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

Efficacy, Safety and Cost-effectiveness of Intranasal Sedation With Ketamine and Midazolam in Pediatric Dentistry: a Randomized Clinical Trial

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

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.

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