Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation

PURPOSE: The optimal sedative regime that provides the greatest comfort and the lowest risk for procedural sedation in young children remains to be determined. The aim of this randomized, blinded, controlled, parallel-design trial was to evaluate the efficacy of intranasal ketamine and midazolam as the main component of the behavioral guidance approach for preschoolers during dental treatment. MATERIALS AND METHODS: Children under seven years of age, with caries and non-cooperative behavior, were randomized into three groups: (KMIN) intranasal ketamine and midazolam; (KMO) oral ketamine and midazolam; or (MO) oral midazolam. The dental sedation appointments were videotaped, and the videos were analyzed using the Ohio State University Behavioral Rating Scale (OSUBRS) to determine the success of the sedation in each group. Intra- and postoperative adverse events were recorded. Data analysis involved descriptive statistics and non-parametric tests (P < 0.05, IBM SPSS). RESULTS: Participants were 84 children (28 per group; 43 boys), with a mean age of 3.1 years (SD 1.2). Children's baseline and the dental sedation session characteristics were balanced among groups. The success of the treatment as assessed by the dichotomous variable 'quiet behavior for at least 60% of the session length' was: KMIN 50.0% (n = 14; OR 2.10, 95% CI 0.71 to 6.30), KMO 46.4% (n = 13; OR 1.80, 95% CI 0.62 to 5.40), MO 32.1% (n = 9) (P = 0.360). Adverse events were minor, occurred in 37 of 84 children (44.0%), and did not differ among groups (P = 0.462). CONCLUSION: All three regimens provided moderate dental sedation with minor adverse events, with marked variability in the behavior of children during dental treatment. The potential benefit of the ketamine-midazolam combination should be further investigated in studies with larger samples. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02447289. Registered on 11 May 2015, named "Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment (NASO)."