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Morphine-Augmented Periarticular Injection Reduces Early Postoperative Pain and Analgesic Consumption After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial

This randomized controlled trial demonstrates that adding morphine to a ropivacaine-based periarticular injection significantly reduces early postoperative pain and analgesic consumption in patients undergoing anterior cruciate ligament reconstruction without increasing adverse events.

Original authors: Yong-Beom Park, Seong Hwan Kim, Han-Jun Lee

Published 2026-07-17

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Yong-Beom Park, Seong Hwan Kim, Han-Jun Lee

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Imagine your body is a high-tech fortress, and sometimes, the guards (your nerves) get a little too excited after a major renovation project inside the walls. This happens when surgeons rebuild a crucial stabilizer in the knee, called the anterior cruciate ligament (ACL). It's like fixing a broken hinge on a heavy door; the work is necessary, but the immediate aftermath is a noisy, chaotic construction site that screams in pain. To quiet this down, doctors usually use "local anesthetics," which are like temporary silence spells that numb the area. But there's a catch: these spells wear off quickly, leaving the patient in pain just as the real healing needs to begin. The big question in the medical world has been: Can we mix in a longer-lasting "pain-fighter" to keep the silence going without waking up the whole fortress with side effects?

This is exactly the puzzle a team of surgeons at Chung-Ang University set out to solve. They wanted to see if adding a tiny amount of morphine—a powerful painkiller usually given through an IV—directly into the "cocktail" of medicine injected around the knee joint could make a difference. Think of the local anesthetic as a short-term fire extinguisher that puts out the immediate flames of pain, while morphine acts like a slow-burning fire retardant that keeps the heat from flaring up again for hours. The researchers wondered if this simple mix would be the secret sauce for a smoother, less painful recovery after knee surgery.

The Experiment: Mixing the Magic Potion

In this study, the researchers treated 34 patients who were having their ACLs rebuilt. They split these patients into two teams, like two groups of gamers trying different strategies. Both groups got the standard "base" injection: a large dose of ropivacaine (the local anesthetic) mixed with other helpful ingredients like steroids and anti-inflammatories. This base cocktail was injected right around the knee joint before the surgery was finished.

The difference was in the "secret ingredient."

Team A (The R Group): Got the base cocktail alone.
Team B (The RM Group): Got the exact same base cocktail, but with 10 mg of morphine added to the mix.

The goal was to see who felt less pain in the first few days after surgery. The researchers checked the pain levels using a standard "pain ruler" (called a Visual Analog Scale or VAS) where patients rate their pain from 0 (no pain) to 100 (worst pain imaginable). They also kept a close eye on how much extra "rescue" pain medicine the patients needed and if anyone got sick from the treatment.

The Results: A Clear Winner in the Early Hours

The findings were quite clear, especially for the first two days. The team with the morphine mix (Team B) had a much easier time than the team without it.

At 8 hours after surgery: The morphine group had an average pain score of 30.6, while the group without morphine was at 38.2. That's a noticeable difference, and statistically, it wasn't just luck.
At 24 hours: The gap widened slightly. The morphine group was at 27.4, while the other group was at 34.1.
At 48 hours: The morphine group still held the advantage with a score of 31.2 compared to 35.6 for the others.

However, the magic didn't last forever. By the time 72 hours (three days) rolled around, the pain levels in both groups had dropped so much that the difference between them disappeared. Also, at the very early 4-hour mark, the morphine group was already feeling better, but the difference wasn't quite big enough to be considered statistically significant yet.

The Side Effects and Extra Medicine

One of the biggest worries with adding morphine is that it might make patients feel nauseous, sleepy, or have trouble peeing. The researchers kept a sharp eye out for these "unwanted guests." The results showed that the morphine group did not have more side effects than the group without it. Nausea and urinary retention happened at similar rates in both groups, and no one had serious trouble with breathing or severe drowsiness.

There was also a hint that the morphine group needed less "rescue" pain medicine (like fentanyl) when their pain got too high. While the difference wasn't huge enough to be called a definitive victory, the trend suggested that the morphine mix might help patients rely less on strong opioids later on.

The Bottom Line

This study suggests that adding a small amount of morphine to the standard pain-killing injection around the knee is a smart, simple move for the first two days after ACL surgery. It acts like a longer-lasting shield against pain, keeping patients more comfortable when they need to start moving and rehabbing their knee. It doesn't seem to bring any extra baggage in terms of side effects, making it a promising tool for surgeons looking to make the early recovery phase a little less painful. While the effect fades after three days, that early window is crucial for getting patients back on their feet, and this "morphine-augmented" cocktail seems to do the job well.

Technical Summary: Morphine-Augmented Periarticular Injection in ACL Reconstruction

Problem Statement
Effective pain management following anterior cruciate ligament reconstruction (ACLR) is critical for facilitating early rehabilitation and preventing complications such as restricted range of motion and excessive reliance on systemic opioids. While peri-articular injection (PAI) is a widely used, motor-sparing alternative to regional nerve blocks, its efficacy is often limited by the short duration of action of local anesthetics. Although the synergistic effect of adding opioids to local anesthetics has been explored in general arthroscopic surgery, there is a scarcity of clinical evidence regarding a standardized PAI regimen specifically using ropivacaine (chosen for its favorable safety profile) combined with morphine in the context of modern ACLR protocols.

Methodology
The study was designed as a prospective, randomized, single-blind controlled trial conducted at Chung-Ang University Hospital.

Participants: 34 patients scheduled for primary arthroscopic ACLR using allograft tissue were randomized 1:1 into two groups: the Ropivacaine–Morphine (RM) group ( $n=17$ ) and the Ropivacaine-only (R) group ( $n=17$ ).
Intervention: At the conclusion of surgery, prior to wound closure, a peri-articular injection was administered.
- RM Group: Received a multimodal cocktail containing 40 mL ropivacaine, 10 mg morphine, 40 mg methylprednisolone, 50 mg ketoprofen, and epinephrine.
- R Group: Received the identical cocktail excluding morphine.
- Injection Sites: Infrapatellar fat pad, medial and lateral joint capsules, and surrounding subcutaneous tissues.
Postoperative Protocol: All patients received standardized intravenous patient-controlled analgesia (IV-PCA) with fentanyl, ketorolac, and ramosetron, followed by oral multimodal analgesics. Rescue analgesia was administered based on Visual Analog Scale (VAS) thresholds.
Outcomes: The primary outcome was the VAS pain score at 24 hours postoperatively. Secondary outcomes included VAS scores at 4, 8, 48, and 72 hours, rescue analgesic consumption (ketorolac and fentanyl), and adverse events (nausea, urinary retention, sedation, etc.).

Key Results

Pain Scores: The RM group demonstrated significantly lower pain scores compared to the R group at 8 hours ( $30.6 \pm 5.3$ vs. $38.2 \pm 7.7$ , $p=0.002$ ), 24 hours ( $27.4 \pm 5.9$ vs. $34.1 \pm 5.4$ , $p=0.001$ ), and 48 hours ( $31.2 \pm 5.7$ vs. $35.6 \pm 5.0$ , $p=0.023$ ). No statistically significant differences were observed at 4 hours ( $p=0.059$ ) or 72 hours ( $p=0.251$ ).
Analgesic Consumption: While the reduction in total ketorolac use was not statistically significant, there was a notable trend toward reduced opioid rescue requirements in the RM group. Specifically, fentanyl was required by only 1 patient (5.9%) in the RM group compared to 5 patients (29.4%) in the R group ( $p=0.078$ ).
Safety: No significant differences were found in adverse events, including nausea and urinary retention. No serious adverse events (e.g., respiratory depression, severe sedation) occurred in either group.

Key Contributions
This study provides Level I evidence that augmenting a ropivacaine-based peri-articular injection with 10 mg of morphine significantly enhances early postoperative analgesia (up to 48 hours) following primary ACLR. It specifically addresses the gap in literature regarding morphine use in peri-articular (as opposed to intra-articular) multimodal cocktails for ACLR, demonstrating that this simple addition extends the duration of pain relief beyond that of local anesthetic alone without increasing the risk of opioid-related side effects.

Significance and Claims
The authors conclude that adding morphine to a ropivacaine-based peri-articular injection is an effective, reproducible multimodal analgesic strategy. The study claims that this approach significantly improves early postoperative pain control and facilitates recovery without increasing adverse events. The authors suggest that the mechanism likely involves the activation of peripheral opioid receptors in inflamed tissues, providing prolonged analgesia that complements the shorter duration of ropivacaine. The paper positions this strategy as a practical alternative to regional nerve blocks, offering effective pain management while avoiding motor weakness and the technical complexities associated with nerve localization.

The Experiment: Mixing the Magic Potion

The Results: A Clear Winner in the Early Hours

The Side Effects and Extra Medicine

The Bottom Line

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