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

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.

To understand the effects of perioperative ketorolac on nonunion after spine fusion.

Systematic review with meta-analysis.

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.

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.

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.