Preoperative Skin Antisepsis With Iodine Povacrylex Produced Fewer SSIs Compared With Chlorhexidine Gluconate Among Those With Closed Fracture
In this video, Gerard Slobogean, MD, MPH, reviews his recent study that compared two well-known preoperative skin antisepsis solutions with alcohol for patients with either closed or open extremity fractures. Dr Slobogean also discusses the practical implications of the study results and whether the study results are a practice changer for orthopedic surgeons.
Additional Resource:
- PREP-IT Investigators, Sprague S, Slobogean G, et al. Skin Antisepsis before Surgical Fixation of Extremity Fractures. N Engl J Med. 2024;390(5):409-420. doi:10.1056/NEJMoa2307679
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TRANSCRIPTION:
Gerard Slobogean, MD: My name is Gerard Slobogean. I'm an orthopedic trauma surgeon at the R Adams Cowley Shock Trauma Center, which is at the University of Maryland's Medical Center. I'm also the Director of Clinical Research for the Department of Orthopedics at the University of Maryland School of Medicine, as well as at the Center of Orthopedic Injury Research Innovation.
Consultant360: What was the impetus for this study? Why now?
Dr Slobogean: Yeah, I think skin antisepsis prior to surgery is a universal question. It's a step that occurs for every single surgery regardless of what you're planning on doing. So it's a very practical question. And we realized that chlorhexidine gluconate in alcohol has really become the standard practice for most people for at least a decade now. But there's been newer iodine solutions that have come out. And certainly this one, the 0.7% iodine povacrylex in alcohol, has sort of been the other commonly used one, but really not that commonly used, and sets itself up for a nice comparative effectiveness study because if one of these interventions showed a benefit, it would be very easy to change practice and it would be something that would apply to every single surgery.
C360: Can you provide an overview of the study results?
Dr Slobogean: Sure. So this study included both open and closed fracture populations. But, the analysis and the design was always planned to treat them separately. They're very different patient populations and how we sort of approach them both surgically, and we think about them and the baseline risk is very different between the two. So in the closed fracture population, that is where the broken bone isn't sticking through the skin at the time of injury. We saw a significant improvement, a 26% odds reduction for infection in the iodine povacrylex group. And this translated into a 0.8 % absolute reduction in risk of infection. And that's a big percentage. It's only about 1% absolute, but the infection rate is only 3.5% or so in this population. And so if you can drop it by almost a full percentage point, that's worth doing. In the open fractures, we didn't see a difference. You know, the point estimate kind of follows the closed fractures. So I think that gives me a little bit more confidence as well.
And in fact, absolute difference was 0.9%. But that wasn't statistically significant. The event rates a lot higher in open fractures. The sample size was smaller. But I think it gives me at least enough confidence to know that iodine isn't harmful. And so if you're going to change for your closed fractures, it just sort of makes it easier from a policy perspective to probably change for your open fractures and just treat everybody with one solution. But ultimately the results really only support practice change in the closed fractures.
C360: Are the study results a practice changer for orthopedic surgeons as it relates to pre-surgical infection control?
Dr Slobogean: Yeah, I think it does. We've done a lot of work with stakeholders and the surgical community, and I think the vast majority of people are ready to switch pretty quickly, actually. I did mention that both these products tend to be available ubiquitously across hospitals in North America, so the change is easy. And for most hospitals, most surgeons, it's really just a matter of choosing which one on the shelf, they're side by side. So I think because of the rigor of the trial, because of the sample size, almost 6785 patients closed fractures and 1700 open fractures, almost 8500 patients total. I think it gives a lot of confidence that the result is correct. is actually pretty robust. It's generalizable. It was done at 25 hospitals. So I think surgeons have a lot of confidence in this result.
C360: Do orthopaedic surgeons typically have a preference for the type of skin antisepsis used prior to surgery?
Dr Slobogean: Yeah, that's an interesting question. I'll tell you, you know, just some of the background, even when I was training 11 years ago, we were doing everything with iodine, but it was, you know, commonly the betadine product which is iodine in water, not in alcohol. And in around 2010, 2011, a few papers were coming out that showed this chlorhexidine in alcohol was better than iodine in water. And so that really switched practice. And I think it was a pretty easy switch. But that's where the controversy started to lay was, you know, this is an alcohol to water comparison, you know, is this a fair comparison or whatever. But it sort of didn't matter because that chlorhexidine and alcohol was better than what we were doing before. So we all switched.
I will say that some surgeons have expressed some reservation about switching to iodine povacrylex because it's actually a little stickier and they kind of don't like it, you know, you put your hand on the patient's skin while you're operating right over and it has a little bit of a sticky film and, you know, according to the manufacturers, that actually may be why it works better. And we allude to this in the paper that this really not may not be an iodine versus chlorhexidine thing, this may be an iodine povercrylex, which is apparently supposed to have a more sustained activity and sort of makes it a little water insoluble, keeps the iodine active a little longer. So this may be due to that, as opposed to iodine being more effective than chlorhexidine. I think that's really the nuance that that can be lost very quickly if you don't understand that.
C360: After the results of your study, are there any gaps that still remain?
Dr Slobogean: Yeah, I think, you know, this study was designed very pragmatically, meaning lots of surgeons have different ways that they prep or at least different steps. Some people will sort of wipe the limb down with alcohol or scrub it with a brush. They may do a few steps prior to them putting the final skin antisepsis solution on. And the trial was just designed to do the final skin antisepsis solution, right? So, the other pre -prep solutions or steps that they do, we didn't dictate that they must do this or that All that we did dictate was that they continued all those pre -preps steps throughout the trial So when they must do this or that. All that we did dictate was that they continued all those pre -preps steps throughout the trial. So when we switched back and forth between the solutions, they were still doing all the same thing. So, I have had a few surgeons ask me, well, I like to do this or I like to floss the toes or whatever, you know, does that make a difference? And we can't answer that question, but we can tell you that doing that doesn't differentially affect how the two study solutions work. And I think we're good with that. We're going to leave it at that. This is certainly very easy to implement and understand. And then lastly, you know, I guess where we still don't know is this open fractures. As I mentioned, we saw a signal that's similar to the closed fractures, but there's still pretty wide uncertainty there. And that's why it's not statistically significant and stuff like that. And you need a pretty large sample to try and differentiate that difference there. And I'm not, again, I'm not sure that it's worth the effort and the money to do so. Open fractures are really challenging. We've had a lot of studies trying to reduce the risk of infection. And ultimately, I think you just, you have trouble undoing the magnitude of the injury and the bacterial contamination that occurs right away you know from the environment at the time of injury.
C360: What was the take-home message from your study?
Dr Slobogean: Sure you know I think the take home message is the conclusion from the trial, right, which is for patients undergoing fixation of a closed extremity fracture, iodine povacrylex in alcohol reduces the risk of infection compared to the standard that we're using, which is chlorhexidine gluconate in alcohol. For open fractures, it's still unknown, but you know, from a pure policy and ease of implementation perspective, we think it's very reasonable to just start using idempovacrylx for both open and closed fractures, but that has to really be kind of done at the surgeon level, at the hospital level, and I think each practitioner is going to have their own perspective on that.
C360: Do these results apply to other surgical specialties?
Dr Slobogean: I can't really make any definitive statements, right? There were only fracture patients in this trial, but having said that, this is good data that compares the two most commonly used solutions, particularly for closed fractures where the skin is intact. And we're hoping that that's what the antisepsis sort of does is decrease the skin flora right before incision. That probably does transport to other surgical disciplines. And I think, again, we want as many surgical disciplines to look at this data and decide whether it applies to their practice. But I think it is a pretty transportable result.
C360: What does it take to put a study like this together?
Dr Slobogean: So this was a multicenter trial, 25 sites, 8500 patients. And so we had 300 collaborators that helped make this happen. And really, I had an excellent co-PI at McMaster, Sheila Sprague. She runs the methodology center at McMaster University and it really is multidisciplinary in terms of both the clinical knowledge and the clinical trialist knowledge and organization to make a successful collaboration. And, you know, we're really grateful for the team that was able to pull this off.