Published in:
Open Access 01-07-2015 | Reports of Original Investigations
Celecoxib pharmacogenetics and pediatric adenotonsillectomy: a double-blinded randomized controlled study
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 7/2015
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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.