JOA - 2026-09-21 - Journal Article
Periarticular Injection Cocktails for Pain Management After Total Knee Arthroplasty: A Systematic Review of Randomized Controlled Trials.
Ng MK, Mastrokostas LE, Mastrokostas PG, Mont MA
Topics
Key Takeaway
Across 78 RCTs and 8,515 TKA patients, multimodal periarticular injection consistently reduced pain and opioid consumption versus placebo, but no single cocktail formulation proved superior to others, and liposomal bupivacaine showed equivalence—not superiority—to standard cocktails in most trials.
Summary Depth
Choose how much analysis to show on this article page.
Summary
This PRISMA-compliant systematic review of RCTs searched PubMed, Embase, and CENTRAL through June 2025 to determine the optimal periarticular injection (PAI) formulation for post-TKA analgesia. PAI outperformed placebo for pain, opioid consumption, and early function; pain control was equivalent to nerve blocks though opioid sparing slightly favored nerve blocks. Corticosteroid-containing cocktails showed consistent analgesic benefit, while liposomal bupivacaine matched but did not exceed standard cocktails, and only one study demonstrated cost-effectiveness of liposomal bupivacaine over adductor canal block.
Key Limitation
Inability to perform pooled meta-analysis due to cocktail heterogeneity means no evidence-based dosing protocol or optimal formulation can be extracted from the 78 included trials.
Original Abstract
BACKGROUND
Total knee arthroplasty (TKA) is a common and effective treatment for end-stage knee osteoarthritis, but postoperative pain remains a major barrier to recovery and may increase opioid use. Periarticular infiltration (PAI) with multimodal drug cocktails is a promising analgesic strategy, though the optimal formulation remains unclear.
METHODS
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and CENTRAL were searched from inception through June 1, 2025, for randomized controlled trials (RCTs) evaluating local infiltration analgesia in TKA. Studies were included if they compared multimodal PAI cocktails to placebo, nerve blocks, or alternative cocktails and reported clinical or economic outcomes. Dual independent screening, data extraction, and risk of bias assessment (using the JADAD scale) were performed. There were 78 RCTs comprising 8,515 patients that met inclusion criteria.
RESULTS
Compared to placebo, PAI cocktails consistently reduced postoperative pain and opioid consumption and improved early functional outcomes. In comparisons with nerve blocks, pain control was generally equivalent, though opioid use slightly favored nerve blocks. Head-to-head comparisons between different cocktail formulations showed no consistently superior combination, though cocktails containing corticosteroids were associated with improved analgesia. Liposomal bupivacaine (LB) demonstrated comparable effectiveness to standard cocktails and nerve blocks in most studies, with several trials reporting meaningful benefits in pain reduction, opioid sparing, and patient satisfaction. Only one study reported LB to be more cost-effective than adductor canal block. Study heterogeneity limited pooled analysis and direct formulation comparisons.
CONCLUSION
Multimodal PAI improves early postoperative outcomes after TKA, especially versus placebo. Corticosteroid-containing cocktails may provide added benefit, but variation in formulations, dosing, and outcomes prevents identification of a single optimal regimen. The LB is a promising component, with some studies showing better pain control, lower opioid use, and higher patient satisfaction. Standardized, high-quality trials with economic endpoints are still needed.