title: Celecoxib pharmacogenetics and pediatric adenotonsillectomy: a double-blinded randomized controlled study.
abstract: BACKGROUND
  Pediatric adenotonsillectomy (A&T) is associated with prolonged pain and functional limitation. Celecoxib is an effective analgesic in adult surgery patients; however, its analgesic efficacy on pain and functional recovery in pediatric A&T patients is unknown.
  
  
  METHODS
  During 2009-2012, children (age 2-18 yr) scheduled for elective A&T were enrolled in a single-centre double-blind randomized controlled trial. Study participants received either oral placebo or celecoxib 6 mg·kg(-1) preoperatively, followed by 3 mg·kg(-1) twice daily for five doses. The primary outcome was the mean "worst 24-hr pain" scores during postoperative days (PODs) 0-2 on a 100-mm visual analogue scale (VAS). Secondary outcomes for PODs 0-7 included co-analgesic consumption, adverse events, and functional recovery. The impact of the CYP2C9*3 allele - associated with reduced celecoxib hepatic metabolism - on recovery was considered.
  
  
  RESULTS
  Of the 282 children enrolled, 195 (celecoxib = 101, placebo = 94) were included in the primary outcome analysis. While on treatment, children receiving celecoxib experienced a modest reduction in the average pain experienced over PODs 0-2 (7 mm on a VAS; 95% confidence interval [CI]: 0.3 to 14; P = 0.04) and a "clinically significant" reduction (≥ 10 mm on a VAS; P ≤ 0.01) on PODs 0 and 1. During PODs 0-2, the mean acetaminophen consumption was lower in the celecoxib group vs the placebo group (78 mg·kg(-1); 95% CI: 68 to 89 vs 97 mg·kg(-1); 95% CI: 85 to 109, respectively; P = 0.03). No differences in adverse events, functional recovery, or satisfaction were observed by POD 7. The CYP2C9*3 allele was associated with less pain and improved functional recovery.
  
  
  CONCLUSIONS
  A three-day course of oral celecoxib reduces early pain and co-analgesic consumption; however, an increase in dose, dose frequency, and duration of dose may be required for sustained pain relief in the pediatric setting. The CYP2C9*3 allele may influence recovery. This trial was registered at: ClinicalTrials.gov: NCT00849966.
authors.affiliation: Department of Anesthesiology, Children's Hospital of Eastern Ontario (CHEO), University of Ottawa, 401 Smyth Rd., Ottawa, ON, K1H 8L1, Canada, Kmurto@cheo.on.ca.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Murto
authors.forename: Christine
authors.initials: C
authors.lastname: Lamontagne
authors.forename: Colleen
authors.initials: C
authors.lastname: McFaul
authors.forename: Johnna
authors.initials: J
authors.lastname: MacCormick
authors.forename: Kelly-Ann
authors.initials: KA
authors.lastname: Ramakko
authors.forename: Mary
authors.initials: M
authors.lastname: Aglipay
authors.forename: David
authors.initials: D
authors.lastname: Rosen
authors.forename: Regis
authors.initials: R
authors.lastname: Vaillancourt
mesh_terms: D000233:Adenoidectomy / Q000379:methods*; D000293:Adolescent; D000068579:Celecoxib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy; D010597:Pharmacogenetics; D014068:Tonsillectomy / Q000379:methods*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000068579:Celecoxib
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