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Berend v. Meneghini: Liposomal Bupivacaine Injectables: Game Changers in Pain Management

OTW Staff • Fri, August 18th, 2017

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This week’s Orthopaedic Crossfire® debate was part of the 17th Annual Current Concepts in Joint Replacement® (CCJR), Spring meeting. This week’s topic is “Liposomal Bupivacaine Injectables: Game Changers in Pain Management.” For the proposition Michael E. Berend, M.D., Midwest Center for Joint Replacement, Indianapolis, Indiana. Opposing is R. Michael Meneghini, M.D., Indiana University School of Medicine, Indianapolis, Indiana. Moderating is Thomas S. Thornhill, M.D., Harvard Medical School, Boston, Massachusetts.

Dr. Berend: I’d like to share with you our experience with a new type of pharmacologic technology and I think it has made a big difference in our practice.

The definition of a game changer is an event or an idea or a procedure that effects a significant shift in the current manner of doing or thinking about something. Liposomal bupivacaine is part of a series of events that’s really changed our practice from inpatient surgery to better pain control and outpatient surgery.

Liposomal bupivacaine was a game changer for us. It’s basically Marcaine held in a fatty membrane. Those fatty membranes are grouped together, injected into the pericapsular tissues and then with body heat and pH, the membranes erode and release the medication—sort of a time release capsule for local anesthesia.

We’ve experienced a lot of other game changing things in arthroplasty: the comprehensive joint replacement project, or bundled payment care, which will certainly pressure us into reducing costs and other system changes. This has forced us to reexamine the entire care pathway for joint replacement and I think liposomal bupivacaine plays a role in that algorithm.

Our current protocol focuses on preemptive pain control with preoperative medications of Celebrex and Neurontin and acetaminophen. We’ve eliminated narcotic spinals in favor of short-acting local anesthesia spinals. We use an adductor canal block administered under ultrasound which conserves the quadriceps function. We use a general anesthesia with a laryngeal mask for rapid induction. Tranexamic acid has now eliminated the need for post-operative laboratory monitoring. We use a pericapsular injectable cocktail—some with liposomal bupivacaine at the hospital some with a different recipe at our ASC [ambulatory surgery center], and a whole host of medications aimed at pain control and nausea control.

Zero percent of our patients went home the same day in 2010, now it’s over 50% in 2016. And there’s obviously significant cost savings associated with this type of procedure.

Mike has done a good job to question the superiority of this type of medication. In a retrospective study, an inpatient study I would highlight, with a length of stay of two days, comparing to narcotic spinals, really no difference between liposomal bupivacaine and a standard pericapsular injection.

I think it allowed us to ask ‘Is it worth the cost in our individual environment?’

In our clinical experience of outpatient arthroplasty over the last two years—1,200 hips, knees and partial knees—we saw no readmissions for pain control using this type of medication. It really surprises me in the postoperative care of arthroplasty patients that pain control has largely been solved with a multi-modal program.

Our readmission rate is under 2%. If you take out manipulations, it’s under 1%, and that’s significantly reduced from what’s reported in the literature.

Our average length of stay now for partial knee is just under three hours and for other total joint arthroplasty procedures is under five hours.

And importantly, if you look at patient satisfaction over the last two years running, 98% good to great using this type of program.

So I think multi-modal programs are worth your time, whether you resurface the patella or not. Outpatient joint replacement, I believe to be the future of our craft. Liposomal bupivacaine does play a role. There are obviously advantages and disadvantages, and cost is one consideration.

Dr. Meneghini: Mike and I were in practice early on together and as a young surgeon, many of my senior partners were very influential on me and Mike was no exception. I have a tremendous respect for Mike as a surgeon, as a partner, and he came up with some memorable quotes. One is ‘if you’re a farmer and you have really bad knee arthritis, you can put the knee in backwards and they’ll still do great’. Turns out that’s supported by the data. Robert Barrack would tell you that if the disease is really, really bad that a knee replacement will do very, very well.

Is liposomal bupivacaine a game changer? Let’s look and see if it is supported by the data.

We published a somewhat controversial study in 2014 that brought to light some of the issues around this cocktail. We did a retrospective cohort study with two surgeons looking at just traditional periarticular injection versus liposomal bupivacaine and we did 85 knees with traditional and 65 knees with liposomal bupivacaine. Once the spinal wore off, we found that for the remainder of their hospital stay, the liposomal bupivacaine group had higher pain scores.

When we looked at those patients who rated their pain as mild, the liposomal bupivacaine group (after the first 24 hours) had fewer patients that rated their pain as mild. So we actually did better with the traditional group.

Now let’s look at the highest quality research. Let’s look at prospective randomized trials because now we have a few of them on liposomal bupivacaine to pull from. A study out of University of Louisville just published—105 knees—looking at liposomal bupivacaine versus a modified Ranawat protocol with a mixture of ropivacaine, epinephrine, ketorolac, and clonidine. No difference in the groups between narcotic usage or range of motion.

Another randomized prospective trial, Journal of Arthroplasty, 2015, by Bill Schroer presented at AAHKS on 111 knees. Liposomal bupivacaine against a control group of just plain 0.25% bupivacaine. Again no difference between groups in VAS pain scores and narcotic usage.

One from Jefferson…162 TKAs in a double-blinded prospective randomized control trial…88 patients with liposomal bupivacaine and 74 with a controlled or standard bupivacaine. Again, no difference between groups in VAS pain scores or narcotic consumption.

I think the highlight is the cost. The liposomal bupivacaine, right now, is $320 and standard bupivacaine is $5.00. So a dramatic difference. And in the era of bundled payments, couldn’t agree with Mike more…bundled payments are going to force us to make decisions. Good decisions.

We were challenged on whether our technique was what the manufacturer recommended and so we added a third arm. We just published a study in the Journal of Knee Surgery. We added 41 patients using the same protocols across the board, and just used the manufacturer’s recommended technique of a ton of injection sites, a very small needle, and still came up with the same conclusions. Again, no difference.

In summary, I do think liposomal bupivacaine does not offer a substantial benefit over traditional periarticular injection. Now if you don’t have a lot of pain control, or if you don’t have the proper pain protocols in place, or your anesthesiologists are doing dermal nerve blocks, I think it may offer a benefit. But compared to a traditional injection, it comes at a significant greater cost. The real game changers…and Mike alluded to this, I think we agree completely on this…multi-modal pain protocols and patient education expectations have been the real game changers in getting patients out of the hospital with better pain control.

Moderator Thornhill: Mike, let me ask you something. You put in your multi-modal thing of pericapsular injectables. What is that?

Dr. Berend: It’s either group A or group B from what Mike presented. So in the hospital we currently use the liposomal bupivacaine mixed with Marcaine. In our outpatient center, for cost, we use the same ropivacaine, clonidine, and ketorolac…a narcotic-free injection. So we use some type of pericapsular injection. What the recipe is, how you’re going to balance the cost structure in your own environment…I think that’s up to you.

Moderator Thornhill: Correct me if I’m wrong, but my understanding with liposomal bupivacaine, you can use regular bupivacaine, you can’t use lidocaine, you can’t use ropivacaine, you can’t use Toradol, you can’t use clonidine, you can’t use epinephrine.

Dr. Berend: I would defer to the manufacturer for what you can add/mix with it. Whether it’s on label or off-label. The short answer is you don’t want to use anything that will lyse the liposomals too early and cause a rapid release of Marcaine. I think if you’re using topical betadine in the wound, you’re using some other tranexamic acid, we’re worried about anything additional that you are doing.

Moderator Thornhill: I actually asked the manufacturers because I didn’t know and I wanted to see and it turns out you’re right, you can’t add anything else. You can add bupivacaine, but they will not recommend adding medications.

Dr. Berend: In a certain ratio, that is correct.

Moderator Thornhill: Okay, Mike, help me out with this. I use ropivacaine, clonidine, Toradol, epinephrine, QS it with saline. To me it’s every bit as important in where you put it and how you put it in as what you use. Tell us how to put it in.

Dr. Meneghini: Couldn’t agree more. I think what we’ve learned the optimal technique for periarticular injection…when we’re done with the procedure we inject the periosteum, we inject the synovium, we inject the retinaculum. And we use the same cocktail that you and Mike both alluded to. But we do not inject the posterior capsule…there’s some data out of Duke years ago that the posterior capsule may not be as advantageous. A lot of people propose that it is. We just choose to stay away from those structures in the back of the knee; stay safe at the anterior aspect of the knee.

Moderator Thornhill: I actually think putting it in posteriorly maybe the most important thing. What I do is I use…of the 100cc that I use, 20cc on the medial side, and I put 10cc on mesial side of the lateral side. If it put it out laterally I’ve had a couple of transient perineal nerve palsies. But I think it gets rid of that posterior pain and hitting the periosteum is key. I don’t put anything superficial to the capsule. Where do you inject and how do you inject?

Dr. Berend: I do it exactly the same. I do put it in the posterior capsule, but only on the medial side. I think there are 20 things you’ve got to consider in the care map of the knee arthroplasty patient. This is one of them. What flavor you use is important. But I think there’s cost throughout the entire care map that we’re now challenged to consider in terms of bundled care, for an episode of care. Whether you use post-operative therapy or knee immobilizer, those may be much larger cost issues than whether you use an expensive medication. So it may be of significant value for you to shift your hospital to shorter length of stay, which saves $1,200 a day, which is worth the cost of the medication.

Moderator Thornhill: But every little thing counts and if you look at Mike’s point of the $300 bucks versus $6 bucks or something like that, if you say it doesn’t really change the length of stay in the studies he showed us, and it isn’t any better in pain control, isn’t that $300 bucks just added to “detract” from the bundle?

Dr. Berend: Absolutely and that’s why when we’re paying the bill at a surgeon-owned center, we don’t use it. When it’s part of a global cost where you’re negotiating with the vendors, hospital relationships, you’re worrying about a Foley catheter, and A-line laboratory things—things that you can largely eliminate now—I think it’s one of 10 things you’re going to consider in the cost of the care of the patient. And it may be worth it in some environments. It may not in others.

Moderator Thornhill: Tell me if I heard you right. Are you saying that in a place like an ambulatory center where you have a real dog in the fight, you don’t use it? Whereas in the hospital you do?

Dr. Berend: That’s what I’m saying. The hospital and I aren’t getting along particularly well right now.

Moderator Thornhill: What do you think if you could prolong the nerve block efficacy? With this or any other type of medication—whether you mix epinephrine, clonidine or anything to potentiate the effect of the local, I think that’s where the real value is going to be. If you can do a sensory only block that’s extended, I think that’s of significant value.

Dr. Meneghini: I fully agree.

Moderator Thornhill: I think we’re looking at the data. I appreciate your Midwestern honesty and your evidence-based medicine. Good job.

Please visit to register for the 2017 CCJR Winter Meeting, – December 13 - 16 in Orlando.

Senior Editor: Jay D. Mabrey, M.D., whose 35 year career in orthopedics included residency at Duke University Medical Center, service in the United States Army Medical Corps, Fellowship at the Hospital for Special Surgery and a long, distinguished career at Baylor University Medical Center where, in addition to his overall leadership at that institution, developed the Joint Wellness Program that helped patients get up after surgery more quickly, developed the first virtual reality surgical simulator for knee arthroscopy and chaired the FDA Orthopaedic Device Panel, is Orthopedics This Week’s newest contributing writer and editor.

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