High‐Dose Celecoxib for Pain After Pediatric Tonsillectomy: A Randomized Controlled Trial

Abstract

Objective Pediatric tonsillectomy causes significant postoperative pain. Newer nonsteroidal anti-inflammatory drugs such as celecoxib control pain without increasing bleeding risk, but in prior studies provided only modest pain reduction at standard doses. We aimed to determine if high-dose celecoxib (double the usual pediatric dose) is effective for pain, without increasing bleeding or other risks. Study Design Randomized double-blind trial. Setting Pediatric tertiary center. Methods Children aged 3 to 11 years undergoing total tonsillectomy were randomized to receive celecoxib (6 mg/kg/dose) or placebo, twice daily, for up to 10 days. All cases were supplemented with acetaminophen and oxycodone as needed. All participants and personnel were blinded to treatment group. Subjects recorded coanalgesic consumption, pain, diet, and activity. Results The celecoxib group (n = 68) consumed 0.72 mg/kg of oxycodone, as compared with 1.12 mg/kg in the placebo group (n = 62), a 36% difference that was not significant. However, multivariate analysis by treatment group, separate from pain levels, confirmed that this reduction was due to celecoxib treatment ( P = .03). In subjects with more prolonged pain (n = 88), celecoxib reduced consumption by 52% ( P = .02). Celecoxib showed greater benefit for subjects in the prolonged pain group than for those in the lesser pain group ( P = .006). Incidence of adverse events was similar between groups. Minor hemorrhage occurred in 4.6% (5 placebo, 3 celecoxib). Conclusion High-dose celecoxib is effective in controlling pain after tonsillectomy, with no adverse effects in this relatively small sample. It reduces narcotic consumption, and its impact appears greater in children with higher degrees of pain. Celecoxib can be considered an effective alternative to ibuprofen after tonsillectomy. This trial was registered at ClinicalTrials.gov: NCT02934191.

Does Celecoxib Prescription for Pain Management Affect Post-tonsillectomy Hemorrhage Requiring Surgery? A Retrospective Observational Cohort Study

“…49 Given the uncertain risk of bleeding with nonselective NSAIDs, the benefits of COX-2–specific inhibitors in terms of analgesic efficacy and platelet sparing effects, even at supra-therapeutic plasma levels, 19 are noteworthy and have been the focus of a recent meta-analysis 21 and demonstrated in five randomized controlled trials. 4,22,23,50,51 Celecoxib is an ideal analgesic for tonsillectomy because its oral suspension formulation can be administered both preoperatively and postoperatively in a twice-daily dosing schedule with a low parental burden for analgesia administration 52 and as part of a multimodal analgesic regimen after discharge. In adults, selective COX-2 inhibition is a recognized way to reliably reduce antiplatelet effects and bleeding risk.…”

“…Given its shorter half-life, either a mid-day 3 mg/kg dose or a higher twice-daily maintenance dose (6 to 7 mg/kg) is required to safely sustain analgesic levels in children, as reported in a recent publication. 23…”

Modeling adult COX‐2 cerebrospinal fluid pharmacokinetics to inform pediatric investigation

“…An understanding of the pharmacokinetic‐pharmacodynamic relationship (PKPD) of celecoxib and valdecoxib allows the use of modeling and simulation to drive further clinical study (Table 5). Celecoxib shows promise as an analgesic for children who have undergone tonsillectomy, 24,27 but future studies should be guided by PKPD understanding. Pharmacokinetic‐pharmacodynamic models can be used to improve trial design (e.g., dose finding studies), understand benefits of combination therapy (e.g., celecoxib and acetaminophen) and to predict outcomes before a child is even enrolled in a study, provided information used to construct the model is accurate 48 .…”

“…The bigger target effect of 4/10 VAS reduction associated with a CSF concentration of 1.7 μg L −1 after celecoxib 3 mg kg −1 may prove a better choice. Good analgesia has been reported with celecoxib 6 mg kg −1 in children after adenotonsillectomy, 27 but analgesic effect was not quantified. 5).…”

“…We report CSF pharmacokinetics for three selective COX-2 inhibitors (celecoxib, valdecoxib, and rofecoxib), demonstrate analgesic hysteresis associated with these drugs and suggest that CSF concentration can explain, in part, the temporal delay observed for analgesic effect. Celecoxib use remains limited in children 24,26,27 and an understanding of pharmacokinetic-pharmacodynamic relationships can drive future investigation. Quantification of the temporal relationship between plasma and CSF concentration is rarely reported, yet is useful in order to interpret differences in effect onset, offset and to better identify analgesic target concentrations.…”