Celecoxib pharmacogenetics and pediatric adenotonsillectomy: a double-blinded randomized controlled study

Abstract

BackgroundPediatric 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.MethodsDuring 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.ResultsOf 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.ConclusionsA 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12630-015-0376-1) contains supplementary material, which is available to authorized users.

Pharmacokinetics and analgesic effectiveness of intravenous parecoxib for tonsillectomy ± adenoidectomy

“…Single nuclear polymorphisms for CYP2C9 are described and may contribute to clearance variability. Children given celecoxib with the genotype CYP2C9 *3 had less pain and improved functional recovery after tonsillectomy .…”

Pain management in the acute care setting: Update and debates

“…The main issue in acute care is that coxibs do not inhibit platelet activity. They may be pro‐thrombotic in adult coronary and cerebrovascular disease but are an option for the child in pain post‐tonsillectomy or post haemophiliac bleed . As the renal effects of NSAIDs occur via a cox‐2 mechanism, it is essential that renal output is established before use.…”

A new analgesic paradigm for pediatric tonsillectomy: Are we dragging our heels?

“…Li et al studied 60 children who were undergoing tonsillectomy or adenotonsillectomy and randomized to receive either parecoxib 1 mgÁkg -1 or saline at induction of anesthesia. The authors found that the saline group had significantly worse median Children's Hospital of Eastern Ontario Pain Scale pain scores (placebo, 9 [8-11] vs parecoxib, 7 [5][6][7][8]; P \ 0.001) in the postanesthesia care unit (PACU), needed more analgesic rescues with morphine (relative risk [RR], 1.5; 95% confidence interval [CI], 1.0 to 2.1; P = 0.024), needed rescue analgesics 61 min earlier (95% CI, 27 to 91; P = 0.001), and consumed 53% more overall morphine (P = 0.017). In addition, the saline group had more postoperative nausea and sedation (RR, 2.8; 95% CI, 1.0 to 7.7; P = 0.037).…”

“…In the July 2015 issue of the Journal, Murto et al 5 published a similar and important study using celecoxib (also a COX-2 inhibitor) for the treatment of tonsillectomy pain in children ages two to 18 yr. Celecoxib is available in North America but not as an intravenous formulation. Children in the treatment group received 6 mgÁkg -1 of celecoxib orally preoperatively followed by 3 mgÁkg -1 twice daily for five doses.…”

“…a porté sur 60 enfants subissant une amygdalectomie ou une adéno-amygdalectomie qui ont été aléatoirement répartis à recevoir soit 1 mgÁkg -1 de parécoxib, soit une solution physiologique à l'induction de l'anesthésie. Les auteurs ont observé que les enfants du groupe recevant la solution physiologique affichaient des scores de douleur moyens significativement plus élevés sur l'É chelle de douleur de l'hôpital (placebo, 9 [8][9][10][11] vs parécoxib, 7 [5][6][7][8]; P \ 0,001) en salle de réveil, avaient besoin de plus d'analgésie de secours avec morphine (risque relatif [RR], 1,5; intervalle de confiance [IC] 95 %, 1,0 à 2,1; P = 0,024), avaient besoin d'analgésie de secours 61 minutes plus tôt (IC 95 %, 27 à 91; P = 0,001) et avaient consommé globalement 53 % plus de morphine (P = 0,017). De plus, le groupe solution physiologique a davantage souffert de nausées et de sédation postopératoires (RR, 2,8; IC 95 %, 1,0 à 7,7; P = 0,037).…”