BackgroundLocal periarticular infiltration (PAI) analgesia has emerged as an important component of multimodal approaches to treat total knee arthroplasty postoperative pain. Liposomal bupivacaine may provide prolonged analgesic duration when injected into the surrounding tissues. The purpose of this study was to compare the analgesic efficacy and serum bupivacaine levels of a continuous femoral nerve block (CFNB) with bupivacaine to PAI with liposomal bupivacaine. MethodsSixty-five patients undergoing primary unilateral total knee arthroplasty were randomized into 2 groups: (1) CFNB and PAI with bupivacaine (CFNB group) or (2) PAI with bupivacaine:liposomal bupivacaine mixture at the end of surgery (LB group). The primary outcome was pain intensity at maximum knee flexion 24 hours following surgery. Secondary outcomes included pain intensities at rest and movement at timed intervals and serum bupivacaine levels. ResultsPatients in the CFNB group experienced lower pain scores at maximum knee flexion at 24 hours (7.91; 95% confidence interval, 7.19-8.61) compared to the LB group (8.95; 95% confidence interval, 8.42-9.48; P = .02). The mean peak serum bupivacaine level in the LB group up to 72 hours was 0.55 μg/mL versus 1.4 μg/mL for CFNB group (P = .0008) with one patient in the CFNB group exceeding the reported minimum serum bupivacaine threshold for toxicity. ConclusionWhile similar pain control was observed on the day of surgery for both groups, patients with a CFNB experienced lower pain intensities during maximum knee flexion at 24 hours. Total serum concentrations in LB group remained below the toxicity threshold over the study period.