Research Summary

Acetaminophen or Opioid Added to Ibuprofen Does Not Improve Pain Relief in Pediatric Musculoskeletal Injury

Edited by:
Kate Young

Key Highlights

  • In two emergency department–based randomized trials, adding acetaminophen or hydromorphone to ibuprofen did not significantly improve pain scores at 60 minutes in children with acute nonoperative musculoskeletal injuries.
  • Hydromorphone coadministration was associated with a fourfold increase in adverse events compared with ibuprofen alone.
  • The pooled analysis included 699 children aged 6 to 17 years with moderate to severe pain presenting within 24 hours of injury.

Children presenting to emergency departments with acute nonoperative limb injuries often experience significant pain, and ibuprofen monotherapy is standard first-line therapy. However, the additive benefit of combining ibuprofen with either acetaminophen or opioids has been unclear. In a study published online January 8, 2026, in JAMA, researchers report data from two randomized, double-masked, placebo-controlled clinical trials evaluating these combinations in pediatric patients.

Investigators conducted two complementary trials across six tertiary care pediatric emergency departments in Canada between April 2019 and March 2023. Eligible children were aged 6 to 17 years, presented within 24 hours of a nonoperative acute limb injury, and had a verbal numerical rating scale (vNRS) pain score of at least 5 out of 10 at baseline. One trial compared ibuprofen plus hydromorphone, ibuprofen plus acetaminophen, and ibuprofen alone; the other compared ibuprofen plus acetaminophen and ibuprofen alone. Dosing regimens included ibuprofen at 10 mg/kg (up to 600 mg), acetaminophen at 15 mg/kg (up to 1000 mg), and hydromorphone at 0.05 mg/kg (up to 5 mg). The primary efficacy outcome was self-reported vNRS pain score at 60 minutes post-administration; safety outcomes included adverse events related to study drugs.

Study Findings
A total of 699 children were randomized, and 653 were included in efficacy analyses. Mean (SD) age was 11.5 (3.5) years, with 47.4% female participants. Pooled mean vNRS scores at 60 minutes after medication were similar across groups: 4.8 (2.6) for ibuprofen plus hydromorphone, 4.6 (2.4) for ibuprofen plus acetaminophen, and 4.6 (2.3) for ibuprofen alone (P = .78), indicating no significant pain relief benefit from additive agents. Adverse events occurred more frequently in the hydromorphone group (28.2%) compared with the acetaminophen plus ibuprofen group (6.1%) and ibuprofen alone group (5.8%), with no serious adverse events reported.

Clinical Implications
These findings suggest that routine addition of acetaminophen or hydromorphone to ibuprofen does not improve short-term pain relief for children with nonoperative musculoskeletal injuries and may increase the risk of adverse events when opioids are used. As pain management strategies evolve in pediatric emergency care, clinicians should weigh the lack of additional analgesic benefit against potential safety concerns, particularly with opioid coadministration. The study’s conclusions are grounded in trial data without extrapolation beyond the reported outcomes.

Expert Commentary
“For children with acute nonoperative musculoskeletal injury, pain scores at 60 minutes after drug administration did not improve with ibuprofen plus acetaminophen or ibuprofen plus hydromorphone compared with ibuprofen alone. Adverse events were 4-fold more frequent with hydromorphone,” the researchers concluded.

Reference
Ali S, Klassen TP, Candelaria P, et al. Acetaminophen (paracetamol) or opioid analgesia added to ibuprofen for children’s musculoskeletal injury: two randomized clinical trials. JAMA. Published online January 8, 2026. doi:10.1001/jama.2025.25033