Is it time to reconsider the use of hydrogen peroxide in hip and knee arthroplasty?

Listen to Andrew Duckworth, Fares Haddad and Dominic Meek discuss the editorial 'Is it time to reconsider the use of hydrogen peroxide in hip and knee arthroplasty?' published in the February 2023 issue of The Bone & Joint Journal.

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Transcript

[00:00:00] Welcome everyone to one of our BJJ podcasts for the month of February. I'm Andrew Duckworth and a warm welcome from your team here at the Bone & Joint Journal. We'd like to thank you all for your continued comments and support for our general podcast series as well. It's a big thanks to our many authors and colleagues who have taken part.

The topic of our podcast today I think will be of real interest to many of our listeners and readers and likely relevant to several of our practices. So firstly, have the pleasure again of being joined by our Editor-In- Chief here at the BJJ, Professor Fares Haddad. Welcome Prof. It's great to have you back with us.

Andrew, thanks for asking me. Fares and I are delighted to be joined by another of our editorial board colleagues here at the general Professor Dominic Meek from Glasgow to discuss their editorial entitled, 'Is it Time to Reconsider the Use of Hydrogen Peroxide in Hip and Knee Arthroplasty'? Welcome Dominic. Thank you so much for taking the time to join us today.

Thank you. It's a pleasure. So Prof, maybe I come to you first. No. Sort of to kick us off, I suppose, you know what, why did Dominic, yourself and your co-authors decide to write an editorial on this topic in particular? So a co a couple of things. I mean, this is something that we published many years ago when we [00:01:00] started popularizing single stage revision.

And tho those protocols, which I think were fairly influential in changing the way North America views single stage revision and increasing its adoption. It was no longer an endo clinic thing. It was now a wider thing with some evidence from the UK had hydrogen peroxide in them and were copied by some of the North American

big big centres including the Ortho Carolina Study. So rather embarrassingly in recent times we've faced a situation where we're having discussions with colleagues abroad who are using it, and we are no longer meant to be using it. So that's always at the back of my mind and something we are considering.

And then Dominic, and as, as, as you may know, Dominic is the, the next President of the British Hip Society and has been you know, the powerhouse behind all good things happening at the British Hip Society for the last few years. And Dominic and his team were approached by BHS members really asking what the state of play is and what could be done.

And that went through the BHS Professional Affairs [00:02:00] Committee. So really it came from two angles and coming at it together, we thought it was just a good time to, to really have a look at how this has come about, where we stand right now and how we can help colleagues to reconsider what the role of hydrogen peroxide is at the moment and what we could do potentially to change that.

Yeah, that's great. S really like, say, I think I've certain on our centre as well as this sort of grumbling in the background of, of, of this issue and actually bringing it back to the forefront is very much this editorial. I think it's, it's great that it's done that and, and, and the reasons why were very clear there.

And Dominic, if I could come to you next, you know, before we look at, maybe, I thought we would maybe touch em on infection as, as well as the content of your editorial about hydrogen peroxide. But could you give us a brief overview of what you think the, the current practice is in the UK. Well, sure. They, I mean, the current practice has had a marked reduction because of the MHRA review in 2014.

So really it's, it's confined really to vented situations you use, it wouldn't use it in a [00:03:00] closed cavity situation where oxygen may get into the systemic situation, and it's reduced in concentration as well. Traditionally, it was 3%, it's down to 1.5%. And it's, you're doing it with limited lavages if you are using it and washing it away with saline rather than, and drying it rather than leaving it to do it bathing effect that you often did.

 As Fares has suggested, it had been used in combination with povidone-iodine and chlorhexidine in the past. And that sometimes makes it a little bit difficult to work out exactly what those individual solutions have effect by themselves compared in combination. And that's where a lot of the, the future research will lie.

But in terms of where it was previously used in terms of cemented sockets and in the cemented femur that's really dependent on local availability, which is markedly reduced now. So basically it's not used very much in its traditional role, which was the, the primary cemented hip replacement.

Yeah. That's interesting. Cause actually it's something again, came up in our centre recently about the, the limited supply [00:04:00] of it currently. And I think that is, is likely potentially getting worse. And, and maybe if we move on to sort of the details more about how it, you know, some of the evidence. For and against it.

I thought we'd maybe just touch on the issue of infection, which is often the, as as as Fares has said the situation in which it's been purported to be useful. What in terms of PJ- PJI at the moment, where, where are we in terms of, you know, the, the current definition for diagnosis to kick off?

Yeah, sure. I mean I think ultimately it's useful if we have one definition, single definition of PJI. And in the UK we've really wanted to go with Europe. For once and the European Bone and Joint Infection Society definition. It really looks like the natural successor to the previous ones, like the MSIS definition in 2013.

And it's nice cuz it's just got a simple free level approach to it. Classifying it as, 'infection unlikely', 'infection likely' and 'infection confirmed'. So it's nice and easy to use. And these are just based in fairly [00:05:00] simple clinical and radiological and laboratory fact factors. Making if infections unlikely, there's no positive test to suggest that or confirm it if infection is likely.

There's some positive clinical features such as the raised serums, CRP. And another positive test like synovial fluid microbiology or tology or nuclear imaging. And then infection is confirmed if any of the real tests from the confirmatory criteria are positive. And, and it gives it fairly simple and effective management plan for, for clinical treatment.

And interesting, just recently in the DGR last year, Sigmund et al compared this to the international consensus meeting 2018 and the IDSA one from 2013. Found it was more sensitive. And it was better at reducing the number of uncertain diagnoses. So we are basically joined with Europe for this one.

Yeah, no, absolutely. I think it's really nice over you've, you've given there and like you say, it seems to be something which is, like you say nicely simplistic and actually very relevant to clinical practice. And in terms of, you [00:06:00] know, moving on to the treatment of infection at the moment, where are we in terms of antibiotic sort of advice at the moment, I suppose, particularly in terms of length of treatment?

Sure. I mean, that's a great topic and one we probably could spend over an hour just in itself with too much really to discuss in a very short time. But to summarize, really, the courses of antibiotic are getting shorter. We're looking much more with our multidisciplinary teams for rapid switching to oral antibiotics rather than parentral advantages are getting shorter, staying getting patients home.

And ultimately there's a big increase in the number of one stage revisions occurring now. So naturally that's going to reduce the number of needing antibiotics between stages in any case. Yeah. So I also believe that there's a pragmatic approach to the Sheffield Group will reduce the use of antibiotic twin cases as well.

And actually there is a good paper coming from that group, which will be in The Bone & Joint Journal soon. So keep a lookout for that. And then that comes on to really sort of after implantation as well. And that remains a hotly debated subject. Some people say [00:07:00] just treat it as an aseptic, just go back in one dose of pre-op antibiotics.

Others like 24, 48 hours. No real consensus at the moment, and that's where groups like the UK Periprosthetic Joint Infection Group are looking at, maybe, hopefully trials with the recorded by Jere, et cetera, will help. Some will go for extended cultures running up to about 10 days sometimes, but again, that seems quite long.

Room for contamination might false positive, et cetera. But basically, as I say, it needs more research in that. Yeah. And then if extended cultures are positive, usually people will give either a three to six month course of further antibiotics for that patient. Yeah. But that's being reduced by a, a, a lot of cohorts as well.

So, so lots of different things and room for lots of good research to try and work out what the best combination is. Absolutely. Prof, anything you wanted to add to that? Andrew, a couple of things really. I think the, the, the first one is that sometimes when there is new data, even if it's [00:08:00] randomized data, it needs to be replicated and people need to look at it critically.

And there is one North American multicentre study. That is not without flaws, that has popularized increasing length of antibiotic usage after second stage surgery. And that's kind of rattled the cage a little bit. And people are a little bit confused as to, you know, do you treat it as aseptic? Do you give a little, you know, few days of antibiotics?

Or frankly, should you give three months And it is an RCT. It is a high level of evidence, but again, it's not an RCT without flaws. And I think this is one area where the UK and you know, if we can depoliticize the collaboration between infection centres and make it research productive, then that's potentially something that we can help with and do as on a UK setting.

I think the, the other thing to highlight here, and I'm sorry, take up a few more seconds. Is that this is never a homogeneous population. And that's where you know, Dominic mentioned the MDTs. In reality, hosts are different. Infections are different. Polymicrobial infections, [00:09:00] fungal infections. And so I think you need to treat the patient, the organism the, the, the, the challenge that you are facing at the time.

And that's where that simple rule just, I don't think can exist. Yeah, no, a absolutely a a And as I suppose related to that, probably, you know, we've talked about the research that's required in, in relation to antibiotics, things like that. But how, how are we, how do we define success of treatment? Because actually that really is the key outcome, isn't it, in terms of then assessing how effective these these interventions are.

Yeah, no, you know, that's a hobby horse of mine, and thank you for, for, for asking in that I lived through two consensus meetings and in the first one in 2013, a, a very promising future high flyer for was I think a fellow at the time presented a, a wonderful paper and a set of slides on a, an outcome metric for infection that didn't even mention the patient.

So it, it, it was all about, you know, everything was focused on whether you needed another operation or whether you needed antibiotics or not. And, [00:10:00] and the reality is, I think we've learned. You know, with all aspects of outcomes that it should all be about the patient. And, you know, sometimes some patients you know, can be on antibiotic suppression for life and be very happy with it.

You know, other patients can have very successful multi-stage surgery and be crippled. So it's about the outcome for the patient rather than just the arthroplasty. And it's not just about the microbiology. And so I think we're not there yet. Is the answer, but we need a bit more qualitative work and we need ultimately a quantifiable system that looks at patient perception, looks at the outcome of the arthroplasty, if you like, in mechanical terms, and also looks at the outcome in terms of organisms and antibiotic usage.

And that's, I think that's a good area for people to research and really look at this, but a bit like if we can't agree the definition. We'll keep changing the definition. We're gonna confuse the literature. Yeah. If we can't agree what the right outcome is, we're also gonna struggle. So I think that scenario, I'm really keen that people should focus on over the next few years.

No, abso [00:11:00] absolutely. And, and bef maybe before we move back to your editorial, the, the last thing I just wanted to touch upon was in terms of, you know, there's this sort of been discussions, a lot of discussions about centralization of services to manage PJI, what, what, what are your thoughts on that and where are we with that at the moment do you think?

Maybe I'll kick off and hand on, hand on to Dominic. I mean, I think, you know, France has moved very strongly in that direction. We are clearly doing so in an Oxford, started with an infection centre many years ago, and then. Other centres. We did that. And you know, Dominic's group have done that and people are increasingly doing it.

There's no doubt the right thing to do for these complex cases is to have a strong, multidisciplinary team, and you cannot have the, the big expanded multidisciplinary team, including infectious diseases, microbiology, plastics, clinical nurse specialists, et cetera, everywhere. So I, I think that's a natural drift.

I think there is a danger as ever that politics takes over and impose. Some kind of structures on us, but you know, this [00:12:00] is an area that is absolutely right for centralizing in centres that can treat these patients well, give them the care they deserve in a timely manner, and also record data. Yeah.

You know, that the, the critical thing here is recording the data so we can learn, we can learn from it. Absolutely. Dominic, anything you'd add to that at all. Yeah, I mean, I think centralization, I think it's, it's not the absolute bit of it, it, it's a secondary to what's developing anyway. We've looked in the British Hip Society at the revision hip networks and we found that actually locally, these have been evolving over time anyway, with natural networks established.

And the people who are interested are getting together as far says these multidisciplinary groups with. pharmacists, microbiologists, plastic surgeons, infectious diseases, et cetera. And so naturally they're already there. So by default it does centralize with, with those networks. And it's obviously important.

You have to get these diagnoses of these organisms very quickly, and it's only by having that 24/7 availability of diagnosis and then [00:13:00] treatment that you're gonna be able to get the improvement results for the, the patients. And I think a lot of the society guidelines from BASK and BHS support that.

And obviously once they're implemented, that, that, that will occur by default anyway. Absolutely. Absolutely. No. Dominic, just stick with you. I think we moving, I know we've veered a bit away from the editorial, but that was a really interesting discussion about how, where, where we are with the

diagnosis and management of PJI. If we come back to sort of the hydrogen peroxide question though, you know you know, a as you've already said, and you're saying the editorial you know, it's traditionally been employed during hip and knee arthroplasty with purported benefits. What, what, what are those?

If just gives us our listeners a brief overview, what are those benefits that we, we might see that people think that we see with it? Okay. Well, I mean, traditionally it's been about cementing and the main literature, to be fair actually, really, really supports pulse lavage. Yeah. For preparing the, the, the, the, the, the cancellous bone.

And obviously there have been papers showing that it's effective of hydrogen peroxide, but really hydrogen peroxide ceiling, there's probably [00:14:00] not that much difference between them. There is however, plenty of efficacy, e evidence about his efficacy's a topical antiseptic. A 3% solution will directly affect the DNA and oxidation of micro microbial proteins, and so is effective at killing them.

But the real interest I think is particularly when use of this dreading the biofilm. That we all find terrible to be able to treat, which typically we have previously done by excision i.e. taking all the components out. But similar to some of the work that's been on ascetic acid, hydrogen peroxide seems to be able to de disrupt that biofilm and allow more effective treatment.

Pres demonstrated the spectrum of Staphyloccus, epidermidis, biofilms and it's been used clinically in arthoplasty infected revision cases series. However, the trouble of those series is it's difficult to actually tease out because they're just cases what the factors are because they're used in a whole combination of our, everyone's, as far has said, povodine-iodine or chlorhexidine in combination with it.

So which one needs a good clinical trial [00:15:00] to actually see what, what, what, what is important in that? No, absolutely. I thought it was the, one of the really interesting takeaway messages from the editorial was it's really hard to tease out from not only the, is the literature quite limited and small in some ways, but it's actually teasing out actually what effect is it actually happening?

Cuz lots of things are, are being, are contributing to it or are potentially so I thought it was a really interesting part. Prof, if I come back to you, you know, that those are the, the, the benefits obviously, as, as it's sort of been mentioned, you know, in 2014, the MHRA issued alert relating to the risk associated with using hydrogen peroxide.

Could you just give us a brief overview about what, what, how that really came about? Yeah, I mean, and they got a non-fatal yellow card alert in relation to cavitary surgery and basically gas embolism. And that triggered a, a review by whoever was advising the MHRA at the time. And they looked at the literature and, and within the literature there were a number of cases of cardio respiratory collapse within

sort of seconds or minutes of the [00:16:00] installation of hydrogen peroxide within a cavity. And th the, this wasn't just to collapse. There was sometimes surgical emphysema a pneumocephalus on one occasion gas and central lines and so on. So it was very real. It was a gas embolism phenomenon. And that sort of led to a, a very much a finite decision that you could not use it in those settings.

You know, one of the unintended consequences, if you like, has been the impact on, on orthopedics. There, there was only one orthopedic case from, from John Timperley and his colleagues about it. But it, it, orthopedics has been a, a bit of a secondary victim here, and many of the changes that come through for good safety reasons often have unintended consequences.

Yeah. And, and this, this sadly is one of those that's, that's really interesting. And again, in your editorial that you go on to say how that hasn't necessarily happened throughout the world and I thought it was interesting. Obviously we've got a little listeners from the US as well. It's still used there off-label.

Is that correct? In the management of [00:17:00] PJI. It is. And you know, I think, you know, P- PJI creates all sorts of challenges. And in, in the, in the US it is still used by some centres. There's a lot of debate over, you know, very much as Dominic was saying, which solution do you use of which organism, at which stage in the operation?

You know, there, there, there's so much alchemy about the management of, of, of infection. So it's, it's tricky from that point of view, but it's only adopted in the Ortho Carolina Protocol and a bit like the Informed Study in the UK . The Ortho Carolina one stage versus two stage study is gonna be a, a, a, a fundamental study in our, in our thinking about one stage versus two stage revision.

Absolutely. And, and, and Dominic, can you, we've already mentioned it a couple of times, the alternatives. What, what is the evidence of that? Is there any good high level evidence for any alternative solutions that are better? Or, or, or, as effective. Sure, I mean, one, one of the main ones that's recently been discussed is the Calkins et al paper 2020.

And that was dilute Betadine as a randomized controlled tile with saline and it demonstrated [00:18:00] no detriment of the Betadine on wound healing per se, which is one of the things people get concerned about putting anti septic in the wound. However, it did reduce the infection, the periprosthetic joint infection.

There were a few caveats to this trial. Although it was randomized, the PJI rate in the saline group was actually over 3%, which is actually quite high. And that makes you wonder whether there were other confounders that we don't know about that actually were, despite them being matched in various principles.

Also, the way they actually applied the Betadine, it was bathed in the Betadine where it was just a bit of a wiping with the saline as opposed to it's not the same. Same sort of way. The, the skin preparation was slightly different as well. So really, you know, not, not entirely, but interesting. And I think the core to where we are going to go is with more randomized trials in that it would be interesting to compare with Chlorhexidine as opposed to Betadine.

Topical antibiotics have also been used by some of our spinal and upper limb colleagues. Now they may have different bacteria to what [00:19:00] we are used to, but again, recent meta-analysis don't support the use of topical antibiotic powder it directly into the wound and NICE only recommend that if it's part of a clinical trial.

Yeah. So various things interesting where, where we should be going with it. But again, really a lack of hard evidence. Absolutely. I think what, from your summary there, Dominic, I think it highlights the importance of, of the, of the, of the studies and the trials moving forward, how important the design of them is going to be to actually give us the answers that, that we need.

And so maybe to finish off, maybe Dominic, I'll start with you and I'll come to you, Prof. Wh wh where do people stand here for our listeners who, who manage PJI every day? Where do we stand on the use of hydrogen peroxide at the moment, do you think? It's, I mean, I think it's a case by case basis then, then availability.

I, I think it shouldn't be absolutely banned, but you have to be aware that as we're saying, there isn't any literature to back you up if something goes wrong clinically. So really on the back of that, I think we do need more clinical trials for it. Yeah. And that's [00:20:00] the only way forward, isn't it?

No. Prof anything you'd add to that? No, no. I tend to agree. I think you've gotta look at what your local policy is, but in principle right now, in a UK setting you, you shouldn't really be using it in a cavity. You may get in trouble if you do elsewhere in the world. You probably still can. I think the way it could be used in the UK would be in a, in a, in an approved, validated study setting and someone needs to set that up.

And I think this is a, you know, a tip of a bit of an iceberg. I think we're gonna see more and more things that we thought were established suddenly being challenged because there's no evidence. And, you know, we're talking about one particular product here, but with EUMDR, UKCA coming in, you'll suddenly see things that you thought were commonplace, particularly implants disappearing all of a sudden because.

There isn't the data that they need to have. So I think this is one area where good research is needed if people want to bring it back. And it may be a heavy lift and it may be tough to fund be because we're looking primarily at the infections. But I think it's worth looking at. That's really, really nice point to finish on.

So to [00:21:00] both are really sincere thanks for joining, joining us today and, and putting under the spotlight a really important and, and relevant issue. And it was really good to have that discussion about PJI as well. It was really informative and, and so nice to talk to you both. And so our listeners, we do hope you've enjoyed joining us and we encourage you to share your thoughts and comments through social media and like, feel free to tweet or post about anything we've discussed here today.

And thanks again for joining us. Everyone. Take care.