Liposomal Bupivacaine in Periarticular Injection Cocktails for Pain Management After Total Knee Arthroplasty: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Postoperative pain remains a major barrier to recovery after total knee arthroplasty (TKA), contributing to delayed mobilization, prolonged opioid use, and extended hospitalization. Liposomal bupivacaine (LB), an extended-release local anesthetic, has gained interest as a component of periarticular injection (PAI) protocols to improve analgesia and reduce opioid use. However, its utility remains debated due to inconsistent findings. This systematic review aimed to assess (1) the effectiveness of LB in improving postoperative pain control; (2) its impact on short-term opioid consumption; and (3) its influence on functional recovery, patient satisfaction, and adverse events.

METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and searched PubMed and Embase through July 28, 2025, for randomized controlled trials (RCTs) evaluating LB delivered via PAI in patients undergoing TKA. Inclusion criteria required comparison with non-liposomal bupivacaine or multimodal cocktails and reporting of clinical or economic outcomes. Studies using nerve blocks or lacking randomization were excluded. Methodologic quality was assessed using the modified Coleman Methodology Score (mCMS), and only high-quality studies (mCMS ≥ 85) were included.

RESULTS: There were eight RCTs encompassing 1,334 patients that met inclusion criteria. Use of LB was associated with improved early postoperative pain control in five of eight studies, particularly within the first 24 hours postoperatively. Several trials also reported reductions in opioid consumption and higher patient satisfaction without increased adverse events. Functional recovery metrics, such as ambulation and discharge readiness, showed variable benefit. No study reported inferior outcomes with LB. Across trials, LB demonstrated a consistent safety profile and favorable early analgesic effects.

CONCLUSION: Liposomal bupivacaine administered via PAI provides improvements in postoperative pain and short-term opioid reduction after TKA, with potential benefits on functional recovery. These findings support its role in multimodal pain pathways, particularly in fast-track or outpatient protocols.