged 2 to 6 years old. Children will be selected among those with dental decay that do not allow dental treatment to be performed, and need at least two restorations under local anesthesia and rubber dam isolation. It is estimated a preliminarily a sample of 84 children equally divided into three groups: A) Ketamine (4.0 mg / kg up to 100 mg) + midazolam (0.2 mg / kg, maximum 5 mg) intranasally; B) ketamine (4.0 mg / kg up to 100 mg) + midazolam (0.5 mg / kg, maximum 20 mg) orally; C) midazolam (1.0 mg / kg, maximum 20 mg) orally. The hypothesis is that ketamine / midazolam combination, administered intranasally, it constitutes an effective sedative regime, safe and cost-effective for use in pediatric dentistry in the public service. The primary endpoint is the behavior of the child. Secondary endpoints are: sedative administration acceptance, procedure memory and salivary cortisol levels within each intervention group. Additionally, we will evaluate: the occurrence of pain and associated changes in facial expressions with potentially painful stimuli in children sedated for dental care; caregivers and paediatric dentists' stress and perception about sedation; adverse events that occur during and after administration of sedatives; cost-effectiveness of the sedative protocols. The experimental design is planned to minimize systematic and random errors and to contribute to higher level of evidence in future systematic reviews. The outcomes of this study have potential impact on public and private health practice, and may support institutional guidelines dealing with this theme.

    Participant Groups

    • Intranasal administration of ketamine (4.0 mg/kg, max. 100 mg) and midazolam (0.2 mg/kg, max. 5 mg)

    • Oral administration of ketamine (4.0 mg/kg, max. 100 mg) and midazolam (0.5 mg/kg, max. 20 mg)

    • Oral administration of midazolam (1.0 mg/kg, max. 20 mg)

    Eligibility Criteria

    Sex: All
    Minimum Age: 2
    Maximum Age: 6
    Age Groups: Child
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * American Society of Anesthesiologists I (healthy) or II (mild and controlled systemic disease such as persistent asthma)
    * Small risk of airway obstruction (Mallampati less than 2 or tonsillar hypertrophy occupying less than 50% of the oropharynx)
    * No medical history of neurological or cognitive changes
    * Absence of facial deformities
    * Term birth
    * No use of drugs that may impair cognitive functions
    * At least two teeth with cavities without pulp involvement, requiring dental restoration under local anesthesia and rubber dam

    Exclusion Criteria:

    * Positive or definitely positive behavior (Frankl et al, 1962) in a dental treatment session conducted by the research team

    Primary Outcomes

    • Children's behavior assessed by OSUBRS (Ohio State University Behavioral Rating Scale) in digital videos recorded during the administration. Scores: 1 - quiet, 2 - cry with movement, 3 - movement without cry; 4 - struggling. Satisfactory behavior means more than 60% of score 1 during the entire appointment.

    Secondary Outcomes

    • Acceptance of the sedative administration, assessed by OSUBRS (Ohio State University Behavioral Rating Scale) minute by minute in digital videos recorded during the administration. Scores: 1 - quiet, 2 - cry with movement, 3 - movement without cry; 4 - struggling.

    • Occurrence of stress during dental procedure, assessed by salivary cortisol in children, their accompanying parent and the dentist in charge; the ELISA test will determine changes in cortisol level during dental treatment

    • Occurrence of pain and associated changes in body expressions with potentially painful stimuli in children sedated for dental care

    • Perception of caregivers and dentists on sedation, through self-report

    • Child's perception concerning the dental treatment under sedation

    • Memory of the dental procedure, according to test with figures validated in Brazil. Amnesia will be reported if children do not recall the figures showed after sedative administration

    • Memory of the dental procedure, according to test with figures validated in Brazil. Amnesia will be reported if children do not recall the figures showed after sedative administration

    • Occurrence of adverse events assessed by the World SIVA tool; adverse events will be categorised into minor, sentinel and major

    • Occurrence of adverse events while child is in the recovery room and after discharge, assessed by the World SIVA tool; adverse events will be categorised into minor, sentinel and major

    • Cost-effectiveness of different sedation protocols according to the methodology of health technologies assessment; the cost of each intervention will be compared

    More Details

    NCT Number: NCT02447289
    Acronym: NASO
    Other IDs: 041530
    Study URL: https://clinicaltrials.gov/study/NCT02447289
    Last updated: Sep 29, 2023