Impact of UGT1A9 Expression on Analgesic Efficacy and Safety of Postoperative Ketorolac in Thyroid Cancer Surgery: A Prospective Cohort Study

Xitong Zhang, Xiunan Jia, Dongmei Fu, Dongxin Wang, Xiaoyu Zhang, Dongxue Li, Shuyi Yang, Zongming Liu, Shiqi DiaoDepartment of Anesthesiology, Jilin Province Cancer Hospital, Changchun, 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongming Liu; Shiqi Diao, Email zongmingliu7567@163.com; dsq66668888@163.comBackground and Objectives: Ketorolac tromethamine is a key opioid-sparing analgesic in Enhanced Recovery After Surgery (ERAS) protocols for thyroid cancer surgery; however, clinically significant interindividual variability in its analgesic efficacy and adverse-event profile is frequently observed. Because UDP-glucuronosyltransferase 1A9 (UGT1A9) plays a central role in the metabolic clearance of ketorolac, we hypothesized that preoperative UGT1A9 expression levels would be associated with differences in postoperative analgesic outcomes.Methods: This prospective observational cohort study enrolled 150 ASA I–II patients undergoing elective total thyroidectomy with central lymph node dissection. Preoperative peripheral blood UGT1A9 protein expression was quantified by enzyme-linked immunosorbent assay (ELISA; optical density, OD). Patients were stratified by median OD into a high-expression cohort (Group I, n = 75) and a low-expression cohort (Group II, n = 75). All received 30 mg intravenous ketorolac at wound closure; no patient-controlled analgesia was used. Primary outcome: resting VAS pain scores at 4 h (T1), 6 h (T2), 8 h (T3), and 12 h (T4). Secondary outcomes: serum IL-6 and CRP at 12 h, adverse events, and length of hospital stay (LOS).Results: Baseline characteristics were comparable (all p > 0.05). From T2 onward, Group II (low expression) demonstrated lower VAS scores than Group I (e.g. T3: 1.47 ± 0.55 vs. 2.00 ± 0.90; p < 0.001; Cohen’s d = 0.70). At 12 h, IL-6 and CRP were significantly lower in Group II (both p < 0.001). LOS was shorter in Group II (7.19 ± 1.44 vs. 8.69 ± 1.85 days; p < 0.001). The incidence of mild dizziness was higher in Group II (9.3% vs. 1.3%; p = 0.029, Fisher’s exact test).Conclusion: These preliminary findings suggest that preoperative UGT1A9 expression may be associated with postoperative ketorolac analgesic response in thyroid cancer surgery. This study provides hypothesis-generating evidence for future pharmacokinetic/pharmacodynamic validation studies exploring pharmacogenomic individualization of perioperative NSAID analgesia.Keywords: UGT1A9, thyroid cancer, ketorolac tromethamine, ERAS, pharmacogenomics, NSAIDs, postoperative analgesia