title: Intranasal sedation using ketamine and midazolam for pediatric dental treatment (NASO): study protocol for a randomized controlled trial.
abstract: 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)."
authors.affiliation: Dentistry Graduate Program, Faculdade de Odontologia (FO), Universidade Federal de Goiás (UFG), Goiânia, GO, 74605-220, Brazil.
authors.forename: Heloisa Sousa
authors.initials: HS
authors.lastname: Gomes
authors.affiliation: Dentistry Graduate Program, Faculdade de Odontologia (FO), Universidade Federal de Goiás (UFG), Goiânia, GO, 74605-220, Brazil.
authors.forename: Analya Rodrigues
authors.initials: AR
authors.lastname: Miranda
authors.affiliation: Dentistry Graduate Program, Faculdade de Odontologia (FO), Universidade Federal de Goiás (UFG), Goiânia, GO, 74605-220, Brazil.
authors.forename: Karolline Alves
authors.initials: KA
authors.lastname: Viana
authors.affiliation: Department of Stomatology (Oral Pathology), FO/UFG, Goiânia, GO, 74605-220, Brazil.
authors.forename: Aline Carvalho
authors.initials: AC
authors.lastname: Batista
authors.affiliation: Department of Pediatrics, Faculdade de Medicina (FM), UFG, Goiânia, GO, 74605-020, Brazil.
authors.forename: Paulo Sucasas
authors.initials: PS
authors.lastname: Costa
authors.affiliation: Dentistry Graduate Program, Faculdade de Odontologia (FO), Universidade Federal de Goiás (UFG), Goiânia, GO, 74605-220, Brazil.
authors.forename: Anelise
authors.initials: A
authors.lastname: Daher
authors.affiliation: Dentistry Graduate Program, Faculdade de Odontologia (FO), Universidade Federal de Goiás (UFG), Goiânia, GO, 74605-220, Brazil.
authors.forename: Geovanna de Castro Morais
authors.initials: GC
authors.lastname: Machado
authors.affiliation: Health Sciences Graduate Program, FM/UFG, Goiânia, GO, 74605-020, Brazil.
authors.forename: Joji
authors.initials: J
authors.lastname: Sado-Filho
authors.affiliation: Department of Oral Health, FO/UFG, Goiânia, GO, 74605-220, Brazil.
authors.forename: Liliani Aires Candido
authors.initials: LA
authors.lastname: Vieira
authors.affiliation: Dentistry Graduate Program, Faculdade de Odontologia (FO), Universidade Federal de Goiás (UFG), Goiânia, GO, 74605-220, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Corrêa-Faria
authors.affiliation: Pediatric Dentistry, Division of Population and Patient Health, King's College London Dental Institute, Bessemer Road, London, SE5 9RS, UK.
authors.forename: Marie Therese
authors.initials: MT
authors.lastname: Hosey
authors.affiliation: Department of Oral Health, FO/UFG, Goiânia, GO, 74605-220, Brazil. lsucasas@ufg.br.|Faculdade de Odontologia, Universidade Federal de Goiás, Primeira Avenida, Setor Universitário, CEP: 74605-220, Goiânia, Goiás, Brazil. lsucasas@ufg.br.
authors.forename: Luciane Rezende
authors.initials: LR
authors.lastname: Costa
mesh_terms: D000281:Administration, Intranasal; D002648:Child; D002675:Child, Preschool; D016292:Procedural Sedation / Q000379:methods*; D003793:Dental Restoration, Permanent / Q000379:methods*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects; D017063:Outcome Assessment, Health Care; D018401:Sample Size
chemical_list: D007649:Ketamine; D008874:Midazolam
keywords: Administration intranasal; Amnesia; Child behavior; Conscious sedation; Dental care for children; Ketamine; Midazolam; Pain assessment; Patient satisfaction; Physiological; Stress