Adding acetaminophen or hydromorphone to ibuprofen does not provide better pain relief than ibuprofen alone for children presenting to the emergency department for nonoperative musculoskeletal injuries, according to pooled results from two Canadian randomized controlled trials.

In the trials, which analyzed more than 650 children, mean pain scores were essentially identical between the three treatment groups (ibuprofen plus hydromorphone, ibuprofen plus acetaminophen, and ibuprofen alone) at 60 minutes. The group that received hydromorphone had significantly more adverse events than the other groups; however, only about 20% of the children achieved a pain score < 3.

“Our data show that for simple and uncomplicated fractures and sprains, ibuprofen is the best choice for children,” lead author Samina Ali, MD, professor of pediatrics at the University of Alberta in Edmonton and chair of Pediatric Emergency Research Canada, told Medscape News Canada.

The research was published online on January 8 in JAMA.

Children’s Pain Matters

“Children’s pain matters. We know that if we don’t treat children’s pain in the short term, it can result in long-term complications. These children are more likely to develop chronic pain conditions and more likely to develop fear of medical encounters as adults, so it’s important that we treat it,” Ali said.

“The reason we chose fractures and sprains is because one out of 5 children will have a broken bone before the age of 18 years, so it’s a common problem,” she said.

The two trials were conducted in six university-affiliated, tertiary care Canadian pediatric emergency departments from April 2019 to March 2023. Children aged 6-17 years (mean age, 11.5 years) presenting within 24 hours of sustaining a nonoperative acute limb injury and a pain score of ≥ 5 on a verbal numerical rating scale (vNRS; where 0 = no pain and 10 = worst pain) were enrolled.

At study entry, the mean vNRS score was 6.4. The primary endpoint was the self-reported pain score at 60 minutes after drug administration.

The studies randomly assigned 699 (47.4% female) children to receive a single oral dose of either ibuprofen (10 mg/kg) alone, ibuprofen (10 mg/kg) plus acetaminophen (15 mg/kg), or ibuprofen (10 mg/kg) plus hydromorphone (0.05 mg/kg).

The three drug regimens were associated with similar reductions in pain scores. At 60 minutes, the mean vNRS score was 4.6 in the ibuprofen alone group, 4.6 in the ibuprofen plus acetaminophen group, and 4.8 in the ibuprofen plus hydromorphone group. The same pattern persisted at 90 and 120 minutes.

Importantly, adverse events were more than four times more frequent in the group that received hydromorphone (28.2%) compared with ibuprofen alone (5.8%) or ibuprofen plus acetaminophen (6.1%). Adverse events that occurred with hydromorphone included sleepiness, dizziness, abdominal pain, stomach upset, nausea, and vomiting.

Results Somewhat Surprising

The results were somewhat surprising, said Ali. “You’d think that if one medicine is good, then two would be better, especially when you are using a strong drug like oral hydromorphone. But the mechanism of pain in children with sprains and fractures is mostly related to inflammation. Ibuprofen is not just anti-pain; it’s anti-swelling. We think that accounts for its power in this scenario,” she said.

She also emphasized that the focus of these two studies was on acute, nonoperative musculoskeletal injuries, and therefore the results cannot be generalized to more complex fractures that require surgery.

“Just to be clear, if someone is going to the operating room with a broken femur or needs surgery, that is different. They should get opioids, which are usually given intravenously or intranasally, and that is totally appropriate. What we are talking about in this research are simple, uncomplicated fractures and sprains in the kids that go home from the emergency room,” Ali said.

In an accompanying editorial, Jessica B. Calihan, MD, instructor in pediatrics at Harvard Medical School in Boston, and colleagues wrote that the study authors present “critical new clinical trial data” that should reassure clinicians that avoiding opioids for acute musculoskeletal pain is not undertreatment but likely best practice.

The editorialists called for future research to explore the need for further pain relief once children have left the emergency department and how quickly children with such injuries are able to return to school, sleep normally, and resume their usual physical activities. 

Ibuprofen ‘Likely the Best Choice’

Commenting on the findings for Medscape News Canada, Ran Goldman, MD, professor of pediatrics at the University of British Columbia in Vancouver, said, “This study is an excellent addition to the scientific community when seeking better pain care after injury.” Goldman did not participate in the study.

“For years, we asked ourselves in the emergency room what is the best treatment for children who were injured from a fall or after playing their favorite sport. Just like parents, pediatricians want to give children everything we have and to dispense the entire hospital medicine cabinet,” Goldman said.

“But this study taught us, somewhat surprisingly, that it is not ‘the more, the merrier.’ We need to be selective and find the single best medicine to manage pain. Ibuprofen, with its anti-inflammatory properties, is likely the best choice for those injuries,” he said.

“After 25 years of seeing children in the emergency department and studying pain reduction techniques, I continue to learn that we need to go back to basics and remember that ibuprofen was always recommended as first-line therapy for acute musculoskeletal pain. This study reinforces that thought. Pain can leave scars, and I can tell you that some adults do not go to the doctor and do not want to get vaccines because they remember pain they suffered as children. We know today that managing pain facilitates healing,” Goldman said.

This research was supported by the Canadian Institutes of Health Research, the Children’s Hospital Research Institute of Manitoba, the Centre Hospitalier Universitaire Sainte-Justine, the Department of Pediatrics of the University of Western Ontario, the Alberta Children’s Hospital Research Institute, the Women and Children’s Health Research Institute, the Children’s Hospital of Eastern Ontario Research Institute, and the Hospital for Sick Children Research Institute. Ali and Goldman reported having no relevant financial relationships.