Longer-Acting Nerve Block Drugs After Knee Replacement:
What a New Small Trial Found

What the study asked

Two nerve blocks are often combined for total knee replacement (TKA): the adductor canal block (ACB), which targets sensory nerves supplying the front and inner side of the knee, and the iPACK block, which targets small sensory branches at the back of the knee. Both are designed to reduce pain while leaving the main thigh muscles working, so that walking and physiotherapy can start early. (There is a fuller explanation in our article on nerve blocks after knee replacement.)

The practical limitation is time. A standard single injection of local anaesthetic typically wears off within the first day, while pain from the operation and from early rehabilitation continues for several days. Two strategies are commonly used to try to stretch the effect: adding dexamethasone (a steroid that can prolong how long a conventional local anaesthetic works), or using liposomal bupivacaine, a formulation in which the anaesthetic is packaged in tiny fat-based particles so that it is released slowly.

Ren and colleagues set out to compare these two complete drug combinations, each given through the same ACB + iPACK technique, to see which provided better pain relief and early thigh-muscle strength over the first three days after TKA.

Who was studied and how

This was a randomized controlled trial at a single hospital in China. Adults aged 55 to 80 having a first, one-sided knee replacement for osteoarthritis were enrolled during the first half of 2026. Sixty-eight patients were randomized, and 60 (30 in each group) were included in the final analysis.

• Liposomal group: liposomal bupivacaine combined with a standard dose of plain bupivacaine.
• Dexamethasone group: the same dose of plain bupivacaine combined with 5 mg of dexamethasone, diluted to the same total volume.

All blocks were placed under ultrasound by one experienced anaesthesiologist, and all patients then had general anaesthesia. After surgery, both groups used the same patient-controlled intravenous pain pump, with an injectable pain medicine available as "rescue" if pain stayed high. The people who measured pain and muscle strength did not know which group a patient was in, but the patients themselves did, because the two solutions looked different.

The main outcome was pain at rest 24 hours after surgery, scored on a 0–10 scale. The researchers also recorded pain at rest and with movement at 12, 48 and 72 hours, quadriceps (front-of-thigh) strength, pain-pump use, rescue medication, and side effects. Follow-up ended at 72 hours.

What the researchers found

The authors themselves point out that the 24-hour pain difference was smaller than the roughly 1-point change usually considered noticeable to patients on a 0–10 scale. In other words, the gap was statistically detectable but modest. The difference in pain-pump use at 48 hours was also very small in absolute terms (median 99.75 mL versus 100 mL).

Limitations — why these results are preliminary

This is a small, single-centre trial, and its findings should be treated as preliminary rather than practice-changing. The main reasons:

• Size: 60 analysed patients is enough to test the main question, but too few to judge rare side effects or block-related complications, which were not collected as separate study outcomes.
• Unequal comparison: the liposomal group received extra local anaesthetic on top of the shared plain bupivacaine dose, so the study compared two whole recipes rather than one drug against another. Some of the difference could simply reflect more total anaesthetic.
• Incomplete blinding: patients knew which solution they received, which can influence how pain is reported.
• Strength measurement: quadriceps strength was graded manually, without formal testing of how consistent the graders were.
• Many secondary comparisons: results other than 24-hour resting pain were not adjusted for multiple testing, so they are best viewed as exploratory.
• Short follow-up and narrow outcomes: the study stopped at 72 hours and did not measure walking distance, knee bending, length of stay, or function after discharge.
• Different overall pain plan: apart from the pain pump and rescue medicine, no scheduled non-opioid pain medicines were used after surgery. Many pain-relief pathways include these, so the results may not carry over directly.

Earlier trials of liposomal bupivacaine in nerve blocks for the knee have reported mixed results, which the authors also acknowledge. A single small study is unlikely to settle the question.

What this means for patients

In plain terms: in this group of patients, the slow-release recipe was associated with slightly lower average pain scores on days one to three and less need for extra pain medicine, but the size of the pain difference was small and the study has important limitations. It does not show that one approach leads to a better knee, faster walking, or a better long-term result — those things were not measured.

The study does reinforce a broader point: pain after knee replacement is managed with a combination of methods, and the nerve block is only one part. How long a block lasts, which medicines are added, and what is given by mouth or vein afterward all fit together. If you are anxious about pain after surgery, it is reasonable to ask your team how long the block is expected to last and what the plan is for when it wears off.

How this relates to the approach in this practice

For knee replacement, this practice uses the ACB + iPACK combination as a standard part of the pain-relief pathway. The blocks are placed under ultrasound guidance after general anaesthesia has been started, as single injections, alongside scheduled oral anti-inflammatory medication after surgery. The specific medicines and doses used in this trial are not necessarily the same as those used here, and the trial does not compare against this practice's pathway. Studies like this one are part of the ongoing evidence we follow when reviewing how pain relief is delivered.