Outpatient pediatric sedation is challenging. This study aimed to test intranasal dexmedetomidine efficacy as a single drug or combined with ketamine (DK) to sedate children undergoing dental treatment. Children < 7 years were randomized into dexmedetomidine 2 mcg/kg and ketamine 1 mg/kg (DK) or dexmedetomidine 2.5 mcg/kg (D) groups. Videos from the dental sedation allowed the systematic assessment of children’s behavior (primary outcome) according to the Ohio State University Behavioral Rating Scale (OSUBRS). Secondary outcomes were parental and dentist satisfaction, adverse events, and recovery time. The data were analyzed descriptively and through regression models. Participants were 88 children (44 per group; 50 boys). The duration of quiet behavior (OSUBRS) was higher than 50% (DK mean 58.4 [standard deviation 38.1]; D 55.2 [39.1]; p = 0.225). Parents (DK 78.0 [32.2]; D 72.7 [35.1]; p = 0.203) and dentists (KD 62.7 [41.0]; D 62.8 [40.1]; p = 0.339) were overall satisfied. Adverse events occurred in 16 cases (DK n = 10, 62.5%; D n= 6, 37.5%; p = 0.104) and were minor. The median recovery time in the DK group was 1.3 times greater than in group D (p < 0.05). Intranasal sedation with dexmedetomidine alone is equally efficacious and satisfactory for pediatric sedation with fewer adverse events and faster recovery than the DK combination.

Uncooperative children may need to receive dental treatment under sedation, which is indicated when nonpharmacological behavior guidance is unsuccessful. There are randomized controlled trials (RCTs) comparing different sedative protocols for dental procedures; however, the evidence for superiority of one form over another is weak. The primary aim of this study is to investigate the efficacy of intranasally administered ketamine plus midazolam for the dental treatment of children. We have designed a three-armed, parallel RCT to assess intranasal sedation using ketamine/midazolam in terms of the following measures: efficacy, safety, and cost-effectiveness. Two- to 6-year-old healthy children, referred for dental treatment in a dental sedation center in Brazil due to uncooperative behavior and requiring restorative dental procedures, will be recruited. Each child will be randomly assigned to one of the three groups: A – Intranasal administration of ketamine (4.0 mg/kg, maximum 100 mg) and midazolam (0.2 mg/kg, maximum 5.0 mg); B – Oral administration of ketamine (4.0 mg/kg, maximum 100 mg) and midazolam (0.5 mg/kg, maximum 20 mg); and C – Oral administration of midazolam (1.0 mg/kg, maximum 20 mg). The primary outcome is the child’s behavior assessed through an observational scale using digital videos of the restorative dental treatment under sedation. The secondary outcomes are as follows: acceptance of sedative administration; memory of intraoperative events; the child’s stress; adverse events; the child’s pain during the procedure; the parent’s, dentists’, and child’s perceptions of sedation; and economic analysis. Measures will be taken at baseline and drug administration and during and after the dental procedure. The necessary sample size was estimated to be 84 children after a blinded interim analysis of the first 30 cases. This study will provide data that can substantially add to science and pediatric dentistry as it examines the effect of sedative regimes from different perspectives (outcomes). 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).”

There is little evidence on the long-term effects of pharmacological management in children undergoing dental treatment. This study aimed to assess children’s behavior in consecutive dental sessions following oral rehabilitation using different pharmacological regimens for behavioral control. Participants were preschoolers who were previously treated for caries under one of the following: no sedative, oral sedation with midazolam, oral sedation with midazolam/ketamine, or general anesthesia. The children’s behavior in the follow-up sessions was assessed using the Ohio State University Behavioral Rating Scale (OSUBRS); higher scores represented less cooperative behavior (range 5–20). Follow-up assessments were conducted on 50 children under four years old for up to 29 months. Data were analyzed by the Friedman/Wilcoxon tests and Cox regression model. OSUBRS mean (standard deviation) scores for the whole sample decreased from 11.9 (5.4) before treatment to 6.8 (3.2) at the final recall session (p < 0.001). Moderate sedation with midazolam (OR 2.9, 95%CI 1.2–6.9) or midazolam/ketamine (OR 4.3, 95%CI 1.6–11.4) improved children’s future behavior. The general anesthesia group (n = 4) had a small sample size and the results should be considered with caution. Although invasive dental treatment negatively affected the child’s behavior in the dental chair, they became more cooperative over time. Moderately sedated children showed better prospective behavior than those in the non-sedation group.

There is a lack of evidence on the correlation between salivary biomarkers and subjective measures of dental fear and anxiety in children. This systematic review aimed to retrieve the scientific evidence comparing the results of dental anxiety measured by salivary biomarkers with patient-reported outcomes in pediatric dental setting. The PECOS was as follows: population: pediatric patients aged ≤ 18 years; exposure: patient-reported outcome measures, such as scales and/or questionnaires; comparator: salivary biomarkers; outcome: anxiety, fear, phobia or stress during dental treatment; study design: observational studies or controlled trials. Electronic searches were conducted in PubMed, Scopus, Web of Science, and Ovid databases. Studies that compared scales/questionnaires and salivary biomarkers for the evaluation of dental anxiety, fear, and stress in children/adolescents during dental treatment were included. Certainty of evidence was assessed with GRADE. Risk of bias of the included studies was assessed with the Cochrane tool or the University of Adelaide tool. From the 314 studies identified, eight were included. Participants' age ranged from three to 13 years. The most used salivary biomarkers and instruments were cortisol and the Dental Subscale of the Children's Fear Survey Schedule, respectively. Most studies showed a weak correlation between objective and subjective measures. The main issues regarding bias were on allocation concealment, blinding of assessors, follow up, and exposure assessment. Certainty of evidence was low/very low. Evidence of salivary biomarkers and patient-reported outcome measures to investigate anxiety, fear and stress in children during in the dental environment is limited. There was no correlation between subjective and objective measures in almost all included studies.