title: Intranasal sufentanil/ketamine analgesia in children.
abstract: BACKGROUND
  The management of procedural pain in children ranges from physical restraint to pharmacological interventions. Pediatric formulations that permit accurate dosing, are accepted by children and a have a rapid onset of analgesia are lacking.
  
  
  OBJECTIVE
  To investigate a pediatric formulation of intranasal sufentanil 0.5 mcg·kg(-1) and ketamine 0.5 mg·kg(-1) for procedural pain and to characterize the pharmacokinetic (PK) profile.
  
  
  METHODS
  Fifty children (≥10 kg) scheduled for a painful procedure were included in this prospective nonrandomized open-label clinical trial. Thirteen of these children had central venous access for drug assay sampling; enabling a compartmental PK analysis using nonlinear mixed-effects models. Pain intensity before and during the procedure was measured using age-appropriate pain scales. Heart rate, oxygen saturation and sedation were recorded.
  
  
  RESULTS
  Children had a mean age of 8.8 (sd 4.9) years and weight 35.2 (sd 20.1) kg. Sufentanil/ketamine nasal spray was effective (procedural pain intensity scores ≤5 (0-10)) in 78% of the painful procedures. The spray was well accepted by 94% of the children. Oxygen saturation and heart rate remained stable, and sedation was minimal. The bioavailability of sufentanil and ketamine was 24.6% and 35.8%, respectively. Maximum plasma concentration (Cmax) of sufentanil was 0.042 mcg·l(-1) (coefficient of variation (CV) 12.9%) at 13.8 min (CV 12.4%) (Tmax). Cmax for ketamine was 0.102 mg·l(-1) (CV 10.8%), and Tmax was 8.5 min (CV 17.3%).
  
  
  CONCLUSIONS
  Sufentanil/ketamine nasal spray provided rapid onset of analgesia for a variety of painful procedures with few adverse effects and has promising features for use in pediatric procedural pain management.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Paediatric Pain Service, Department of Anaesthesiology, The Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bettina N
authors.initials: BN
authors.lastname: Nielsen
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Friis
authors.forename: Janne
authors.initials: J
authors.lastname: Rømsing
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreirós
authors.forename: Sandra
authors.initials: S
authors.lastname: Labocha
authors.forename: Steen W
authors.initials: SW
authors.lastname: Henneberg
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000778:Anesthetics, Dissociative / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007223:Infant; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D016343:Monitoring, Intraoperative; D010147:Pain Measurement / Q000187:drug effects; D011446:Prospective Studies; D017409:Sufentanil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000701:Analgesics, Opioid; D000778:Anesthetics, Dissociative; D007649:Ketamine; D017409:Sufentanil
keywords: analgesia; children; intranasal administration; ketamine; pharmacokinetics; sufentanil