Substitution of liposomal bupivacaine for lidocaine reduces incidence of injection-emergent adverse events after intraarticular therapies for knee osteoarthritis: a prospective cohort study

Abstract Local anesthetics as a part of intraarticular therapies (IATs) are widely used for treating knee osteoarthritis (KOA). Whether substitution of liposomal bupivacaine (LB) for lidocaine is safe and effective in reducing incidence of injection-emergent adverse events after IATs remains unclear. Methods We recruited outpatients who had a clinical diagnosis of KOA and decided to receive IATs from November 2023 to April 2024. The type of IAT (glucocorticoids, platelet-rich plasma and hyaluronic acid) for each participant was decided by the preference of patients after consulting with his or her treating physicians. Using lidocaine or LB as local anesthetics was determined by enrollment timing due to considerations on safety. The primary outcome was injection-emergent adverse events after IATs. Secondary outcome measures included Visual Analogue Scale (VAS) pain scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. Results In this study, 123 and 103 patients respectively received lidocaine and LB according to their enrollment date. Compared with lidocaine, using LB yielded reduced incidence of AE in the overall two weeks (LB versus lidocaine, 30.1% versus 45.5%, P = 0.018) and Week1 (LB versus lidocaine, 23.3% versus 39.8%, P = 0.008). After adjusting for sex, baseline BMI, age, baseline WOMAC pain subscale score and K-L grade, substitution of LB for lidocaine was significantly associated with the reduced incidence of AE in two weeks (OR [95%CI], 0.484 [0.274-0.853], P = 0.012). In the initial three days, the LB groups reported better outcomes in terms of VAS pain score (change from baseline of VAS pain, LB versus lidocaine, Day 1 − 8.3 ± 8.9 versus − 1.9 ± 9.3, P < 0.001; Day 2 − 20.6 ± 16.1 versus − 13.7 ± 19.4, P = 0.005; Day 3 − 22.3 ± 18.5 versus − 16.3 ± 19.3, P = 0.020). The changes from baseline of WOMAC pain subscale at Day 14 were similar between the two groups (LB versus lidocaine, − 32.2 ± 11.7 versus − 29.4 ± 11.3, P = 0.073). Conclusion With substitution of LB for lidocaine, patient might reported reduced incidence of AEs, mainly derived from the superiority in Week 1. The substitution of LB for lidocaine was safe in different scenarios of IATs and future randomized clinical trials were warranted by the current study.