Dr. Chris Tucker:
Welcome to the Arthroscopy Journal Podcast. I'm Dr. Chris Tucker from the Walter Reed National Military Medical Center and founding editor of the podcast. Today, we are discussing the use of tranexamic acid or TXA in ACL reconstruction surgery. I'm excited to be joined for this episode by Dr. Michael Alaia, associate professor and co-fellowship director at NYU Langone Health. Dr. Alaia is active with multiple professional societies, including AANA, and he was my co-fellow on the 2017 traveling fellowship. Dr. Alaia was the senior author on the article titled Tranexamic Acid Has No Effect On Postoperative Hemarthrosis Or Pain Control After Anterior Cruciate Ligament Reconstruction Using Bone-Patella Tendon-Bone Autograft, A Double Blind Randomized Controlled Trial. Which was published in the June 2021 issue of the Arthroscopy Journal. His coauthors include Jordan Fried, David Bloom, Eoghan Hurley, Samuel Baron, Jovan Popovic, Kirk Campbell, Eric Strauss, and Laith Jazrawi. Mike, congratulations on your work and welcome to the podcast.
Dr. Michael Alaia:
Pleasure to be here, Chris, thanks to you and all you do for the journal, all you do for the podcast. You as well as Clayton, just have done remarkable things. And it's always a great thing to see somebody I know and respect and love do so much good work out in the community. So, thanks again for having me on this, Chris. I'm excited to be here.
Dr. Chris Tucker:
Well, thanks Mike. Yeah, I'm excited to have you. So can we start off by having you set the stage for our discussion and give us some background on the origin for this study and how your idea came about?
Dr. Michael Alaia:
Well, over the past 10, 15 years or so, if you look at the literature, there's been really an inordinate amount of studies looking at tranexamic acid and its use with respect to postoperative bleeding. I think the origins for this in orthopedics really came about from trauma surgery and adult reconstruction, particularly with revisions, these cases where there's a significant amount of blood loss, spine surgery as well. And a lot of the studies have really found the benefit of tranexamic acid in preventing bleeding. Limits the need for transfusion, improves patient outcomes, et cetera. But what we don't really know is its use in sports medicine to see if it's actually useful.
So one of the procedures that we do most in sports medicine, obviously as you know, is ACL reconstruction. So things pertinent to ACL reconstruction that tranexamic acid could potentially have helped with would be not so much blood loss because there's really not a lot of blood loss in ACL surgery. But when you think about postoperative hemarthrosis these cause a lot of pain for patients, stiffness, scar tissue can potentially lead to poor outcomes. So perhaps TXA has the opportunity to reduce hemarthrosis postoperatively.
And if it does so, the question is, does it also reduce pain? Does it improve motion? Does it improve the reactivation of the quadriceps? So there's a lot of questions that really were not answered. There have been a few studies relating to hamstring autograft with the use of postoperative drains, but really not relevant to ACL reconstruction in the United States setting. I don't think any people really in the USA use drains, it's very uncommon. I know some people do, but there's certainly no good data to support the use. So we really wanted to see if there was any kind of clinical relevance of using TXA in patients with BTB autografted ACLs.
Dr. Chris Tucker:
That's a great intro. Thanks, Mike. You already answered my first question about just the particulars of why perioperative blood loss can have a negative effect on ACL patients. Like you said, it's mainly a concern about the effect on their postop rehab, some delayed motion, development of arthrofibrosis. But also the hemarthrosis being cytotoxic to articular cartilage, which as you highlighted in your paper, can contribute to postop pain and stiffness and potentially this negative quadriceps activation. So just briefly for those listeners unfamiliar with TXA, can you briefly explain its mechanism of action and how we're currently using it in orthopedic surgery?
Dr. Michael Alaia:
If you asked me about 15 years ago, what this was, I would tell you that I have no clue. I remember, and I actually entered this in part of an editorial commentary that we wrote for the journal. But there was actually a question on TXA on my boards. I remember this, it was 2012 and I had absolutely no idea what the medication was. Thankfully, now I know we use it so much in orthopedics. But TXA essentially is an antifibrinolytic. It really inhibits competitively the activation of plasminogen to plasmin. So essentially what happens is it reduces the opportunity for plasminogen and fibrin to bind and in doing such really limits bleeding.
Dr. Chris Tucker:
Sure. I think that's a nice, simplistic explanation for those of us potentially unfamiliar with it or need a quick refresher. The stated purpose of your study now was to evaluate the use of IV TXA in patients undergoing primary ACL reconstructions with autograft BTB grafts. With respect to their development of postoperative hemarthrosis, pain, opioid consumption and quadriceps atrophy. Can you tell us the methodology and how you went around studying this and then summarize your findings for us?
Dr. Michael Alaia:
Yeah, sure. So this was meant to be a controlled randomized double-blinded study and we ran a power analysis initially with hemarthrosis as our main primary outcome. And we found that we needed about 110 patients roughly, more or less, including to really be able to determine significance in terms of hemarthrosis postoperatively. So, that was really our primary outcome. And in doing such our secondary outcomes included quad atrophy, range of motion, pain consumption of opioids. So all of those were secondary outcomes. And like I said before, this was a double-blinded controlled randomized study where the surgeons [inaudible 00:06:21] the patients really did not know which arm the patients were allotted to.
And essentially on the first postoperative visit, which should have been between about seven and 10 days postoperatively, the surgeons would really assess the quality of the knee and they would essentially see how big the hemarthrosis was. So, if we thought that there was less than 20 ccs of fluid in there, we weren't going to perform an aspiration. And if you wanted to correlate that with the [inaudible 00:06:48] criteria, anything which was a grade zero or a grade one would not have been aspirated, but anything that was two or above would have been aspirated. So if patients had a palpable fluid wave or perhaps a palatable patella where you push it down and it bounces right back up, or certainly attends hemarthrosis, those patients were getting aspirations.
At the time, we would also see how much fluid we would aspirate from the knees, mark that down and ultimately compare the two groups. We followed these patients for about three months postoperatively as well to ascertain range of motion data, quadriceps activation data, in terms of the actual girth of their thigh compared out to the non-operative side, we would assess for their opioid consumption in terms of MMEs and then really go from there.
Dr. Chris Tucker:
Sure. So what did y'all find?
Dr. Michael Alaia:
Well, it's a really short answer. We found that it didn't do anything. We really thought that we were going to have some kind of significant differences in there when it comes down to blood loss, not so much intraoperatively, but postoperatively with respect to hemarthrosis. I certainly thought that patients that had the TXA were going to have a much less chance of needing to be aspirated or higher numbers in terms of the actual amount of fluid that was aspirated from the knee. But when we ran our statistics, we found that the numbers were virtually equal in terms of each group for patients that either needed a hemarthrosis as well as the amount of fluid that was aspirated from the joints. I think it was about maybe a seven or eight point difference in terms of the actual fluid volume that was aspirated. That was not statistically significant.
And when it came down to the number of patients in each group that actually required an aspiration, I think it was separated by about two or three patients. So out of those 110, there's only a separation about two patients. So it was really a striking lack of a difference in my mind when it came to this.
Our secondary outcomes, again, really similar. Really no difference in opioid consumption, no difference in VAS. As we, as you would have expected, the VAS certainly improved over day one, to day two, to day four, to day seven, to week two, et cetera. And then we look at quad atrophy, range of motion, again, really no differences between the groups. So really it had absolutely no impact on the postoperative progression or care on these patients.
Dr. Chris Tucker:
So I find that interesting, I think a lot of readers did. And I think it's the most striking finding of your study was that using TXA didn't have any reduction in hemarthrosis, pain or opioids. And then also, like you said, their early postoperative recovery, which you assessed by the range of motion, the straight leg raise, quad activation. Obviously this is in contrast to several other randomized control trials that have evaluated TXA for ACL surgery. So can you just dive into that a little bit more and share your thoughts with us for that?
Dr. Michael Alaia:
Yeah. So I think if we're going to compare our study to their study, it's really like comparing apples to oranges because they didn't do the same study. Those were all papers out of Asia, I believe. And they all studied hamstring autografts and they used postoperative drains and these patients were really admitted for a day for observation.
That's really not standard of care in the United States. So those are all well done studies and if I did ACLs and took care of patients postoperatively like they did in those studies, then 100% I'm going to buy-in to the findings that they had. But I think our paper is much more reflective of a United States practice, where we discharge our patients on postoperative day zero. We don't place drains perioperatively pretty much ever and we certainly don't admit the patients overnight for observation. So I think that we have to look at this with a grain of salt and we're not trying to disprove other studies, we're trying to look at it in a certain population. So, for me, I think our data is clear in the fact that it doesn't really help in terms of BTB autografts in our practice without a drain that aren't getting admitted overnight for observation.
Dr. Chris Tucker:
Yeah. I think that's an important point that the external validity of your study is higher for United States surgeons or surgeons in any other place where you perform outpatient ACL surgery, you don't place a drain and they're not maintained overnight for observation. Do you think the lack of a drain, which was used in all prior ACL TXA studies, do you think that that accounts for the entirety of the different findings? You think there's something else at play?
Dr. Michael Alaia:
Well, I think it really accounts for something. We know from lots of studies in different literature, particularly joint reconstruction, joint replacement, that when you have a drain, the knee tends to bleed. You're going to have more perioperative blood loss because you're essentially having a suction effect of the drain, you're preventing clot formation and you're really restricting tamponade within the joint. So I know the arthroplasty literature definitely supports this rationale. There probably are other factors at play here that I'm not particularly sure of, including the exact rehabilitation while they're in the hospital.
Dr. Chris Tucker:
So one other issue or point I was hoping you could maybe comment on, just from your expertise and experience in studying this firsthand, I believe there was a difference in the administration of TXA in your study versus the dosage and mode of delivery in prior studies. Just for clarification for the listeners, can you explain exactly what your administration routine or regimen was so that everybody can understand what your results are representative of?
Dr. Michael Alaia:
Yeah. So that's a great question because right now there is no dominant form of TXA administration. There's been a recent network meta-analysis done by Fellingham and they found really that no formulation dosing, number of TXA doses, show, any sorts of superiority in the setting of total knee arthroplasty. Obviously that's not really been extrapolated to sports medicine, but in three of the studies that we're comparing our results to, they all had a different way to administer TXA.
So for us, we basically gave one gram just prior to the incision and one gram just prior to closure, intravenous. Other papers have looked at the efficacy of intraarticular TXA, which I'm still really not 100% set on because of its potential for [inaudible 00:13:33] toxicity. Some people have studied just using one gram of TXA given IV, some have looked at a certain type of infusion, whether it be 15 mgs per kg perioperatively and then 10 milligrams per kilogram postoperatively for a few hours after an ACL reconstruction. But none of these have really proved to be the dominant way of treating these. We certainly don't have comparative studies looking to see if one is more efficacious than the other. So now we have a fair amount of work to do with regards to the study of TXA. But from my standpoint, I think the one gram pre, one gram post has been used in a lot of the arthroplasty research and certainly can be used nationwide in the United States as well.
Dr. Chris Tucker:
Sure. I think that's great commentary. That's what I was hoping to glean from your experience with this. So let's discuss a few of the limitations to your study that you marked in the paper, such as your potential observer bias based on the clinical decision, whether or not to perform the aspiration on the postoperative knee. You also mentioned the potential confounding effects of meniscus procedures on some of your ACL reconstructions and then the lack of patient reported outcomes scores. Could you just address some of those for us?
Dr. Michael Alaia:
Yeah, so I think the patient reported outcomes scores at three months are probably not that relevant. We know that patients are not going to be perfect three months after the surgery. And to be honest in my mind, what I care about is how they're doing one year, two years, especially moving further down the line. When you look at the potential for bias, that's clearly there in this study because the decision to aspirate was made by the surgeons. So the [inaudible 00:15:24] criteria is essentially, there're some elements of objectivity there in terms of what you think might be a grade one to grade two to grade three. Or saying to yourself in the back of your head, "Well, I think this is less than 20 ccs of fluids. We're not going to aspirate this." So obviously there's a significant amount of bias that can be done with this.
But I think that when you look at it over the surgeons that were involved in this study, we really didn't have a difference in the rate of aspiration, which is nice when we ran on regression. After we did this, we found that the surgeon didn't matter, which was a nice thing to look at. And the same thing with the meniscus, when we ran an analysis afterwards for meniscus procedures, having one versus not having one really didn't change the outcomes at all of this. So despite the limitations, I still think that our data does hold water, but the limitations that are addressed, they're legitimate and I would certainly applaud anyone for taking these limitations seriously.
Dr. Chris Tucker:
I think that's an excellent explanation. And I think it's just another good example of how to deal with practical, clinical studies. And there are limitations in how to perform them. I think your group handled it very nicely and laid it out there.
Dr. Michael Alaia:
I actually asked the smarter, better looking Alaia it in my family whether or not a ultrasound would have given us a better volumetric analysis of how much fluid was in the joint. And she resoundingly told me that it wouldn't. So I also had to take that for what it was worth.
Dr. Chris Tucker:
Sure. Yeah. I read that you had considered that and then ruled it out as a really useful tool. So, I think you addressed it appropriately and it just, like I said, highlights how there are some limitations to how we conduct these studies. Okay. So all that being said with your study conclusions and findings, what does that boil down to you now in your current approach to using TXA in the clinical setting?
Dr. Michael Alaia:
So for me in sports medicine, I'm only using TXA with certain procedures. So my group recently just looked at osteotomies. We did an RCT looking at osteotomies with TXA. We hope to present and publish that data shortly. Unfortunately, again, we found no difference in postoperative pain, no difference in postoperative motion with the use of TXA. I still have been using it with osteotomies, despite the data that we procured from our institution. I think it's more just anecdotal for me in using it for osteotomies because the bigger incision, the bone cut, et cetera. I use it in multi-ligament knee reconstructions because, again, these are patients that can have a significant amount of swelling, multiple incisions around the knee. And anything that I can do to avoid bleeding will be better for the patients. And we know the TXA doesn't really come with a significant side effect profile. So it's a very safe medication. It's a very inexpensive medication.
So you have to think to yourself, does the benefit outweigh the risk and the great majority of the time? I think for TXA, the answer is yes, it absolutely does. So even though some of the data doesn't support its use, I still think that there might be some benefit which we haven't currently extrapolated yet. When it comes to shoulders, I think TSA has been shown to really have a good effect in terms of shoulder replacements. And I know that one of my colleagues, Dr. Hurley, also did some publications on the use of TXA in Latarjets and they found a substantial increase in their outcome scores with the use of TXA as well. So I have been using it for Latarjets.
But again, I'm still weeding through the facts here trying to figure out what it's really good for and what it's really not good for. But I can sure as heck tell you that for ACLs and in our practice here at NYU is nobody's using it because we don't think the data is supported at this point.
Dr. Chris Tucker:
Sure. I think we're all working through this clinical question together and I applaud you and your group for contributing to our knowledge and helping push this forward. So any other parting thoughts or comments for us before we conclude?
Dr. Michael Alaia:
No, not really. I think what I said before about trying to weed out comparing apples and oranges is really important. So when you look at this study and you try and compare it to the other studies that are out there, remember in the back of your heads that we're not looking at the same thing. So if you're going to do your ACL reconstructions the way that they've been reported in the Asian literature, then I think is perfectly appropriate to use TXA when you're using a drain for hamstrings. I think their data is very strong. But in terms of what we do here from a clinical point of view, I don't think that TXA's uses is potentially supported in BTB ACL reconstructions at this time.
Dr. Chris Tucker:
Well, I certainly appreciate your expertise and sharing your insight into your study with us all today. So in conclusion, Mike, I just want to make sure I congratulate you and your coauthors again for your work. Thank you for sharing your time and your thoughts with us today.
Dr. Michael Alaia:
My pleasure, Chris. I'm always happy to be a part of this.
Dr. Chris Tucker:
Dr. Alaia's article titled Tranexamic Acid Has No Effect On Postoperative Hemarthrosis Or Pain Control After Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone Autograft, A Double Blind Randomized Control Trial can be found in the June 2021 issue of the Arthroscopy Journal, which is available online at www.arthroscopyjournal.org. This concludes this edition of the Arthroscopy Journal Podcast. The views expressed in the podcast do not necessarily represent the views of the Arthroscopy Association or the Arthroscopy Journal. Thank you for listening. Please join us again next time.