Liposomal bupivacaine after hip fracture surgery: no clear advantage over placebo

Polish version: Liposomalna bupiwakaina po złamaniu bliższego końca kości udowej — bez wyraźnej przewagi nad placebo

A multicentre double-blind randomized pilot trial found no clear benefit from local liposomal bupivacaine after surgery for low-energy proximal femoral fracture. Opioid use, pain and delirium were similar to saline placebo. A small benefit cannot be excluded, but the results do not support routine use of the more expensive formulation.

Why this study matters

Inadequate analgesia can delay mobilisation after hip fracture, while greater opioid exposure may contribute to nausea, sedation and confusion. Liposomal bupivacaine aims to prolong local anaesthesia, but its clinical value in orthopaedics remains debated. This trial compared the liposomal formulation alone with placebo, without adding conventional bupivacaine.

Study design

The analysis included 53 patients older than 55 with isolated low-energy OTA/AO 31A or 31B fractures: 25 received liposomal bupivacaine and 28 saline. Treatment involved intramedullary nailing, a sliding hip screw or hemiarthroplasty. The study injection was given locally near the end of surgery. All procedures used general anaesthesia without peripheral nerve blocks.

The main outcome was opioid consumption in morphine milligram equivalents (MME) during the first 72 hours. Pain, confusion assessed with the Confusion Assessment Method, complications and feasibility of serial data collection were also evaluated.

Main results

• Mean opioid consumption through 72 hours was 65.4 mg MME with placebo and 52.5 mg MME with liposomal bupivacaine (P = 0.37).
• No significant differences were found at 24 or 48 hours.
• Pain did not differ significantly at any assessed time point.
• Episodes of confusion or delirium and medical or surgical complications did not differ.
• Complete 72-hour data were available for only a small proportion; 48-hour assessment proved more practical.

Clinical interpretation for an orthopaedic surgeon

The opioid difference favoured liposomal bupivacaine but was small relative to variability and nonsignificant. The authors estimated that approximately 518 patients would be needed to detect a 20% difference reliably. They also noted that potential benefit was likely modest, the drug relatively costly and effects potentially dependent on infiltration technique.

Another randomized trial published in The Journal of Bone and Joint Surgery in 2026 likewise failed to improve its prespecified primary endpoint after hip fracture surgery, despite favourable secondary outcomes. Together, these findings suggest a possible signal without strong support for routine treatment of every patient.

Limitations

• The pilot sample of 53 lacked power for small effects.
• Three different surgical treatments increased clinical heterogeneity.
• Patients with substantial cognitive impairment were excluded, limiting delirium conclusions in the most vulnerable older adults.
• All patients received general anaesthesia without regional blocks; contemporary multimodal pathways may differ.
• Many patients left hospital before 72 hours, weakening that assessment.

Implications for practice

The findings argue against automatically adding liposomal bupivacaine to every hip fracture pathway. Carefully designed multimodal analgesia, appropriate regional blockade and judicious opioid reduction may be more relevant. Related discussions cover PENG block and opioid-sparing anaesthesia for TKA.

The study does not establish complete ineffectiveness or exclude benefit in particular protocols or subgroups. It indicates that the expected effect is not large and that routine adoption of a costly intervention requires a clear clinically important benefit.

References

1. Matuszewski PE, Jo J, Aneja A, Diwan A, Kraus MT, Moghadamian ES, Wright RD, Siegel J, Thompson K, Swart EF. Liposomal bupivacaine surgical site injection for decrease of narcotic use in hip fractures: a pilot multicenter randomized trial. OTA International. 2026;9(3):e504. DOI: 10.1097/OI9.0000000000000504. PMID 42602754.
2. Yu X, Yuan Y, Zhao S, et al. Incisional Infiltration of Liposomal Bupivacaine in Geriatric Hip Fracture Surgery: A Randomized Parallel-Group Trial. J Bone Joint Surg Am. Published online 16 June 2026. DOI: 10.2106/JBJS.25.01498. PMID 42302095.

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Content prepared by: Tomasz Poboży - orthopaedic surgeon.