Effect of Ketorolac Administration on the Rate of Nonunion of Operatively Treated Pediatric Long-Bone Fractures

Background: Nonunion is a rare yet serious complication in pediatric fracture healing that can lead to patient morbidity and economic burden. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased risk of fracture nonunion in adults, but data are lacking in the pediatric population. This study examines the relationship between postoperative ketorolac administration and nonunion in operatively managed pediatric long-bone fractures. Methods: A retrospective cohort study was conducted with use of TriNetX, a research network that encompasses data from the United States, Canada, and Western Europe. A total of 462,260 patients from 52 health-care organizations met the inclusion criteria. Patients <18 years old with operatively managed upper or lower-extremity long-bone fractures were included. The exposure of interest was ketorolac administration within 30 days postoperatively between 2003 and 2023. Nonunion was identified and verified with use of the pertinent medical codes. Absolute risks and hazard ratios (HRs) were calculated for both study groups. Significance was set at p < 0.05. Results: After propensity score matching, 48,778 patients were identified per group. The incidence of nonunion was 2.19% in the ketorolac group and 0.93% in the non-ketorolac group (HR, 2.71; 95% confidence interval [CI]: 2.46, 3.21; p < 0.0001). Subgroup analyses demonstrated a higher risk of nonunion in patients with lower-extremity fractures (HR, 3.45; 95% CI: 3.14, 3.75; p < 0.0001) than in those with upper-extremity fractures (HR, 2.11; 95% CI: 1.84, 2.32; p < 0.0001). Among the fracture location subgroups, the greatest HR for nonunion was observed in patients with femoral fractures, followed sequentially by those with tibial and/or fibular fractures, humeral fractures, and radial and/or ulnar fractures. Conclusions: To our knowledge, this is the largest study to date to explore postoperative ketorolac use and nonunion in the setting of operatively managed pediatric long-bone fractures. Nonunion in children was rare, occurring in <1% of all included patients. Ketorolac administration was associated with a 2 to 3-fold increase in nonunion risks, with pronounced implications for patients with lower-extremity fractures, particularly those with femoral fractures. Clinicians should weigh the therapeutic advantages of non-opiate analgesia with ketorolac against the risk of nonunion in order to optimize postoperative pain management and recovery. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.