The Association between Postoperative Ketorolac Administration and Pseudoarthrosis Following Anterior Cervical Discectomy and Fusion

Study Design. Retrospective cohort study. Objective. We tested the hypothesis of no significant association between early postoperative ketorolac administration and pseudoarthrosis compared to matched controls prescribed acetaminophen, as measured by risk ratio (RR), through four years’ follow-up. Summary of Background Data. The potential association between ketorolac use and pseudoarthrosis following anterior cervical discectomy and fusion (ACDF) remains largely unexplored, despite concerns about its potential to hinder bone healing. Methods. This retrospective cohort study used the TriNetX database to examine adults (≥18 y old) undergoing primary ACDF from 2004 to 2020. Patients were divided into cohorts based on whether they received ketorolac (ketorolac cohort) or acetaminophen (control cohort) ≤2 days after ACDF. Risk factors for pseudoarthrosis were propensity matched. The primary outcome was the RR for pseudoarthrosis with 95% confidence intervals (CI). Secondary outcomes explored risk of reoperation, postoperative bleeding, and risk/count of oral opioid prescriptions. Results. There were 3,475 patients per cohort (mean age=53 y) after matching. Through four years’ follow-up after ACDF, comparing the ketorolac versus control cohorts, there was no statistically significant increase in risk of pseudoarthrosis [95% CI] (14.8% vs. 16.4%; RR=0.90 [0.81,1.01]; P =0.069), reoperation (7.8% vs. 7.6%; RR=1.03 [0.88,1.21]; P =0.719), or severe postoperative bleeding (0.5% vs. 0.5%; RR=1.00 [0.52,1.92]; P =1.000). Regarding oral opioids, the ketorolac cohort had a small, statistically significant increase in risk of prescription (79.3% vs. 74.2%; RR=1.07 [1.04,1.10]; P <0.001), yet no significant difference in mean prescription count (6.1 vs. 5.5; P =0.064). Conclusion. Receiving ketorolac within two days after ACDF does not appear to be associated with an increased risk of pseudoarthrosis through four years follow-up in adults. Furthermore, there appears to be no meaningful difference in risk of reoperation, severe bleeding, and oral opioid prescriptions, although secondary outcomes should be interpreted with caution. Further corroboration is warranted.