Does perioperative ketorolac use impact union rate in spine surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Spinal arthrodesis is widely used for degenerative, deformity, traumatic, and neoplastic conditions, yet nonunion remains a major source of pain, hardware failure, and revision surgery. Multimodal analgesia often includes ketorolac to reduce opioid exposure, but early single-center cohorts linked postoperative ketorolac to higher nonunion, while more recent randomized trials and large database studies using short, protocolized regimens have not shown increased nonfusion. PURPOSE: To understand the effects of perioperative ketorolac on nonunion after spine fusion. STUDY DESIGN: Systematic review with meta-analysis. METHODS: We conducted a PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD420251137564) of eligible studies that enrolled adults undergoing any spinal fusion, compared perioperative ketorolac with no ketorolac or no NSAID, and reported fusion outcomes. Risk of bias was assessed using ROBINS-I for observational studies and RoB-2 for randomized trials. Random-effects models pooled odds ratios for nonunion. Prespecified subgroups assessed study design, spine region, outcome definition, and exposure windows by time and dose. RESULTS: Across 41,365 patients (20,713 ketorolac vs 20,652 controls), perioperative ketorolac was not associated with higher nonunion overall (OR 1.10, 95% CI 0.82 to 1.49, p=.52, I²=57.0%). Statistically significant increases appeared only in specific contexts: older retrospective single-center cohorts (OR 2.59, 95% CI 0.68 to 9.91, p=.024), and exposures longer than 48 hours or exceeding 240 mg (each OR 2.17, 95% CI 1.21 to 3.90, p<.01), supported by significant subgroup contrasts for study type and exposure thresholds. Subanalyses by study type and spine region did not show a significant difference. CONCLUSIONS: Perioperative ketorolac, when limited to short, protocolized courses of less than 48 hours at moderate doses (less than 240 mg or 2.5 mg/hour), was not associated with a clinically meaningful increase in nonunion after spinal fusion. Elevated risk described in older single-center cohorts appears related to longer or less standardized exposure. These findings support ketorolac as a component of multimodal analgesia within defined time and dose limits and justify prospective dose-stratified trials to refine exposure thresholds for complex and multilevel constructs.